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Background: It is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper-responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood., Methods: We searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21-26) and include at least one candidate risk factor., Results: Of the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow-up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non-affected individuals until peak function was attained., Clinical Implications and Future Research: Deficits in lung function growth develop in early childhood, and children with asthma, BHR and early-life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at-risk subjects and provide treatment aimed at preventing long-term sequelae of lung function., (© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Why do only some of patients who are prescribed angiotensin converting enzyme inhibitors (ACE-I) develop cough? The pathogenesis of ACE-I-induced cough remains controversial and requires further studies., Objective: We aim to investigate whether asthma is a contributing cause of ACE-I-induced cough., Methods: Patients attending a cardiology clinic between March 2016 and March 2017 who were diagnosed with ACE-I induced cough were included in this study. ACE-I-induced cough was defined as cough which developed within 4 weeks after initiation of ACE-I therapy and which improved within 4 weeks after discontinuation of the ACE-I. Patients who had received ACE-I treatment for at least 6 months without side effects were included in the study as a control group. Face-to-face questionnaires, pulmonary function tests (PFT) and skin prick tests were applied to all the patients. If there was discordance between asthma history and PFT results, a methacholine bronchial provocation test (BPT) was performed., Results: A total of 43 patients with ACE-I induce cough were compared with 50 controls. Bronchial hyperreactivity (BHR), rhinitis, atopy and family history of asthma were more frequent in patients with ACE-I induced cough (P < .001). Patients with ACE-I-induced cough had significantly higher incidence of diagnosed asthma [OR = 8.28 (95%CI: 3.26-21.03) P < .001]., Conclusions: Asthma and an atopic background constitute a substantial risk factor for ACE-I induced cough. The presence of underlying asthma should be investigated in patients diagnosed with ACE inhibitor induced cough. However, the fact that most asthma patients tolerate ACE-I therapy, indicates that other cofactors are likely involved., (© 2020 John Wiley & Sons Ltd.)

Background: Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy., Methods: Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms., Results: z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV 1 ), FEV 1 /FVC ratio, and DRS were not different from 11 to 18 years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18., Conclusion: Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls., (© 2019 The Authors. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.)

Background: Preterm-born survivors have increased respiratory symptoms and decreased lung function, but the nature of bronchial hyper-responsiveness (BHR) is unclear. We conducted a systematic review and meta-analysis for BHR in preterm-born survivors including those with and without chronic lung disease in infancy (CLD) comparing results to term-born subjects., Methods: We searched eight databases up to December 2016. Included articles compared BHR in preterm-born and term-born subjects. Studies reporting BHR as decreases in forced expiratory volume in 1 second (FEV 1 ) after provocation stimuli were included. The analysis used Review Manager V5.3., Results: From 10 638 titles, 265 full articles were screened, and 28 included in a descriptive analysis. Eighteen articles were included in a meta-analysis as they reported the proportion of subjects who had BHR. Pooled odds ratio (OR) estimates (95% confidence interval) for BHR comparing the preterm and term-born groups was 1.88 (1.32, 2.66). The majority of the studies reported BHR after a methacholine challenge or an exercise test. Odds ratio was 1.89 (1.12, 3.19) after methacholine challenge and 2.59 (1.50, 4.50) after an exercise test. Nine of fifteen articles reporting BHR in CLD subjects were included in a meta-analysis. Differences for BHR including for methacholine (OR 4.35; 2.36, 8.03) and exercise (OR 5.13; 1.82, 14.47) were greater in the CLD group compared to the term group., Conclusions: Preterm-born subjects especially those who had CLD had increased rates of BHR to direct (methacholine) and indirect (exercise) stimuli compared to term-born subjects suggesting subgroups might benefit from anti-inflammatory or bronchodilator therapies., (© 2018 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.)

