Predictors for the severity of bronchial hyperreactivity in childhood asthma.

Bronchial hyperreactivity (BHR) is a common characteristic of asthma and is shown to be a risk factor in the development and outcome of asthma. In this study, we aimed to assess the risk factors at referral for the severity of BHR, which was determined at the end of a mean of 3 yr of follow-up in 98 children with asthma [mean (+/- SD) age, 11.0 (+/- 3.4) yr, male/female = 50/48]. We also evaluated the cross-sectional risk factors for the severity of BHR in the observed children. Information on risk factors at referral was collected from the computer records of the patients followed by an end-of-study visit. Lung function, skin-prick, and bronchial provocation tests were done and total serum IgE level was measured on this visit. The relationship between BHR and risk factors was investigated by multiple linear regression analysis. A lower level of FEV1 % at referral was found to be an important predictor of more severe BHR at the end of the follow-up. None of the other risk factors evaluated predicted the severity of current BHR. We concluded that decreased lung function at referral is associated with a more severe BHR determined at the end of a 3-yr follow-up in children with asthma.     

Sensitization to individual allergens and bronchial responsiveness in the ECRHS. European Community Respiratory Health Survey.

Little is known about the relation of bronchial responsiveness (BHR) to sensitization to individual allergens, or its variation between countries. Data were obtained for BHR, specific immunoglobulin E and confounding variables from 11,215 subjects, aged 20-44 yrs at the start of the European Community Respiratory Health Survey, in 34 centres in 15 countries. The relation of BHR to sensitization to cat, house dust mite, timothy grass and Cladosporium was estimated by means of multiple regression for each centre, and combined across centres by random effects meta-analysis, controlling for baseline lung function, height, sex, season of testing, age, smoking and age/sex and age/smoking interactions. BHR was greater, on average, in those sensitized to cat (p=0.023), house dust mite (p<0.001) and timothy grass (p=0.018), but not to Cladosporium (p=0.60), and increased with degree of sensitization (p<0.001). All relations showed heterogeneity between centres, although to a lesser extent in the relation to sensitization to house dust mite. More variation in bronchial responsiveness was explained by sensitization and degree of sensitization to the individual allergens than by atopy defined as any positive test in each centre, but the relative importance of each allergen varied. The use of atopy as a single variable in relation to bronchial hyperresponsiveness may be misleading.     

Development of Lung Function in Relation to Increased Degree of Bronchial Responsiveness

To study the relationship between development of lung function and bronchial responsiveness, we examined 106 subjects recruited from a random sample of 527 subjects, aged 8-18 years, from Copenhagen. Lung function and bronchial responsiveness to inhaled histamine were measured at two occasions, in 1986 and 1988. The participating subjects (n = 106) were divided into three groups: (a) 20 asthmatics with bronchial hyperresponsiveness (BHR), (b) 42 nonasthmatic subjects with BHR in 1986, and (c) 44 controls without BHR. In 1986, FEV₁ expressed as percentage of predicted value, was found to be similar in the three groups (91%, 94%, and 99%, respectively). The increase in height during the observation period was found to be 5, 6, and 6 cm, respectively, in the three groups. However, at the second examination, in 1988, FEV₁ was found to be significantly reduced in both asthmatics (87%) and nonasthmatic subjects (85%) compared with the controls (103%). In 1988, 16 asthmatics (80%) and 24 (57%) nonasthmatic subjects were found to have BHR, whereas none of the controls were found to have BHR. A multiple regression analysis was used to determine the correlation between change in FEV₁ and potential factors of importance. The change in FEV₁ was highly correlated with the presence of BHR in 1986, however, no correlation was found between change in FEV₁ and change in bronchial responsiveness. In conclusion, nonasthmatic subjects with former BHR showed signs of airflow obstruction and less increase in lung function during growth irrespective of the change in level of bronchial responsiveness, which may suggest a risk for subsequent development of obstructive lung disease.     

Risk factors from childhood to adulthood for bronchial responsiveness at age 32-42 yr.

