Familial aggregation and heritability of asthma-associated quantitative traits in a population-based sample of nuclear families

Asthma is a common, genetically complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, variably reduced spirometric measures and increased airway responsiveness (AR) are physiological traits which are characteristic of asthma. We investigated the genetic and environmental components of variance of serum total and specific IgE levels, blood eosinophil counts, the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and AR in an Australian population-based sample of 232 Caucasian nuclear families. With the exception of FVC levels, all traits were closely associated with clinical asthma in this population. Loge total serum IgE levels had a narrow-sense heritability (h2N) of 47.3% (SE = 10. 0%). Specific serum IgE levels against house dust mite and Timothy grass, measured as a RAST Index, had a h2N of 33.8% (SE = 7.3%). FEV1 levels had a h2N of 6.1% (SE = 11.6%), whilst FVC levels had a h2N of 30.6% (SE = 26.8%). AR, quantified by the loge dose-response slope to methacholine (DRS), had a h2N of 30.3% (SE = 12.3%). These data are consistent with the existence of important genetic determinants of the pathophysiological traits associated with asthma. Our study suggests that total and specific serum IgE levels, blood eosinophil counts and airways responsiveness to inhaled agonist are appropriate phenotypes for molecular investigations of the genetic susceptibility to asthma.     

The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics

Smoking is associated with poor symptom control and impaired therapeutic responses in asthma. A total of 843 patients with asthma were recruited. The patients received treatment for 1 yr according to the severity of their asthma. We compared the forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 to forced vital capaity (FVC), atopy, total IgE, emphysema on high-resolution computed tomography (HRCT), the number of near-fatal asthma attacks, and physiological fixed airway obstruction between the smoking and nonsmoking groups. The study population consisted of 159 (18.8%) current smokers, 157 (18.7%) ex-smokers, and 525 (62.5%) nonsmokers. Although the prevalence of atopy was not different between the smoking and nonsmoking groups, the total IgE was higher among the smokers than the nonsmokers. Compared with the nonsmoking group, the smokers had a lower FEV1 % predicted and forced expiratory flow between 25 and 75% of FVC. A greater prevalence of emphysema and a significantly higher number of asthmatic patients with fixed airway obstruction were detected in the smoking versus nonsmoking group. The 37.5% of asthmatic patients who were former or current smokers showed decreased pulmonary function and increased IgE, emphysema on HRCT, and fixed airway obstruction, indicating that smoking can modulate the clinical and therapeutic responses in asthma.     

Basement membrane thickening and clinical features of children with asthma

BACKGROUND: Asthma is a chronic inflammatory disease, characterized by airway inflammation, bronchial hyper-responsiveness, and airway obstruction. Although asthma induces partially reversible airway obstruction, obstruction can sometimes become irreversible. This may be a consequence of airway remodeling, which includes a number of structural changes, such as epithelial detachment, basement membrane (BM) thickening, smooth muscle hypertrophy, and new vessel formation. This study evaluated children with asthma for the presence of BM thickening. METHODS: Eighteen children with asthma and 24 control subjects underwent flexible bronchoscopy with endobronchial biopsy. Light microscopy was used to measure BM thickness in paraffin-embedded biopsy sections. The association between BM thickening and age, sex, duration of asthma, asthma severity, FEV(1), FEV(1)/FVC, FEF(25-75%), methacholine PC(20), eosinophil count, and presence of atopy was examined. RESULTS: Basement membrane thickness was greater in subjects with asthma (8.3 +/- 1.4 microM) than in control subjects (6.8 +/- 1.3 microM, P = 0.0008). Multiple regression analysis revealed that sex, FEV(1)/FVC, total IgE, and atopy (IgE for Dermatophagoides pteronyssinus >0.34 kUA/l) were significant predictive factors for BM thickness. There was no significant association between BM thickness and age, duration of asthma, FEV(1), FEF(25-75%), methacholine PC(20), eosinophil count, or asthma severity. CONCLUSIONS: Basement membrane thickening has been known to be present in children with asthma. In addition, we report an association between BM thickness and sex, FEV(1)/FVC, total IgE, and the presence of IgE specific to D. pteronyssinus.     

Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up

BACKGROUND: A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7-year follow-up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development. METHODS: Twenty-eight children (6-15 years) with AR were studied. At enrollment (T(0)), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)(1) fall (PD(20)FEV(1)) and as dose-response slope (D(RS)). Subjects were reassessed after 7 years (T(1)) using the same criteria. RESULTS: At T(0), 13 children (46%), showing a PD(20)FEV(1) <1526 microg of Mch, had BHR (Mch+), although PEF variability (PEFv) was within normal limits. None of the children with negative methacholine test developed bronchial asthma after 7 years. Of the 13 Mch+, only two reported asthma symptoms after 7 years. No significant change was seen in the other parameters of atopy considered. CONCLUSION: Children with allergic rhinitis present a high prevalence of BHR. Nevertheless, their PEFv is normal and the rate of asthma development low.     

The -403 G-->A promoter polymorphism in the RANTES gene is associated with atopy and asthma

Asthma is a complex inflammatory condition often associated with bronchial hyperreactivity and atopy. Genetic and environmental factors are implicated and several candidate genes have been implicated. Of these, the chemokine RANTES is responsible for the recruitment of inflammatory cells such as eosinophils and T-lymphocytes. We have recently identified a polymorphism within the RANTES promoter (-403 G-->A) and have examined its role, using a PCR-RFLP assay, in the development of atopy and asthma in 201 Caucasian subjects. Atopic status was determined using skin prick testing and serum IgE levels. Severity of airway dysfunction was assessed using spirometric measurement (FEV1) and methacholine challenge (PC20). The -403 A allele was associated with an increased susceptibility to both atopy and asthma. Thus, the proportion of subjects carrying this allele was higher in each of atopic non-asthmatics, non-atopic asthmatics and atopic asthmatics compared with non-atopic, non-asthmatic controls. In particular, this allele was associated with skin test positivity but not IgE level. Homozygosity for the -403 A allele conferred a 6.5-fold increased risk of moderate/severe airway obstruction (FEV1 < or = 80% predicted), a marker for established asthma. Our data, whilst preliminary, indicate that the association of RANTES genotype with both atopy and asthma reflect independent effects, suggesting different mechanisms for the role of this chemokine in atopy and development of airway obstruction.     

Histamine hyperresponsiveness of the extrathoracic airway in patients with asthmatic symptoms

Functional abnormalities of the extrathoracic airway (EA) may produce symptoms mimicking bronchial asthma. We assessed the bronchial (B) and EA responsiveness to inhaled histamine in 40 patients with asthmatic symptoms and in nine asymptomatic controls. FEV1 and maximal mid-inspiratory flow (MIF50) were used as index of bronchial and EA narrowing. Hyperresponsiveness of the intra-(BHR) or extra-(EA-HR) thoracic airway was diagnosed when the provocative concentrations of histamine (PC20FEV1 or PC25MIF50) were less than 8 mg/ml. Fiberoptic laryngoscopy was performed in nine patients and three controls. The glottal region was measured at mid-volume of maximal inspiration (AgMI) and expiration (AgME) before and after histamine. Predominant EA-HR was found in 13 patients, predominant BHR in 12, equivalent BHR and EA-HR in another 12; no significant airway narrowing was observed in three patients and in the nine controls. EA-HR was significantly associated with female sex, sinusitis, post-nasal drip, dysphonia; BHR with atopy, wheezing and lower MEF50. The percent change in AgMI after histamine was closely related to the PC25MIF50 (r = 0.87, P less than 0.001), that of AgME to the PC20FEV1 (r = 0.78, P less than 0.01). These findings suggest that the assessment of EA responsiveness may be useful in the evaluation of asthmatic symptoms, especially in patients with no BHR.     

Respiratory symptoms, bronchial hyper-responsiveness, and eosinophilic airway inflammation in patients with moderate-to-severe atopic dermatitis

BACKGROUND: Patients with atopic dermatitis (AD) often have symptoms suggestive of asthma or rhinitis. The prevalence and signs of respiratory disease in AD patients have been studied to a limited extent. OBJECTIVES: To assess the prevalence and clustering of respiratory symptoms, bronchial hyper-responsiveness (BHR), and eosinophilic airway inflammation in patients with moderate-to-severe AD. METHODS: Eighty-six consecutive patients with moderate-to-severe AD and 49 randomly selected control subjects without AD were studied by questionnaire, flow volume spirometry, histamine challenge to detect BHR, induced sputum test to detect eosinophilic airway inflammation, and skin prick tests (SPTs) and total serum immunoglobulin (Ig)E measurements to detect atopy. RESULTS: The patients with AD showed increased risk of physician-diagnosed asthma (36% vs. 2%, odds ratio (OR) 10.1, confidence interval (CI) 1.3-79.7, P=0.03), physician-diagnosed allergic rhinitis (AR) (45% vs. 6%, OR 4.5, CI 1.2-16.7, P=0.02), BHR (51% vs. 10%, OR 5.5, CI 1.5-20.1, P=0.01), and sputum eosinophilia (81% vs. 11%, OR 76.1, CI 9.3-623.5, P<0.0001) compared with the control subjects. In AD patients, elevated s-IgE and positive SPTs were associated with the occurrence of physician-diagnosed asthma and AR, BHR, and the presence of sputum eosinophilia. CONCLUSIONS: BHR and eosinophilic airway inflammation are more common in patients with AD than in control subjects. The highest prevalences were seen in patients with AD who were SPT positive and had high IgE levels. Longitudinal studies are needed to assess the outcome of patients with signs of airway disease, in order to identify those who need early initiation of asthma treatment.     