Background: Interaction between respiratory multimorbidity and lung function has not been examined in longitudinal population studies. We aimed to assess the association of multimorbidity of asthma and rhinitis with lung function and bronchial hyperresponsiveness in comparison with single and no allergies from early school age to young adulthood., Methods: In 1990, the Multicenter Allergy Study birth cohort recruited 1314 newborns from 5 German cities. At 7, 13, and 20 years, we performed lung function and bronchial challenge tests. We assessed symptoms, medications, and doctor's diagnoses for asthma and rhinitis for 3 outcomes: current multimorbidity (both coexisting), asthma only, and rhinitis only., Results: From 7 to 20 years, multimorbidity prevalence more than doubled from 3.5% to 7.7%, current asthma only (without rhinitis co-occurring) decreased by half from 2.8% to 1.3%, and current rhinitis only (without asthma co-occurring) increased from 14.3% to 41.6%. Resting lung function parameters differed between allergic and asymptomatic participants but showed no considerable differences between the allergic phenotypes. Frequency and severity of bronchial hyperresponsiveness were particularly associated with multimorbidity. At the age of 20 years, participants with multimorbidity showed a clearly higher severity in hyperresponsiveness compared to participants who suffered only asthma (P = .049) or rhinitis (P = .008) or were asymptomatic (P < .001)., Conclusion: Single lung function measurements from childhood ongoing do not seem to discriminate between subjects with multimorbidity, single allergies, and no allergy. Our results show that multimorbidity is associated with more severe symptoms compared to those suffering only a single allergic disease., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: 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)., Methods: 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., Results: 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., Conclusions: 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.)

Background: Childhood asthma frequently has allergic comorbidities. However, there is limited knowledge of the longitudinal development of asthma comorbidites and their association to bronchial hyper-responsiveness (BHR) and airway inflammation markers. We therefore aimed to assess the association between childhood asthma with allergic comorbidities and BHR and fractional exhaled nitric oxide (FE(NO)) and the impact of gender on these associations., Methods: Based on data from 550 adolescents in the prospective birth cohort 'Environment and Childhood Asthma' study, asthma was defined for the three time periods 0-2, 2-10 and 10-16 years of age, using recurrent bronchial obstruction (rBO) 0-2 years of age as a proxy for early asthma. Asthma comorbidities included atopic dermatitis (AD) and allergic rhinitis (AR) from 10 to 16 years. At age 16 years BHR, assessed by metacholine bronchial challenge, and airway inflammation, assessed by FE(NO), were compared between the groups of asthma with or without the two comorbidities, to a reference group with no never asthma, and subsequently stratified by gender., Results: Boys with asthma and AR, regardless of AD had significantly more severe BHR and higher FE(NO) than the other asthma phenotypes. Almost half of the children remained in the asthma and AR category from 10 to 16 years, the entire difference being determined by new incident cases from 10 to 16 years., Conclusions: Asthma phenotypes characterized by allergic comorbidities and AR in particular appears closely associated with BHR and FE(NO), especially among boys., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Epidemiological data have linked obesity with an increased risk of asthma, but the mechanisms responsible for this relationship remain unknown. One possible mechanism, which has received little attention, could be the effect of cholesterol metabolism on airway smooth muscle function. The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]., Methods: Associations between AHR, BMI and plasma lipoproteins were assessed in a population-based cohort at ages 14 and 20 years., Results: In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P < 0.05). HDL, LDL/HDL ratio and total cholesterol were not associated with AHR. In multiple regression analyses adjusted for sex, lung function, smoking and asthma, only higher levels of BMI at age 14 or 20 years were significantly associated with increased AHR at age 20 years, while neither LDL, HDL and LDL/HDL ratio nor total cholesterol were significantly associated with AHR., Conclusion: We confirmed that in teenagers there is a strong association between BMI and AHR to methacholine. This association seems to be independent of the plasma lipoprotein levels at that age., (© 2012 John Wiley & Sons Ltd.)

Background: Many patients present with a mixture of respiratory problems such as shortness of breath, heavy breathing, coughing and odour intolerance. If these patients are diagnosed as asthma, it might sometimes be a false diagnosis. Concepts such as sensory hyperreactivity, hyperventilation, asthma-like symptoms, odour intolerance and dysfunctional breathing are used to refer to these patients. Non-respiratory symptoms such as headache, fatigue and bloating are sometimes also part of the clinical picture. Our aim was to use factor analysis to increase our understanding of breathing-related symptoms in a general-population frame., Methods: A respiratory questionnaire was answered by 10 108 subjects in a general-population sample. Items aiming to identify individuals with breathing-related symptoms and asthma were included. We used factor analysis with Varimax rotation to extract discriminatory components (i.e. groups of symptoms), based on the questionnaire items. The aim was to find groups of items (factors) as distinct as possible, still allowing overlap and showing the importance of each item in the separated factor., Results: Five distinct factors were identified in the factor analysis, representing dysfunctional breathing, odour intolerance, asthma, bronchitis and a group with mixed symptoms, respectively. These five factors explained 55% of the variance., Conclusions: Based on our findings, we conclude that non-asthmatic breathing-related symptoms may be separated into at least two categories in a general population, odour intolerance and dysfunctional breathing. These two categories seem to be two distinct groups of subjects with breathing-related symptoms and may represent different clinical entities separated from asthma and bronchitis., (© 2012 Blackwell Publishing Ltd.)