Bronchial responsiveness (BR) is an important risk factor for the development and outcome of asthma. This study assessed childhood risk factors for both the severity of BR in adulthood and either improvement or worsening of BR over time. Finally, we studied cross-sectional risk factors of BR in adulthood. Between 1966 and 1969, 119 allergic asthmatic children (5-14 yr of age) were studied. Of these, 101 (85%) subjects were reinvestigated at age 22-32 yr (visit 2), and at age 32-42 yr (visit 3). Spirometry, PC10 histamine, skin tests, blood eosinophils, and serum total IgE were measured and a questionnaire was used. Higher FEV1 values in childhood were associated with less severe BR at age 32-42 yr independent of other potential risk factors. Larger increases in FEV1 values both from visit 1 to 2 and from visit 2 to 3, a longer time interval from visit 1 to 3, and having pets in childhood were associated with less severe BR at age 32-42 yr. The same factors were found to be associated with less deterioration of BR from visit 2 to 3. In nonsmokers a higher IgE level at visit 2 was a risk factor for an increase in BR. At age 32-42 yr, a low level of lung function and the presence of asthma symptoms were associated with more severe BR, and older age and having pets were associated with less severe BR. IgE was related to more severe BR only in nonsmokers. Conclusions: A lower lung function in childhood and less improvement in FEV1 over time were associated with more severe BR in adulthood.     

Risk factors for bronchial hyperresponsiveness in workers exposed to acid anhydrides.

Risk factors for bronchial hyperresponsiveness have previously been established in the general community. In settings where occupational asthma is a risk, it has not been established whether occupational sensitization or measures of exposure are important. Bronchial responsiveness to histamine was measured in a cohort of 506 workers exposed to acid anhydrides. Skin-prick tests were performed with conjugates of phthalic, maleic and trimellitic anhydride with human serum albumin and with common inhalant allergens. Employment and smoking histories were recorded. Occupational exposure was measured using personal air samplers and estimates of past exposure made by retrospective exposure assessment. Three hundred and seventy workers (73%) had bronchial responsiveness measured (median age 39 yrs, range 18-77) and 46 (12%) of these were hyperresponsive (provocative dose causing a 20% fall in forced expiratory volume in one second (FEV1; PD20) < or = 8 micromol). Twelve (3%) of these responsive workers had a skin-prick test reaction to an acid anhydride conjugate, 124 (34%) to a common inhalant allergen, and 148 (40%) were current smokers. Multivariate analysis showed that occupational sensitization, sensitization to a common inhalant allergen, age, and pack-years of smoking were independent risk factors for bronchial hyperresponsiveness. Of these only occupational sensitization was completely independent of baseline FEV1. It is concluded that sensitization to acid anhydrides is a significant risk factor for bronchial hyperresponsiveness. However, measures of personal acid anhydride exposure were not associated with bronchial hyperresponsiveness.     

Bronchial responsiveness in a Norwegian community

Bronchial responsiveness to methacholine was examined in a Norwegian general population sample (n = 490) 18 to 73 yr of age. Altogether, 20 and 6% of the sample had PC20 less than or equal to 32 mg/ml and PC20 less than or equal to 8 mg/ml, respectively. The relationship of bronchial responsiveness to the following potential predictors were examined: sex, age, smoking habits, airway caliber (FEV1), FEV1 percent predicted (%FEV1), urban-rural area of residence, occupational airborne exposure in present job, and total serum IgE. After adjusting for age and FEV1, the odds ratio for PC20 less than or equal to 32 mg/ml was higher for men than for women in smokers and in ex-smokers, but did not vary by sex in nonsmokers, the adjusted odds ratio for PC20 less than or equal to 32 mg/ml in male compared with female smokers being 8.4 (95% Cl: 2.5-37.4). Irrespective of smoking status the sex- and FEV1-adjusted odds ratio for PC20 less than or equal to 32 mg/ml fell with increasing age. For every 10-yr increase in age the adjusted odds ratio for PC20 less than or equal to 32 mg/ml methacholine in nonsmokers decreased by 2.0 (95% Cl: 1.3-3.3). Also FEV1 and %FEV1 were predictors of PC20 less than or equal to 32 mg/ml after adjusting for sex and age irrespective of smoking status. Bronchial responsiveness (PC20 less than or equal to 8 mg/ml) was more prevalent in rural than in urban areas, the adjusted odds ratio being 2.5 (95% Cl: 1.1-5.9) for bronchial responsiveness in rural compared with urban residents after adjusting for sex, age, smoking habits, and FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory consequences of light and moderate smoking in young adults in Chile.

