Association between body mass index and allergy in teenage girls in Taiwan

BACKGROUND: The prevalence of atopy and asthma is affected by age, sex and lifestyle factors. Obesity was reported to be a risk factor for asthmatic symptoms in children and adults. OBJECTIVE: To examine the relation between body mass index (BMI) and the prevalence of atopy, rhinitis, wheezing and bronchial responsiveness in adolescents. METHODS: BMI (kg/m2), skin-prick test, bronchial hyperresponsiveness (BHR) to methacholine, and self-reported rhinitis and airway symptoms were assessed in a cross-sectional survey in 1459 eighth-grade students (age 13.2 to 15.5, mean 13.6 years) of seven junior high schools in northern Taiwan. RESULTS: The prevalence of atopy was 42% in boys and 27% in girls. The study population was grouped into quintiles of BMI by sex. Girls in the highest BMI quintile had higher prevalence of atopy and rhinitis symptoms. Compared with the middle three quintiles, they had increased risk of atopy in multivariate analyses adjusted for area of living, sibling number, parent education level and family history of asthma (odds ratio = 1.77, 95% confidence interval = 1.15-2.73). Girls with the lowest BMI quintile had lower prevalence of BHR and wheezing. Compared with the middle three quintiles, they had reduced risk of BHR in multivariate analyses adjusted for area of living, atopy, family history of asthma, and baseline pulmonary function (odds ratio = 0.40, 95% confidence interval = 0.20-0.81). No association between BMI and atopy or BHR was seen in boys. CONCLUSION: BMI was a significant predictor of atopy, allergic symptoms and BHR in teenage girls.     

Prevalence of childhood asthma based on questionnaires and methacholine bronchial provocation test in Korea

Background In most epidemiological survey studies, only subjective symptoms and past medical history of asthma have been used as diagnostic criteria. Even though a questionnaire survey can be performed in a large population study at low cost, limitations such as lack of objectivity and poor predictability in non-specific bronchial hyperresponsiveness cannot be avoided. Objectives The purpose of this study was to elucidate the prevalence of current asthma based on questionnaires and methacholine bronchial provocation test, and the prevalence of atopy in Korea. Methods We performed modified ATS respiratory questionnaires and allergen skin-prick test with 10 common inhalant allergens among 3219 subjects aged 7–19 years in Seoul and a rural part of a small city, Chungju in Korea. Methacholine bronchial provocation tests were also performed among those who had asthma symptoms according to the questionnaire. The criteria of asthma was presence of both asthma symptoms and non-specific bronchial hyperresponsiveness. Atopy was defined as when an allergen induced weal size is same or larger than that caused by histamine. Results The prevalence of asthma based on questionnaires and methacholine bronchial provocation tests was 4.6%, while the prevalence of wheeze was 8.2% and 19.3% of total population complained of one or more respiratory symptoms related to asthma on the questionnaires. There was no significant difference according to age, sex and living area. The mean prevalence of atopy was 35.0% and the most common allergens were Dermatophagoides farinae (30.9%), Dermatophagoides pteronyssinus (27.5%), cat fur (20.4%) and cockroach (11.8%). The atopy prevalence in Chungju area was higher than that in Seoul and males showed a higher prevalence than females. The asthma prevalence was higher among atopies (6.8%) than among non-atopies (2.7%). None of questionnaire items were enough to predict the presence of bronchial hyperresponsiveness in terms of sensitivity, specificity and positive predictive value. Conclusion The prevalence rate of current asthma in Korea was 4.6% and the prevalence rate of atopy in Korea was 35.0%. Questionnaire-based surveys are not enough to predict the actual prevalence of asthma.     

Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air

BACKGROUND: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries. OBJECTIVE: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross-sectional study of a cohort of 670 children, aged 10-13 years. METHODS: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR. RESULTS: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 +/- 0.48] compared to those in rural [31.9% (52/163), 9.84 +/- 0.83] and coastal [33.3% (67/201), 7.17 +/- 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P < 0.007]. Schoolchildren with atopy had lower PC20 than those without atopy (5.98 +/- 0.60 vs 8.15 +/- 0.45, P < 0.001). Positive allergy skin tests and living in a polluted area were risk factors in multivariate analyses adjusted for sex, parents' smoking habits, age, body mass index, nose symptoms and lung symptoms (odds ratio for location = 2.4875, confidence interval 1.6542-3.7406, P < 0.000; odds ratio for allergy skin test = 1.5782, confidence interval 1.1130-2.2379, P < 0.0104). CONCLUSION: Our findings demonstrate that more children living in polluted areas have airway hyperresponsiveness than do those living in less polluted areas.     