Sensitization to Ascaris lumbricoides and severity of childhood asthma in Costa Rica

BACKGROUND: Little is known about sensitization (defined as a positive IgE) to helminths and disease severity in patients with asthma. OBJECTIVES: To examine the relationship between sensitization (defined as a positive IgE) to Ascaris lumbricoides and measures of asthma morbidity and severity in a Costa Rican population with low prevalence of parasitic infection but high prevalence of parasitic exposure. METHODS: Cross-sectional study of 439 children (ages 6 to 14 years) with asthma. Linear regression and logistic regression were used for the multivariate statistical analysis. RESULTS: After adjustment for parental education and other covariates, sensitization to Ascaris lumbricoides was associated with having at least 1 positive skin test to allergens (odds ratio, 5.15; 95% CI, 2.36-11.21; P < .001), increased total serum IgE and eosinophils in peripheral blood, reductions in FEV(1) and FEV(1)/forced vital capacity, increased airway responsiveness and bronchodilator responsiveness, and hospitalizations for asthma in the previous year (odds ratio, 3.08; 95% CI, 1.23-7.68; P = .02). CONCLUSION: Sensitization to Ascaris lumbricoides is associated with increased severity and morbidity of asthma among children in Costa Rica. This association is likely mediated by an increased degree of atopy among children with asthma who are sensitized to Ascaris. CLINICAL IMPLICATIONS: In areas with a low prevalence of helminthiasis such as Costa Rica, Ascaris sensitization may be an important marker of severe atopy and disease morbidity in children with asthma.     

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.     

Factors influencing symptom expression in children with bronchial hyperresponsiveness at 10 years of age

OBJECTIVES: We sought to identify factors associated with wheezing symptoms in children found to have bronchial hyperresponsiveness (BHR) at 10 years of age. METHODS: Children were seen at birth, 1, 2, 4 and 10 years of age in an entire population birth cohort study (n = 1456). At each stage information was collected prospectively on genetic and environmental risk factors for BHR. Skin prick testing was performed at 4 and 10 years of age. Spirometry and methacholine bronchial challenge were conducted at 10 years of age when BHR was considered present if PC(20) FEV(1) was < 4.0 mg/mL. In children with BHR at 10 years of age, factors independently associated with current wheezing were determined by logistic regression. RESULTS: BHR was identified in 169 10-year-olds at bronchial challenge, 55.6% of whom manifested current wheeze. In children with BHR, current wheezers had higher Log(10) total IgE and greater BHR than those who had never wheezed. Symptomatic BHR was independently associated with atopic sensitization (P <.001) and maternal asthma (P =.011) at 10 years of age. If only factors present in the first 4 years of life were considered, parental smoking at 4 years of age (P =.021), maternal asthma (P =.017), and atopic sensitization at 4 years of age (P =.004) were independently associated with symptomatic BHR at 10 years of age. CONCLUSIONS: Symptomatic BHR is associated with greater degrees of BHR and higher total IgE. Heredity, atopy, and environmental exposure might influence symptom expression in children with BHR.     

Relationship Between Atopy and Bronchial Hyperresponsiveness

Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.     

