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.     

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.     

Intestinal helminth infestation is associated with increased bronchial responsiveness in children

Non-atopic asthma is the predominant phenotype in non-affluent parts of Latin America. We recently reported that infestation with Ascaris lumbricoides increased the risk of non-atopic asthma in less affluent areas of Brazil but the mechanism is unclear. The present study was conducted to determine whether helminth infestation is associated with heightened bronchial responsiveness (BHR), a common finding in asthma. A random sample of 50 asthmatic and 50 non-asthmatic controls (mean age 10.1 years) were selected from a larger cohort (n = 1,011) without knowledge of their helminth infestation status. Three stool samples were collected from each child on different days and each sample was analyzed by the Kato-Katz method for quantitative determination of helminth eggs. Bronchial provocation tests were performed with inhaled 4.5% hypertonic saline using the ISAAC Phase II standardized protocol. There was no difference between the prevalence of positive BHR in the asthmatics (20.4%) compared with the controls (14.6%) (P = 1.0). Helminth infestation was detected in 24.0% of children, with A. lumbricoides being the most common. Children with high load infestation (>or=100 eggs/g) were five times more likely to have BHR than children with low load or no infestation. Despite the small sample size the results of the present study suggest that the link between high load helminth infestation and non-atopic asthma may be mediated via heightened bronchial responsiveness, possibly due to an inflammatory response to the pulmonary phase of the helminth life cycle.     

The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.     

Bronchial Sensitivity to Histamine in Former Asthmatics: Redevelopment of Symptoms During a Year of Followup

The aim of this protocol was to study bronchial responsiveness in 23 former asthmatics who were free of symptoms for at least 5 years. Bronchial hyperreactivity (BHR) was evaluated with histamine challenge test and the results were compared with those of 20 normal subjects and 20 current asthmatic patients. Among the former asthmatics 65% fulfilled the criteria of BHR. During 1 year of followup, two former asthmatics redeveloped asthma symptoms. Interestingly, one patient had no BHR when initially tested. These findings suggest that the absence of BHR does not guarantee the nonrecurrence of asthma symptoms in former asthmatics.     

Astograph法支气管激发试验对哮喘诊断价值的研究

目的 评价Astograph法支气管激发试验在哮喘诊断中的价值.方法 测定80例哮喘患者和125例非哮喘患者的肺功能和气道反应性、敏感性,应用统计学方法分析两组指标间的差异,寻找能够诊断哮喘的指标及其临界值.结果 肺功能各项指标哮喘组均低于非哮喘组(FVC除外).激发试验指标Dmin和PD35哮喘组低于非哮喘组(P<0.01),但Rrs、Grs、SGrs、SGrs/Grs间的差异无统计学意义(P>0.05).哮喘组中SGrs与Dmin、PD35正相关(P<0.01;r=0.5029,0.2937).非哮喘组SGrs与PD35相关(P<0.01,r=-0.4264).以Dmin诊断哮喘,ROC曲线下面积为0.956,临界值5.9165,敏感性0.966,特异性0.925.以PD35诊断哮喘,ROC曲线下面积为0.949,临界值13.277,敏感性0.977,特异性0.895.结论 Astograph法气道激发试验有助于支气管哮喘的诊断,其中以Dmin≤5.9165 Unit或PD35≤13.277 Unit为阳性标准有较好的特异性及敏感性.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