Sex differences in asthma, atopy, and airway hyperresponsiveness in a university population.

BACKGROUND: A male predominance in atopy, a preadolescent male predominance in asthma, and a female predominance in airway hyperresponsiveness (AHR) have been previously documented, mostly in separate populations. OBJECTIVE: We examined gender differences in a single population of 500 randomly selected university students from a previous publication which addressed sensitivity and specificity of histamine bronchoprovocation (Cockcroft et al. J Allergy Clin Immunol. 1992;89:23-30). METHODS: In these 500 subjects (age 21.8 +/- 1.5 years) we assessed gender differences in asthma, atopy, and AHR. We compared our findings with those in the literature from a PUBMED search using the keywords gender, asthma, atopy, AHR, and bronchial reactivity. RESULTS: A diagnosis of asthma made by another physician was seen in 31, a male-to-female ratio of 2.9:1 (P = 0.004). Our definition of asthma increased the total to 52 and reduced the male-to-female ratio to 1.2:1. Atopy was seen in 190, male-to-female ratio of 1.5:1 (P = 0.001). Borderline to mild AHR had a female predominance with a male-to-female ratio of 1:1.5 (P = 0.02), whereas moderate AHR had a marked predominance with a male-to-female ratio of 7:1 (P = 0.03). CONCLUSIONS: In our population, the associations among gender and asthma, atopy, and AHR were similar to those seen in the literature with the exception of males having more severe AHR. This may be the one factor contributing to the higher prevalence of asthma (including previous doctor-diagnosed asthma in our population) in boys and young men.     

Family patterns of asthma, atopy and airway hyperresponsiveness: an epidemiological study

BACKGROUND: The patterns of inheritance of asthma have largely been explored using data of symptom history collected by questionnaires which are subject to bias and which may therefore distort the measured relationship. OBJECTIVE: The purpose of this study was to examine family patterns of allergic disease using objective measurements of atopy and of airway hyperresponsiveness (AHR). METHODS: A large random sample of children aged 8-11 years was studied and 3 months later, their parents were also invited for study. Of the sample of 1655 children, both parents of 661 children were studied. In all subjects, respiratory illness history was measured by questionnaire, atopy by skin tests and AHR by responsiveness to histamine. RESULTS: The odds ratio for a child to have AHR if either parent had the same condition was approximately 2. 0, which was the same as the odds ratio for wheeze or diagnosed asthma in the presence of the same condition in either parent. The odds ratio for atopy was smaller (approximately 1.4, NS) but the risk of a nonatopic child having AHR if the parent had AHR was 3.0 (P = 0.01). The correlation between weal size in the child and parent was poor and the severity of AHR in the child was only modestly correlated with the severity of AHR in the parent (R = 0.51, P = 0.04). CONCLUSION: The use of objective measurements did not strengthen the association between atopic or asthmatic conditions in the parent and child, but did suggest that atopy and AHR are inherited independently.     

Duration of postviral airway hyperresponsiveness in children with asthma: effect of atopy

BACKGROUND: Respiratory viruses induce asthma exacerbations and airway hyperresponsiveness (AHR). Atopy is an important risk factor for asthma persistence. OBJECTIVE: We sought to evaluate whether atopy is a risk factor for prolonged AHR after upper respiratory tract infections (URIs). METHODS: Twenty-five children (13 atopic and 12 nonatopic children) with intermittent virus-induced asthma were studied. Clinical evaluation, skin prick tests, methacholine bronchoprovocation, questionnaires, and a nasal wash specimen were obtained at baseline. For 9 months, subjects completed diary cards with respiratory symptoms. During their first reported cold, a nasal wash specimen was obtained. Methacholine provocation was performed 10 days and 5, 7, 9, and 11 weeks later. In case a new cold developed, the provocation schedule was followed from the beginning. RESULTS: Viruses were detected in 17 (68%) of 25 patients during their first cold, with rhinovirus being most commonly identified (82%). AHR increased significantly 10 days after the URI, equally in both groups (P = .67), and remained so up to the fifth week. Duration of AHR in subjects experiencing a single URI ranged from 5 to 11 weeks, without a significant difference between groups. In the duration of the study, atopic children experienced more colds and asthma exacerbations than nonatopic children. Thus for duration of AHR, significant prolongation was noted in the atopic group when assessed cumulatively. CONCLUSION: In asthmatic children the duration of AHR after a single natural cold is 5 to 11 weeks. However, an increased rate of symptomatic cold and asthma episodes in atopic children is associated with considerable cumulative prolongation of AHR, which might help explain the role of atopy as a risk factor for asthma persistence.     