OBJECTIVE: To assess the association between smoking and respiratory symptoms, lung function and bronchial hyperresponsiveness (BHR) in young adults in Chile. SETTING: Selected sample of 1232 subjects aged 22-28 years. DESIGN: In this cross-sectional study, the outcome measures were: respiratory symptoms, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25% and 75% (FEF25-75), FEV1/FVC and BHR. RESULTS: Among the 1232 subjects, 67.7% of the men and 49.4% of the women were smokers; the median cigarettes smoked per day was four for men and three for women. Smoking was associated with wheezing, waking up with a cough, breathlessness following exercise and persistent cough, with odds ratios (OR) between 1.94 (95% CI 1.41-2.66) and 3.12 (95% CI 2.21-4.40) among those smoking > or = 5 cigarettes per day, compared to non-smokers. Smoking < 5 cigarettes was significantly associated with wheezing and waking up with a cough. Smokers had a lower FEV1/FVC than non-smokers by approximately 0.8%. Smoking was not associated with FEV1, FEF25-75 or BHR status. CONCLUSIONS: This study highlights the early effects of smoking on respiratory symptoms. It could help governments in Latin America take vigorous action to deter young people from starting smoking.     

Toward a definition of asthma for epidemiology.

Because there is no "gold standard" for defining asthma for epidemiology, we have defined current asthma as bronchial hyperresponsiveness (BHR) plus recent wheeze (in the 12 months prior to study). To describe the characteristics of groups categorized by these measurements, we studied two samples of children aged 7 to 12 yr: 210 from a population sample and 142 self-identified asthmatics. Bronchial responsiveness to histamine was measured by the rapid method, respiratory symptom history, and asthma medication use by self-administered questionnaire to parents and atopy by skin prick tests to 14 allergens. Children recorded daily Airflometer readings and symptom scores for 2 wk. Children with current asthma had more severe bronchial responsiveness, greater Airflometer variability, more symptoms, more atopy (particularly to house dust mites), and used more asthma medication than children with BHR or recent wheeze alone. Children with BHR, but not with recent wheeze, were intermediate between the current asthma and normal groups in terms of bronchial responsiveness, Airflometer variability, and atopy. Children with recent wheeze and normal responsiveness differed from the normal group only in symptoms and medication use. Our definition of current asthma discriminates a group of children that is clearly different in terms of both clinical features and physiologic measures. As such, it is the most useful definition to date for measuring the prevalence of clinically important asthma in populations.     

Bronchial hyperresponsiveness and adult onset wheeze: the influence of atopy.

The commonly held belief that adult onset wheezing illness is primarily nonatopic in nature suggests that the role of atopy in the pathophysiology of bronchial hyperresponsiveness (BHR) in adult onset wheeze may be minimal. This study examined risk factors for BHR (BHR: provocative dose causing a 20% fall in forced expiratory volume in one second PD20 < or =16.38 micromol methacholine) among 82 subjects with adult onset wheeze and among 191 subjects who had never wheezed. Subjects were identified from a cohort of subjects aged 39-45 yrs who were known to have had no childhood wheeze and who were involved in a 30 yr follow-up survey. Risk factors for BHR were examined among all subjects with BHR and among subjects with BHR stratified according to whether or not they had ever wheezed. The prevalence of BHR was 40% (33/82) among the subjects with adult onset wheeze and 11% (21/191) among the subjects who had never wheezed. Lower baseline lung function (odds ratio (OR) = 0.94; 95% confidence interval (CI) = 0.92-0.97 per unit forced expiratory volume (FEV1)% predicted) and atopy (OR = 7.23; CI = 2.53-20.64 for all three measures of atopic compared to nonatopic) were associated with BHR, while smoking and family history showed no statistically significant relation to BHR. This pattern was also apparent in analyses stratified by symptom status. A family history of atopy increased the risk that BHR was accompanied by wheezing symptoms (OR = 4.75; CI = 1.53-14.72 for more than one affected relative compared to no affected relatives). These findings suggest that atopy is associated with bronchial hyperresponsiveness in adults known to have had no childhood wheeze. A familial factor reflecting genetic influences and/or shared environmental factors may influence whether bronchial hyperresponsiveness is associated with symptoms.     

