Natural History Of Asthma Research Articles

Asthma exacerbations and lung function in patients with severe or difficult-to-treat asthma

Asthma exacerbations and lung function in patients with severe or difficult-to-treat asthma

Long‐term inhaled corticosteroid treatment and severe asthma in children ‐ the impact on body height and weight

Background Chronic conditions such as asthma are usually stigmatized as one of the reasons for short stature. A widespread belief also is that prolonged long-term treatment with corticosteroids will lead to elevated body weight and also could lead to short stature. Therefore we evaluated the height and weight status in the children admitted in the hospital for asthma attack regarding the asthma severity, the natural history of asthma and inhaled corticosteroid (ICS) treatment period.

Serum Levels Evaluation of Heat Shock Protein70 during Gestation and Fetal Birth Weight in Asthmatic Women of Thi-QAR Province, Iraq

Asthma is a multifactorial inflammatory disease of the upper airways and its one of the most common diseases complicating pregnancy and represents a risk factor for several maternal and perinatal complications. The natural history of asthma is known to change in pregnancy, but very few data are available in the terms of pathomechanism of this change during gestation. Circulating heat shock protein 70 (Hsp70) levels are decreased in healthy pregnancy, which might reflect physiological immunotolerance. The aim of our study was to determine the serum levels of Hsp70 in asthmatic women during gestation. Fifty pregnant women with bronchial asthma and 50 healthy pregnant women matched for maternal and gestational age were involved in this case-control study. Serum Hsp70 levels were measured using the Bioassay ELISA Kit. In asthmatic pregnant women, an increase of serum Hsp70 levels was observed compared to healthy pregnant women (median18- 75 percentile): 0.46 ng/ml versus 0.16 ng/ml p 0.05). A statistically significant negative correlation between maternal age and serum Hsp70 concentrations (p<0.05) and a significant were detected in healthy pregnant women. This study proves an elevation of circulating Hsp70 levels during asthmatic pregnancy compared to healthy pregnant women.

Oral Corticosteroid Use and Health Outcomes in Patients with Severe or Difficult-to-Treat Asthma

There are limited studies in asthma examining the association between oral corticosteroid (OCS) use and health outcomes, including death, with especially few studies examining dose-response effects. Patients aged ≥6 years with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) 3-year, observational study were included (N=4,756). OCS exposure was examined as a dichotomous (yes/no) variable and per 10mg dose increase. Longitudinal health outcomes were assessed semi-annually. Analyses included patients without a given condition at baseline. Multivariable Cox models assessed associations between baseline OCS exposure and risk of new-onset morbidities or death. After adjusting for age, sex, education, race/ethnicity, and asthma control, baseline OCS exposure (yes/no) was associated with an over five-fold increased risk of death (hazard ratio (HR): 5.26, p<0.001). Each 10mg increment in baseline OCS dosage was associated with a HR: 1.40 (p<0.001) increased risk of death. OCS exposure was associated with an increased risk of osteoporotic fractures (HR: 2.26, p=0.005); an association with dose was not observed. An association between OCS exposure and risk of cataracts was borderline significant (HR: 1.46, p=0.069); no association with OCS dose was observed. There were no associations between OCS exposure and new-onset diabetes or new-onset obesity. OCS exposure was associated with an increased risk of death and osteoporotic fractures in this population, with a dose-response effect observed for death. Although we adjusted for potential confounders, the extent to which these associations were due to OCS itself or the requirement for OCS is uncertain.