Bronchial hyperresponsiveness in childhood: A narrative review

Bronchial hyperresponsiveness (BHR) is an important but not asthma-specific characteristic and can be assessed by direct and indirect methods, based on the stimulus causing airway obstruction. BHR has been proposed as a prognostic marker of asthma severity and persistence, and may also be used to control pharmacological management of asthma. The most recent data on the prevalence and development of BHR in childhood and its predictive value for subsequent asthma development in late adolescence and adulthood is discussed in this review. According to the BHR-related scientific articles written in the English language and indexed in the publicly searchable PubMed database, the prevalence of BHR varies based upon the methods used to assess it and the population examined. In general, however, BHR prevalence is reduced as children grow older, in both healthy and asthmatic populations. While asthma can be predicted by BHR, the predictive value is limited. Reduced lung function, allergic sensitization, female sex, and early respiratory illness have been identified as risk factors for BHR. The collective studies further indicate that BHR is a dynamic feature related to asthma, but asymptomatic BHR is also common. Ultimately, the prevalence of BHR varies depending on the population, the environment, and the evaluation methods used. While both the methacholine challenge and the exercise test may predict asthma in adolescence or early adulthood, the predictive value is higher for the methacholine challenge compared to the exercise test. The collective data presented in the present study demonstrate how BHR develops through childhood and its relation to bronchial asthma.     

Real-life environmental tobacco exposure does not affect exhaled nitric oxide levels in asthmatic children.

Serial measurement of exhaled nitric oxide (eNO) has been shown to be a good noninvasive marker of asthma control. Active smoking decreases eNO levels. The effect of real-life environmental exposure to tobacco smoke (ETS) on eNO levels is not known. Our objective was to study the impact of environmental tobacco exposure on eNO levels in asthmatic and non-asthmatic children. Single breath off-line collection of eNO was performed in asthmatic and non-asthmatic children with and without ETS. Urine was collected for cotinine/nicotine analysis. Fifty-seven children were enrolled, of which 25 were asthmatic and 32 had smoke exposure. One active smoker was excluded from the data analysis. The mean eNO was 11.1 ppb (n = 31; SD = 18.5) in those passively exposed vs. 11.1 ppb (n = 25; SD = 19.9) among the unexposed (not statistically significant). The mean eNO was 6.1 (n = 32; SD = 4.4) among the non-asthmatics and 17.8 (n = 24; SD = 27.4) among the asthmatics (p = 0.02; CI: 1.9-21.6). Real-life environmental tobacco exposure does not appear to decrease eNO levels in asthmatic children. Off-line collection of exhaled nitric oxide with a Mylar collection device helps differentiate asthmatics from non-asthmatics.     

Vocational and working career of asthmatic adolescents is only slightly affected

INTRODUCTION: The aim of this study was to investigate whether teenagers and adolescents (10-22 years) with asthma or asymptomatic bronchial hyperresponsiveness, were more likely to experience vocational or professional career limitations in the future, as compared to non-asthmatic contemporaries. METHODS: Data were used from a 14-year follow-up study in general practice, investigating the relationship between respiratory health in childhood and adolescence. At follow-up, the respiratory health status and information about career limitations were obtained. RESULTS: There were no statistical significant differences between asthmatics (n=52) and non-asthmatics (n=154) in the proportion currently employed subjects, or contract type. Most examined career limitations were infrequently reported in both groups, but seemed to occur slightly more frequent among asthmatics. Asthmatics seemed to have an increased risk for limitations in daily activities both attributable to their respiratory health (OR=2.6, 95% CI [1.0; 7.0]) and all-cause (OR=1.8, 95% CI [0.9; 3.3]), and for absence from work all-cause (OR=1.7, 95% CI [0.9; 3.3]). However, the differences were in most cases in the magnitude of only a few days per year. Neither lung function nor bronchial hyperresponsiveness did predict absence from work, or limitations in daily activities. CONCLUSION: Asthmatic young adults seem to experience somewhat more limitations in their vocational and professional careers. Nonetheless, the majority of the young asthmatics seem to be only slightly limited in their careers. In non-asthmatic young adults the presence of asymptomatic bronchial hyperresponsiveness does not seem to lead to career limitations.     

