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Sample records for severe allergic asthma

  1. Omalizumab therapy for children and adolescents with severe allergic asthma.

    Science.gov (United States)

    Romano, Ciro

    2015-01-01

    Omalizumab, a therapeutic humanized monoclonal antibody specific for human IgE, was introduced in clinical practice more than a decade ago as an add-on therapy for moderate-to-severe allergic asthma in patients aged ≥12 years. Omalizumab has been demonstrated to be effective in adults with uncontrolled persistent asthma, with an excellent safety profile. In simple terms, omalizumab works by inhibiting the allergic cascade, that is, by neutralization of the circulating free IgE. This leads to reduction in the quantity of cell-bound IgE, downregulation of high-affinity IgE receptors, and, eventually, prevention of mediator release from effector cells. Evidence is far less abundant on the role of omalizumab in pediatric asthma. Although efficacy and safety of omalizumab in children and adolescents with uncontrolled, persistent allergic asthma has been recognized as well, further studies are needed to clarify a number of open questions in this specific patient population.

  2. 4-month omalizumab efficacy outcomes for severe allergic asthma: the Dutch National Omalizumab in Asthma Registry

    NARCIS (Netherlands)

    Snelder, S. M.; Weersink, E. J. M.; Braunstahl, G. J.

    2017-01-01

    Background: Omalizumab is licensed as add-on therapy for patients with severe allergic asthma. Response is in most studies scored by the physician's global evaluation of treatment effectiveness (GETE). A good clinical and validated parameter for treatment response is currently missing. Also, there

  3. Response to omalizumab in patients with severe allergic asthma

    DEFF Research Database (Denmark)

    Zierau, Louise; Walsted, Emil Schwarz; Thomsen, Simon Francis

    2017-01-01

    INTRODUCTION: Omalizumab is a humanized monoclonal anti-IgE antibody, which is widely used for patients with severe uncontrolled asthma. Treatment with omalizumab is known to decrease the number of exacerbations and GETE score (Global Evaluation of Treatment Effectiveness) - but little is known...

  4. Omalizumab in Japanese children with severe allergic asthma uncontrolled with standard therapy.

    Science.gov (United States)

    Odajima, Hiroshi; Ebisawa, Motohiro; Nagakura, Toshikazu; Fujisawa, Takao; Akasawa, Akira; Ito, Komei; Doi, Satoru; Yamaguchi, Koichi; Katsunuma, Toshio; Kurihara, Kazuyuki; Kondo, Naomi; Sugai, Kazuko; Nambu, Mitsuhiko; Hoshioka, Akira; Yoshihara, Shigemi; Sato, Norio; Seko, Noriko; Nishima, Sankei

    2015-10-01

    Omalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng/ml (target level of suppression). Thirty-eight Japanese children (6-15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg/day fluticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open-label study. The geometric mean serum free IgE level at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were significantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p omalizumab decreased free IgE levels to less than 25 ng/mL. Omalizumab improved asthma control and was well-tolerated, as well. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  5. Omalizumab Treatment Response in a Population With Severe Allergic Asthma and Overlapping COPD.

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    Maltby, Steven; Gibson, Peter G; Powell, Heather; McDonald, Vanessa M

    2017-01-01

    Asthma and COPD are common airway diseases. Individuals with overlapping asthma and COPD experience increased health impairment and severe disease exacerbations. Efficacious treatment options are required for this population. Omalizumab (anti-IgE) therapy is effective in patients with severe persistent asthma, but limited data are available on efficacy in populations with overlapping asthma and COPD. Data from the Australian Xolair Registry were used to compare treatment responses in individuals with asthma-COPD overlap with responses in patients with severe asthma alone. Participants were assessed at baseline and after 6 months of omalizumab treatment. We used several different definitions of asthma-COPD overlap. First, we compared participants with a previous physician diagnosis of COPD to participants with no COPD diagnosis. We then made comparisons based on baseline lung function, comparing participants with an FEV 1 80% predicted after bronchodilator use. In the population with an FEV 1 Omalizumab treatment markedly improved asthma control and health-related quality of life in all populations assessed based on the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. Omalizumab treatment did not improve lung function (FEV 1 , FVC, or FEV 1 /FVC ratio) in populations that were enriched for asthma-COPD overlap (diagnosis of COPD or FEV 1  omalizumab improves asthma control and health-related quality of life in individuals with severe allergic asthma and overlapping COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful in the management of severe asthma with COPD overlap. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  6. 'Real-life' effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review.

    Science.gov (United States)

    Abraham, I; Alhossan, A; Lee, C S; Kutbi, H; MacDonald, K

    2016-05-01

    We reviewed 24 'real-life' effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short- and long-term benefit of anti-IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life - thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2-4 years, and the majority of omalizumab-treated patients may benefit for many years. Omalizumab has positive short- and long-term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Therapy with omalizumab for patients with severe allergic asthma improves asthma control and reduces overall healthcare costs.

    LENUS (Irish Health Repository)

    Costello, R W

    2012-02-01

    BACKGROUND: Patients with asthma who have persistent symptoms despite treatment with inhaled steroids and long-acting beta agonists are considered to have severe asthma. Omalizumab is a monoclonal antibody directed against IgE, which is used as an add-on treatment for patients who have severe persistent allergic asthma. AIMS: The aim of this study was to assess the clinical benefit and healthcare utilisation of patients who responded to omalizumab therapy and to establish an overall cost implication. METHODS: This was an observational retrospective cohort study designed to investigate the effect of omalizumab on exacerbations of asthma before and after 6 months of treatment in Irish patients. RESULTS: Centres who had treated patients with severe allergic asthma for the 6 months prior and post omalizumab treatment were audited with a standardised assessment tool. Sixty-three (32 male) patients were studied. In the 6 months prior to omalizumab 41 of 63 (66%) had been hospitalised, and this fell to 15 of 63 (24%), p < 0.0001 in the 6 months after treatment was started. Hospital admissions reduced from 2.4 +\\/- 0.41 to 0.8 +\\/- 0.37 and the mean number of bed days occupied was reduced from 16.6 +\\/- 2.94 to 5.3 +\\/- 2.57 days, p < 0.001. The number of oral corticosteroid doses used fell from 3.1 +\\/- 0.27 to 1.2 +\\/- 0.17, p < 0.001. The overall cost saving per omalizumab responder patients for 6 months was 834. CONCLUSIONS: Six months therapy with omalizumab reduced the number of bed days, the number of hospitalisations and the use of oral corticosteroids compared to the 6 months prior to commencement. Despite the cost of the additional therapy there were overall savings in health costs.

  8. Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives

    Directory of Open Access Journals (Sweden)

    Konstantinos Samitas

    2015-12-01

    Full Text Available Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes.

  9. Autoimmune polyendocrine syndrome type 2 in patient with severe allergic asthma treated with omalizumab.

    Science.gov (United States)

    Rams, Anna; Żółciński, Marek; Zastrzeżyńska, Weronika; Polański, Stanisław; Serafin, Agnieszka; Wilańska, Joanna; Musiał, Jacek; Bazan-Socha, Stanisława

    2018-01-04

    Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.

  10. Longterm clinical outcomes of omalizumab therapy in severe allergic asthma: Study of efficacy and safety.

    Science.gov (United States)

    Mansur, Adel H; Srivastava, Sapna; Mitchell, Verity; Sullivan, Julie; Kasujee, Ismail

    2017-03-01

    Omalizumab has been shown to be an effective add-on therapy for patients with uncontrolled severe persistent allergic asthma. There has been a steady accumulation of evidence on the long-term effectiveness of omalizumab; however, data on real-life outcomes beyond one year of treatment is limited. In this study, we report on long-term outcomes of omalizumab treatment. We collected data from our severe asthma registry on hospitalisations, exacerbations, corticosteroid sparing, asthma control, lung function, biomarkers and side effects, to determine if the benefit was sustained and treatment was safe on the long term. Forty-five patients [mean age 44.9 years (range 19-69), females 37/45 (82%), mean duration of omalizumab treatment = 60.7 ± 30.9 months (range 23-121) were included in the analysis. We observed a reduction in the annual acute asthma related hospital admissions for the total population from 207 at baseline to 40 on treatment (80.7% reduction), whilst the per patient annual hospitalisations were reduced from a mean of 4.8 to 0.89 post-omalizumab treatment (p omalizumab therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Therapy with omalizumab for patients with severe allergic asthma improves asthma control and reduces overall healthcare costs.

    LENUS (Irish Health Repository)

    Costello, R W

    2011-05-11

    BACKGROUND: Patients with asthma who have persistent symptoms despite treatment with inhaled steroids and long-acting beta agonists are considered to have severe asthma. Omalizumab is a monoclonal antibody directed against IgE, which is used as an add-on treatment for patients who have severe persistent allergic asthma. AIMS: The aim of this study was to assess the clinical benefit and healthcare utilisation of patients who responded to omalizumab therapy and to establish an overall cost implication. METHODS: This was an observational retrospective cohort study designed to investigate the effect of omalizumab on exacerbations of asthma before and after 6 months of treatment in Irish patients. RESULTS: Centres who had treated patients with severe allergic asthma for the 6 months prior and post omalizumab treatment were audited with a standardised assessment tool. Sixty-three (32 male) patients were studied. In the 6 months prior to omalizumab 41 of 63 (66%) had been hospitalised, and this fell to 15 of 63 (24%), p < 0.0001 in the 6 months after treatment was started. Hospital admissions reduced from 2.4 ± 0.41 to 0.8 ± 0.37 and the mean number of bed days occupied was reduced from 16.6 ± 2.94 to 5.3 ± 2.57 days, p < 0.001. The number of oral corticosteroid doses used fell from 3.1 ± 0.27 to 1.2 ± 0.17, p < 0.001. The overall cost saving per omalizumab responder patients for 6 months was 834. CONCLUSIONS: Six months therapy with omalizumab reduced the number of bed days, the number of hospitalisations and the use of oral corticosteroids compared to the 6 months prior to commencement. Despite the cost of the additional therapy there were overall savings in health costs.

  12. Omalizumab therapy for refractory allergic fungal rhinosinusitis patients with moderate or severe asthma.

    Science.gov (United States)

    Gan, Eng Cern; Habib, Al-Rahim R; Rajwani, Alykhan; Javer, Amin R

    2015-01-01

    1. To assess the efficacy of omalizumab therapy in improving sinonasal outcomes in refractory allergic fungal rhinosinusitis (AFRS) patients with moderate or severe asthma. 2. To determine if omalizumab therapy reduces the usage of corticosteroids or antifungal therapy in AFRS patients The clinical charts of patients with AFRS with moderate or severe asthma who received at least three subcutaneous injections of omalizumab therapy between 1st January 2012 and 1st May 2014 were retrospectively reviewed. These patients had undergone bilateral functional endoscopic sinus surgery (FESS) and failed adjunct medical treatments (oral or topical corticosteroids and/or antifungal therapy) prior to omalizumab therapy. Seven patients met the inclusion criteria and were included in this study. The mean age of the patients was 48.14. The average number of subcutaneous omalizumab injections was 7.57 (range 6-11) with a mean dosage of 287mg (range 225-375mg). The mean pre-omalizumab treatment Sino-Nasal Outcome Test-22 (SNOT-22) score was 52.14 while the mean post-omalizumab treatment SNOT-22 score was 35.86 (31% improvement). The mean pre-omalizumab therapy Phillpott-Javer endoscopic score (over the last one year before omalizumab therapy) was 36 while the mean post-omalizumab therapy endoscopic score (from the last clinic visit) was 14 (61% improvement). Omalizumab therapy reduced the dependence of AFRS patients on corticosteroid and antifungal treatments. Omalizumab therapy can be considered as a potential adjunct for the treatment for patients with refractory AFRS with moderate or severe asthma. However, larger prospective studies to confirm the findings of this study will be required. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  13. Anti-IgE: lessons from clinical trials in patients with severe allergic asthma symptomatic despite optimised therapy

    Directory of Open Access Journals (Sweden)

    R. Buhl

    2007-09-01

    Full Text Available The efficacy of omalizumab has been extensively investigated in clinical trials in patients with severe persistent allergic (pre-treatment total immunoglobulin E 30–700 IU·mL–1 asthma including the Investigation of Omalizumab in Severe Asthma Treatment (INNOVATE study, which enrolled patients with inadequately controlled severe persistent allergic asthma despite receiving high-dose inhaled corticosteroid in combination with a long-acting beta2-agonist, and also additional controller medication if required. In the INNOVATE study, add-on omalizumab significantly reduced clinically significant exacerbation rates by 26% (0.68 versus 0.91, severe exacerbation rates by 50% (0.24 versus 0.48 and emergency visit rates by 44% (0.24 versus 0.43 and significantly improved asthma-related quality of life (QoL compared with placebo. In a pooled analysis of data from seven studies, add-on omalizumab significantly reduced asthma exacerbation rates by 38% (0.91 versus 1.47 and total emergency visits by 47% (0.332 versus 0.623. In addition, omalizumab significantly improved QoL versus current asthma therapy in a pooled analysis of data from six studies. Omalizumab has demonstrated a good safety and tolerability profile in completed phase-I, -II and -III studies involving >7,500 patients with asthma, rhinitis or related conditions. Omalizumab represents a major advance for the treatment of severe persistent allergic asthma that is inadequately controlled despite treatment with inhaled corticosteroids and a long-acting beta2-agonist.

  14. Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria.

    Science.gov (United States)

    Hew, M; Gillman, A; Sutherland, M; Wark, P; Bowden, J; Guo, M; Reddel, H K; Jenkins, C; Marks, G B; Thien, F; Rimmer, J; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Wright, C; Bint, M; Yozghatlian, V; Burgess, S; Sivakumaran, P; Yan, K Y; Kritikos, V; Peters, M; Baraket, M; Aminazad, A; Robinson, P; Jaffe, A; Powell, H; Upham, J W; McDonald, V M; Gibson, P G

    2016-11-01

    Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg. © 2016 John Wiley & Sons Ltd.

  15. Cost-Effectiveness of Bronchial Thermoplasty, Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Zafar Zafari

    Full Text Available Bronchial thermoplasty (BT is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy.To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA.A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]. A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs and exacerbations as the outcomes.For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%.Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes

  16. Cost-Effectiveness of Bronchial Thermoplasty, Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma.

    Science.gov (United States)

    Zafari, Zafar; Sadatsafavi, Mohsen; Marra, Carlo A; Chen, Wenjia; FitzGerald, J Mark

    2016-01-01

    Bronchial thermoplasty (BT) is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy. To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA. A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]). A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs) and exacerbations as the outcomes. For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER) of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP) of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI) was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%. Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes cost

  17. Allergy in severe asthma.

    Science.gov (United States)

    Del Giacco, S R; Bakirtas, A; Bel, E; Custovic, A; Diamant, Z; Hamelmann, E; Heffler, E; Kalayci, Ö; Saglani, S; Sergejeva, S; Seys, S; Simpson, A; Bjermer, L

    2017-02-01

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Sibship Characteristics and Risk of Allergic Rhinitis and Asthma

    DEFF Research Database (Denmark)

    Westergaard, Tine; Rostgaard, Klaus; Wohlfahrt, Jan

    2005-01-01

    asthma; birth order; hypersensitivity; rhinitis; allergic; perennial; rhinitis; allergic; seasonal; risk factors; siblings......asthma; birth order; hypersensitivity; rhinitis; allergic; perennial; rhinitis; allergic; seasonal; risk factors; siblings...

  19. Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

    Science.gov (United States)

    Gibson, P G; Reddel, H; McDonald, V M; Marks, G; Jenkins, C; Gillman, A; Upham, J; Sutherland, M; Rimmer, J; Thien, F; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Robinson, P; Wright, C; Yozghatlian, V; Burgess, S; Sivakumaran, P; Jaffe, A; Bowden, J; Wark, P A B; Yan, K Y; Kritikos, V; Peters, M; Hew, M; Aminazad, A; Bint, M; Guo, M

    2016-09-01

    Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting. © 2016 Royal Australasian College of Physicians.

  20. Optimizing the position and use of omalizumab for severe persistent allergic asthma using cost-effectiveness analysis.

    Science.gov (United States)

    Faria, Rita; McKenna, Claire; Palmer, Stephen

    2014-12-01

    There has been some controversy on whether the costs of omalizumab outweigh its benefits for severe persistent allergic asthma. This study aimed to resolve the uncertainties and limitations of previous analyses and establish the cost-effectiveness of omalizumab under the list price and Patient Access Scheme (PAS) discounted price for the UK National Health Service. A decision-analytic model was developed to evaluate the long-term cost-effectiveness of omalizumab under the perspective of the National Health Service. Outcomes were expressed as quality-adjusted life-years (QALYs). Patient subgroups were defined post hoc on the basis of data collected in clinical trials: previous hospitalization, on maintenance oral corticosteroids, and three or more previous exacerbations. The incremental cost-effectiveness ratio varied from £30,109 to £57,557 per QALY gained depending on the population considered using the PAS price; incremental cost-effectiveness ratios were over a third higher using the list price. Omalizumab is likely to be cost-effective at the threshold of £30,000 per QALY gained in the severe subgroups if the improvement in health-related quality of life from omalizumab is mapped from an asthma-specific measure to the EuroQol five-dimensional questionnaire (vs. the EuroQol five-dimensional questionnaire directly collected from patients) or asthma mortality refers to death after hospitalization from asthma (vs. asthma-mortality risk in the community). Although the cost-effectiveness of omalizumab is more favorable under the PAS price, it represents good value for money only in severe subgroups and under optimistic assumptions regarding asthma mortality and improvement in health-related quality of life. For these reasons, omalizumab should be carefully targeted to ensure value for money. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. The link between allergic rhinitis and allergic asthma

    DEFF Research Database (Denmark)

    Linneberg, A; Henrik Nielsen, N; Frølund, L

    2002-01-01

    BACKGROUND: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. METHODS: Participants in a population-based study of 15-69-year-olds in 1990 were ...

  2. Effects of Omalizumab Treatment on Some Biomarkers in Severe Allergic Asthma Patients

    Directory of Open Access Journals (Sweden)

    Seda Tural Önür

    2017-08-01

    Full Text Available Objective: The mechanism of biological treatment molecule called omalizumab used in asthma treatment is thought to be versatile; however, the mechanism still remains unknown. This study was undertaken in severe asthma patients underwent omalizumab treatment, in order to investigate the relationship between biomarker expression and disease characteristics related to the immune system. Methods: Consecutive patients with severe asthma disease (n=15; Group IA, pretreatment and Group IB, post-treatment underwent omalizumab treatment. Control group was age- and sex-matched including 25 healthy in Group II. Blood samples from both the groups were taken during their first visit (Group IA and II and then after 12 months of treatment in asthmatic patients (Group IB. Serum levels of homocysteine (Hcy, eosinophil cationic peptide (ECP, 25-hydroxyvitamin D (25(OHD, interleukin-1β (IL-1β, soluble OX2 (sCD200 and clinical follow-up tests including fractional exhaled nitric oxide (FeNO, asthma control test (ACT, and pulmonary function tests were evaluated. Results: After the treatment, 25(OHD levels and pulmonary function tests, including forced expiratory volume in 1 second (FEV1 and forced vital capacity (FVC levels, were significantly increased. Furthermore, total immunoglobulin E (IgE, Hcy, ECP, FeNO, and sCD200 levels were dramatically diminished. Regression analysis revealed positive correlations between ACT-FEV1 and ACT- FVC and between FeNO-age and FeNO-ECP for Group IA patients. Negative correlations were detected between ACT-IgE, age-FEV1, FeNO-FEV1, and FeNO-FVC for Group IA patients. Conclusion: Our results suggest that the potential use of serum biomolecules in concordance to the clinical status of the asthmatic patients might be a follow-up tool for the omalizumab therapy.

  3. Tartrazine exclusion for allergic asthma.

    Science.gov (United States)

    Ardern, K D; Ram, F S

    2001-01-01

    Tartrazine is the best known and one of the most commonly used food additives. Food colorants are also used in many medications as well as foods. There has been conflicting evidence as to whether tartrazine causes exacerbations of asthma with some studies finding a positive association especially in individuals with cross-sensitivity to aspirin. To assess the overall effect of tartrazine (exclusion or challenge) in the management of asthma. A search was carried out using the Cochrane Airways Group specialised register. Bibliographies of each RCT was searched for additional papers. Authors of identified RCTs were contacted for further information for their trials and details of other studies. RCTs of oral administration of tartrazine (as a challenge) versus placebo or dietary avoidance of tartrazine versus normal diet were considered. Studies which focused upon allergic asthma, were also included. Studies of tartrazine exclusion for other allergic conditions such as hay fever, allergic rhinitis and eczema were only considered if the results for subjects with asthma were separately identified. Trials could be in either adults or children with asthma or allergic asthma (e.g. sensitivity to aspirin or food items known to contain tartrazine). Study quality was assessed and data abstracted by two reviewers independently. Outcomes were analysed using RevMan 4.1.1. Ninety abstracts were found, of which 18 were potentially relevant. Six met the inclusion criteria, but only three presented results in a format that permitted analysis and none could be combined in a meta-analysis. In none of the studies did tartrazine challenge or avoidance in diet significantly alter asthma outcomes. Due to the paucity of available evidence, it is not possible to provide firm conclusions as to the effects of tartrazine on asthma control. However, the six RCTs that could be included in this review all arrived at the same conclusion. Routine tartrazine exclusion may not benefit most patients

  4. The real world effect of omalizumab add on therapy for patients with moderate to severe allergic asthma: The ASTERIX Observational study.

    Science.gov (United States)

    Bhutani, Mohit; Yang, William H; Hébert, Jacques; de Takacsy, Frederica; Stril, Jean-Louis

    2017-01-01

    Omalizumab is a non-steroidal medication indicated for the treatment of poorly controlled moderate-to-severe allergic asthmatics. This observational study examines the "real world" effectiveness of omalizumab in this population. This is a one year open-label observational study that compared clinical outcomes including total oral corticosteroid use, exacerbation history, measures of quality of life and inflammation in patients with moderate-to-severe allergic asthma, who were prescribed omalizumab as part of their treatment with the year prior to therapy. A total of 99 patients were enrolled at 25 sites in Canada. During the study period, the mean total annual OCS dose was reduced from 2301.5 mg (prednisone equivalents) in the year prior to omalizumab to 1130.0 mg (pomalizumab remained exacerbation free when compared to the year prior to study entry. Associated with this was reduced health care utilization. There were significant improvements in the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life questionnaire (AQLQ) Patients with an elevated FeNO at baseline showed a better response to treatment. No new safety issues were identified during the study period. Our study demonstrates that in "real world" clinical practice, after initiating omalizumab, there is a reduction in total OCS use and exacerbation frequency in patients with moderate-to-severe allergic asthma. Patients on treatment reported improved asthma control and quality of life. FeNO may be a useful biomarker to identify patients who may benefit with omalizumab treatment.

  5. The real world effect of omalizumab add on therapy for patients with moderate to severe allergic asthma: The ASTERIX Observational study.

    Directory of Open Access Journals (Sweden)

    Mohit Bhutani

    Full Text Available Omalizumab is a non-steroidal medication indicated for the treatment of poorly controlled moderate-to-severe allergic asthmatics. This observational study examines the "real world" effectiveness of omalizumab in this population.This is a one year open-label observational study that compared clinical outcomes including total oral corticosteroid use, exacerbation history, measures of quality of life and inflammation in patients with moderate-to-severe allergic asthma, who were prescribed omalizumab as part of their treatment with the year prior to therapy.A total of 99 patients were enrolled at 25 sites in Canada. During the study period, the mean total annual OCS dose was reduced from 2301.5 mg (prednisone equivalents in the year prior to omalizumab to 1130.0 mg (p<0.0001. There was a 71% reduction in asthma exacerbations and 56% of patients on omalizumab remained exacerbation free when compared to the year prior to study entry. Associated with this was reduced health care utilization. There were significant improvements in the Asthma Control Questionnaire (ACQ and Asthma Quality of Life questionnaire (AQLQ Patients with an elevated FeNO at baseline showed a better response to treatment. No new safety issues were identified during the study period.Our study demonstrates that in "real world" clinical practice, after initiating omalizumab, there is a reduction in total OCS use and exacerbation frequency in patients with moderate-to-severe allergic asthma. Patients on treatment reported improved asthma control and quality of life. FeNO may be a useful biomarker to identify patients who may benefit with omalizumab treatment.

  6. Predictors of response to therapy with omalizumab in patients with severe allergic asthma - a real life study.

    Science.gov (United States)

    Kallieri, Maria; Papaioannou, Andriana I; Papathanasiou, Evgenia; Ntontsi, Polyxeni; Papiris, Spyridon; Loukides, Stelios

    2017-08-01

    Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician's global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders. Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV 1 and FEV 1 /FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV 1 (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709). Lower baseline FEV 1 and higher IL-13 levels in induced sputum supernatant were predictors of response

  7. B-Glucan exacerbates allergic asthma independent of fungal ...

    Science.gov (United States)

    BackgroundAllergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity.ObjectiveWe sought to determine the mechanism by which fungi affect asthma development and severity.MethodsWe integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity.ResultsWe report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc−/− mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity.ConclusionOur data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. To describe th

  8. The influence of sublingual immunotherapy on several parameters of immunological response in children suffering from atopic asthma and allergic rhinitis depending on asthma features.

    Science.gov (United States)

    Ciepiela, Olga; Zawadzka-Krajewska, Anna; Kotuła, Iwona; Demkow, Urszula

    2014-01-01

    The clinical efficacy of sublingual immunotherapy (SLIT) has already been proven and is known to be high. Its influence on the immunological system of patients suffering from bronchial asthma was also examined. However, it is still unclear how the polysensitisation, coexistence of other atopic disease and asthma treatment step influence the response to treatment with specific immunotherapy. Herein we evaluate the impact of one-year SLIT on selected markers of immunological response depending on different individual and clinical factors of children suffering from atopic asthma and allergic rhinitis. Twenty-five patients aged 8.1 ± 3.1 years (range 5-15 years), 21 boys and 4 girls, suffering from asthma and allergic rhinitis with polysensitisation to seasonal and non-seasonal allergens, shortlisted for SLIT, were included in the study. Th1 cell and Th2 cell percentages, Bcl-2 expression in T cells, and basophil activation after allergen challenge (house dust mite and/or grass pollen antigen in solution used for skin prick tests) in peripheral blood were measured using flow cytometry. The association between clinical features of asthma and the influence of SLIT on immunological parameters was evaluated with exact Fisher test. No association between the influence of one-year sublingual immunotherapy on immunological system and patients' age, polysensitisation, asthma treatment step, or coexistence of any other atopic diseases was observed. However, an increase of the Th1 percentage in children sensitised against more than three allergens was found more often (at the limit of statistical significance) than in the group of children sensitised against three or less allergens. Based on our results, we cannot point to any subgroup isolated in the study, in which the response of the immunological system to sublingual immunotherapy is more satisfactory than any other. Nevertheless, the increase of Th1 cells may be more specific for polysensitised children.

  9. Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

    Science.gov (United States)

    Suzuki, Cibele; Lopes da Silva, Nilceia; Kumar, Praveen; Pathak, Purnima; Ong, Siew Hwa

    2017-08-01

    Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross

  10. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    International Nuclear Information System (INIS)

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2012-01-01

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  11. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Brent C. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); Constant, Stephanie L. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Patierno, Steven R. [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); GW Cancer Institute, The George Washington University, Washington, DC 20037 (United States); Jurjus, Rosalyn A. [Department of Anatomy and Regenerative Biology, The George Washington University, Washington, DC 20037 (United States); Ceryak, Susan M., E-mail: phmsmc@gwumc.edu [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States)

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  12. Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

    Science.gov (United States)

    Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

    2018-04-19

    Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

  13. [Epigenetics in allergic diseases and asthma].

    Science.gov (United States)

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Genetics Home Reference: allergic asthma

    Science.gov (United States)

    ... links) Health Topic: Allergy Health Topic: Asthma Health Topic: Asthma in Children Additional NIH Resources (1 link) National Heart, Lung, and Blood Institute Educational Resources (12 links) American Academy of Allergy Asthma and Immunology: Allergies Asthma and Allergy Foundation of America: What ...

  15. Allergy in severe asthma

    NARCIS (Netherlands)

    Del Giacco, Stefano R.; Bakirtas, A.; Bel, E.; Custovic, A.; Diamant, Z.; Hamelmann, E.; Heffler, E.; Kalayci, O.; Saglani, S.; Sergejeva, S.; Seys, S.; Simpson, A.; Bjermer, Leif

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps

  16. Co-morbidities in severe asthma

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste; Menzies-Gow, Andrew

    2017-01-01

    Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma...... to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical...... impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD...

  17. Impact of omalizumab on treatment of severe allergic asthma in UK clinical practice: a UK multicentre observational study (the APEX II study).

    Science.gov (United States)

    Niven, Robert M; Saralaya, Dinesh; Chaudhuri, Rekha; Masoli, Matthew; Clifton, Ian; Mansur, Adel H; Hacking, Victoria; McLain-Smith, Susan; Menzies-Gow, Andrew

    2016-08-09

    To describe the impact of omalizumab on asthma management in patients treated as part of normal clinical practice in the UK National Health Service (NHS). A non-interventional, mixed methodology study, combining retrospective and prospective data collection for 12 months pre-omalizumab and post-omalizumab initiation, respectively. Data were collected in 22 UK NHS centres, including specialist centres and district general hospitals in the UK. 258 adult patients (aged ≥16 years; 65% women) with severe persistent allergic asthma treated with omalizumab were recruited, of whom 218 (84.5%) completed the study. The primary outcome measure was change in mean daily dose of oral corticosteroids (OCS) between the 12-month pre-omalizumab and post-omalizumab initiation periods. A priori secondary outcome measures included response to treatment, changes in OCS dosing, asthma exacerbations, lung function, employment/education, patient-reported outcomes and hospital resource utilisation. The response rate to omalizumab at 16 weeks was 82.4%. Comparing pre-omalizumab and post-omalizumab periods, the mean (95% CIs) daily dose of OCS decreased by 1.61 (-2.41 to -0.80) mg/patient/day (pomalizumab period. The mean number of A&E visits, inpatient hospitalisations, outpatient visits (excluding for omalizumab) and number of bed days/patient decreased significantly (pomalizumab period. These data support the beneficial effects of omalizumab on asthma-related outcomes, quality of life and resource utilisation in unselected patients treated in 'real-world' clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  18. Severe chronic allergic (and related) diseases

    DEFF Research Database (Denmark)

    Bousquet, J; Anto, J M; Demoly, P

    2012-01-01

    -up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic...... and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness...... and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies....

  19. Omalizumab for severe allergic asthma in clinical trials and real-life studies: what we know and what we should address.

    Science.gov (United States)

    Caminati, Marco; Senna, Gianenrico; Guerriero, Massimo; Dama, Anna Rita; Chieco-Bianchi, Fulvia; Stefanizzi, Giorgia; Montagni, Marcello; Ridolo, Erminia

    2015-04-01

    Randomized clinical trials (RCTs) are the gold standard for the assessment of any therapeutic intervention. Real-life (R-L) studies are needed to verify the provided results beyond the experimental setting. This review aims at comparing RCTs and R-L studies on omalizumab in adult severe allergic asthma, in order to highlight the concurring results and the discordant/missing data. The results of a selective literature research, including "omalizumab, controlled studies, randomized trial, real-life studies" as key words are discussed. Though some similarities between RCTs and R-L studies strengthen omalizumab efficacy and safety outcomes, significant differences concerning study population features, follow-up duration, local adverse events and drop-out rate for treatment inefficacy emerge between the two study categories. Furthermore the comparative analysis between RCTs and R-L studies highlights the need for further research, concerning in particular long-term effects of omalizumab and its impact on asthma comorbidities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

    Science.gov (United States)

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2011-01-01

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

  1. Breastfeeding, Childhood Asthma, and Allergic Disease.

    Science.gov (United States)

    Oddy, Wendy H

    2017-01-01

    The worldwide prevalence of childhood asthma has been increasing considerably, and the protection afforded by breastfeeding in its development has been the subject of controversy for more than 80 years. Previous systematic reviews have generally found a protective effect of breastfeeding on allergic outcomes, although many studies have methodological limitations. Although breastfeeding is protective against lower respiratory tract infection during infancy, such protection has not been demonstrated for asthma in all studies. Breastfeeding has health benefits for the mother and child. Exclusive breastfeeding for the first 6 months of an infant's life, with continued breastfeeding for up to 2 years or longer, is recognized as the "gold" standard for infant feeding because human milk is uniquely suited to the human infant, and its nutritional content and bioactivity promote a healthy development. There is increasing concern that the practice of delaying complementary foods until 6 months may exacerbate the risk of allergic disease. Breast milk contains immunological components that protect against infections and allergic disease in infancy. The composition of human breast milk is complex, containing factors that interact with the infant immune system and intestinal milieu including allergens, cytokines, immunoglobulins, polyunsaturated fatty acids, and chemokines. Transforming growth factor β is a cytokine in human milk involved in maintaining intestinal homeostasis, inflammation regulation, and oral tolerance development. Modern day society, with increased standards of hygiene, has changed the gut flora of Western infants, potentially impacting the risk of developing immune-mediated diseases including allergic disease and asthma. Microbial diversity is intrinsic to healthy immune maturation and function. Compared to breastfed infants, formula-fed infants had lower bacterial diversity and an altered intestinal microbiota in the first few weeks of life associated with

  2. Determinants of allergic rhinitis in young children with asthma.

    Directory of Open Access Journals (Sweden)

    Lise Moussu

    Full Text Available BACKGROUND: In the preschool period, allergic rhinitis (AR is infrequent and thus under-diagnosed. However, recent works have highlighted the occurrence of AR in toddlers although the causes of AR in this young population remain unknown. The objective of this study was to identify determinants of AR in young children with asthma. METHODS: We carried out a case-control study of 227 children with active asthma and enrolled in the Trousseau Asthma Program. AR and other allergic diseases (asthma, food allergy and eczema were diagnosed by medical doctors using standardized questionnaires. Parental history of AR and asthma, biological markers of atopy (total IgE, blood eosinophilia, allergic sensitization towards food and aeroallergens and environmental parameters were also collected. RESULTS: Forty one of the children (18.1% had AR. By univariate logistic regression analysis, AR was mainly associated with peanut sensitization (OR = 6.75; p = 0.002; food allergy (OR = 4.31; p = 0.026; mold exposure (OR = 3.81 p<0.01 and parental history of AR (OR = 1.42; p = 0.046. Due to the strong link between food allergy and peanut sensitization three models of multivariate logistic regression were performed and confirmed that AR is associated with peanut sensitization but also food allergy and mold exposure. A random forest analysis was also performed to explain AR. The results reinforced the logistic analysis that peanut sensitization and mold exposure were the principal determinants of AR. CONCLUSIONS & CLINICAL RELEVANCE: These results stress the importance of investigating AR in young children with asthma to potentially diagnose a particularly severe allergic asthmatic phenotype. Moreover, these data evoke the hypothesis that peanut could be an aeroallergen.

  3. Allergic asthma biomarkers using systems approaches

    Directory of Open Access Journals (Sweden)

    Gaurab eSircar

    2014-01-01

    Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

  4. Therapeutic interventions in severe asthma.

    Science.gov (United States)

    Canonica, Giorgio Walter; Senna, Gianenrico; Mitchell, Patrick D; O'Byrne, Paul M; Passalacqua, Giovanni; Varricchi, Gilda

    2016-01-01

    The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy. Omalizumab, an anti-IgE antibody, has been the only biologic treatment available on the market for severe asthma during the last decade. It prevents the linkage of the IgE and the receptors, thereby inhibiting mast cell degranulation. In clinical practice omalizumab significantly reduced the asthma exacerbations as well as the concomitant use of oral glucocorticoids. In the "Th2-high asthma" phenotype, the hallmarks are increased levels of eosinophils and other markers (such as periostin). Because anti-IL-5 in this condition plays a crucial role in driving eosinophil inflammation, this cytokine or its receptors on the eosinophil surface has been studied as a potential target for therapy. Two different anti-IL-5 humanized monoclonal antibodies, mepolizumab and reslizumab, have been proven effective in this phenotype of asthma (recently they both came on the market in the United States), as well as an anti-IL-5 receptor alpha (IL5Rα), benralizumab. Other monoclonal antibodies, targeting different cytokines (IL-13, IL-4, IL-17 and TSLP) are still under evaluation, though the preliminary results are encouraging. Finally, AIT, Allergen Immunotherapy, a prototype of Precision Medicine, is considered, also in light of the recent evidences of Sublingual Immunotherapy (SLIT) tablet efficacy and safety in mite allergic asthma patients. Given the high costs of these therapies

  5. Severe asthma in childhood

    International Nuclear Information System (INIS)

    Ciznar, P.

    2013-01-01

    Patients with severe asthma are clinically, physiologically and biologically a heterogeneous group. About half of children referred for medical examination for severe asthma have true severe, therapy resistant asthma. The rest of referred patients have difficult to treat asthma. Symptoms persist mostly due to drug non-compliance, inappropriate inhalation technique, persistent environmental exposures or co-morbid conditions. Compared with adults have children more frequently atopic form of severe asthma. This is associated with eosinophilia in peripheral blood and sensitization to inhaled allergens. The IgE levels are high. Therapy of co-morbidities and improvement of treatment compliance lead in most cases to full asthma control. Proportion of children will benefit from biologics like anti-IgE monoclonal antibody, administered by subcutaneous injections in 2 to 4 week intervals. By this therapy it is not only possible to suppress symptoms, but also decrease the total steroid dose and the risk of adverse effects associated with its long-term administration. By achieving a full asthma control we lower future risk of exacerbations and probably improve long-term prognosis of disease, frequently persisting for the rest of life. (author)

  6. Risk factors associated with allergic and non-allergic asthma in adolescents.

    Science.gov (United States)

    Janson, Christer; Kalm-Stephens, Pia; Foucard, Tony; Alving, Kjell; Nordvall, S Lennart

    2007-07-01

    Risk factors for asthma have been investigated in a large number of studies in adults and children, with little progress in the primary and secondary prevention of asthma. The aim of this investigation was to investigate risk factors associated with allergic and non-allergic asthma in adolescents. In this study, 959 schoolchildren (13-14 years old) answered a questionnaire and performed exhaled nitric oxide (NO) measurements. All children (n = 238) with reported asthma, asthma-related symptoms and/or increased NO levels were invited to a clinical follow-up which included a physician evaluation and skin-prick testing. Asthma was diagnosed in 96 adolescents, whereof half had allergic and half non-allergic asthma. Children with both allergic and non-allergic asthma had a significantly higher body mass index (BMI) (20.8 and 20.7 vs. 19.8 kg/m(2)) (p < 0.05) and a higher prevalence of parental asthma (30% and 32% vs. 16%) (p < 0.05). Early-life infection (otitis and croup) [adjusted odds ratio (OR) (95% confidence interval (CI)): 1.99 (1.02-3.88) and 2.80 (1.44-5.42), respectively], pets during the first year of life [2.17 (1.16-4.04)], window pane condensation [2.45 (1.11-5.40)] and unsatisfactory school cleaning [(2.50 (1.28-4.89)] was associated with non-allergic but not with allergic asthma. This study indicates the importance of distinguishing between subtypes of asthma when assessing the effect of different risk factors. While the risk of both allergic and non-allergic asthma increased with increasing BMI, associations between early-life and current environmental exposure were primarily found in relation to non-allergic asthma.

  7. Advances and Evolving Concepts in Allergic Asthma.

    Science.gov (United States)

    Tung, Hui-Ying; Li, Evan; Landers, Cameron; Nguyen, An; Kheradmand, Farrah; Knight, J Morgan; Corry, David B

    2018-02-01

    Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis. Phthalates, another common class of chemical pollutant found in the built environment, are emerging as potentially important mediators or attenuators of asthma. Other biological products such as endotoxin have also been confirmed to be protective in both the indoor and outdoor contexts. Proasthmatic factors are believed to activate, and in some instances initiate, pathologic inflammatory cascades through complex interactions with pattern recognition receptors (PRRs) expressed on many cell types, but especially airway epithelial cells. PRRs initiate the release of proallergic cytokines such as interleukin (IL)-33, IL-25, and others that coordinate activation of innate lymphoid cells type 2 (ILC2), T helper type 2 cells, and immunoglobulin E-secreting B cells that together promote additional inflammation and the major airway remodeling events (airway hyperresponsiveness, mucus hypersecretion) that promote airway obstruction. Proteinases, with airway fungi and viruses being potentially important sources, are emerging as critically important initiators of these inflammatory cascades in part through their effects on clotting

  8. Asthma and Allergic Diseases in Pregnancy: A Review

    OpenAIRE

    Pali-Sch?ll, Isabella; Motala, Cassim; Jensen-Jarolim, Erika

    2009-01-01

    Asthma and allergic disorders can affect the course and outcome of pregnancy. Pregnancy itself may also affect the course of asthma and related diseases. Optimal management of these disorders during pregnancy is vital to ensure the welfare of the mother and the baby. Specific pharmacological agents for treatment of asthma or allergic diseases must be cautiously selected and are discussed here with respect to safety considerations in pregnancy. Although most drugs do not harm the fetus, this k...

  9. SEVERE CHRONIC ALLERGIC (AND RELATED DISEASES: A UNIFORM APPROACH — A MEDALL-GA2LEN-ARIA POSITION PAPER IN COLLABORATION WITH THE WHO COLLABORATING CENTER FOR ASTHMA AND RHINITIS (ENGLISH & RUSSIAN VARIANTS

    Directory of Open Access Journals (Sweden)

    J. Bousquet

    2011-01-01

    Full Text Available Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria, atopic dermatitis in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as co-morbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related diseases for clinical practice, research (including epidemiology, public health purposes, education and the discovery of novel therapies.Key words: IgE, allergy, severity, control, risk, asthma, rhinitis, rhinosinusitis, urticaria, atopic dermatitis.

  10. Asthma and allergic rhinitis in adoptees and their adoptive parents.

    Science.gov (United States)

    Smith, J M; Cadoret, R J; Burns, T L; Troughton, E P

    1998-08-01

    Since the highest risk for the development of atopic disease is in early life, environmental risk factors need to be separated from the genetic component in this high risk period. Adoptees removed at birth and placed in adoptive families present a way to separate environmental and genetic factors at this early susceptible age. An opportunity for a pilot study of asthma and allergic rhinitis in adoptive families was presented when a psychiatrist (RC) was planning a behavioral study of young adult adoptees and their adoptive parents. A detailed questionnaire about allergic rhinitis and asthma was added after the psychiatrists' interview. Placement was not influenced by a history of allergy in adoptive or natural parents. The adoptee and at least one adoptive parent completed questionnaires in 367 families. The adoptees had been removed at birth and placed in the adoptive family within 3 months (83% within 1 month). Compared with adoptive families without asthma or allergic rhinitis, an adoptive mother with asthma or rhinitis, when the adoptive father was not affected, increased the risk for asthma in the adoptee (OR = 3.2, P adoptive mother alone (OR = 3.2, P Adoptive father asthma or allergic rhinitis showed a trend toward increased asthma in the adoptee (OR = 1.9, P adoption by parents with asthma or allergic rhinitis suggests that further well planned adoptee studies should be made.

  11. Omalizumab in the management of patients with allergic (IgE-mediated asthma

    Directory of Open Access Journals (Sweden)

    Thomas Sandström

    2009-05-01

    Full Text Available Thomas SandströmDepartment of Respiratory Medicine and Allergy, University Hospital, Umeå, SwedenAbstract: Immunoglobulin E (IgE is central to the pathophysiology of allergic asthma. Omalizumab, an anti-IgE monoclonal antibody, binds to the FcεRI binding site on free IgE. As a result, circulating free IgE is reduced, IgE is prevented from attaching to mast cells and basophils, and FcεRI receptor expression is down-regulated. The inflammatory response to allergens and the acute and chronic effector phases of allergic inflammation are thereby attenuated. In clinical trials in adults and adolescents, omalizumab reduced asthma exacerbations, severe asthma exacerbations, inhaled corticosteroid requirements, and emergency visits, as well as significantly improving asthma-related quality of life, morning peak expiratory flow and asthma symptom scores in patients with severe allergic (IgE-mediated asthma. Results from clinical trials in children (< 12 years are consistent with those in the adult population. It is difficult to predict which patients will respond to omalizumab. Responders to omalizumab should be identified after a 16-week trial of therapy using the physician’s overall assessment. When treatment is targeted to these responders, omalizumab provides a cost-effective therapy for inadequately controlled severe allergic (IgE-mediated asthma. Long-term therapy with omalizumab shows the potential for disease-modification in asthma. Ongoing studies are also evaluating the use of omalizumab in other non-asthma IgE-mediated conditions.Keywords: omalizumab, IgE, allergic asthma

  12. Allergic rhinitis is associated with poor asthma control in children with asthma.

    Science.gov (United States)

    de Groot, Eric P; Nijkamp, Anke; Duiverman, Eric J; Brand, Paul L P

    2012-07-01

    Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence. To date, no study has examined the impact of comorbid allergic rhinitis on asthma control in children. To examine the prevalence of allergic rhinitis in children with asthma, and the impact of the disease and its treatment on asthma control. A cross-sectional survey in 203 children with asthma (5-18 years) using validated questionnaires on rhinitis symptoms (stuffy or runny nose outside a cold) and its treatment, and the paediatric Asthma Control Questionnaire (ACQ). Fraction of nitric oxide in exhaled air (FeNO) was measured with a Niox Mino analyser; total and specific IgE levels were assessed by the Immunocap system. 157 children (76.2%) had symptoms of allergic rhinitis but only 88 of these (56.1%) had been diagnosed with the condition by a physician. ACQ scores were worse in children with allergic rhinitis than in those without the condition (p=0.012). An ACQ score ≥ 1.0 (incomplete asthma control) was significantly more likely in children with allergic rhinitis than in those without (OR 2.74, 95% CI 1.28 to 5.91, p=0.0081), also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy, allergic rhinitis was no longer associated with incomplete asthma control (OR 0.72, 95% CI 0.47 to 1.12, p=0.150). Allergic rhinitis is common in children with asthma, and has a major impact on asthma control. The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children, but randomised clinical trials are needed to test this hypothesis.

  13. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma

    DEFF Research Database (Denmark)

    Virchow, Johann Christian; Backer, Vibeke; Kuna, Piotr

    2016-01-01

    moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events. RESULTS: Among 834 randomized...... in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13...... corticosteroid (ICS) reduction period. DESIGN, SETTINGS, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products...

  14. Current concepts of severe asthma

    Science.gov (United States)

    Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

    2016-01-01

    The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

  15. Targeting phosphoinositide 3-kinase δ for allergic asthma.

    Science.gov (United States)

    Rowan, Wendy C; Smith, Janet L; Affleck, Karen; Amour, Augustin

    2012-02-01

    Chronic inflammation in the lung has long been linked to the pathogenesis of asthma. Central to this airway inflammation is a T-cell response to allergens, with Th2 cytokines driving the differentiation, survival and function of the major inflammatory cells involved in the allergic cascade. PI3Kδ (phosphoinositide 3-kinase δ) is a lipid kinase, expressed predominantly in leucocytes, where it plays a critical role in immune receptor signalling. A selective PI3Kδ inhibitor is predicted to block T-cell activation in the lung, reducing the production of pro-inflammatory Th2 cytokines. PI3Kδ is also involved in B-cell and mast cell activation. Therefore the inhibition of PI3Kδ should dampen down the inflammatory cascade involved in the asthmatic response through a wide breadth of pharmacology. Current anti-inflammatory therapies, which are based on corticosteroids, are effective in controlling inflammation in mild asthmatics, but moderate/severe asthmatic patients remain poorly controlled, experiencing recurrent exacerbations. Corticosteroids have no effect on mast cell degranulation and do not act directly on B-cells, so, overall, a PI3Kδ inhibitor has the potential to deliver improvements in onset of action, efficacy and reduced exacerbations in moderate/severe asthmatics. Additionally, PI3Kδ inhibition is expected to block effects of Th17 cells, which are increasingly implicated in steroid-insensitive asthma.

  16. Allergic rhinitis and asthma: inflammation in a one-airway condition

    Directory of Open Access Journals (Sweden)

    Haahtela Tari

    2006-11-01

    Full Text Available Abstract Background Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. Discussion In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria. Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli. Structural alterations (that is, remodeling of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. Conclusion Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.

  17. Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma

    NARCIS (Netherlands)

    Hellings, P. W.; Vandekerckhove, P.; Claeys, R.; Billen, J.; Kasran, A.; Ceuppens, J. L.

    2003-01-01

    Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone. This study was aimed to explore the effect of exogenously administered

  18. [ARIA (Allergic Rhinitis and its Impact on Asthma). Achievements in 10 years and future needs in Latin America].

