Atopic dermatitis in a high-risk cohort: natural history, associated allergic outcomes, and risk factors.

BACKGROUND: Atopic dermatitis (AD) is commonly associated with asthma and other atopic disorders in childhood. OBJECTIVE: To evaluate the natural history of AD and its association with other allergic outcomes in a high-risk cohort through the age of 7 years. METHODS: A total of 373 high-risk infants, who had undergone a randomized controlled trial with intervention measures for primary prevention of asthma applied during the first year of life, were assessed for asthma, AD, and allergic sensitization at 1, 2, and 7 years. RESULTS: The multifaceted intervention program did not reduce AD despite reducing the prevalence of asthma significantly. Sixty-two children (16.6%) had AD during the first 2 years (early-onset AD); of these, 26 continue to have AD at the age of 7 years (persistent), whereas 36 no longer had the disease (nonpersistent) at the age of 7 years. Twenty-three children (6.2%) developed AD only after the age of 2 years (late-onset AD). Early-onset AD, persistent or nonpersistent, was associated with increased risk of allergic sensitization to food allergens within the first 2 years of life and asthma diagnosis at year 7. However, only persistent AD was associated with an increased risk of other atopic diseases and allergic sensitization to food and aeroallergens at year 7. Late-onset AD was not associated with atopic diseases or allergic sensitization at year 7 with the exception of Alternaria alternans. CONCLUSION: In this cohort of infants at high risk of asthma, early-onset persistent AD, which was highly associated with atopic sensitization, increased the risk of atopic diseases in later childhood and thus appears to be part of the atopic march.

Cotinine versus questionnaire: early-life environmental tobacco smoke exposure and incident asthma.

BACKGROUND: The use of biomarkers has expanded considerably, as an alternative to questionnaire-based metrics of environmental tobacco smoke (ETS); few studies have assessed the affect of such alternative metrics on diverse respiratory outcomes in children, and we aimed to do so. METHODS: We evaluated various measures of birth-year ETS, in association with multiple respiratory endpoints early years of life, in the novel context of a birth cohort at high risk for asthma. We administered questionnaires to parents, both at the end of pregnancy and at one year of life, and measured cotinine in cord blood (CCot; in 275 children) and in urine (UCot; obtained at 12 months in 365 children), each by radioimmunoassay. Multiple logistic regression was used to assess the association of the various metrics with recurrent wheeze at age 2 and with bronchial hyperresponsiveness (BHR) and asthma at age 7. RESULTS: Self-reported 3rd trimester maternal smoking was associated with significantly increased risk for recurrent wheeze at age 2 (odds ratio 3.5 [95% confidence interval = 1.2,10.7]); the risks associated with CCot and 3rd trimester smoking in any family member were similar (OR 2.9 [1.2,7.0] and 2.6 [1.0,6.5], respectively). No metric of maternal smoking at 12 months appeared to significantly influence the risk of recurrent wheeze at age 2, and no metric of ETS at any time appeared to significantly influence risk of asthma or BHR at age 7. CONCLUSIONS: Biomarker- and questionnaire-based assessment of ETS in early life lead to similar estimates of ETS-associated risk of recurrent wheeze and asthma.

Occupational exposure influences on gender differences in respiratory health.

BACKGROUND: The aim of this study was to evaluate gender differences in the respiratory health of workers exposed to organic and inorganic dusts. METHODS: Meta-analysis techniques incorporating logistic regression were applied to a combined file of 12 occupational health studies. RESULTS: Meta-analysis of data on 1,367 women and 4,240 men showed that women had higher odds of shortness of breath whether exposed to inorganic dust or having no occupational exposure, with an overall odds ratio (OR) of 2.07 (95% confidence interval [CI] = 1.57-2.73) adjusted for smoking status, age, body mass index (BMI), ethnic status, atopy, and job duration. Inorganic dust exposure was associated with the highest odds of asthma (adjusted OR = 8.38, 95% CI = 1.72-40.89) for women compared to men, but no differences were found for unexposed workers. With organic dust exposure, men had elevated odds for occasional wheeze and worse lung function compared to women. CONCLUSION: Within the limitations of this analysis, gender differences in respiratory health, as suggested by population-based studies, were confirmed in our analysis of occupational health studies, with the general type of exposure, organic or inorganic, generally determining the extent of differences. The higher risks for women compared to men for shortness of breath were robust regardless of work exposure category, with the highest odds ratios found for asthma.