Epithelial Apoptosis and Loss in Airways of Children with Asthma

Objective. To examine loss and apoptosis of bronchial epithelial cells in children with asthma. Methods. We examined endobronchial biopsies from 13 asthmatic children and 11 non-asthmatic control subjects with other respiratory diseases. Postmortem samples were obtained from six children who died from non-respiratory diseases. We examined bronchial epithelial shedding by morphology; expression of caspase-3 and terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) were used to study bronchial epithelial apoptosis. Results. We found epithelial loss to be increased in asthmatic children compared with non-asthmatic control subjects (p = .001) and postmortem children (p = .001). Caspase-3⁺ epithelial cells were significantly greater in children with asthma compared with both non-asthmatic control subjects (p = .001) and the postmortem group (p = .002); TUNEL⁺ epithelial cells were also increased in columnar cells in the asthmatic children compared with the non-asthmatic control subjects (p = .002) and the postmortem group (p = .001). Eosinophilia was absent in 11 of 13 asthmatic children, although they tended to have submucosal lymphocyte infiltration. Smooth muscle and mucus gland hyperplasia were seen in some asthmatic children whose biopsy specimens included these structures. Basement membranes of childhood asthmatics were thicker than in non-asthmatic controls (p = .002) and postmortem subjects (p = .001). Conclusion. Generally, apoptosis and loss of bronchial epithelial cells were increased in childhood asthma; increased apoptosis might be related to epithelial loss.     

双盲对照吸入倍氯以一年对道高反应性与哮喘的防治作用

目的 探讨长期吸入糖皮质激素对哮喘患的治疗作用和无症状的气道高反应性（ＢＨＲ）发生哮喘的预防作用。方法 以随机、双盲对照法比较５９例ＢＨＲ学生，年龄１２－１８岁，吸入倍氯米松粉剂（ＢＤＰ，６００μｇ／ｄ）安慰剂１年对气道反应性及哮喘症关诉作用。结果 试试验１年后哮喘ＢＤＰ组气道高反应性（使ＦＥＶ１较基础值下降２０％的累积吸入组胺量的对数ｌｇＰＤ２０－ＦＥＶ１）显下降（分别为０．３８５±０．４     

Measuring morbidity in adult asthmatics.

SETTING: Whereas prevalence studies usually involve a general population sample, morbidity studies often involve the evaluation of factors that affect asthma severity within an asthmatic population. OBJECTIVE: To review methods of measuring morbidity in adult asthmatics, and to assess the appropriateness of the available methods in a variety of research contexts. FINDINGS: As in prevalence studies, symptoms are the cornerstone of studies of asthma morbidity. These may be supplemented by physiological measures including daily peak flow measurement, but bronchial hyper-responsiveness (BHR) testing is usually impractical, and there is no simple relationship between current asthma severity and current levels of BHR in individuals. Health service and medication usage are often taken as measures of asthma morbidity, but they may be inappropriate in studies in which increased contact with the health services is an intended or unintended effect of participation. Measures of quality of life can be a useful complement to more 'objective' methods. CONCLUSIONS: In studies of morbidity in adult asthmatics, the emphasis should be on using 'appropriate methodology', and methods that may be appropriate in one context may be completely inappropriate in another.     

Allergy and asthma

An increased prevalence of sensitization to inhalants in asthmatic children is well known. Bronchial hyperresponsiveness is regarded as a major characteristic of bronchial asthma and is partly acquired during life as a result of a permanent airway irritation to inhaled allergens. We investigated 704 schoolchildren of two different climate areas for existing bronchial hyperreactivity (cumulative carbachol test) and sensitization to ten common aeroallergens (by skin prick test). Additional information on residential factors, passive smoking, and clinical symptoms for asthma was obtained by a standardized interview and compared with the clinical results. Among 35 of 704 children who were considered as asthmatics, 83% demonstrated a sensitization to one or more allergens. On the contrary, only one third of the nonasthmatic population (n = 669) showed sensitization in the skin test. The relative risk for allergy in children with bronchial hyperreactivity was increased (odds ratio 3.0). Therefore we regard sensitization to common inhalants as an important predictor of asthma in childhood.     