    Science.gov (United States)

    Baena-Cagnani, Carlos E; Sánchez-Borges, Mario; Zernotti, Mario E; Larenas-Linnemann, Désireé; Cruz, Alvaro A; González-Díaz, Sandra N; Ivancevich, Juan C; Aldrey-Palacios, Oscar; Sisul, Juan C; Solé, Dirceu; Cepeda, Alfonso M; Jares, Edgardo J; Calvo Gil, Mario; Valentin-Rostán, Marylin; Yáñez, Anahí; Gereda, José; Cardona-Villa, Ricardo; Rosario, Nelson; Croce, Víctor H; Bachert, Claus; Canonica, G Walter; Demoly, Pascal; Passalacqua, Giovanni; Samolinski, Boleslaw; Schünemann, Holger J; Yorgancioglu, Arzu; Ansotegui, Ignacio J; Khaltaev, Nikolai; Bedbrook, Anna; Zuberbier, Torsten; Bousquet, Jean

    2013-01-01

    Allergic rhinitis and asthma represent global problems of public health affecting all age groups; asthma and allergic rhinitis frequently coexist in the same patients. In Latin American prevalence of allergic rhinitis, although variable, is very high. Allergic rhinitis and its Impact on Asthma (ARIA) started during a workshop of the World Health Organization performed in 1999 and was published in 2001. ARIA proposed a new classification of allergic rhinitis in intermittent or persistent and mild or moderate-severe. This approach of classification reflects more nearly the impact of allergic rhinitis in patients. In its review of 2010 ARIA developed guidelines for diagnosis and treatment of allergic rhinitis and of clinical practices for management of comorbidities of allergic rhinitis and asthma based on GRADE (Grading of Recommendations, Development and Evaluation). ARIA has been spread and implemented in more than 50 countries. In Latin American an intense activity has been developed to spread these recommendations in almost all the countries of the region and it is important to record the obtained goals in the diffusion and implementation of ARIA, as well as to identify the unsatisfied needs from the clinical, research and implementation points of view. Final objective is to reinforce the priority that allergy and asthma should have, especially in children, in the programs of public health, as they have been prioritized in European Union in 2011.

  19. A Population-based Clinical Study of Allergic and Non-allergic Asthma

    DEFF Research Database (Denmark)

    Knudsen, T.B.; Thomsen, S.F.; Nolte, H.

    2009-01-01

    Background. The aim of this study was to describe differences between allergic and non-allergic asthma in a large community-based sample of Danish adolescents and adults. Methods. A total of 1,186 subjects, 14 to 44 years of age, who in a screening questionnaire had reported a history of airway...... symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms, and furthermore skin test reactivity, lung function, and airway responsiveness were measured. Results. A total of 489...

  20. Prevalence of asthma, allergic rhinitis and dermatitis in primary ...

    African Journals Online (AJOL)

    Objective: to establish the relative increase in the prevalence of asthma, allergic rhinitis and eczema in primary school children aged 13-14 years over a six year interval. Design: Cross sectional comparative study. Setting: Primary schools in three rural divisions at Uasin Gishu district in the Rift Valley Province of Kenya.

  1. December 2004 45 Bronchial Asthma, Allergic Rhinitis and chole

    African Journals Online (AJOL)

    user

    2004-12-02

    Dec 2, 2004 ... Background: Gallbladder has not been associated with any allergic condition what so ever. However, certain patients with bronchial asthma and cholelithiasis have reported to the author improvement in their asthmatic attack after cholecystectomy. Methods: This was an observational study on 22 bronchial ...

  2. Allergen immunotherapy for allergic asthma: Protocol for a systematic review

    NARCIS (Netherlands)

    Dhami, S. (Sangeeta); Nurmatov, U. (Ulugbek); I. Agache; S. Lau (Susanne); Muraro, A. (Antonella); M. Jutel (M.); G. Roberts; C.A. Akdis; M. Bonini (Matteo); M. Calderon (Moises); T.B. Casale (Thomas); Cavkaytar, O. (Ozlem); L. Cox (Linda); P. Demoly; Flood, B. (Breda); Hamelmann, E. (Eckard); Izuhara, K. (Kenji); O. Kalayci; J. Kleine-Tebbe (Jörg); A. Nieto (Antonio); N. Papadopoulos; O. Pfaar (Oliver); L. Rosenwasser (Lanny); D. Ryan (Dermot); C.B. Schmidt-Weber; S.J. Szefler; U. Wahn (Ulrich); R. Gerth van Wijk (Roy); Wilkinson, J. (Jamie); A. Sheikh (Aziz)

    2016-01-01

    textabstractBackground: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of

  3. Examining the unmet need in adults with severe asthma

    Directory of Open Access Journals (Sweden)

    M. R. Partridge

    2007-09-01

    Full Text Available Asthma currently affects an estimated 300 million people worldwide and the number is expected to rise to 400 million by 2025. Asthma morbidity remains high and the economic burden is significant. Approximately 20% of patients have severe persistent asthma. As patients with severe asthma often have a variety of conditions that may coexist with or be mistaken for asthma, careful diagnosis and management are essential, and adhering to a protocol for investigations is helpful. For patients with severe persistent asthma, the Global Initiative for Asthma 2005 guidelines recommend the use of high-dose inhaled corticosteroids in combination with a long-acting beta2-agonist, with one or more additional controller medications if required (step 4 therapy. However, recent studies have shown that asthma remains inadequately controlled in many patients with severe asthma, despite treatment in accordance with guidelines. Patients with severe asthma have the highest healthcare utilisation and mortality, and there is clearly an unmet need for the effective and safe treatment of patients with severe persistent allergic asthma who remain symptomatic despite optimised standard treatment. The latest guidelines suggest that omalizumab may address this unmet need.

  4. Allergic rhinitis, atopic dermatitis, and asthma are associated with differences in school performance among Korean adolescents.

    Science.gov (United States)

    Kim, So Young; Kim, Min-Su; Park, Bumjung; Kim, Jin-Hwan; Choi, Hyo Geun

    2017-01-01

    Several studies have reported negative relations between allergic diseases and school performance but have not simultaneously considered various allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, and only examined a limited number of participants. The present study investigated the associations of allergic rhinitis, asthma, and atopic dermatitis with school performance in a large, representative Korean adolescent population. A total of 299,695 7th through 12th grade students participated in the Korea Youth Risk Behaviour Web-based Survey (KYRBWS) from 2009 to 2013. The subjects' history of allergic rhinitis, asthma, and atopic dermatitis and number of school absences due to these diseases in the previous 12 months were examined and compared. School performance was classified into 5 levels. The relations between allergic disorders and school performance were analyzed using multiple logistic regressions with complex sampling and adjusted for the subjects' durations of sleep, days of physical activity, body mass indexes (BMIs), regions of residence, economic levels, parents' education levels, stress levels, smoking status, and alcohol use. A subgroup analysis of the economic groups was performed. Allergic rhinitis was positively correlated with better school performance in a dose-dependent manner (adjusted odds ratios, AOR, [95% confidence interval, CI] = 1.50 [1.43-1.56 > 1.33 [1.28-1.38] > 1.17 [1.13-1.22] > 1.09 [1.05-1.14] for grades A > B > C > D; P school performance (AOR [95% CI] = 0.74 [0.66-0.83], 0.87 [0.79-0.96], 0.83 [0.75-0.91], 0.93 [0.85-1.02] for performance A, B, C, and D, respectively; P school performance. The subgroup analysis of the students' economic levels revealed associations between allergic diseases and school performance. Compared to other allergic disorders, the asthma group had more school absences due to their symptoms (P School performance was positively correlated with allergic rhinitis and negatively

  5. The allergic march

    African Journals Online (AJOL)

    allergic rhinitis (Fig. 1). Several studies have demonstrated the allergic march from atopic ... Boys appear to be at greater risk of developing the typical progression of allergic .... childhood asthma: lessons from the German. Multicentre Study ...

  6. Secular trends of allergic asthma in Danish adults. The Copenhagen Allergy Study

    DEFF Research Database (Denmark)

    Linneberg, A; Nielsen, N H; Madsen, F

    2001-01-01

    Numerous studies have reported increases in asthma prevalence among children world-wide. Less is known about similar trends in adults. We aimed to investigate whether the prevalence of allergic asthma symptoms had increased in an adult general population. Two cross-sectional surveys using identical......, the prevalence of allergic asthma symptoms increased significantly in this adult general population over a 9-year period....

  7. The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Chia-Rui Shen

    2015-11-01

    Full Text Available Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.

  8. Asthma Is More Severe in Older Adults

    Science.gov (United States)

    Dweik, Raed A.; Comhair, Suzy A.; Bleecker, Eugene R.; Moore, Wendy C.; Peters, Stephen P.; Busse, William W.; Jarjour, Nizar N.; Calhoun, William J.; Castro, Mario; Chung, K. Fan; Fitzpatrick, Anne; Israel, Elliot; Teague, W. Gerald; Wenzel, Sally E.; Love, Thomas E.; Gaston, Benjamin M.

    2015-01-01

    Background Severe asthma occurs more often in older adult patients. We hypothesized that the greater risk for severe asthma in older individuals is due to aging, and is independent of asthma duration. Methods This is a cross-sectional study of prospectively collected data from adult participants (N=1130; 454 with severe asthma) enrolled from 2002 – 2011 in the Severe Asthma Research Program. Results The association between age and the probability of severe asthma, which was performed by applying a Locally Weighted Scatterplot Smoother, revealed an inflection point at age 45 for risk of severe asthma. The probability of severe asthma increased with each year of life until 45 years and thereafter increased at a much slower rate. Asthma duration also increased the probability of severe asthma but had less effect than aging. After adjustment for most comorbidities of aging and for asthma duration using logistic regression, asthmatics older than 45 maintained the greater probability of severe asthma [OR: 2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma continued to increase in men, but not in women. Conclusions Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma. PMID:26200463

  9. [Allergic asthma and interleukins 2, 4, 5, 6 and 12 and gamma interferon levels].

    Science.gov (United States)

    Bastida Segura, Diana Lyzbeth; López Velásquez, Benjamin; Castrejón Vázquez, María Isabel; Galicia Tapía, Jorge; Cano Altamirano, Silvia; Miranda Feria, Alfonso Javier

    2004-01-01

    Asthma is an inflammatory chronic illness, in which mastocyt cells, basophils, T lymphocytes, eosinophils and cytokines play a role. Its association with the production of TH2 cytokines is not well known, but it is considered an aberrant immune response, yielding the activation and recruitment of a number of effector cells (mastocyts/eosinophils) and the appearance of clinical symptoms. To determine the serum values of the interleukins 2, 4, 5, 6 and 12 and gamma interferon in relation to the severity degree of asthma and the time of immunotherapy in patients with stable chronic allergic bronchial asthma. Clinical records of allergic asthmatic patients from the external consultation at Servicio de Alergia e Immunología Clínica were reviewed in a period of 12 months (1st January 2002 to 1st January 2003) and those of healthy volunteers, forming three groups: Group 1, allergic asthmatics with immunotherapy less than 24 months; Group 2, allergic asthmatics with more than 24 months of immunotherapy, and Group 3, healthy volunteers (control group). Previous informed consent, a serum sample was taken of all subjects. Ninety-two subjects were included: 41 (45%) allergic asthmatics and 51 (55%) healthy volunteers. Significant differences were found in interleukins 2, 4, 5, 6 and 12 levels between healthy volunteers and asthmatics without relating the immunotherapy time. In the total group gamma interferon levels were not found. A relation of interleukins Th2 levels with the severity degree of asthma was not found. Differences of serum interleukins Th1 and Th2 in allergic patients related to immunotherapy time were not significant; even though, irrespective of immunotherapy time, IgG levels were always high. Patients with allergic asthma have a predominance of serum interleukins Th2 and, despite of the immunotherapy, in the maintaining phase, these continue high, which may be due to an immune system dysregulation maybe including other factors. Immunotherapy continues

  10. Estrogen signaling modulates allergic inflammation and contributes to sex differences in asthma.

    Directory of Open Access Journals (Sweden)

    Aleksander eKeselman

    2015-11-01

    Full Text Available Asthma is a chronic airway inflammatory disease that afflicts approximately 300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or hard-to-treat asthma. Puberty, menstruation, pregnancy, menopause, and oral contraceptives are known to contribute to disease outcome in women, potentially suggesting a role for estrogen and other hormones impacting allergic inflammation. Currently, the mechanisms underlying these sex differences are poorly understood, although the effect of sex hormones, such as estrogen, on allergic inflammation is gaining interest. Asthma presents as a heterogeneous disease. In typical Th2-type allergic asthma, interleukin-4 and interleukin-13 predominate, driving IgE production and recruitment of eosinophils into the lungs. Chronic Th2-inflammation in the lung results in structural changes and activation of multiple immune cell types, leading to a deterioration of lung function over time. Most immune cells express estrogen receptors (ERα, ERβ, or the membrane-bound G-protein-coupled estrogen receptor to varying degrees and can respond to the hormone. Together these receptors have demonstrated the capacity to regulate a spectrum of immune functions, including adhesion, migration, survival, wound healing, and antibody and cytokine production. This review will cover the current understanding of estrogen signaling in allergic inflammation and discuss how this signaling may contribute to sex differences in asthma and allergy.

  11. Eicosapentaenoic Acid Enhances the Effects of Mesenchymal Stromal Cell Therapy in Experimental Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Soraia Carvalho Abreu

    2018-05-01

    Full Text Available Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited. We aimed to investigate whether pre-treatment with eicosapentaenoic acid (EPA potentiates the therapeutic properties of MSCs in experimental allergic asthma. Seventy-two C57BL/6 mice were used. House dust mite (HDM extract was intranasally administered to induce severe allergic asthma in mice. Unstimulated or EPA-stimulated MSCs were administered intratracheally 24 h after final HDM challenge. Lung mechanics, histology, protein levels of biomarkers, and cellularity in bronchoalveolar lavage fluid (BALF, thymus, lymph nodes, and bone marrow were analyzed. Furthermore, the effects of EPA on lipid body formation and secretion of resolvin-D1 (RvD1, prostaglandin E2 (PGE2, interleukin (IL-10, and transforming growth factor (TGF-β1 by MSCs were evaluated in vitro. EPA-stimulated MSCs, compared to unstimulated MSCs, yielded greater therapeutic effects by further reducing bronchoconstriction, alveolar collapse, total cell counts (in BALF, bone marrow, and lymph nodes, and collagen fiber content in airways, while increasing IL-10 levels in BALF and M2 macrophage counts in lungs. In conclusion, EPA potentiated MSC-based therapy in experimental allergic asthma, leading to increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β, modulation of macrophages toward an anti-inflammatory phenotype, and reduction in the remodeling process. Taken together, these modifications may explain the greater improvement in lung mechanics obtained. This may be a promising novel

  12. Iron supplementation decreases severity of allergic inflammation in murine lung.

    Directory of Open Access Journals (Sweden)

    Laura P Hale

    Full Text Available The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans.

  13. Mechanical ventilation for severe asthma.

    Science.gov (United States)

    Leatherman, James

    2015-06-01

    Acute exacerbations of asthma can lead to respiratory failure requiring ventilatory assistance. Noninvasive ventilation may prevent the need for endotracheal intubation in selected patients. For patients who are intubated and undergo mechanical ventilation, a strategy that prioritizes avoidance of ventilator-related complications over correction of hypercapnia was first proposed 30 years ago and has become the preferred approach. Excessive pulmonary hyperinflation is a major cause of hypotension and barotrauma. An appreciation of the key determinants of hyperinflation is essential to rational ventilator management. Standard therapy for patients with asthma undergoing mechanical ventilation consists of inhaled bronchodilators, corticosteroids, and drugs used to facilitate controlled hypoventilation. Nonconventional interventions such as heliox, general anesthesia, bronchoscopy, and extracorporeal life support have also been advocated for patients with fulminant asthma but are rarely necessary. Immediate mortality for patients who are mechanically ventilated for acute severe asthma is very low and is often associated with out-of-hospital cardiorespiratory arrest before intubation. However, patients who have been intubated for severe asthma are at increased risk for death from subsequent exacerbations and must be managed accordingly in the outpatient setting.

  14. Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma

    DEFF Research Database (Denmark)

    Maloney, J; Durham, S; Skoner, D

    2015-01-01

    BACKGROUND: Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with....../without conjunctivitis (AR/C), AE frequencies were determined in adults and children with and without reported asthma. METHODS: Data from randomized, double-blind, placebo-controlled trials of Timothy grass SLIT-tablet MK-7243 (2800 BAU/75 000 SQ-T, Merck/ALK-Abelló) were pooled for post hoc analyses. Subjects...... with asthma treated with grass SLIT-tablet versus subjects without asthma in or outside of pollen season. There were 6/120 asthma-related TRAEs assessed as severe with grass SLIT-tablet and 2/60 with placebo, without a consistent trend among subjects with and without asthma (5 and 3 events, respectively...

  15. Differential effect of omalizumab on pulmonary function in patients with allergic asthma with and without chronic rhinosinusitis.

    Science.gov (United States)

    Clavenna, Matthew J; Turner, Justin H; Samuelson, Madeleine; Tanner, S Bobo; Duncavage, James; Chandra, Rakesh K

    2016-01-01

    Omalizumab, an anti-immunoglobulin E monoclonal antibody, is approved by the U.S. Food and Drug Administration for the management of patients with allergic asthma and with refractory disease, and has also proven beneficial in the management of selected patients with chronic rhinosinusitis (CRS). The common airway model indicates that patients with both allergic asthma and CRS may be more challenging to manage clinically. This is the first study to evaluate the response of omalizumab in patients with asthma and CRS versus those with asthma alone. To compare pulmonary function test (PFT) responses in omalizumab-treated patients with asthma with CRS with omalizumab-treated patients with asthma without CRS. This was a retrospective case-control study at a tertiary university clinic. Between 2007 and 2014, a total of 259 patients with allergic asthma had been prescribed omalizumab for asthma. Outcome measures were absolute, and the percentage changes in PFT results were compared with the baseline. Overall, 81 patients had serial PFT results available for evaluation, among whom 59 (73%) had CRS. Average treatment duration was 27.2, 27.7, and 25.8 months for the entire sample, for patients with asthma and CRS, and for patients with asthma and without CRS, respectively. Overall, PFT metrics improved across all parameters (forced expiratory volume in 1 second, forced vital capacity, forced expiratory volume in 1 second to forced vital capacity ratio, and forced expiratory flow 25-75%). Significant improvement (p omalizumab manifested some improvement in PFT scores. CRS may add to the overall symptom burden experienced by patients with asthma, especially in those with increasing severity, but comorbid CRS did not adversely impact the therapeutic potential of omalizumab. In fact, the benefit of omalizumab was more likely to be observed in patients with asthma and with CRS than in patients with asthma and without CRS.

  16. Lower prevalence and greater severity of asthma in hot and dry climate

    Directory of Open Access Journals (Sweden)

    Marco Aurélio de Valois Correia Junior

    2017-03-01

    Conclusion: Asthma prevalence in this low‐humidity environment was lower, but more severe than those reported in other Brazilian cities. The dry climate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population.

  17. [Allergic Rhinitis and its Impact on Asthma (ARIA) in Latin America].

    Science.gov (United States)

    Baena-Cagnani, Carlos E

    2002-01-01

    Allergic rhinitis is the commonest chronic respiratory disorder in children and young adults having an important impact for those suffering this condition, as well as for the public health. Allergic rhinitis is frequently associated to other co-morbidities, particularly asthma and conjunctivitis but, also, sinusitis and otitis media. Most of patients suffering rhinitis are cared by GPs and pediatricians and there are evidences that allergic rhinitis is undertreated, particularly the moderate/severe persistent forms. Clinical guidelines have become an important tool providing recommendations for diagnosis and treatment of different medical conditions. They help the process of decision making for GPs and pediatricians, and many of them, contain an update on basic science and epidemiology. In respiratory medicine, guidelines on asthma and rhinitis are available; however, they do not look at the patients globally and focus the disorder on an organ-specific basis without recommendations on co-morbidities. ARIA, Allergic rhinitis and its impact on asthma, has not been developed only to update specialists in allergy/immunology, otorhinolaryngology and neumology on rhinitis and its comorbidities but, also, to provide recommendations for non-specialists. A new classification and severity of allergic rhinitis is proposed replacing the classic perennial and seasonal forms for persistent and intermittent, mild to moderate/severe. ARIA is an initiative in collaboration with the World Health Organization and the master document has been endorsed by many national and international scientific societies and organizations. ARIA is an evidence-based document also stressing on pediatric aspects and providing recommendations for low-income countries.

  18. Control of Allergic Rhinitis and Asthma Test (CARAT) : dissemination and applications in primary care

    NARCIS (Netherlands)

    Azevedo, Pedro; Correia-de-Sousa, Jaime; Bousquet, Jean; Bugalho-Almeida, Antonio; Del Giacco, Stefano R.; Demoly, Pascal; Haahtela, Tari; Jacinto, Tiago; Garcia-Larsen, Vanessa; van der Molen, Thys; Morais-Almeida, Mario; Nogueira-Silva, Luis; Pereira, Ana M.; Roman-Rodrigues, Miguel; Silva, Barbara G.; Tsiligianni, Ioanna G.; Yaman, Hakan; Yawn, Barbara; Fonseca, Joao A.

    Asthma frequently occurs in association with allergic rhinitis and a combined management approach has been suggested. The Control of Allergic Rhinitis and Asthma Test (CARAT) is the first questionnaire to assess control of both diseases concurrently. However, to have an impact on healthcare it needs

  19. Environmental and Personal Factors Related to Asthma Severity among Children: Hospital Based Study, Egypt

    Directory of Open Access Journals (Sweden)

    Omaima Ibrahim AboElkheir

    2016-09-01

    Full Text Available Background: Childhood asthma is a complex disorder in which many environmental and personal factors play a role. However, the contribution of these factors to asthma severity is poorly understood. This study aims to determine the relationship between environmental exposures, personal factors and asthma severity among asthmatic children. Methods: This cross-sectional hospital based study was conducted on 180 asthmatic children; they were divided into mild, moderate and severe asthma according to forced expiratory volume in first second. Environmental factors (indoor and outdoor, food allergy, history of other allergic diseases, family history of allergic disorders, time trend of attacks as well as asthma outcome were reported. Results: Children with severe asthma were younger than those with mild or moderate asthma. Severe asthma was significantly linked to family history of allergy, presence of co-morbid allergic diseases, fish, egg and milk allergy, as well as exposure to passive smoking (73.7% and poor housing conditions. Also, it was significantly linked to presence of unauthorized factories in residential area (31.6 %, p=0.001. As well as, contact with pets (42.1%. Children with severe asthma had more limitations of physical activities (73.7%, missed school days (81.5%, with poor school performance (p=0.04 than those with mild moderate or asthma. Conclusion: Severe asthma was linked to female gender and younger age, co-morbid allergic diseases, family history of atopy and food allergy. It was higher among children residing in places with unauthorized factories and living in substandard housing condition. Children with severe asthma had poor asthma outcome.

  20. Perinatal and Early Childhood Environmental Factors Influencing Allergic Asthma Immunopathogenesis

    Science.gov (United States)

    Gaffin, Jonathan M.; Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda

    2014-01-01

    Background The prevalence of asthma has increased dramatically over the past several decades. While hereditary factors are highly important, the rapid rise outstrips the pace of genomic variation. Great emphasis has been placed on potential modifiable early life exposures leading to childhood asthma. Methods We reviewed the recent medical literature for important studies discussing the role of the perinatal and early childhood exposures and the inception of childhood asthma. Results and Discussion Early life exposure to allergens (House dust mite (HDM), furred pets, cockroach, rodent and mold)air pollution (nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), and particulate matter (PM)) and viral respiratory tract infections (Respiratory syncytial virus (RSV) and human rhinovirus (hRV)) have been implicated in the development of asthma in high risk children. Conversely, exposure to microbial diversity in the perinatal period may diminish the development of atopy and asthma symptoms. PMID:24952205

  1. Asthma and Allergic Rhinitis Correlation in Palm Tree Workers of Jahrom City in 2016

    OpenAIRE

    Farahmand Fard, Mohammad Amin; Khanjani, Narges; Arabi Mianroodi, Aliasghar; Ashrafi Asgarabad, Ahad

    2017-01-01

    Introduction: Allergic rhinitis and asthma can be related to occupation. The present study aimed to investigate the correlation between asthma or allergic rhinitis and employment in the palm tree gardens of Jahrom, Iran.   Materials and Methods: This was a cross-sectional study including 50 palm tree garden workers and a control group of 50 office employees. Data collection included demographics, as well as standard International Study of Asthma and Allergies in Childhood (ISAAC) and A New Sy...

  2. The TLR5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens

    OpenAIRE

    Wilson, Rhonda H.; Maruoka, Shuichiro; Whitehead, Gregory S.; Foley, Julie F.; Flake, Gordon P.; Sever, Michelle L.; Zeldin, Darryl C.; Kraft, Monica; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N.

    2012-01-01

    Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction 1 . Exposure to indoor allergens is a clear risk factor for asthma, but this disease is also associated with high household levels of total and Gram-negative bacteria 2 . The ability of bacterial products to act as adjuvants 3 suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust e...

  3. Appropriate selection for omalizumab treatment in patients with severe asthma?

    DEFF Research Database (Denmark)

    Nygaard, Leo; Henriksen, Daniel Pilsgaard; Madsen, Hanne

    2017-01-01

    Background: Omalizumab improves asthma control in patients with uncontrolled severe allergic asthma; however, appropriate patient selection is crucial. Information in this field is sparse. Objective: We aimed to estimate whether potential omalizumab candidates were appropriately selected according...... to guidelines, and the clinical effect of omalizumab treatment over time. Design: We performed a retrospective observational study on adult patients with asthma treated with omalizumab during 2006-2015 at the Department of Respiratory Medicine at Odense University Hospital (OUH), Denmark. Data were obtained...... from the Electronic Patient Journal of OUH and Odense Pharmaco-Epidemiological Database. Guideline criteria for omalizumab treatment were used to evaluate the appropriateness of omalizumab candidate selection, and the Asthma Control Test (ACT) to assess the clinical effects of omalizumab at weeks 16...

  4. Severe bronchial asthma in children: the role of clinical and anamnestic indices in diagnosis verification

    Directory of Open Access Journals (Sweden)

    Kolyubakina L.V.

    2016-03-01

    Full Text Available The paper presents comparative analysis of results of clinical and anamnestic examination of children depending on the asthma severity. Severe asthma in schoolchildren relative to moderate phenotype characterized by birth overweight, more burdened individual allergic history, highly infectious index, drug or combined (medication, food and household allergies, seasonal exacerbations (mainly from November to March, what associated with the trigger role of ARVI and meteorological factors, inadequate asthma control during standard basic therapy.

  5. Omalizumab in children with uncontrolled allergic asthma: Review of clinical trial and real-world experience.

    Science.gov (United States)

    Chipps, Bradley E; Lanier, Bob; Milgrom, Henry; Deschildre, Antoine; Hedlin, Gunilla; Szefler, Stanley J; Kattan, Meyer; Kianifard, Farid; Ortiz, Benjamin; Haselkorn, Tmirah; Iqbal, Ahmar; Rosén, Karin; Trzaskoma, Benjamin; Busse, William W

    2017-05-01

    Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Geo-climatic heterogeneity in self-reported asthma, allergic rhinitis and chronic bronchitis in Italy

    Energy Technology Data Exchange (ETDEWEB)

    Pesce, G., E-mail: giancarlo.pesce@univr.it [Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona (Italy); Bugiani, M. [Unit of Respiratory Medicine and Allergology, CPA-ASL TO-2, Turin (Italy); Marcon, A.; Marchetti, P. [Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona (Italy); Carosso, A. [Unit of Respiratory Medicine and Allergology, CPA-ASL TO-2, Turin (Italy); Accordini, S. [Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona (Italy); Antonicelli, L. [Dept of Internal Medicine, Immuno-Allergic and Respiratory Diseases, Ospedali Riuniti di Ancona, Ancona (Italy); Cogliani, E. [Casaccia Research Centre, Italian National Agency for New Technologies, Energy, and Substainable Economic Development (ENEA), Rome (Italy); Pirina, P. [Institute of Respiratory Diseases, University of Sassari, Sassari (Italy); Pocetta, G. [Dept of Experimental Medicine, University of Perugia, Perugia (Italy); Spinelli, F. [Casaccia Research Centre, Italian National Agency for New Technologies, Energy, and Substainable Economic Development (ENEA), Rome (Italy); Villani, S. [Dept of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia (Italy); Marco, R. de [Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona (Italy)

    2016-02-15

    Background: Several studies highlighted a great variability, both between and within countries, in the prevalence of asthma and chronic airways diseases. Aim: To evaluate if geo-climatic variations can explain the heterogeneity in the prevalence of asthma and respiratory diseases in Italy. Methods: Between 2006 and 2010, a postal screening questionnaire on respiratory health was administered to 18,357 randomly selected subjects, aged 20–44, living in 7 centers in northern, central, and southern Italy. A random-effects meta-analysis was fitted to evaluate the between-centers heterogeneity in the prevalence of asthma, asthma-like symptoms, allergic rhinitis, and chronic bronchitis (CB). A principal component analysis (PCA) was performed to synthetize the geo-climatic information (annual mean temperature, range of temperature, annual rainfalls, global solar radiations, altitude, distance from the sea) of all the 110 Italian province capital towns. The associations between these geo-climatic components obtained with PCA and the prevalence of respiratory diseases were analyzed through meta-regression models. Results: 10,464 (57%) subjects responded to the questionnaire. There was a significant between-centers heterogeneity in the prevalence of asthma (I{sup 2} = 59.5%, p = 0.022) and CB (I{sup 2} = 60.5%, p = 0.019), but not in that of asthma-like symptoms or allergic rhinitis. Two independent geo-climatic components explaining together about 80% of the overall geo-climatic variability were identified: the first principally summarized the climatic variables; the second the topographic ones. Variations in the prevalence of asthma across centers were significantly associated with differences in the climatic component (p = 0.017), but not with differences in the topographic one. Conclusions: Our findings suggest that climate play a role in determining the between-center heterogeneity in the prevalence of asthma in Italy, with higher prevalence in dry-hot Mediterranean

  7. Geo-climatic heterogeneity in self-reported asthma, allergic rhinitis and chronic bronchitis in Italy

    International Nuclear Information System (INIS)

    Pesce, G.; Bugiani, M.; Marcon, A.; Marchetti, P.; Carosso, A.; Accordini, S.; Antonicelli, L.; Cogliani, E.; Pirina, P.; Pocetta, G.; Spinelli, F.; Villani, S.; Marco, R. de

    2016-01-01

    Background: Several studies highlighted a great variability, both between and within countries, in the prevalence of asthma and chronic airways diseases. Aim: To evaluate if geo-climatic variations can explain the heterogeneity in the prevalence of asthma and respiratory diseases in Italy. Methods: Between 2006 and 2010, a postal screening questionnaire on respiratory health was administered to 18,357 randomly selected subjects, aged 20–44, living in 7 centers in northern, central, and southern Italy. A random-effects meta-analysis was fitted to evaluate the between-centers heterogeneity in the prevalence of asthma, asthma-like symptoms, allergic rhinitis, and chronic bronchitis (CB). A principal component analysis (PCA) was performed to synthetize the geo-climatic information (annual mean temperature, range of temperature, annual rainfalls, global solar radiations, altitude, distance from the sea) of all the 110 Italian province capital towns. The associations between these geo-climatic components obtained with PCA and the prevalence of respiratory diseases were analyzed through meta-regression models. Results: 10,464 (57%) subjects responded to the questionnaire. There was a significant between-centers heterogeneity in the prevalence of asthma (I"2 = 59.5%, p = 0.022) and CB (I"2 = 60.5%, p = 0.019), but not in that of asthma-like symptoms or allergic rhinitis. Two independent geo-climatic components explaining together about 80% of the overall geo-climatic variability were identified: the first principally summarized the climatic variables; the second the topographic ones. Variations in the prevalence of asthma across centers were significantly associated with differences in the climatic component (p = 0.017), but not with differences in the topographic one. Conclusions: Our findings suggest that climate play a role in determining the between-center heterogeneity in the prevalence of asthma in Italy, with higher prevalence in dry-hot Mediterranean climates

  8. Current issues on sublingual allergen-specific immunotherapy in children with asthma and allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Živković Zorica

    2016-01-01

    Full Text Available In 1993 the European Academy of Allergy and Clinical Immunology was the first official organization to recognize that sublingual administration could be “promising route” for allergic desensitization. A few years later, the World Health Organization recommended this therapy as “a viable alternative to the injection route in adults.” The first meta-analysis showed sublingual allergen specific immunotherapy (SLIT effectiveness for allergic rhinitis and another study showed SLIT can actually help prevent the development of asthma both in adults and in children. The main goal of this review article is to present insight into the most up-to-date understanding of the clinical efficacy and safety of immunotherapy in the treatment of pediatric patients with allergic rhinitis and asthma. A literature review was performed on PubMed from 1990 to 2015 using the terms “asthma,” “allergic rhinitis,” “children,” “allergen specific immune therapy.” Evaluating data from double-blind placebo-controlled randomized clinical trials (DB-PC-RCTs, the clinical efficacy (assessed as the reduction of symptom score and the need of rescue medicament of SLIT for allergic rhinitis and allergic asthma, has been confirmed in various meta-analysis Outcomes such as rhinoconjunctivitis score and medication scores, combined scores, quality of life, days with severe symptoms, immunological endpoints, and safety parameters were all improved in the SLIT-tablet compared with placebo group. SLIT safety has been already proven in many DB-PC-RCTs and real-life settings. In accordance with all of the above mentioned, the goals for future trials and studies are the development of comprehensive guidelines for clinical practice on immunotherapy, embracing all the different potential participants. The importance of allergen immunotherapy is of special relevance in the pediatric age, when the plasticity and modulability of the immune system are maximal, and when

  9. The treatment of allergic rhinitis improves the recovery from asthma and upper respiratory infections

    Directory of Open Access Journals (Sweden)

    Willy Sarti

    Full Text Available Forty-six asthmatic children with repeated respiratory infections presented symptoms of allergic rhinitis. All patients were treated locally for allergic rhinitis either with disodium cromoglycate or beclomethasone dipropionate. After six months of treatment, 95% of the children showed improvement of allergic rhinitis and 84% improvement of bronchial asthma, as well as fewer infections. We concluded that allergic rhinitis plays an important role in facilitating infections of the upper respiratory tract, and a possible association of rhinitis, viral infections and bronchial asthma is discussed.

  10. Type 2 innate lymphoid cells: at the cross-roads in allergic asthma.

    Science.gov (United States)

    van Rijt, Leonie; von Richthofen, Helen; van Ree, Ronald

    2016-07-01

    Allergic asthma is a chronic inflammatory disease of the lower airways that affects millions of people worldwide. Allergic asthma is a T helper 2 cell (Th2)-mediated disease, in which Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 are closely associated with the symptoms. IL-4 is needed by B cells to switch toward an IgE response, IL-5 recruits and activates eosinophils while IL-13 increases mucus production. The identification of type 2 innate lymphoid cells (ILC2), which are able to rapidly produce large amounts of IL-5 and IL-13 in response to epithelial derived cytokines, implicated a new key player besides Th2 cells. ILCs constitute a family of innate lymphocytes distinct from T and B cells. ILC2s are located in various epithelial compartments in mice and human, including the lung. The recent finding of increased numbers of ILC2s in the airways of severe asthma patients prompts further research to clarify their immunological function. Murine studies have shown that ILC2s are an early innate source of IL-5 and IL-13 after allergen exposure, which induce airway eosinophilic infiltration, mucus hyperproduction, and airway hyperresponsiveness but not allergen-specific IgE production. ILC2s contribute to the initiation as well as to the maintenance of the adaptive type 2 immune response. Here, we review the recent progress on our understanding of the role of ILC2s in the immunopathology of allergic asthma, in particular by studies using murine models which have elucidated fundamental mechanisms by which ILC2s act.

  11. Managing problematic severe asthma: beyond the guidelines.

    Science.gov (United States)

    Pike, Katharine C; Levy, Mark L; Moreiras, John; Fleming, Louise

    2018-04-01

    This review discusses issues related to managing problematic severe asthma in children and young people. A small minority of children have genuinely severe asthma symptoms which are difficult to control. Children with genuinely severe asthma need investigations and treatments beyond those described within conventional guidelines. However, the majority of children with poor symptom control despite high-intensity treatment achieve improvement in their asthma control once attention has been paid to the basics of asthma management. Basic asthma management requires optimisation of inhaler technique and treatment adherence, avoidance of environmental triggers and self-management education. It is also important that clinicians recognise risk factors that predispose patients to asthma exacerbations and potentially life-threatening attacks. These correctable issues need to be tackled in partnership with children and young people and their families. This requires a coordinated approach between professionals across healthcare settings. Establishing appropriate infrastructure for coordinated asthma care benefits not only those with problematic severe asthma, but also the wider asthma population as similar correctable issues exist for children with asthma of all severities. Investigation and management of genuine severe asthma requires specialist multidisciplinary expertise and a systematic approach to characterising patients' asthma phenotypes and delivering individualised care. While inhaled corticosteroids continue to play a leading role in asthma therapy, new treatments on the horizon might further support phenotype-specific therapy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Comparative study of specific IgE for cockroach between asthma and allergic rhinitis patients

    International Nuclear Information System (INIS)

    Guo Yinshi; Xu Yiping; Zhu Lijun; Wang Limin; Cao Lingxian; Yao Suhang

    2005-01-01

    To compare the degrees of allergic reaction and the cross-reactive allergens for three strains of cockroach (Periplanceta fuliginosa , Periplaneta americana and Blattella germanica) between patients with asthma and allergic rhinitis, the specific IgE(sIgE) in asthma and allergic rhinitis for these three strains of cockroach were determined with ELISA. The results showed that the sIgE positive rates for Periplaneta americana, Periplaneta fuliginosa and Blattella germanica in patients with asthma were 23.5%, 16.0% and 14.8%, respectively. The reactive coincidence rate between Periplaneta americana and Periplaneta fuliginoas was 74.0%, between Periplaneta americana and Blattella germanica was 73.5%, and between Periplaneta fuliginosa and Blattella germanica was 85.0% in asthma patients. The IgE positive rates for Periplaneta americana, Periplaneta fuliginosa and Blattella gerraanica in allergic rhinitis patients were 24.8%, 17.6% and 15.8%, respectively. The reactive coincidence rate between Periplaneta americana and Periplaneta fuliginosa was 73.9%, between Periplaneta americana and Blattella germanica was 75.2%, and between Periplaneta fuliginosa and Blattella germanica was 86.1% in allergic rhinitis patients. There was no significant difference between asthma and allergic rhinitis patients although the sIgE positive rates of allergic rhinitis patients were higher than those of asthma patients for these three strains of cock- roach. All these results indicated that the degrees of allergic reaction are similar between asthma and allergic rhinitis patients and there are some cross-reactive allergic components among these three strains of cockroach. (authors)

  13. Asthma and Allergic Rhinitis Correlation in Palm Tree Workers of Jahrom City in 2016.

    Science.gov (United States)

    Farahmand Fard, Mohammad Amin; Khanjani, Narges; Arabi Mianroodi, Aliasghar; Ashrafi Asgarabad, Ahad

    2017-05-01

    Allergic rhinitis and asthma can be related to occupation. The present study aimed to investigate the correlation between asthma or allergic rhinitis and employment in the palm tree gardens of Jahrom, Iran. This was a cross-sectional study including 50 palm tree garden workers and a control group of 50 office employees. Data collection included demographics, as well as standard International Study of Asthma and Allergies in Childhood (ISAAC) and A New Symptom-Based Questionnaire for Predicting the Presence of Asthma (ASQ) questionnaires. Data were analyzed using SPSS22. Descriptive statistics, chi-square test, t-test, and logistics regression were used to analyze data. The correlation between asthma and occupation was significant ( P=0.046); and asthma prevalence was higher in palm tree garden workers. However, no relationship was observed between age, duration of employment, smoking cigarettes, hookah, or opium addiction with asthma. Furthermore, in this study, no significant relation was observed between the prevalence of asthma and contact with dust, contact with pets' skin and hair, family history of asthma, or the use of perfume and air freshener. The symptoms of allergic rhinitis (including sneezing, runny nose, and blocked nose) were significantly greater in palm tree garden workers (P=0.038). These symptoms in both workers and office employees were higher in spring. In our study, allergic rhinitis and asthma were more common in palm tree garden workers than in the general population. According to our study, people working in this occupation should take necessary precautions.

  14. Hormonal factors and incident asthma and allergic rhinitis during puberty in girls.

    Science.gov (United States)

    Wei, Junxiang; Gerlich, Jessica; Genuneit, Jon; Nowak, Dennis; Vogelberg, Christian; von Mutius, Erika; Radon, Katja

    2015-07-01

    Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty. To determine whether age at menarche and use of hormonal contraceptives predict new-onset allergic rhinitis and asthma after puberty in young German women. A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model. Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio [OR] 0.32, 95% confidence interval [CI] 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty. This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Decreased expression of indolamine 2,3-dioxygenase in childhood allergic asthma and its inverse correlation with fractional concentration of exhaled nitric oxide.

    Science.gov (United States)

    Hu, Ying; Chen, Zhiqiang; Jin, Ling; Wang, Mei; Liao, Wei

    2017-11-01

    The tryptophan metabolic pathway mediated by indolamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays an important role in controlling the development of allergic inflammation. The fractional concentration of exhaled nitric oxide (FeNO) is closely associated with the allergic state and is extensively used for the clinical evaluation of airway allergic inflammation. Clinical trials have rarely assessed the expression of IDO in childhood allergic asthma and its correlation with FeNO. To evaluate the IDO level in children with childhood allergic asthma and the relation between IDO levels and FeNO. Thirty children older than 5 years who were diagnosed the first time with allergic asthma were selected from the pediatric outpatient department. Another 30 healthy children were selected as controls. The subjects were evaluated by complete medical history, pulmonary function test results, skin prick test reaction, FeNO concentration test result, eosinophil count, and a disease severity score. Peripheral venous blood and induced sputum were obtained to measure the concentrations of IDO metabolites (ie, tryptophan and kynurenine). The IDO levels in the peripheral blood and induced sputum were significantly lower in patients with childhood allergic asthma than in children in the control group. The IDO level was negatively correlated with FeNO but was not significantly correlated with age, sex, blood eosinophil count, or disease severity scale. The expression of IDO was significantly lower in childhood allergic asthma, particularly in children with high FeNO levels. There was no significant relation between IDO levels and asthma severity. Chinese Clinical Trial Register (www.chictr.org.cn) Identifier: ChiCTR-COC-15006080. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. RItA: The Italian severe/uncontrolled asthma registry.

    Science.gov (United States)

    Maio, S; Baldacci, S; Bresciani, M; Simoni, M; Latorre, M; Murgia, N; Spinozzi, F; Braschi, M; Antonicelli, L; Brunetto, B; Iacovacci, P; Roazzi, P; Pini, C; Pata, M; La Grasta, L; Paggiaro, P; Viegi, G

    2018-03-01

    The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV 1 % pred of 75.1%, median values of 300/mm 3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  17. Anaphylaxis, contact urticaria, and allergic asthma caused by persulfates in hair bleaching products

    NARCIS (Netherlands)

    Hoekstra, Miriam; Schuttelaar, M.L.; Coenraads, P.J.

    2010-01-01

    Background: Persulfate salts are potent oxidizing agents in hair bleach products that accelerate the bleaching process. Ammonium and potassium persulfates may cause delayedtype and immediate skin reactions. Also allergic asthma and rhinitis have been described. Objectives: Ammonium and potassium

  18. Lower prevalence and greater severity of asthma in hot and dry climate.

    Science.gov (United States)

    Correia Junior, Marco Aurélio de Valois; Sarinho, Emanuel Sávio Cavalcanti; Rizzo, José Angelo; Sarinho, Silvia Wanick

    To estimate asthma prevalence, severity, and associated factors in adolescents who live in a low relative humidity environment. In this cross-sectional study, adolescents aged 13-14 years from the city of Petrolina located in the Brazilian semiarid region answered the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The possible explanatory variables of the study were gender, family income, mother's education, smokers in the household, parental history of asthma, personal history of allergic rhinitis or atopic dermatitis, and physical activity level. Poisson regression analysis was used to assess the association between asthma and the explanatory variables. A total of 1591 adolescents participated in the study, of whom 49.7% were male. The prevalence of active asthma, severe asthma, and physician-diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with asthma missed more school days than their peers (33 vs. 22 days/year; pclimate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. The TLR5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens

    Science.gov (United States)

    Wilson, Rhonda H.; Maruoka, Shuichiro; Whitehead, Gregory S.; Foley, Julie F.; Flake, Gordon P.; Sever, Michelle L.; Zeldin, Darryl C.; Kraft, Monica; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N.

    2012-01-01

    Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction1. Exposure to indoor allergens is a clear risk factor for asthma, but this disease is also associated with high household levels of total and Gram-negative bacteria2. The ability of bacterial products to act as adjuvants3 suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen presenting dendritic cells (DC) in vitro and promote allergic sensitization to inhaled innocuous proteinsin vivo4. It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen of microbial products for their adjuvant activity in the airway revealed that the bacterial protein, flagellin (FLA) stimulated strong allergic responses to an innocuous inhaled protein. Moreover, toll-like receptor (TLR)5, the mammalian receptor for FLA5,6, was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, the incidence of human asthma was associated with high serum levels of FLA-specific antibodies. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens. PMID:23064463

  20. Lower prevalence and greater severity of asthma in hot and dry climate

    Directory of Open Access Journals (Sweden)

    Marco Aurélio de Valois Correia Junior

    Full Text Available Abstract Objective: To estimate asthma prevalence, severity, and associated factors in adolescents who live in a low relative humidity environment. Methods: In this cross-sectional study, adolescents aged 13-14 years from the city of Petrolina located in the Brazilian semiarid region answered the International Study of Asthma and Allergies in Childhood (ISAAC questionnaire. The possible explanatory variables of the study were gender, family income, mother's education, smokers in the household, parental history of asthma, personal history of allergic rhinitis or atopic dermatitis, and physical activity level. Poisson regression analysis was used to assess the association between asthma and the explanatory variables. Results: A total of 1591 adolescents participated in the study, of whom 49.7% were male. The prevalence of active asthma, severe asthma, and physician-diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with asthma missed more school days than their peers (33 vs. 22 days/year; p < 0.03. Associated factors that remained significant after adjustment were history of asthma in parents (PR = 2.65, p < 0.001 and personal diagnosis of allergic rhinitis (PR = 1.96, p < 0.001 and/or atopic dermatitis (PR = 2.18, p < 0.001. Conclusion: Asthma prevalence in this low-humidity environment was lower, but more severe than those reported in other Brazilian cities. The dry climate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population.

  1. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

    NARCIS (Netherlands)

    Ferreira, Manuel A; Vonk, Judith M; Baurecht, Hansjörg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; van Dongen, Jenny; Lu, Yi; Rüschendorf, Franz; Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Boomsma, Dorret I

    2017-01-01

    Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that

  2. Evaluation of long-term safety and efficacy of omalizumab in elderly patients with uncontrolled allergic asthma.

    Science.gov (United States)

    Tat, Tugba Songul; Cilli, Aykut

    2016-11-01

    Severe asthma management in elderly patients may be difficult because of increased comorbid conditions, polypharmacy, physiologic changes that occur with aging, incorrect use of inhaler devices, and poor adherence. To evaluate the long-term safety and efficacy of the anti-IgE antibody omalizumab in elderly (aged ≥65 years) patients with uncontrolled allergic asthma. The efficiency and adverse effects of omalizumab treatment were evaluated based on data extracted from medical records. Patients were evaluated monthly for efficacy and adverse reactions. Treatment efficacy was evaluated by level of asthma symptom control, using the Global Initiative for Asthma guideline. Nineteen consecutive elderly patients with asthma (female to male ratio, 14:5) formed our cohort. The mean (SD) age, disease duration, and total IgE level were 69.3 (5.8) years, 19.4 (8.6) years, and 299.1 (197.2) IU/mL, respectively. The mean (SD) duration of omalizumab treatment was 35.6 (17.8) months (range, 9-66 months). All the patients had at least 1 perennial inhalant allergen sensitivity and had uncontrolled allergic asthma. Elderly patients experienced no significantly important adverse reaction considered to be related to omalizumab treatment. Only 1 patient had a local adverse reaction and 1 had myalgia that was considered to be drug related. After omalizumab treatment, asthma symptoms were well controlled in 9 patients (47.4%) and partly controlled in 8 patients (42.1%). Two of the patients (10.5%) still had uncontrolled asthma. Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with uncontrolled asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Report of a patient with complex composites of hepatitis B virus, allergic asthma and diabetes

    Directory of Open Access Journals (Sweden)

    Seyyed Shamsadin Athari

    2014-05-01

    Full Text Available HBV is a non-cytopathic virus and cell mediated immune response against this. Humoral mediated immune response are responsible for allergic diseases. Balance between these two subsets of Th CD4+ cells are result of the immune system response. A 56 year old woman presented with chronic HBV infection, allergic asthma, type 2 diabetes mellitus and high blood pressure and high blood lipid. Patients should be followed for the allergic and autoimmune diseases along with their viral reactivation.

  4. Acute severe asthma presenting in late pregnancy.

    Science.gov (United States)

    Holland, S M; Thomson, K D

    2006-01-01

    Asthma is the commonest pre-existing medical condition to complicate pregnancy. Acute severe asthma in pregnancy is rare, but poses difficult problems. In particular, the decision about when and where to deliver the fetus is complex, since maternal response to asthma treatment is unpredictable. We report the successful management of a parturient presenting with acute severe asthma at 37 weeks' gestation. The controversies involved and the importance of adopting a multi-disciplinary team approach to optimise maternal and neonatal outcomes are discussed.