Congenital anomalies in the offspring of nurses: association with area of employment during pregnancy.

The purpose of this study was to determine whether registered nurses in specific areas of employment during pregnancy had a higher risk for congenital anomalies in their offspring. An offspring cohort (n = 22,611) was created through linkage of the British Columbia Vital Statistics Agency live and stillbirth records from 1986 to 2000, to a female cohort database of registered nurses. Of these, 16,005 (70.8%) were registered in a specific area of employment when pregnant. Odds ratios were calculated using generalized estimating equations (GEE), binary logistic regression with adjustment for sex, mother's age, and year of birth. Elevated risks of congenital anomalies were found for the singleton offspring of nurses employed in the following areas: operating rooms and pediatric nursing units (heart anomalies); maternal newborn units (integument); emergency room (respiratory system); and psychiatry (upper alimentary tract). Further research is needed to determine whether these are chance or consistent findings and whether exposure patterns might provide biological plausibility.

Association between endotoxin and mite allergen exposure with asthma and specific sensitization at age 7 in high-risk children.

The role of endotoxin and house dust mite allergen (HDM) in allergen sensitization and asthma is unclear. The timeframe of exposure and asthma assessment appears critical. We aimed to determine, in children at 7 yr of age, the association between current exposure to endotoxin and HDM and risks of recurrent wheeze, paediatric allergist diagnosed asthma and allergen sensitization. Three hundred and eighty children who had an increased risk of asthma because of family background were assessed at age 7 yr by a questionnaire-standardized interview, allergen skin testing and clinical examination by a paediatric allergist. Dust samples were collected from their homes and analysed for levels of endotoxin and HDM (Der p 1 and Der f 1). Levels of endotoxin in dust samples were associated with protection from paediatric allergist diagnosed asthma with inhaled steroid use (OR 0.69, 95% CI 0.53-0.91) and specific sensitization to dog allergen (OR 0.68, 95% CI 0.51-0.90) at the age of 7 yr; both endotoxin and HDM were associated with decreased risk of sensitization to dog allergen. In high-risk children at age 7, endotoxin levels were associated with decreased sensitization to dog, as well as with decreased asthma.

Respiratory health of two cohorts of terminal grain elevator workers studied 30 years apart.

INTRODUCTION: We evaluated the respiratory health of two cohorts of grain terminal elevator workers who participated in one of either respiratory health surveys undertaken in 1978 and 2008. METHODS: Questionnaire and spirometry data from 584 workers from the 1978 survey and 215 workers from the 2008 survey were compared using logistic regression and general linear modeling. RESULTS: The geometric means of area samples of grain dust averaged 8.28 mg/m(3) in 1978 and 2.06 mg/m(3) in 2008. Workers in the 1978 survey had a significantly higher prevalence of respiratory symptoms (with the largest adjusted odds ratio of 3.78, 95% CI 2.07-7.25, for shortness of breath), a lower prevalence of atopic conditions and lower mean lung function. CONCLUSION: Current grain workers had a lower risk of respiratory health consequences and a greater prevalence of atopic conditions than workers surveyed 30 years prior, most likely associated with reduced exposure to grain dust in the terminal elevator environment.

Airway hyperresponsiveness to methacholine in 7-year-old children: sensitivity and specificity for pediatric allergist-diagnosed asthma.