Factors associated with bronchial hyperresponsiveness in Australian adults and children.

To accurately assess putative risk factors for bronchial hyperresponsiveness (BHR), we have used multivariate models to analyse data from 4,366 children living in four regions and from 878 adults. A standard protocol was used to measure bronchial responsiveness to histamine. The prevalence of BHR was high at 7-9 yrs (16-18%), decreased significantly at 11-14 yrs (7-8%), and then increased in adults (12-14%). Atopy was the most important risk factor for BHR at all ages. In children, parental asthma, early respiratory illness and being born in Australia also had a significant influence, and eating fish more than once a week had a protective effect. No effect of parental smoking, gender or race was found. In adults, BHR was associated with being female and with smoking history. It appears that many factors have a significant influence on the presence of BHR, with environmental factors, particularly atopy, birthplace and diet, being the most important.     

Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up

The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non-asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non-asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR.     

Bronchial hyperresponsiveness in patients with squamous cell lung cancer

OBJECTIVE: The aim of this study was to examine the relationship between bronchial hyperresponsiveness, both in vivo and in vitro, and the type of lung cancer (squamous cell or adenocarcinoma). METHODOLOGY: We measured airway responsiveness by methacholine inhalation test in 33 patients with squamous cell lung cancer and 44 patients with lung adenocarcinoma. In addition, airway smooth muscle reactivity to acetylcholine was measured in vitro in specimens from some patients. RESULTS: Seventeen of 33 patients with squamous cell cancer and three of 44 patients with adenocarcinoma showed bronchial hyperresponsiveness (BHR). Multiple regression analysis as used to assess the log of the minimum cumulative dose to decrease respiratory conductance vs six variables: cancer phenotype, FEV1 (% predicted), FEV1/FVC (%), smoking pack years, gender and the location of tumour. The phenotype (squamous cell cancer) was the only factor associated with BHR. However, there was no significant difference in airway smooth muscle reactivity to acetylcholine in vitro in bronchial muscle samples from squamous cell cancer patients (n = 6) and adenocarcinoma patients (n = 6). CONCLUSION: The present findings suggest that bronchial hyperresponsiveness in patients with squamous cell lung cancer is not determined solely by bronchial smooth muscle hyperreactivity.     

Interleukin-4 is involved in allergen-induced airway eosinophilic inflammation and bronchial hyperresponsiveness independent of genetic background

The role of interleukin (IL)-4 in the development of allergen-induced airway inflammation and bronchial hyperresponsiveness (BHR) is still controversial. To investigate the role of IL-4 in the development of antigen-induced airway inflammation and BHR, we used two different inbred IL-4 gene-knockout mice; one was BALB/c, which is known to be a high IgE responder, and the other was C57BL/6, known to be a low IgE responder and a lower responder to acetylcholine (ACh) in the airways. Mice were immunized with antigen at intervals of 12 days. Starting 10 days after the second immunization, mice were exposed to antigen three times every fourth day. Twenty-four hours after the last antigen challenge, bronchial responsiveness to ACh was measured and bronchoalveolar lavage was performed. In sensitized BALB/c mice, repeated aeroallergen challenge induced dramatic eosinophilia in the airways and severe increases in bronchial responsiveness to intravenous ACh, along with increases in serum antigen-specific IgE. In contrast, immunized C57BL/6 mice, after antigen provocation, developed a minor influx of eosinophils into the airways and only moderate increases in bronchial responsiveness without antigen-specific IgE in serum, indicating that the genetic background influenced not only IgE synthesis, but also the degree of airway inflammation and BHR. Moreover, disruption of the IL-4 gene in both strains of mice abolished allergen-induced BHR, airway eosinophilia and IgE response. Together, these findings suggest that the differences in genetic background can directly influence the pathophysiology of bronchial asthma, including the role of IgE, and that IL-4 has a crucial role in the development of allergen-induced BHR independent of genetic background.     