  5. Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial

    NARCIS (Netherlands)

    de Boer, J. Daan; Berger, Marieke; Majoor, Christof J.; Kager, Liesbeth M.; Meijers, Joost C. M.; Terpstra, Sanne; Nieuwland, Rienk; Boing, Anita N.; Lutter, René; Wouters, Diana; van Mierlo, Gerard J.; Zeerleder, Sacha S.; Bel, Elisabeth H.; van't Veer, Cornelis; de Vos, Alex F.; van der Zee, Jaring S.; van der Poll, Tom

    2015-01-01

    Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.We conducted a randomised, double-blind,

  6. Air pollution and asthma severity in adults

    Science.gov (United States)

    Rage, Estelle; Siroux, Valérie; Künzli, Nino; Pin, Isabelle; Kauffmann, Francine

    2009-01-01

    Objectives There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. Methods Asthma severity over the last 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The 4-class severity score integrated clinical events and type of treatment. The 5-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991–1995. The second consisted in spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). Results Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O3-8hr) and the number of days (O3-days) with 8-hour ozone averages above 110 μg.m−3 (for a 36-day increase, equivalent to the inter quartile range, in O3-days, odds ratio (95% confidence interval) 2.22 (1.61–3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO2. Both exposure assessment methods and severity scores resulted in very similar findings. SO2 correlated with severity but reached statistical significance only for the model based assignment of exposure. Conclusions The observed associations between asthma severity and air pollution, in particular O3, support the hypothesis that air pollution at levels far below current standards increases asthma severity. PMID:19017701

  7. A review of omalizumab for the management of severe asthma.

    Science.gov (United States)

    Lin, Ching-Hsiung; Cheng, Shih-Lung

    2016-01-01

    Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating immunoglobulin E, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be focused on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response, as well as extending its indications.

  8. Allergic rhinitis and its impact on asthma update (ARIA 2008)--western and Asian-Pacific perspective.

    Science.gov (United States)

    Pawankar, Ruby; Bunnag, Chaweewan; Chen, Yuzhi; Fukuda, Takeshi; Kim, You-Young; Le, Lan Thi Tuyet; Huong, Le Thi Thu; O'Hehir, Robyn E; Ohta, Ken; Vichyanond, Pakit; Wang, De-Yun; Zhong, Nanshan; Khaltaev, Nikolai; Bousquet, Jean

    2009-12-01

    The prevalence of allergic diseases such as allergic rhinitis (AR) and asthma is markedly increasing worldwide as societies adopt western life styles. Allergic sensitization is an important risk factor for asthma and AR, and asthma often co-exists with AR. An estimated 300 million people worldwide have asthma, about 50% of whom live in developing countries and about 400 million people suffer from AR. Yet, AR is often under-diagnosed and under-treated due to a lack of appreciation of the disease burden and its impact on quality of life, as well as its social impact at school and at the workplace. However, AR with or without asthma is a huge economic burden. Thus, there was clearly a need for a global evidence-based document which would highlight the interactions between the upper and lower airways including diagnosis, epidemiology, common risk factors, management and prevention. The Allergic Rhinitis and its Impact on Asthma (ARIA) document was first published in 2001 as a state-of-the-art guideline for the specialist, the general practitioner and other health care professionals. Subsequent new evidence regarding the pathomechanisms, new drugs and increased knowledge have resulted in the publication of the ARIA 2008 update. The present review summarizes the ARIA update with particular emphasis on the current status of AR and asthma in the Asia-Pacific region and discusses the Western and Asian perspective.

  9. Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma

    Directory of Open Access Journals (Sweden)

    Jelena Skuljec

    2017-09-01

    Full Text Available Cellular therapy with chimeric antigen receptor (CAR-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR and a chronic, T helper-2 (Th2 cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.

  10. Treatment of allergic asthma: Modulation of Th2 cells and their responses

    Directory of Open Access Journals (Sweden)

    Erb Klaus J

    2011-08-01

    Full Text Available Abstract Atopic asthma is a chronic inflammatory pulmonary disease characterised by recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell-mediated inflammatory response in the airways. It is currently treated and, more or less, controlled depending on severity, with bronchodilators e.g. long-acting beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs such as corticosteroids (inhaled or oral, leukotriene modifiers, theophyline and anti-IgE therapy. Unfortunately, none of these treatments are curative and some asthmatic patients do not respond to intense anti-inflammatory therapies. Additionally, the use of long-term oral steroids has many undesired side effects. For this reason, novel and more effective drugs are needed. In this review, we focus on the CD4+ Th2 cells and their products as targets for the development of new drugs to add to the current armamentarium as adjuncts or as potential stand-alone treatments for allergic asthma. We argue that in early disease, the reduction or elimination of allergen-specific Th2 cells will reduce the consequences of repeated allergic inflammatory responses such as lung remodelling without causing generalised immunosuppression.

  11. Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma.

    Science.gov (United States)

    Brüggenjürgen, Bernd; Reinhold, Thomas; Brehler, Randolf; Laake, Eckard; Wiese, Günther; Machate, Ulrich; Willich, Stefan N

    2008-09-01

    Specific immunotherapy is the only potentially curative treatment in patients with allergic rhinitis and allergic asthma. Health economic evaluations on this treatment, particularly in a German context, are sparse. To evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in addition to symptomatic treatment (ST) compared with ST alone in a German health care setting. The analysis was performed as a health economic model calculation based on Markov models. In addition, we performed a concomitant expert board composed of allergy experts in pediatrics, dermatology, pneumology, and otolaryngology. The primary perspective of the study was societal. Additional sensitivity analyses were performed to prove our results for robustness. The SCIT and ST combination was associated with annual cost savings of Euro140 per patient. After 10 years of disease duration, SCIT and ST reach the breakeven point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787 per quality-adjusted life-year (QALY), with a range that depended on patient age (adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a third-party payer's perspective, SCIT was associated with slightly additional costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients. Additional SCIT was associated with improved medical outcomes and cost savings compared with symptomatic treatment alone according to a societal perspective. Taking a European accepted ICER threshold of up to Euro50,000 per QALY into account, additional SCIT is considered clearly cost-effective compared with routine care in Germany. The degree of cost-effectiveness is strongly affected by costs related to SCIT and the target population receiving such treatment.

  12. Association of Polysensitization, Allergic Multimorbidity, and Allergy Severity: A Cross-Sectional Study of School Children.

    Science.gov (United States)

    Ha, Eun Kyo; Baek, Ji Hyeon; Lee, So-Yeon; Park, Yong Mean; Kim, Woo Kyung; Sheen, Youn Ho; Lee, Seung Jin; Bae, Youngoh; Kim, Jihyeon; Lee, Kee-Jae; Ahn, Kangmo; Kwon, Ho-Jang; Han, Man Yong

    2016-01-01

    Aeroallergen sensitization is related to the coexistence of allergic diseases, but the nature of this relationship is poorly understood. The aim of this study was to clarify the relationship of polysensitization with allergic multimorbidities and the severity of allergic diseases. This study is a cross-sectional analysis of 3,368 Korean children aged 6-7 years-old. We defined IgE-mediated allergic diseases based on structured questionnaires, and classified the sensitivity to 18 aeroallergens by logistic regression and the Ward hierarchical clustering method. The relationship of polysensitization (positive IgE responses against 2 or more aeroallergens classes) with allergic multimorbidities (coexistence of 2 or more of the following allergic diseases: asthma, rhinitis, eczema, and conjunctivitis) and severity of allergic diseases was determined by ordinal logistic regression analysis. The rate of polysensitization was 13.6% (n = 458, 95% CI 12.4-14.8) and that of allergic multimorbidity was 23.5% (n = 790, 95% CI 22.0-24.9). Children sensitized to more aeroallergens tended to have more allergic diseases (rho = 0.248, p school (1 allergen: aOR 1.96, 3 allergens: aOR 2.08), and severity of nasal symptoms (1 allergen: aOR 1.61, 4 or more allergens: aOR 4.38). Polysensitization was weakly related to multimorbidity. However, the number of allergens to which a child is sensitized is related to the severity of IgE-mediated symptoms. © 2017 S. Karger AG, Basel.

  13. MODERN APPROACHES TO FRACTIONAL EXHALED NITRIC OXIDE AS A USEFUL BIOMARKER FOR ALLERGIC ASTHMA PHENOTYPING AND MANAGEMENT.

    Science.gov (United States)

    Mgaloblishvili, N; Gotua, M

    2017-12-01

    Asthma is a pathologically heterogeneous disease, consisting of several phenotypes. Different types of airway inflammation are the cornerstone feature of this condition. Fraction of nitric oxide in exhaled air (FENO) has been proposed as a noninvasive, specific biomarker for eosinophilic airway inflammation and has been shown to be elevated in patients with allergic asthma phenotype. More recent studies indicate that FeNO identifies T-helper cell type 2 (Th2)-mediated airway inflammation with a high predictive value for identifying inhaled corticosteroid (ICS) responsive airway inflammation. Taking into account the accumulated evidence,it is possible to consider, that FeNO testing has an important role in the assessment of patients with suspected asthma and in the management of established asthmadiagnosis. In conjunction with symptom scores and lung function tests, FeNO measurement could provide a more useful and effective approach for asthma in terms of: (1) detecting the presence of Th2-mediated airway inflammation, (2) determining the likelihood of ICS responsive (and lack of course), (3) monitoring of airway inflammation to determine risk for future impairment or loss of asthma control during reduction/cessation of ICS treatment, (4) unmasking (otherwise unsuspected) non-adherence to corticosteroid therapy and (5) in severe asthma cases tailoring treatment with biological drugs. However, more work is still needed to address outstanding questions about its exact role in guiding asthma management and better define the use of FENO in different clinical settings.

  14. Asthma and Allergic Rhinitis Correlation in Palm Tree Workers of Jahrom City in 2016

    Science.gov (United States)

    Farahmand Fard, Mohammad Amin; Khanjani, Narges; Arabi Mianroodi, Aliasghar; Ashrafi Asgarabad, Ahad

    2017-01-01

    Introduction: Allergic rhinitis and asthma can be related to occupation. The present study aimed to investigate the correlation between asthma or allergic rhinitis and employment in the palm tree gardens of Jahrom, Iran. Materials and Methods: This was a cross-sectional study including 50 palm tree garden workers and a control group of 50 office employees. Data collection included demographics, as well as standard International Study of Asthma and Allergies in Childhood (ISAAC) and A New Symptom-Based Questionnaire for Predicting the Presence of Asthma (ASQ) questionnaires. Data were analyzed using SPSS22. Descriptive statistics, chi-square test, t-test, and logistics regression were used to analyze data. Results: The correlation between asthma and occupation was significant ( P=0.046); and asthma prevalence was higher in palm tree garden workers. However, no relationship was observed between age, duration of employment, smoking cigarettes, hookah, or opium addiction with asthma. Furthermore, in this study, no significant relation was observed between the prevalence of asthma and contact with dust, contact with pets’ skin and hair, family history of asthma, or the use of perfume and air freshener. The symptoms of allergic rhinitis (including sneezing, runny nose, and blocked nose) were significantly greater in palm tree garden workers (P=0.038). These symptoms in both workers and office employees were higher in spring. Conclusion: In our study, allergic rhinitis and asthma were more common in palm tree garden workers than in the general population. According to our study, people working in this occupation should take necessary precautions. PMID:28589108

  15. Asthma and Allergic Rhinitis Correlation in Palm Tree Workers of Jahrom City in 2016

    Directory of Open Access Journals (Sweden)

    Mohammad Amin Farahmand fard

    2017-05-01

    Full Text Available Introduction: Allergic rhinitis and asthma can be related to occupation. The present study aimed to investigate the correlation between asthma or allergic rhinitis and employment in the palm tree gardens of Jahrom, Iran.   Materials and Methods: This was a cross-sectional study including 50 palm tree garden workers and a control group of 50 office employees. Data collection included demographics, as well as standard International Study of Asthma and Allergies in Childhood (ISAAC and A New Symptom-Based Questionnaire for Predicting the Presence of Asthma (ASQ questionnaires. Data were analyzed using SPSS22. Descriptive statistics, chi-square test, t-test, and logistics regression were used to analyze data.   Results: The correlation between asthma and occupation was significant (       P=0.046; and asthma prevalence was higher in palm tree garden workers. However, no relationship was observed between age, duration of employment, smoking cigarettes, hookah, or opium addiction with asthma. Furthermore, in this study, no significant relation was observed between the prevalence of asthma and contact with dust, contact with pets’ skin and hair, family history of asthma, or the use of perfume and air freshener. The symptoms of allergic rhinitis (including sneezing, runny nose, and blocked nose were significantly greater in palm tree garden workers (P=0.038. These symptoms in both workers and office employees were higher in spring.   Conclusion: In our study, allergic rhinitis and asthma were more common in palm tree garden workers than in the general population. According to our study, people working in this occupation should take necessary precautions.

  16. A review of omalizumab for the management of severe asthma

    Directory of Open Access Journals (Sweden)

    Lin CH

    2016-07-01

    Full Text Available Ching-Hsiung Lin,1–3 Shih-Lung Cheng4,5 1Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, Republic of China; 2Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan, Republic of China; 3School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan, Republic of China; 5Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli City, Taoyuan County, Taiwan, Republic of China Abstract: Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating immunoglobulin E, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be focused on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response, as well as extending its indications. Keywords: severe asthma, IgE, omalizumab, exacerbation, chronic idiopathic urticarial, inhaled corticosteroid

  17. Effect of intranasal mometasone furoate administered in children with coexisting allergic rhinitis and asthma towards asthma attacks and lung function

    Directory of Open Access Journals (Sweden)

    Ellen P. Gandaputra

    2009-12-01

    during the study. There was >50% improvement in allergic rhinitis symptoms after 4 weeks of treatment (P50% after 8 weeks of treatment (P50% of asthma symptoms, however it is not followed with significant improvement in lung function. No side effects are reported during 8 weeks use of intranasal mometasone furoate.

  18. Severe asthma and acute attacks: diagnosis and management in ...

    African Journals Online (AJOL)

    Patients who continue to have symptoms with frequent attacks of asthma despite being adherent to treatment with multiple asthma medications, have severe asthma. Severe asthma has significant implications for the affected individual and utilise a disproportionate share of the health care costs associated with asthma.

  19. Children with problematic severe asthma: A biopsychosocial perspective

    NARCIS (Netherlands)

    Verkleij, M.

    2016-01-01

    This thesis focuses on problematic severe asthma in children and its treatment from a biopsychosocial perspective. Asthma is a chronic inflammatory disease of the airways. In children with problematic severe asthma, asthma is not under control despite optimal medical treatment. Asthma control is the

  20. Prevalence of asthma and allergic rhinitis among adults in Yaounde, Cameroon.

    Directory of Open Access Journals (Sweden)

    Eric Walter Pefura-Yone

    Full Text Available Population-based estimates of asthma and allergic rhinitis in sub-Saharan African adults are lacking. We assessed the prevalence and determinants of asthma and allergic rhinitis in urban adult Cameroonians.A community-based survey was conducted from December 2013 to April 2014 among adults aged 19 years and above (N = 2,304, 57.3% women, selected through multilevel stratified random sampling across all districts of Yaounde (Capital city. Internationally validated questionnaires were used to investigate the presence of allergic diseases. Logistic regressions were employed to investigate the determinants of allergic conditions.Prevalence rates were 2.7% (95% CI: 2.1-3.4 for asthma-ever, 6.9% (5.9-7.9 for lifetime wheezing, 2.9% (92.2-3.6 for current wheezing and 11.4% (10.1-12.7 for self-reported lifetime allergic rhinitis; while 240 (10.4% participants reported current symptoms of allergic rhinitis, and 125 (5.4% had allergic rhino-conjunctivitis. The prevalence of current asthma medication use and self-reported asthma attack was 0.8 (0.4-1.2 and 1 (0.6-1.4 respectively. Multivariable adjusted determinants of current wheezing were signs of atopic eczema [2.91 (1.09-7.74] and signs of allergic rhinitis [3.24 (1.83-5.71]. Age group 31-40 years [0.27(0.09-0.78, p = 0.016] was an independent protective factor for wheezing. Determinants of current rhinitis symptoms were active smoking [2.20 (1.37-3.54, p<0.001], signs of atopic eczema [2.84 (1.48-5.46] and current wheezing [3.02 (1.70-5.39].Prevalence rates for asthma and allergic rhinitis among adults in this population were at the lower tails of those reported in other regions of the world. Beside the classical interrelation between allergic diseases found in this study, active smoking was an independent determinant of allergic rhinitis symptoms. Nationwide surveys are needed to investigate regional variations.

  1. Validating app and 1-week version of the ´Control of allergic rhinitis and asthma test´ (CARAT)

    NARCIS (Netherlands)

    de Jong, Corina; Flokstra-de Blok, Bertine M.J.; de Kroon, Jorn; van Heijst, Elisabeth; Tsiligianni, Ioanna; Fonseca, Joao; van der Molen, Thys

    2016-01-01

    The Control of allergic rhinitis and asthma test (CARAT) has been designed to assess control of both asthma and allergic rhinitis (AR), covering a 4 week period, using paper-and-pencil (4wCARAT). It met al COSMIN criteria for patient reported outcomes. The aim is validation of the 1-week digital

  2. Characteristics and severity of asthma in children with and without atopic conditions : a cross-sectional study

    NARCIS (Netherlands)

    Arabkhazaeli, Ali; Vijverberg, Susanne J H; van Erp, Francine C; Raaijmakers, Jan A M; van der Ent, Cornelis K.; Maitland van der Zee, Anke H

    2015-01-01

    BACKGROUND: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children

  3. Characteristics and severity of asthma in children with and without atopic conditions: A cross-sectional study

    NARCIS (Netherlands)

    Arabkhazaeli, Ali; Vijverberg, Susanne J. H.; van Erp, Francine C.; Raaijmakers, Jan A. M.; van der Ent, Cornelis K.; Maitland van der Zee, Anke H.

    2015-01-01

    Background: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children

  4. Palivizumab Exposure and the Risk of Atopic Dermatitis, Asthma and Allergic Rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Stokholm, Lonny; Linder, Marie

    2017-01-01

    -mediated diseases atopic dermatitis, asthma, and allergic rhinoconjunctivitis after palivizumab exposure. AIM: Our objective was to investigate whether exposure to palivizumab was associated with atopic dermatitis, asthma, or allergic rhinoconjunctivitis in childhood. METHODS: This was a cross-national population......, and children with hemodynamic significant heart disease were defined. RESULTS: Of the 1,351,265 children included, 1192 (0.09%) were exposed to palivizumab. An increased risk of asthma after palivizumab exposure was observed in the total birth cohort (hazard ratio [HR] 1.49; 95% confidence interval [CI] 1.......32-1.68) and in the sub-cohort of preterm children (HR 1.24; 95% CI 1.07-1.44). However, post hoc analyses using the propensity score to balance confounding factors found no increased risk of asthma in preterm children (HR 0.91; 95% CI 0.56-1.48). No increased risks of atopic dermatitis (HR 1.18; 95% CI 0...

  5. The prevalence and risk factors of asthma and allergic diseases among working adolescents.

    Science.gov (United States)

    Cakir, Erkan; Ersu, Refika; Uyan, Zeynep Seda; Oktem, Sedat; Varol, Nezih; Karakoc, Fazilet; Karadag, Bulent; Akyol, Mesut; Dagli, Elif

    2010-01-01

    Certain occupational groups are known to be at particularly high risk of developing allergic diseases. The objective of the present study was to evaluate the prevalence of allergic diseases among working adolescents. The International Study of Asthma and Allergies in Childhood questionnaire was used. Four hundred and thirty six adolescents working in motor, lathe-finish, coiffure and textile and 366 high school students as control group were enrolled to the study. Mean age was 16.8 +/- 1.2 years and 82.9% of them were male. There was no significant difference among groups for ever and current wheezing while doctor diagnosed asthma was higher in lathe- finish group (p = 0.036). Family history of allergy, history of allergic rhinitis, and active smoking were found to be risk factors for asthma and related symptoms. Working in coiffure (p = 0.054), and textile (p = 0.003) were significant risk factors for ever allergic rhinitis. Working in lathe finish (p = 0.023), coiffure (p = .002), and textile (p lathe-finish was associated with doctor diagnosed asthma and active smoking was a risk factor for asthma and related symptoms. Working in coiffure, textile and lathe- finish were risk factors for rhinitis, and working in coiffure was a risk factor for eczema. Preventive measures should be taken at the onset of employment in order to prevent or reduce the detrimental effects of exposures in these occupational groups.

  6. The Differences in Serum Quantitative Specific IgE Levels Induced by Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis Sensitization in Intermittent and Persistent Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Agus Joko Susanto

    2018-01-01

    Full Text Available Background: house dust mites (HDM are an important inhalant allergen in allergic asthma. However, molecular diagnostic study of specific IgE to HDM allergens has not been done in Indonesia. In addition, the association of quantitative specific IgE measurement with asthma severity has not been investigatedd. This study aimed to investigate the difference of serum quantitative specific IgE levels induced by Dermatophagoides (D. pteronyssinus, D. farinae and Blomia tropicalis sensitization in intermittent and persistent allergic asthma. Methods: this was a cross-sectional study on adult allergic asthma patients who were invited for serum specific IgE testing. This study was a part of a larger study within the Division of Allergy and Immunology, Cipto Mangunkusumo Hospital. Asthma severity was defined based on Global Initiative on Asthma (GINA 2015 criteria and were grouped as intermittent or persistent. Quantitative specific IgE testing was done on blood serum using a multiple allergosorbent test (Polycheck Allergy, Biocheck GmbH, Munster, Germany. The HDM allergens tested were D. pteronyssinus, D. farinae, and Blomia tropicalis. Difference between two groups were analyze using Mann-Whitney test. Results: a total of 87 subjects were enrolled in this study; 69 (79.3% were women. Mean patients’ age was 40, 2 years. Sixty-three (72.4% subjects had asthma and allergic rhinitis. Fifty-eight (66.7% subjects were classified as persistent asthma. The prevalence of sensitization was 62.1% for D. farinae, 51.7% for D. pteronyssinus, and 48.3% for Blomia tropicalis. The median of specific IgE levels were significantly higher in persistent asthma compares to intermittent asthma induced by D. farinae (median 1.30 vs. 0.0 kU/L; p=0.024 and B. tropicalis (median 0.57 vs. 0.0 kU/L; p=0.015 sensitization. Level of Specific IgE  D. pteronyssinus was also to be higher in persistent asthma than the level measured in intermittent asthma (0.67 vs. 0.00 kU/L; p=0

  7. Perceived exercise limitation in asthma: The role of disease severity, overweight, and physical activity in children.

    Science.gov (United States)

    Westergren, Thomas; Berntsen, Sveinung; Lødrup Carlsen, Karin C; Mowinckel, Petter; Håland, Geir; Fegran, Liv; Carlsen, Kai-Håkon

    2017-02-01

    Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA). The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/m 2 or above at 18 years), exercise-induced bronchoconstriction (forced expiratory volume in one-second (FEV 1 ) pre- and post-exercise), methacholine bronchial challenge (severe BHR; provocative dose causing ≥20% decrease in FEV 1 ≤ 1 μmol), and asthma severity score (dose of controller medication and exacerbations last 12 months). Multivariate logistic regression analyses were conducted to assess associations with perceived EL. In the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEV 1 post-exercise (OR: 1.48 (1.10, 1.98)) and overweight (OR: 2.15 (1.13, 4.08) and 2.53 (1.27, 5.03)) explained 9.7% and 8.4% of perceived EL, respectively. Perceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Fish intake during pregnancy and the risk of child asthma and allergic rhinitis - longitudinal evidence from the Danish National Birth Cohort.

    Science.gov (United States)

    Maslova, Ekaterina; Strøm, Marin; Oken, Emily; Campos, Hannia; Lange, Christoph; Gold, Diane; Olsen, Sjurdur F

    2013-10-01

    Maternal fish intake during pregnancy may influence the risk of child asthma and allergic rhinitis, yet evidence is conflicting on its association with these outcomes. We examined the associations of maternal fish intake during pregnancy with child asthma and allergic rhinitis. Mothers in the Danish National Birth Cohort (n 28 936) reported their fish intake at 12 and 30 weeks of gestation. Using multivariate logistic regression, we examined the associations of fish intake with child wheeze, asthma and rhinitis assessed at several time points: ever wheeze, recurrent wheeze (>3 episodes), ever asthma and allergic rhinitis, and current asthma, assessed at 18 months (n approximately 22,000) and 7 years (n approximately 17,000) using self-report and registry data on hospitalisations and prescribed medications. Compared with consistently high fish intake during pregnancy (fish as a sandwich or hot meal > or equal to 2-3 times/week), never eating fish was associated with a higher risk of child asthma diagnosis at 18 months (OR 1·30, 95% CI 1·05, 1·63, P=0·02), and ever asthma by hospitalisation (OR 1·46, 95% CI 0·99, 2·13, P=0·05) and medication prescription (OR 1·37, 95% CI 1·10, 1·71, P=0·01). A dose-response was present for asthma at 18 months only (P for trend=0·001). We found no associations with wheeze or recurrent wheeze at 18 months or with allergic rhinitis. The results suggest that high (v. no) maternal fish intake during pregnancy is protective against both early and ever asthma in 7-year-old children.

  9. Weighted road density and allergic disease in children at high risk of developing asthma.

    Directory of Open Access Journals (Sweden)

    Anna L Hansell

    Full Text Available Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS, potentially susceptible to air pollution effects because of a family history of asthma.We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density, as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs, total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis.Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR for house dust mite (HDM positive SPT was 1.25 (95% CI: 1.06-1.48, for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01-1.41 and for allergic rhinitis was 1.30 (95% CI: 1.03-1.63 per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children.Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma.

  10. Effect of asthma severity on symptom perception in childhood asthma

    Directory of Open Access Journals (Sweden)

    A.L.B. Cabral

    2002-03-01

    Full Text Available Individual ability to perceive airway obstruction varies substantially. The factors influencing the perception of asthma are probably numerous and not well established in children. The present study was designed to examine the influence of asthma severity, use of preventive medication, age and gender on the association between respiratory symptoms (RS and peak expiratory flow (PEF rates in asthmatic children. We followed 92 asthmatic children, aged 6 to 16 years, for five months. Symptom scores were recorded daily and PEF was measured twice a day. The correlations among variables at the within-person level over time were analyzed for each child and for the pooled data by multivariate analysis. After pooling the data, there was a significant (P<0.05 correlation between each symptom and PEF; 60% of the children were accurate perceivers (defined by a statistically significant correlation between symptoms and PEF across time for diurnal symptoms and 37% for nocturnal symptoms. The accuracy of perception was independent of asthma severity, age, gender or the use of preventive medication. Symptom perception is inaccurate in a substantial number of asthmatic children, independently of clinical severity, age, gender or use of preventive medication. It is not clear why some asthmatic patients are capable of accurately perceiving the severity of airway obstruction while others are not.

  11. Meta-analysis of the comorbidity rate of allergic rhinitis and asthma in Chinese children.

    Science.gov (United States)

    Kou, Wei; Li, Xuelei; Yao, Hongbing; Wei, Ping

    2018-04-01

    Allergic rhinitis (AR) and asthma often occur concomitantly and are the two most common inflammatory conditions of the airways in children. Large-scale studies investigating the comorbidity of asthma and AR in children are rare. So, we performed a meta-analysis to describe the comorbidity rate of asthma and AR in Chinese children. We retrieved related studies from Pubmed, Science, Springer, Elsevier, Embase, BMJ, and four Chinese biomedical databases, including Wanfang Data, VIP, CBM, and CNKI. From these individual studies, the comorbidity rate of asthma and AR in Chinese children was extracted and pooled to generate summary effect estimates in R version 3.2.3. The meta-analysis included 25 cross-sectional studies. The results indicated that in China, the incidence of asthma in children with AR is 35.01% (95% CI: 32.32%-37.70%) and the incidence of AR in children with asthma is 54.93% (95% CI: 53.05%-56.80%). The comorbidity of AR and asthma is high in Chinese children. Statistically, the prevalence of AR was higher in children with asthma, as opposed to the prevalence of asthma in children with AR. The comorbidity rate of AR and asthma signifies the importance of improving the recognition and treatment under both conditions by respiratory physicians and otolaryngologists. Copyright © 2018. Published by Elsevier B.V.

  12. Assessment of problematic severe asthma in children

    DEFF Research Database (Denmark)

    Carlsen, K. C. L.; Hedlin, G.; Bush, A.

    2011-01-01

    Assessment of problematic severe asthma in children should be performed in a stepwise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessm......Assessment of problematic severe asthma in children should be performed in a stepwise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi......-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps...... in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small...

  13. Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis

    Science.gov (United States)

    Lai, Tianwen; Wang, Shaobin; Xu, Zhiwei; Zhang, Chao; Zhao, Yun; Hu, Yue; Cao, Chao; Ying, Songmin; Chen, Zhihua; Li, Wen; Wu, Bin; Shen, Huahao

    2015-01-01

    Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ≥52 weeks) was performed, and six studies met our final inclusion criteria (n = 2,749). Omalizumab was associated with significant improvements in quality of life and the Global Evaluation of Treatment Effectiveness. Omalizumab also allowed patients to completely withdraw from inhaled corticosteroid therapy and did not increase the overall incidence of adverse events. However, there was insufficient evidence that omalizumab reduced the incidence of exacerbations, and the cost-effectiveness of omalizumab varied across studies. Our data indicated that omalizumab use for at least 52 weeks in patients with persistent uncontrolled allergic asthma was accompanied by an acceptable safety profile, but it lacked effect on the asthma exacerbations. Use of omalizumab was associated with a higher cost than conventional therapy, but these increases may be cost-effective if the medication is used in patients with severe allergic asthma. PMID:25645133

  14. Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma

    NARCIS (Netherlands)

    van Aalderen, W. M.; Postma, D. S.; Koëter, G. H.; Knol, K.

    1991-01-01

    A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine

  15. Allergen-specific subcutaneous immunotherapy in allergic asthma : immunologic mechanisms and improvement

    NARCIS (Netherlands)

    Taher, Yousef A.; Henricks, Paul A. J.; van Oosterhout, Antoon J. M.

    2010-01-01

    Allergic asthma is a disease characterized by persistent allergen-driven airway inflammation, remodeling, and airway hyperresponsiveness. CD4(+) T-cells, especially T-helper type 2 cells, play a critical role in orchestrating the disease process through the release of the cytokines IL-4, IL-5, and

  16. Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis.

    Directory of Open Access Journals (Sweden)

    Arancha Hevia

    Full Text Available Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 ± 10.98 years old and compare it with the fecal microbiota of 22 healthy controls (age 39.29 ± 9.21 years old using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha-diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long-term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients.

  17. A functional CD86 polymorphism associated with asthma and related allergic disorders

    DEFF Research Database (Denmark)

    Corydon, Thomas Juhl; Haagerup, Annette; Jensen, Thomas Gryesten

    2007-01-01

    BACKGROUND: Several studies have documented a substantial genetic component in the aetiology of allergic diseases and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21, at which linkage to multiple atopy phenotypes has been reported. This region harbours the CD8......, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders....... gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulates the immune response upon allergen challenge. METHODS: We sequenced the CD86 gene in patients with atopy from 10 families that showed...... evidence of linkage to 3q21. Identified polymorphisms were analysed in a subsequent family-based association study of two independent Danish samples, respectively comprising 135 and 100 trios of children with atopy and their parents. Functional analysis of the costimulatory effect on cytokine production...

  18. Allergic asthma is associated with increased risk of infections requiring antibiotics

    DEFF Research Database (Denmark)

    Woehlk, Christian; von Bülow, Anna; Kriegbaum, Margit

    2018-01-01

    : To investigate allergy as a risk factor for respiratory infections requiring antibiotics based on register data from a nationwide population of patients with asthma. METHODS: A register-based prospective follow-up study was performed using the Danish prescription database. In the inclusion period from 2010......BACKGROUND: Viral infection and allergy have been identified as major risk factors for exacerbation in asthma, especially in the presence of both. However, whether patients with allergic asthma are more susceptible to respiratory infections requiring antibiotics remains unknown. OBJECTIVE...... asthma was associated with an increased risk of filling at least 2 antibiotic prescriptions per year compared with nonallergic asthma (odds ratio 1.28, 95% confidence interval 1.24-1.33, P effect of immunotherapy against the risk...

  19. Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Haruka Aoki

    2014-01-01

    Full Text Available An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR, infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1 and acid-sensing ion channels (ASICs in severe acidic pH (of less than 6.0-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases.

  20. Influence of antibiotic use in early childhood on asthma and allergic diseases at age 5.

    Science.gov (United States)

    Yamamoto-Hanada, Kiwako; Yang, Limin; Narita, Masami; Saito, Hirohisa; Ohya, Yukihiro

    2017-07-01

    In the past few decades, the prevalence of allergic diseases has increased rapidly worldwide. At the same time, the overuse of antibiotics has been observed, especially in Japan. To elucidate the association of early childhood antibiotic use with allergic diseases in later childhood at 5 years of age. Relevant data were extracted from the hospital-based birth cohort study, the Tokyo Children's Health, Illness and Development Study. To identify signs of asthma and allergic diseases in children, the International Study of Asthma and Allergies in Childhood questionnaire was used. Logistic regression models were applied to estimate the effect of antibiotic use on outcomes in later life. Antibiotic exposure in children within the first 2 years of life was associated with current asthma (adjusted odds ratio [aOR] 1.72, 95% confidence interval [CI] 1.10-2.70), current atopic dermatitis (aOR 1.40, 95% CI 1.01-1.94), and current allergic rhinitis (aOR 1.65, 95% CI 1. 05-2.58) at 5 years of age. Analysis of the associations by type of antibiotics showed that cephem was associated with current asthma (aOR 1.97, 95% CI 1.23-3.16) and current rhinitis (aOR 1.82, 95% CI 1.12-2.93), and macrolide was associated with current atopic dermatitis (aOR 1.58, 95% CI 1.07-2.33). Our findings suggest that antibiotic use within the first 2 years of life was a risk factor for current asthma, current atopic dermatitis, and current allergic rhinitis in 5-year-old children. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Th17 immunity in children with allergic asthma and rhinitis: a pharmacological approach.

    Directory of Open Access Journals (Sweden)

    Giusy Daniela Albano

    Full Text Available Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss, nasal wash (NW and plasma (P from Healthy Controls (HC and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested "in vitro" on IL-17A, RORγ(t and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of 12 weeks of treatment with Budesonide and Formoterol was tested "in vivo" in T-lymphocytes from mild-moderate asthma/persistent rhinitis patients. IL-17A was increased in Ss, NW and P from children with mild-moderate asthma compared with intermittent and HC. In cultured T-lymphocytes IL-17A and RORγ(t expression were higher in mild-moderate asthma/persistent rhinitis than in mild-moderate asthma/intermittent rhinitis, while FOXP3 was reduced. Budesonide with Formoterol reduced IL-17A and RORγ(t, while increased FOXP3 in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis, and reduced the IL-8 release mediated by IL-17A present in NW and Ss from mild-moderate asthma/persistent rhinitis in nasal and bronchial epithelial cells. Finally, Budesonide with Formoterol reduced IL-17A levels in P and Ss, CD4(+IL-17A(+T-cells, in naïve children with mild-moderate asthma/persistent rhinitis after 12 weeks of treatment. Th17 mediated immunity may be involved in the airway disease of children with allergic asthma and allergic rhinitis. Budesonide with Formoterol might be a useful tool for its therapeutic control.

  2. ALLERGIC ASTHMA AND THE DEVELOPING IMMUNE SYSTEM: A PILOT STUDY

    Science.gov (United States)

    Rationale: The predisposition towards atopic disease begins early in life, and that the risk of developing asthma is heightened following prenatal exposure to some compounds. Nonetheless, the effect of gestational aeroallergen exposure on the developing immune system is unclear....

  3. The Prevalence of Allergic Diseases among Children with Asthma ...

    African Journals Online (AJOL)

    2018-03-15

    Mar 15, 2018 ... small-sized family were both associated with asthma exacerbations. Most children studied ..... effect of urbanization and adoption of “western habits.” .... associations between parent-reported biological indoor environment and ...

  4. Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

    Science.gov (United States)

    Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

    2015-08-01

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

  5. Asthma and other allergic diseases among Saudi schoolchildren in Najran: the need for a comprehensive intervention program.

    Science.gov (United States)

    Alqahtani, Jobran M

    2016-01-01

    In the last three decades, an increasing incidence of allergic diseases has been associated with increasing morbidity and mortality in children and young adults. The study aimed to investigate the prevalence and risk factors associated with allergic diseases among Saudi schoolchildren in the southwestern Saudi region of Najran, and to determine the sensitization of patients to a set of allergens. Cross-sectional observational study. Primary, intermediate and secondary schools, Najran, Saudi Arabia. All participants completed the Arabic version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Skin prick tests (SPT) were performed, using a panel of standardized allergenic extracts. Prevalence and risk factors associated with pediatric allergic diseases. The study included 1700 Saudi schoolchildren. The overall prevalence of physician-diagnosed asthma, allergic rhinitis and atopic dermatitis was 27.5%, 6.3% and 12.5%, respectively. Multivariate analysis showed that male gender (adjusted odds ratio [aOR], 1.27), fast food consumption (aOR, 1.53), trucks passing near houses (aOR, 1.86), and having a dog or cat at home (aOR, 1.85) were significant risk factors. A total of 722 (42.5%) children had a positive SPT result to at least one allergen. The most prevalent allergens were grass pollens (60%), cat fur (41.6%), and house dust mites (25%). The findings of this study highlight the urgent need for developing an effective interven- tion program including several components working in harmony to control and reduce the burden of allergic diseases. These results may not be generalizable to the rest of Saudi Arabia.

  6. Vitamin D in atopic dermatitis, asthma and allergic diseases.

    Science.gov (United States)

    Searing, Daniel A; Leung, Donald Y M

    2010-08-01

    This review examines the scientific evidence behind the hypothesis that vitamin D plays a role in the pathogenesis of allergic diseases, along with a focus on emerging data regarding vitamin D and atopic dermatitis. Elucidated molecular interactions of vitamin D with components of the immune system and clinical data regarding vitamin D deficiency and atopic diseases are discussed. The rationale behind the sunshine hypothesis, laboratory evidence supporting links between vitamin D deficiency and allergic diseases, the clinical evidence for and against vitamin D playing a role in allergic diseases, and the emerging evidence regarding the potential use of vitamin D to augment the innate immune response in atopic dermatitis are reviewed. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma.

    Science.gov (United States)

    Kim, Dong Eon; Lee, Yonghyun; Kim, MinGyo; Lee, Soyoung; Jon, Sangyong; Lee, Seung-Hyo

    2017-09-01

    Although asthma, a chronic inflammatory airway disease, is relatively well-managed by inhaled corticosteroids, the side effects associated with the long-term use of these agents precipitate the need for alternative therapeutic options based on differing modes of action. Bilirubin, a potent endogenous antioxidant, and anti-inflammatory molecule have been shown to ameliorate asthmatic symptoms; however, its clinical translation has been limited owing to its water insolubility and associated potential toxicity. Here we report the first application of bilirubin-based nanoparticles (BRNPs) as a nanomedicine for the treatment of allergic lung inflammatory disease. BRNPs were prepared directly from self-assembly of PEGylated bilirubin in aqueous solution and had a hydrodynamic diameter of ∼100 nm. Because allergen-specific type 2 T-helper (Th2) cells play a key role in the pathogenesis and progression of allergic asthma, the effects of BRNPs on Th2 immune responses were investigated both in vivo and in vitro. BRNPs after intravenous injection (i.v.) showed much higher serum concentration and a longer circulation time of bilirubin than the intraperitoneal injection (i.p.) of BRNPs or unconjugated bilirubin (UCB). The anti-asthmatic effects of BRNPs were assessed in a mouse model of allergen-induced asthma. Compared with UCB, treatment with BRNPs suppressed the symptoms of experimental allergic asthma and dramatically ameliorated Th2-related allergic lung inflammation. Consistent with these results, BRNPs caused a reduction of Th2 cell populations and the expression of related cytokines by antibody-stimulated CD4 + T cells in vitro. Therefore, our results establish BRNPs as an important immunomodulatory agent that may be useful as a therapeutic for allergic lung inflammatory disease and other immune-mediated disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics.

    Science.gov (United States)

    Konradsen, Jon R; Nordlund, Björn; Onell, Annica; Borres, Magnus P; Grönlund, Hans; Hedlin, Gunilla

    2014-03-01

    Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. Children with severe asthma had lower asthma control (p Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

    Directory of Open Access Journals (Sweden)

    Tabatabaian F

    2018-04-01

    Full Text Available Farnaz Tabatabaian, Dennis K Ledford Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA Abstract: Asthma is a heterogeneous syndrome with numerous underlining molecular and inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes. Multiple therapies targeting severe asthma with type 2 (T2 high inflammation are or soon will be available. T2 high inflammation is defined as inflammation associated with atopy or eosinophilia or an increase in cytokines associated with T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody and the first biologic therapy approved for moderate–severe allergic asthma. Despite the specificity of biologic therapies like omalizumab, clinical response is variable, with approximately 50% of treated patients achieving the primary outcome. A prior identification of the ideal candidate for therapy would improve patient outcomes and optimize the use of health care resources. As the number of biologic therapies for asthma increases, the goal is identification of biomarkers or clinical phenotypes likely to respond to a specific therapy. This review focuses on potential biomarkers and clinical history that may identify responders to omalizumab therapy for asthma. Keywords: severe persistent asthma, asthma phenotype and endotype, T2 high inflammation, omalizumab, asthma biomarkers, eosinophils, fractional exhaled nitric oxide, IgE

  10. The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma

    Directory of Open Access Journals (Sweden)

    Tomomitsu Miyasaka

    2018-01-01

    Full Text Available Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a “neuropsychiatry phenotype” in asthma.

  11. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

  12. The Prevalence of Symptoms of Asthma and Allergic Diseases through ISSAC Method in Teenagers

    Directory of Open Access Journals (Sweden)

    Jafar Hassanzadeh

    2012-04-01

    Full Text Available Background: Asthma is the most important chronic disease in children and one of the causes of school absenteeism, which is getting more prevalent by the increase of environmental pollutants and industrial life. This study was planned and performed to estimate the prevalence of asthma and other allergic diseases.Materials and Methods: This cross-sectional study was conducted in 2009 on 3000 female and male students of first grade of guidance school, who were selected by multistage sampling. Data were collected by standard questionnaire and after data collection and entering ISSAC SPSS software the prevalence of asthma and allergic diseases was estimated. Statistical analysis was performed using χ2 statistical test at significance level of 0.05.Results: Prevalence of asthma, hives, eczema and atopic disease was respectively 3.8 percent, 10.4%, 18.3% and 42%. Prevalence of hives, eczema, atopic disease, watery eyes and wheezing after exercise in both genders showed a statistically significant difference (p 0.05Conclusion: The results of this study indicated that although the prevalence of asthma in Shirazi children is less than some other cities, the increased development of disease in recent years will be a threatening risk and this phenomenon requires serious attention and planning by authorities as well as health policymakers.

  13. Atopy, but not obesity is associated with asthma severity among children with persistent asthma.

    Science.gov (United States)

    Lu, Kim D; Phipatanakul, Wanda; Perzanowski, Matthew S; Balcer-Whaley, Susan; Matsui, Elizabeth C

    2016-12-01

    Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma. A cross-sectional analysis of 832 children and adolescents, age range 5-17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA. Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step. Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States.

  14. The burden of severe asthma in childhood and adolescence

    DEFF Research Database (Denmark)

    Fleming, Louise; Murray, Clare; Bansal, Aruna T

    2015-01-01

    U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches. A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53...... in the severe wheeze cohort. Almost all participants in each cohort were atopic and had a normal body mass index. Asthma-related quality of life, as assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), was worse...... and mild/moderate cohorts were clinically very similar. Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life that is associated with poor control and airflow limitation: a very different phenotype from adult severe asthma. In-depth phenotyping...

  15. The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens.

    Science.gov (United States)

    Wilson, Rhonda H; Maruoka, Shuichiro; Whitehead, Gregory S; Foley, Julie F; Flake, Gordon P; Sever, Michelle L; Zeldin, Darryl C; Kraft, Monica; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N

    2012-11-01

    Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction. Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria. The ability of bacterial products to act as adjuvants suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen-presenting dendritic cells (DCs) in vitro and promote allergic sensitization to inhaled innocuous proteins in vivo. It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen for adjuvant activity of microbial products revealed that the bacterial protein flagellin (FLA) stimulated strong allergic airway responses to an innocuous inhaled protein, ovalbumin (OVA). Moreover, Toll-like receptor 5 (TLR5), the mammalian receptor for FLA, was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, individuals with asthma have higher serum levels of FLA-specific antibodies as compared to nonasthmatic individuals. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens.

  16. Total and specific serum IgE decreases with age in patients with allergic rhinitis, asthma and insect allergy but not in patients with atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Neuber Karsten

    2005-05-01

    Full Text Available Abstract Concerning allergic diseases, the incidence of allergic symptoms, as well as their severity, seems to decrease with age. The decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total and specific IgE. Atopic disorders are complex diseases that involve interactions among several physiological systems, e.g. skin, lung, mucosae, and the immune system. It was the aim of this study to compare the effects of age on total and specific IgE in patients with atopic dermatitis (AD, allergic rhinitis or asthma, and insect allergy, respectively. The study population consisted of 559 individuals (male: 229 and female: 330. Total and allergen specific IgE was measured in every individual. From the whole study population, 113 patients suffered from atopic dermatitis (AD, 132 had allergic rhinitis or asthma, and 314 were tested because of insect allergy. Total and specific serum IgE was significantly decreased as a function of age in patients with allergic rhinitis and asthma and with insect allergy. In contrast, no significant decrease of total and specific serum IgE in old individuals with AD was observed. Additionally, in the group of patients with a total IgE 300 kU/l showed no correlation with age. Immunosenescence does not affect increased IgE levels in atopic patients with AD and/or high serum IgE levels indicating that in these subgroups of patients the atopic propensity remains into advanced age. One may hypothesize that either onset of allergic sensitization during life or the kind of atopic disease influences the correlation between age and IgE synthesis.

  17. The Prevalence of Severe Asthma and Low Asthma Control Among Danish Adults

    DEFF Research Database (Denmark)

    von Bülow, Anna; Kriegbaum, Margit; Backer, Vibeke

    2014-01-01

    asthma, the extent of asthma control, and contact with specialist care. METHODS: A descriptive cross-sectional register study was performed. By using a nationwide prescription database, we identified current patients with asthma (age, 18-44 years) in 2010. Severity was classified as severe versus mild......-moderate asthma according to the level of antiasthma treatment. We investigated prescription drug use, hospitalizations, emergency department visits, and outpatient clinic visits according to severity. RESULTS: Among a nationwide population, we identified 61,583 current patients with asthma. Based on the level...... asthma and low asthma control were not managed by specialist care. Patients with severe asthma with specialist contact more frequently had impaired asthma control compared with subjects not treated by a specialist (44.4% vs 33.1%, P

  18. [Severe uncontrolled asthma in patients over 75 years old: Treatment with omalizumab].

    Science.gov (United States)

    Romand, P; Kelkel, E; Saint-Raymond, C; Glas, N; Caillaud, D; Devouassoux, G

    2016-05-01

    With an aging population and an increase in the prevalence of asthma, this disease is becoming more common in the elderly. Nevertheless, the management of severe asthma can be complex, due to an increased risk of uncontrolled disease in patients over 65 years old and partly to the inherent characteristics of old age: comorbidities, underestimation of the role of allergies, poor adherence, difficulties with inhalation devices, etc. We report two cases of women over 75 with severe persistent allergic asthma not controlled by high doses of inhaled corticosteroids and long-acting beta-2-agonists in whom treatment with omalizumab was initiated. Following treatment with omalizumab a decrease in the number and severity of exacerbations, improved asthma control and dose reduction or discontinuation of systemic corticosteroids were observed. The tolerance of omalizumab was good in both cases. Omalizumab is to be considered an effective and well-tolerated therapeutic option for elderly patients with inadequately controlled severe allergic asthma. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Vitamin D in Atopic Dermatitis, Asthma and Allergic Diseases

    OpenAIRE

    Searing, Daniel A; Leung, Donald YM

    2010-01-01

    This review examines the scientific evidence behind the hypothesis that vitamin D plays a role in the pathogenesis of allergic diseases, with a particular focus on emerging data regarding vitamin D and atopic dermatitis. Both elucidated molecular interactions of vitamin D with components of the immune system, as well as clinical data regarding vitamin D deficiency and atopic diseases are discussed. The rationale behind the “sunshine hypothesis,” laboratory evidence supporting links between vi...

  20. Physical Activity, Sedentary Habits, Sleep, and Obesity are Associated with Asthma, Allergic Rhinitis, and Atopic Dermatitis in Korean Adolescents.