Impact of Asthma Exacerbations and Asthma Triggers on Asthma-related Quality of Life in Patients with Severe or Difficult-to-Treat Asthma

Few data are available that evaluate the relationship among asthma exacerbations, asthma triggers, and asthma-related quality of life (QoL). To evaluate the impact of asthma exacerbations and asthma triggers on QoL. Patients with severe or difficult-to-treat asthma, ages ≥ 13 years (n = 2679) from the TENOR (The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens) 3-year observational study were included. Exacerbations were defined hierarchically in descending order of severity (hospitalization, emergency department [ED] visit, steroid burst, no exacerbation) by using data from months 6 and 12. The total number (frequency) of exacerbations was assessed. Asthma-related QoL was measured at month 12 by using the Mini-Asthma QoL Questionnaire (Mini-AQLQ); self-reported asthma triggers were collected at baseline and annually. We used 1-way ANOVA to test for differences in Mini-AQLQ domain scores across asthma exacerbation severity, the total number of asthma exacerbations, and the number of asthma triggers. A significant decrease (P < .001) in Mini-AQLQ domain scores was seen with increasing severity of asthma exacerbation (no exacerbation, steroid burst, ED visit, and hospitalization); symptom (5.5, 4.8, 4.3, and 4.2), activity (5.8, 5.2, 4.6, and 4.4), emotional (5.6, 5.0, 4.4, and 4.2), exposure (5.0, 4.5, 4.0, and 3.9); and overall (5.5, 4.9, 4.3, and 4.1). Increasing exacerbation frequency and the number of baseline asthma triggers also were associated with significant decreases in Mini-AQLQ domain scores. An increasing number of asthma triggers were associated with an increase in severity and frequency of exacerbations. Avoidance of asthma triggers may reduce exacerbation rates and improve asthma-related QoL in patients with severe or difficult-to-treat asthma. Interventional studies are warranted to further explore these outcomes.

Airway remodelling in asthma: role for mechanical forces

Asthma is a chronic airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness and airflow obstruction. Airway structural changes or airway remodelling consist of epithelial injury, goblet cell hyperplasia, subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis. These changes were previously considered as a consequence of chronic airway inflammation. Even though inhaled corticosteroids can suppress airway inflammation, the natural history of asthma is still unaltered after inhaled corticosteroid treatment. As such there is increasing evidence for the role of mechanical forces within the asthmatic airway contributing to airway structural changes.

Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma

Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.

Measuring and imaging small airways dysfunction in asthma

Asthma is a chronic inflammatory disorder of the airways causing typical symptoms, and the diagnosis is supported by evidence of airflow obstruction which is variable, reversible or inducible. However, standard assessment of lung function with spirometry does not measure dysfunction in small airways which are < 2 mm in diameter towards the periphery of the lung. These airways make only a small contribution to airway resistance under normal circumstances. Nevertheless, there is mounting evidence that pathology and dysfunction in these small airways are implicated in the pathogenesis and natural history of asthma. Using forced oscillation and the multibreath nitrogen washout techniques, uneven ventilation (ventilation heterogeneity) due to small airways dysfunction has been shown to be an important marker of asthma disease activity, even in the absence of abnormalities in standard spirometric measurements. Recent advances in imaging research, particularly with hyperpolarised gas magnetic resonance imaging, have also given insights into the significance and dynamic nature of ventilation heterogeneity in asthma. The challenge is to integrate these new physiological and imaging insights to further our understanding of asthma and facilitate potential new treatments.

Advances in pediatric asthma in 2012: Moving toward asthma prevention

Last year's "Advances in pediatric asthma: moving forward" concluded the following: "Now is also the time to utilize information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions in order to maintain control that can lead to disease remission and prevention." This year's summary will focus on recent advances in pediatric asthma on modifying disease activity, preventing asthma exacerbations, managing severe asthma, and risk factors for predicting and managing early asthma, as indicated in Journal of Allergy and Clinical Immunology publications in 2012. Recent reports continue to shed light on methods to improve asthma management through steps to assess disease activity, tools to standardize outcome measures in asthma, genetic markers that predict risk for asthma and appropriate treatment, and interventions that alter the early presentation of asthma to prevent progression. We are well on our way to creating a pathway around wellness in asthma care and also to use new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.