Associations between reduced diffusing capacity and airflow obstruction in community-based subjects

INTRODUCTION: The purpose of this analysis was to determine if abnormal diffusing capacity of the lung for carbon monoxide (DLco) identified a group of subjects with significantly different characteristics than those with normal lung function or airflow obstruction alone. METHODS: Participants were a random sample of adults aged 45-70 years. They completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of single breath DLco. Subjects were categorized into one of three groups: airflow obstruction only, reduced DLco only, or both airflow obstruction and reduced DLco. RESULTS: Individuals with airflow obstruction and reduced DLco in combination reported more symptoms than those with either condition alone. In subjects with a combination of both airflow obstruction and reduced DLco, a significantly higher proportion reported use of medication and laboratory tests. Current smoking was significantly associated with a reduced DLco alone and in combination with airflow obstruction, however, the association was stronger in those with DLco and airflow obstruction. Bronchial hyperreactivity (BHR) was found to be a risk factor while atopy was associated with a reduced risk of DLco and airflow obstruction. CONCLUSIONS: Reduced DLco plus airflow obstruction together identifies a group of individuals with significantly more symptoms and worse lung function. Current cigarette smoking, early life serious respiratory infection and BHR were strongly associated with reduced DLco in combination with airflow obstruction.     

Bronchial hyperreactivity in patients with mitral stenosis before and after successful percutaneous mitral balloon valvulotomy

OBJECTIVES: We aimed to identify the bronchial response to inhaled methacholine in patients with mitral stenosis (MS) and to clarify whether or not the bronchial hyperreactivity (BHR) is reversible after percutaneous mitral balloon valvulotomy (PBMV). PATIENTS AND SETTING: Thirty patients with MS and 28 age-matched healthy control subjects were prospectively evaluated with pulmonary function tests and methacholine challenge. The productive concentration of methacholine causing 20% decrease in FEV(1) (PC(20)) was calculated and used as a parameter of bronchial responsiveness. BHR was defined as a PC(20) < 8 mg/mL. Mean pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) were recorded in all patients through a Swan-Ganz balloon-tipped catheter. Sixteen patients underwent PMBV, and a methacholine test was repeated after each procedure. RESULTS: Bronchial response to methacholine was significantly increased in patients with MS, so that 53% of them had BHR, whereas all control subjects were nonresponders. The PC(20) was closely correlated with the PAP (r = - 0.777; p < 0.001), PCWP (r = - 0.723; p < 0.001), and mitral valve area (MVA; r = 0.676; p < 0. 001). Balloon valvulotomy was successfully performed in all of the 16 patients, and the cardiac parameters (MVA, PAP, and PCWP) significantly improved after the procedure. In contrast, no significant changes were shown in pulmonary function test variables (total lung capacity, vital capacity [VC], FEV(1), and FEV(1)/VC). Although significant improvement was observed in the mean PC(20) values (from 4.97 +/- 5.24 to 7.47 +/- 6.96 mg/mL; p = 0.0006), BHR was completely eliminated in only one patient. CONCLUSIONS: Our data shows that BHR is fairly common among patients with MS, and severity of bronchial responsiveness is significantly correlated with the severity of MS. Moreover, PMBV leads to significant reduction in pulmonary congestion and a consequent improvement in BHR.     