    Science.gov (United States)

    Lim, Man Sup; Lee, Chang Hee; Sim, Songyong; Hong, Sung Kwang; Choi, Hyo Geun

    2017-09-01

    Since pathophysiologic evidence has been raised to suggest that obesity could facilitate an allergic reaction, obesity has been known as an independent risk factor for allergic disease such as asthma. However, the relationship between sedentary behavior and lifestyle which could lead to obesity, and those allergic diseases remains unclear. We analyzed the relations between physical activity, including sitting time for study, sitting time for leisure and sleep time, and obesity, asthma, allergic rhinitis, and atopic dermatitis using the Korea Youth Risk Behavior Web-based Survey, which was conducted in 2013. Total 53769 adolescent participants (12 through 18 years old) were analyzed using simple and multiple logistic regression analyses with complex sampling. Longer sitting time for study and short sitting time for leisure were associated with allergic rhinitis. High physical activity and short sleep time were associated with asthma, allergic rhinitis, and atopic dermatitis. Underweight was negatively associated with atopic dermatitis, whereas overweight was positively correlated with allergic rhinitis and atopic dermatitis. High physical activity, and short sleep time were associated with asthma, allergic rhinitis, and atopic dermatitis. © Copyright: Yonsei University College of Medicine 2017

  1. The validity of register data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis.

    Science.gov (United States)

    Stensballe, Lone Graff; Klansø, Lotte; Jensen, Andreas; Haerskjold, Ann; Thomsen, Simon Francis; Simonsen, Jacob

    2017-09-01

    The incidence of atopic dermatitis, wheezing, asthma and allergic rhinoconjunctivitis has been increasing. Register-based studies are essential for research in subpopulations with specific diseases and facilitate epidemiological studies to identify causes and evaluate interventions. Algorithms have been developed to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis using register information on disease-specific dispensed prescribed medication and hospital contacts, but the validity of the algorithms has not been evaluated. This study validated the algorithms vs gold standard deep telephone interviews with the caretaker about physician-diagnosed atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis in the child. The algorithms defined each of the three atopic diseases using register-based information on disease-specific hospital contacts and/or filled prescriptions of disease-specific medication. Confirmative answers to questions about physician-diagnosed atopic disease were used as the gold standard for the comparison with the algorithms, resulting in sensitivities and specificities and 95% confidence intervals. The interviews with the caretaker of the included 454 Danish children born 1997-2003 were carried out May-September 2015; the mean age of the children at the time of the interview being 15.2 years (standard deviation 1.3 years). For the algorithm capturing children with atopic dermatitis, the sensitivity was 74.1% (95% confidence interval: 66.9%-80.2%) and the specificity 73.0% (67.3%-78.0%). For the algorithm capturing children with asthma, both the sensitivity of 84.1% (78.0%-88.8%) and the specificity of 81.6% (76.5%-85.8%) were high compared with physician-diagnosed asthmatic bronchitis (recurrent wheezing). The sensitivity remained high when capturing physician-diagnosed asthma: 83.3% (74.3%-89.6%); however, the specificity declined to 66.0% (60.9%-70.8%). For allergic rhinoconjunctivitis, the sensitivity

  2. Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Nur Salme Suhana Shamshuddin

    2018-01-01

    Full Text Available Allergic asthma is a chronic inflammatory disorder of the pulmonary airways. Gelam honey has been proven to possess anti-inflammatory property with great potential to treat an inflammatory condition. However, the effect of ingestion of Gelam honey on allergic asthma has never been studied. This study aimed to investigate the efficacy of Gelam honey on the histopathological changes in the lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into seven groups: control, I, II, III, IV, V and VI group. All groups except the control were sensitized and challenged with ovalbumin. Mice in groups I, II, III, IV, and V were given honey at a dose of 10% (v/v, 40% (v/v and 80% (v/v, dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle respectively, orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h after the last OVA challenged and the lungs were evaluated for histopathological changes by light microscopy. All histopathological parameters such as epithelium thickness, the number of mast cell and mucus expression in Group III significantly improved when compared to Group VI except for subepithelial smooth muscle thickness (p < 0.05. In comparing Group III and IV, all the improvements in histopathological parameters were similar. Also, Gelam honey showed a significant (p < 0.05 reduction in inflammatory cell infiltration and beta-hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we demonstrated that administration of high concentration of Gelam honey alleviates the histopathological changes of mice model of allergic asthma.

  3. Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Mushaben

    Full Text Available The mammalian target of rapamycin (mTOR plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4-6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR, inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4(+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4(+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

  4. Increasing prevalence of asthma, respiratory symptoms, and allergic diseases: Four repeated surveys from 1993-2014.

    Science.gov (United States)

    Brozek, Grzegorz; Lawson, Joshua; Szumilas, Dawid; Zejda, Jan

    2015-08-01

    Published data shows different prevalence trends depending on the region of Europe. The aim of the study was to analyze time trends of the frequency of the respiratory symptoms and allergic diseases in school children (Silesia, Poland) over the last 21 years. We compared the results of four population-based surveys performed in a town of Chorzow in 1993, 2002, 2007 and 2014 in children aged 7-10 years. All four studies had the same study protocol, recruitment (cluster, school-based sampling), questionnaire (WHO respiratory health questionnaire) and the same principal investigator The surveys included 1130 children in 1993, 1421 children in 2002, 1661 children in 2007 and 1698 in 2014. The results covered a 21 year span and showed a statistically significant (p increase in the prevalence of the following physician-diagnosed disorders (1993-2002-2007-2014): asthma (3.4%-4.8%-8.6%-12,6%); allergic rhinitis (4.3%-11.9%-15.9%-13.9%); atopic dermatitis (3.6%-7.9%-12.0%-13.9%); allergic conjunctivitis (4.3%-7.9%-8.3%-7.9%); A simultaneous increasing trend (p increased proportion of treated children (51.3%-51.3%-69.5%-60.7%) and a lower frequency of presenting current symptoms. Our findings are in line with the concept of a real increase in the occurrence of asthma and allergic disease in children. The pattern involves not only physician-diagnosed allergic diseases but also occurrence of symptoms related to respiratory disorders. Diagnosed asthma is better treated and better controlled. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms

    DEFF Research Database (Denmark)

    Mosbech, Holger; Canonica, G Walter; Backer, Vibeke

    2015-01-01

    BACKGROUND: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. OBJECTIVE: To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory...... allergic disease and report the AR results. METHODS: Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication...... score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). RESULTS...

  6. The measurement of cell mediated immunity by radioimmunoassay in desensitizing treatment with acupoints for allergic asthma

    International Nuclear Information System (INIS)

    Zhou Ronglin; Luan Meiling; Wang Mingsuo; Liu Keliang

    1994-05-01

    Three mitogens consisted of PHA, PWM, LPS were used to activate lymphocytes. Lymphocyte transformation with radioisotope incorporation of 3 H-TdR was done in 20 patients with allergic asthma and 14 healthy persons as control groups. Cell mediated immune in these cases of desensitizing treatment with acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, activated by PHA, PWM, LPS, of the allergic asthma patients were P>0.05, P 3 H-TdR in lymphocytes after desensitizing treatment with acupoints compared with that before the treatment tended to be normal. Lymphocyte transformation difference of 3 H-TdR incorporation rates between this group and A or B control groups was significant (P<0.01). This study provides scientific clinical experimental evidences for researching cell mediated immune in attack and curative effects of allergic asthma

  7. Severe asthma: anti-IgE or anti-IL-5?

    Directory of Open Access Journals (Sweden)

    Evgenia Papathanassiou

    2016-11-01

    Full Text Available Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator. Anti-IgE (omalizumab and anti-IL-5 (mepolizumab antibodies are biological agents that interfere in different steps of the Th2 inflammatory cascade and are licensed in severe asthma. Both exhibit a favourable clinical outcome as they reduce exacerbation rate and improve asthma control and quality of life, while mepolizumab also induces an oral steroid sparing effect. Nevertheless, it is still questionable which agent is more suitable in the management of severe allergic asthma since no comparable studies have been conducted. Omalizumab's established effectiveness in clinical practice over a long period is complemented by a beneficial effect on airway remodelling process mediated mainly through its impact on eosinophils and other parameters strongly related to eosinophilic inflammation. However, it is possible that mepolizumab through nearly depleting eosinophils could have a similar effect on airway remodelling. Moreover, to date, markers indicative of the patient population responding to each treatment are unavailable although baseline eosinophils and exacerbation rate in the previous year demonstrate a predictive value regarding anti-IL-5 therapy effectiveness. On the other hand, a better therapeutic response for omalizumab has been observed when low forced expiratory volume in 1 sec, high-dose inhaled corticosteroids and increased IgE concentrations are present. Consequently, conclusions are not yet safe to be drawn based on

  8. INFLUENCE OF THE BRONCHIAL ASTHMA, ALLERGIC RHINITIS AND ATOPIC DERMATITIS ON THE QUALITY OF THE CHILDREN'S LIFE

    Directory of Open Access Journals (Sweden)

    A.A. Dzhumagaziev

    2009-01-01

    Full Text Available This article is devoted to the study of the life quality of the children, suffering from bronchial asthma, allergic rhinitis and atopic dermatitis. The authors identified that children with atopic dermatitis have the lowest level of the life quality, while children, suffering from allergic rhinitis, have the highest values of the given property. It is typical that children and their parents evaluate the life at school extremely low against rather high figures of the physical and emotional functioning.Key words: bronchial asthma, allergic rhinitis, atopic dermatitis, children, life quality.

  9. Age-Specific Characteristics of Inpatients with Severe Asthma Exacerbation

    Directory of Open Access Journals (Sweden)

    Kiyoshi Sekiya

    2013-01-01

    Conclusions: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.

  10. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    Science.gov (United States)

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though

  11. Working while unwell: Workplace impairment in people with severe asthma.

    Science.gov (United States)

    Hiles, Sarah A; Harvey, Erin S; McDonald, Vanessa M; Peters, Matthew; Bardin, Philip; Reynolds, Paul N; Upham, John W; Baraket, Melissa; Bhikoo, Zaheerodin; Bowden, Jeffrey; Brockway, Ben; Chung, Li Ping; Cochrane, Belinda; Foxley, Gloria; Garrett, Jeffrey; Hew, Mark; Jayaram, Lata; Jenkins, Christine; Katelaris, Constance; Katsoulotos, Gregory; Koh, Mariko S; Kritikos, Vicky; Lambert, Marina; Langton, David; Rivero, Alexis Lara; Marks, Guy B; Middleton, Peter G; Nanguzgambo, Aldoph; Radhakrishna, Naghmeh; Reddel, Helen; Rimmer, Janet; Southcott, Anne Marie; Sutherland, Michael; Thien, Francis; Wark, Peter Ab; Yang, Ian A; Yap, Elaine; Gibson, Peter G

    2018-04-20

    Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. To compare workplace productivity - absenteeism and presenteeism - and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. The Severe Asthma Web-based Database (SAWD) is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18 to 88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (pworkplace. Improving asthma control and mental health may be important targets for optimising workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.

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    Aude Aumeunier

    Full Text Available BACKGROUND: Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. METHODS AND FINDINGS: Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL-10 and transforming growth factor (TGF-beta and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses

  13. Modulation of lung inflammation by vessel dilator in a mouse model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Cormier Stephania A

    2009-07-01

    Full Text Available Abstract Background Atrial natriuretic peptide (ANP and its receptor, NPRA, have been extensively studied in terms of cardiovascular effects. We have found that the ANP-NPRA signaling pathway is also involved in airway allergic inflammation and asthma. ANP, a C-terminal peptide (amino acid 99–126 of pro-atrial natriuretic factor (proANF and a recombinant peptide, NP73-102 (amino acid 73–102 of proANF have been reported to induce bronchoprotective effects in a mouse model of allergic asthma. In this report, we evaluated the effects of vessel dilator (VD, another N-terminal natriuretic peptide covering amino acids 31–67 of proANF, on acute lung inflammation in a mouse model of allergic asthma. Methods A549 cells were transfected with pVD or the pVAX1 control plasmid and cells were collected 24 hrs after transfection to analyze the effect of VD on inactivation of the extracellular-signal regulated receptor kinase (ERK1/2 through western blot. Luciferase assay, western blot and RT-PCR were also performed to analyze the effect of VD on NPRA expression. For determination of VD's attenuation of lung inflammation, BALB/c mice were sensitized and challenged with ovalbumin and then treated intranasally with chitosan nanoparticles containing pVD. Parameters of airway inflammation, such as airway hyperreactivity, proinflammatory cytokine levels, eosinophil recruitment and lung histopathology were compared with control mice receiving nanoparticles containing pVAX1 control plasmid. Results pVD nanoparticles inactivated ERK1/2 and downregulated NPRA expression in vitro, and intranasal treatment with pVD nanoparticles protected mice from airway inflammation. Conclusion VD's modulation of airway inflammation may result from its inactivation of ERK1/2 and downregulation of NPRA expression. Chitosan nanoparticles containing pVD may be therapeutically effective in preventing allergic airway inflammation.

  14. Severe exacerbations and decline in lung function in asthma

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Søren; Lamm, Carl Johan

    2009-01-01

    RATIONALE: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. OBJECTIVES: To determine whether severe asthma exacerbations...... with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. MEASUREMENTS AND MAIN RESULTS: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable...... of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). CONCLUSIONS: Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses...

  15. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    International Nuclear Information System (INIS)

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina

    2013-01-01

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca ++ influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  16. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro-Filho, Jaime [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Moraes de Carvalho, Katharinne Ingrid [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Mendes, Diego da [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Melo, Christianne Bandeira [Laboratório de Inflamação, Instituto Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro (Brazil); Martins, Marco Aurélio [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Dias, Celidarque da [Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba (Brazil); Piuvezam, Márcia Regina, E-mail: mrpiuvezam@ltf.ufpb.br [Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  17. Occurrence of allergic bronchopulmonary mycosis in patients with asthma: An Eastern India experience

    Directory of Open Access Journals (Sweden)

    Sarkar Anirban

    2010-01-01

    Full Text Available Background: Allergic bronchopulmonary mycosis (ABPM is a clinical syndrome associated with immune sensitivity to various fungi notably Aspergillus spp. that colonize the airways of asthmatics. Early diagnosis and treatment with systemic corticosteroids is the key in preventing the progression of the disease to irreversible lung fibrosis. Aims: To study the occurrence of ABPM among asthma patients with fungal sensitization attending a chest clinic of a tertiary hospital of eastern India. The clinico-radiological and aetiological profiles are also described. Materials and Methods: All consecutive patients with asthma presenting to the chest clinic over a period of one year were screened for cutaneous hypersensitivity to 12 common fungal antigens. The skin test positive cases were further evaluated for ABPM using standard criteria. Results: One hundred and twenty-six asthma patients were screened using twelve common fungal antigens; forty patients (31.74% were found to be skin test positive, and ABPM was diagnosed in ten patients (7.93%. Of the 10 cases of ABPM, nine cases were those of allergic bronchopulmonary aspergillosis (ABPA and one case was identified as caused by sensitization to Penicillium spp. A majority of the cases of ABPM had advanced disease and had significantly lower FEV1 compared to non-ABPM skin test positive asthmatics. Central bronchiectasis on high resolution CT scan was the most sensitive and specific among the diagnostic parameters. Conclusion: There is a significant prevalence of ABPM in asthma patients attending our hospital and this reinforces the need to screen asthma patients for fungal sensitisation. This will help in early diagnosis and prevention of irreversible lung damage.

  18. Cutaneous sarcoidosis in a patient with severe asthma treated with omalizumab

    Science.gov (United States)

    Yung, Samuel; Han, Duhyun; Lee, Jason K

    2015-01-01

    Omalizumab, a monoclonal anti-immunoglobulin E antibody, has been used as an effective treatment for severe asthma associated with atopy over the past decade. Sarcoidosis is an idiopathic granulomatous disorder in which first-line treatment is usually glucocorticoids. To the authors’ knowledge, the present report describes the first case of an association between omalizumab therapy and revelation of cutaneous sarcoidosis with the withdrawal of systemic glucocorticoids. A 56-year-old woman with severe allergic asthma dependent on oral prednisone initiated omalizumab treatment. As her symptoms of asthma improved over the course of a year, her prednisone was gradually tapered. After being off glucocorticoids, she developed skin nodules that had biopsy characteristics of sarcoidosis. The present case illustrates the need to monitor closely for potential unmasking of glucocorticoid-responsive conditions when transitioning from systemic glucocorticoids to omalizumab therapy. PMID:26401982

  19. Link between environmental air pollution and allergic asthma: East meets West.

    Science.gov (United States)

    Zhang, Qingling; Qiu, Zhiming; Chung, Kian Fan; Huang, Shau-Ku

    2015-01-01

    With the levels of outdoor air pollution from industrial and motor vehicle emissions rising rapidly in the fastly-industrializing countries of South East Asia, the prevalence of asthma and allergic diseases has also been increasing to match those in the West. Epidemiological and experimental exposure studies indicate a harmful impact of outdoor air pollution from vehicles and factories both on the development of allergic diseases and asthma and the increase in asthma symptoms and exacerbations. The level of outdoor pollution in Asia is much higher and more diverse than those encountered in Western countries. This may increase the impact of outdoor pollution on health, particularly lung health in Asia. This review discusses the constituents of air pollution in Asia with a special focus on studies in mainland China and Taiwan where the levels of pollution have reached high levels and where such high levels particularly in winter can cause a thick haze that reduces visibility. The onus remains on regulatory and public health authorities to curb the sources of pollution so that the health effects on the population particularly those with lung and cardiovascular diseases and with increased susceptibility can be mitigated.

  20. News on Climate Change, Air Pollution, and Allergic Triggers of Asthma.

    Science.gov (United States)

    D Amato, M; Cecchi, L; Annesi-Maesano, I; D Amato, G

    2018-01-01

    The rising frequency of obstructive respiratory diseases during recent years, in particular allergic asthma, can be partially explained by changes in the environment, with the increasing presence in the atmosphere of chemical triggers (particulate matter and gaseous components such as nitrogen dioxide and ozone) and biologic triggers (aeroallergens). In allergic individuals, aeroallergens stimulate airway sensitization and thus induce symptoms of bronchial asthma. Over the last 50 years, the earth's temperature has risen markedly, likely because of growing concentrations of anthropogenic greenhouse gas. Major atmospheric and climatic changes, including global warming induced by human activity, have a considerable impact on the biosphere and on the human environment. Urbanization and high levels of vehicle emissions induce symptoms of bronchial obstruction (in particular bronchial asthma), more so in people living in urban areas compared than in those who live in rural areas. Measures need to be taken to mitigate the future impact of climate change and global warming. However, while global emissions continue to rise, we must learn to adapt to climate variability.

  1. Pollen concentrations and prevalence of asthma and allergic rhinitis in Italy: Evidence from the GEIRD study.

    Science.gov (United States)

    Marchetti, Pierpaolo; Pesce, Giancarlo; Villani, Simona; Antonicelli, Leonardo; Ariano, Renato; Attena, Francesco; Bono, Roberto; Bellisario, Valeria; Fois, Alessandro; Gibelli, Nadia; Nicolis, Morena; Olivieri, Mario; Pirina, Pietro; Scopano, Eugenio; Siniscalco, Consolata; Verlato, Giuseppe; Marcon, Alessandro

    2017-04-15

    Pollen exposure has acute adverse effects on sensitized individuals. Information on the prevalence of respiratory diseases in areas with different pollen concentrations is scanty. We performed an ecologic analysis to assess whether the prevalence of allergic rhinitis and asthma in young adults varied across areas with different pollen concentrations in Italy. A questionnaire on respiratory diseases was delivered to random samples of 20-44year-old subjects from six centers in 2005-2010. Data on the daily air concentrations of 7 major allergologic pollens (Poaceae, Urticaceae, Oleaceae, Cupressaceae, Coryloideae, Betula and Ambrosia) were collected for 2007-2008. Center-specific pollen exposure indicators were calculated, including the average number of days per year with pollens above the low or high concentration thresholds defined by the Italian Association of Aerobiology. Associations between pollen exposure and disease prevalence, adjusted for potential confounders, were estimated using logistic regression models with center as a random-intercept. Overall, 8834 subjects (56.8%) filled in the questionnaire. Allergic rhinitis was significantly less frequent in the centers with longer periods with high concentrations of at least one (OR per 10days=0.989, 95%CI: 0.979-0.999) or at least two pollens (OR=0.974, 95%CI: 0.951-0.998); associations with the number of days with at least one (OR=0.988, 95%CI: 0.972-1.004) or at least two (OR=0.985, 95%CI: 0.970-1.001) pollens above the low thresholds were borderline significant. Asthma prevalence was not associated with pollen concentrations. Our study does not support that the prevalence of allergic rhinitis and asthma is greater in centers with higher pollen concentrations. It is not clear whether the observed ecologic associations hold at the individual level. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Asthma Severity in patients initiating controller monotherapy versus combination therapy.

    Science.gov (United States)

    Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

    2011-04-01

    Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

  3. Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma

    Directory of Open Access Journals (Sweden)

    Corrado Pelaia

    2018-01-01

    Full Text Available Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5, released by both T helper 2 (Th2 lymphocytes and group 2 innate lymphoid cells (ILC2. Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA.

  4. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

  5. Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Hadeesha Piyadasa

    2016-02-01

    Full Text Available House dust mite (HDM challenge is commonly used in murine models of allergic asthma for preclinical pathophysiological studies. However, few studies define objective readouts or biomarkers in this model. In this study we characterized immune responses and defined molecular markers that are specifically altered after HDM challenge. In this murine model, we used repeated HDM challenge for two weeks which induced hallmarks of allergic asthma seen in humans, including airway hyper-responsiveness (AHR and elevated levels of circulating total and HDM-specific IgE and IgG1. Kinetic studies showed that at least 24 h after last HDM challenge results in significant AHR along with eosinophil infiltration in the lungs. Histologic assessment of lung revealed increased epithelial thickness and goblet cell hyperplasia, in the absence of airway wall collagen deposition, suggesting ongoing tissue repair concomitant with acute allergic lung inflammation. Thus, this model may be suitable to delineate airway inflammation processes that precede airway remodeling and development of fixed airway obstruction. We observed that a panel of cytokines e.g. IFN-γ, IL-1β, IL-4, IL-5, IL-6, KC, TNF-α, IL-13, IL-33, MDC and TARC were elevated in lung tissue and bronchoalveolar fluid, indicating local lung inflammation. However, levels of these cytokines remained unchanged in serum, reflecting lack of systemic inflammation in this model. Based on these findings, we further monitored the expression of 84 selected genes in lung tissues by quantitative real-time PCR array, and identified 31 mRNAs that were significantly up-regulated in lung tissue from HDM-challenged mice. These included genes associated with human asthma (e.g. clca3, ear11, il-13, il-13ra2, il-10, il-21, arg1 and chia1 and leukocyte recruitment in the lungs (e.g. ccl11, ccl12 and ccl24. This study describes a biosignature to enable broad and systematic interrogation of molecular mechanisms and intervention

  6. Data on the oral CRTh2 antagonist QAW039 (fevipiprant in patients with uncontrolled allergic asthma

    Directory of Open Access Journals (Sweden)

    Veit J. Erpenbeck

    2016-12-01

    Full Text Available This article contains data on clinical endpoints (Peak Flow Expiratory Rate, fractional exhaled nitric oxide and total IgE serum levels and plasma pharmacokinetic parameters concerning the use of the oral CRTh2 antagonist QAW039 (fevipiprant in mild to moderate asthma patients. Information on experimental design and methods on how this data was obtained is also described. Further interpretation and discussion of this data can be found in the article “The oral CRTh2 antagonist QAW039 (fevipiprant: a phase II study in uncontrolled allergic asthma” (Erpenbeck et al., in press [1].

  7. Mild, Moderate, Severe Asthma: What Do Grades Mean?

    Science.gov (United States)

    ... that arise by making this kind of distinction. What Really Matters Is Control, Not Severity It turns out that asthma severity ... Asthma” make a strong point that the overall control of your child’s asthma is really what is most important, not what the severity level ...

  8. Burden of Respiratory Disease in Korea: An Observational Study on Allergic Rhinitis, Asthma, COPD, and Rhinosinusitis.

    Science.gov (United States)

    Yoo, Kwang Ha; Ahn, Hae Ryun; Park, Jae Kyoung; Kim, Jong Woong; Nam, Gui Hyun; Hong, Soon Kwan; Kim, Mee Ja; Ghoshal, Aloke Gopal; Muttalif, Abdul Razak Bin Abdul; Lin, Horng Chyuan; Thanaviratananich, Sanguansak; Bagga, Shalini; Faruqi, Rab; Sajjan, Shiva; Baidya, Santwona; Wang, De Yun; Cho, Sang Heon

    2016-11-01

    The Asia-Pacific Burden of Respiratory Diseases (APBORD) study is a cross-sectional, observational one which has used a standard protocol to examine the disease and economic burden of allergic rhinitis (AR), asthma, chronic obstructive pulmonary disorder (COPD), and rhinosinusitis across the Asia-Pacific region. Here, we report on symptoms, healthcare resource use, work impairment, and associated costs in Korea. Consecutive participants aged ≥18 years with a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Participants and their treating physician completed a survey detailing respiratory symptoms, healthcare resource use, and work productivity and activity impairment. Costs included direct medical cost and indirect cost associated with lost work productivity. The study enrolled 999 patients. Patients were often diagnosed with multiple respiratory disorders (42.8%), with asthma/AR and AR/rhinosinusitis the most frequently diagnosed combinations. Cough or coughing up phlegm was the primary reason for the medical visit in patients with a primary diagnosis of asthma and COPD, whereas nasal symptoms (watery runny nose, blocked nose, and congestion) were the main reasons in those with AR and rhinosinusitis. The mean annual cost for patients with a respiratory disease was US$8,853 (SD 11,245) per patient. Lost productivity due to presenteeism was the biggest contributor to costs. Respiratory disease has a significant impact on disease burden in Korea. Treatment strategies for preventing lost work productivity could greatly reduce the economic burden of respiratory disease.

  9. A study of asthma severity in adult twins

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; van der Sluis, Sophie; Kyvik, Kirsten Ohm

    2012-01-01

    Introduction: The tendency to develop asthma runs in families, but whether the severity of asthma symptoms is inherited is not known. Objectives: The aim of this study was to examine whether genetic factors influence the variation in the severity of asthma. Methods: Of a sample of 21 133 adult......, and markers of airway impairment and allergy were measured. Results: After adjusting for confounders, genetic factors explained 24% (10%-37%), P = 0.0004, of the variation in overall asthma symptom severity, whereas non-shared environment accounted for the remaining 76% of the variation. A significant genetic...

  10. Benralizumab in the treatment of severe asthma: design, development and potential place in therapy

    Directory of Open Access Journals (Sweden)

    Pelaia C

    2018-03-01

    Full Text Available Corrado Pelaia,1 Alessandro Vatrella,2 Andrea Bruni,1 Rosa Terracciano,3 Girolamo Pelaia1 1Department of Medical and Surgical Sciences, Section of Respiratory Diseases, “Magna Græcia” University of Catanzaro, Catanzaro, Italy; 2Department of Medicine, Surgery and Dentistry, Section of Respiratory Diseases, University of Salerno, Salerno, Italy; 3Department of Health Sciences, “Magna Græcia” University of Catanzaro, Catanzaro, Italy Abstract: Asthma is a widespread and heterogeneous inflammatory disease of the airways, which is characterized by several different phenotypes and endotypes. In particular, eosinophilic airway inflammation is a common pathologic trait of both allergic and nonallergic asthma. The key cytokine responsible for maturation, activation, recruitment, and survival of eosinophils is interleukin (IL-5, which is mainly produced by T helper 2 (Th2 lymphocytes and group 2 innate lymphoid cells. Therefore, for uncontrolled patients with severe eosinophilic asthma, who are not fully responsive to corticosteroids, IL-5 represents a very important molecular target for add-on biological therapies. Among these new treatments, anti-IL-5 monoclonal antibodies such as mepolizumab and reslizumab have been developed and clinically evaluated. Furthermore, benralizumab is currently the only available biologic drug that specifically binds to the IL-5 receptor, thus preventing the interaction with its ligand and the consequent pro-inflammatory effects. The effectiveness of benralizumab in improving severe eosinophilic asthma has been well-documented by many randomized controlled trials. Keywords: IL-5, IL-5 receptor, severe eosinophilic asthma, benralizumab

  11. Challenges of a mobile application for asthma and allergic rhinitis patient enablement-interface and synchronization.

    Science.gov (United States)

    Burnay, Eduardo; Cruz-Correia, Ricardo; Jacinto, Tiago; Sousa, Ana Sá; Fonseca, João

    2013-01-01

    Asthma and allergic rhinitis (ARA) are common inflammatory diseases of the airways. Enhancement of a patient's participation on clinical decisions is related to better results in control of diseases. To control ARA, patients should monitor their symptoms, avoid triggers, and follow their treatment plan. This study described the challenges of developing a mobile application, called m.Carat, that records the main events related to ARA. The mobile application m.Carat was developed for Android™ (Google, Mountain View, CA) and iPhone(®) (Apple, San Jose, CA) smartphones. It was developed using PhoneGap, which allows the development of applications for several mobile operating systems. To generate the user interface, jQuery Mobile, HTML, Javascript, and CSS were used. Despite the use of mobile development frameworks, some input and output elements had to be improved. To evaluate the interface, a pilot study was performed with eight users who performed 10 different tasks in the application. To synchronize m.Carat with an online database, an algorithm was developed from scratch. This feature represents a major challenge because all the changes must be reflected in all devices. Currently m.Carat is a mobile application where ARA patients fill out a questionnaire to assess the degree of control of ARA and record their exacerbations, triggers, symptoms, medications, lung function tests, and visits to the doctor or the hospital. They also can receive information and news about ARA, define medication and tasks notifications, and synchronize all records at caratnetwork.org with an online database. The evaluation showed some of the adopted solutions to improve interface usability did not work as expected. Of the 80 total tasks tested the users had no difficulty in 37(46%). Most of the problems observed were easily solved. m.Carat is a mobile application for ARA that may contribute to patient enablement. The development of m.Carat suggests that mobile applications may introduce

  12. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    Science.gov (United States)

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Risk factors for hospitalization among adults with asthma: the influence of sociodemographic factors and asthma severity

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    Eisner Mark D

    2000-12-01

    Full Text Available Abstract Background The morbidity and mortality from asthma have markedly increased since the late 1970s. The hospitalization rate, an important marker of asthma severity, remains substantial. Methods In adults with health care access, we prospectively studied 242 with asthma, aged 18–50 years, recruited from a random sample of allergy and pulmonary physician practices in Northern California to identify risk factors for subsequent hospitalization. Results Thirty-nine subjects (16% reported hospitalization for asthma during the 18-month follow-up period. On controlling for asthma severity in multiple logistic regression analysis, non-white race (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1–8.8 and lower income (OR, 1.1 per $10,000 decrement; 95% CI, 0.9–1.3 were associated with a higher risk of asthma hospitalization. The severity-of-asthma score (OR, 3.4 per 5 points; 95%, CI 1.7–6.8 and recent asthma hospitalization (OR, 8.3; 95%, CI, 2.1–33.4 were also related to higher risk, after adjusting for demographic characteristics. Reliance on emergency department services for urgent asthma care was also associated with a greater likelihood of hospitalization (OR, 3.2; 95% CI, 1.0–9.8. In multivariate analysis not controlling for asthma severity, low income was even more strongly related to hospitalization (OR, 1.2 per $10,000 decrement; 95% CI, 1.02–1.4. Conclusion In adult asthmatics with access to health care, non-white race, low income, and greater asthma severity were associated with a higher risk of hospitalization. Targeted interventions applied to high-risk asthma patients may reduce asthma morbidity and mortality.

  14. Novel monoclonal treatments in severe asthma

    DEFF Research Database (Denmark)

    Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste

    2017-01-01

    articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies. RESULTS: Of the 37 studies investigating biological treatments of asthma, 5 were on the effects of anti-IgE (omalizumab); 12 on anti-IL-5; 8...... TSLP, IL-9, and TNF-α lacked convincing effectiveness. CONCLUSION: Research on the biological treatment of asthma shows promising results. While anti-IgE (omalizumab) has been used in the treatment of asthma for some years, anti-IL-5 has recently been approved for use. The efficacy of results of other...... large studies with a longer duration is needed to draw a firm conclusion. Such studies should not only focus on clinical outcomes, but also consider asthma-related quality of life. Knowledge on the asthma phenotypes and identification of biomarkers associated with these will be useful for physicians...

  15. Risk factors for death in patients with severe asthma

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    Andréia Guedes Oliva Fernandes

    2014-08-01

    Full Text Available OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4. Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality.

  16. Bronchodilator Response in Patients with Persistent Allergic Asthma Could Not Predict Airway Hyperresponsiveness

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    Petanjek Bojana B

    2007-12-01

    Full Text Available Anticholinergics, or specific antimuscarinic agents, by inhibition of muscarinic receptors cause bronchodilatation, which might correlate with activation of these receptors by the muscarinic agonist methacholine. The aim of this study was to determine whether a positive bronchodilator response to the anticholinergic ipratropium bromide could predict airway hyperresponsiveness in patients with persistent allergic asthma. The study comprised 40 patients with mild and moderate persistent allergic asthma. Diagnosis was established by clinical and functional follow-up (skin-prick test, spirometry, bronchodilator tests with salbutamol and ipratropium bromide, and methacholine challenge testing. The bronchodilator response was positive to both bronchodilator drugs in all patients. After salbutamol inhalation, forced expiratory volume in 1 second (FEV1 increased by 18.39 ± 6.18%, p 1 increased by 19.14 ± 6.74%, p 1 decreased by 25.75 ± 5.16%, p 20 FEV1 [provocative concentration of methacholine that results in a 20% fall in FEV1] from 0.026 to 1.914 mg/mL. Using linear regression, between methacholine challenge testing and bronchodilator response to salbutamol, a positive, weak, and stastistically significant correlation for FEV1 was found (p

  17. Complementary and alternative medicine for the treatment and diagnosis of asthma and allergic diseases.

    Science.gov (United States)

    Passalacqua, G; Compalati, E; Schiappoli, M; Senna, G

    2005-03-01

    The use of Complementary/Alternative Medicines (CAM) is largely diffused and constantly increasing, especially in the field of allergic diseases and asthma. Homeopathy, acupuncture and phytotherapy are the most frequently utilised treatments, whereas complementary diagnostic techniques are mainly used in the field of food allergy-intolerance. Looking at the literature, the majority of clinical trials with CAMS are of low methodological quality, thus difficult to interpret. There are very few studies performed in a rigorously controlled fashion, and those studies provided inconclusive results. In asthma, none of the CAM have thus far been proved more effective than placebo or equally effective as standard treatments. Some herbal products, containing active principles, have displayed some clinical effect, but the herbal remedies are usually not standardised and not quantified, thus carry the risk of toxic effects or interactions. None of the alternative diagnostic techniques (electrodermal testing, kinesiology, leukocytotoxic test, iridology, hair analysis) have been proved able to distinguish between healthy and allergic subjects or to diagnose sensitizations. Therefore these tests must not be used, since they can lead to delayed or incorrect diagnosis and therapy.

  18. Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

    Science.gov (United States)

    Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

    2001-01-01

    To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

  19. The level of diagnostic assessment in severe asthma

    DEFF Research Database (Denmark)

    von Bulow, Anna; Backer, Vibeke; Bodtger, Uffe

    2017-01-01

    INTRODUCTION: Systematic assessment of patients with severe asthma is pivotal to decide which patients are eligible to new biological therapies. However, the level of diagnostic work-up in patients with severe asthma is only poorly investigated. AIMS & OBJECTIVES: To describe the diagnostic work-...

  20. Mechanisms Mediating Pediatric Severe Asthma and Potential Novel Therapies

    Directory of Open Access Journals (Sweden)

    Aldara Martin Alonso

    2017-07-01

    Full Text Available Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling. Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma. However, limitations of its use include ineligibility for approximately one-third of patients because of serum IgE levels outside the recommended range and lack of clinical efficacy in a further one-third. Pediatric severe asthma is thus markedly heterogeneous, but our current understanding of the different mechanisms underpinning various phenotypes is very limited. We know that there are distinctions between the factors that drive pediatric and adult disease since pediatric disease develops in the context of a maturing immune system and during lung growth and development. This review summarizes the current data that give insight into the pathophysiology of pediatric severe asthma and will highlight potential targets for novel therapies. It is apparent that in order to identify novel treatments for pediatric severe asthma, the challenge of undertaking mechanistic studies using age appropriate experimental models and airway samples from children needs to be accepted to allow a targeted approach of personalized medicine to be achieved.

  1. Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Antonio Aguilar-Pimentel

    Full Text Available Allergen-specific immunotherapy (AIT is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma.Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways.In C57BL/6J mice, a model of ovalbumin (OVA-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro.AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells.This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

  2. Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

    Science.gov (United States)

    Aguilar-Pimentel, Antonio; Graessel, Anke; Alessandrini, Francesca; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Russkamp, Dennis; Chaker, Adam; Ollert, Markus; Blank, Simon; Gutermuth, Jan; Schmidt-Weber, Carsten B

    2017-01-01

    Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma. Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways. In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

  3. Circulating CXCR5+CD4+ T cells participate in the IgE accumulation in allergic asthma.

    Science.gov (United States)

    Gong, Fang; Zhu, Hua-Yan; Zhu, Jie; Dong, Qiao-Jing; Huang, Xuan; Jiang, Dong-Jin

    2018-05-01

    The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5 + CD4 + T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5 + CD4 + T cells in allergic asthmatics. Here we found the frequency of the circulating CXCR5 + CD4 + T cells was raised in allergic asthma compared with healthy control (HC). Phenotypic assays showed that activated circulating CXCR5 + CD4 + T cells display the key features of Tfh cells, including invariably coexpressed programmed cell death (PD)-1 and inducible costimulator (ICOS). The frequency of interleukin IL-4 + -, IL-21 + -producing CXCR5 + CD4 + T cells was increased in allergic asthma patients compared with HC. Furthermore, sorted circulating CXCR5 + CD4 + T cells from allergic asthma patients boosted IgE production in coculture assay which could be inhibited by IL-4 or IL-21 blockage. Interestingly, IL-4 + -, IL-21 + -CXCR5 + CD4 + T cells positively correlated with total IgE in the blood. Our data indicated that circulating CXCR5 + CD4 + T cells may have a significant role in facilitating IgE production in allergic asthma patients. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  4. Consumption of artificially-sweetened soft drinks in pregnancy and risk of child asthma and allergic rhinitis.

    Science.gov (United States)

    Maslova, Ekaterina; Strøm, Marin; Olsen, Sjurdur F; Halldorsson, Thorhallur I

    2013-01-01

    Past evidence has suggested a role of artificial sweeteners in allergic disease; yet, the evidence has been inconsistent and unclear. To examine relation of intake of artificially-sweetened beverages during pregnancy with child asthma and allergic rhinitis at 18 months and 7 years. We analyzed data from 60,466 women enrolled during pregnancy in the prospective longitudinal Danish National Birth Cohort between 1996 and 2003. At the 25th week of gestation we administered a validated Food Frequency Questionnaire which asked in detail about intake of artificially-sweetened soft drinks. At 18 months, we evaluated child asthma using interview data. We also assessed asthma and allergic rhinitis through a questionnaire at age 7 and by using national registries. Current asthma was defined as self-reported asthma diagnosis and wheeze in the past 12 months. We examined the relation between intake of artificially-sweetened soft drinks and child allergic disease outcomes and present here odds ratios with 95% CI comparing daily vs. no intake. At 18 months, we found that mothers who consumed more artificially-sweetened non-carbonated soft drinks were 1.23 (95% CI: 1.13, 1.33) times more likely to report a child asthma diagnosis compared to non-consumers. Similar results were found for child wheeze. Consumers of artificially-sweetened carbonated drinks were more likely to have a child asthma diagnosis in the patient (1.30, 95% CI: 1.01, 1.66) and medication (1.13, 95% CI: 0.98, 1.29) registry, as well as self-reported allergic rhinitis (1.31, 95% CI: 0.98, 1.74) during the first 7 years of follow-up. We found no associations for sugar-sweetened soft drinks. Carbonated artificially-sweetened soft drinks were associated with registry-based asthma and self-reported allergic rhinitis, while early childhood outcomes were related to non-carbonated soft drinks. These results suggest that consumption of artificially-sweetened soft drinks during pregnancy may play a role in offspring

  5. Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation

    Science.gov (United States)

    2013-01-01

    Background This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured. Methods LA4 cells were stimulated with 100 μg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin. Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 μg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 μl incomplete Freund’s adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 μl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy. Results XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT. Conclusion XQLT alleviated allergic inflammation including AHR, Ig

  6. [Predictive factors associated with severity of asthma exacerbations].

    Science.gov (United States)

    Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

    2008-01-01

    Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

  7. Lung mechanics and histology during sevoflurane anesthesia in a model of chronic allergic asthma.

    Science.gov (United States)

    Burburan, Shirley Moreira; Xisto, Debora Gonçalves; Ferreira, Halina Cidrini; Riva, Douglas Dos Reis; Carvalho, Giovanna Marcella Cavalcante; Zin, Walter Araujo; Rocco, Patricia Rieken Macêdo

    2007-03-01

    There are no studies examining the effects of sevoflurane on a chronically inflamed and remodeled airway, such as that found in asthma. In the present study, we sought to define the respiratory effects of sevoflurane in a model of chronic allergic asthma. For this purpose, pulmonary mechanics were studied and lung morphometry analyzed to determine whether the physiological modifications reflected underlying morphological changes. Thirty-six BALB/c mice (20-25 g) were randomly divided into four groups. In OVA groups, mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. In SAL groups, mice received saline using the same protocol. Twenty-four hours after the last challenge, the animals were anesthetized with pentobarbital sodium (PENTO, 20 mg/kg i.p.) or sevoflurane (SEVO, 1 MAC). Lung static elastance (Est), resistive ([DELTA]P1) and viscoelastic/inhomogeneous ([DELTA]P2) pressure decreases were analyzed by an end-inflation occlusion method. Lungs were fixed and stained for histological analysis. Animals in the OVASEVO group showed lower [DELTA]P1 (38%), [DELTA]P2 (24%), and Est (22%) than animals in the OVAPENTO group. Histology demonstrated greater airway dilation (16%) and a lower degree of alveolar collapse (25%) in the OVASEVO compared with OVAPENTO group. [DELTA]P1 was lower (35%) and airway diameters larger (12%) in the SALSEVO compared with SALPENTO group. Sevoflurane anesthesia acted both at airway level and lung periphery reducing ([DELTA]P1 and [DELTA]P2 pressures, and Est in chronic allergic asthma.

  8. An algorithmic approach for the treatment of severe uncontrolled asthma

    Science.gov (United States)

    Zervas, Eleftherios; Samitas, Konstantinos; Papaioannou, Andriana I.; Bakakos, Petros; Loukides, Stelios; Gaga, Mina

    2018-01-01

    A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute asthma patients, they are responsible for more than half of asthma-related healthcare costs. Here, we review a definition for severe asthma and present all therapeutic options currently available for these severe asthma patients. Moreover, we suggest a specific algorithmic treatment approach for the management of severe, difficult-to-treat asthma based on specific phenotype characteristics and biomarkers. The diagnosis and management of severe asthma requires specialised experience, time and effort to comprehend the needs and expectations of each individual patient and incorporate those as well as his/her specific phenotype characteristics into the management planning. Although some new treatment options are currently available for these patients, there is still a need for further research into severe asthma and yet more treatment options. PMID:29531957

  9. Effects of vernal and allergic conjunctivitis on severity of keratoconus.

    Science.gov (United States)

    Cingu, Abdullah Kursat; Cinar, Yasin; Turkcu, Fatih Mehmet; Sahin, Alparslan; Ari, Seyhmus; Yuksel, Harun; Sahin, Muhammed; Caca, Ihsan

    2013-01-01

    To demonstrate the effects of two different types of allergic conjunctivitis on severity of keratoconus (KC). We retrospectively reviewed the medical records of 171 KC patients referred between June 2010 and June 2011. The KC patients were divided into 3 groups as KC (group A), KC with vernal keratoconjunctivitis (VKC) (group B) and KC with allergic conjunctivitis (AC) (group C). Main outcome measures were demographic and ocular clinical features including age at presentation, gender, spherical equivalent (SE), best spectacle corrected visual acuity (BCVA), mean keratometric measurement (Km), central corneal thickness (CCT), and intraocular pressure (IOP). Groups were compared in term of study variables. The median age at presentation was significantly lower in group B (P<0.001). According to the median SE (P=0.003), BCVA (P=0.022), Km (P<0.001), CCT (P=0.015) and Amsler-Krumeich classification (P<0.001), KC was more severe in group B. There was no significant difference in terms of IOP and corrected IOP among the groups (P=0.44), however there were 4 patients who had increased corrected IOP developed after topical corticosteroid use in group B. The differences among the groups persisted even after controlling for age and gender. Our findings demonstrated a more severe KC in VKC patients despite their younger age which suggests evaluation of VKC patients as a separate group in keratoconus disease.

  10. Effects of vernal and allergic conjunctivitis on severity of keratoconus

    Directory of Open Access Journals (Sweden)

    Muhammed Sahin

    2013-06-01

    Full Text Available AIM: To demonstrate the effects of two different types of allergic conjunctivitis on severity of keratoconus (KC.METHODS: We retrospectively reviewed the medical records of 171 KC patients referred between June 2010 and June 2011. The KC patients were divided into 3 groups as KC (group A, KC with vernal keratoconjunctivitis (VKC (group B and KC with allergic conjunctivitis (AC (group C. Main outcome measures were demographic and ocular clinical features including age at presentation, gender, spherical equivalent (SE, best spectacle corrected visual acuity (BCVA, mean keratometric measurement (Km, central corneal thickness (CCT, and intraocular pressure (IOP. Groups were compared in term of study variables. RESULTS: The median age at presentation was significantly lower in group B (P<0.001. According to the median SE (P=0.003, BCVA (P=0.022, Km (P<0.001, CCT (P=0.015 and Amsler–Krumeich classification (P<0.001, KC was more severe in group B. There was no significant difference in terms of IOP and corrected IOP among the groups (P=0.44, however there were 4 patients who had increased corrected IOP developed after topical corticosteroid use in group B. The differences among the groups persisted even after controlling for age and gender.CONCLUSION: Our findings demonstrated a more severe KC in VKC patients despite their younger age which suggests evaluation of VKC patients as a separate group in keratoconus disease.

  11. The effect of omalizumab on eosinophilic inflammation of the respiratory tract in patients with allergic asthma.

    Science.gov (United States)

    Kupryś-Lipińska, Izabela; Molińska, Katarzyna; Kuna, Piotr

    2016-01-01

    Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab - an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

  12. NOCTURNAL AIR-FLOW OBSTRUCTION, HISTAMINE, AND THE AUTONOMIC CENTRAL-NERVOUS-SYSTEM IN CHILDREN WITH ALLERGIC-ASTHMA

    NARCIS (Netherlands)

    VANAALDEREN, WMC; POSTMA, DS; KOETER, GH; KNOL, K

    A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma,nine with (group 1) and nine

  13. Dupilumab in the management of moderate-to-severe asthma: the data so far

    Directory of Open Access Journals (Sweden)

    Barranco P

    2017-09-01

    Full Text Available Pilar Barranco,1 Elsa Phillips-Angles,2 Javier Dominguez-Ortega,1 Santiago Quirce1 1Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ, CIBER de Enfermedades Respiratorias (CIBERES, Madrid, Spain; 2Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ, Madrid, Spain Abstract: Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem – with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies – particularly, selective targeted monoclonal antibodies (mAbs. It is noteworthy that in approximately 50% of these patients, there is strong evidence of the pathogenic role of T helper type-2 (Th2 cytokines, such as interleukin (IL-4 and IL-13, orchestrating the eosinophilic and allergic inflammatory processes. Among the recently developed antiasthma biologic drugs, the mAb dupilumab is very promising given its ability to inhibit the biological effects of both IL-4 and IL-13. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future. Keywords: dupilumab, asthma, interleukin-4, interleukin-13, monoclonal antibodies, treatment

  14. Novel monoclonal treatments in severe asthma.

    Science.gov (United States)

    Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste; Backer, Vibeke

    2017-12-01

    To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." Only articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies. Of the 37 studies investigating biological treatments of asthma, 5 were on the effects of anti-IgE (omalizumab); 12 on anti-IL-5; 8 on anti-IL-13; 5 on anti-IL-4R-α; 3 on anti-IL-9; one on TNF-α; one on anti-IL-2R-α; one on TSLP (Thymic Stromal Lymphopoietin); and one on OX40L. Sample sizes ranged from 3 to 943 participants. Studies of therapies targeting IgE, IL-2, IL4R-α, IL-5, and IL-13 showed some efficacy, whereas those targeting TSLP, IL-9, and TNF-α lacked convincing effectiveness. Research on the biological treatment of asthma shows promising results. While anti-IgE (omalizumab) has been used in the treatment of asthma for some years, anti-IL-5 has recently been approved for use. The efficacy of results of other large studies with a longer duration is needed to draw a firm conclusion. Such studies should not only focus on clinical outcomes, but also consider asthma-related quality of life. Knowledge on the asthma phenotypes and identification of biomarkers associated with these will be useful for physicians considering the right treatment for the asthma patient.

  15. Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study

    Science.gov (United States)

    Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael

    2016-01-01

    Purpose Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. Methods This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). Results A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; Pquality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile. PMID:27126725

  16. Assessment of asthma severity in adults with ever asthma: A continuous score.

    Directory of Open Access Journals (Sweden)

    Lucia Calciano

    Full Text Available In epidemiological studies, continuous measures of asthma severity should be used to catch the heterogeneity of phenotypes. This study aimed at developing and validating continuous measures of asthma severity in adult patients with ever asthma from the general population, to be used in epidemiological studies.Respiratory symptoms, anti-asthmatic treatment and lung function were measured on 520 patients with ever asthma aged 20-64 years from the general Italian population (GEIRD study; 2007/2010. The variables that represent the same dimension of asthma severity were identified through an exploratory factor analysis and were summarized through a multiple factor analysis.Only respiratory symptoms and anti-asthmatic treatment were summarized in a continuous score (STS. STS ranges from 0 (no symptoms/treatment to 10 (maximum symptom frequency and treatment intensity. STS was positively correlated with the Global Initiative for Asthma classification of asthma severity computed on the 137 cases with a doctor's diagnosis (Spearman's coefficient = 0.61, p-value<0.0001 (concurrent validity. Furthermore, using a cohort of 1,097 European asthmatics (ECRHS II study; 1999/2002, increasing STS levels at baseline (1991/1993 were positively associated with long-term outcomes (hospitalization and lost workdays for breathing problems, asthma attack frequency and use of asthma controllers (predictive validity. Finally, the STS scores computed from the GEIRD and ECRHS II data were comparable (Lin's coefficient = 0.95, p-value<0.0001 (replication analysis.STS is a valid and replicable measure of asthma severity in adults, which could be used in association studies.