Introduction: Bronchial hyperresponsiveness (BHR) elevates the risk for development of respiratory symptoms and accelerates the decline in forced expiratory volume in the first second (FEV1 ). We thus aimed to assess the prevalence, determinants and quantity of BHR in Helsinki., Objectives: This study involved 292 randomly selected subjects age 26-66years, women comprising 58%., Methods: Following a structured interview, a spirometry, a bronchodilation test, and a skin-prick test, we assessed a bronchial challenge test with inhaled histamine using a dosimetric tidal breathing method. Results included the provocative dose inducing a decrease in FEV1 by 15% (PD15 FEV1 ) and the dose-response slope. For statistical risk factor-analyses, the severity of BHR was considered; PD15 values ≤1.6mg (BHR) and ≤0.4mg [moderate or severe BHR (BHRms )] served as cut-off levels., Results: BHR presented in 21.2% and BHRms in 6.2% of the subjects. FEV1<80% of predicted [odds ratio (OR) 4.09], airway obstruction (FEV1 /forced vital capacity<88% of predicted) (OR 4.33) and history of respiratory infection at age <5 (OR 2.65) yielded an increased risk for BHR as ORs in multivariate analysis. For BHRms , the determinants were decreased FEV1 below 80% of predicted (OR 27.18) and airway obstruction (OR 6.16). Respiratory symptoms and asthma medication showed a significant association with BHR., Conclusions: Of the adult population of Helsinki, 21% showed BHR to inhaled histamine. The main determinants were decreased FEV1 and airway obstruction. Quantitative assessment of BHR by different cut-off levels provides a tool for characterization of phenotypes of airway disorders in epidemiologic and clinical studies., (© 2011 Blackwell Publishing Ltd.)

Although it is generally agreed that sensitization is an important risk factor for allergic diseases, the extent to which sensitization accounts for allergic symptoms in children is controversial. As part of the Aalst Allergy Study, this cross-sectional study investigated the prevalence of allergic symptoms and their association with sensitization in an unselected population of Flemish children aged 3.4-14.8 yr. Skin prick testing with the most common aeroallergens was performed and allergic symptoms were documented by a parental questionnaire. In the children older than 6 yr, a significant association of current wheezing, current dyspnea, airway hyperreactivity, rhinoconjunctivitis, and current eczema with sensitization was found, while in the pre-school children these associations were less pronounced. The association with sensitization was strongest for rhinoconjunctivitis and current respiratory symptoms - the association was less striking for children with current eczema. The impact of a positive family history of allergy on the association with sensitization was more important for eczema than for the other analyzed allergic symptoms. Persistent and late-onset wheezers were significantly more likely than non-wheezers and transient early wheezers to be associated with sensitization and a personal history of rhinoconjunctivitis. Late-onset wheezing was associated with a positive family history of allergy, while transient early wheezing was associated with day-care attendance. An association with eczema was found for all three childhood wheezing phenotypes. The association of allergic symptoms with sensitization is significant in the older but less pronounced in pre-school children and is more pronounced for current allergic symptoms. Diagnosis and disease definition of allergy symptoms remains difficult at pre-school age. The influence of a positive family history of allergy on the association of the respective allergic symptoms with sensitization was most important for eczema. Our data confirm the atopic characteristics of the different wheeze phenotypes.