BACKGROUND: The operating characteristics of PC(20) values used as cut-offs to define airway hyperresponsiveness, as it informs the diagnosis of asthma in children, are poorly understood. We examine data from a unique cohort to inform this concern. OBJECTIVE: Determine the sensitivity and specificity of incremental PC(20) cut-offs for allergist-diagnosed asthma. METHODS: Airway reactivity at age 7 was assessed in children within a birth cohort at high risk for asthma; PC(20) for methacholine was determined by standard technique including interpolation. The diagnosis of asthma was considered by the pediatric allergist without knowledge of the methacholine challenge results. Sensitivity and specificity were calculated using a cross-tabulation of asthma diagnosis with incremental PC(20) cut-off values, from 1.0 to 8.0 mg/ml, and plotted as receiver operator characteristic (ROC) curves. The "optimal" cut-off was defined as that PC(20) conferring maximal value for sensitivity plus specificity while the "balanced" cut-off was defined as that PC(20) at which sensitivity and specificity were most equal. RESULTS: 70/348 children (20.1%) were diagnosed with asthma. The optimal and balanced PC(20) cut-offs, both for all children and for females alone, were respectively 3 mg/ml (sensitivity 80.0%, specificity 49.1%) and 2 mg/ml (sensitivity 63.1%, specificity 64.7%). For males alone, the "optimal" and "balanced" PC(20) cut-offs were both 2 mg/ml. CONCLUSION: For this cohort of 7-year olds at high risk for asthma, methacholine challenge testing using a cut-off value of PC(20) 3 mg/ml conferred the maximal sum of specificity plus sensitivity. For contexts in which higher sensitivity or specificity is desired, other cut-offs may be preferred.

Exposure to anesthetic gases and congenital anomalies in offspring of female registered nurses.

BACKGROUND: Studies of offspring of mothers exposed to anesthetic gases have shown associations with congenital anomalies reported by the mothers, but rarely in studies with objectively ascertained outcomes. We conducted a retrospective cohort study to examine associations between registry-ascertained congenital anomalies in offspring and anesthetic gas exposure of mothers employed as nurses. METHODS: A cohort of registered nurses in British Columbia, Canada, was linked to records of births and congenital anomalies from 1990 to 2000. Exposures were assessed via a survey of anesthetic gas use in all hospitals in the province and records of nurses' jobs, departments, and hospitals. RESULTS: Departments most frequently reporting anesthetic gas use were operating rooms, post-anesthetic recovery rooms, and maternity units. In the cohort of 15,317 live-borne children of 9,433 mothers, 1,079 had congenital anomalies. Anomalies were associated with ever and probable maternal exposure to halogenated gases (ORs: 1.49, 95% CI: 1.04-2.13; and 2.61, 95% CI: 1.31-5.18, respectively) and to nitrous oxide (ORs: 1.42, 95% CI: 1.05-1.94; and 1.82, 95% CI: 1.11-2.99). Anomalies most frequently associated with exposure were those of the heart (OR, halogenated gases: 2.31, 95% CI: 1.07-4.97) and integument (OR, halogenated gases: 3.56, 95% CI: 1.53-8.32; OR, nitrous oxide: 3.02, 95% CI: 1.37-6.64). Gases most frequently associated with anomalies were halothane (predominantly used early in the study period), isoflurane, and sevoflurane (predominantly used later in the period). CONCLUSIONS: In this study, where both exposures and outcomes were assessed objectively, certain congenital anomalies were associated with estimated anesthetic gas exposure.

Cancer incidence and adverse pregnancy outcome in registered nurses potentially exposed to antineoplastic drugs.

BACKGROUND: To determine the relationships of potential occupational exposure to antineoplastic drugs with cancer incidence and adverse pregnancy outcomes in a historical prospective cohort study of female registered nurses (RNs) from British Columbia, Canada (BC). METHODS: Female RNs registered with a professional regulatory body for at least one year between 1974 and 2000 formed the cohort (n = 56,213). The identifier file was linked to Canadian cancer registries. An RN offspring cohort from 1986 was created by linkages with the BC Birth and Health Status Registries. Exposure was assessed by work history in oncology or cancer agencies (method 1) and by estimating weighted duration of exposure developed from a survey of pharmacists and nursing unit administrators of all provincial hospitals and treatment centers and the work history of the nurses (method 2). Relative risks (RR) were calculated using Poisson regression for cancer incidence and odds ratios (OR) were calculated for congenital anomaly, stillbirth, low birth weight, and prematurity incidence, with 95% confidence intervals. RESULTS: In comparison with other female RNs, method 1 revealed that RNs who ever worked in a cancer center or in an oncology nursing unit had an increased risk of breast cancer (RR = 1.83; 95% CI = 1.03 - 3.23, 12 cases) and their offspring were at risk for congenital anomalies of the eye (OR = 3.46, 95% CI = 1.08 - 11.14, 3 cases). Method 2 revealed that RNs classified as having the highest weighted durations of exposure to antineoplastic drugs had an excess risk of cancer of the rectum (RR = 1.87, 95% CI = 1.07 - 3.29, 14 cases). No statistically significant increased risks of leukemia, other cancers, stillbirth, low birth weight, prematurity, or other congenital anomalies in the RNs' offspring were noted. CONCLUSIONS: Female RNs having had potential exposure to antineoplastic drugs were not found to have an excess risk of leukemia, stillbirth, or congenital anomalies in their offspring, with the exception of congenital anomalies of the eye, based on only three cases; however, elevated risks of breast and rectal cancer were observed.