Serum IgE levels, atopy, and asthma in young adults: results from a longitudinal cohort study

To explore the natural history of asthma and its relation to allergic responses, we examined the relation between total serum IgE in early adulthood and a history of respiratory symptoms, airway hyperresponsiveness (AHR), and atopy during childhood. We studied 180 subjects aged 18–20 years who had been studied since the age of 8–10 years. We measured wheeze in the previous year by questionnaire, AHR by histamine inhalation test, atopy by skin prick tests, and serum IgE levels by immunoassay. Subjects with AHR in early adulthood had higher IgE levels (mean 257.0 IU/ml) than subjects with past AHR (mean 93.3 IU/ml) or with lifelong normal responsiveness (mean 67.6 lU/ml) ( P< 0.001). Subjects who had symptoms had higher IgE levels (mean 125.9 IU/ml) than those who were lifelong asymptomatic (mean 63.1 IU/ml) ( P< 0.001). Recent wheeze, AHR, and allergic sensitization all had a positive relation to serum IgE, but IgE was not more predictive of AHR than skin prick tests. The finding that young adults who are sensitized to common allergens are highly likely to have AHR even in the absence of symptoms is further evidence of the fundamental role of IgE-mediated responses in the natural history of AHR throughout childhood and into adulthood.     

Airway hyperresponsiveness is negatively associated with obesity or overweight status in patients with asthma

Background: Obesity is a risk factor for asthma in the general population, but the effect of obesity on airway hyperresponsiveness (AFHR) or airway inflammation in asthma is not clear. This study evaluated the relationship between obesity and asthma, assessing aspects of symptoms, AHR, and severity. Methods: In total, 852 patients with asthma diagnosed by asthma specialists based on AHR as confirmed by a methacholine bronchial provocation test, were enrolled from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) adult asthma cohort. The intensity of AHR was assessed by the concentration of methacholine needed to cause a 20% decrease in FEV(1) (PC(20)). Patients were classified into four categories based on body mass index (BMI): underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30). Results: BMI was negatively correlated with FEV(1) (l), FVC (l), and FEV(1)/FVC (%) in lung function tests. The prevalence of wheezing increased with higher BMI after adjustment for age, sex, smoking, medication history, and PC(20) (p < 0.0001). logPC(20) was lower in the normal weight group compared with the overweight group (p = 0.003). The risk of moderate or severe AHR (PC(20) ≤ 4 mg/ml) decreased with increased BMI after adjustment for age, sex, smoking, and medication history (p = 0.035). Conclusions: Obesity is a risk factor for asthma in the general population, but obesity in asthmatic patients is negatively correlated with the intensity of AHR and is not related to asthma severity. Obesity is positively related with the prevalence of wheezing but negatively related to AHR in asthmatic patients.     

Sensitivity to the house dust mite and airway hyperresponsiveness in a young adult population.

BACKGROUND: The pathogenic mechanisms of airway hyperresponsiveness (AHR) in asthma are unknown and only a few studies have examined the importance of sensitivity to antigens in AHR in young adults. OBJECTIVE: We investigated the correlation between AHR and sensitivity to specific antigens, atopy, history of childhood asthma and spirometry in a young adult population. METHODS: Based on the results of interviews with 447 students at our university, 308 non-smoker students were classified into six groups. Group 1 comprised subjects with intermittent mild bronchial asthma; group 2, subjects with history of childhood asthma; group 3, subjects with atopic disease, and a RAST score for Dermatophagoides farinae (Def) of > or = 2; group 4, normal subjects with a RAST score for Def of > or = 2; group 5, subjects with cedar pollinosis; and group 6, normal subjects. We measured AHR to methacholine (MCh), spirometry, immunoglobulin E-radioimmunosorbent test (IgE-RIST), IgE-radioallergosorbent test to six common antigens, eosinophil cationic protein (ECP), and eosinophil count in peripheral blood in each subject. RESULTS: Airway hyperresponsiveness to MCh did not correlate with IgE-RIST, eosinophil count, or ECP. The highest AHR to MCh was present in groups 1 and 2 and lowest in groups 5 and 6. Multiple regression analysis showed that sensitivity to Def was the only factor that significantly influenced AHR to MCh. Airway hyperresponsiveness to MCh of groups with a RAST score for Def of 0/1 was lower than groups with a RAST score of 2 to 6. Airway hyperresponsiveness to MCh did not correlate with the degree of positivity to Def antigen among positive sensitized groups (RAST score 2 to 6). CONCLUSIONS: Sensitivity to mite antigen may be important in the pathogenesis of AHR and Def is a major contributing antigen in young adults in Japan. Once asthma occurs, AHR remains positive for a long time even after the disappearance of asthma-related symptoms.     