Asthma severity,allergy and lung function during young middle life in subjects with asthma in childhood

The further course of asthma severity lung function, bronchial hyperresponsiveness (BHR) to cold air challenge (CACh), clinical allergies and allergic sensitization in young middle adulthood was studied in a cohort of 55 subjects with childhood asthma. All subjects (27 females) have attended all five previous and the current follow-up visit, undertaken at a mean age of 35 years. Twelve subjects (22%) reported no current asthma, 28 (51%) mild/intermittent, and 15 (27%) moderate/severe asthma. Asthma severity changed little in the individual subjects over the last 5-year period. Females continued to have higher asthma severity scores than the males, but the previously noted lower resting and post-bronchodilator % predicted FEV1 in females was not confirmed now. Pathological BHR to CACh tended to be more common among the males. Forty-four subjects were still allergic to animal danders and 35 to pollens. Sensitization rates (skin prick test or RAST) were similar to those recorded 5 years earlier and there was no clear evidence of tolerance developing. Five subjects have never shown evidence of allergy or sensitization. The extent of sensitization to animal danders showed statistically significant relationships to asthma severity and BHR to CACh. Social development and professional careers continued to be good.     

Bronchial responsiveness to beta-adrenergic stimulation and enhanced beta-blockade in asthma

OBJECTIVE: Beta-adrenergic blocking drugs have no effect on the airways of normal subjects but in asthma even small doses may cause severe deterioration. A seemingly obvious explanation for this abnormal sensitivity is that asthmatic airways, but not normal airways, are tonically dilated by the sympatho-adrenal system. However, studies suggest that sympatho-adrenal activity is normal in asthma, as is bronchial sensitivity to beta-agonists. The present study re-examines bronchial beta-adrenergic sensitivity in asthma and also measures antagonism produced in normal and asthmatic bronchi by a beta-blocking drug. METHODOLOGY: The threshold bronchodilator doses of inhaled isoprenaline (dose required for a 35% increase in specific airway conductance 'PD35') was measured in 11 normal and 14 asthmatic adults on two separate occasions. After administering propranolol (inhaled or intravenously) PD35 was remeasured. RESULTS: Sensitivity to isoprenaline was greater in symptomatic asthmatics (PD35 = 0.003 micromol) than in asymptomatic asthmatics (PD35 = 0.021 micromol) and in non-asthmatics (PD35 = 0.123 micromol; P < 0.001 in each case). Symptomatic asthmatics also showed 66-fold more antagonism than non-asthmatics when they were given propranolol by inhalation (P < 0.001) and sixfold more with intravenous propranolol (P = 0.005). CONCLUSIONS: The increased sensitivity of asthmatics to inhaled isoprenaline suggests that they may also be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways. Taken with enhanced antagonism by propranolol, this provides insight into the aggravation of asthma by beta-blocking drugs.     

Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis

In sensitized subjects with allergic rhinitis (AR) or asthma, allergen exposure provokes symptoms. Among non-asthmatics with AR, an association between allergen sensitization, pollen season and lower airway inflammation has been demonstrated. Our aims were to compare AR and asthma with regard to patterns of allergen sensitization, the degree of airway hyperresponsiveness (AHR) and levels of exhaled nitric oxide (ENO). Finally, we wanted to relate our findings to previous or current exposure to household pets. Four hundred and thirty-one adolescents with different clinical phenotypes were randomly selected from a large-scale epidemiological survey. They were investigated with allergy screening, measurements of ENO and a methacholine bronchoprovocation test. Sensitization to pet allergens (cat, dog and horse) was associated with increased AHR and ENO both in asthmatics and non-asthmatics with AR. The risk of being sensitized to cat allergens was significantly reduced in those who had kept cats vs. those who had never kept them. Keeping dogs or horses did not influence the risk of being sensitized to the respective allergens. Only in steroid-naive, non-smoking asthmatics, a trend towards increased ENO in those sensitized and exposed to cat or dog allergens was seen. Although sensitization towards pet allergens was associated with inflammation in the lower airways irrespective of clinical phenotype, keeping pets did not increase the risk of being sensitized to pet allergens.     

Defining asthma in epidemiological studies.