Rates of congenital anomalies and other adverse birth outcomes in an offspring cohort of registered nurses from British Columbia, Canada.

OBJECTIVES: Although there is concern that occupational exposures in some nursing professions may confer reproductive risks, there are few relevant studies. Our objective is to determine if a cohort of female registered nurses (RN) from British Columbia (BC), in comparison to BC women in general, have elevated rates of congenital anomalies, stillbirths, low birth weight, or prematurity in their offspring. METHODS: A cohort of RNs from BC was linked to Vital Statistics birth records and the BC Health Status Registry (HSR) between the years 1986 and 2000. The RN offspring cohort included 23,222 births. For each outcome, odds ratios (OR) with 95% confidence intervals (CI) were determined by comparing rates in the nurses' cohort with the rates in the general population standardized for the year of birth. RESULTS: Apart from chromosomal anomalies, for each of the ICD-9 congenital anomaly categories there were fewer congenital anomalies than expected, resulting in an overall prevalence of congenital anomaly cases (with at least one anomaly) that was significantly lower in the RN cohort (1,567 observed vs. 1,846 expected; OR 0.84, 95% CI 0.78-0.90) in comparison to the general population. Low birth weight (1,138 observed vs. 1,260 expected; OR 0.90, 95% CI 0.83-0.98) was also significantly lower, while prevalence of prematurity and stillbirths were not significantly different than among the general population. CONCLUSION: Offspring of RNs in BC had a lower prevalence of congenital anomalies and low birth weight compared to the rates found among the general population. Further studies are underway to determine if subpopulations within the RN cohort are at risk.

Indoor allergen exposure, sensitization, and development of asthma in a high-risk birth cohort.

Contradictory findings have been observed for the association of house dust mite (HDM), cat, and dog allergen exposure with sensitization and asthma. We sought to determine the relationship between exposures to these allergens, at various points during early childhood, and specific sensitization and asthma at age 7 in a high-risk birth cohort. As part of a multi-faceted Canadian intervention program for the primary prevention of asthma in high-risk infants, children were assessed by pediatric allergists at age 7 for asthma and underwent allergy skin prick testing. House dust samples were analyzed for HDM, cat, and dog allergen levels at several time points during years 1 and 7 of life. Multiple logistic regression analyses were carried out for the combined cohort and separately for the control and intervention groups. Exposure to a higher level of HDM allergen in year 1 or year 7 was associated with a higher risk of year 7 sensitization to HDM but not asthma. Exposure to higher levels of cat allergen in year 1 or year 7 did not affect the risk of year 7 sensitization to cat or asthma. Dog ownership, or exposure to higher levels of dog allergen in year 1 or year 7, did not affect the risk of year 7 sensitization to dog; however, year 7 dog allergen exposure (intervention group only) or ownership was associated with increased year 7 asthma risk. Our findings suggest that in high-risk children, there are allergen-specific associations of exposure with sensitization and with asthma; early life-elevated HDM exposure was associated with risk of sensitization but not asthma while the opposite was true for dog exposure.

Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort.

There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB-IgE in predicting asthma and other IgE-mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE-mediated allergic diseases. CB-IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB-IgE. Fifty-five (19.3%) of infants had detectable CB-IgE (>/=0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB-IgE. CB-IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB-IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention.

Biomarkers of airway acidity and oxidative stress in exhaled breath condensate from grain workers.