The long-term outcomes of persistent childhood allergic asthma: A cross-sectional study from western Anatolia: Childhood persistent asthma in western Anatolia

BackgroundProspective cohort studies have provided useful knowledge about the natural history of asthma. However, most of the studies are conducted in western countries but the course of the disease and long-term outcomes may differ between countries due to environmental and cultural factors. ObjectiveThe aim of this study is to describe the long-term outcomes of childhood asthma, with data from a follow-up study of at least 10 years, in western Anatolia, Turkey. MethodsFifty-two patients diagnosed with persistent allergic asthma participated in the study. The patient's demographics, findings on admission, age at onset of disease, time of diagnosis, history of other allergic conditions, history of parental asthma and allergic disorders, presence of pharmacotherapy and immunotherapy were obtained from patients’ records. The factors influencing remission at the end of 10 years follow-up were evaluated. ResultsA total of 20 patients (38.5%) were on remission at the end of 10 years. The type of allergen, multi-allergen sensitivity, eosinophilia and elevated serum immunoglobulin E on admission, accompanying allergic disorders and atopy in parents, and allergen immunotherapy did not affect the remission rate (p>0.05). ConclusionChildhood persistent asthma is not a homogeneous clinical entity but high clinical remission rates are obtained in western Anatolia. There is no significant predictor of clinical remission in long term follow-up. Prospective studies should be performed in larger asthmatic populations to obtain further data about the natural course of childhood asthma.

Impact of Inhaled Corticosteroids on the Natural History of Asthma in Children

Asthma is a heterogeneous disorder with a variable course. It begins very early in life and of different phenotypes. Mainstay treatment for asthma is corticosteroids as controller therapy and guidelines recommends the add-on and step-up or step-down strategies. This review will focus on the studies that enhanced our understandings of the effects of inhaled corticosteroids on the natural course of asthma in regard to symptoms control, protective effect on lung function and potential side effects encountered during the treatment. Studies that evaluated approaches on steroid sparing effects and the effect of asthma progression in children are also reviewed.

Assessment of asthma control and asthma exacerbations in the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) observational cohort.

Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients.

Foetal exposure to maternal stressful events increases the risk of having asthma and atopic diseases in childhood

The natural history of asthma and atopic diseases begins in utero. Studies investigating the influence of foetal exposure to maternal stressful life events during pregnancy (SLEP) on asthma and atopic diseases are lacking. To test whether the children of mothers who had experienced SLEP are at an increased risk for asthma, atopic eczema and allergic rhinitis. The association between maternal SLEP (at least one among: divorce, mourning or loss of the job) and the occurrence of asthma and atopic diseases in childhood was studied in a population (n = 3854) of children, aged 3-14 yrs, living in Northern Italy. The parents filled in a standardized questionnaire about the children's health and the events occurred to their mothers during pregnancy. Three hundred and thirty-three (9%) of the mothers experienced SLEP. Their children had a statistically significantly higher lifetime prevalence of wheezing (31.6% vs. 23.1%), asthma (8.9% vs. 5.6%), allergic rhinitis (10.9% vs. 7.3%) and atopic eczema (29.7% vs. 21.1%) than those of mothers without SLEP. After adjusting for potential confounders, the foetal exposure to SLEP was positively associated with wheezing (OR: 1.41, 95% CI: 1.03-1.94), asthma (OR: 1.71, 95% CI: 1.02-2.89), allergic rhinitis (OR: 1.75, 95% CI: 1.08-2.84) and atopic eczema (OR: 1.53, 95% CI: 1.11-2.10). The children of mothers who had experienced SLEP were at a moderately increased risk of having wheezing, asthma, eczema and allergic rhinitis during their childhood. Maternal stress during pregnancy might enhance the expression of asthma and atopic phenotypes in children.