Introduction: Asthma is frequent in elite athletes and the high prevalence of asthma might be associated with specific types of sport. It has been suggested that chronic endurance training might increase the number of neutrophils in the airways, and this may reflect airway injury. The use of anti-asthmatic medication in elite athletes is also currently under scrutiny in order to reduce the risk of under-treatment or over treatment., Objectives: Determine the use of anti-asthmatic medication and the prevalence of asthma-like symptoms and asthma in Danish elite athletes. Further, to determine whether elite athletes with asthma-like symptoms have asthma and investigate the airway inflammation and airway reactivity to mannitol., Materials and Methods: Three cross-sectional studies: (i) Applications for Abbreviated Therapeutic Use Exemption (ATUE) certificates in 2005 were studied (N = 694); (ii) a questionnaire survey of elite athletes (N = 418); and (iii) a clinical study of elite athletes. A total of 54 elite athletes (19 with physician-diagnosed asthma) participated together with two control groups: (i) 22 non-athletes with physician-diagnosed asthma (steroid naïve for 4 weeks before the examination) and (ii) 35 non-athletes without asthma., Examinations: questionnaires, exhaled nitric oxide (eNO), spirometry, skin prick test, mannitol test and blood samples. Induced sputum was done in subjects with asthma., Results: (i) Anti-asthmatic medication was included in 445 (64%) of all ATUE certificates. A total of 308 (69%) elite athletes applied for inhaled corticosteroids (ICS), and most ATUE certificates were handled by general practitioners (GP) (78%). (ii) A total of 329 (79%) elite athletes completed the questionnaire; 181 (55%) reported asthma-like symptoms and 46 (14%) had asthma. Anti-asthmatic medication was currently taken by 24 (7%) elite athletes. Elite athletes participating in endurance sports had higher prevalences of asthma-like symptoms (74%), use of anti-asthmatic medication (15%) and current asthma (24%) than all other athletes (P < 0.01). (iii) No difference in lung function, eNO, airway reactivity (AR) to mannitol and atopy between elite athletes with and without asthma-like symptoms was found. Elite athletes with physician-diagnosed asthma had less AR [Response Dose Ratio (RDR) 0.02 (0.004) vs 0.08 (0.018) P < 0.01], and fewer sputum eosinophils [0.8% (0-4.8) vs 6.0% (0-18.5), P < 0.01] than non-athletes with physician-diagnosed asthma., Conclusion: Most applications for ATUE certificates were handled by GPs, and the majority concerned anti-asthmatic medication. We found signs of under-treatment of elite athletes with asthma, and endurance athletes had the highest prevalence of asthma-like symptoms and asthma. The prevalence of asthma-like symptoms was higher than the prevalence of asthma, and we showed that symptoms alone should not be used to diagnose asthma. We demonstrated that asthma-like symptoms are independent of lung function, eNO, RDR and atopy in elite athletes. Elite athletes with physician-diagnosed asthma seem to have less airway reactivity and fewer sputum eosinophils than non-athletes with physician-diagnosed asthma, but more studies are needed to further investigate if and how the asthma phenotype of elite athletes differs from that of classical asthma.

Introduction: The prevalence of respiratory symptoms and airway hyperresponsiveness (AHR) is high in elite athletes; swimmers have one of the highest prevalences. No consensus exists on what airway challenge to use when identifying AHR in elite athletes. Further, knowledge is sparse about when during their active sport career AHR develops and if there is an acute effect on the airway inflammation of a swimming training session., Objectives: We aimed to (i) evaluate the airway response to a methacholine challenge, a eucapnic voluntary hyperpnoea (EVH) test, a field-based exercise test (FBT) and a laboratory-based exercise test (LBT) in adult elite swimmers; (ii) investigate airway responsiveness and airway inflammation in adolescent elite swimmers; and (iii) evaluate the acute effect of a training session in an indoor swimming pool on airway inflammation in adolescent elite swimmers., Materials and Methods: Two groups were studied. (i) In adult elite swimmers (n = 16), we examined airway response in four airway provocation tests: methacholine challenge, EVH test, FBT and LBT. (ii) In adolescent elite swimmers (n = 33), we examined airway responsiveness to EVH and methacholine, and airway inflammation and compared the findings with those in asthmatic adolescents (n = 32) and unselected adolescents (n = 35). Further, we examined the acute effect of swimming on airway inflammation in a subpopulation of the adolescent swimmers (n = 21). Airway inflammation was evaluated using sputum induction, measurements of exhaled nitric oxide (FeNO) and exhaled breath condensate (EBC)., Results: Of 16 adult swimmers, eight (50%) had AHR; five of the eight (63%) were identified with the EVH test, four (50%) with the FBT, four (50%) with the LBT and none with the methacholine challenge [provocative dose of methacholine causing a 20% fall in FEV1 (PD(20))