  17. The validity of register data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Klansø, Lotte; Jensen, Andreas

    2017-01-01

    the algorithms vs gold standard deep telephone interviews with the caretaker about physician-diagnosed atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis in the child. Methods: The algorithms defined each of the three atopic diseases using register-based information on disease-specific hospital...... contacts and/or filled prescriptions of disease-specific medication. Confirmative answers to questions about physician-diagnosed atopic disease were used as the gold standard for the comparison with the algorithms, resulting in sensitivities and specificities and 95% confidence intervals. The interviews...... with the caretaker of the included 454 Danish children born 1997-2003 were carried out May-September 2015; the mean age of the children at the time of the interview being 15.2 years (standard deviation 1.3 years). Results: For the algorithm capturing children with atopic dermatitis, the sensitivity was 74.1% (95...

  18. Th2 cytokines and asthma — The role of interleukin-5 in allergic eosinophilic disease

    Directory of Open Access Journals (Sweden)

    Chapman Richard W

    2001-03-01

    Full Text Available Abstract Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin-5 is a very selective cytokine as a result of the restricted expression of the interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of interleukin-5 is a viable treatment. The present review addresses the data that relate interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-interleukin-5 monoclonal antibodies for the treatment of asthma in humans.

  19. Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

    Science.gov (United States)

    Sulaiman, S. A.

    2017-01-01

    Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO) is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma. PMID:28660089

  20. Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

    Directory of Open Access Journals (Sweden)

    N. A. Kamalaldin

    2017-01-01

    Full Text Available Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma.

  1. Pneumomediastinum from a severe asthma attack.

    Science.gov (United States)

    Hashim, Taimoor; Chaudry, Ayesha H; Ahmad, Khurram; Imhoff, Jennifer; Khouzam, Rami

    2013-07-01

    Spontaneous pneumomediastinum is a rare complication of an asthma exacerbation characterized by chest pain, dyspnea, neck swelling, and subcutaneous emphysema. Although the condition is usually benign and treatment is primarily supportive, surgical intervention may be needed if the patient develops hemodynamic or respiratory failure.

  2. DNA methylation levels associated with race and childhood asthma severity.

    Science.gov (United States)

    Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

    2017-10-01

    Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

  3. Severe angina pectoris in asthma attack: a case report.

    Science.gov (United States)

    Nabavizadeh, Seyed Hesamedin; Farahbakhsh, Nazanin; Fazel, Ali; Mosavat, Fereshteh; Anushiravani, Amir

    2016-06-01

    Asthma is a chronic inflammatory disorder of the airways related to the obstruction of reversible airflow. Asthma presents as recurrent attacks of cough and dyspnea. Poor control causes recurrent admissions to the ICU, and mortality is related to poor drug compliance and follow-up. Angina pectoris is a syndrome of recurrent chest discomfort related to myocardial ischemia. The presence of these two disorders rarely has been reported. We reported a 12-year-old boy who was referred with exacerbation of asthma and developed angina pectoris during hospitalization. He had labored breathing and diffuse wheezing. During treatment of the asthma, the patient developed severe chest pain due to shunt formation and coronary hypoxia, caused by the sole administration of ventolin, since oxygen had been disconnected. After receiving appropriate therapy, both his asthma and angina recovered, and, to date, he has not experienced angina pectoris again.

  4. The Airway Microbiome in Severe Asthma: Associations with Disease Features and Severity

    Science.gov (United States)

    Huang, Yvonne J.; Nariya, Snehal; Harris, Jeffrey M.; Lynch, Susan V.; Choy, David F.; Arron, Joseph R.; Boushey, Homer

    2015-01-01

    Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions

  5. Omalizumab Is Equally Effective in Persistent Allergic Oral Corticosteroid-Dependent Asthma Caused by Either Seasonal or Perennial Allergens: A Pilot Study.

    Science.gov (United States)

    Domingo, Christian; Pomares, Xavier; Navarro, Albert; Rudi, Núria; Sogo, Ana; Dávila, Ignacio; Mirapeix, Rosa M

    2017-02-28

    Omalizumab is marketed for chronic severe asthma patients who are allergic to perennial allergens. Our purpose was to investigate whether omalizumab is also effective in persistent severe asthma due to seasonal allergens. Thirty patients with oral corticosteroid-dependent asthma were treated with Omalizumab according to the dosing table. For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. The dose of oral methyl prednisolone was tapered at a rate of 2 mg every two weeks after the start of treatment with omalizumab depending on tolerance. At each monthly visit, a forced spirometry and fractional exhaled nitric oxide (FeNO) measurement were performed and the accumulated monthly methyl prednisolone dose was calculated. At entry, there were no differences between groups in terms of gender, body mass index or obesity, year exacerbation rate, monthly dose of methyl-prednisolone (MP), FeNO and blood immunoglobuline E (IgE) MP, FeNO and IgE values, or spirometry (perennial: FVC: 76%; FEV₁: 62%; seasonal: FVC: 79%; FEV₁: 70%). The follow-up lasted 76 weeks. One patient in each group was considered a non-responder. Spirometry did not worsen in either group. There was a significant intragroup reduction in annual exacerbation rate and methyl prednisolone consumption but no differences were detected in the intergroup comparison. Omalizumab offered the same clinical benefits in the two cohorts regardless of whether the asthma was caused by a seasonal or a perennial allergen. These results strongly suggest that allergens are the trigger in chronic asthma but that it is the persistent exposure to IgE that causes the chronicity.

  6. Omalizumab Is Equally Effective in Persistent Allergic Oral Corticosteroid-Dependent Asthma Caused by Either Seasonal or Perennial Allergens: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Christian Domingo

    2017-02-01

    Full Text Available Omalizumab is marketed for chronic severe asthma patients who are allergic to perennial allergens. Our purpose was to investigate whether omalizumab is also effective in persistent severe asthma due to seasonal allergens. Thirty patients with oral corticosteroid-dependent asthma were treated with Omalizumab according to the dosing table. For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. The dose of oral methyl prednisolone (MP was tapered at a rate of 2 mg every two weeks after the start of treatment with omalizumab depending on tolerance. At each monthly visit, a forced spirometry and fractional exhaled nitric oxide (FeNO measurement were performed and the accumulated monthly MP dose was calculated. At entry, there were no differences between groups in terms of gender, body mass index or obesity, year exacerbation rate, monthly dose of MP, FeNO and blood immunoglobuline E (IgE values, or spirometry (perennial: FVC: 76%; FEV1: 62%; seasonal: FVC: 79%; FEV1: 70%. The follow-up lasted 76 weeks. One patient in each group was considered a non-responder. Spirometry did not worsen in either group. There was a significant intragroup reduction in annual exacerbation rate and MP consumption but no differences were detected in the intergroup comparison. Omalizumab offered the same clinical benefits in the two cohorts regardless of whether the asthma was caused by a seasonal or a perennial allergen. These results strongly suggest that allergens are the trigger in chronic asthma but that it is the persistent exposure to IgE that causes the chronicity.

  7. Severe allergic hair dye reactions in 8 children

    DEFF Research Database (Denmark)

    Sosted, Heidi; Johansen, Jeanne Duus; Andersen, Klaus Ejner

    2006-01-01

    Serious adverse skin reactions to permanent hair dyes and temporary black tattoos have been reported. As temporary tattoos have become fashionable among adolescents, the risk profile for p-phenylenediamine (PPD) sensitization of the population has changed simultaneously with an increasing use...... of hair dyes in this age group. This investigation reports PPD sensitization in children with regard to cause of sensitization, clinical presentation and consequences. Clinical history and patch test results for consecutive children below 16 years of age with suspected hair dye allergic reactions...... and positive patch tests to PPD were collected over 2 years in 2 Danish dermatology clinics. 8 children aged 12-15 years were collected, and they all reacted to several hair dye ingredients. 5 of the patients were hospitalized, 1 in the intensive care unit. 6 of the patients gave a history of prior reaction...

  8. Application of the asthma phenotype algorithm from the Severe Asthma Research Program to an urban population.

    Directory of Open Access Journals (Sweden)

    Paru Patrawalla

    Full Text Available Identification and characterization of asthma phenotypes are challenging due to disease complexity and heterogeneity. The Severe Asthma Research Program (SARP used unsupervised cluster analysis to define 5 phenotypically distinct asthma clusters that they replicated using 3 variables in a simplified algorithm. We evaluated whether this simplified SARP algorithm could be used in a separate and diverse urban asthma population to recreate these 5 phenotypic clusters.The SARP simplified algorithm was applied to adults with asthma recruited to the New York University/Bellevue Asthma Registry (NYUBAR to classify patients into five groups. The clinical phenotypes were summarized and compared.Asthma subjects in NYUBAR (n = 471 were predominantly women (70% and Hispanic (57%, which were demographically different from the SARP population. The clinical phenotypes of the five groups generated by the simplified SARP algorithm were distinct across groups and distributed similarly to those described for the SARP population. Groups 1 and 2 (6 and 63%, respectively had predominantly childhood onset atopic asthma. Groups 4 and 5 (20% were older, with the longest duration of asthma, increased symptoms and exacerbations. Group 4 subjects were the most atopic and had the highest peripheral eosinophils. Group 3 (10% had the least atopy, but included older obese women with adult-onset asthma, and increased exacerbations.Application of the simplified SARP algorithm to the NYUBAR yielded groups that were phenotypically distinct and useful to characterize disease heterogeneity. Differences across NYUBAR groups support phenotypic variation and support the use of the simplified SARP algorithm for classification of asthma phenotypes in future prospective studies to investigate treatment and outcome differences between these distinct groups.Clinicaltrials.gov NCT00212537.

  9. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold

    2017-01-01

    Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps......, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs...... with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR...

  10. Prevalence, severity and risk factors of allergic disorders among ...

    African Journals Online (AJOL)

    Objectives: To find out the prevalence and risk factors of allergic disorders. Methods: Data ..... with being continuously alert to their eating habits due to fear of allergic ... and fish.6,13,20,23 Genetic factors are known to be incrim- inated with ...

  11. Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis

    OpenAIRE

    Lai, Tianwen; Wang, Shaobin; Xu, Zhiwei; Zhang, Chao; Zhao, Yun; Hu, Yue; Cao, Chao; Ying, Songmin; Chen, Zhihua; Li, Wen; Wu, Bin; Shen, Huahao

    2015-01-01

    Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ?52 weeks) was perfor...

  12. Asthma and lung cancer, after accounting for co-occurring respiratory diseases and allergic conditions: a systematic review protocol.

    Science.gov (United States)

    Denholm, Rachel; Crellin, Elizabeth; Arvind, Ashwini; Quint, Jennifer

    2017-01-16

    Asthma is one of the most frequently diagnosed respiratory diseases in the UK, and commonly co-occurs with other respiratory and allergic diseases, such as chronic obstructive pulmonary disease (COPD) and atopic dermatitis. Previous studies have shown an increased risk of lung cancer related to asthma, but the evidence is mixed when accounting for co-occurring respiratory diseases and allergic conditions. A systematic review of published data that investigate the relationship between asthma and lung cancer, accounting for co-occurring respiratory and allergic diseases, will be conducted to investigate the independent association of asthma with lung cancer. A systematic review will be conducted, and include original reports of cohort, cross-sectional and case-control studies of the association of asthma with lung cancer after accounting for co-occurring respiratory diseases. Articles published up to June 2016 will be included, and their selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A standardised data extraction form will be developed and pretested, and descriptive analyses will be used to summarise the available literature. If appropriate, pooled effect estimates of the association between asthma and lung cancer, given adjustment for a specific co-occurring condition will be estimated using random effects models. Potential sources of heterogeneity and between study heterogeneity will also be investigated. The study will be a review of published data and does not require ethical approval. Results will be disseminated through a peer-reviewed publication. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42016043341. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4

    Directory of Open Access Journals (Sweden)

    Lacoeuille Yannick

    2011-02-01

    Full Text Available Abstract Background Th2 cell activation and T regulatory cell (Treg deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4. Methods T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM allergic rhinitics (R, 18 HDM allergic rhinitics and asthmatics (AR, 13 non allergic asthmatics (A and 20 controls, with or without anti-co-receptors antibodies. Results In asthmatics (A+AR, a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR, allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4. Conclusions T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.

  14. Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts

    DEFF Research Database (Denmark)

    Stratakis, Nikos; Roumeliotaki, Theano; Oken, Emily

    2017-01-01

    Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess...... whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence...... consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood....

  15. Virus-induced asthma attack: The importance of allergic inflammation in response to viral antigen in an animal model of asthma.

    Science.gov (United States)

    Skappak, Christopher; Ilarraza, Ramses; Wu, Ying-Qi; Drake, Matthew G; Adamko, Darryl J

    2017-01-01

    Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes. We hypothesized that animals with immunologic memory to a respiratory virus would also develop airway hyperresponsiveness in response to a UV-inactivated form of the virus if they have pre-existing allergic airway inflammation. Guinea pigs were ovalbumin-sensitized, infected with live parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re-inoculated 60 days later with live or UV-inactivated PIV. Some animals were either treated with dexamethasone prior to the second viral exposure. Lymphocytes were isolated from parabronchial lymph nodes to confirm immunologic memory to the virus. Airway reactivity was measured and inflammation was assessed using bronchoalveolar lavage and lung histology. The induction of viral immunologic memory was confirmed in infected animals. Allergen sensitized and challenged animals developed airway hyperreactivity with eosinophilic airway inflammation when re-exposed to UV-inactivated PIV, while non-sensitized animals did not. Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment with dexamethasone. We suggest that the response of allergic inflammation to virus antigen is a significant factor causing asthma exacerbation. We propose that this is one mechanism explaining how corticosteroids prevent virus-induced asthma attack.

  16. Job strain and the risk of severe asthma exacerbations

    DEFF Research Database (Denmark)

    Heikkilä, K; Madsen, I E H; Nyberg, S T

    2014-01-01

    BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations...... in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe...... asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years...

  17. CYTOLOGICAL AND MORPHOMETRIC ESTIMATE OF THE INFLAMMATION AMONG THE CHILDREN, SUFFERING FROM MODERATELY SEVERE BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    T.R. Dulina

    2007-01-01

    Full Text Available The search for the new noninvasive and information methods to estimate the intensity of the inflammatory processes during the bronchial asthma is an important task for the modern medicine, pediatrics, in particular. We have examined 20 children, suffering from moderately severe bronchial asthma in remission. patients underwent the induction of the sputum by means of nail hypertonic solution, bronchoscopic examination along with the sampling of the lavage fluid and bronchial biopsy, cytometry of the induced sputum and bronchoalveolar lavage fluid, morphometric examination of the biopsy samples of bronchi walls, determination of the nitric oxide contents in the expired air. We revealed high self descriptiveness of the cytological characteristics of the induced sputum. High percentage of neutrophiles and eosinophiles in the induced sputum disclosed during remission of the bronchial asthma, as well as thickness increase of the basilemma, ratio distortion of the ciliated and cyathiform cells in the favor of the latter, especially along with the high nitric oxide contents in the expired air indicate the continuous persistence in the allergic respiratory inflammation.Key words: induced sputum, bronchial asthma, children.

  18. Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis.

    Science.gov (United States)

    Arasi, Stefania; Costa, Stefano; Magazzù, Giuseppe; Ieni, Antonio; Crisafulli, Giuseppe; Caminiti, Lucia; Chiera, Fernanda; Vaccaro, Mario; Del Giudice, Michele Miraglia; Pajno, Giovanni Battista

    2016-03-22

    Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. We present herein the case of a 13-year-old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases.

  19. The effect of encasings on quality of life in adult house dust mite allergic patients with rhinitis, asthma and/or atopic dermatitis

    NARCIS (Netherlands)

    Terreehorst, I.; Duivenvoorden, H. J.; Tempels-Pavlica, Z.; Oosting, A. J.; de Monchy, J. G. R.; Bruijnzeel-Koomen, C. A. F. M.; van Wijk, R. Gerth

    2005-01-01

    BACKGROUND: Environmental control has been put forward as an integral part of the management of house dust mite (HDM) allergy in sensitized patients. To validate this statement allergic disorders involved in HDM allergy--allergic asthma, rhinitis and atopic eczema/dermatitis syndrome (AEDS)--should

  20. The effect of encasings on quality of life in adult house dust mite allergic patients with rhinitis, asthma and/or atopic dermatitis

    NARCIS (Netherlands)

    Terreehorst, [No Value; Duivenvoorden, HJ; Tempels-Pavlica, Z; Oosting, AJ; de Monchy, JGR; Bruijnzeel-Koomen, CAFM; van Wijk, R.

    Background: Environmental control has been put forward as an integral part of the management of house dust mite (HDM) allergy in sensitized patients. To validate this statement allergic disorders involved in HDM allergy - allergic asthma, rhinitis and atopic eczema/dermatitis syndrome (AEDS) -

  1. Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview

    NARCIS (Netherlands)

    Asaria, M.; Dhami, S.; van Ree, R.; Gerth van Wijk, R.; Muraro, A.; Roberts, G.; Sheikh, A.

    2018-01-01

    Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we

  2. Features of Atopic Reactivity in Schoolchildren with Severe Bronchial Asthma

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    U.I. Marusyk

    2014-11-01

    Full Text Available The study involved 30 students with severe bronchial asthma and 30 children with moderate to severe course. Patients with severe bronchial asthma revealed a clear tendency to increase the relative content of interleukin 4 in peripheral blood, which indirectly indicates the severity of inflammation in the bronchi. Almost every second child suffering from severe bronchial asthma reported an increase in the concentration of immunoglobulin E (more than 545.3 IU/ml, and the odds ratio was 1.9 (95% CI 1.1–3.4. In the group of patients with severe bronchial asthma, cases of increased skin sensitivity to household allergens were significantly more frequent compared to the second group. Thus, the size of hyperemia over 15.0 mm was recorded in 81.5 % of children of the first group and only in 51.9 % of persons (Pϕ < 0.05 in the second one. Clinical and epidemiological risk and diagnostic value of individual indicators of atopic reactivity were determined to verify the phenotype of severe bronchial asthma.

  3. Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age.

    Science.gov (United States)

    Bowatte, Gayan; Lodge, Caroline J; Knibbs, Luke D; Lowe, Adrian J; Erbas, Bircan; Dennekamp, Martine; Marks, Guy B; Giles, Graham; Morrison, Stephen; Thompson, Bruce; Thomas, Paul S; Hui, Jennie; Perret, Jennifer L; Abramson, Michael J; Walters, Haydn; Matheson, Melanie C; Dharmage, Shyamali C

    2017-01-01

    Traffic-related air pollution (TRAP) exposure is associated with allergic airway diseases and reduced lung function in children, but evidence concerning adults, especially in low-pollution settings, is scarce and inconsistent. We sought to determine whether exposure to TRAP in middle age is associated with allergic sensitization, current asthma, and reduced lung function in adults, and whether these associations are modified by variants in Glutathione S-Transferase genes. The study sample comprised the proband 2002 laboratory study of the Tasmanian Longitudinal Health Study. Mean annual residential nitrogen dioxide (NO 2 ) exposure was estimated for current residential addresses using a validated land-use regression model. Associations between TRAP exposure and allergic sensitization, lung function, current wheeze, and asthma (n = 1405) were investigated using regression models. Increased mean annual NO 2 exposure was associated with increased risk of atopy (adjusted odds ratio [aOR], 1.14; 95% CI, 1.02-1.28 per 1 interquartile range increase in NO 2 [2.2 ppb]) and current wheeze (aOR, 1.14; 1.02-1.28). Similarly, living less than 200 m from a major road was associated with current wheeze (aOR, 1.38; 95% CI, 1.06-1.80) and atopy (aOR, 1.26; 95% CI, 0.99-1.62), and was also associated with having significantly lower prebronchodilator and postbronchodilator FEV 1 and prebronchodilator forced expiratory flow at 25% to 75% of forced vital capacity. We found evidence of interactions between living less than 200 m from a major road and GSTT1 polymorphism for atopy, asthma, and atopic asthma. Overall, carriers of the GSTT1 null genotype had an increased risk of asthma and allergic outcomes if exposed to TRAP. Even relatively low TRAP exposures confer an increased risk of adverse respiratory and allergic outcomes in genetically susceptible individuals. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Therapeutic potential of anti-IL-1β IgY in guinea pigs with allergic asthma induced by ovalbumin.

    Science.gov (United States)

    Wei-xu, Hu; Qin, Xiang; Zhu, Wen; Yuan-yi, Chen; Li-feng, Zeng; Zhi-yong, Liu; Dan, He; Xiao-mu, Wu; Guo-zhu, Hu

    2014-03-01

    Interleukin-1 beta (IL-1β) plays pivotal roles in the progression of allergic airway inflammation. This study aims to determine whether the blockade of IL-1β can inhibit airway inflammation in guinea pigs with allergic asthma induced by the inhalation of aerosolized ovalbumin (OVA). Healthy guinea pigs treated with saline were used as normal controls (group C). The guinea pigs with allergic asthma induced by the inhalation of aerosolized OVA were randomly divided into three groups: (1) the M group containing negative control animals treated with saline; (2) the Z1 group containing animals treated by the inhalation of atomized 0.1% anti-IL-1β immunoglobulin yolk (IgY); and (3) the Z2 group containing positive control animals that were treated with budesonide. The inflammatory cells in the peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were evaluated using methylene blue and eosin staining. Cytokine concentrations were measured using an enzyme-linked immunosorbent assay. Pulmonary sections were examined using hematoxylin-eosin staining. Allergic inflammation and damage to the pulmonary tissues were decreased in the Z1 group compared to the M group. Eosinophils and neutrophils in the PB and BALF were significantly decreased in the Z1 group compared to the M group (Pguinea pigs with allergic asthma. The inhibitory activity may be due to the decrease in the numbers of eosinophils and neutrophils and the reduced levels of inflammatory cytokines and IgE in the PB and BALF. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination.

    Science.gov (United States)

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold; Osuna, Christa Elyse; Petersen, Maria Skaalum; Steuerwald, Ulrike; Nielsen, Flemming; Poulsen, Lars K; Weihe, Pál; Grandjean, Philippe

    2017-12-01

    Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs - Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) - were measured at three timepoints (maternal serum in pregnancy week 34-36 and child serum at ages 5 and 13 years) and their association with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR-unvaccinated children, higher levels of the five PFASs at age 5 years were associated with increased odds of asthma at ages 5 and 13. The associations were reversed among MMR-vaccinated children. Prenatal PFAS exposure was not associated with childhood asthma or allergic diseases regardless of MMR vaccination status. In conclusion, PFAS exposure at age 5 was associated with increased risk of asthma among a small subgroup of MMR-unvaccinated children but not among MMR-vaccinated children. While PFAS exposure may impact immune system functions, this study suggests that MMR vaccination might be a potential effect-modifier.

  6. Management preferences of pediatricians in moderate and severe acute asthma.

    Science.gov (United States)

    Arga, Mustafa; Bakirtas, Arzu; Catal, Ferhat; Derinoz, Oksan; Topal, Erdem; Demirsoy, M Sadik; Turktas, Ipek

    2013-05-01

    To assess and compare management preferences of physicians for moderate and severe acute asthma based on case scenarios and to determine the factors influencing their decisions. A questionnaire based on the Global Initiative on Asthma (GINA) guideline and comprising eight questions on management of acute asthma was delivered to participants of two national pediatric congresses. Management of moderate and severe acute asthma cases was evaluated by two clinical case scenarios for estimation of acute attack severity, initial treatment, treatment after 1h, and discharge recommendations. A uniform answer box comprising the possible choices was provided just below the questions, and respondents were requested to tick the answers they thought was appropriate. Four-hundred and eighteen questionnaires were analyzed. All questions regarding moderate and severe acute asthma case scenarios were answered accurately by 15.8% and 17.0% of physicians, respectively. The initial treatment of moderate and severe cases was known by 100.0% and 78.2% of physicians, respectively. Knowledge of the appropriate plan for treatment after 1h was low both for moderate (45.0%) and severe attacks (35.4%). Discharge recommendations were adequate in 32.5% and 70.8% of physicians for moderate and severe attacks, respectively. Multiple logistic regression analysis revealed that working at a hospital with a continuing medical education program was the only significant predictor of a correct response to all questions regarding severe attacks (p = .04; 95%CI, 1.02-3.21). No predictors were found for information on moderate attacks. Pediatricians have difficulty in planning treatment after 1 hour both for moderate and severe asthma attacks. Postgraduate education programs that target physicians in hospitals without continuing medical education facilities may improve guideline adherence.

  7. Lower prevalence and greater severity of asthma in hot and dry climate

    Directory of Open Access Journals (Sweden)

    Marco Aurélio de Valois Correia Junior

    2017-03-01

    Full Text Available Objective: To estimate asthma prevalence, severity, and associated factors in adolescents who live in a low relative humidity environment. Methods: In this cross-sectional study, adolescents aged 13–14 years from the city of Petrolina located in the Brazilian semiarid region answered the International Study of Asthma and Allergies in Childhood (ISAAC questionnaire. The possible explanatory variables of the study were gender, family income, mother's education, smokers in the household, parental history of asthma, personal history of allergic rhinitis or atopic dermatitis, and physical activity level. Poisson regression analysis was used to assess the association between asthma and the explanatory variables. Results: A total of 1591 adolescents participated in the study, of whom 49.7% were male. The prevalence of active asthma, severe asthma, and physician-diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with asthma missed more school days than their peers (33 vs. 22 days/year; p < 0.03. Associated factors that remained significant after adjustment were history of asthma in parents (PR = 2.65, p < 0.001 and personal diagnosis of allergic rhinitis (PR = 1.96, p < 0.001 and/or atopic dermatitis (PR = 2.18, p < 0.001. Conclusion: Asthma prevalence in this low-humidity environment was lower, but more severe than those reported in other Brazilian cities. The dry climate might hamper disease control and this may have contributed to the higher school absenteeism observed. The association of asthma with allergic rhinitis and atopic dermatitis as well as a history of asthma in parents suggests that atopy is an important risk factor for asthma in this population. Resumo: Objetivo: Estimar a prevalência, a gravidade e os fatores associados à asma em adolescentes que vivem em uma região de baixa umidade relativa do ar. Métodos: Estudo transversal em adolescentes de 13 e 14 anos do semiárido brasileiro. Os

  8. The airway microbiome in patients with severe asthma: Associations with disease features and severity.

    Science.gov (United States)

    Huang, Yvonne J; Nariya, Snehal; Harris, Jeffrey M; Lynch, Susan V; Choy, David F; Arron, Joseph R; Boushey, Homer

    2015-10-01

    Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. We sought to evaluate relationships between the bronchial microbiome and features of severe asthma. Bronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41). In patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index (P PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01), sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values (per square millimeter, P = .07). Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5), an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria. No taxa were associated with a TH2-related epithelial gene expression signature, but expression of TH17-related genes was associated with Proteobacteria. Patients with severe asthma compared with healthy control subjects or patients with mild-to-moderate asthma were significantly enriched in Actinobacteria, although the largest differences

  9. Phthalate exposure through different pathways and allergic sensitization in preschool children with asthma, allergic rhinoconjunctivitis and atopic dermatitis

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Callesen, Michael; Weschler, Charles J.

    2015-01-01

    Studies in rodents indicate that phthalates can function as adjuvants, increasing the potency of allergens. Meanwhile, epidemiological studies have produced inconsistent findings regarding relationships between phthalate exposures and allergic disease in humans. The present study examined phthala...

  10. Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hwa Jung

    2016-09-01

    Full Text Available Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR. Current therapeutic options for the management of asthma include inhaled corticosteroids and β2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2, one of the major components of bee venom (BV, to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30. The infiltration of immune cells, such as Th2 cytokines in the lungs, and the lung histology, were assessed in the OVA-challenged mice in the presence and absence of an intratracheal administration of bvPLA2. We showed that the intratracheal administration of bvPLA2 markedly suppressed the OVA-induced allergic airway inflammation by reducing AHR, overall area of inflammation, and goblet cell hyperplasia. Furthermore, the suppression was associated with a significant decrease in the production of Th2 cytokines, such as IL-4, IL-5, and IL-13, and a reduction in the number of total cells, including eosinophils, macrophages, and neutrophils in the airway.

  11. Neuropsychiatry phenotype in asthma: Psychological stress-induced alterations of the neuroendocrine-immune system in allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Isao Ohno

    2017-09-01

    Full Text Available Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation. The mechanisms underlying this process may involve a pathological series of events from the brain to the lungs, which is attracting attention as a conceptually advanced phenotype in asthma pathogenesis. This review presents insights into the critical role of psychological stress in the development and exacerbation of allergic asthma, with a special focus on our own data that emphasizes on the continuity from the central sensing of psychological stress to enhanced eosinophilic airway inflammation.

  12. Association of pediatric asthma severity with exposure to common household dust allergens

    International Nuclear Information System (INIS)

    Gent, Janneane F.; Belanger, Kathleen; Triche, Elizabeth W.; Bracken, Michael B.; Beckett, William S.; Leaderer, Brian P.

    2009-01-01

    Background: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. Objective: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. Methods: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. Results: Der p 1 house dust mite allergen concentration of 2.0 μg/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 μg/g and OR 2.55 95% CI 1.13, 5.73 for ≥10.0 μg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). Conclusion: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

  13. Association of pediatric asthma severity with exposure to common household dust allergens

    Energy Technology Data Exchange (ETDEWEB)

    Gent, Janneane F., E-mail: janneane.gent@yale.edu [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Belanger, Kathleen [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Triche, Elizabeth W. [Brown University, Department of Community Health/Epidemiology, Providence, RI (United States); Bracken, Michael B. [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States); Beckett, William S. [Mount Auburn Hospital, Department of Internal Medicine, Cambridge, MA (United States); Leaderer, Brian P. [Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, One Church Street, 6th Floor, New Haven, CT 06510 (United States)

    2009-08-15

    Background: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. Objective: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. Methods: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. Results: Der p 1 house dust mite allergen concentration of 2.0 {mu}g/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 {mu}g/g and OR 2.55 95% CI 1.13, 5.73 for {>=}10.0 {mu}g/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). Conclusion: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

  14. Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model.

    Science.gov (United States)

    Liang, Lin; Hur, Jung; Kang, Ji Young; Rhee, Chin Kook; Kim, Young Kyoon; Lee, Sook Young

    2018-04-19

    The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

  15. A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.

    Science.gov (United States)

    Harris, Jeffrey M; Maciuca, Romeo; Bradley, Mary S; Cabanski, Christopher R; Scheerens, Heleen; Lim, Jeremy; Cai, Fang; Kishnani, Mona; Liao, X Charlene; Samineni, Divya; Zhu, Rui; Cochran, Colette; Soong, Weily; Diaz, Joseph D; Perin, Patrick; Tsukayama, Miguel; Dimov, Dimo; Agache, Ioana; Kelsen, Steven G

    2016-03-18

    Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. ClinicalTrials.gov NCT01582503.

  16. Frequency, severity and causes of unexpected allergic reactions to food: A systematic literature review

    NARCIS (Netherlands)

    Versluis, A.; Knulst, A.C.; Kruizinga, A.G.; Michelsen, A.; Houben, G.F.; Baumert, J.L.; Os-Medendorp, H. van

    2015-01-01

    Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

  17. Frequency, severity and causes of unexpected allergic reactions to food : A systematic literature review

    NARCIS (Netherlands)

    Versluis, A.; Knulst, A. C.; Kruizinga, A. G.; Michelsen, A.; Houben, G. F.; Baumert, J. L.; van Os-Medendorp, H.

    2015-01-01

    Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

  18. A systematic review on the development of asthma and allergic diseases in relation to international immigration: the leading role of the environment confirmed.

    Directory of Open Access Journals (Sweden)

    Báltica Cabieses

    Full Text Available The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been contradictory, particularly on the interplay between allergic diseases and understudied social determinants of health like migration status. This review aimed at providing evidence for the association between migration status and asthma and allergies, and to explore the mechanisms between migration status and the development of asthma and allergies.Systematic review on asthma and allergies and immigration status in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA statement. The pooled odds ratio (OR of the prevalence of asthma in immigrants compared to the host population was 0.60 (95% CI 0.45-0.84, and the pooled OR for allergies was 1.01 (95% CI 0.62-1.69. The pooled OR for the prevalence of asthma in first generation versus second generation immigrants was 0.37 (95% CI 0.25-0.58. Comparisons between populations in their countries of origin and those that emigrated vary depending on their level of development; more developed countries show higher rates of asthma and allergies.Our findings suggest a strong influence of the environment on the development of asthma and allergic diseases throughout the life course. The prevalence of asthma is generally higher in second generation than first generation immigrants. With length of residence in the host country the prevalence of asthma and allergic diseases increases steadily. These findings are consistent across study populations, host countries, and children as well as adults. Differences have been found to be significant when tested in a linear model, as well as when comparing between early and later age of migration, and between shorter and longer time of residence.

  19. A Systematic Review on the Development of Asthma and Allergic Diseases in Relation to International Immigration: The Leading Role of the Environment Confirmed

    Science.gov (United States)

    Cabieses, Báltica; Uphoff, Eleonora; Pinart, Mariona; Antó, Josep Maria; Wright, John

    2014-01-01

    Background The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been contradictory, particularly on the interplay between allergic diseases and understudied social determinants of health like migration status. This review aimed at providing evidence for the association between migration status and asthma and allergies, and to explore the mechanisms between migration status and the development of asthma and allergies. Methods and Findings Systematic review on asthma and allergies and immigration status in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled odds ratio (OR) of the prevalence of asthma in immigrants compared to the host population was 0.60 (95% CI 0.45–0.84), and the pooled OR for allergies was 1.01 (95% CI 0.62–1.69). The pooled OR for the prevalence of asthma in first generation versus second generation immigrants was 0.37 (95% CI 0.25–0.58). Comparisons between populations in their countries of origin and those that emigrated vary depending on their level of development; more developed countries show higher rates of asthma and allergies. Conclusions Our findings suggest a strong influence of the environment on the development of asthma and allergic diseases throughout the life course. The prevalence of asthma is generally higher in second generation than first generation immigrants. With length of residence in the host country the prevalence of asthma and allergic diseases increases steadily. These findings are consistent across study populations, host countries, and children as well as adults. Differences have been found to be significant when tested in a linear model, as well as when comparing between early and later age of migration, and between shorter and longer time of residence. PMID:25141011

  20. Benralizumab: a unique IL-5 inhibitor for severe asthma

    Directory of Open Access Journals (Sweden)

    Tan LD

    2016-04-01

    Full Text Available Laren D Tan,1 Jennifer M Bratt,2 Dorottya Godor,3 Samuel Louie,2 Nicholas J Kenyon2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 2Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, USA; 3School of Medicine, Semmelweis University, Budapest, Hungary Abstract: The presence of eosinophilic inflammation is a characteristic feature of chronic and acute inflammation in asthma. An estimated 5%–10% of the 300 million people worldwide who suffer from asthma have a severe form. Patients with eosinophilic airway inflammation represent approximately 40%–60% of this severe asthmatic population. This form of asthma is often uncontrolled, marked by refractoriness to standard therapy, and shows persistent airway eosinophilia despite glucocorticoid therapy. This paper reviews personalized novel therapies, more specifically benralizumab, a humanized anti-IL-5Rα antibody, while also being the first to provide an algorithm for potential candidates who may benefit from anti-IL-5Rα therapy. Keywords: asthma, eosinophils, asthma treatments, benralizumab, IL-5, IL-5Rα, MEDI-563

  1. Comparative immunology of allergic responses.

    Science.gov (United States)

    Gershwin, Laurel J

    2015-01-01

    Allergic responses occur in humans, rodents, non-human primates, avian species, and all of the domestic animals. These responses are mediated by immunoglobulin E (IgE) antibodies that bind to mast cells and cause release/synthesis of potent mediators. Clinical syndromes include naturally occurring asthma in humans and cats; atopic dermatitis in humans, dogs, horses, and several other species; food allergies; and anaphylactic shock. Experimental induction of asthma in mice, rats, monkeys, sheep, and cats has helped to reveal mechanisms of pathogenesis of asthma in humans. All of these species share the ability to develop a rapid and often fatal response to systemic administration of an allergen--anaphylactic shock. Genetic predisposition to development of allergic disease (atopy) has been demonstrated in humans, dogs, and horses. Application of mouse models of IgE-mediated allergic asthma has provided evidence for a role of air pollutants (ozone, diesel exhaust, environmental tobacco smoke) in enhanced sensitization to allergens.

  2. The unfavorable effects of concomitant asthma and sleeplessness due to the atopic eczema/dermatitis syndrome (AEDS) on quality of life in subjects allergic to house-dust mites.

    Science.gov (United States)

    Terreehorst, I; Duivenvoorden, H J; Tempels-Pavlica, Z; Oosting, A J; de Monchy, J G R; Bruijnzeel-Koomen, C A F M; Post, M W M; Gerth van Wijk, R

    2002-10-01

    Allergic rhinitis, asthma or the atopic eczema/dermatitis syndrome (AEDS) may independently impair quality of life in patients. However, although many allergic patients may suffer from more than one disorder, the effect of concomitant disease -- in particular, the impact of AEDS -- is largely unknown. As part of a large multicenter clinical trial on the efficacy of mattress casings in house-dust mite (HDM) allergy, generic quality of life in a mixed population of 224 subjects with rhinitis (n = 198) and/or asthma (n = 111) and/or AEDS (n = 64) was studied. The study aimed to estimate quality of life impairment in these atopic patients and to address the question/issue of whether one atopic disorder goes beyond other existing allergic diseases, thereby causing further impairment to quality of life. Generic quality of life was assessed by SF-36. Quality of life in the atopic group was compared with a Dutch norm population. Multiple linear regression was used to determine the effects of disease (i.e. the presence of allergic rhinitis, asthma or AEDS) or disease severity, as assessed by visual analog scores (VAS) for asthma, rhinitis, VAS sleeplessness and VAS itching being considered as major symptoms in AEDS on SF-36 domains. Compared to the norm group, atopic patients were impaired in: physical functioning; role physical functioning; general health; vitality; and social functioning. The diagnosis of asthma was negatively associated with the SF-36 subscales for physical functioning (P = 0.02), and general health (P health (P health (P = 0.01), mental health (P < 0.01), social functioning (P < 0.01), and vitality (P < 0.01). In contrast, neither the diagnosis of allergic rhinitis or AEDS, nor VAS itching as an outcome parameter of AEDS, exerted additional effects on the SF-36 domains. Patients with atopic disease based on HDM allergy may have impaired quality of life. The majority of these patients have allergic rhinitis. The (co)existence of asthma, expressed in

  3. [Role of serum S1P levels during asthma attack in the evaluation of asthma severity].

    Science.gov (United States)

    Zhao, Yunwei; Xu, Yiqin; Li, Shuang; Wei, Yu; Wang, Chunling

    2017-09-01

    To observe the changes of serum sphingosine-1-phosphate (S1P) level in asthmatic patients with different severity of bronchial asthma, and to explore the evaluation value of S1P on the severity of asthma. A prospective observational study was conducted. Fifty-two patients with asthma admitted to Department of Respiratory Medicine of the First Affiliated Hospital of Jiamusi University from November 2015 to January 2017 were enrolled. According to the severity of the disease, the patients were divided into mild, moderate and severe groups. In the same period, 25 healthy subjects were served as healthy control group. All the subjects got the peripheral venous blood collection in the morning fasting, the level of serum S1P was determined by enzyme linked immunosorbent assay (ELISA), the peripheral blood eosinophil (EOS) was counted, and the pulmonary function test was performed. The correlation among the parameters was analyzed by Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted, and the value of serum S1P on evaluating the severity of asthma was analyzed. Fifty-two asthma patients were enrolled, including 17 patients of the mild, 19 of the moderate, and 16 of the severe. Compared with the healthy control group, serum S1P level and peripheral blood EOS in different degree asthma groups were significantly increased, and forced expiratory volume in 1 second (FEV1) was decreased significantly; and with asthma exacerbations, serum S1P levels and peripheral blood EOS were gradually increased [mild, moderate and severe S1P (nmol/L) were 1 537.0±120.3, 1 980.7±149.5, 2 202.2±117.2 (F = 274.624, P = 0.001); EOS (×10 9 /L) were 0.13±0.06, 0.20±0.07, 0.37±0.14 , respectively (F = 44.093, P = 0.001)], and FEV1 was decreased gradually [mild, moderate and severe were 0.89±0.05, 0.63±0.06, 0.42±0.10, respectively (F = 159.756, P = 0.001)]. Correlation analysis showed that there were significant positive correlations between serum S1P

  4. Accurate prediction of severe allergic reactions by a small set of environmental parameters (NDVI, temperature).

    Science.gov (United States)

    Notas, George; Bariotakis, Michail; Kalogrias, Vaios; Andrianaki, Maria; Azariadis, Kalliopi; Kampouri, Errika; Theodoropoulou, Katerina; Lavrentaki, Katerina; Kastrinakis, Stelios; Kampa, Marilena; Agouridakis, Panagiotis; Pirintsos, Stergios; Castanas, Elias

    2015-01-01

    Severe allergic reactions of unknown etiology,necessitating a hospital visit, have an important impact in the life of affected individuals and impose a major economic burden to societies. The prediction of clinically severe allergic reactions would be of great importance, but current attempts have been limited by the lack of a well-founded applicable methodology and the wide spatiotemporal distribution of allergic reactions. The valid prediction of severe allergies (and especially those needing hospital treatment) in a region, could alert health authorities and implicated individuals to take appropriate preemptive measures. In the present report we have collecterd visits for serious allergic reactions of unknown etiology from two major hospitals in the island of Crete, for two distinct time periods (validation and test sets). We have used the Normalized Difference Vegetation Index (NDVI), a satellite-based, freely available measurement, which is an indicator of live green vegetation at a given geographic area, and a set of meteorological data to develop a model capable of describing and predicting severe allergic reaction frequency. Our analysis has retained NDVI and temperature as accurate identifiers and predictors of increased hospital severe allergic reactions visits. Our approach may contribute towards the development of satellite-based modules, for the prediction of severe allergic reactions in specific, well-defined geographical areas. It could also probably be used for the prediction of other environment related diseases and conditions.

  5. Comparative effectiveness of mepolizumab and omalizumab in severe asthma: An indirect treatment comparison.

    Science.gov (United States)

    Cockle, Sarah M; Stynes, Gillian; Gunsoy, Necdet B; Parks, Daniel; Alfonso-Cristancho, Rafael; Wex, Jaro; Bradford, Eric S; Albers, Frank C; Willson, Jenny

    2017-02-01

    Severe asthma is a heterogeneous disease. Patients with both eosinophilic and allergic asthma phenotypes may be eligible for treatment with mepolizumab and omalizumab. Evidence on the relative effectiveness of these treatments in this 'overlap' population would be informative for clinical and payer decision making. A systematic literature review and indirect treatment comparison (Bayesian framework) were performed to assess the comparative effectiveness and tolerability of mepolizumab and omalizumab, as add-ons to standard of care. Studies included in the primary analysis were double-blind, randomized controlled trials, ≥12 weeks' duration enrolling patients with severe asthma with a documented exacerbation history and receiving high-dose inhaled corticosteroids plus ≥1 additional controller. Two populations were examined: patients potentially eligible for 1) both treatments (Overlap population) and 2) either treatment (Trial population). In the Overlap population, no differences between treatments in clinically significant exacerbations and exacerbations requiring hospitalization were found, although trends favored mepolizumab (rate ratio [RR]:0.66 [95% credible intervals (Crl):0.37,1.19]; 0.19[0.02,2.32], respectively). In the Trial population, mepolizumab treatment produced greater reductions in clinically significant exacerbations (RR:0.63 [95% CrI:0.45,0.89]) but not exacerbations requiring hospitalization compared with omalizumab (RR:0.58 [95% Crl: 0.16,2.13]), although the trend favored mepolizumab. Both treatments had broadly comparable effects on lung function, and similar tolerability profiles. Whilst this analysis has limitations due to a restricted evidence base and residual heterogeneity, it showed that in patients with severe asthma, mepolizumab seems to be at least as effective as omalizumab and that the tolerability profiles of the two treatments did not meaningfully differentiate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Helicobacter pylori neutrophil-activating protein: A potential Treg modulator suppressing allergic asthma?

    Directory of Open Access Journals (Sweden)

    Anjna eSehrawat

    2015-06-01

    Full Text Available The ultimate aim of immunology is to kill the pathogen without being harmful to the host. But what if eliminating the pathogen in itself is discomforting for the host? One such emerging case is of Helicobacter pylori. Modern medicine, infantile vaccination and ultra-hygienic conditions have led to progressive disappearance of H. pylori in different parts of the world. However, the adversities caused by H. pylori’s absence are much larger than those caused by its presence. Asthma is rising as an epidemic in last few decades and several reports suggest an inverse-relationship between H. pylori’s persistence and early-life onset asthma. Regulatory T cells play an important role in both the cases. This is further supported by experiments on mouse-models. Hence, need of the hour is to discern the relationship between H. pylori and its host and eliminating its negative impacts without disturbing our indigenous microbiota. To resolve whether H. pylori is a pathogen or an amphibiont is another important side. This review explores the biological basis of H. pylori-induced priming of immune system offering resistance to childhood-onset asthma. HP-NAP-Tregs interaction has been predicted using molecular docking and dynamic simulation.

  7. A new perspective on concepts of asthma severity and control

    NARCIS (Netherlands)

    D.R. Taylor; E.D. Bateman (Eric); L.P. Boulet; H.A. Boushey; W.W. Busse; T.B. Casale (Thomas); P. Chanez; P.L. Enright (Paul); P.G. Gibson; J.C. de Jongste (Johan); H.A. Kerstjens; S.C. Lazarus; M.L. Levy (Mark); P. O'byrne; M.R. Partridge; I.D. Pavord; M.R. Sears; P.J. Sterk (Peter); S.W. Stoloff; S.J. Szefler; S.D. Sullivan (Sean); M.D. Thomas; S.E. Wenzel; H.K. Reddel

    2008-01-01

    textabstractConcepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European

  8. A new perspective on concepts of asthma severity and control

    NARCIS (Netherlands)

    Taylor, D. R.; Bateman, E. D.; Boulet, L.-P.; Boushey, H. A.; Busse, W. W.; Casale, T. B.; Chanez, P.; Enright, P. L.; Gibson, P. G.; de Jongste, J. C.; Kerstjens, H. A. M.; Lazarus, S. C.; Levy, M. L.; O'Byrne, P. M.; Partridge, M. R.; Pavord, I. D.; Sears, M. R.; Sterk, P. J.; Stoloff, S. W.; Szefler, S. J.; Sullivan, S. D.; Thomas, M. D.; Wenzel, S. E.; Reddel, H. K.

    2008-01-01

    Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society

  9. A new perspective on concepts of asthma severity and control

    NARCIS (Netherlands)

    Taylor, D. R.; Bateman, E. D.; Boulet, L-P.; Boushey, H. A.; Busse, W. W.; Casale, T. B.; Chanez, P.; Enright, P. L.; Gibson, P. G.; de Jongste, J. C.; Kerstjens, H. A. M.; Lazarus, S. C.; Levy, M. L.; O'Byrne, P. M.; Partridge, M. R.; Pavord, I. D.; Sears, M. R.; Sterk, P. J.; Stoloff, S. W.; Szefler, S. J.; Sullivan, S. D.; Thomas, M. D.; Wenzel, S. E.; Reddel, H. K.

    Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society

  10. Exacerbations of asthma - A descriptive study of 425 severe exacerbations

    NARCIS (Netherlands)

    Tattersfield, AE; Postma, DS; Barnes, PJ; Svensson, K; Bauer, CA; O'Byrne, PM; Lofdahl, CG; Pauwels, RA; Ullman, A

    The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue p-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high

  11. CD8+ T Cells Mediate Female-Dominant IL-4 Production and Airway Inflammation in Allergic Asthma

    OpenAIRE

    Ito, Chihiro; Okuyama-Dobashi, Kaori; Miyasaka, Tomomitsu; Masuda, Chiaki; Sato, Miki; Kawano, Tasuku; Ohkawara, Yuichi; Kikuchi, Toshiaki; Takayanagi, Motoaki; Ohno, Isao

    2015-01-01

    The prevalence and severity of bronchial asthma are higher in females than in males after puberty. Although antigen-specific CD8+ T cells play an important role in the development of asthma through their suppressive effect on cytokine production, the contribution of CD8+ T cells to sex differences in asthmatic responses remains unclear. In the present study, we investigated the sex-specific effect of CD8+ T cells in the suppression of asthma using an ovalbumin mouse model of asthma. The numbe...