A case of difficult-to-treat eosinophilic asthma controlled with clarithromycin

Difficult-to-treat asthma is a major health problem that has been intensively researched. Patients with difficult-to-treat asthma have the highest incidence of hospitalizations and emergency department visits, [1] Dolan C.M. Fraher K.E. Bleecker E.R. et al. Design and baseline characteristics of the epidemiology and natural history of asthma: Outcomes and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma. Ann Allergy Asthma Immunol. 2004; 92: 32-39 Abstract Full Text PDF PubMed Scopus (267) Google Scholar have the greatest risk of fatal asthma attacks, [2] Tough S.C. Hessel P.A. Ruff M. Green F.H. Mitchell I. Butt J.C. Features that distinguish those who die from asthma from community controls with asthma. J Asthma. 1998; 35: 657-665 Crossref PubMed Scopus (72) Google Scholar and use up to 3 times more resources. [3] Van Ganse E. Laforest L. Pietri G. et al. Persistent asthma: disease control, resource utilisation and direct costs. Eur Respir J. 2002; 20: 260-267 Crossref PubMed Scopus (116) Google Scholar Previous studies of patients using macrolides for 6 to 16 weeks have reported lung function and symptom improvement in asthma patients with evidence of Chlamydia pneumoniae or Mycoplasma pneumoniae infection in the upper or lower airways. [4] Friedlander A.L. Albert R.K. Chronic macrolide therapy in inflammatory airways diseases. Chest. 2010; 138: 1202-1212 Crossref PubMed Scopus (124) Google Scholar Besides antibiotic effects, macrolides have anti-inflammatory and immunomodulating properties. For instance, macrolides regulate the production of the proinflammatory cytokines tumor necrosis factor α and interleukin 8 (IL-8) by decreasing the binding of transcription factors NF-κB and AP-1. [5] Shinkai M. Henke M.O. Rubin B.K. Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action. Pharmacol Ther. 2008; 117: 393-405 Crossref PubMed Scopus (181) Google Scholar Macrolides effectively inhibit IL-8 release and induce apoptosis in eosinophils. 6 Kohyama T. Takizawa H. Kawasaki S. Akiyama N. Sato M. Ito K. Fourteen-member macrolides inhibit interleukin-8 release by human eosinophils from atopic donors. Antimicrob Agents Chemother. 1999; 43: 907-911 PubMed Google Scholar , 7 Adachi T. Motojima S. Hirata A. et al. Eosinophil apoptosis caused by theophylline, glucocorticoids, and macrolides after stimulation with IL-5. J Allergy Clin Immunol. 1996; 98: S207-S215 Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Long-term treatment with macrolides is recommended in a few lung diseases, such as diffuse panbronchiolitis, cystic fibrosis, posttransplantation bronchiolitis obliterans, and chronic obstructive pulmonary disease. 4 Friedlander A.L. Albert R.K. Chronic macrolide therapy in inflammatory airways diseases. Chest. 2010; 138: 1202-1212 Crossref PubMed Scopus (124) Google Scholar , 8 Albert R.K. Connett J. Bailey W.C. et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011; 365: 689-698 Crossref PubMed Scopus (917) Google Scholar Results from a recent randomized controlled trial demonstrated that azithromycin taken for 1 year decreased exacerbations of chronic obstructive pulmonary disease. [8] Albert R.K. Connett J. Bailey W.C. et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011; 365: 689-698 Crossref PubMed Scopus (917) Google Scholar The authors attributed these results to the antibacterial properties of this antibiotic; however, one must assume that the immunomodulatory effects of macrolides played an important role as well. Until now, evidence has been insufficient to support long-term macrolide use in asthma, but it might be beneficial in a subgroup of asthma patients.

Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study

Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n=3489 adults ≥ 18 years of age, n=497 adolescents 13-17 years of age, and n=770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life. We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients. IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.

Dexamethasone and salbutamol stimulate human lung fibroblast proliferation.

BackgroundAsthma is characterized by bronchial hyperreactivity and airway remodeling. Subepithelial fibrosis, a feature of remodeling, is accompanied by activation of fibroblasts to myofibroblasts, with excessive proliferation and increased collagen, extracellular matrix protein, and profibrogenic cytokine production. Mast cells are important in the development of asthma and its fibrotic changes.ObjectiveIn this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids (dexamethasone) and shortacting β2-agonists (salbutamol), on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin.MethodsSubconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs (24 h) 6 activators, and [3H]-Thymidine was added (24 h) to measure their proliferation. IL-6 production in the supernatants of confluent monolayers cultured in the presence of the drugs or forskolin (24 h) was analyzed by enzyme-linked immunosorbent assay.ResultsBoth drugs alone and in the presence of the activators enhanced fibroblast proliferation in a seemingly synergistic way for both fetal and bronchial fibroblasts. Dexamethasone was found to decrease IL-6 production, while salbutamol increased it.ConclusionsThese observations if corroborated by in vivo data may possibly account for the deleterious effect of long-term therapy with β2-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.