RATIONALE: Grain workers report adverse respiratory symptoms due to exposures to grain dust and endotoxin. Studies have shown that biomarkers in exhaled breath condensate (EBC) vary with the severity of airway inflammation. OBJECTIVES: The purpose of the study was to evaluate biomarkers of airway acidity (pH and ammonium [NH(4)(+)]) and oxidative stress (8-isoprostane) in the EBC of grain workers. METHODS: A total of 75 workers from 5 terminal elevators participated. In addition to EBC sampling, exposure monitoring for inhalable grain dust and endotoxin was performed; spirometry, allergy testing, and a respiratory questionnaire derived from that of the American Thoracic Society were administered. MEASUREMENTS AND MAIN RESULTS: Dust and endotoxin levels ranged from 0.010 to 13 mg/m(3) (median, 1.0) and 8.1 to 11,000 endotoxin units/m(3) (median, 610) respectively. EBC pH values varied from 4.3 to 8.2 (median, 7.9); NH(4)(+) values from 22 to 2,400 microM (median, 420); and 8-isoprostane values from 1.3 to 45 pg/ml (median, 11). Univariate and multivariable analyses revealed a consistent effect of cumulative smoking and obesity with decreased pH and NH(4)(+), and intensity of grain dust and endotoxin with increased 8-isoprostane. Duration of work on the test day was associated with decreased pH and NH(4)(+), whereas duration of employment in the industry was associated with decreased 8-isoprostane. CONCLUSIONS: Chronic exposures are associated with airway acidity, whereas acute exposures are more closely associated with oxidative stress. These results suggest that the collection of EBC may contribute to predicting the pathological state of the airways of workers exposed to acute and chronic factors.

Early environmental determinants of asthma risk in a high-risk birth cohort.

Environmental exposures during early life have been suggested to have the greatest impact on childhood asthma. Our aim was to evaluate the risk factors associated with asthma at age 7 yr in a high-risk cohort that participated in a randomized controlled study on the primary prevention of asthma. Indoor exposures were characterized before birth and at 2 weeks, 4, 8, 12, 18, and 24 months after birth and again at 7 yr. Nasal scrapings for respiratory viruses were done at the same intervals during the first 2 yr. At age 7, the children were assessed by a pediatric allergist and had allergy skin tests. Logistic regression analysis was undertaken to evaluate the effect of exposures on asthma for the entire cohort with adjustment for group allocation. In addition to the lower risk of asthma in the intervention group, we found a higher prevalence of asthma at age 7 for males, those having a positive history of asthma in mother, father, or older siblings, for children residing in Winnipeg and for atopic subjects. Upon adjustment for intervention group assignment and baseline factors, significant environmental risk factors during year 1 included dog ownership and respiratory syncytial viral infection detected at 12 months while maternal smoking was protective. Dog ownership was a significant risk factor in year 2, but highly correlated with dog ownership in year 1. Indoor environmental exposures during year 7 were not associated with asthma at age 7. Maternal smoking at year 7 was associated with a reduced risk of asthma at 7 yr. Early-life exposures were more important determinants than those in later years. A 'window of opportunity' exists for intervention measures to be applied.

Within- and between-person variability of exhaled breath condensate pH and NH4+ in never and current smokers.

Recent studies have suggested that the collection of exhaled breath condensate (EBC) may be a viable method in occupational field studies to sample secretions of the lower airway because it is simple to perform and non-invasive. However, there are unresolved questions about whether certain laboratory conditions may influence the analysis of EBC biomarker measurements. A total of 12 subjects performed 116 EBC tests. The effect of short and long-term sample storage and sample volume on two biomarkers of acid stress, pH and NH4+, in EBC were investigated and did not significantly influence either marker measurement after argon deaeration. We also investigated the variability and the effect of smoking on the biomarkers by collecting six samples each from five adult never smokers and five adult current smokers over a period of 1 month (n=60 total). For pH, the within-person and between-person variability was larger in current smokers compared to never smokers. Similar results were found for NH4+. Cigarette packs smoked per day now was also associated with both pH (p=0.01) and NH4+ (p=0.04) using mixed effects regression analysis. The variability and smoking results suggest that repeated measurements of EBC pH and NH4+ from the same individual may accurately predict the biological state of the airways of current smokers when compared to never smokers.

Environmental and occupational exposures: do they affect chronic obstructive pulmonary disease differently in women and men?