  12. Maternal waterpipe smoke exposure and the risk of asthma and allergic diseases in childhood: A post hoc analysis

    Directory of Open Access Journals (Sweden)

    Mirna Waked

    2015-02-01

    Full Text Available Introduction This analysis was conducted with the objective of evaluating association between waterpipe passive smoking exposure and asthma, and allergies among Lebanese children. Material and methods Data were taken from a crosssectional study on children from public and private schools. A sample of 22 schools participated in the study, where standardized written core questionnaires were distributed. From 5 to 12-year-old students filled in the questionnaires at home, while 13–14-year-old students filled it in in the class. In total, 5522 children were evaluated for the prevalence of asthma, allergic rhinitis and atopic eczema, and their associated factors, including waterpipe exposure due to parents’ smoking. Results The descriptive results of parental smoking were, as follows: among mothers: 1609 (29% mothers smoked cigarettes, 385 (7% smoked waterpipe and 98 (1.8% smoked both; among fathers: 2449 (44.2% smoked cigarettes, 573 (10.3% smoked waterpipe and 197 (3.5% smoked both. Maternal waterpipe smoking was significantly and moderately associated with allergic diseases (p < 0.001; ORa = 1.71, including probable asthma, rhinitis and dermatitis (p < 0.001 for all. Quite on the opposite, father’s waterpipe smoking was not associated with any of the diseases. Parental cigarette smoking demonstrated some positive effects: father’s cigarette smoking did not show association with dermatitis or asthma diagnosed by a physician, while mother’s cigarette smoking showed a positive association only with probable asthma. Moreover, no interactions between cigarette and waterpipe smoking were observed. Conclusions Maternal waterpipe smoking should be regarded as a high risk behavior; however, additional studies are necessary to confirm this finding.

  13. An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

    Science.gov (United States)

    Norris Reinero, Carol R; Decile, Kendra C; Berghaus, Roy D; Williams, Kurt J; Leutenegger, Christian M; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

    2004-10-01

    Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

  14. Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma.

    Science.gov (United States)

    Phillips, Jonathan E; Renteria, Lorena; Burns, Lisa; Harris, Paul; Peng, Ruoqi; Bauer, Carla M T; Laine, Dramane; Stevenson, Christopher S

    2016-06-01

    In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR. Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation.

  15. Increased mast cell density and airway responses to allergic and non-allergic stimuli in a sheep model of chronic asthma.

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    Joanne Van der Velden

    Full Text Available BACKGROUND: Increased mast cell (MC density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM allergen. METHODOLOGY/PRINCIPAL FINDINGS: MC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MC(T and MC(TC respectively was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase. MC(T and MC(TC density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05. The MC(TC/MC(T ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05. MC(T and MC(TC density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05. MC(T density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01. CONCLUSIONS: MC(T and MC(TC density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation.

  16. [The degree of asthma severity in children and the level of maternal anxiety and depression].

    Science.gov (United States)

    Witkowska-Płusa, Urszula

    2015-02-01

    Care for sick children most often falls to mothers, which may affect their mental state, causing the states of depression and anxiety. The aim of this study was to determine the relationship between the severity of asthma in children and the level of anxiety and depression in mothers, taking into account the importance of the material status of the family, the educational level of the mothers, the presence of critical events, as well as the coexistence of allergic diseases in other family members. The study included 60 mothers of children with bronchial asthma. Age of mothers in the investigated families was on average 37.28 +/- 6.24 years, and most had a high school education (55.0%) or higher (28.3%). 16.7% of mothers and 8.3% fathers suffered from asthma. 13.3% of mothers of children with asthma were brought child alone. To assess the level of anxiety the inventory for measuring state and trait anxiety (STAI - State Trait Anxiety Inventory) developed by Spielberger, Gorsuch'a and Lushene'a was applied. To determine the changes in depressive the Beck Depression Inventory (BDI - Beck Depression Inventory questionnaire) was used. The Student's t test was included for two independent populations and a comparison of the results obtained in the questionnaire for diagnosing the level of anxiety and depression. For other parameters the correlation coefficient r-Pearson rank and Kendall's tau were performed. Mothers of children with moderate asthma compared to mothers of children with mild asthma had higher levels of anxiety (both state and properties), and also a slightly higher level of depression. Maternal age was connected positively and moderately strongly with the number held by children (r = 0.380; p = 0.003) and age of a child with asthma (r = 0.613, p = 0.0005). The duration of the child's disease was associated positively and moderately strongly with the level of state anxiety mother (X-1) (r = 0.345; p = 0.007) and a bit less and also positively with the

  17. Prevention and treatment of allergic asthma in pregnancy: from conventional drugs to new therapeutical approaches.

    Science.gov (United States)

    Cadavid, Angela P; Bannenberg, Gérard L; Arck, Petra C; Fitzgerald, Justine S; Markert, Udo R

    2011-05-01

    Different conventional anti-asthmatic and anti-allergic drugs are commonly used in pregnancy, including inhaled corticosteroids, long- and short-acting β-agonists, leukotriene modifiers, cromolyn, and theophylline. Alternatively, immunotherapy with allergens before and during pregnancy is accepted as a causal treatment of allergies, but the allergy specifity and severity in combination with a variety of application protocols and procedures cause wide heterogenity of this treatment principle. Furthermore, the pharmacokinetic characteristics and the US Food and Drug Administration (FDA) classification of conventional anti-allergic drugs and immunological implications of immunotherapy are summarized in this review, and insights on fetal programming of allergies are introduced. We propose a potential perspective of treatment with anti-inflammatory and pro-resolving mediators, such as lipoxins, resolvins and protectins; these are lipid mediators physiologically generated during the immune response from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. This proposal fits with the recently appreciated approaches to allergy prevention for the newborn child by a balanced maternal nutrition and omega-3 long-chain polyunsaturated fatty acid consumption.

  18. Allergic Rhinitis

    Science.gov (United States)

    ... immunologist)? Resources American College of Allergy, Asthma and Immunology Medline Plus, Allergic Rhinitis Last Updated: December 8, 2017 This article was contributed by: familydoctor.org editorial staff Categories: ...

  19. Klippel-Feil syndrome with associated agenesis of lung and gall bladder presenting with asthma and allergic rhinitis

    International Nuclear Information System (INIS)

    Khanna, Puneet; Panjabi, Chandramani; Shah, Ashok

    2005-01-01

    Klippel-Feil syndrome (KFS), a triad of short neck, limitation of neck movement and low posterior hairline, is characterized by the presence of congenitally fused cervical vertebrae and is often associated with multiple congenital anomalies. A 35-year-old male was referred for evaluation of an 'opaque hemithorax'. This led to a diagnosis of KFS, agenesis of left lung and gall bladder. The patient had history of wheezing dyspnea with nasal symptoms, which were diagnosed as asthma and allergic rhinitis. A high index of suspicion is required to recognize such a patient, and efforts should be made to seek other congenital anomalies. (author)

  20. Examining Profiles of Family Functioning in Pediatric Asthma: Longitudinal Associations With Child Adjustment and Asthma Severity.

    Science.gov (United States)

    Al G Hriwati, Nour; Winter, Marcia A; Everhart, Robin S

    2017-05-01

    Identify profiles of functioning in families of children with asthma and examine whether profile membership predicts subsequent child mental and physical well-being. Primary caregivers and children ( N  = 1,030) from the Childhood Asthma Management Program completed questionnaires assessing family functioning and child adaptation at five time points. Asthma severity was also assessed via spirometry. Latent profile analyses identified a four-profile solution as best fitting the data: cohesive, permissive, controlling/disengaged, and controlling/enmeshed families. Distal outcome analyses using Bolck-Croon-Hagenaars techniques suggested that children from families that were more cohesive had fewer internalizing and externalizing symptoms. These associations remained stable across time. Family profiles did not differ with regards to child asthma severity. Results highlight the importance of looking beyond the effects of distinct components of family functioning and instead using pattern-based approaches. Recommendations for incorporating screenings and services for families in pediatric care settings are provided. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Lingling Tang

    2017-10-01

    Full Text Available Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1 are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR, immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.

  2. Single systemic administration of Ag85B of mycobacteria DNA inhibits allergic airway inflammation in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Karamatsu K

    2012-12-01

    Full Text Available Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B

  3. Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

    Science.gov (United States)

    Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G

    2017-08-01

    Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.

  4. Effect of healthcare associated infections and broad spectrum antibiotic use in newborn period on development of asthma, allergic rhinitis and atopic dermatitis in early childhood

    Directory of Open Access Journals (Sweden)

    Hacer Yapicioglu Yildizdas

    2017-03-01

    Full Text Available Purpose: The iam of this study was to investigate the effect of healthcare associated infections (HAIs and broad spectrum antibiotic use in newborn period on asthma, allergic rhinitis and atopic dermatitis. Material and Methods: Seventy three children treated for HAIs in newborn period in Neonatal Intesive Care Unitin a 6 years period, and their 41 siblings who were healthy in newborn period were included in the study. Parents answered a detailed questionnaire, children were examined and complete blood count, serum total Ig E and specific Ig E levels were studied. Results: Ventilator associated pneumonia was observed in 32 (45.2%, blood stream infection in 28 (38.4% and clinic sepsis in 12 (16.4% of 73 children with HAIs. Asthma was significantly higher in HAIs group compared to sibling group (32.9% vs. 4.9, whereas there was no significant difference in allergic rhinitis (4.1% vs.2.4% and atopic dermatitis (6.8% vs. 0% among groups. When non-allergic 85 subjects and allergic 29 children compared, children who had been hospitalised and treated with broad-spectrum antibiotics in newborn period were almost 11.5 times as likely to have an allergic disease. Conclusion: Asthma was significantly higher in HAI group, and allergic disease risk seems to increase in children treated with broad-spectrum antibiotics for HAIs in newborn period. [Cukurova Med J 2017; 42(1.000: 132-139

  5. Association between severe asthma and changes in the stomatognathic system.

    Science.gov (United States)

    Carvalho-Oliveira, Mayra; Salles, Cristina; Terse, Regina; D'Oliveira, Argemiro

    2016-01-01

    To describe orofacial muscle function in patients with severe asthma. This was a descriptive study comparing patients with severe controlled asthma (SCA) and severe uncontrolled asthma (SUA). We selected 160 patients, who completed a sociodemographic questionnaire and the 6-item Asthma Control Questionnaire (ACQ-6), as well as undergoing evaluation of orofacial muscle function. Of the 160 patients evaluated, 126 (78.8%) and 34 (21.2%) presented with SCA and SUA, respectively, as defined by the Global Initiative for Asthma criteria. Regardless of the level of asthma control, the most frequent changes found after evaluation of muscle function were difficulty in chewing, oronasal breathing pattern, below-average or poor dental arch condition, and difficulty in swallowing. When the sample was stratified by FEV1 (% of predicted), was significantly higher proportions of SUA group patients, compared with SCA group patients, showed habitual open-mouth chewing (24.8% vs. 7.7%; p de controle da asma grave, as alterações mais frequentes observadas na avaliação miofuncional foram problemas de mastigação, padrão de respiração oronasal, estado de conservação da arcada dentária médio ou ruim e problemas na deglutição. Quando a amostra foi estratificada pelo VEF1 (% do previsto), os resultados foram significativamente maiores no grupo AGNC que no grupo AGC quanto a mastigação habitual com boca aberta (24,8% vs. 7,7%; p de água com dificuldade (33,7% vs. 17,3%; p de voz (81,2% vs. 51,9%; p resultados do grupo AGNC foram significativamente maiores que no grupo AGC quanto à deglutição de pão com dificuldade (66,6% vs. 26,6%; p de alterações do sistema estomatognático parece ser alta em adultos com asma grave independentemente do nível de controle da doença. No grupo AGNC, algumas dessas alterações foram significativamente mais frequentes que no grupo AGC.

  6. Sensitization to Casuarina equisetifolia and Pinus spp Pollen in Patients with Allergic Rhinitis and Asthma in Mexico City

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    Andrea Aída Velasco-Medina

    2014-01-01

    Full Text Available Background: Pollinosis studies at Mexico City have found a considerable amount of Casuarina equisetifolia and Pinus spp pollen, its sensitization frequency is unknown. In Mexico, some allergens are not considered related to asthma or allergic rhinitis, even though reports in other coun- tries have been demonstrated their relevance as aeroallergens. Objective: To estimate the frequency of sensitization to Casuarina eq- uisetifolia and Pinus spp pollen. Patients and method: A transversal, descriptive trial was done at Hos- pital General de Mexico. Previous informed consent 142 patients with allergic rhinitis and asthma, 3 to 55 years old, were included to the study. A complete clinical evaluation, laboratory tests and skin prick tests were performed. Results: We included 142 patients, 44 children (64% males and 98 adults (73% females. We found that 8 (18.18% children and 35 (35.7% adults had a positive skin prick test to Casuarina equisetifolia. None of the patients included in the study had a positive skin prick test to Pinus spp. Conclusions: Sensitization to Casuarina equisetifolia is as important as other pollens found in Mexico City. These results suggest that it should be included when skin prick tests are performed. Pinus spp pollen is considered an aeroallergen in European countries but we did not cor- roborate sensitization in our population.

  7. Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

    Science.gov (United States)

    Cai, Yeping; Zhou, Jiansheng; Webb, Dianne C

    2009-01-01

    Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

  8. Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma

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    Zaagsma Johan

    2006-01-01

    Full Text Available Abstract Background Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO production – due to competition with neuronal NO-synthase (nNOS for the common substrate, L-arginine. Furthermore, in a guinea pig model of allergic asthma, airway arginase activity is markedly increased after the early asthmatic reaction (EAR, leading to deficiency of agonist-induced, epithelium-derived NO and subsequent airway hyperreactivity. In this study, we investigated whether increased arginase activity after the EAR affects iNANC nerve-derived NO production and airway smooth muscle relaxation. Methods Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz-induced relaxation was measured in tracheal open-ring preparations precontracted to 30% with histamine in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nω-nitro-L-arginine (L-NNA, 100 μM, while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA, 10 μM. Furthermore, the role of substrate availability to nNOS was measured in the presence of exogenous L-arginine (5.0 mM. Results At 6 h after ovalbumin-challenge (after the EAR, EFS-induced relaxation (ranging from 3.2 ± 1.1% at 0.5 Hz to 58.5 ± 2.2% at 16 Hz was significantly decreased compared to unchallenged controls (7.1 ± 0.8% to 75.8 ± 0.7%; P P P Conclusion The results clearly demonstrate that increased arginase activity after the allergen-induced EAR contributes to a deficiency of iNANC nerve-derived NO and decreased airway smooth muscle relaxation, presumably via increased substrate competition with nNOS.

  9. Predictive factors for moderate or severe exacerbations in asthma patients receiving outpatient care

    OpenAIRE

    Guti?rrez, Francisco Javier ?lvarez; Galv?n, Marta Ferrer; Gallardo, Juan Francisco Medina; Mancera, Marta Barrera; Romero, Beatriz Romero; Falc?n, Auxiliadora Romero

    2017-01-01

    Background Asthma exacerbations are important events that affect disease control, but predictive factors for severe or moderate exacerbations are not known. The objective was to study the predictive factors for moderate (ME) and severe (SE) exacerbations in asthma patients receiving outpatient care. Methods Patients aged?>?12?years with asthma were included in the study and followed-up at 4-monthly intervals over a 12-month period. Clinical (severity, level of control, asthma control test [AC...

  10. An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case-case-control study.

    Science.gov (United States)

    Amarin, Justin Z; Naffa, Randa G; Suradi, Haya H; Alsaket, Yousof M; Obeidat, Nathir M; Mahafza, Tareq M; Zihlif, Malek A

    2017-11-15

    Asthma and allergic rhinitis are respiratory diseases with a significant global burden. Forkhead box O3 (FOXO3) is a gene involved in the etiology of a number of respiratory diseases. The objective of this study is to assess the association of rs13217795, an intronic FOXO3 single-nucleotide polymorphism, with asthma and allergic rhinitis. In this case-case-control genetic association study, genotyping was conducted using the PCR-RFLP method. Genotype-based associations were investigated under the general, recessive, and dominant models of disease penetrance using binomial logistic regression; and, allele-based associations were tested using Pearson's chi-squared test. The final study population consisted of 94 controls, 124 asthmatics, and 110 allergic rhinitis patients. The general and recessive models of disease penetrance were statistically significant for both case-control comparisons. Under the general model, the odds of the asthma phenotype were 1.46 (0.64 to 3.34) and 3.42 (1.37 to 8.57) times higher in heterozygotes and derived allele homozygotes, respectively, compared to ancestral allele homozygotes. The corresponding odds ratios for the allergic rhinitis phenotype were 1.05 (0.46 to 2.40) and 2.35 (0.96 to 5.73), respectively. The dominant model of disease penetrance was not statistically significant. The minor allele in all study groups was the ancestral allele, with a frequency of 0.49 in controls. There was no deviation from Hardy-Weinberg equilibrium in controls. Both case-control allele-based associations were statistically significant. Herein we present the first report of the association between rs13217795 and allergic rhinitis, and the first independent verification of the association between rs13217795 and asthma. Marker selection in future genetic association studies of asthma and allergic rhinitis should include functional polymorphisms in linkage disequilibrium with rs13217795.

  11. The "physician on call patient engagement trial" (POPET): measuring the impact of a mobile patient engagement application on health outcomes and quality of life in allergic rhinitis and asthma patients.

    Science.gov (United States)

    Cingi, Cemal; Yorgancioglu, Arzu; Cingi, Can Cemal; Oguzulgen, Kıvılcım; Muluk, Nuray Bayar; Ulusoy, Seçkin; Orhon, Nezih; Yumru, Cengiz; Gokdag, Dursun; Karakaya, Gul; Çelebi, Şaban; Çobanoglu, H Bengü; Unlu, Halis; Aksoy, Mehmet Akif

    2015-06-01

    In this prospective, multicenter, randomized, controlled, double-blind study, we investigated the impact of a mobile patient engagement application on health outcomes and quality of life in allergic rhinitis (AR) and asthma patients. In total, 327 patients with diagnoses of persistent AR or mild-to-severe persistent asthma were randomized into 2 intervention groups and 2 control groups upon their admission at outpatient clinics. The intervention groups (POPET-AR and POPET-Asthma) received a mobile phone application ("physician on call patient engagement trial" [POPET]), enabling them to communicate with their physician, and record their health status and medication compliance. The AR groups completed the Rhinitis Quality of Life Questionnaire (RQLQ) at initiation and at the first month of the study. The asthma groups completed the Asthma Control Test (ACT) at initiation and at the third month of the study. The POPET-AR group showed better clinical improvement than the control group in terms of the overall RQLQ score as well in measures of general problems, activity, symptoms other than nose/eye, and emotion domains (p 19) compared with the control group (27%); this was statistically significant (p mobile engagement platform, such as POPET, can have a significant impact on health outcomes and quality of life in both AR and asthma, potentially decreasing the number of hospital admissions, repeat doctor visits, and losses in productivity. Improvements were seen in domains related to activity, productivity, perception of disease, and emotion. © 2015 ARS-AAOA, LLC.

  12. Prevalence of asthma and allergic diseases in adolescents: nine-year follow-up study (2003-2012

    Directory of Open Access Journals (Sweden)

    Dirceu Solé

    2015-02-01

    Full Text Available OBJECTIVE: To determine the prevalence of symptoms of asthma, rhinitis, and atopic eczema in adolescents (AD; 13-14 years living in seven Brazilian cities, by applying the standardized written questionnaire (WQ of the International Study of Asthma and Allergies in Childhood (ISAAC, and to evaluate the time trend nine years after the last assessment of ISAAC phase 3 (ISP3. METHODS: The ISAAC-WQ was answered by 20,099 AD from the Northern, Northeastern, Southeastern, and Southern Brazilian regions. Values obtained were compared to those observed in ISP3 using nonparametric (chi-squared or Fisher tests, and the ratio of annual increment/decrement was established for each of the centers, according to the symptom assessed. RESULTS: Considering the national data and comparing to values of ISP3, there was a decrease in the mean prevalence of active asthma (18.5% vs. 17.5% and an increase in the frequency of severe asthma (4.5% vs. 4.7% and physician-diagnosed asthma (14.3% vs. 17.6%. An increase in prevalence of rhinitis, rhinoconjunctivitis, and atopic eczema was also observed. CONCLUSIONS: The prevalence of asthma, rhinitis, and atopic eczema in Brazil was variable; higher prevalence values, especially of asthma and eczema, were observed in regions located closer to the Equator.

  13. Efficacy of omalizumab (Xolair®) in patients with moderate to severe predominately chronic oral steroid dependent asthma in Taiwan: a retrospective, population-based database cohort study.

    Science.gov (United States)

    Chen, Hao-Cheng; Huang, Chien-Da; Chang, Erin; Kuo, Han-Pin

    2016-01-08

    Omalizumab (Xolair®), a recombinant monoclonal anti-IgE antibody, has demonstrated efficacy in clinical trials conducted in patients with moderate to severe persistent allergic asthma. We aimed to investigate the efficacy, discontinuation and medical resource utilization of omalizumab in the real-life setting in Taiwan. This study was a retrospective, population-based database cohort study using the Taiwan NHIRD from 2007 to 2011 assessing the efficacy of omalizumab therapy over 4 months on changes in asthma medication, asthma control, frequency of exacerbations and hospitalization rates at baseline and after omalizumab discontinuation. There was a reduction in asthma medication post omalizumab therapy and severe exacerbations and hospitalizations from baseline (31.2%, n = 282) to the end of follow-up (11.8%, n = 144, p omalizumab, the cost of ER medical expenses decreased from New Taiwan dollars (NTD) 3934 at 2 months to NTD 2860 at 12 months. Patients who received omalizumab therapy for over 4 months were more likely to reduce the use of other asthma medications and less likely to experience an asthma exacerbation, ER visits, and hospitalization, even after the discontinuation of omalizumab. These data suggest that omalizumab has efficacy in improving health outcomes in patients with moderate to severe predominately chronic oral steroid dependent asthma in the real-life setting in Taiwan.

  14. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma

    NARCIS (Netherlands)

    Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

    2015-01-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 +/- A 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups

  15. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma

    NARCIS (Netherlands)

    Verkleij, Marieke; van de Griendt, E-J.; Colland, V.; Van Loey, N.E.E.; Beelen, A.; Geenen, R.

    2015-01-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in

  16. TEAR AND SERUM EOSINOPHIL CATIONIC PROTEIN AS A MARKER OF DISEASE SEVERITY IN ALLERGIC OCULAR DISEASES

    International Nuclear Information System (INIS)

    SOLIMAN, S.ET.; KHALIFA, R.A.

    2007-01-01

    The Eosinophil is a major cellular component in the late allergic response. In its activated state, the Eosinophil liberates performed basic proteins; the most sensitively quantifiable of them is the Eosinophil cationic protein (ECP).In the present study ECP was measured in tear and serum in different forms of ocular allergy to assess its value as a marker of disease severity and usefulness to evaluate topical therapy.Tears and serum were collected from 65 patients with allergic Keratoconjunctivitis, 20 healthy volunteers (6 of them children) with no history or evidence of allergic diseases, as well as, 5 patients with non allergic and untreated blepharo-conjunctivitis. Patients were classified according to their clinical signs and symptoms into four groups:Seasonal allergic conjunctivitis (SAC), 15 patients, Vernal Keratoconjunctivitis (VKC), 15 Palpebral and 6 Limbal, Atopic Keratoconjunctivitis (AKC), 17 patients and, Giant papillary conjunctivitis (GPC), 8 contact lens-induced and 4 suture-induced.Tears were collected by capillary tubes for cytological examination and measurement of ECP using radioimmunoassay methods. Serum was collected for measurement of ECP and atopy screening.Tear-ECP evaluation showed statistically significant elevation in all allergic subjects (p<0.001). Patients with VKC and AKC had significantly higher tear ECP values than patients with GPC and SAC. There was significant correlation between tear ECP values and disease severity.On the contrary, serum ECP values were only elevated significantly in atopic patients, and did not correlate to tear ECP values. Tear cytology was not sensitive to evaluate disease severity. These data demonstrated that tear ECP in contrast to serum ECP is a useful marker for disease severity in allergic ocular diseases and as such could become a valuable objective variable in treatment studies and as an adjunctive diagnostic tool in chronic conditions

  17. The effect of encasings on quality of life in adult house dust mite allergic patients with rhinitis, asthma and/or atopic dermatitis.

    Science.gov (United States)

    Terreehorst, I; Duivenvoorden, H J; Tempels-Pavlica, Z; Oosting, A J; de Monchy, J G R; Bruijnzeel-Koomen, C A F M; van Wijk, R Gerth

    2005-07-01

    Environmental control has been put forward as an integral part of the management of house dust mite (HDM) allergy in sensitized patients. To validate this statement allergic disorders involved in HDM allergy--allergic asthma, rhinitis and atopic eczema/dermatitis syndrome (AEDS)--should be taken together and studied in terms of the efficacy of environmental control. Because a generic quality of life questionnaire exceeds the border of disease, this may be used as major outcome parameter. To study the effects of bedding encasings in HDM allergic patients with asthma, rhinitis and AEDS. A total of 224 adult HDM allergic patients with rhinitis and/or asthma and/or dermatitis were randomly allocated impermeable or nonimpermeable encasings for mattress, pillow and duvet. Short form 36 (SF-36) was filled in at baseline and after 12 months. Lower physical (P = 0.01) and emotional (P effect was seen of encasings on either sumscore. Bedding encasings do not improve quality of life in a mixed population of subjects with combinations with rhinitis, asthma and atopic dermatitis and sensitized to HDMs.

  18. Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review.

    Science.gov (United States)

    Corren, Jonathan; Kavati, Abhishek; Ortiz, Benjamin; Colby, Jennifer A; Ruiz, Kimberly; Maiese, Brett A; Cadarette, Sarah M; Panettieri, Reynold A

    2017-07-01

    There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma. The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinical trials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. Studies that evaluated omalizumab use in patients omalizumab RCTs. Overall, the mean rate of annual exacerbations was significantly lower after 6 months to 2 years of treatment with omalizumab in both RCTs and RWS. In two RCTs and three RWS, inhaled corticosteroid use was significantly reduced in patients who used omalizumab. Similar reductions in the use of rescue medication were also observed in the RCTs and RWS on omalizumab. Real-world evidence demonstrated improvement in forced expiratory volume in the first second of expiration (% predicted) in patients treated with omalizumab as well as significant improvement in the level of asthma control observed over 1 year. There also was evidence that omalizumab treatment reduced health care resource utilization, including fewer hospitalizations, emergency department visits, and unscheduled medical visits. Safety outcomes in all five RWS showed no new safety signals and demonstrated that omalizumab was well tolerated. Overall, RCT evidence strongly supported omalizumab efficacy and safety as add-on treatment in children 6 to 11 years old with moderate-to-severe persistent allergic asthma. RWS data confirmed these findings in an extended patient population of children and adolescents that is more generalizable to the actual day-to-day management of these patients.

  19. Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

    Science.gov (United States)

    Nakamoto, Keitaro; Watanabe, Masato; Sada, Mitsuru; Inui, Toshiya; Nakamura, Masuo; Honda, Kojiro; Wada, Hiroo; Mikami, Yu; Matsuzaki, Hirotaka; Horie, Masafumi; Noguchi, Satoshi; Yamauchi, Yasuhiro; Koyama, Hikari; Kogane, Toshiyuki; Kohyama, Tadashi; Takizawa, Hajime

    2016-01-01

    Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. PMID:27776186

  20. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma

    NARCIS (Netherlands)

    Gevaert, Philippe; Calus, Lien; van Zele, Thibaut; Blomme, Katrien; de Ruyck, Natalie; Bauters, Wouter; Hellings, Peter; Brusselle, Guy; de Bacquer, Dirk; van Cauwenberge, Paul; Bachert, Claus

    2013-01-01

    Background: Adult patients with nasal polyps often have comorbid asthma, adding to the serious effect on the quality of life of these patients. Nasal polyps and asthma might represent a therapeutic challenge; inflammation in both diseases shares many features, such as airway eosinophilia, local IgE

  1. Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta(2) agonist and steroid response

    NARCIS (Netherlands)

    Vonk, Judith M.; Postma, Dirkje S.; Maarsingh, Harm; Bruinenberg, Marcel; Koppelman, Gerard H.; Meurs, Herman

    Rationale Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta(2) agonists. Objectives We investigated the association between arginase 1

  2. Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

    Science.gov (United States)

    Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

    2017-06-01

    Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

  3. Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

    Science.gov (United States)

    Versluis, A; Knulst, A C; Kruizinga, A G; Michelsen, A; Houben, G F; Baumert, J L; van Os-Medendorp, H

    2015-02-01

    Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary. © 2014 John Wiley & Sons Ltd.

  4. A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.

    Science.gov (United States)

    Jin, Peng; Andiappan, Anand Kumar; Quek, Jia Min; Lee, Bernett; Au, Bijin; Sio, Yang Yie; Irwanto, Astrid; Schurmann, Claudia; Grabe, Hans Jörgen; Suri, Bani Kaur; Matta, Sri Anusha; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Sun, Liangdan; Zhang, Xuejun; Liu, Hong; Zhang, Furen; Larbi, Anis; Xu, Xin; Poidinger, Michael; Liu, Jianjun; Chew, Fook Tim; Rotzschke, Olaf; Shi, Li; Wang, De Yun

    2015-06-01

    Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR. We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR. Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays. The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood. A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Temporal relationship of allergic rhinitis with asthma and other co-morbidities in a Mediterranean country: a retrospective study in a tertiary reference allergy clinic.

    Science.gov (United States)

    Makris, M; Koulouris, S; Koti, I; Aggelides, X; Sideri, K; Chliva, C; Vassilatou, E; Kalogeromitros, D

    2010-01-01

    Allergic rhinitis is a global health problem which causes major illness and represents a risk factor for asthma. The primary aim of the study was to record the clinical pattern of allergic rhinitis and its temporal relation with asthma in a Greek population. Three-hundred and sixteen subjects with documented diagnosis of allergic rhinitis in a two-year period were included in this study. All participants completed a standardised questionnaire with full retrospective epidemiological data for rhinitis; in addition, serum IgE measurement and skin prick tests with 22 common inhalant allergens were carried out, while spirometry was performed in subjects with self-reported or doctor-diagnosed asthma. All subjects with at least one positive skin test were included in study analysis. One-hundred and sixty five out of 316 patients (49.1%) stated self reported-asthma while in 63/316 (19.9%) asthma was documented with spirometry. One hundred out of 165 (60.6%) had rhinitis as first clinical manifestation while in 24/165 (14.5%) asthma symptoms appeared first; the remaining 31/165 (24.9%) reported simultaneous onset of upper and lower airways' symptoms. About 68.5% were sensitised to seasonal allergens exclusively, while 50% were sensitised to ≥ 1 of Parietaria, grasses sp., Olea eur. The duration of rhinitis in the subpopulation of patients with self-reported asthma (n=165) was significantly higher compared with non-asthmatics (mean=3.22 years, p<0.001). Survival analysis for the estimation of asthma onset showed that the mean time interval with rhinitis only is 16.6 years (median 12 years, incidence 0.0596). The unique environmental conditions and the aerobiology of each area clearly affect the clinical features of respiratory allergy. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  6. Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity

    International Nuclear Information System (INIS)

    Dullin, Christian; Larsson, Emanuel; Tromba, Giuliana; Markus, Andrea M.; Alves, Frauke

    2015-01-01

    Synchrotron inline phase-contrast computed tomography in combination with single-distance phase retrieval enables quantification of morphological alterations in lungs of mice with mild and severe experimental allergic airways disease in comparison with healthy controls. Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, ‘Elettra’, Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma

  7. Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity

    Energy Technology Data Exchange (ETDEWEB)

    Dullin, Christian, E-mail: christian.dullin@med.uni-goettingen.de [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Larsson, Emanuel [Elettra-Sincrotrone Trieste, Strada Statale 14, km 163,5 in AREA Science Park, Basovizza (Trieste) 34149 (Italy); University of Trieste, Trieste (Italy); Linkoeping University, SE-581 83 Linkoeping (Sweden); Tromba, Giuliana [Elettra-Sincrotrone Trieste, Strada Statale 14, km 163,5 in AREA Science Park, Basovizza (Trieste) 34149 (Italy); Markus, Andrea M. [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Alves, Frauke [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Max Planck Institut for Experimental Medicine, Hermann-Rein-Strasse 3, Goettingen, Lower Saxony 37075 (Germany)

    2015-06-17

    Synchrotron inline phase-contrast computed tomography in combination with single-distance phase retrieval enables quantification of morphological alterations in lungs of mice with mild and severe experimental allergic airways disease in comparison with healthy controls. Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, ‘Elettra’, Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.

  8. Right ventricular function during acute exacerbation of severe equine asthma.

    Science.gov (United States)

    Decloedt, A; Borowicz, H; Slowikowska, M; Chiers, K; van Loon, G; Niedzwiedz, A

    2017-09-01

    Pulmonary hypertension has been described in horses with severe equine asthma, but its effect on the right ventricle has not been fully elucidated. To evaluate right ventricular structure and function after a 1-week period of pulmonary hypertension secondary to acute exacerbation of severe equine asthma. Prospective study. A clinical episode of severe equine asthma was induced experimentally in six susceptible horses. Examinations in remission and on day 7 of the clinical episode included a physical examination with clinical scoring, echocardiography, arterial blood gas measurements, venous blood sampling for cardiac biomarkers, intracardiac pressure measurements, right ventricular and right atrial myocardial biopsies, airway endoscopy and bronchoalveolar lavage. After 1 month of recovery, physical examination, echocardiography and cardiac biomarker analysis were repeated. Echocardiographic and pressure measurements were compared with those in 10 healthy control horses. All horses developed clinical signs of acute pulmonary obstruction. Right heart pressures increased significantly. Altered right ventricular function could be detected by tissue Doppler and speckle tracking echocardiography. Cardiac troponin concentrations did not increase significantly, but were highly elevated in one horse which exercised in the paddock prior to sampling. Focal neutrophil infiltration was present in two myocardial samples. Even in remission, asthmatic horses showed a thicker right ventricular wall, an increased left ventricular end-systolic eccentricity index at chordal level and decreased right ventricular longitudinal strain compared with controls. The induced clinical episode was rather mild and the number of horses was limited because of the invasive nature of the study. Pulmonary obstruction in asthmatic horses induces pulmonary hypertension with right ventricular structural and functional changes. © 2017 EVJ Ltd.

  9. Serum IL-33 Is Elevated in Children with Asthma and Is Associated with Disease Severity.

    Science.gov (United States)

    Bahrami Mahneh, Sedigheh; Movahedi, Masoud; Aryan, Zahra; Bahar, Mohammad Ali; Rezaei, Arezou; Sadr, Maryam; Rezaei, Nima

    2015-01-01

    The role of IL-33, a member of the IL-1 family, in airway hyperresponsiveness and asthma has still to be fully understood. This study is aimed at investigating serum IL-33 in children with asthma and its association with asthma severity. This age- and sex-matched case-control study comprised 61 children with asthma and 63 healthy controls. The mean age of the participants was 9.21 years (range: 6-14). Serum IL-33 was measured using ELISA and was compared between children with asthma and controls. In addition, the association of serum IL-33 with asthma severity was investigated. The level of serum IL-33 was significantly higher in children with asthma than in controls (15.17 ± 32.3 vs. 0.61 ± 2.16 pg/ml; p = 0.028). It was significantly increased proportionately to asthma severity, namely 9.92 ± 30.26 pg/ml in children with mild asthma, 13.68 ± 29.27 pg/ml in children with moderate asthma and 31.92 ± 41.45 pg/ml in children with severe asthma (p = 0.026). Serum IL-33 is increased in children with asthma and is associated with disease severity. © 2016 S. Karger AG, Basel.

  10. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies

    Directory of Open Access Journals (Sweden)

    Wagner James G

    2012-07-01

    Full Text Available Abstract Background Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5 are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. Methods We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs or filtered air for 8 h (7:00 AM - 3:00 PM. Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Results Similar CAPs mass concentrations were generated in Detroit (542 μg/m3 and Grand Rapids (519 μg/m3. Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase, eosinophils (90%, and total protein (300% compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Conclusions Despite inhalation exposure to the same mass concentration of urban PM2

  11. Clinical experience with Omalizumab in a Portuguese severe asthma unit

    Directory of Open Access Journals (Sweden)

    S. Alfarroba

    2014-03-01

    Full Text Available Background: It is widely recognized that asthma control is not always possible in patients with very severe asthma despite available treatment. The aim of this study was to evaluate the efficacy of Omalizumab on asthma control as an add‐on therapy in patients from the “Severe Asthma Outpatient Service” of Pulido Valente Hospital in Lisbon, Portugal. Methods: A retrospective study was conducted to assess asthma control by the ACT score and by GINA classification, frequency and severity of exacerbations, medication use and pulmonary function in patients treated with Omalizumab. Clinical information was collected from medical records from the start of treatment and at 6‐, 12‐ and 24‐month follow‐ups. Results: 26 patients started the treatment with Omalizumab, and all (100% were classified by GINA with uncontrolled asthma prior to treatment. Mean ACT score was 11.5. All the patients had treatment with fixed‐dose ICS and LABA and 34.6% also had an anti‐cholinergic inhaler. 42.3% of patients were also treated with oral glucocorticosteroids for control. Patients reported an average of 1.8 moderate and 3.1 severe exacerbations/year. Statistical differences were found at 6‐month follow‐up in most end‐points: GINA score improved: 60.9% of patients with partially controlled asthma and only 39.1% with uncontrolled asthma (Wilcoxon 0.00; ACT score improved to 19.52 (Wilcoxon 0.00; mean FEV1 improved to 76.7% (Wilcoxon 0.025; the proportion of patients requiring oral glucocorticosteroid therapy reduced to 17.4% (Wilcoxon 0.014; and the number of moderate and severe exacerbations also decreased to 1.04 and 1.83 respectively (Wilcoxon 0.007; Wilcoxon 0.002 respectively. Conclusions: The current analysis shows evidence that omalizumab is successful in improving asthma control as an add‐on therapy GINA step 5 treatment. Resumo: Introdução: Está bem documentado que o controlo de asma nem

  12. Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

    Science.gov (United States)

    Boita, Monica; Heffler, Enrico; Omedè, Paola; Bellocchia, Michela; Bussolino, Claudia; Solidoro, Paolo; Giorgis, Veronica; Guerrera, Francesco; Riva, Giuseppe; Brussino, Luisa; Bucca, Caterina; Rolla, Giovanni

    2018-01-01

    Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity. © 2018 S. Karger AG, Basel.

  13. Point-of-care blood eosinophil count in a severe asthma clinic setting.

    Science.gov (United States)

    Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

    2017-07-01

    One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Short-term Effects of Ambient Air Pollution on Emergency Department Visits for Asthma: An Assessment of Effect Modification by Prior Allergic Disease History

    Directory of Open Access Journals (Sweden)

    Juhwan Noh

    2016-09-01

    Full Text Available Objectives The goal of this study was to investigate the short-term effect of ambient air pollution on emergency department (ED visits in Seoul for asthma according to patients’ prior history of allergic diseases. Methods Data on ED visits from 2005 to 2009 were obtained from the Health Insurance Review and Assessment Service. To evaluate the risk of ED visits for asthma related to ambient air pollutants (carbon monoxide [CO], nitrogen dioxide [NO2], ozone [O3], sulfur dioxide [SO2], and particulate matter with an aerodynamic diameter <10 μm [PM10], a generalized additive model with a Poisson distribution was used; a single-lag model and a cumulative-effect model (average concentration over the previous 1-7 days were also explored. The percent increase and 95% confidence interval (CI were calculated for each interquartile range (IQR increment in the concentration of each air pollutant. Subgroup analyses were done by age, gender, the presence of allergic disease, and season. Results A total of 33 751 asthma attack cases were observed during the study period. The strongest association was a 9.6% increase (95% CI, 6.9% to 12.3% in the risk of ED visits for asthma per IQR increase in O3 concentration. IQR changes in NO2 and PM10 concentrations were also significantly associated with ED visits in the cumulative lag 7 model. Among patients with a prior history of allergic rhinitis or atopic dermatitis, the risk of ED visits for asthma per IQR increase in PM10 concentration was higher (3.9%; 95% CI, 1.2% to 6.7% than in patients with no such history. Conclusions Ambient air pollutants were positively associated with ED visits for asthma, especially among subjects with a prior history of allergic rhinitis or atopic dermatitis.

  15. Allergic Rhinitis Quiz

    Science.gov (United States)

    ... rhinitis, allergic asthma, conjunctivitis (eye allergy) or stinging insect allergy. Allergy shots often lead to lasting relief ... AAAAI Foundation Donate American Academy of Allergy Asthma & Immunology 555 East Wells Street Suite 1100, Milwaukee , WI ...

  16. Influence of β(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol.

    Science.gov (United States)

    Giubergia, Verónica; Gravina, Luis; Castaños, Claudio; Chertkoff, Lilien

    2013-03-01

    New evidence suggests that different β(2)-adrenergic receptor (β2AR) polymorphisms may influence asthma control in patients receiving long-acting β(2)agonists (LABAs) as regular therapy. To determine the influence of β2AR polymorphisms on asthma exacerbations in children with severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs regularly. Ninety-seven children with severe asthma were genotyped for polymorphisms of β2AR at codons 16 and 27. The number of severe exacerbations, the time of first asthma exacerbation, and the number of hospitalizations during 12 months were assessed. Changes on pulmonary function from the beginning to the end of the study were also evaluated. The number of overall asthma exacerbations and the proportion of children with these events were similar among β2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position 27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was similar among individuals carrying different β2AR polymorphisms. No β2AR genotype association was found in relation to the number of hospitalizations. Longitudinal analysis of forced expiratory volume in 1 second from baseline to the end of the study also showed no differences among β2AR genotypes at position 16 or 27. No association was observed among the 3 most common haplotypes (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of participants with asthmatic crisis or with the overall number of exacerbations. β2AR polymorphisms were not associated with an increased risk of having asthma exacerbations or lung function decline in a population of Argentinian children with severe asthma receiving ICS and LABAs regularly. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Factors associated with persistent airflow limitation in severe asthma

    NARCIS (Netherlands)

    ten Brinke, A.; Zwinderman, A. H.; Sterk, P. J.; Rabe, K. F.; Bel, E. H.

    2001-01-01

    Persistent airflow limitation can develop in nonsmoking patients with asthma. However, the prevalence and risk factors for airways obstruction with incomplete reversibility in asthma are unknown. We assessed the prevalence of persistent airflow limitation (defined as postbronchodilator FEV(1) or

  18. The development of allergic inflammation in a murine house dust mite asthma model is suppressed by synbiotic mixtures of non-digestible oligosaccharides and Bifidobacterium breve M-16V.

    Science.gov (United States)

    Verheijden, K A T; Willemsen, L E M; Braber, S; Leusink-Muis, T; Jeurink, P V; Garssen, J; Kraneveld, A D; Folkerts, G

    2016-04-01

    The incidence and severity of allergic asthma is rising, and novel strategies to prevent or treat this disease are needed. This study investigated the effects of different mixtures of non-digestible oligosaccharides combined with Bifidobacterium breve M-16V (BB) on the development of allergic airway inflammation in an animal model for house dust mite (HDM)-induced allergic asthma. BALB/c mice were sensitized intranasally (i.n.) with HDM and subsequently challenged (i.n.) with PBS or HDM while being fed diets containing different oligosaccharide mixtures in combination with BB or an isocaloric identical control diet. Bronchoalveolar lavage fluid (BALF) inflammatory cell influx, chemokine and cytokine concentrations in lung homogenates and supernatants of ex vivo HDM-restimulated lung cells were analyzed. The HDM-induced influx of eosinophils and lymphocytes was reduced by the diet containing the short-chain and long-chain fructo-oligosaccharides and BB (FFBB). In addition to the HDM-induced cell influx, concentrations of IL-33, CCL17, CCL22, IL-6, IL-13 and IL-5 were increased in supernatants of lung homogenates or BALF and IL-4, IFN-γ and IL-10 were increased in restimulated lung cell suspensions of HDM-allergic mice. The diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination of galacto-oligosaccharides and long-chain fructo-oligosaccharides with BB was less potent in this model. These findings show that synbiotic dietary supplementation can affect respiratory allergic inflammation induced by HDM. The combination of FFBB was most effective in the prevention of HDM-induced airway inflammation in mice.

  19. Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

    Science.gov (United States)

    Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2016-12-01

    Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child.

    Science.gov (United States)

    1998-08-01

    There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (> or = 30 kU/l) or specific IgE (> or = 0.35 kUA/l) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the

  1. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

    Science.gov (United States)

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-12-16

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

  2. Does traffic exhaust contribute to the development of asthma and allergic sensitization in children: findings from recent cohort studies

    Directory of Open Access Journals (Sweden)

    Forsberg Bertil

    2009-04-01

    Full Text Available Abstract The aim of this review was to assess the evidence from recent prospective studies that long-term traffic pollution could contribute to the development of asthma-like symptoms and allergic sensitization in children. We have reviewed cohort studies published since 2002 and found in PubMed in Oct 2008. In all, 13 papers based on data from 9 cohorts have evaluated the relationship between traffic exposure and respiratory health. All surveys reported associations with at least some of the studied respiratory symptoms. The outcome varied, however, according to the age of the child. Nevertheless, the consistency in the results indicates that traffic exhaust contributes to the development of respiratory symptoms in healthy children. Potential effects of traffic exhaust on the development of allergic sensitization were only assessed in the four European birth cohorts. Long-term exposure to outdoor air pollutants had no association with sensitization in ten-year-old schoolchildren in Norway. In contrast, German, Dutch and Swedish preschool children had an increased risk of sensitization related to traffic exhaust despite fairly similar levels of outdoor air pollution as in Norway. Traffic-related effects on sensitization could be restricted to individuals with a specific genetic polymorphism. Assessment of gene-environment interactions on sensitization has so far only been carried out in a subgroup of the Swedish birth cohort. Further genetic association studies are required and may identify individuals vulnerable to adverse effects from traffic-related pollutants. Future studies should also evaluate effects of traffic exhaust on the development and long term outcome of different phenotypes of asthma and wheezing symptoms.

  3. The natural course of eczema from birth to age 7 years and the association with asthma and allergic rhinitis: a population-based birth cohort study.

    Science.gov (United States)

    Shen, Chian-Yin; Lin, Ming-Chih; Lin, Heng-Kuei; Lin, Ching-Heng; Fu, Lin-Shien; Fu, Yun-Chin

    2013-01-01

    Although "atopic march" is a popular concept, the relationship between eczema and subsequent asthma is far from clear. However, some cohort studies have shown the possibility of two different allergic phenotypes in those who present with early eczema in terms of their persistency. We checked the cohort data from 308,849 children born in 2000 in Taiwan, to evaluate the different courses of eczema and their relationships to subsequent asthma and allergic rhinitis (AR) at age 7 years. We examined the age prevalence of eczema, asthma, and AR up to 7 years of age. We grouped all cases according to their course of eczema, as well as wheezing, and determined the rates of asthma and AR at age 7 years. We checked the adjusted risk factors by multiple logistic regression model. We also examined the distributions of wheezing types in different eczema groups. We found the "atopic march" pattern of allergic diseases based on their age prevalence. Early eczema was associated with asthma and AR at the age of 7 years. Those with eczema symptoms persisting after 36 months of age had a higher risk than those with transient eczema. Early wheeze also contributed to asthma and AR later in childhood. In addition, late-onset eczema had a completely different wheeze distribution compared with other groups and also had a higher risk for asthma and AR than transient eczema. In conclusion, different eczema phenotypes could be found in this population-based cohort. This article emphasizes the special attention to the persistency and late-onset eczema in clinical practice.

  4. Which functional parameters can help differentiate severe asthma from COPD?

    Directory of Open Access Journals (Sweden)

    Ricardo Marques Dias

    2010-03-01

    Full Text Available The aim of this study was to identify the respiratory function parameters that help in the accurate diagnosis of asthma and COPD. We studied 20 asthma and 30 COPD patients who underwent lung function tests including spirometry and plethysmography both with bronchodilator test and diffusion with carbon monoxide (DLCO. The tests were performed according to International Guidelines (ATS/ERS. The asthma patients were younger (mean age = 48 than those in the COPD group (mean age = 59 and this group also had more female patients (65% than the COPD group (40%. The results showed a more severe obstruction in the asthma group: FEV1/FVC = 59% versus 66% for COPD. There was also a greater bronchodilator response as shown by changes in absolute and percentage values for FEV1 in the asthma group. Average DLCO values were normal in the asthma group (103%P and lower in the COPD (69%. In plethysmography the asthma group had a higher residual volume (%P and a higher airway resistance. We concluded that many functional parameters were useful in distinguishing the asthma and COPD groups. In individual analysis, DLCO was the parameter which best aided in an accurate diagnosis in both groups, with a higher specificity for COPD. The bronchodilator response measured by changes in FEV1 showed a higher sensitivity for asthma. Thus, these two tests are highlighted in the differential diagnosis of obstructive diseases. Resumo: Com o objectivo de identificar parâmetros funcionais respiratórios que contribuam para o diagnóstico diferencial entre asma e DPOC, estudámos 20 asmáticos e 30 bronquíticos, com ou sem enfisema, com os exames usuais de função pulmonar: espirografia, pletismografia e DLCO, pré e pós-broncodilatação para os dois primeiros exames. Os grupos apresentam diferenças significativas na sua constituição. Os asmáticos são mais jovens, média de 48 anos, contra 59 anos no grupo com DPOC, e o

  5. Asthma and Allergy Foundation of America

    Science.gov (United States)

    ... Triggers Allergens and Allergic Asthma Tobacco Smoke Air Pollution Indoor Air Quality Respiratory Infections Pneumococcal Disease Flu (Influenza) Exercise Weather Asthma Symptoms Asthma Diagnosis ...