Economic burden of impairment in children with severe or difficult-to-treat asthma

The cost associated with asthma impairment in children with severe asthma has not been determined. To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment. Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines' impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed. Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P < .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline. The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness.

Coughing and wheezing but not asthma: delay in diagnosis

Asthma usually appears in childhood. Late onset is less common within the context of the natural history of asthma and should, therefore, alert physicians to the possibility of differential diagnoses such as heart failure, gastroesophageal reflux and other forms of airway obstruction. Here, we report the case of a female patient diagnosed with asthma since childhood who, despite having complied with the treatment prescribed, presented over the years clinical worsening. At the age of 29 years she was diagnosed that a vascular malformation was responsible for the symptoms. The patient was therefore referred for cardiac surgery and presented marked improvement of her symptoms after the procedure.

Dexamethasone and Salbutamol Stimulate Human Lung Fibroblast Proliferation

Background Asthma is characterized by bronchial hyperreactivity and airway remodeling. Subepithelial fibrosis, a feature of remodeling, is accompanied by activation of fibroblasts to myofibroblasts, with excessive proliferation and increased collagen, extracellular matrix protein, and profibrogenic cytokine production. Mast cells are important in the development of asthma and its fibrotic changes.Objective In this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids (dexamethasone) and shortacting β2-agonists (salbutamol), on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin.Methods Subconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs (24 h) 6 activators, and [3H]-Thymidine was added (24 h) to measure their proliferation. IL-6 production in the supernatants of confluent mono-layers cultured in the presence of the drugs or forskolin (24 h) was analyzed by enzyme-linked immunosorbent assay.Results Both drugs alone and in the presence of the activators enhanced fibroblast proliferation in a seemingly synergistic way for both fetal and bronchial fibroblasts. Dexamethasone was found to decrease IL-6 production, while salbutamol increased it.Conclusions These observations if corroborated by in vivo data may possibly account for the deleterious effect of long-term therapy with β2-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.

Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR

In children and adolescents with difficult-to-treat asthma, few data exist characterizing the relationships between basic patient characteristics (e.g., age, sex) and atopic indicators in asthma. These associations were examined in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR), an observational study of a large cohort of patients with severe or difficult-to-treat asthma. To characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and airflow in young patients with severe or difficult-to-treat asthma. A total of 1261 patients from the TENOR study were stratified into four age groups at baseline (6-8, 9-11, 12-14, and 15-17 yr). The objective was to characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and ratio of pre-bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV(1) /FVC) in young patients with severe or difficult-to-treat asthma. The chi-square test for categorical variables and analysis of variance for continuous variables were used to identify significant differences among age groups. Multivariable linear regression was used to evaluate the association between IgE and FEV(1) /FVC. Allergic rhinitis was reported in approximately two-thirds of patients. Up to 25% of patients had atopic dermatitis, which differed across age groups in boys (p < 0.05). Positive allergen skin test rate differed across age groups in boys (p < 0.05). Rates of asthma triggers were higher and differed across age groups in girls (p < 0.05), particularly around menarche (12-14 yr). IgE levels were higher in boys and differed across age groups in boys (p < 0.01) and girls (p < 0.05). IgE was associated with a lower FEV(1) /FVC after adjusting for age and sex (p < 0.01). Severe or difficult-to-treat asthma in children and adolescents is characterized by high frequencies of comorbid allergic diseases, allergen sensitization, and high IgE levels. This burden is amplified by the association of more airflow limitation with higher IgE levels, suggesting the need for allergy evaluations.