Introduction: The role of inhaled corticosteroids (ICS) on disease progression in asthmatic children is not yet clear., Aims: This study was conducted (i) to determine how often ICS were used for treatment of obstructive airways disease (OAD) in early childhood; (ii) to assess if ICS treatment had an effect on lung function in young children with recurrent bronchial obstruction (rBO); (iii) to explore if early ICS treatment in children with OAD during the first 2 years of life can modify occurrence of current asthma in school children; (iv) to define a severity score for severity of OAD during the first 2 years of life and assess if the severity score can be used to predict asthma in school children; and (v) to investigate the prevalence of asthma in children in an urban population., Subjects and Methods: The present study is part of a 10-year follow-up of children in the prospective birth cohort (n = 3754), the Environment and Childhood Asthma study in Oslo. For aim 1, all children from the entire cohort who had completed follow-up questionnaires as well as all children defined with rBO were assessed. For aim 2, 54 children with rBO (with and without ICS treatment) and 15 controls with tidal flow volume measurements upon presentation of the disease and 2 years of age were studied. For aims 3 and 4, 459 subjects (with and without rBO at 2 years of age) from the case control study who attended 10-year follow-up were studied. For aim 5, the 616 of 803 subjects who had lung function measurements performed after birth were reinvestigated at the age of 10 years., Results: A total of 2.1% of all the children in the cohort and 21% of children with rBO had received ICS treatment by 2 years of age. The mean difference of change in baseline tidal breathing (the ratio of time to peak expiratory flow to total expiratory time) was significantly higher in the ICS-treated group only by 2 years of age and correlated significantly with duration of ICS treatment. However, in rBO children, the use of ICS treatment before 2 years of age was not associated with reduced risk of current asthma at 10 years of age. The risk (odds ratio, 95% confidence interval) of current asthma among rBO subjects with a severity score above five was 20.2, 9.9-41.3 compared to controls. In 10-year-old children, the lifetime prevalence of asthma was 20.2%., Conclusions: One-fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids by age 2 years. Lung function appeared to improve in children using ICS from the start of symptoms of OAD until 2 years of age, mostly in children with the longest duration of treatment. However, use of ICS during the first 2 years of life in children with OAD did not reduce asthma present 8 years later. A scoring system based on severity and frequency of OAD during the first 2 years of life predicted current asthma at 10 years of age. One in five 10-year-old children in the city of Oslo at some time had asthma.

Secretory IgA in mucosal secretions has a broad protective function. The insufficient protection provided by the respiratory mucosa in children with selective IgA deficiency (sIgAD) might facilitate the development of bronchial hyper-responsiveness (BHR) and consequently asthma symptoms. This study was conducted to clarify the prevalence of BHR in sIgAD children and the relationship with atopic status. A cohort of 20 children (group A) aged 6.4-20.1 yr (median: 12.6) with sIgAD (serum IgA <6 mg/dl) were evaluated for BHR using inhaled hypertonic saline test as well as for atopy by skin prick testing (SPT) to eight common aero-allergens. Seventy other children with normal levels of serum IgA, but sensitized to aero-allergens (group B) and 102 with normal IgA and negative SPTs (group C) were also evaluated. Baseline spirometry demonstrated that forced vital capacity (FVC) values in group A were significantly lower than in C. Forced expiratory volume in 1 s values were similar in all groups, but impairment of the forced expiratory flow over the middle half of the FVC was detected in group B. The prevalence of BHR was similar among group A (30.0%) and group B (35.7%) (p = 0.79) but they differed from group C (5.9%) (p = 0.005). An association between BHR and reported current (p = 0.001) but not lifetime asthma symptoms among group A was also observed. There was no association between atopy and BHR in group A but only to mites' sensitization (p = 0.03). In conclusion, these results indicate that sIgAD constitutes a risk factor for development of BHR but it appears to be related to sensitization to mites.