  6. Bronchial and nasal responsiveness in atopic asthma and allergic rhinitis patients: Relationship of local responsiveness to cytokine production by peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Keiji Maeda

    1998-01-01

    Full Text Available To investigate the relationship between local responsiveness and allergic symptoms, bronchial and nasal responsiveness were measured in the following four groups of subjects: (i bronchial asthma patients with serum house dust mite (HDM-specific IgE antibody; (ii allergic rhinitis patients with serum HDM-specific IgE antibody; (iii normal control subjects with HDM-specific IgE antibody; and (iv normal control subjects without IgE antibody specific for 10 common aero-allergens. Bronchial hyperresponsiveness was detected in all subjects with asthma (group 1 and in some subjects from groups 2 and 3, but not in subjects from group 4. Nasal hyperresponsiveness was found in all subjects with allergic rhinitis (group 2 and in some subjects from groups 1 and 3, but not in subjects from group 4. These findings indicate that local hyperresponsiveness of the non-diseased organ is influenced by an individual's atopic status. Interleukin (IL-4 and IL-5 production by peripheral blood mononuclear cells (PBMC was measured after stimulation with HDM in groups 1, 2 and 3 and was found to be similar in all three groups. A correlation between bronchial hyperresponsiveness and in vitro cytokine production was noted in asthma patients. These results suggest that the capacity of IL-4 or IL-5 production by PBMC may reflect local hyperresponsiveness in case of asthma.

  7. DOES VITAMIN D DEFICIENCY CONTRIBUTE TO THE SEVERITY OF ASTHMA IN CHILDREN AND ADULTS?

    Science.gov (United States)

    Ahmed, Syed Zaryab; Jaleel, Anila; Hameed, Kamran; Qazi, Salman; Suleman, Ahsan

    2015-01-01

    Role of vitamin D in the health of bones has been well established for over decades; It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named "the sunshine vitamin". As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma.

  8. Does vitamin d deficiency contribute to the severity of asthma in children and adults

    International Nuclear Information System (INIS)

    Ahmed, S.Z.A.; Hameed, K.; Jaleel, A.

    2015-01-01

    Role of vitamin D in the health of bones has been well established for over decades. It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named t he sunshine vitamin . As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma. (author)

  9. Projections of the effects of climate change on allergic asthma: the contribution of aerobiology.

    Science.gov (United States)

    Cecchi, L; D'Amato, G; Ayres, J G; Galan, C; Forastiere, F; Forsberg, B; Gerritsen, J; Nunes, C; Behrendt, H; Akdis, C; Dahl, R; Annesi-Maesano, I

    2010-09-01

    Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.

  10. Projections of the effects of climate change on allergic asthma : the contribution of aerobiology

    NARCIS (Netherlands)

    Cecchi, L.; D'Amato, G.; Ayres, J. G.; Galan, C.; Forastiere, F.; Forsberg, B.; Gerritsen, J.; Nunes, C.; Behrendt, H.; Akdis, C.; Dahl, R.; Annesi-Maesano, I.

    Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies

  11. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision

    NARCIS (Netherlands)

    Brożek, Jan L.; Bousquet, Jean; Agache, Ioana; Agarwal, Arnav; Bachert, Claus; Bosnic-Anticevich, Sinthia; Brignardello-Petersen, Romina; Canonica, G. Walter; Casale, Thomas; Chavannes, Niels H.; Correia de Sousa, Jaime; Cruz, Alvaro A.; Cuello-Garcia, Carlos A.; Demoly, Pascal; Dykewicz, Mark; Etxeandia-Ikobaltzeta, Itziar; Florez, Ivan D.; Fokkens, Wytske; Fonseca, Joao; Hellings, Peter W.; Klimek, Ludger; Kowalski, Sergio; Kuna, Piotr; Laisaar, Kaja-Triin; Larenas-Linnemann, Désirée E.; Lødrup Carlsen, Karin C.; Manning, Peter J.; Meltzer, Eli; Mullol, Joaquim; Muraro, Antonella; O'Hehir, Robyn; Ohta, Ken; Panzner, Petr; Papadopoulos, Nikolaos; Park, Hae-Sim; Passalacqua, Gianni; Pawankar, Ruby; Price, David; Riva, John J.; Roldán, Yetiani; Ryan, Dermot; Sadeghirad, Behnam; Samolinski, Boleslaw; Schmid-Grendelmeier, Peter; Sheikh, Aziz; Togias, Alkis; Valero, Antonio; Valiulis, Arunas; Valovirta, Erkka; Ventresca, Matthew; Wallace, Dana; Waserman, Susan; Wickman, Magnus; Wiercioch, Wojtek; Yepes-Nuñez, Juan José; Zhang, Luo; Zhang, Yuan; Zidarn, Mihaela; Zuberbier, Torsten; Schünemann, Holger J.

    2017-01-01

    Background: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than

  12. Polymorphism 4G/5G of the plasminogen activator inhibitor 1 gene as a risk factor for the development of allergic rhinitis symptoms in patients with asthma.

    Science.gov (United States)

    Lampalo, Marina; Jukic, Irena; Bingulac-Popovic, Jasna; Marunica, Ivona; Petlevski, Roberta; Pavlisa, Gordana; Popovic-Grle, Sanja

    2017-06-01

    Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein which has a role in tissue remodelling after inflammatory processes. The objective is to investigate the frequency of PAI-1 gene polymorphism (4G/5G) in patients with a lung ventilation dysfunction in asthma and allergic rhinitis. Genomic DNA was isolated and genotypes of polymorphism of PAI-1 4G/5G and ABO were determined using the methods of RT-PCR and PCR-SSP. Study group includes 145 adult patients diagnosed with chronic asthma, with all clinically relevant parameters and the laboratory markers of pO 2 , IgE and eosinophils in sputum and nasal swab. In the processing of data, appropriate statistical tests (Kolmogorov-Smirnov test, median, interquartile ranges, χ 2 and Mann-Whitney U tests) were used. Patients with symptoms of allergic rhinitis were significantly younger and had an almost four time higher levels of IgE (P = 0.001), higher pO 2 (P = 0.002) and PEF (P = 0.036), compared to those who do not have these symptoms. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. Carriers of the genotype 4G/5G also have a borderline statistical significance. There were no statistically significant difference in the incidence of allergic rhinitis in the carriers of any ABO genotypes. The frequency of PAI genotype 4G/4G is significantly more common in patients with allergic rhinitis. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma.

  13. The C5a/C5aR1 axis controls the development of experimental allergic asthma independent of LysM-expressing pulmonary immune cells.

    Directory of Open Access Journals (Sweden)

    Anna V Wiese

    Full Text Available C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1. Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs and monocyte-derived DCs (moDCs during the allergic effector phase using a floxed green fluorescent protein (GFP-C5aR1 knock-in mouse. Here, we determined the role of C5aR1 signaling in neutrophils, moDCs and macrophages for the pulmonary recruitment of such cells and the importance of C5aR1-mediated activation of LysM-expressing cells for the development of allergic asthma. We used LysM-C5aR1 KO mice with a specific deletion of C5aR1 in LysMCre-expressing cells and confirmed the specific deletion of C5aR1 in neutrophils, macrophages and moDCs in the airways and/or the lung tissue. We found that alveolar macrophage numbers were significantly increased in LysM-C5aR1 KO mice. Induction of ovalbumin (OVA-driven experimental allergic asthma in GFP-C5aR1fl/fl and LysM-C5aR1 KO mice resulted in strong but similar airway resistance, mucus production and Th2/Th17 cytokine production. In contrast, the number of airway but not of pulmonary neutrophils was lower in LysM-C5aR1 KO as compared with GFP-C5aR1fl/fl mice. The recruitment of macrophages, cDCs, moDCs, T cells and type 2 innate lymphoid cells was not altered in LysM-C5aR1 KO mice. Our findings demonstrate that C5aR1 is critical for steady state control of alveolar macrophage numbers and the transition of neutrophils from the lung into the airways in OVA-driven allergic asthma. However, C5aR1 activation of LysM-expressing cells plays a surprisingly minor role in the recruitment and activation of such cells and the development of the allergic phenotype in OVA-driven experimental

  14. IL-13 and the IL-13 receptor as therapeutic targets for asthma and allergic disease.

    Science.gov (United States)

    Mitchell, Jesse; Dimov, Vesselin; Townley, Robert G

    2010-05-01

    It is widely accepted that T-helper 2 cell (Th2) cytokines play an important role in the maintenance of asthma and allergy. Emerging evidence has highlighted the role of IL-13 in the pathogenesis of these diseases. In particular, IL-13 is involved in the regulation of IgE synthesis, mucus hypersecretion, subepithelial fibrosis and eosinophil infiltration, and has been associated with the regulation of certain chemokine receptors, notably CCR5. Thus, targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. Pharmaceutical and biotechnology companies are researching various strategies, based on this approach, aimed at binding IL-13, increasing the level of the IL-13 decoy receptor, IL-13Ralpha2, or blocking the effect of the chemokine receptor CCR5. This review focuses on the therapeutic potential of anti-IL-13 agents and their role in the treatment of asthma and allergy.

  15. Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study.

    Directory of Open Access Journals (Sweden)

    Guang-Hui Dong

    Full Text Available BACKGROUND: Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship. METHODOLOGY/PRINCIPAL FINDINGS: 30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM(10, sulfur dioxide (SO(2, nitrogen dioxides (NO(2, ozone (O(3 and carbon monoxide (CO. A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs per interquartile changes for PM(10, SO(2, NO(2, O(3, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM(10 (ORs = 1.36 per 31 µg/m(3; 95% CI, 1.08-1.72, SO(2 (ORs = 1.38 per 21 µg/m(3; 95%CI, 1.12-1.69 only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO(2 (ORs = 1.48 per 21 µg/m(3; 95%CI, 1.21-1.80, NO(2 (ORs = 1.26 per 10 µg/m(3; 95%CI, 1.01-1.56, and current asthma with

  16. Gender Differences and Effect of Air Pollution on Asthma in Children with and without Allergic Predisposition: Northeast Chinese Children Health Study

    Science.gov (United States)

    Dong, Guang-Hui; Chen, Tao; Liu, Miao-Miao; Wang, Da; Ma, Ya-Nan; Ren, Wan-Hui; Lee, Yungling Leo; Zhao, Ya-Dong; He, Qin-Cheng

    2011-01-01

    Background Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship. Methodology/Principal Findings 30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxides (NO2), ozone (O3) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM10, SO2, NO2, O3, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM10 (ORs = 1.36 per 31 µg/m3; 95% CI, 1.08–1.72), SO2 (ORs = 1.38 per 21 µg/m3; 95%CI, 1.12–1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO2 (ORs = 1.48 per 21 µg/m3; 95%CI, 1.21–1.80), NO2 (ORs = 1.26 per 10 µg/m3; 95%CI, 1.01–1.56), and current asthma with O3 (ORs = 1

  17. Innate lymphoid cells and asthma.

    Science.gov (United States)

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  18. Pathway discovery using transcriptomic profiles in adult-onset severe asthma

    DEFF Research Database (Denmark)

    Hekking, Pieter-Paul; Loza, Matt J; Pavlidis, Stelios

    2017-01-01

    in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung...... injury were less enriched in adult-onset severe asthma. CONCLUSIONS: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma....

  19. The urgent need for a harmonized severity scoring system for acute allergic reactions

    DEFF Research Database (Denmark)

    Muraro, Antonella; Fernandez-Rivas, Montserrat; Beyer, Kirsten

    2018-01-01

    The accurate assessment and communication of the severity of acute allergic reactions is important to patients, clinicians, researchers, the food industry, public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating...... of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical...... the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach and none has been validated...

  20. Anti-IgE and other new immunomodulation-based therapies for allergic asthma

    NARCIS (Netherlands)

    Jonkers, R. E.; van der Zee, J. S.

    2005-01-01

    Understanding of the cellular and molecular mechanisms in asthma has lead to the recognition of a number of potential therapeutic targets, a few of which have been evaluated in clinical studies. Parenteral administrations of both anti-IL-5 and IL-12 inhibit eosinophil recruitment to the airways, but

  1. Allergies, asthma, and molds

    Science.gov (United States)

    Reactive airway - mold; Bronchial asthma - mold; Triggers - mold; Allergic rhinitis - pollen ... Things that make allergies or asthma worse are called triggers. Mold is a common trigger. When your asthma or allergies become worse due to mold, you are ...

  2. Serum YKL-40 and assessment of severity of bronchial asthma in ...

    African Journals Online (AJOL)

    EL-HAKIM

    YKL-40 and asthma severity. 95. Table 1. Characteristics of the studied groups. Variable. Control. (n=15). Mild-Moderate asthma. (n=15). Severe asthma. (n=15). Age (yrs) mean±SD. 7.7±4.7. 6.6±4.9. 3.3±2.7. Gender (male); n (%). 10 (67%). 9 (60%). 8 (50%). PAS score. 0-4 (normal). 5-7 (mild attack). 8-11(moderate).

  3. The unfavorable effects of concomitant asthma and sleeplessness due to the atopic eczema/dermatitis syndrome (AEDS) on quality of life in subjects allergic to house-dust mites

    NARCIS (Netherlands)

    Terreehorst, I.; Duivenvoorden, H. J.; Tempels-Pavlica, Z.; Oosting, A. J.; de Monchy, J. G. R.; Bruijnzeel-Koomen, C. A. F. M.; Post, M. W. M.; Gerth van Wijk, R.

    2002-01-01

    BACKGROUND: Allergic rhinitis, asthma or the atopic eczema/dermatitis syndrome (AEDS) may independently impair quality of life in patients. However, although many allergic patients may suffer from more than one disorder, the effect of concomitant disease -- in particular, the impact of AEDS -- is

  4. The unfavorable effects of concomitant asthma and sleeplessness due to the atopic eczema/dermatitis syndrome (AEDS) on quality of life in subjects allergic to house-dust mites

    NARCIS (Netherlands)

    Terreehorst, [No Value; Duivenvoorden, HJ; Tempels-Pavlica, Z; Oosting, AJ; de Monchy, JGR; Bruijnzeel-Koomen, CAFM; Post, MWM; Gerth van Wijk, R

    2002-01-01

    Background: Allergic rhinitis, asthma or the atopic eczema/dermatitis syndrome (AEDS) may independently impair quality of life in patients. However, although many allergic patients may suffer from more than one disorder, the effect of concomitant disease - in particular, the impact of AEDS - is

  5. Airway wall thickness of allergic asthma caused by weed pollen or house dust mite assessed by computed tomography.

    Science.gov (United States)

    Liu, Liping; Li, Guangrun; Sun, Yuemei; Li, Jian; Tang, Ningbo; Dong, Liang

    2015-03-01

    Little was known about Airway wall thickness of asthma patients with different allergen allergy. So we explored the possible difference of Airway wall thickness of asthma patients mono-sensitized to weed pollen or HDM using high-resolution computed tomography. 85 severe asthma patients were divided into weed pollen group and HDM group according to relevant allergen. 20 healthy donors served as controls. Airway wall area, percentage wall area and luminal area at the trunk of the apical bronchus of the right upper lobe were quantified using HRCT and compared. The values of pulmonary function were assessed as well. There were differences between HDM group and weed pollen group in WA/BSA,WA% and FEF25-75% pred, and no significant difference in FEV1%pred, FEV1/FVC and LA/BSA. In weed pollen group, WA/BSA was observed to correlate with the duration of rhinitis, whereas in HDM group, WA/BSA and LA/BSA was observed to correlate with the duration of asthma. In weed pollen group, FEV1/FVC showed a weak but significant negative correlation with WA%, but in HDM group FEV1/FVC showed a significant positive correlation with WA% and a statistical negative correlation with LA/BSA. FEV1/FVC and FEF25-75% pred were higher and WA/BSA and LA/BSA were lower in healthy control group than asthma group. FEV1%pred and WA% was no significant difference between asthma patients and healthy subjects. There are differences between HDM mono-sensitized subjects and weed pollen mono-sensitized subjects, not only in airway wall thickness, but also small airway obstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Fibrinogen cleavage products and Toll-like receptor 4 promote the generation of programmed cell death 1 ligand 2-positive dendritic cells in allergic asthma.

    Science.gov (United States)

    Cho, Minkyoung; Lee, Jeong-Eun; Lim, Hoyong; Shin, Hyun-Woo; Khalmuratova, Roza; Choi, Garam; Kim, Hyuk Soon; Choi, Wahn Soo; Park, Young-Jun; Shim, Inbo; Kim, Byung-Seok; Kang, Chang-Yuil; Kim, Jae-Ouk; Tanaka, Shinya; Kubo, Masato; Chung, Yeonseok

    2017-10-14

    Inhaled protease allergens preferentially trigger T H 2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on induction of T H 2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce T H 2-favorable DCs in the airway remains unclear. We sought to determine a subset of DCs responsible for T H 2 cell responses in allergic asthma and the mechanism by which protease allergens induce the DC subset in the airway. Mice were challenged intranasally with protease allergens or fibrinogen cleavage products (FCPs) to induce allergic airway inflammation. DCs isolated from mediastinal lymph nodes were analyzed for surface phenotype and T-cell stimulatory function. Anti-Thy1.2 and Mas-TRECK mice were used to deplete innate lymphoid cells and mast cells, respectively. Adoptive cell transfer, bone marrow DC culture, anti-IL-13, and Toll-like receptor (TLR) 4-deficient mice were used for further mechanistic studies. Protease allergens induced a remarkable accumulation of T H 2-favorable programmed cell death 1 ligand 2 (PD-L2) + DCs in mediastinal lymph nodes, which was significantly abolished in mice depleted of mast cells and, to a lesser extent, innate lymphoid cells. Mechanistically, FCPs generated by protease allergens triggered IL-13 production from wild-type mast cells but not from TLR4-deficient mast cells, which resulted in an increase in the number of PD-L2 + DCs. Intranasal administration of FCPs induced an increase in numbers of PD-L2 + DCs in the airway, which was significantly abolished in TLR4- and mast cell-deficient mice. Injection of IL-13 restored the PD-L2 + DC population in mice lacking mast cells. Our findings unveil the "protease-FCP-TLR4-mast cell-IL-13" axis as a molecular mechanism for generation of T H 2-favorable PD-L2 + DCs in allergic asthma and suggest that targeting the PD-L2 + DC pathway might be effective in suppressing allergic T-cell responses in the airway

  7. Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview.

    Science.gov (United States)

    Asaria, M; Dhami, S; van Ree, R; Gerth van Wijk, R; Muraro, A; Roberts, G; Sheikh, A

    2018-02-01

    The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions. We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling

  8. Studying the Effects of Fasting during Ramadan on Pulmonary Functioning Test and Asthma Severity

    Directory of Open Access Journals (Sweden)

    Seyyed Hassan Adeli

    2015-03-01

    Full Text Available Background and Objectives: Studies have shown that fasting can have an impact on the course and severity of chronic diseases. There are a few studies on the association of fasting and asthma. Therefore, this study has been conducted with the purpose of examining the effects of fasting on asthma severity and pulmonary functioning tests. Methods: 30 patients with asthma who attended a pulmonology clinic in Qom were enrolled in this study. The severity of patients’ asthma has been studied by questionnaire and spirometry of pulmonary functioning in the month of Shaban, Ramadan and Shawwal. The results of Asthma Control Questionnaire and the pulmonary functioning tests in three months have been compared. Results: The average age of patients was 43.42 years and 43.3% of patients were males. The Average score for asthma severity questionnaire in three months were 20.4, 21 and 20.17 respectively. Statistically, there haven’t been any significant differences between the results of pulmonary functioning test and asthma severity before Ramadan (Shaban, during Ramadan and after that (Shawwal. Conclusion: The findings of this study showed that fasting in patients with asthma has no effect on pulmonary function and asthma severity.

  9. Upregulation of Tim-3 on CD4(+) T cells is associated with Th1/Th2 imbalance in patients with allergic asthma.

    Science.gov (United States)

    Tang, Fei; Wang, Fukun; An, Liyun; Wang, Xianling

    2015-01-01

    T cell Ig and mucin domain-containing molecule-3 (Tim-3) is a negative regulator preferentially expressed on Th1 cells. Allergic asthma is a clinical syndrome well characterized by Th1/Th2 imbalance. To investigate the role of Tim-3 in the pathogenesis of asthma and its relationship with Th1/Th2 imbalance, a total of 40 patients with allergic asthma and 40 healthy controls were enrolled. Expression of Tim-3 and Th1/Th2 imbalance as well as the relationship between them was analyzed by flow cytometry and real-time PCR. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro and anti-Tim-3 was used to block Tim-3 signaling; Th1/Th2 cytokines in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). CD4(+) T cells and B cells were sorted and co-cultured in vitro, and anti-Tim-3 was used to block Tim-3 signaling; Total IgG/IgE in the culture supernatant was detected by ELISA. The mRNA level of T-bet and IFN-γ were significantly decreased in allergic asthma patients, while GATA-3 and IL-4 were significantly increased. Expression of Tim-3 on CD4(+) T cells was much higher in allergic asthma patients and it was negatively correlated with T-bet/GATA-3 ratio or IFN-γ/IL-4 ratio. Blocking of Tim-3 significantly increased Th1 cytokines (TNF-α and IFN-γ) and decreased Th2 cytokines (IL-4, IL-5, IL-13) in the culture supernatant of PBMCs. Blocking of Tim-3 dramatically reduced the production of IgG and IgE in the co-culture supernatant of CD4(+) T cells and B cells. In conclusion, Tim-3 was up-regulated in allergic asthma patients and related with the Th1/Th2 imbalance. Blocking of Tim-3 may be of therapeutic benefit by enhancing the Th1 cytokines response, down-regulating the Th2 cytokines response, and reducing IgG/IgE production.

  10. Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma.

    Science.gov (United States)

    Altman, Matthew C; Whalen, Elizabeth; Togias, Alkis; O'Connor, George T; Bacharier, Leonard B; Bloomberg, Gordon R; Kattan, Meyer; Wood, Robert A; Presnell, Scott; LeBeau, Petra; Jaffee, Katy; Visness, Cynthia M; Busse, William W; Gern, James E

    2018-03-05

    Childhood asthma in inner-city populations is a major public health burden, and understanding early-life immune mechanisms that promote asthma onset is key to disease prevention. Children with asthma demonstrate a high prevalence of aeroallergen sensitization and T H 2-type inflammation; however, the early-life immune events that lead to T H 2 skewing and disease development are unknown. We sought to use RNA sequencing of PBMCs collected at age 2 years to determine networks of immune responses that occur in children with allergy and asthma. In an inner-city birth cohort with high asthma risk, we compared gene expression using RNA sequencing in PBMCs collected at age 2 years between children with 2 or more aeroallergen sensitizations, including dust mite, cockroach, or both, by age 3 years and asthma by age 7 years (cases) and matched control subjects who did not have any aeroallergen sensitization or asthma by age 7 years. PBMCs from the cases showed higher levels of expression of natural killer (NK) cell-related genes. After cockroach or dust mite allergen but not tetanus antigen stimulation, PBMCs from the cases compared with the control subjects showed differential expression of 244 genes. This gene set included upregulation of a densely interconnected NK cell-like gene network reflecting a pattern of cell activation and induction of inflammatory signaling molecules, including the key T H 2-type cytokines IL9, IL13, and CCL17, as well as a dendritic cell-like gene network, including upregulation of CD1 lipid antigen presentation molecules. The NK cell-like response was reproducible in an independent group of children with later-onset allergic sensitization and asthma and was found to be specific to only those children with both aeroallergen sensitization and asthma. These findings provide important mechanistic insight into an early-life immune pathway involved in T H 2 polarization, leading to the development of allergic asthma. Copyright © 2018 American

  11. Topical tacrolimus for the treatment of severe allergic keratoconjunctivitis in children

    Directory of Open Access Journals (Sweden)

    Vera Lucia Liendo

    Full Text Available ABSTRACT Purpose: Administration of eye drops containing antihistamines or sodium cromoglycate and its derivatives for the treatment of allergic keratoconjunctivitis is often insufficient and usually requires the addition of corticosteroids. However, the risk of complications, such as glaucoma and cataract, limits the use of corticosteroids to short courses, resulting in inadequate long-term treatment response. Immunosuppressive drugs have been considered as a valid alternative to steroids for atopic keratoconjunctivitis and vernal keratoconjunctivitis. This study aimed to evaluate the use of topical tacrolimus (TCL in improving the clinical signs of severe allergic keratoconjuctivitis in children. Methods: Patients with severe allergic keratoconjunctivitis associated with corneal epitheliopathy, gelatinous limbal infiltrates, and/or papillary reaction, along with a history of recurrences and resistance to conventional topical anti-allergy agents, were included in this open clinical trial. Patients were treated with 0.03% TCL ointment for ocular use. A severity score ranging from 0 to 9, with 9 being the highest and 0 being the lowest, was assigned based on signs observed on biomicroscopy prior to and following TCL treatment. Results: Analyses included 66 eyes of 33 patients. After a mean follow-up period of 13 months (range, 12-29 months, TCL treatment significantly decreased the mean symptom score severity for the right (from 5.56 ± 1.18 to 2.76 ± 1.5; p<0.001 and left (from 5.94 ± 1.16 to 2.86 ± 1.64; p<0.001. Conclusion: Topical TCL was effective and significantly improved the clinical signs of allergic keratoconjuctivitis in children. Thus, it is a potential new option for severe and challenging cases of ocular allergy.

  12. Impact of Aspergillus fumigatus in allergic airway diseases

    Directory of Open Access Journals (Sweden)

    Chaudhary Neelkamal

    2011-06-01

    Full Text Available Abstract For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA, known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF. The goal of this review is to discuss new understandings of host-pathogen interactions in the genesis of allergic airway diseases caused by A. fumigatus. Host and pathogen related factors that participate in triggering the inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed.

  13. Design and recruitment for the GAP trial, investigating the preventive effect on asthma development of an SQ-standardized grass allergy immunotherapy tablet in children with grass pollen-induced allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Valovirta, Erkka; Berstad, Aud Katrine Herland; de Blic, Jacques

    2011-01-01

    Allergic rhinoconjunctivitis is a risk factor for asthma development. Treating the underlying allergy may represent an attractive method of asthma prevention. No regulatory guidance exists in this area, and, to our knowledge, no clinical investigations meeting modern regulatory standards have bee...

  14. Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

    DEFF Research Database (Denmark)

    Bush, A; Pedersen, S; Hedlin, G

    2011-01-01

    There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided......, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both...

  15. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

    DEFF Research Database (Denmark)

    Shaw, Dominick E; Sousa, Ana R; Fowler, Stephen J

    2015-01-01

    U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe...... asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations...

  16. Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.

    Science.gov (United States)

    El Shabrawy, Reham M; Atta, Amal H; Rashad, Nearmeen M

    2016-01-01

    Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of population worldwide. A key feature of autoimmune thyroiditis is the presence of anti TPO antibodies, and some mutation of the TPO gene. Association between autoimmune thyroiditis and other autoimmune disorders has been reported but little is known about association with allergic diseases. In this study, we aimed to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and examine possible relationship between anti-TPO levels and polymorphism at the TPO gene A2173/C exon 12 and different types of allergens. The study included 50 adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50 controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4) and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti-TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was analyzed using restriction fragment length polymorphism (RFLP). Skin prick test was done to assess allergic response in patients. Serum levels of T3, T4 and TSH did not show any statistical significant difference between patients and groups. However, mean serum anti-TPO level was statistically higher in patients than controls, and correlated positively with body mass index, age, diastolic blood pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in allergic patients than in control group. 2173A>C Genotyping revealed that the frequency of C allele is increased in the patient group. C allele represents a risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value C polymorphism may be considered as a risk factor for developing autoimmune thyroiditis in patients with allergic rhinitis and asthma and that these patients should regularly be checked for hidden thyroiditis. Copyright© by the Egyptian Association of

  17. Immunopathogenesis of allergic rhinitis

    African Journals Online (AJOL)

    EL-HAKIM

    Druce HM. Allergic and non allergic rhinitis. In: Middleton EM Jr, Reed CE, Ellis EF, Adkinson NF. Jr, Yunginger JW, Busse WW, eds. Allergy: Principles and Practice. 5th ed. St. Louis,. Mo: Mosby, Year-Book;1998.p.1005-16. 3. Blaiss MS. Quality of life in allergic rhinitis. Ann. Allergy Asthma Immunol 1999;83(5):449-54. 4.

  18. The Norwegian National Reporting System and Register of Severe Allergic Reactions to Food

    Directory of Open Access Journals (Sweden)

    Martinus Løvik

    2009-10-01

    Full Text Available The Norwegian National Reporting System and Register of Severe Allergic Reactions to Food, or the Food Allergy Register, is a nation-wide, government-funded permanent reporting and registration system for severe allergic reactions to food. The Food Allergy Register collects information based on a one-page reporting form, serum samples for specific IgE analysis, and food samples for food allergen analysis. Reporting physicians receive in return an extensive commentary on the reported case and the relevant allergies, and results of the specific IgE analysis and food allergen analysis.The Food Allergy Register has, after being active for a little more than four years, given valuable information about several important aspects of food allergy in Norway. The Food Allergy Register has revealed food safety problems in relation to allergy that probably could be discovered only with the help of a systematic, nation-wide registration of cases. The reactions of peanut allergic individuals to lupine flour in bakery products is an example of how the Food Allergy Register is able to reveal potentially serious problems that would otherwise probably have gone unnoticed and certainly unexplained. The amount and the value of the information from the Food Allergy Register are increasing as new reports of more cases are added. The typical Norwegian patient with a severe allergic reaction to food appears to be a young adult, female rather than male. The offending meal is consumed at a restaurant or fast-food stand or in a private party away from home, and peanuts, nuts and shellfish are among the most common offending foods, while fish allergy appears to be rather rare.

  19. Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Singh, Shashi P; Chand, Hitendra S; Langley, Raymond J; Mishra, Neerad; Barrett, Ted; Rudolph, Karin; Tellez, Carmen; Filipczak, Piotr T; Belinsky, Steve; Saeed, Ali I; Sheybani, Aryaz; Exil, Vernat; Agarwal, Hemant; Sidhaye, Venkataramana K; Sussan, Thomas; Biswal, Shyam; Sopori, Mohan

    2017-05-15

    Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies. Copyright © 2017 by The American Association of Immunologists, Inc.

  20. Association of Body Mass Index with Asthma Severity and Pulmonary Function among Asthmatic Children

    Directory of Open Access Journals (Sweden)

    Rasuol Nasiri Kalmarzi

    2016-09-01

    Full Text Available Background Asthma is a chronic inflammatory disease in respiratory system and obesity is another inflammatory disease which incidence rate is increasing. Although, many studies have been conducted on severity of asthma and its relationship with obesity, but different results have been obtained. This study aimed to determine a relationship between asthma severity, Body Mass Index (BMI and pulmonary function in Kurdistan province, Iran. Materials and Methods: In this cross sectional study 90 asthmatic patients referred to referral hospital in Kurdistan, North West of Iran, were selected by simple random method. BMI was calculated by dividing weight by height.Pulmonary Function Test (PFT and bronchial-stimulation-test were used for confirmation and investigation of asthma severity. Data were analyzed using SPSS-15 and Chi-square and spearman correlation coefficient tests. Results: Relationship between BMI and severity of asthma (mild, medium and severe was evaluated, there was a relationship and positive relationship between them (P

  1. Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells

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    Eric R. Secor

    2013-01-01

    Full Text Available The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr, a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA-induced murine model of allergic airway disease (AAD. However, sBr’s effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL, spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes. OVA-specific IgE and OVA TET+ cells were decreased. sBr reduced CD11c+ dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena.

  2. Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma.

    Science.gov (United States)

    Zhang, Guqin; Nie, Hanxiang; Yang, Jiong; Ding, Xuhong; Huang, Yi; Yu, Hongying; Li, Ruyou; Yuan, Zhuqing; Hu, Suping

    2011-12-01

    Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.

  3. Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin-induced allergic response in a mouse model of asthma.

    Science.gov (United States)

    Jung, Hyo Won; Kang, Seok Yong; Kang, Jong Seong; Kim, A Ryun; Woo, Eun-Rhan; Park, Yong-Ki

    2014-11-01

    The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)-induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Allergic conjunctivitis in Asia.

    Science.gov (United States)

    Thong, Bernard Yu-Hor

    2017-04-01

    Allergic conjunctivitis (AC), which may be acute or chronic, is associated with rhinitis in 30%-70% of affected individuals, hence the term allergic rhinoconjunctivitis (AR/C). Seasonal and perennial AC is generally milder than the more chronic and persistent atopic and vernal keratoconjunctivitis. Natural allergens like house dust mites (HDM), temperate and subtropical grass and tree pollen are important triggers that drive allergic inflammation in AC in the Asia-Pacific region. Climate change, environmental tobacco smoke, pollutants derived from fuel combustion, Asian dust storms originating from central/north Asia and phthalates may also exacerbate AR/C. The Allergies in Asia Pacific study and International Study of Asthma and Allergies in Childhood provide epidemiological data on regional differences in AR/C within the region. AC significantly impacts the quality of life of both children and adults, and these can be measured by validated quality of life questionnaires on AR/C. Management guidelines for AC involve a stepped approach depending on the severity of disease, similar to that for allergic rhinitis and asthma. Topical calcineurin inhibitors are effective in certain types of persistent AC, and sublingual immunotherapy is emerging as an effective treatment option in AR/C to grass pollen and HDM. Translational research predominantly from Japan and Korea involving animal models are important for the potential development of targeted pharmacotherapies for AC.

  5. Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma.

    Science.gov (United States)

    Youroukova, Vania M; Dimitrova, Denitsa G; Valerieva, Anna D; Lesichkova, Spaska S; Velikova, Tsvetelina V; Ivanova-Todorova, Ekaterina I; Tumangelova-Yuzeir, Kalina D

    2017-06-01

    Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms. To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters. Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included. All underwent clinical assessment, anthropometric measurements, skin prick testing, standard spirometry and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum total IgE and periostin levels were determined. Two-step cluster approach, hierarchical clustering method and k-mean analysis were used for identification of the clusters. We have identified four clusters. Cluster 1 (n=14) - late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) - late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity, eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma. Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

  6. Sub-optimal patient and physician communication in primary care consultations: its relation to severe and difficult asthma

    NARCIS (Netherlands)

    Moffat, M.; Cleland, J.; Van der Molen, T.; Price, D.

    2006-01-01

    Introduction: Asthma control can be influenced by a range of non-medical issues, including psychosocial factors. Little is known about the views of patients, particularly those with severe and/or difficult asthma, towards their asthma control and their asthma-related primary care consultations. Aims

  7. The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma

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    Galbraith Deirdre

    2004-05-01

    Full Text Available Abstract Background The anti-inflammatory effects of the selective phosphodiesterase (PDE inhibitors cilostazol (PDE 3, RO 20-1724 (PDE 4 and sildenafil (PDE 5 were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control. Methods Control and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days. Results When used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil. Conclusions These results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor.

  8. Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models.

    Science.gov (United States)

    Lew, D Betty; Michael, Christie F; Overbeck, Tracie; Robinson, W Scout; Rohman, Erin L; Lehman, Jeffrey M; Patel, Jennifer K; Eiseman, Brandi; LeMessurier, Kim S; Samarasinghe, Amali E; Gaber, M Waleed

    2017-01-01

    One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

  9. Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models

    Directory of Open Access Journals (Sweden)

    D. Betty Lew

    2017-01-01

    Full Text Available One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM remodeling effects. The mannose receptor (MR family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR and that mannan derived from Saccharomyces cerevisiae (SC-MN inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2 expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

  10. Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma

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    Charleston Ribeiro Pinto

    2013-06-01

    Full Text Available OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx associated with the use of inhaled corticosteroids (ICSs in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5% were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5% were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5% reported at least one adverse effect, and 131 (65.5% had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5% and 154 (77.0% of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here.

  11. Management of severe asthma: targeting the airways, comorbidities and risk factors.

    Science.gov (United States)

    Gibson, Peter G; McDonald, Vanessa M

    2017-06-01

    Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA. © 2017 Royal Australasian College of Physicians.

  12. Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma

    NARCIS (Netherlands)

    Rossios, Christos; Pavlidis, Stelios; Hoda, Uruj; Kuo, Chih-Hsi; Wiegman, Coen; Russell, Kirsty; Sun, Kai; Loza, Matthew J.; Baribaud, Frederic; Durham, Andrew L.; Ojo, Oluwaseun; Lutter, Rene; Rowe, Anthony; Bansal, Aruna; Auffray, Charles; Sousa, Ana; Corfield, Julie; Djukanovic, Ratko; Guo, Yike; Sterk, Peter J.; Chung, Kian Fan; Adcock, Ian M.

    2018-01-01

    Sputum analysis in asthmatic patients is used to define airway inflammatory processes and might guide therapy. We sought to determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared with nonsmoking patients with mild/moderate asthma. Induced

  13. Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

    NARCIS (Netherlands)

    Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

    2015-01-01

    In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

  14. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): A multicentre randomised double-blind placebo-controlled trial

    NARCIS (Netherlands)

    G.G. Brusselle (Guy); C. VanderStichele (Christine); P. Jordens (Paul); R. Deman (René); H. Slabbynck (Hans); V. Ringoet (Veerle); G. Verleden (Geert); I.K. Demedts (Ingel); K.M.C. Verhamme (Katia); A. Delporte (Anja); B. Demeyere (Bénédicte); T. Claeys (Tine); J. Boelens (Jerina); E. Padalko (Elizaveta); J. Verschakelen (Johny); G. van Maele (Georges); E. Deschepper (Ellen); G.F. Joos (Guy)

    2013-01-01

    markdownabstract__Background:__ Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases

  15. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

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    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  16. Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.

    Science.gov (United States)

    Mikolka, P; Mokra, D; Drgova, A; Petras, M; Mokry, J

    2012-04-01

    In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma.

  17. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma.

    Science.gov (United States)

    Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

    2015-09-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in previous research, scores on the Parenting Stress Index in mothers and fathers of the children with problematic severe asthma were low. Higher parenting stress was associated with higher levels of internalizing and externalizing behavioral problems in children (Child Behavior Checklist). Higher parenting stress in mothers was also associated with higher airway inflammation (FeNO). Thus, although parenting stress was suggested to be low in this group, higher parenting stress, especially in the mother, is associated with more airway inflammation and greater child behavioral problems. This indicates the importance of focusing care in this group on all possible sources of problems, i.e., disease exacerbations and behavioral problems in the child as well as parenting stress.

  18. Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

    Science.gov (United States)

    Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba

    2012-01-01

    Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma. PMID:23209480

  19. Increased body mass index predicts severity of asthma symptoms but not objective asthma traits in a large sample of asthmatics

    DEFF Research Database (Denmark)

    Bildstrup, Line; Backer, Vibeke; Thomsen, Simon Francis

    2015-01-01

    AIM: To examine the relationship between body mass index (BMI) and different indicators of asthma severity in a large community-based sample of Danish adolescents and adults. METHODS: A total of 1186 subjects, 14-44 years of age, who in a screening questionnaire had reported a history of airway...... symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore height and weight, skin test reactivity, lung function, and airway responsiveness were measured...

  20. IgE sensitization and sociodemographic conditions as determinant factors in asthma severity

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    Rodrigo Gaviria

    2017-12-01

    Full Text Available Background: In Latin America there are few data about the factors that influence the control and severity of asthma. Objective: To describe the association between IgE sensitization to intra-home allergens and housing conditions in the severity of asthma. Methods: Sensitization to aero-allergens was evaluated by skin prick test and socio-demographic data by a questionnaire in a population between 6 and 14 years of age with diagnosis of asthma. Asthma control was measured according to spirometric results and to the application of the ACT (Asthma Control Test; the severity and symptom control was evaluated according to the GINA guideline. Results: A total of 150 resident patients from the Aburra Valley (Colombia were included. The median age of participants was 11 years, 95 (63.3 % male. 92 % of the patients resided in the urban area. Mite sensitization was the most prevalent in controlled and uncontrolled patients. Sensitization to cockroach and some poverty conditions were risk factors for asthma severity. Conclusion: Poverty conditions appear to favor the development of severe asthma and in turn IgE sensitization to cockroaches. This sensitization could serve as a biomarker of severity.

  1. The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts

    NARCIS (Netherlands)

    Fleming, Louise; Murray, Clare; Bansal, Aruna T.; Hashimoto, Simone; Bisgaard, Hans; Bush, Andrew; Frey, Urs; Hedlin, Gunilla; Singer, Florian; van Aalderen, Wim M.; Vissing, Nadja H.; Zolkipli, Zaraquiza; Selby, Anna; Fowler, Stephen; Shaw, Dominick; Chung, Kian Fan; Sousa, Ana R.; Wagers, Scott; Corfield, Julie; Pandis, Ioannis; Rowe, Anthony; Formaggio, Elena; Sterk, Peter J.; Roberts, Graham; Tariq, Kamran; Dennison, Patrick; Behndig, Annelie F.; Lutter, Rene; Wagener, Ariane; van Drunen, Kees; Hekking, Pieter-Paul; Brinkman, Paul; Zwinderman, Koos; Mores, Nadia; Santini, Giuseppe; Valente, Salvatore; Rossios, Christos; Gibeon, David; Hoda, Uruj; Rocha, João Pedro Carvalho da Purificação; Sogbesan, Adesimbo; Gent, Julaiha; Menzies-Gow, Andrew; Campagna, Davide; Bigler, Jeannette; Boedigheimer, Michael J.; Yu, Wen; Hu, Xugang; Fichtner, Klaus; Nething, Katja

    2015-01-01

    U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches. A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53

  2. Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma.

    Science.gov (United States)

    Iribarren, Carlos; Rahmaoui, Abdelkader; Long, Aidan A; Szefler, Stanley J; Bradley, Mary S; Carrigan, Gillis; Eisner, Mark D; Chen, Hubert; Omachi, Theodore A; Farkouh, Michael E; Rothman, Kenneth J

    2017-05-01

    EXCELS, a postmarketing observational cohort study, was a commitment to the US Food and Drug Administration to assess the long-term safety of omalizumab in an observational setting, focusing predominantly on malignancies. The aim of this study was to examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS. Patients (≥12 years of age) with moderate to severe allergic asthma and who were being treated with omalizumab (n = 5007) or not (n = 2829) at baseline were followed up for ≤5 years. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATEs), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, and unstable angina. A prespecified analysis of the end point of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events. At baseline, the 2 cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus the non-omalizumab group (50% vs 23%). Omalizumab-treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1,000 person years [PYs]) than did non-omalizumab-treated patients (8.1 per 1,000 PYs). The ATE rates per 1,000 PYs were 6.66 (101 patients/15,160 PYs) in the omalizumab cohort and 4.64 (46 patients/9,904 PYs) in the non-omalizumab cohort. After control for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91-1.91). This observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus the non-omalizumab cohort. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. CD8+ T Cells Mediate Female-Dominant IL-4 Production and Airway Inflammation in Allergic Asthma.

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    Chihiro Ito

    Full Text Available The prevalence and severity of bronchial asthma are higher in females than in males after puberty. Although antigen-specific CD8+ T cells play an important role in the development of asthma through their suppressive effect on cytokine production, the contribution of CD8+ T cells to sex differences in asthmatic responses remains unclear. In the present study, we investigated the sex-specific effect of CD8+ T cells in the suppression of asthma using an ovalbumin mouse model of asthma. The number of inflammatory cells in bronchoalveolar lavage (BAL fluid, lung type 2 T-helper cytokine levels, and interleukin-4 (IL-4 production by bronchial lymph node cells were significantly higher in female wild-type (WT mice compared with male mice, whereas no such sex differences were observed between male and female cd8α-disrupted mice. The adaptive transfer of male, but not female, CD8+ T cells reduced the number of inflammatory cells in the recovered BAL fluid of male recipient mice, while no such sex difference in the suppressive activity of CD8+ T cells was observed in female recipient mice. Male CD8+ T cells produced higher levels of IFN-γ than female CD8+ T cells did, and this trend was associated with reduced IL-4 production by male, but not female, CD4+ T cells. Interestingly, IFN-γ receptor expression on CD4+ T cells was significantly lower in female mice than in male mice. These results suggest that female-dominant asthmatic responses are orchestrated by the reduced production of IFN-γ by CD8+ T cells and the lower expression of IFN-γ receptor on CD4+ T cells in females compared with males.

  4. Smoke-free air laws and asthma prevalence, symptoms, and severity among nonsmoking youth.

    Science.gov (United States)

    Dove, Melanie S; Dockery, Douglas W; Connolly, Gregory N

    2011-01-01

    We investigated the association between smoke-free laws and asthma prevalence, symptoms, and severity among nonsmoking youth (aged 3-15 years). We examined data from the 1999-2006 National Health and Nutrition Examination Survey, a cross-sectional survey designed to monitor the health and nutritional status of the US population. Survey locations were dichotomized as having or not having at least 1 smoke-free workplace, restaurant, or bar law at the county or state level that covered the entire county population. Asthma prevalence was assessed as self-reported current asthma and as ever having asthma with current symptoms. Asthmatic symptoms included persistent wheeze, chronic night cough, and wheeze-medication use. We also examined asthma severity (asthma attack or emergency-department visit for asthma) and persistent ear infection. Smoke-free laws were not associated with current asthma but were significantly associated with lower odds of asthmatic symptoms (odds ratio [OR]: 0.67 [95% confidence interval (CI): 0.48-0.93]) among nonsmoking youth. The association between smoke-free laws and ever having asthma with current symptoms approached significance (OR: 0.74 [95% CI: 0.53-1.03]). Smoke-free laws were associated with lower odds of asthma attacks (OR: 0.66 [95% CI: 0.28-1.56]) and emergency-department visits for asthma (OR: 0.55 [95% CI: 0.27-1.13]), although these results were not statistically significant. Our results suggest that smoke-free laws reduce asthmatic symptoms, including persistent wheeze, chronic night cough, and wheeze-medication use in nonsmoking youth.

  5. Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma.

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    Guerra, Evelyn Santos; Lee, Chrono K; Specht, Charles A; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R; Mueller, Christian; Levitz, Stuart M

    2017-01-01

    Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.

  6. Infection with Mycoplasma pneumoniae is not related to asthma control, asthma severity, and location of airway obstruction

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    Khalil Ansarin,Siavoush Abedi,Reza Ghotaslou

    2010-12-01

    Full Text Available Khalil Ansarin1, Siavoush Abedi1, Reza Ghotaslou1, Mohammad Hossein Soroush1, Kamyar Ghabili1, Kenneth R Chapman21Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Asthma and Airway Centre, Toronto Western Hospital, University Health Network, Toronto, ON, CanadaBackground: Mycoplasma pneumoniae is an organism that reportedly has a strong relationship to asthma. However, asthma severity and location of airway obstruction have not been compared between asthmatic patients with and without evidence for remote mycoplasma infection.Objectives: The aim of this research was to study the relationship between previous M. pneumoniae infections in asthmatic patients and presence of any predilection for the involvement of central or peripheral airways, the severity of the disease, and asthma control.Methods: Sixty-two patients with asthma were assessed by a validated asthma control test (ACT. All patients underwent spirometry and lung volume studies by body plethysmography. The forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, total lung capacity (TLC, residual volume (RV, and functional residual capacity (FRC were measured. An oropharyngeal swab was obtained for polymerase chain reaction analysis to detect the mycoplasma antigen. Moreover, blood samples were obtained to measure the titration of antimycoplasma immunoglobulin M (IgM and IgG antibodies. The asthmatic patients with a positive IgG for mycoplasma and negative PCR and negative IgM antibody were considered to have remote history of mycoplasma infection. The relationship between the asthma control using ACT score and pulmonary function variables were compared in patients with and without evidence for remote mycoplasma infection.Results: The incidence of postnasal drip was higher among the patients with asthma who had no evidence for remote mycoplasma infection (61.3% vs 32%, P = 0.035. The median ACT score was 16.5 (11–22 and

  7. The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

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    Rojanasarot, Sirikan; Carlson, Angeline M

    2018-04-01

    The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

  8. Cost-effectiveness analysis of a state funded programme for control of severe asthma

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    Loureiro Sebastião

    2007-05-01

    Full Text Available Abstract Background Asthma is one of the most common chronic diseases and a major economical burden to families and health systems. Whereas efficacy of current therapeutical options has been clearly established, cost-effectiveness analysis of public health interventions for asthma control are scarce. Methods 81 patients with severe asthma (12–75 years joining a programme in a reference clinic providing free asthma medication were asked retrospectively about costs and events in the previous 12 months. During 12 months after joining the programme, information on direct and indirect costs, asthma control by lung function, symptoms and quality of life were collected. The information obtained was used to estimate cost-effectiveness of the intervention as compared to usual public health asthma management. Sensitivity analysis was conducted. Results 64 patients concluded the study. During the 12-months follow-up within the programme, patients had 5 fewer days of hospitalization and 68 fewer visits to emergency/non scheduled medical visits per year, on average. Asthma control scores improved by 50% and quality of life by 74%. The annual saving in public resources was US$387 per patient. Family annual income increased US$512, and family costs were reduced by US$733. Conclusion A programme for control of severe asthma in a developing country can reduce morbidity, improve quality of life and save resources from the health system and patients families.

  9. ANTI-IGE THERAPY FOR SEVERE ASTHMA IN CHILDREN: TWO-YEAR TRIAL

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    T.Yu. Kulichenko

    2010-01-01

    Full Text Available The article summarizes a two-year experience of treating children and adolescents with severe uncontrolled atopic asthma using Omalizumab. This treatment facilitated to achieve full asthma control in 70% of patients and partial control in 30% of patients. Anti-Ig Etherapy contributes to reduce the frequency of asthma relapses 77%, and the number of those seeking emergency medical treatment, particularly no need for in-patient asthma care. Thanks to treatment, lung function parameters improve, particularly in children with low bronchial patency parameters even after administration of broncholytics. Thanks to treatment with omalizumab, the dosage of inhalant glucocorticosteroids is reduced 1.5 to 2.5 times in 75% patients. Treatment tolerance in all children is satisfactory, no serious adverse events associated with the medication or any system side effects are registered in patients. Anti-IgE therapy is a good alternative to use of high and ultra-high doses of inhalant glucocorticosteroids in children with severe atopic asthma. Key words: omalizumab, anti-IgE-antibodies, treatment-resistant asthma, atopic asthma, treatment, children, adolescents, asthma control. (Pediatric Pharmacology. – 2010; 7(3:57-65

  10. Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma.