It has been suggested that, in epidemiological studies, asthma should be defined as symptomatic bronchial hyperresponsiveness (BHR). This paper critically examines the validity of this and alternative methods of defining asthma by reviewing population-based studies validating BHR and symptom questionnaires against asthma defined on the basis of a clinical assessment. It is emphasized that a single definition of asthma will not be applicable to all studies. When the aim of a study is to compare differences in prevalence of asthma between populations, Youden's Index (sensitivity + specificity - 1) is the best single measure of validity. BHR has similar or better specificity, but much worse sensitivity, and therefore a worse Youden's Index, than symptom questionnaires. When the aim is to estimate relative risks, the validity of the definition of asthma depends more on its positive predictive value. Therefore, more specific methods of detecting asthmatics, such as severe symptoms, diagnoses of asthma, or symptomatic BHR may be most useful in cohort and case-control studies. In contrast, conversely, the method of choice for the first phase of prevalence comparisons is standardized written or video symptom questionnaires. In order to explore reasons for the differences in asthma prevalence, and to estimate possible differential symptom reporting, questionnaires can be supplemented with bronchial hyperresponsiveness and other testing in subsamples of the symptomatic and nonsymptomatic subjects. However, symptoms and bronchial hyperresponsiveness should usually be analysed separately rather than combined due to the poor agreement between bronchial hyperresponsiveness and clinical asthma.     

Matrix metalloproteinase-9 expression in asthma: effect of asthma severity,allergen challenge,and inhaled corticosteroids

BACKGROUND: Asthma is associated with remodeling of the extracellular matrix (ECM) and increased airway obstruction, and the mechanisms of this process are unknown. Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP). STUDY OBJECTIVE:s: To determine whether severe, persistent asthma is associated with increased levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels. DESIGN: Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge and in BALF after inhaled steroid therapy. PATIENTS: Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum studied. Fourteen of the patients with mild asthma underwent allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks treatment with inhaled budesonide, 800 micro g bid, or placebo. RESULTS: Patients with severe asthma had increased levels and activity of sputum MMP-9 in their sputum compared with patients with mild asthma and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients with mild asthma. CONCLUSIONS: MMP-9 may play a role in chronic airway inflammation and remodeling in asthma, as concentrations are increased in severe, persistent asthma and following allergen challenge. Inhaled steroids may not affect MMP-9 and TIMP in patients with mild asthma, and additional studies in patients with more severe asthma are needed.     

Bronchial Responsiveness,Spirometry and Mortality in a Cohort of Adults

Objective. Prospective population studies have reported that pulmonary function, measured by forced expiratory volume in one second (FEV₁), is an independent predictor for mortality. Besides, several studies found that death from all causes is higher in asthmatics than in non-asthmatics. However, none of these studies examined whether bronchial hyperresponsiveness (BHR), one of the key features in asthma, can be used as a predictor for mortality. Thus, the aim of this study was to analyze the association between BHR, FEV_1, and all-cause mortality in a population-based cohort of adults. Methods. Within the cross-sectional survey ECRHS-I Erfurt (1990–1992), 1162 adults aged 20–65 years performed lung function tests, including spirometry and BHR testing by methacholine inhalation up to a cumulative dose of 2 mg. BHR was assessed from the methacholine dose nebulized at ≥ 20% fall of FEV₁. After circa 20 years of follow-up, the association between baseline lung function, BHR, and mortality was investigated. Results. A total of 85 individuals (7.3%) died during a mean follow-up period of 17.4 years (SD = 2.4). FEV₁, but not forced vital capacity (FVC), was a predictor for mortality. In men, BHR increased the mortality risk (OR = 2.6, 95% CI: 1.3–5.3; adjusted for age and BMI). Additional adjustment for asthma did not change the results (OR = 2.4, 95% CI: 1.2–5.0). However, after an additional adjustment for pack years of cigarette smoking or airway obstruction, the association was not statistically significant anymore (OR = 1.8, 95% CI: 0.8–4.0, OR = 1.9, 95% CI: 0.9–4.3, respectively). Conclusions. BHR was associated with an increased mortality risk in men. Potential explanatory factors for this association are cigarette smoking, chronic obstructive pulmonary disease (COPD), or asthma. Thus, BHR might be an indirect predictor for all-cause mortality. FEV₁ was an independent predictor for all-cause mortality.