Histamine plays an important role in the allergic inflammation. Histamin N-Methyltransferase (HNMT) catalyses the major pathway of histamine metabolism in the human lung. A common functional single nucleotide polymorphism (SNP) within the HNMT gene (C314T) was recently related to asthma. We tested this SNP for associations with asthma and asthma associated traits in two German pediatric populations (1. MAS-cohort, n=888, 85 children with asthma; 2. asthmatic children from Freiburg, n=176). Non-asthmatic (n=515) and non-atopic (n=211) children from the MAS-cohort were used as controls. For genotyping melting curve analyses (Light Cycler System) were applied. In contrast to a previous study, no association of the HNMT 314T allele with asthma, bronchial hyperresponsiveness (BHR) or other asthma related phenotypes could be observed in either study population. We conclude that this SNP might not play a major role in the pathogenesis of asthma or BHR in German children.

The objective of the study was to evaluate the risk of asthma in children who had undergone an adenoidectomy, an operation frequently performed on children with glue ear or recurrent otitis media. Two surveys were carried out, a nation-wide questionnaire returned by 483 individuals (survey A) and a survey of hospital discharge records involving 1616 children who had undergone an adenoidectomy and 161 control children who had undergone probing of the nasolacrimal duct due to congenital obstruction (survey B). The questionnaire (survey A) showed that an adenoidectomy before the age of 4 years was associated with asthma (OR 3.19, 95% CI 1.25; 8.13) and with allergy to animal dust (OR 2.50, 95% CI 1.27; 4.95). In survey B, asthma diagnosis was retrieved from the national asthma register. It showed also that adenoidectomy at an early age was associated with an increased risk of asthma (OR 6.74, 95% CI 2.99; 15.2). There was an association between asthma and adenoidectomy, even before adenoidectomy had actually been performed. The risk of asthma was highest among children who had had adenoidectomy because of recurrent otitis media. The observed association between an adenoidectomy and asthma may be explained by an underlying factor predisposing to both recurrent otitis media and asthma.

Twenty years ago, the prevalence of atopic sensitization and bronchial hyper-responsiveness (BHR) in Xhosa children in a rural location in South Africa was very low. The aim of this study was to document the current prevalence of these two indices by comparing traditional rural Xhosa children, recently urbanized Xhosa children and established city white children, and to consider factors that may account for the observed increase in all of these groups. One thousand four hundred and fifty-seven school children aged 10-14 years from the rural Transkei, from a recently urbanized peri-urban area and from urban Cape Town areas were studied using a questionnaire. Four hundred and eighteen children had histamine challenges, and 492 tests for atopy were also conducted. As determined by bronchial challenge with histamine, 17% of rural and 34.4% of recently urbanized Xhosa children had increased BHR, a marked increase from the 0.03% and 3.17% prevalence of increased BHR previously found using the exercise challenge. The prevalence of increased BHR in white urban children was 33%. Sensitization to one or more aero-allergens, as indicated by CAP RAST tests, was present in 36.6% of the rural Xhosa children with normal BHR and in 62.5% of those with increased BHR, a striking increase from that of previous studies. Atopic sensitization to one or more aero-allergens, as indicated by a skin prick test (SPT), was found in 42.3% of the recently urbanized Xhosa children and 45% of urbanized white children. We have also documented sensitization to house dust mites in the rural Xhosa children for the first time. Passive cigarette smoking was not identified as a risk factor for increased BHR or atopy. Wood smoke in the indoor environment did not play a role in the rural Xhosa children's BHR. Ascaris infection does not appear to play any modifying role in the development of increased BHR in the rural or urban children. We have found that increases in BHR in the rural and recently urbanized Xhosa children develop independently of increases in atopy. Our results challenge the 'hygiene' hypothesis as a complete explanation for the recent dramatic worldwide increases in allergic diseases.