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. III. Effect of exposure to environmental allergens

Two populations of schoolchildren, one living in an area where the predominant allergens are house dust mites and the other in an area where the predominant allergens are pollens, were studied to investigate in more detail the associations between atopy, bronchial hyperresponsiveness (BHR) and symptoms of asthma. The prevalence of atopy (39%) was the same in both towns but the prevalence of BHR was higher in the inland 'pollen' area (19% vs 15%). Atopic children had an increased risk of having BHR and, to a lesser extent, respiratory symptoms, diagnosed asthma and hay fever. The risk of BHR was further increased in children atopic to both pollens and house dust mites, and in children with a high index of atopy (derived from the number and size of the skin reactions to four allergen groups). In addition, the relationship between atopy and BHR was quantitative in that the severity of BHR increased with the severity of atopy. We conclude that there is not a direct causal relationship between atopy and BHR but there may be a common mechanism involved in their development. It appears that, within the atopic population, the type of allergen to which the individual is sensitized, the quantity of aeroallergen present in the environment and the degree of atopy, as measured by the number and size of the skin reactions, are all factors that may interact to increase the risk of BHR.     

A prospective study of bronchial hyperresponsiveness and respiratory symptoms in a population of Australian schoolchildren

To examine the relationship between bronchial hyperresponsiveness (BHR) and respiratory symptoms associated with asthma, we studied a sample of 380 schoolchildren on three occasions at 2-yr intervals. The age of the children at the first study was 8-10 yr. Respiratory symptoms history was assessed by questionnaire, BHR was measured by a histamine inhalation test and atopy was assessed by skin-prick tests to 13 allergens. The cumulative prevalence of BHR in this sample was 27%. The severity of BHR was categorized as severe, moderate, mild or slight. The distribution of severe, moderate and mild BHR was similar at each of the studies. At the third study, when the children were aged 12-14 yr, the prevalence of slight BHR decreased. Children with severe or moderate BHR at age 8-10 yr were atopic, reported current symptoms during the 4 yr of the study and had a high prevalence of severe or moderate BHR in later studies. In this group, 87% of children had current respiratory symptoms and 73% were using asthma medication at age 12-14 yr. In children with mild or slight BHR when first studied, the prevalence of atopy, continuing respiratory symptoms and medication use was much lower. We conclude that severe or moderate BHR is an important risk factor for ongoing morbidity and that comparisons of the prevalence of this severity of BHR in populations may be more informative than comparisons of BHR defined by present criteria.     

Determinants of bronchial responsiveness in the European Community Respiratory Health Survey in Italy: evidence of an independent role of atopy, total serum IgE levels, and asthma symptoms

The aim of the analysis was to test whether total serum IgE levels, specific serum IgE levels, and asthma symptoms are independent predictors of bronchial hyperresponsiveness (BHR), after controlling for known risk factors or potential confounders. The study was carried out on a sample of 875 young adults, 20–44 years old, who took part in the European Community Respiratory Health Survey in Italy The subjects underwent a dose-response methacholine challenge test. We also measured airway caliber as the baseline FEV, in absolute terms and as percentage of forced vital capacity (FVC); skin wheal response to 11 common environmental allergens; and total and specific serum IgE levels to mites, molds, pets, and respiratory symptoms by means of a standardized questionnaire. Atopy (positive skin prick test and/or positive specific IgE assay), total IgE, asthma symptoms, airway caliher, and age appeared to be independent predictors of BHR. When all the other risk factors were taken into account, atopy and total IgE were associated with a threefold increase in BHR risk and thus emerged as the main determinants of BHR. The importance of symptom status as a determinant of BHR decreased remarkably after controlling for atopy and IgE: the odds ratio of current asthmatics to asymptomatic subjects decreased from 15.3 to 8.8. When controlling for symptoms and atopy, a family history of allergic diseases and early respiratory infections was not found to be associated with BHR. Both FEVi and FEV/FVC were strongly and inversely associated with BHR. When airway caliher was taken into account, older age was associated with decreased responsiveness, and the level of responsiveness did not differ significantly between males and females and between smokers and nonsmokers. The results from this analysis indicate that at any given age, irrespective of sex and smoking habits, total serum IgE, specific IgE, airway caliber, and asthma symptoms are the main independent factors influencing the occurrence of BHR in a young adult sample.     