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    Miraglia Del Giudice, Michele; Indolfi, Cristiana; Capasso, Michele; Maiello, Nunzia; Decimo, Fabio; Ciprandi, Giorgio

    2017-03-07

    Allergic rhinitis (AR) and allergic asthma are caused by an IgE-mediated inflammatory reaction. Probiotics may exert anti-inflammatory and immune-modulatory activity. Thus, this study aimed at investigating whether a Bifidobacteria mixture could be able to relieve nasal symptoms, and affect quality of life (QoL) in children with AR and intermittent asthma due to Parietaria allergy. The present study was conducted as placebo-controlled, double-blinded, and randomized. Globally, 40 children (18 males; mean age 9 ± 2.2 years) were enrolled. They were treated with probiotics or placebo: 1 sachet/day for 4 weeks. AR symptoms, and QoL were assessed at baseline and after treatment. Use of rescue medications, such as cetirizine syrup and salbutamol spray, was also permitted and recorded. Children treated with probiotic mixture achieved a significant improvement of symptoms (p < 0.005), and QoL ((p < 0.001). Placebo group had worsening of symptoms (p < 0.005) and QoL (p < 0.001). The use of rescue medications was overlapping in the two groups. The intergroup analysis showed that probiotic mixture was significantly superior than placebo for all parameters. The current study demonstrated that a Bifidobacteria mixture was able of significantly improving AR symptoms and QoL in children with pollen-induced AR and intermittent asthma. ClinicalTrials.gov ID NCT02807064 .

  11. TREATMENT POLICY OF PEDIATRICIANS AGAINST ACUTE AND CHRONIC ALLERGIC PATHOLOGIES IN CHILDREN. DESLORATADINE

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    E.A. Vishneva

    2009-01-01

    Full Text Available Allergic rhinitis, bronchial asthma, chronic idiopathic nettle rash, atopic dermatitis have been characterized by a stable growth in the prevalence of the allergic pathology over the last several decades. A similar pathogenesis of allergic diseases makes it possible to regard them as different manifestations of a systemic allergic inflammation. Histamine is one of the main mediators of an allergic inflammation, therefore first-line medications (drug of choice in the treatment of an allergic pathology, first of all, rhinitis and chronic nettle rash, are second-generation blockers of Н1-receptors. The proposed article discusses the issues connected with the use of antihistamines for children.Key words: allergic rhinitis, bronchial asthma, nettle rash, atopic dermatitis, treatment, antihistamines, children.

  12. Outcomes Following Discontinuation of E. coli l-Asparaginase Upon Severe Allergic Reactions in Children With Acute Lymphoblastic Leukemia.

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    Yen, Hsiu-Ju; Chang, Wan-Hui; Liu, Hsi-Che; Yeh, Ting-Chi; Hung, Giun-Yi; Wu, Kang-Hsi; Peng, Ching-Tien; Chang, Yu-Hsiang; Chang, Te-Kao; Hsiao, Chih-Cheng; Sheen, Jiunn-Ming; Chao, Yu-Hua; Chang, Tai-Tsung; Chiou, Shyh-Shin; Lin, Pei-Chin; Wang, Shih-Chung; Lin, Ming-Tsan; Ho, Wan-Ling; Chen, Yu-Chieh; Liang, Der-Cherng

    2016-04-01

    Discontinuation of E. coli l-asparaginase in patients with acute lymphoblastic leukemia (ALL) is unavoidable upon severe allergic reaction. We sought to examine outcomes following E. coli l-asparaginase discontinuation due to severe allergic reactions. We evaluated the outcome of children enrolled in Taiwan Pediatric Oncology Group-2002-ALL protocol between 2002 and 2012, who had E. coli l-asparaginase discontinued due to severe allergic reactions, and compared the outcomes of those who continued with Erwinia l-asparaginase (Erwinase) with those who did not. Among 700 patients enrolled in this study, 33 patients had E. coli l-asparaginase treatment discontinued due to severe allergic reactions. Five-year overall survival did not differ significantly among the 648 patients without discontinuation (81 ± 1.6%, mean ± SE), compared to 17 patients with allergic reactions and treated with Erwinase (88 ± 7.8%) and 16 patients with allergic reactions but not treated with Erwinase (87 ± 8.6%). Among 16 patients who did not receive Erwinase, all 10 who received ≥50% of the scheduled doses of E. coli l-asparaginase before discontinuation survived without events. Erwinase treatment may not be needed for some ALL patients with severe allergy to E. coli l-asparaginase if ≥50% of prescribed doses were received and/or therapy is augmented with other agents. © 2015 Wiley Periodicals, Inc.

  13. Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

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    Yii, A C A; Tan, J H Y; Lapperre, T S; Chan, A K W; Low, S Y; Ong, T H; Tan, K L; Chotirmall, S H; Sterk, P J; Koh, M S

    2017-09-01

    Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently

  14. GENE EXPRESSION DYNAMICS IN PATIENTS WITH SEVERE THERAPY-RESISTANT ASTHMA DURING TREATMENT PERIOD

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    Ye. S. Kulikov

    2014-01-01

    Full Text Available Introduction: The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma in dynamic during treatment period.Methods: Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip. Cluster analysis was performed.Results and conclusion: According to our data several mechanisms of therapy resistance may be considered: increased levels of nitric oxide and beta2-agonists nitration, dysregulation of endogenous steroids secretion and involvement in the pathogenesis of Staphylococcus aureus. Absence of suppression of gene expression KEGG-pathway “asthma" may reflect the low efficiency or long period of anti-inflammatory therapy effect realization.

  15. March1 E3 Ubiquitin Ligase Modulates Features of Allergic Asthma in an Ovalbumin-Induced Mouse Model of Lung Inflammation

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    Osama A. Kishta

    2018-01-01

    Full Text Available Membrane-associated RING-CH-1 (March1 is a member of the March family of E3 ubiquitin ligases. March1 downregulates cell surface expression of MHC II and CD86 by targeting them to lysosomal degradation. Given the key roles of MHC class II and CD86 in T cell activation and to get further insights into the development of allergic inflammation, we asked whether March1 deficiency exacerbates or attenuates features of allergic asthma in mice. Herein, we used an acute model of allergy to compare the asthmatic phenotype of March1-deficient and -sufficient mice immunized with ovalbumin (OVA and later challenged by intranasal instillation of OVA in the lungs. We found that eosinophilic inflammation in airways and lung tissue was similar between WT and March1−/− allergic mice, whereas neutrophilic inflammation was significant only in March1−/− mice. Airway hyperresponsiveness as well as levels of IFN-γ, IL-13, IL-6, and IL-10 was lower in the lungs of asthmatic March1−/− mice compared to WT, whereas lung levels of TNF-α, IL-4, and IL-5 were not significantly different. Interestingly, in the serum, levels of total and ova-specific IgE were reduced in March1-deficient mice as compared to WT mice. Taken together, our results demonstrate a role of March1 E3 ubiquitin ligase in modulating allergic responses.

  16. Performance of a novel clinical score, the Pediatric Asthma Severity Score (PASS), in the evaluation of acute asthma.

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    Gorelick, Marc H; Stevens, Molly W; Schultz, Theresa R; Scribano, Philip V

    2004-01-01

    To evaluate the reliability, validity, and responsiveness of a new clinical asthma score, the Pediatric Asthma Severity Score (PASS), in children aged 1 through 18 years in an acute clinical setting. This was a prospective cohort study of children treated for acute asthma at two urban pediatric emergency departments (EDs). A total of 852 patients were enrolled at one site and 369 at the second site. Clinical findings were assessed at the start of the ED visit, after one hour of treatment, and at the time of disposition. Peak expiratory flow rate (PEFR) (for patients aged 6 years and older) and pulse oximetry were also measured. Composite scores including three, four, or five clinical findings were evaluated, and the three-item score (wheezing, prolonged expiration, and work of breathing) was selected as the PASS. Interobserver reliability for the PASS was good to excellent (kappa = 0.72 to 0.83). There was a significant correlation between PASS and PEFR (r = 0.27 to 0.37) and pulse oximetry (r = 0.29 to 0.41) at various time points. The PASS was able to discriminate between those patients who did and did not require hospitalization, with area under the receiver operating characteristic curve of 0.82. Finally, the PASS was shown to be responsive, with a 48% relative increase in score from start to end of treatment and an overall effect size of 0.62, indicating a moderate to large effect. This clinical score, the PASS, based on three clinical findings, is a reliable and valid measure of asthma severity in children and shows both discriminative and responsive properties. The PASS may be a useful tool to assess acute asthma severity for clinical and research purposes.

  17. How should treatment approaches differ depending on the severity of asthma?

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    Kupczyk, Maciej; Kuna, Piotr

    2017-12-01

    Asthma is nowadays regarded as a syndrome of various overlapping phenotypes with defined clinical characteristics, different underlying inflammatory mechanisms, identifiable genetic background, environmental risk factors and possible biomarkers. There are no doubts that due to the diversity of asthma, a 'one size fits all' management of the disease is no longer valid. Areas covered: Nowadays asthma management is based on the control of the disease, and the goals of asthma treatment are defined as good symptom control, decreased future risk of exacerbations, fixed airflow limitation, and side-effects of treatment. Alternative strategies for adjusting asthma treatment such as sputum or exhaled nitric oxide guided protocols have been evaluated and despite some effectiveness, are regarded as impractical in every-day clinical conditions. Further studies in the field of asthma phenotypes/endotypes and biomarkers are warranted with the main goal to define which of those possible subgroups will be useful in clinical practice in regards to the potential allocation of successful treatment. Expert commentary: Despite the availability of guidelines on the diagnosis and management of asthma, it seems that the disease is still not optimally controlled. Addressing unmet needs in every day care, improving education, adherence/compliance and inhalation technique may significantly improve asthma control across all severities of the disease.

  18. Asthma

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    Kim Harold

    2011-11-01

    Full Text Available Abstract Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICSs represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonists (LABA inhalers are preferred for most adults who fail to achieve control with ICS therapy. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma, but should only be prescribed by physicians with appropriate training in allergy. Regular monitoring of asthma control, adherence to therapy and inhaler technique are also essential components of asthma management. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma.

  19. Diagnóstico de asma alérgica en consultas de alergología y neumología Diagnosis of allergic asthma in allergy and pneumology outpatient clinics

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    Luis Borderías

    2006-12-01

    these patients. Methods: Systematic random sampling was used to retrospectively include 382 patients aged between 12 and 65 years old with a diagnosis of persistent asthma (according to GINA criteria who had attended allergy or pneumology outpatient clinics during the previous year. Allergic asthma was defined as the presence of sensitization to any common allergen according to the results of specific IgE determinations and/or skin tests. Data on the treatment of asthma were gathered. Results: Allergy studies were performed in 99.5% of the patients attending allergy centers and in 76.5% of those attending pneumology centers. A diagnosis of allergic asthma was made in 90.6% (95% CI: 86.5-94.7 and 46.1% (95% CI: 39.0-53.2, respectively. The prevalence of allergic asthma was highest in young male patients with less severe asthma. According to the GINA criteria, 14.1% of patients from allergy centres and 23.0% of those from pneumology centers were classified as having severe persistent asthma. Twenty-four percent of patients attending allergy clinics and 5.7% of those attending pneumology centers received bronchodilator treatment exclusively. Conclusions: Diagnosis of allergic asthma was much higher in allergy clinics than in pneumology centres. Although some of this difference may be due to more frequent performance of allergy studies in allergy clinics, the most probable explanation lies in the differences observed in the profiles of patients attending the two types of center.

  20. Interplay of T Helper 17 Cells with CD4+CD25high FOXP3+ Tregs in Regulation of Allergic Asthma in Pediatric Patients

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    Amit Agarwal

    2014-01-01

    Full Text Available Background. There is evidence that Tregs are important to prevent allergic diseases like asthma but limited literature exists on role of TH17 cells in allergic diseases. Methods. Fifty children with asthma and respiratory allergy (study group and twenty healthy children (control group were recruited in this study. Total IgE levels and pulmonary function tests were assessed. The expression of Tregs and cytokines was determined by flow cytometry. Results. The average level of total IgE in study group (316.8 ± 189.8 IU/mL was significantly higher than controls (50 ± 17.5 IU/mL, P<0.0001. The frequency of TH17 cells and culture supernatant level of IL-17 in study group (12.09 ± 8.67 pg/mL was significantly higher than control group (2.01 ± 1.27 pg/mL, P<0.001. Alternatively, the frequency of FOXP3 level was significantly lower in study group [(49.00 ± 13.47%] than in control group [(95.91 ± 2.63%] and CD4+CD25+FOXP3+ to CD4+CD25+ ratio was also significantly decreased in study group [(6.33 ± 2.18%] compared to control group [(38.61 ± 11.04%]. The total serum IgE level is negatively correlated with FOXP3 level (r=-0.5273, P<0.0001. The FOXP3 expression is negatively correlated with the IL-17 levels (r=-0.5631, P<0.0001 and IL-4 levels (r=-0.2836, P=0.0460. Conclusions. Imbalance in TH17/Tregs, elevated IL-17, and IL-4 response and downregulation of FOXP3 were associated with allergic asthma.

  1. Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice.

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    Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

    2016-02-03

    Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA)-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA-sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes

  2. Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status

    DEFF Research Database (Denmark)

    Kerstjens, Huib A M; Moroni-Zentgraf, Petra; Tashkin, Donald P

    2016-01-01

    performed in parallel in patients with severe symptomatic asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, time to first severe exacerbation, time to first episode of asthma worsening, and seven-question Asthma Control Questionnaire responder rate were......BACKGROUND: Many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic...... asthma. OBJECTIVE: To determine whether the efficacy of tiotropium add-on therapy is dependent on patients' baseline characteristics. METHODS: Two randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat(®) 5 μg add-on to ICS plus a LABA were...

  3. Non-invasive ventilation in severe asthma attack, its possibilities and problems.

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    Murase, K; Tomii, K; Chin, K; Niimi, A; Ishihara, K; Mishima, M

    2011-06-01

    Asthma attack is characterized by episodic attacks of cough, dyspnea and wheeze occurring due to bronchoconstriction, airway hyperresponsiveness and mucous hypersecretion. Although nationwide clinical guidelines have been published to establish the standard care of asthma, choices in the treatment of fatal asthma attacks remain of clinical significance. Especially, in a severe asthma attack, despite the application of conventional medical treatment, respiratory management is critical. Even though non-invasive ventilation (NIV) has been shown to be effective in a wide variety of clinical settings, reports of NIV in asthmatic patients are scarce. According to a few prospective clinical trials reporting promising results in favour of the use of NIV in a severe asthma attack, a trial of NIV prior to invasive mechanical ventilation seems acceptable and may benefit patients by decreasing the need for intubation and by supporting pharmaceutical treatments. Although selecting the appropriate patients for NIV use is a key factor in successful NIV application, how to distinguish such patients is quite controversial. Larger high quality clinical trails are urgently required to confirm the benefits of NIV to patients with severe asthma attack. In this article, we focus on the body of evidence supporting the use of NIV in asthma attacks and discuss its advantages as well its problems.

  4. Neonatal size in term children is associated with asthma at age 7, but not with atopic dermatitis or allergic sensitization

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    Sevelsted, A; Bisgaard, H

    2012-01-01

    We hypothesized that anthropometrics in the newborn is associated with development of asthma later in life.......We hypothesized that anthropometrics in the newborn is associated with development of asthma later in life....

  5. Cannabis-Associated Asthma and Allergies.

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    Chatkin, J M; Zani-Silva, L; Ferreira, I; Zamel, N

    2017-09-18

    Inhalation of cannabis smoke is its most common use and the pulmonary complications of its use may be the single most common form of drug-induced pulmonary disease worldwide. However, the role of cannabis consumption in asthma patients and allergic clinical situations still remains controversial. To review the evidence of asthma and allergic diseases associated with the use of marijuana, we conducted a search of English, Spanish, and Portuguese medical using the search terms asthma, allergy, marijuana, marihuana, and cannabis. Entries made between January 1970 and March 2017 were retrieved. Several papers have shown the relationship between marijuana use and increase in asthma and other allergic diseases symptoms, as well as the increased frequency of medical visits. This narrative review emphasizes the importance to consider cannabis as a precipitating factor for acute asthma and allergic attacks in clinical practice. Although smoking of marijuana may cause respiratory symptoms, there is a need for more studies to elucidate many aspects in allergic asthma patients, especially considering the long-term use of the drug. These patients should avoid using marijuana and be oriented about individual health risks, possible dangers of second-hand smoke exposure, underage use, safe storage, and the over smoking of marijuana.

  6. Omalizumab for pediatric asthma.

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    Townley, Robert G; Agrawal, Swati; Sapkota, Kiran

    2010-11-01

    Omalizumab is of proven efficacy in the treatment of severe allergic bronchial asthma and works through inhibiting the activity of IgE and the allergic immune mechanism IgE mediates. It has been demonstrated to be efficacious in children with asthma but is not approved by the FDA for use in children below 12 years of age. Omalizumab is a 95% humanized monoclonal antibody that binds to circulating IgE at the same site on the Fc domain as the high-affinity IgE receptor, FcϵRI. This blocks the interaction between IgE and mast cells and basophils, thereby preventing the release of inflammatory mediators that cause allergic signs and symptoms. From the review of the literatures and statements from the FDA, Genentec and Novartis, the reader will gain a better appreciation of the value of omalizumab in treatment of severe asthma and the current status of its reported side effects. Omalizumab is of proven efficacy in adults and children with severe asthma and allows a markedly reduced dependence on oral and inhaled corticosteroids and decreased hospitalizations. A potential mechanism of omalizumab's effect on thrombus formation and cardiovascular effect is postulated.

  7. Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

    Science.gov (United States)

    de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

    2017-06-24

    Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10 5 human AD-MSCs, or EVs (released by 10 5  AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3 + CD4 + T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3 + CD4 + T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3 + CD4 + T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different

  8. Associations between self-rated health, sickness behaviour and inflammatory markers in primary care patients with allergic asthma: a longitudinal study.

    Science.gov (United States)

    Lodin, Karin; Lekander, Mats; Syk, Jörgen; Alving, Kjell; Andreasson, Anna

    2017-12-18

    Allergic asthma is a chronic inflammatory disorder associated with elevated levels of immunoglobulin E (IgE), serum eosinophilic cationic protein (S-ECP), plasma eosinophil-derived neurotoxin (P-EDN) and fraction of exhaled nitric oxide (F E NO). Poor self-rated health and sickness behaviour has repeatedly been associated with inflammatory markers, but the nature of this relationship in chronic inflammatory disease is not known. Likewise, such findings largely rely on cross-sectional investigations. Self-rated health (How would you rate your general state of health?), sickness behaviour (mean rating of satisfaction with energy, sleep, fitness, appetite and memory), IgE, S-ECP, P-EDN, and F E NO were assessed in 181 non-smoking primary care patients with asthma in a 1-year longitudinal study. Associations between repeated measurements were calculated using mixed regression models and Spearman's correlations for change scores. Poor self-rated health was associated with high levels of seasonal IgE (p = 0.05) and food IgE (p = 0.04), but not total IgE or inflammatory markers. An increase over 1 year in perennial IgE was associated with a worsening of self-rated health (ρ = 0.16, p = 0.04). Poor self-rated health was associated with more pronounced sickness behaviour (p sickness behaviour was associated with a worsening of self-rated health over time (ρ = 0.21, p = 0.007). The study corroborates the importance of sickness behaviour as a determinant of self-rated health by showing that these factors co-vary over a 1-year period in a group of patients with allergic asthma. The importance of specific IgE for perceived health in primary care patients with mild to moderate asthma needs further investigation.

  9. Beneficial Effects of Treatment With Anti-IgE Antibodies (Omalizumab) in a Patient With Severe Asthma and Negative Skin-Prick Test Results

    NARCIS (Netherlands)

    van den Berge, Maarten; Pauw, Ronald G.; de Monchy, Jan G. R.; van Minnen, Cees A.; Postma, Dirkje S.; Kerstjens, Huib A. M.

    It is now well recognized that treatment with anti-IgE antibodies like omalizumab is a valuable option in patients with allergic asthma who remain symptomatic despite optimal treatment. To our knowledge, treatment with omalizumab in patients with nonallergic asthma has not been reported. We present

  10. Cow's milk allergic children - Can component resolved diagnostics predict duration and severity?

    DEFF Research Database (Denmark)

    Petersen, Thomas Houmann; Mortz, Charlotte Gotthard; Bindslev-Jensen, Carsten

    2018-01-01

    BACKGROUND: Cow's Milk Allergy (CMA) affects 2% of all children. This study investigates CRD to cow's milk proteins in children suspected for CMA, by correlating the level of CRD with outcome of the oral challenge. Furthermore, we evaluate the ability of serial CRD measurements to distinguish....... Furthermore, a correlation between s-IgE level to cow's milk and Casein and the severity of the allergic reaction elicited by food challenges was found. CONCLUSION: Oral food challenge cannot be replaced by s-IgE to whole milk protein or milk components nor SPT in the diagnosis of CMA, however high levels...... children with persistent CMA from children developing tolerance. METHODS: We included data from 78 children referred to the Allergy Centre during a 13 years period. Results from oral food challenges including threshold, severity and sensitization data (IgE antibodies to whole milk protein, IgE components...

  11. The allergic scholar

    African Journals Online (AJOL)

    as allergic rhinitis and asthma, have increased in prevalence, particularly in industrialised .... within the alveolar macrophages, eosinophils, mast cells, platelets, basophils and ..... world allergy organization position statement. World Allergy ...

  12. Calcium sensors as new therapeutic targets for asthma

    NARCIS (Netherlands)

    Broeke, R. (Robert) ten

    2002-01-01

    In this thesis, the effects of the two calcium -like peptides CALP1 and CALP2 on several cell types involved in asthma are examined. Furthermore, we tested the effects of these peptides in a guinea pig model for allergic asthma. Calcium is a key secondary messenger, whose function is tightly

  13. Gas cooking, kitchen ventilation, and asthma, allergic symptoms and sensitization in young children - the PIAMA study

    NARCIS (Netherlands)

    Willers, SM; Brunekreef, B; Oldenwening, M; Smit, HA; Kerkhof, M; Gerritsen, J; De Jongste, JC; De Vries, H.

    Background: Several studies reported inconsistent associations between using gas for cooking and respiratory symptoms or lung function in children. Kitchen ventilation characteristics may modify the relationship between gas cooking and respiratory health. The aim of this study was to investigate the

  14. Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

    Science.gov (United States)

    Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

    2017-04-01

    To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. February 2015 pulmonary case of the month: severe asthma

    Directory of Open Access Journals (Sweden)

    Uppalapu S

    2015-02-01

    Full Text Available No abstract available. Article truncated at 150 words. History of present illness: A 50-year-old African-American woman with a history of asthma presented to the emergency department with a chief complaint of shortness of breath for 2 weeks. She reported some chest tightness, wheezing and dry cough. She denied fever, chills, myalgias or arthralgias at the time of admission. PMH, SH and FH: In addition to asthma, she has a past medical history of type 2 diabetes mellitus, hypertension, and multiple sclerosis. She admitted to social smoking but states she quit 6 to 7 months ago. She denies alcohol, recreational drug use, or a family history of early coronary artery disease, strokes or cancers. Medications: montelukast 10 mg daily; salmeterol/fluticasone 250/50 inhaled twice a day; albuterol inhaler as needed for shortness of breath; metformin 500 mg bid; dimethyl fumarate 240 mg bid; omega 3 fish oil; calcium carbonate 600 mg daily; naproxen 500 mg bid; lisinopril 10 mg daily ...

  16. A new era of targeting the ancient gatekeepers of the immune system: toll-like agonists in the treatment of allergic rhinitis and asthma.

    Science.gov (United States)

    Aryan, Zahra; Holgate, Stephen T; Radzioch, Danuta; Rezaei, Nima

    2014-01-01

    Toll-like receptors (TLR) belong to a large family of pattern recognition receptors known as the ancient 'gatekeepers' of the immune system. TLRs are located at the first line of defense against invading pathogens as well as aeroallergens, making them interesting targets to modulate the natural history of respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or prophylactic preparations useful for asthma/allergic rhinitis (AR) patients. MPL® (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9 agonist, show strong immunogenicity effects that make them appropriate adjuvants for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific allergen immunotherapy, currently the only available 'curative' treatment for respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so far reported with such compounds targeting TLRs, with the most common adverse effects being transient and local irritation (e.g. redness, swelling and pruritus). Many other compounds that target TLRs have been found to suppress airway inflammation, eosinophilia and airway hyper-responsiveness in various animal models of allergic inflammation. Indeed, in the future a wide variability of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are likely to emerge. © 2014 S. Karger AG, Basel.

  17. Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their immunoregulatory capacity and exerts antiallergic effects on Th2-mediated allergic asthma in mice.

    Science.gov (United States)

    Lee, Chen-Chen; Lin, Chu-Lun; Leu, Sy-Jye; Lee, Yueh-Lun

    2018-02-01

    Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation. Furthermore, adoptive transfer of OVA-stimulated DLL1-DCs into asthmatic mice alleviated the cardinal features of allergic asthma, including immunoglobulin E (IgE) production, airway hyperresponsiveness (AHR), airway inflammation, and production of Th2-type cytokines. Notably, enhanced levels of the Th1-biased IgG 2a response and interferon (IFN)-γ production were observed in these mice. Taken together, these data indicate that DLL1-DCs promoted Th1 cell development to alter the Th1/Th2 ratio and ameliorate Th2-mediated allergic asthma in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The effect of long-term administered CRAC channels blocker on the functions of respiratory epithelium in guinea pig allergic asthma model.

    Science.gov (United States)

    Sutovska, Martina; Kocmalova, Michaela; Joskova, Marta; Adamkov, Marian; Franova, Sona

    2015-04-01

    Previously, therapeutic potency of CRAC channels blocker was evidenced as a significant decrease in airway smooth muscle hyperreactivity, antitussive and anti-inflammatory effects. The major role of the respiratory epithelium in asthma pathogenesis was highlighted only recently and CRAC channels were proposed as the most significant route of Ca2+ entry into epithelial cells. The aim of the study was to analyse the impact of long-term administered CRAC channels blocker on airway epithelium, e.g. cytokine production and ciliary beat frequency (CBF) using an animal model of allergic asthma. Ovalbumin-induced allergic airway inflammation of guinea pigs was followed by long-term (14 days lasted) therapy by CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA). The influence of long-term therapy on cytokines (IL-4, IL-5 and IL-13) in BALF and in plasma, immunohistochemical staining of pulmonary tissue (c-Fos positivity) and CBF in vitro were used for analysis. Decrease in cytokine levels and in c-Fos positivity confirmed an anti-inflammatory effect of long-term administered FPCA. Cytokine levels in BALF and distribution of c-Fos positivity suggested that FPCA was a more potent inhibitor of respiratory epithelium secretory functions than budesonide. FPCA and budesonide reduced CBF only insignificantly. All findings supported CRAC channels as promising target in the new strategy of antiasthmatic treatment.

  19. Allergies, asthma, and pollen

    Science.gov (United States)

    Reactive airway - pollen; Bronchial asthma - pollen; Triggers - pollen; Allergic rhinitis - pollen ... Things that make allergies or asthma worse are called triggers. It is important to know your triggers because avoiding them is your first step toward feeling better. ...

  20. Fenótipos clínicos de asma grave Clinical phenotypes of severe asthma

    Directory of Open Access Journals (Sweden)

    Roseliane de Souza Araújo Alves

    2008-09-01

    specialized outpatient clinic. A systematic protocol for patient evaluation and follow-up was applied. Treatment compliance and control of the disease at the end of follow-up were defined by clinical and functional data. Patients who did not meet asthma control criteria after six months despite compliance with treatment and correct use of medication were characterized as treatment-resistant. Phenotypes were determined by factorial analysis and compared using various tests. RESULTS: At the end of follow-up, 88 patients were considered treatment compliant and 23 were considered noncompliant. Factorial analysis of the compliant patients identified four phenotypes: phenotype 1 (28 patients comprised patients who were treatment-resistant, more often presenting nocturnal symptoms and exacerbations, as well as more often using rescue bronchodilators; phenotype 2 (48 patients comprised patients with persistent airflow limitation, lower ratios of forced expiratory volume in one second/forced vital capacity at baseline, more advanced age and longer duration of symptoms; phenotype 3 (42 patients comprised patients with allergic rhinosinusitis who were nonsmokers and presented predominantly reversible airflow obstruction; and phenotype 4 (15 patients comprised cases with a history of aspirin intolerance to acetylsalicylic acid associated with near-fatal asthma. Conclusions: A significant number of patients with severe asthma are noncompliant with treatment. Although many patients with severe asthma have persistent airflow obstruction, the most relevant clinical phenotype comprises patients who are resistant to the typical treatment.

  1. Advances in asthma 2015: Across the lifespan.

    Science.gov (United States)

    Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

    2016-08-01

    In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Prevalence, severity and determinations of asthma in Danish five-year-olds

    DEFF Research Database (Denmark)

    Hermann, Christian; De Fine Olivarius, Niels; Høst, Arne

    2006-01-01

    regarding respiratory symptoms and our own questions on sociodemography and tobacco exposure. RESULTS: "Wheeze ever" was reported in 38.3%, "doctor-diagnosed asthma ever" in 10.5%, "childhood bronchitis ever" in 30.0%, "current wheeze" (3 episodes) in 3.......9% of the children. Current wheeze was associated with male gender (OR 1.63, 95% CI 1.35-1.96), low parental post-primary education (OR 1.29, 95% CI 1.02-1.63 for or =3 y) and current maternal smoking (OR 1.69, 95% CI 1.39-2.04). "Severe current wheeze" was recognized as asthma in six and childhood......BACKGROUND: The prevalence of asthma and wheeze is increasing. AIM: To study the annual and cumulative prevalence of asthma and wheeze in 5-y-old Danish children. METHODS: We obtained data on 3052 (82.0% of eligible) Danish children by a postal parental questionnaire including ISAAC questions...

  3. Comparing high altitude treatment with current best care in Dutch children with moderate to severe atopic dermatitis (and asthma): Study protocol for a pragmatic randomized controlled trial (DAVOS trial)

    NARCIS (Netherlands)

    K.B. Fieten (Karin); W.T. Zijlstra (Wieneke); H. van Os-Medendorp (Harmieke); Y. Meijer (Yolanda); M.U. Venema (Monica); L. Rijssenbeek-Nouwens (Lous); M.P. l' Hoir (Monique); C.A. Bruijnzeel-Koomen; S.G.M.A. Pasmans (Suzanne)

    2014-01-01

    textabstractBackground: About 10 to 20% of children in West European countries have atopic dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome also consists of allergic asthma, allergic rhinitis and food allergy. Treatment approaches for atopic dermatitis and asthma

  4. Comparing high altitude treatment with current best care in Dutch children with moderate to severe atopic dermatitis (and asthma): Study protocol for a pragmatic randomized controlled trial (DAVOS trial)

    NARCIS (Netherlands)

    Fieten, K.B.; Zijlstra, W.T.; Os-Medendorp, H. van; Meijer, Y.; Venema, M.U.; Rijssenbeek-Nouwens, L.; Hoir, M.P. l; Bruijnzeel-Koomen, C.A.; Pasmans, S.G.M.A.

    2014-01-01

    Background: About 10 to 20% of children in West European countries have atopic dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome also consists of allergic asthma, allergic rhinitis and food allergy. Treatment approaches for atopic dermatitis and asthma include

  5. Simvastatin Inhibits Goblet Cell Hyperplasia and Lung Arginase in a Mouse Model of Allergic Asthma: A Novel Treatment for Airway Remodeling?

    Science.gov (United States)

    Zeki, Amir A.; Bratt, Jennifer M.; Rabowsky, Michelle; Last, Jerold A.; Kenyon, Nicholas J.

    2010-01-01

    Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function, and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. The statins are cholesterol-lowering drugs that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting step of cholesterol biosynthesis in the mevalonate pathway. These drugs have been associated with improved respiratory health and ongoing clinical trials are testing their therapeutic potential in asthma. We hypothesized that simvastatin treatment of ovalbumin-exposed mice would attenuate early features of airway remodeling, by a mevalonate-dependent mechanism. BALB/c mice were initially sensitized to ovalbumin, and then exposed to 1% ovalbumin aerosol for 2 weeks after sensitization for a total of six exposures. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) were injected intraperitoneally before each ovalbumin exposure. Treatment with simvastatin attenuated goblet cell hyperplasia, arginase-1 protein expression, and total arginase enzyme activity, but did not alter airway hydroxyproline content or transforming growth factor-β1. Inhibition of goblet cell hyperplasia by simvastatin was mevalonate-dependent. No appreciable changes to airway smooth muscle cells were observed in any of the control or treatment groups. In conclusion, in an acute mouse model of allergic asthma, simvastatin inhibited early hallmarks of airway remodeling, indicators that can lead to airway thickening and fibrosis. Statins are potentially novel treatments for airway remodeling in asthma. Further studies utilizing sub-chronic or chronic allergen exposure models are needed to extend these initial findings. PMID:21078495

  6. Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.

    Science.gov (United States)

    Macchiaverni, P; Rekima, A; Turfkruyer, M; Mascarell, L; Airouche, S; Moingeon, P; Adel-Patient, K; Condino-Neto, A; Annesi-Maesano, I; Prescott, S L; Tulic, M K; Verhasselt, V

    2014-03-01

    There is an urgent need to identify environmental risk and protective factors in early life for the prevention of allergy. Our study demonstrates the presence of respiratory allergen from house dust mite, Der p 1, in human breast milk. Der p 1 in milk is immunoreactive, present in similar amounts as dietary egg antigen, and can be found in breast milk from diverse regions of the world. In a mouse model of asthma, oral exposure to Der p through breast milk strongly promotes sensitization rather than protect the progeny as we reported with egg antigen. These data highlight that antigen administration to the neonate through the oral route may contribute to child allergic sensitization and have important implications for the design of studies assessing early oral antigen exposure for allergic disease prevention. The up-to-now unknown worldwide presence of respiratory allergen in maternal milk allows new interpretation and design of environmental control epidemiological studies for allergic disease prevention. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

    Science.gov (United States)

    Green, Benjamin J; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B; Kehagia, Valia; Lau, Laurie; Carroll, Mary P; Bruce, Kenneth D; Howarth, Peter H

    2014-01-01

    Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that

  8. Patient and physician evaluation of the severity of acute asthma exacerbations

    Directory of Open Access Journals (Sweden)

    Atta J.A.

    2004-01-01

    Full Text Available We studied the ability of patients not experienced in the use of peak expiratory flow meters to assess the severity of their asthma exacerbations and compared it to the assessment of experienced clinicians. We also evaluated which data of physical examination and medical history are used by physicians to subjectively evaluate the severity of asthma attacks. Fifty-seven adult patients (15 men and 42 women, with a mean (± SD age of 37.3 ± 14.5 years and 24.0 ± 17.9 years of asthma symptoms with asthma exacerbations were evaluated in a University Hospital Emergency Department. Patients and physicians independently evaluated the severity of the asthma attack using a linear scale. Patient score, physician score and forced expiratory volume at the first second (FEV1 were correlated with history and physical examination variables, and were also considered as dependent variables in multiple linear regression models. FEV1 correlated significantly with the physician score (rho = 0.42, P = 0.001, but not with patient score (rho = 0.03; P = 0.77. Use of neck accessory muscles, expiratory time and wheezing intensity were the explanatory variables in the FEV1 regression model and were also present in the physician score model. We conclude that physicians evaluate asthma exacerbation severity better than patients and that physician's scoring of asthma severity correlated significantly with objective measures of airway obstruction (FEV1. Some variables (the use of neck accessory muscles, expiratory time and wheezing intensity persisted as explanatory variables in physician score and FEV1 regression models, and should be emphasized in medical schools and emergency settings.

  9. Patient and physician evaluation of the severity of acute asthma exacerbations

    Directory of Open Access Journals (Sweden)

    J.A. Atta

    2004-09-01

    Full Text Available We studied the ability of patients not experienced in the use of peak expiratory flow meters to assess the severity of their asthma exacerbations and compared it to the assessment of experienced clinicians. We also evaluated which data of physical examination and medical history are used by physicians to subjectively evaluate the severity of asthma attacks. Fifty-seven adult patients (15 men and 42 women, with a mean (± SD age of 37.3 ± 14.5 years and 24.0 ± 17.9 years of asthma symptoms with asthma exacerbations were evaluated in a University Hospital Emergency Department. Patients and physicians independently evaluated the severity of the asthma attack using a linear scale. Patient score, physician score and forced expiratory volume at the first second (FEV1 were correlated with history and physical examination variables, and were also considered as dependent variables in multiple linear regression models. FEV1 correlated significantly with the physician score (rho = 0.42, P = 0.001, but not with patient score (rho = 0.03; P = 0.77. Use of neck accessory muscles, expiratory time and wheezing intensity were the explanatory variables in the FEV1 regression model and were also present in the physician score model. We conclude that physicians evaluate asthma exacerbation severity better than patients and that physician's scoring of asthma severity correlated significantly with objective measures of airway obstruction (FEV1. Some variables (the use of neck accessory muscles, expiratory time and wheezing intensity persisted as explanatory variables in physician score and FEV1 regression models, and should be emphasized in medical schools and emergency settings.

  10. The effectiveness of the treatment of severe exercise-induced asthma in schoolchildren

    Directory of Open Access Journals (Sweden)

    M.N. Garas

    2017-03-01

    Full Text Available Background. Bronchial asthma is one of the most common chronic multifactorial diseases of the lungs. At least 10–12 % of patients with bronchial asthma are suffering from a severe form of the disease. One aspect of inadequate severe asthma control is its phenotypic heterogeneity, interest of experts increases to the problem of exercise-induced asthma. The purpose of the study was to increase efficiency of treatment for severe exercise-induced asthma in schoolchildren based on the analysis of the attack dynamics and to achieve disease control according to main inflammatometric and spirometric indices. Materials and methods. We examined 46 children with severe persistent bronchial asthma, in particular, 15 schoolchildren suffering from severe exercise-induced asthma, the second clinical group (comparison one consisted of 31 children suffering from severe type of the disease, with no signs of exercise-induced bronchoconstriction. Basic therapy effectiveness was determined prospectively by assessing the disease control using AST-test with an interval of 3 months. The severity of bronchial obstruction syndrome in patients on admission to hospital during exacerbation was assessed by score scale. Airway hyperresponsiveness was evaluated according to the results of bronchoprovocation with histamine. Results. Children of I clinical group had more significant manifestations of bronchial obstruction during the week of inpatient treatment than the comparison group of patients, including significantly more severe manifestations of bronchial obstruction were verified on 1st and 7th day of hospitalization. Due to the analysis of basic therapy effectiveness, only a quarter of I clinical group patients and a larger part of schoolchildren in comparison group achieved the partial control after a 3-month course of anti-inflammatory treatment. Eosinophilic inflammation was observed in most children with severe exercise-induced asthma (60.1 % and in 47.2 % of

  11. Advances in pediatric asthma and atopic dermatitis.

    Science.gov (United States)

    Foroughi, Shabnam; Thyagarajan, Ananth; Stone, Kelly D

    2005-10-01

    Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.

  12. Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

    Science.gov (United States)

    Ono, Emiko; Dutile, Stefanie; Kazani, Shamsah; Wechsler, Michael E.; Yang, Jun; Hammock, Bruce D.; Douda, David Nobuhiro; Tabet, Yacine; Khaddaj-Mallat, Rayan; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric; Martin, Richard; Sutherland, E. Rand; Castro, Mario; N. Jarjour, Nizar; Israel, Elliot

    2014-01-01

    Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. Objectives: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. Methods: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte–platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. Measurements and Main Results: 8-Isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r = −0.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte–platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor–induced increases in leukocyte–platelet aggregates (70.8% inhibition [LXA4 100 nM], 78.3% inhibition [15-epi-LXA4 100 nM]) and 15-epi-LXA4 markedly inhibited tumor necrosis factor-α–induced increases in bronchial contraction. Conclusions: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach

  13. Bee moth (Galleria mellonella) allergic reactions are caused by several thermolabile antigens.

    Science.gov (United States)

    Villalta, D; Martelli, P; Mistrello, G; Roncarolo, D; Zanoni, D

    2004-09-01

    Exposure and contact with bee moth (Galleria mellonella) larvae (Gm) can cause an allergic reaction both in anglers and breeders. We described the case of an amateur fisherman who experienced an allergic reaction using Gm but not using heat-treated Gm (h-Gm) (mummies). The aim of this study was to demonstrate by immunoblotting and radioallergosorbent test (RAST)-inhibition experiments the loss of allergenic epitopes in h-Gm extracts. Galleria mellonella larvae and h-Gm were homogenized and extracted at 10% (w/v) in 0.5 M phosphate-buffered saline, pH 7.4 containing 0.5% NaN(3) for 16 h at 4 degrees C. Gm and h-Gm extracts were electrophoresed in a 10% polyacrylamide precast Nupage Bis-Tris gel at 180 mA for 1 h and the resolved proteins stained with 0.1% Coomassie brilliant blue and the molecular weight calculated. For the immunoblotting detection of allergenic components the resolved extracts were transferred onto a nitrocellulose membrane and incubated with the patient's serum. Bound specific-IgE was detected by peroxidase-conjugated anti-human IgE. RAST inhibition experiments were performed according to the Ceska method. The protein profile of Gm and h-Gm extracts resulted markedly different in number, intensity and the position of bands, indicating that heat-treatment modifies the chemical-physical characteristics of the protein contents. The Gm extract showed a strong-coloured band at 73 kDa and more than 20 components ranging from 12 to 133 kDa; h-Gm showed two main band at 77 and 38 kDa and about 15 faint bands between 20 and 133 kDa apparently without any correspondence to the bands present in the Gm extract. Immunoblotting with the patient's serum demonstrated several bands of reactivity with the Gm extract ranging from 20 to 100 kDa and no recognizable bands, but only a diffuse smear with h-Gm. When used in a RAST inhibition experiment the h-Gm extract demonstrated an inability to compete with the Gm one for the binding to patient's IgE serum. The h

  14. Outcome of short-term hospitalization for children with severe asthma.

    Science.gov (United States)

    Weinstein, A G; Faust, D S; McKee, L; Padman, R

    1992-07-01

    This study presents results of a family-centered, short-term residential program in which medical, behavioral, and treatment assessments were provided to the child with severe asthma and the family. After a median stay of 15 days, forty-four consecutively admitted children with severe asthma achieved a 93% reduction in hospital days (median, 7 hospital days for the year before treatment versus median 0 hospital days per patient per year at 20 1/2-month follow-up; p less than 0.001) and an 81% reduction in emergency care (median, 4 visits for the year previously versus median, 0.4 visits per patient per year at follow-up; p less than 0.01). There was also a significant reduction in corticosteroid bursts and improvement in FEV1. Unique to this program was mandatory family participation focusing on the child's and family's adaptation to severe asthma and development of family-specific interventions to promote compliance with the treatment regimen. Child and family functioning was assessed at admission and follow-up. Hospital use at follow-up was greater for children from dysfunctional families. Families demonstrating difficulties in disciplining the child with asthma required more hospital days both before admission and at follow-up. Short-term hospitalization for children with severe asthma is associated with significant improvement in pulmonary morbidity when the family of the child is included in assessment and treatment.

  15. Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children.

    Science.gov (United States)

    Jochmann, Anja; Artusio, Luca; Jamalzadeh, Angela; Nagakumar, Prasad; Delgado-Eckert, Edgar; Saglani, Sejal; Bush, Andrew; Frey, Urs; Fleming, Louise J

    2017-12-01

    International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma.Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period.93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21-99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups.Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic. Copyright ©ERS 2017.

  16. Omalizumab: Clinical Use for the Management of Asthma

    OpenAIRE

    Thomson, Neil C.; Chaudhuri, Rekha

    2012-01-01

    Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β 2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduce...

  17. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

  18. Transfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - EIP on AHA Twinning Reference Site (GARD research demonstration project).

    Science.gov (United States)

    Bousquet, J; Agache, I; Aliberti, M R; Angles, R; Annesi-Maesano, I; Anto, J M; Arnavielhe, S; Asayag, E; Bacci, E; Bedbrook, A; Bachert, C; Baroni, I; Barreto, B A; Bedolla-Barajas, M; Bergmann, K C; Bertorello, L; Bewick, M; Bieber, T; Birov, S; Bindslev-Jensen, C; Blua, A; Bochenska Marciniak, M; Bogus-Buczynska, I; Bosnic-Anticevich, S; Bosse, I; Bourret, R; Bucca, C; Buonaiuto, R; Burguete Cabanas, M T; Caillaud, D; Caimmi, D P; Caiazza, D; Camargos, P; Canfora, G; Cardona, V; Carriazo, A M; Cartier, C; Castellano, G; Chavannes, N H; Cecci, L; Ciaravolo, M M; Cingi, C; Ciceran, A; Colas, L; Colgan, E; Coll, J; Conforti, D; Correia de Sousa, J; Cortés-Grimaldo, R M; Corti, F; Costa, E; Courbis, A L; Cousein, E; Cruz, A A; Custovic, A; Cvetkovski, B; Dario, C; da Silva, J; Dauvilliers, Y; De Blay, F; Dedeu, T; De Feo, G; De Martino, B; Demoly, P; De Vries, G; Di Capua Ercolano, S; Di Carluccio, N; Doulapsi, M; Dray, G; Dubakiene, R; Eller, E; Emuzyte, R; Espinoza-Contreras, J G; Estrada-Cardona, A; Farrell, J; Farsi, A; Ferrero, J; Fokkens, W J; Fonseca, J; Fontaine, J F; Forti, S; Gálvez-Romero, J L; García-Cobas, C I; Garcia Cruz, M H; Gemicioğlu, B; Gerth van Wijk, R; Guidacci, M; Gómez-Vera, J; Guldemond, N A; Gutter, Z; Haahtela, T; Hajjam, J; Hellings, P W; Hernández-Velázquez, L; Illario, M; Ivancevich, J C; Jares, E; Joos, G; Just, J; Kalayci, O; Kalyoncu, A F; Karjalainen, J; Keil, T; Khaltaev, N; Klimek, L; Kritikos, V; Kull, I; Kuna, P; Kvedariene, V; Kolek, V; Krzych-Fałta, E; Kupczyk, M; Lacwik, P; La Grutta, S; Larenas-Linnemann, D; Laune, D; Lauri, D; Lavrut, J; Lessa, M; Levato, G; Lewis, L; Lieten, I; Lipiec, A; Louis, R; Luna-Pech, J A; Magnan, A; Malva, J; Maspero, J F; Matta-Campos, J J; Mayora, O; Medina-Ávalos, M A; Melén, E; Menditto, E; Millot-Keurinck, J; Moda, G; Morais-Almeida, M; Mösges, R; Mota-Pinto, A; Mullol, J; Muraro, A; Murray, R; Noguès, M; Nalin, M; Napoli, L; Neffen, H; O'Hehir, R E; Onorato, G L; Palkonen, S; Papadopoulos, N G; Passalacqua, G; Pépin, J L; Pereira, A M; Persico, M; Pfaar, O; Pozzi, A C; Prokopakis, E; Pugin, B; Raciborski, F; Rimmer, J; Rizzo, J A; Robalo-Cordeiro, C; Rodríguez-González, M; Rolla, G; Roller-Wirnsberger, R E; Romano, A; Romano, M; Romano, M R; Salimäki, J; Samolinski, B; Serpa, F S; Shamai, S; Sierra, M; Sova, M; Sorlini, M; Stellato, C; Stelmach, R; Strandberg, T; Stroetmann, V; Stukas, R; Szylling, A; Tan, R; Tibaldi, V; Todo-Bom, A; Toppila-Salmi, S; Tomazic, P; Trama, U; Triggiani, M; Valero, A; Valovirta, E; Valiulis, A; van Eerd, M; Vasankari, T; Vatrella, A; Ventura, M T; Verissimo, M T; Viart, F; Williams, S; Wagenmann, M; Wanscher, C; Westman, M; Wickman, M; Young, I; Yorgancioglu, A; Zernotti, E; Zuberbier, T; Zurkuhlen, A; De Oliviera, B; Senn, A

    2018-01-01

    The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  19. Prevalence of rhinitis allergic in populations of several states of Mexico

    Directory of Open Access Journals (Sweden)

    Eleazar Mancilla-Hernández

    2015-07-01

    Conclusions: With the use of the questionnaire diagnosis of allergic rhinitis for epidemiological studies in the four cities in four different states, we found a prevalence of allergic rhinitis of 15% in ≥13 yearpopulation and 13% in ≤12 year-old children.

  20. Successful Use of Extracorporeal Life Support after Double Traumatic Tracheobronchial Injury in a Patient with Severe Acute Asthma

    Directory of Open Access Journals (Sweden)

    Xavier Valette

    2011-01-01

    Full Text Available We report the case of an asthmatic patient with blunt trachea and left main bronchus injuries who developed acute severe asthma after surgical repair. Despite medical treatment and ventilatory support, asthma persisted with high airway pressures and severe respiratory acidosis. We proposed venovenous extracorporeal life support for CO2 removal which allowed arterial blood gas normalization and airway pressures decrease. Extracorporeal life support was removed on day five after medical treatment of acute severe asthma. So we report the successful use of extracorporeal life support for operated double blunt tracheobronchial injury with acute severe asthma.