Variance components analyses of multiple asthma traits in a large sample of Australian families ascertained through a twin proband

BACKGROUND: Intermediate phenotypes are often measured as a proxy for asthma. It is largely unclear to what extent the same set of environmental or genetic factors regulate these traits. OBJECTIVE: Estimate the environmental and genetic correlations between self-reported and clinical asthma traits. METHODS: A total of 3,073 subjects from 802 families were ascertained through a twin proband. Traits measured included self-reported asthma, airway histamine responsiveness (AHR), skin prick response to common allergens including house dust mite (Dermatophagoides pteronyssinus [D. pter]), baseline lung function, total serum immunoglobulin E (IgE) and eosinophilia. Bivariate and multivariate analyses of eight traits were performed with adjustment for ascertainment and significant covariates. RESULTS: Overall 2,716 participants completed an asthma questionnaire and 2,087 were clinically tested, including 1,289 self-reported asthmatics (92% previously diagnosed by a doctor). Asthma, AHR, markers of allergic sensitization and eosinophilia had significant environmental correlations with each other (range: 0.23-0.89). Baseline forced expiratory volume in 1 s (FEV(1)) showed low environmental correlations with most traits. Fewer genetic correlations were significantly different from zero. Phenotypes with greatest genetic similarity were asthma and atopy (0.46), IgE and eosinophilia (0.44), AHR and D. pter (0.43) and AHR and airway obstruction (-0.43). Traits with greatest genetic dissimilarity were FEV(1) and atopy (0.05), airway obstruction and IgE (0.07) and FEV(1) and D. pter (0.11). CONCLUSION: These results suggest that the same set of environmental factors regulates the variation of many asthma traits. In addition, although most traits are regulated to great extent by specific genetic factors, there is still some degree of genetic overlap that could be exploited by multivariate linkage approaches.     

Atopy in childhood. III. Relationship with pulmonary function and airway responsiveness

The relationship between atopy and pulmonary function in children, and how these relate directly or indirectly to airway hyperresponsiveness, is uncertain. We have examined these relationships in a sample of 13-year-old children. A questionnaire on respiratory symptoms, skin-prick tests to 11 common allergens, spirometry and an abbreviated methacholine challenge test were completed by 662 members (341 boys) of a birth cohort of New Zealand children followed longitudinally to age 13. There was a significant relationship between the presence and degree of atopy, and baseline pulmonary function. Low FEV1/VC ratios were associated with a greater likelihood of airway responsiveness, not only in subjects with diagnosed asthma, but also in the full cohort and in the sub-group of 426 children who denied asthma or current wheeze. The relationships between baseline FEV1/VC and airway responsiveness were stronger in atopic than in non-atopic children, with the strongest relationships in children sensitive to house dust mite and/or cat dander. In the presence of atopy, progressively lower levels of lung function were strongly associated with a higher prevalence of airway responsiveness (P<0.001). In non-atopic subjects, only those with the most impaired lung function (FEV1/VC < 75%) showed any substantive prevalence of airway responsiveness. The relationship between the degree of atopy and the FEV1/VC ratio, although significant in univariate analysis, became completely non-significant after accounting for airway responsiveness. In 13-year-old children, atopy, especially to house dust mite and cat dander, was correlated with pulmonary function expressed as FEV1/VC ratio. Airway responsiveness likewise correlated with impaired baseline lung function. The apparent relationship of lung function to atopy occurred primarily as a result of the relationship between atopy and airway responsiveness. Atopy and impaired lung function were additive factors predicting airway responsiveness.     

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.     

CTLA-4 polymorphisms in allergy and asthma and the TH1/ TH2 paradigm

BACKGROUND: Several genomic regions are reported to be associated with the development of asthma and allergy, including chromosome 2q33. This region harbors the candidate gene cytotoxic T-lymphocyte antigen 4 (CTLA-4), an important regulator of T-cell activation and differentiation. OBJECTIVE: We sought to explore possible associations between CTLA-4 polymorphisms and allergy and asthma. METHODS: Seven single nucleotide polymorphisms (SNPs; MH30, -1147CT, +49AG, CT60, JO31, JO30, JO27_1) in CTLA-4 were analyzed for associations with total serum IgE, allergic sensitization (positive skin prick test to common allergens), bronchial hyperresponsiveness (BHR) to methacholine, asthma, and lung function (FEV1 % of predicted) in 364 asthmatic families from 3 European countries. RESULTS: Transmission disequilibrium test analysis showed that several SNPs were significantly associated with serum IgE levels, allergy, asthma, and FEV1 % predicted below 80%, but not with BHR, and CTLA-4 polymorphisms of potentially direct pathogenic significance in atopic disorders were identified. CONCLUSION: We identified associations between 4 newly discovered SNPs in the CTLA-4 gene and serum IgE levels, allergy, asthma, and reduced lung function, but not BHR, suggesting an important role for CTLA-4 in atopy and reduced lung function in asthmatic subjects rather than asthma per se. The particular SNP alleles found positively associated with our phenotypes were recently shown to be associated negatively with autoimmune disorders. Although a skewing toward a TH1 reactivity pattern is believed to characterize autoimmune diseases, atopic diseases are considered TH2-mediated. Hence, our data suggest a role for CTLA-4 polymorphisms in determining the TH1/TH2 balance and identify CTLA-4 signaling as a potential therapeutic target in atopic disease.     

Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity

BACKGROUND: Exposure to perfume and fragrance products may, in some individuals, cause symptoms from the eyes and airways. The localization, character and risk factors of such symptoms in the general population are unknown. OBJECTIVE: To investigate both the localization and character of symptoms from the eyes and airways elicited by fragrance products, and the associations between such symptoms and skin prick test reactivity (atopy), methacholine bronchial hyper-reactivity (BHR), allergic rhinitis and asthma. METHODS: A questionnaire on mucosal symptoms elicited by fragrance products was posted to 1189 persons who had participated in a Danish population-based study of allergic diseases in 1997/1998. The study included measurement of BHR, atopy, forced expiratory volume in 1 s (FEV1), and serum eosinophilic cationic protein (serum ECP). RESULTS: The response rate was 79.6%. Symptoms from the eyes or airways elicited by fragrance products were reported by 42%. BHR (adjusted odds ratio 2.3, 95% confidence interval 1.5-3.5) was independently associated with symptoms from the eyes and airways elicited by fragrance products. There were no significant associations between these symptoms and atopy, FEV1 or serum ECP. CONCLUSIONS: Mucosal symptoms from the eyes and airways were common in this population. BHR was a significant and independent predictor of these symptoms. The lack of association with atopy suggested that IgE-mediated allergic mechanisms do not play a major role in the development of these symptoms.     

Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma

Purpose

Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5''-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma.

Methods

The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed.

Results

The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r²=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively).

Conclusions

Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.     

Acid anhydrides and asthma

We have studied asthma caused by inhaled acid anhydrides as a model of hapten-induced airway hyperresponsiveness. Inhalation tests with the relevant anhydride in sensitised individuals reproducibly provoked a significant increase in non-specific airway responsiveness identifiable 3 h after the test and prior to the development of the late asthmatic reaction. Seven cases of asthma caused by tetrachlorophthalic anhydride (TCPA) had specific IgE in their serum to a TCPA-human serum albumin conjugate. RAST inhibition studies showed the anhydride to be involved in the antibody-combining site. Survey of the factory population where these 7 cases worked allowed investigation of the determinants of the specific IgE response: its presence was associated with intensity of exposure and current cigarette smoking; in addition smoking interacted with atopy to increase the prevalence of specific IgE. During a 5-year period of avoidance of exposure to TCPA specific IgE declined exponentially with a half-life of one year, suggesting continuing IgE secretion. Five years after avoidance of exposure, airway hyperresponsiveness remained increased in several cases.     

Asthmatics Without Rhinitis Have More Fixed Airway Obstruction Than Those With Concurrent Rhinitis

Purpose

Rhinitis and asthma usually occur together. There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. The aim of this study is to evaluate clinical parameters and therapeutic response in patients with between asthma and asthma with AR.

Methods

Four-hundred eighty-five patients with asthma and 428 asthmatics with AR, who had lesser than 50 years old and smoked less than 10 pack-years were recruited. We compared FEV1 and FEV1/FVC following bronchodilator, atopy, IgE, emphysema on HRCT, and aspirin intolerance between two groups. Also we compared physiologic fixed airway obstruction defined using FEV1/FVC and FEV1 less than 75% following anti-asthmatic drug for 1 year.

Results

46.8% (428/913) asthmatics suffered from AR. There were no differences of total IgE, body mass index, PC20, sputum eosinophils and emphysema on HRCT between two groups. The age in asthmatics was higher than that in those with AR. FEV1/FVC was lower in asthmatics than in those with AR. The prevalence of atopy was higher in asthmatics with AR than in asthmatics. Aspirin intolerance was higher in asthmatics with AR than in asthmatics (42/218 vs 13/109, P=0.001). Fixed airway obstruction were more observed in asthmatics than in those with AR (39/319 vs 28/355, P=0.001) after anti-asthmatic drug for 1 year.

Conclusions

Asthmatics with AR had more atopy and aspirin intolerance than asthmatics, and asthmatics had poor response to anti-inflammatory drugs than those with concurrent rhinitis, indicating that asthmatics have more fixed airway obstruction than those with concurrent rhinitis.