Allergy and asthma in elite summer sport athletes

Exercise may increase ventilation up to 200 L/min for short periods of time in speed and power athletes, and for longer periods in endurance athletes, such as long-distance runners and swimmers. Therefore highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many pollen allergens in spring and summer. Competitive swimmers inhale and microaspirate large amounts of air that floats above the water surface, which means exposure to chlorine derivatives from swimming pool disinfectants. In the summer Olympic Games, 4% to 15% of the athletes showed evidence of asthma or used antiasthmatic medication. Asthma is most commonly found in endurance events, such as cycling, swimming, or long-distance running. The risk of asthma is especially increased among competitive swimmers, of which 36% to 79% show bronchial hyperresponsiveness to methacholine or histamine. The risk of asthma is closely associated with atopy and its severity among athletes. A few studies have investigated occurrence of exercise-induced bronchospasm among highly trained athletes. The occurrences of exercise-induced bronchospasm vary from 3% to 35% and depend on testing environment, type of exercise used, and athlete population tested. Mild eosinophilic airway inflammation has been shown to affect elite swimmers and cross-country skiers. This eosinophilic inflammation correlates with clinical parameters (ie, exercise-induced bronchial symptoms and bronchial hyperresponsiveness). Athletes commonly use antiasthmatic medication to treat their exercise-induced bronchial symptoms. However, controlled studies on their long-term effects on bronchial hyperresponsiveness and airway inflammation in the athletes are lacking. Follow-up studies on asthma in athletes are also lacking. What will happen to bronchial hyperresponsiveness and airway inflammation after discontinuation of competitional career is unclear. In the future, follow-up studies on bronchial responsiveness and airway inflammation, as well as controlled studies on both short- and long-term effects of antiasthmatic drugs in the athletes are needed.     

Asthma and the elite athlete: summary of the International Olympic Committee's consensus conference, Lausanne, Switzerland, January 22-24, 2008

Respiratory symptoms cannot be relied on to make a diagnosis of asthma and/or airways hyperresponsiveness (AHR) in elite athletes. For this reason, the diagnosis should be confirmed with bronchial provocation tests. Asthma management in elite athletes should follow established treatment guidelines (eg, Global Initiative for Asthma) and should include education, an individually tailored treatment plan, minimization of aggravating environmental factors, and appropriate drug therapy that must meet the requirements of the World Anti-Doping Agency. Asthma control can usually be achieved with inhaled corticosteroids and inhaled beta(2)-agonists to minimize exercise-induced bronchoconstriction and to treat intermittent symptoms. The rapid development of tachyphylaxis to beta(2)-agonists after regular daily use poses a dilemma for athletes. Long-term intense endurance training, particularly in unfavorable environmental conditions, appears to be associated with an increased risk of developing asthma and AHR in elite athletes. Globally, the prevalence of asthma, exercise-induced bronchoconstriction, and AHR in Olympic athletes reflects the known prevalence of asthma symptoms in each country. The policy of requiring Olympic athletes to demonstrate the presence of asthma, exercise-induced bronchoconstriction, or AHR to be approved to inhale beta(2)-agonists will continue.     

Atopy in childhood. II. Relationship to airway responsiveness, hay fever and asthma