This workshop summary examines current research that addresses the question: Are women more susceptible than men to the effects of inhaled pollutants, namely those found in work or residential environments? A systematic literature review was performed in preparation for the workshop. A total of 73 recent (since 2000) articles were retrieved reporting on occupational and environmental exposures and their impact on chronic obstructive pulmonary disease, of which only nine provided gender-stratified results. In two mortality studies, results were contrary (one finding increased chronic obstructive pulmonary disease mortality in relation to traffic among elderly women compared with men, the other finding no gender difference). Two other environmental studies suggested small gender differences with slightly greater effect of biomass or traffic-related pollution among women. Four of five occupational studies also found increased effects of workplace pollutant exposure on measures of chronic airflow obstruction or bronchitis symptoms in women; again the differences were small. Preliminary findings from analysis of pooled data from six cross-sectional occupational surveys by our team also indicated increased relative risk for airflow obstruction in relation to work in industrial or service jobs among women compared with men, but only when airflow obstruction was measured using a gender-specific approach to determining the lower limit of normal. Workshop participants identified five key gaps and research needs, including the development of gender-sensitive tools for conducting future research in this area.

Mortality and cancer incidence in a cohort of registered nurses from British Columbia, Canada.

BACKGROUND: A retrospective cohort study of provincial registered nurses (RNs) from British Columbia, Canada was undertaken to determine risks of mortality and cancer incidence; in particular for breast cancer and leukemia. METHODS: Cohort records of RNs from 1974 to 2000 were linked to Canadian death and cancer registries. Analyses included standardized mortality (SMR) and incidence ratios (SIR) as well as relative risks for internal comparisons. RESULTS: There were 58,125 RNs in the cohort (96.7% females). The SMR for all causes of mortality for female RNs was low, at 0.61 (95% CI, 0.58-0.64). The only elevated SIR for female RNs was for malignant melanoma (1.27; 95% CI, 1.10-1.46). Ever working in a hospital, medical surgical specialties or maternal/pediatrics showed some elevated cancer risks. CONCLUSIONS: Low SMRs for the female RN cohort suggest healthful lifestyles and a healthy worker effect. Length of employment as a nurse, in hospitals and in specific fields was associated with some increased risks of cancer.

Quality of life and employment status of workers with Western red cedar asthma.

OBJECTIVE: The impact of current employment status and other factors on quality of life was evaluated for workers diagnosed with western red cedar asthma in British Columbia, Canada. METHODS: Telephone interviews by questionnaire included the Short Form 36 (SF-36) and Marks Asthma quality-of-life instruments. RESULTS: Of the 302 subjects contacted, 70.5% (n = 213) participated. Employment status was the most consistent predictor of quality-of-life domains, with highest scores for employed subjects, particularly those who were no longer exposed to red cedar. Subjects who had quit work because of their asthma had worse scores, particularly for vitality and general health perceptions. Other factors independently associated with specific aspects of poor quality of life were having asthma-like symptoms, taking medication, and not being married. CONCLUSIONS: Continued employment was associated with better quality of life for workers with western red cedar asthma.

Airflow obstruction in young adults in Canada.

OBJECTIVE: Airflow obstruction is relatively uncommon in young adults, and may indicate potential for the development of progressive disease. The objective of the present study was to enumerate and characterize airflow obstruction in a random sample of Canadians aged 20 to 44 years. SETTING: The sample (n=2962) was drawn from six Canadian sites. DESIGN: A prevalence study using the European Community Respiratory Health Survey protocol was conducted. Airflow obstruction was assessed by spirometry. Bronchial responsiveness, skin reactivity to allergens and total serum immunoglobulin E were also measured. Logistic regression was used for analysis. RESULTS: Airflow obstruction was observed in 6.4% of the sample, not associated with sex or age. The risk of airflow obstruction increased in patients who had smoked and in patients who had lung trouble during childhood. Adjusted for smoking, the risk of airflow obstruction was elevated for subjects with past and current asthma, skin reactivity to allergens, elevated levels of total immunoglobulin E and bronchial hyper-responsiveness. Of the subjects with airflow obstruction, 21% were smokers with a history of asthma, 50% were smokers without asthma, 12% were nonsmokers with asthma and 17% were nonsmokers with no history of asthma. Bronchial hyper-responsiveness increased the prevalence of airflow obstruction in each of these groups. CONCLUSION: Smoking and asthma, jointly and individually, are major determinants of obstructive disorders in young adults. Bronchial hyper-responsiveness contributes to obstruction in both groups.