The hypertonic saline challenge test is the recommended method to assess bronchial hyperresponsiveness in the International Study of Asthma and Allergies in Childhood (ISAAC). The sensitivity of this procedure to assess asthma symptoms, however, has been reported to vary among study centers. The purpose of our study was to evaluate the value of this provocation test in an epidemiological survey in children, and to relate the degree of bronchial hyperresponsiveness to the severity of asthma symptoms. All 11-13-year-old children from 16 randomly selected schools in Linköping, Sweden received a questionnaire regarding respiratory symptoms and allergic disease. Skin prick tests with eight inhalant allergens were performed. In addition, all children with wheeze over the past 12 months (current wheeze) and a random sample of children without current wheeze were invited to perform hypertonic saline provocation tests. A complete data set was available for 170 children, including 50 with and 120 without current wheeze. Bronchial hyperresponsiveness (BHR) was defined as at least 15% decline in FEV1. The degree of BHR was represented by the response/dose ratio, i.e. the fall in FEV1 divided by total dose of inhaled saline. The severity of asthma symptoms was classified by the number of wheezing episodes over the past 12 months. 'Asthma ever' was defined by a combination of symptoms in the questionnaires. Children with 'asthma ever' and current wheeze were considered as having current asthma. Current atopic asthma was defined as current asthma with at least one positive skin prick test. The sensitivity of the procedure to detect 'asthma ever', current asthma and current atopic asthma was 62, 61 and 83%, and the specificity 83, 81 and 60%, respectively. The positive challenge rate was 52, 34, 13 and 7% among current wheezers, previous wheezers, non-wheezers with a history of allergy and healthy children. The degree of bronchial hyperresponsiveness increased with the number of wheezing episodes. Thus, the median and range of the response/dose ratio were 4.8%/ml (2.1-14.8), 2.6%/ml (0.7-8.6) and 1.3%/ml (0.8-2.7), respectively, for children with >/= 4 episodes, 1-3 episodes and no wheezing episodes over the past 12 months (p<0.001). In conclusion, hypertonic saline provocation test is useful as a tool to detect asthma in epidemiological studies in children. The degree of bronchial hyperresponsiveness, as represented by the response/dose ratio, reflects the severity of asthma symptoms.

The purpose of the study was to investigate whether the duration of sensitization to food allergens during early childhood is related to later development of IgE mediated hypersensitivity to inhalant allergens and of allergic rhinitis and asthma in 5-year-old children and whether long-lasting food-sensitization may be used to predict subsequent allergic airway diseases. Five hundred and eight children of a prospective birth cohort study with available serum samples at one and two years of age were included and followed up until five years of age. Specific sensitization to food and inhalant allergens and the occurrence of subsequent allergic airway diseases were determined. Children with a long-lasting sensitization to food allergens (persistently sensitized for more than one year) produced significantly higher total IgE and specific IgE levels than children who were only transiently food-sensitized by two years of age. Children persistently sensitized to food had a 3.4 fold higher risk of developing allergic rhinitis and a 5.5 fold higher risk of developing asthma than infants who were only transiently food sensitized. Persistent food sensitization in combination with a positive atopic family history was a strong predictor for the development of allergic rhinitis and asthma at five years of age. The risks for these children are up to 50%, and 67% respectively. Persistently detectable sensitization to food over more than one year in early childhood is a strong prognostic factor for subsequent allergic airway disease. Persistently food-sensitized children especially in atopic families have to be regarded as a high-risk group and should be considered for preventive measures against respiratory atopy.

There is a lack of established criteria to identify asthma and bronchial hyperreactivity (BHR) in epidemiological studies, although both conditions appear to bear some relationship to atopy, at least in children. Recent studies indicate a low prevalence of atopy in former Socialist countries in Europe, yet the prevalence of BHR has been reported to be high. We have analysed the relationship between the outcome of various lung function tests, atopy and clinical symptoms of bronchial asthma in an epidemiological survey of Estonian 10-12 year old schoolchildren. Metacholine provocation test (four steps with the cumulative doses 100, 300, 700 and 1100 micrograms), exercise challenge test and PEF-variability over two weeks were done in 806 children in Tallinn (coastal, industrialised city) and 774 children in Tartu (inland, university town). A positive response to the metacholine challenge test was recorded in 19% in Tallinn and in 32% in Tartu (p < 0.001). A similar tendency was observed for a more than 15% decrease of FEV1 in the exercise challenge test, i.e. 6% in Tallinn and 18% in Tartu. There was only a weak relationship between BHR, as defined by either a positive metacholine challenge and/or exercise test, diagnosed asthma and reported wheezing. Thus, 47% of the wheezing children and 30% of the children with asthma had negative test results. Only 17% of the children with a positive metacholine challenge were atopic, as defined by at least one positive skin prick test. In conclusion, none of the methods employed to assess bronchial hyperresponsiveness were very useful for the identification of wheezing and asthmatic children in this epidemiological study. In contrast to the results of studies in Western Europe, most children with bronchial hyperreactivity in Estonia are not atopic.