While airway hyperresponsiveness is usually associated with a diagnosis of asthma or symptoms of wheezing, some individuals with rhinitis show airway hyperresponsiveness as do some with no symptoms whatsoever. We have studied the correlations between symptoms, airway hyperresponsiveness and atopy as determined by skin-prick tests in a cohort of New Zealand children. A total of 662 members of a birth cohort were studied at age 13 years using a respiratory questionnaire, skin-prick tests to 11 common allergens, and an abbreviated validated methacholine challenge test to determine airway responsiveness. Airway hyperresponsiveness (methacholine PC20 FEV1 < or = 8 mg/ml) was strongly correlated with reported asthma and current wheezing (P<0.0001) and also with atopy, especially to house dust mite and cat (P<0.0001). As weal size for both house dust mite and cat increased, so did the proportion of children with airway hyperresponsiveness. All children with diagnosed asthma and airway hyperresponsiveness were atopic. Skin-test reactions to house dust mite and cat were strongly correlated with any degree of measurable airway responsiveness (PC20 FEV1 < or = 25 mg/ml) in children with rhinitis (P<0.00001), and remained significantly correlated even in children without current asthma, without asthma ever and without rhinitis (P<0.001). Atopy is a major determinant of airway hyperresponsiveness in children, not only in those with reported histories of asthma and wheezing, but also in the absence of any history suggesting asthma and rhinitis.     

The epidemiology of atopic dermatitis in Italian schoolchildren

BACKGROUND: Atopic dermatitis (AD) is common in children in industrialized countries. Only one large population study on its prevalence has been conducted in Italy, based on self-report questionnaire. The present study was designed to estimate the prevalence of AD in schoolchildren in Italy by dermatologists' assessment and by UK Working Party criteria, and to investigate associated symptoms and factors. METHODS: Cross-sectional survey on a random sample of 9-year-old schoolchildren from seven Italian cities. Children were examined by experienced dermatologists. Parents and teachers answered standardized questionnaires. RESULTS: Of the 1369 children examined, 88 had a diagnosis of AD, with an estimated point prevalence of 5.8% (95% CI 4.5-7.1) in the reference population. The reported lifetime prevalence was 15.2 (95% CI 12.2-18.2) for AD, 11.9% (95% CI 9.0-14.8) for asthma, and 17.6% (95% CI 14.6-20.7) for rhino-conjunctivitis. The strongest associated factor was the presence of AD in at least one parent. No association of AD with maternal smoking during pregnancy, birth weight, maternal age at the time of the child birth and breast-feeding was observed. The environmental characteristics of the house and the school did not correlate with the prevalence of AD. Episodes of lower respiratory tract infections were associated with asthma, and to a lower extent also with AD and rhinitis. CONCLUSIONS: The prevalence of doctor-diagnosed AD in Italian schoolchildren is comparable to those reported for other developed countries. Family history of atopy was the single most important associated factor, while the complex interplay of environmental factors remains to be elucidated.     

Atopy may be an important determinant of subepithelial fibrosis in subjects with asymptomatic airway hyperresponsiveness

The bronchial pathology of asymptomatic airway hyperreponsiveness (AHR) subjects is not well understood, and the role of atopy in the development of airway remodeling is unclear. The aim of this study was to evaluate whether atopy is associated with airway remodeling in asymptomatic AHR subjects. Five groups, i.e., atopic or non-atopic subjects with asymptomatic AHR, atopic or non-atopic healthy controls, and subjects with mild atopic asthma, were evaluated by bronchoscopic biopsy. By electron microscopy, mean reticular basement membrane (RBM) thicknesses were 4.3+/-1.7 microm, 3.4+/-1.8 microm, 2.5+/-1.5 microm, 2.6+/-1.1 microm, and 2.3+/-1.2 microm in the mild atopic asthma, atopic and non-atopic asymptomatic AHR, atopic and nonatopic control groups, respectively (p=0.002). RBM thicknesses were significantly higher in the mild atopic asthma group and in the atopic asymptomatic AHR group than in the other three groups (p=0.048). No significant difference in RBM thickness was observed between the atopic asymptomatic AHR group and the mild atopic asthma group (p>0.05), nor between non-atopic asymptomatic AHR group and the two control groups (p>0.05). By light microscopy, subepithelial layer thicknesses between the groups showed the same results. These findings suggest that RBM thickening occurs in subjects with atopic asymptomatic AHR, and that atopy plays an important role in airway remodeling.     

Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness

Human bronchial asthma is characterized by airway hyperresponsiveness (AHR), eosinophilic airway inflammation, mucus hypersecretion and high serum level of IgE. IL-18 was originally regarded to induce T(h)1-related cytokines from Th1 cells in the presence of IL-12. However, our previous reports clearly demonstrated that IL-18 with IL-2 promotes Th2 cytokines production from T cells and NK cells. Furthermore, IL-18 with IL-3 stimulates basophils and mast cells to produce Th2 cytokines. Thus, we examined the capacity of IL-2 and IL-18 to induce AHR, airway eosinophilic inflammation and goblet cell metaplasia. Intranasal administration of IL-2 and IL-18 induces AHR, mucus hypersecretion and eosinophilic inflammation in the lungs of naive mice. CD4+ T cells are prerequisite for this IL-2 plus IL-18-induced bronchial asthma, because CD4+ T cells-depleted or Rag-2-deficient (Rag-2-/-) mice did not develop bronchial asthma after IL-2 plus IL-18 treatment. Both STAT6-/- mice and IL-13-neutralized wild-type mice failed to develop AHR, goblet cell metaplasia and airway eosinophilic inflammation, while IL-4-/- mice almost normally developed, suggesting that IL-13 is a major causative factor and IL-4 mainly enhances the degree of AHR and eosinophilic inflammation. Both IL-4 and IL-13 equally induce eotaxin in mouse embryonic fibroblasts. However, only IL-13 blockade inhibited asthma symptoms, suggesting that IL-13 but not IL-4 is produced abundantly and plays a critical role in the pathogenesis of bronchial asthma in this model. As airway epithelial cells store robust IL-18, IL-18 might be critically involved in pathogen-induced bronchial asthma, in which pathogens stimulate epithelial cells to produce IL-18 without IL-12 induction.     

Presence and timing of cat ownership by age 18 and the effect on atopy and asthma at age 28

BACKGROUND: Asthma and allergic sensitization to cats frequently coexist, although recent studies show less atopic disease among people who had pets in infancy. However, no longterm evaluations have been performed thus far. OBJECTIVE: We sought to evaluate the relationship between cat ownership at different age periods (< 18, > 18, and both periods and atopic disease at age 28. METHODS: Australian school children aged 8 to 10 years were recruited in 1982 and participated in follow-up surveys until 2002. Cat ownership was defined by surveys in 1992 and 2002 as having a cat before age 18 only, after age 18 only, or in both periods of life. Health outcomes were defined at a mean age of 28.5 years. RESULTS: Complete data were available for 224 subjects, 50 of whom had a cat before 18 years of age only, 14 after age 18 only, and 70 in both periods. Compared with 90 subjects that never had a cat, having a cat before age 18 protected against atopy to outdoor allergens, airway hyperresponsiveness (AHR) to histamine, current wheeze, and current asthma (P < .05). In contrast, subjects who acquired their first cat after age 18 showed a trend toward higher prevalence rates for asthma symptoms and AHR (P > .10). CONCLUSIONS: Having had a cat before 18 years of age protects against adult asthma and atopy.     

Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients

Background Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect airway inflammation more closely compared with AHR measured by stimuli that act directly on BSM. Methods Fifty‐three adult non‐smoking asthmatics (28 females, 18–56 years) who were not taking inhaled steroids were challenged with mannitol (up to 635 mg) and methacholine (up to 8 μmol). Induced sputum eosinophils, exhaled nitric oxide (eNO), peak flow variation and clinical severity of asthma according to the Global Initiative for Asthma guidelines were measured in addition to the health‐related quality‐of‐life score using the Juniper asthma quality‐of‐life questionnaire. Findings Both AHR to mannitol as well as to methacholine was associated with elevated markers of airway inflammation: in 83% of asthma patients with AHR to mannitol, and in 88% of asthma patients with AHR to methacholine, the eNO level was >20 p.p.b. Sputum% eosinophils >1% was measured in 70% of asthma patients with AHR to mannitol and in 77% of asthma patients with AHR to methacholine. In asthma patients without AHR, 15% had an eNO level >20 p.p.b., but none had sputum% eosinophils >1%. AHR to mannitol was more closely associated with the percentage of sputum eosinophils (PD₁₅ to mannitol vs. sputum% eosinophils: r: ?0.52, P<0.05), compared with AHR to methacholine (PD₂₀ to methacholine vs. sputum% eosinophils: r: ?0.28, NS). Furthermore, there was a stronger correlation between AHR to mannitol and the level of eNO [PD₁₅ to mannitol vs. eNO (p.p.b.): r: ?0.63, P<0.001], compared with AHR to methacholine [PD₂₀ to methacholine vs. eNO (p.p.b.): r: ?0.43, P<0.05]. Interpretation In asthma patients not being treated with steroids, AHR to mannitol and to methacholine indicated the presence of airway inflammation. AHR to mannitol reflected the degree of airway inflammation more closely when compared with methacholine.