Bronchial hyper-responsiveness and exhaled nitric oxide in chronic obstructive pulmonary disease

Several lung diseases including asthma and chronic obstructive pulmonary disease (COPD) involve chronic inflammation of the airways. Therefore, there is great interest in non-invasive methods assessing airway inflammation. Measurement of bronchial hyper-responsiveness (BHR) and exhaled nitric oxide (NO) are such indirect markers of airway inflammation. Additional information about severity of disease, prognosis and possible response to anti-inflammatory treatment with inhaled corticosteroids can be gained by these methods. However, they are not yet established in assessing patients with COPD in clinical routine. BHR has long been recognised as a hallmark of asthma. Less is known about prevalence and clinical relevance of BHR in the general population and in COPD patients. Longitudinal studies have shown that BHR in healthy persons is a risk factor for development of respiratory symptoms, asthma and COPD. BHR has also been shown to increase the detrimental effect of cigarette smoke and is associated with a decline in lung function. Furthermore, studies indicate that the presence of BHR is a prognostic factor in COPD. Increased BHR to histamine has been shown to be a predictor for mortality in COPD patients. Based on current guidelines, treatment of patients with severe COPD (GOLD stage III and IV) and regular exacerbations includes therapy with inhaled corticosteroids. Inhaled corticosteroids have been shown to reduce frequency of exacerbations but they have not been shown to modify long-term decline in FEV1. However, one small study found that BHR to inhaled mannitol could possibly predict responsiveness to inhaled corticosteroids in patients with moderately severe COPD and identify a subgroup of patients that is likely to benefit from this treatment. Exhaled NO has been shown to correlate with other inflammatory markers and to be elevated in asthma. In COPD patients, data is inconsistent. However, measuring exhaled NO may have a role in the identification of patients with severe, unstable COPD who were shown to have higher NO levels compared to patients with stable COPD. This suggests that exhaled NO might be a method to assess and monitor disease activity in COPD. Possible explanations for the contradictory results are different measurement techniques of exhaled NO and different smoking histories of patients in various studies. Smoking has been found to be a confounding factor by reducing NO levels significantly, an effect which might counteract the potentially increased exhaled NO due to airway inflammation. In conclusion, measuring BHR and exhaled NO in patients with COPD might provide additional information about disease severity, prognosis and possible response to anti-inflammatory medical treatment. However, to establish these methods in clinical routine in COPD patients, more data is clearly needed.     

The relation of adult bronchial responsiveness to serious childhood respiratory illness in the ECRHS

BACKGROUND: Respiratory symptoms in adulthood have been found to be associated with childhood respiratory infection, but few studies have analyzed adult bronchial responsiveness (BHR) with adequate adjustment for known risk factors. OBJECTIVE: To estimate the relation of BHR with serious childhood respiratory infections in a large population study. METHODS: The European Community Respiratory Health Survey (ECRHS) was a cross-sectional population-based survey in 34 centers. Data on serious respiratory infections before the age of 5 years and possible confounders were obtained from a questionnaire administered in the clinic. Blood samples were taken for measurement of total immunoglobulin E (IgE) and specific IgE to four common allergens, and spirometry and bronchial challenge with methacholine were performed. A continuous measure of BHR was analyzed by multiple regression, in 11,282 participants, in relation to serious respiratory infection and other potential risk factors, adjusted for center and major determinants of adult BHR. RESULTS: Those reporting a serious childhood respiratory infection had greater BHR, by an amount corresponding to approximately 0.23 doubling doses (95% confidence interval 0.02-0.44) of the amount of methacholine causing a 20% fall (PD(20)) in forced expiratory volume in 1s (FEV(1)). All childhood factors explained less than 0.3% of variation in BHR in addition to over 20% by factors measured in adulthood. The relation of BHR to BMI was confined to smokers. CONCLUSIONS: We found an effect of serious childhood respiratory infection on adult BHR, but this was small in comparison to relations of BHR to IgE-sensitization and airway caliber.     

吸烟者慢性阻塞性肺疾病易患因素的研究

目的　通过病例对照研究,探讨吸烟者慢性阻塞性肺疾病（ＣＯＰＤ） 的易患因素。方法病例组为１５４ 例吸烟指数（每日平均吸烟支数×吸烟年数） ≥３００ 、无慢性呼吸道疾病症状的ＣＯＰＤ 患者,其一秒钟用力呼气容积占用力肺活量的比值（ＦＥＶ１／ＦＶＣ）＜ ７０％ ;在同居住地（乡镇）按１：１ 配对选择同年龄（ ±３ 岁） 、同性别的吸烟者（无慢性呼吸道疾病症状, 且ＦＥＶ１／ＦＶＣ≥７５ ％） 作为吸烟对照组;另检查了２３ 名从不吸烟、无慢性呼吸道疾病症状,且ＦＥＶ１／ＦＶＣ≥７５ ％ 者作为正常对照组。做问卷、查体、心电图、Ｘ线胸片、肺功能、支气管反应性及包括α１ 抗胰蛋白酶（α１ＡＴ） 活性、弹性蛋白酶活性、丙二醛（ＭＤＡ）、前胶原Ⅲ肽（ＰⅢＰ）、ＩｇＥ、ＩｇＧ等血清学检查。结果　两组一般情况的均衡性检验无显著性差异,资料有可比性。血清学检查：病例组α１ＡＴ活性明显低于吸烟对照组和正常对照组,差异有非常显著意义（ Ｐ＜ ０－０５） ,后两组间差异无显著意义;病例组与吸烟对照组间ＰⅢＰ及ＩｇＥ无显著性差异,但均高于正常对照组。病例组支气管反应性阳性率为７８ ％ ,ＰＣ２０ 为（１－４ ±１－６）ｇ／Ｌ;吸烟对照组阳性率为２８％ ,Ｐ     

Bronchial hyperresponsiveness in two populations with different prevalences of atopy.

SETTING: Random population samples of young adults from Tartu, Estonia (n = 307) and Uppsala, Sweden (n = 498) in the framework of the European Community Respiratory Health Survey (ECRHS). OBJECTIVE: To compare the prevalence and risk factors for bronchial hyperresponsiveness (BHR) to methacholine in two centres with similar climate and ethnicity but differences in the prevalence of atopy, asthma and respiratory symptoms. DESIGN: General population-based cross-sectional survey. RESULTS: The prevalence of BHR using the cut-off points 1.5, 1.0 and 0.5 mg was 19%, 12% and 8% in Tartu and 11%, 7% and 2%, respectively, in Uppsala. Current smoking was a common risk factor for BHR in both centres. Female sex (odds ratio [OR] 2.9), sensitisation to cat (OR 5.9) and visible mould in the home (OR 2.4) were independent risk factors for BHR in Tartu. In Uppsala, BHR was significantly associated with total IgE levels (OR 2.0) and exposure to environmental tobacco smoke (OR 3.3). CONCLUSION: The high prevalence of BHR can explain the high prevalence of respiratory symptoms in Tartu and indicates that causes other than asthma and atopy can be responsible for the high prevalence of BHR in a population.     

A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status.

This study describes the natural history of atopic and wheezy disorders from birth to adult life in a cohort at risk of atopy. One hundred subjects born in Poole, England, were selected at birth in 1976 on the basis that at least one parent was atopic. Subjects were examined annually in the preschool years, and at the ages of 11 and 22 yr. Skin prick tests and total serum immunoglobulin E (IgE) were performed at each visit, and at 11 and 22 yr, bronchial hyperresponsiveness (BHR) to inhaled histamine was measured. Sixty-three subjects remained on follow-up at 22 yr. The annual prevalence of both wheeze and atopy increased with age. Twenty-five percent of adults showed both wheeze and BHR (asthma). Remission of wheeze was common in subjects younger than 5 yr of age and likely if wheezing occurred on less than two occasions, but wheeze at 11 yr was likely to persist. Sixty percent of the adult subjects with asthma developed sensitivity to common allergens by the age of 2 yr and were showing BHR by mid-childhood. Sensitization to dietary allergens occurred in infancy and waned after early childhood but predicted the early sensitization to inhalant allergens. In conclusion, adults with asthma can begin wheezing at any age but tend to sensitize early and have abnormal airway characteristics by the age of 11 yr.