Margaret W. Gerbase

Bronchial hyperresponsiveness and the development of asthma and COPD in asymptomatic individuals: SAPALDIA Cohort Study

Background: Bronchial hyperresponsiveness (BHR) is a common feature of asthma. However, BHR is also present in asymptomatic individuals and its clinical and prognostic significance is unclear. We hypothesised that BHR might play a role in the development of chronic obstructive pulmonary disease (COPD) as well as asthma. Methods: In 1991 respiratory symptoms and BHR to methacholine were evaluated in 7126 of the 9651 participants in the SAPALDIA cohort study. Eleven years later 5825 of these participants were re-evaluated, of whom 4852 performed spirometric tests. COPD was defined as an FEV1/FVC ratio of <0.70. Results: In 1991 17% of participants had BHR, of whom 51% were asymptomatic. Eleven years later the prevalence of asthma, wheeze, and shortness of breath in formerly asymptomatic subjects with or without BHR was, respectively, 5.7% v 2.0%, 8.3% v 3.4%, and 19.1% v 11.9% (all p<0.001). Similar differences were observed for chronic cough (5.9% v 2.3%; p = 0.002) and COPD (37.9% v 14.3%; p<0.001). BHR conferred an adjusted odds ratio (OR) of 2.9 (95% CI 1.8 to 4.5) for wheezing at follow up among asymptomatic participants. The adjusted OR for COPD was 4.5 (95% CI 3.3 to 6.0). Silent BHR was associated with a significantly accelerated decline in FEV1 by 12 (5–18), 11 (5–16), and 4 (2–8) ml/year in current smokers, former smokers and never smokers, respectively, at SAPALDIA 2. Conclusions: BHR is a risk factor for an accelerated decline in FEV1 and the development of asthma and COPD, irrespective of atopic status. Current smokers with BHR have a particularly high loss of FEV1.

Long-term decline in lung function, utilisation of care and quality of life in modified GOLD stage 1 COPD

Background: Little is known about the long-term outcomes of individuals with mild chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Methods: A population cohort of 6671 randomly selected adults without asthma was stratified into categories of modified GOLD-defined COPD (prebronchodilator spirometry). Further stratification was based on the presence or absence of respiratory symptoms. After 11 years, associations between baseline categories of COPD and decline in forced expiratory volume in 1 s (FEV1), respiratory care utilisation and quality of life as measured by the SF-36 questionnaire were examined after controlling for age, sex, smoking and educational status. Results: At baseline, modified GOLD criteria were met by 610 (9.1%) participants, 519 (85.1%) of whom had stage 1 COPD. At follow-up, individuals with symptomatic stage 1 COPD (n = 224) had a faster decline in FEV1 (−9 ml/year (95% CI −13 to −5)), increased respiratory care utilisation (OR 1.6 (95% CI 1.0 to 2.6)) and a lower quality of life than asymptomatic subjects with normal lung function (n = 3627, reference group). In contrast, individuals with asymptomatic stage 1 COPD (n = 295) had no significant differences in FEV1 decline (−3 ml/year (95% CI −7 to +1)), respiratory care utilisation (OR 1.05 (95% CI 0.63 to 1.73)) or quality of life scores compared with the reference group. Conclusions: In population-based studies, respiratory symptoms are of major importance for predicting long-term clinical outcomes in subjects with COPD with mild obstruction. Population studies based on spirometry only may misestimate the prevalence of clinically relevant COPD.

The Cost of Persistent Asthma in Europe : An International Population-Based Study in Adults

Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30–54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30–54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.

Traffic-Related Air Pollution Correlates with Adult-Onset Asthma among Never-Smokers

Background: Traffic-related pollution is associated with the onset of asthma in children. Its effect on adult-onset asthma is poorly investigated. The SAPALDIA cohort study was used to investigate associations between the 11-year change (1991–2002) in home outdoor traffic-related particulate matter up to 10 μm in diameter (TPM10) and the incidence of asthma. Methods: Never-smokers without asthma at baseline aged 18–60 years in 1991 were eligible for inclusion in the study. Subjects reporting doctor-diagnosed asthma at follow-up were considered incident cases. TPM10 at baseline and follow-up was predicted and interpolated to subjects’ place of residence by dispersion models using emission and meteorological data. Cox proportional hazard models for time to asthma onset were adjusted (age, gender, baseline atopy, body mass index, bronchial reactivity, maternal allergies). Results: Of 2725 never-smokers, 41 reported asthma onset in 2002. Home outdoor TPM10 concentrations improved during the interval (mean −0.6; range −9 to +7.2; IQR 0.6 μg/m3). The incidence of asthma was associated with a change in TPM10. The hazard ratio (1.30; 95% CI 1.05 to 1.61) per 1 μg/m3 change in TPM10 (IQR) was not sensitive to further adjustments (education, workplace exposure, passive smoking, parental asthma or allergies, random area effects, lung function or co-pollutants such as regional, secondary, total PM10 or proximity to busy roads). Conclusion: The data suggest a role for traffic-related pollution in adult-onset asthma. Space, time and source-specific individual assignment of exposure to traffic-related pollution is a key strength of SAPALDIA. It may explain why findings were statistically significant despite the limited number of new cases. As traffic-related pollution prevails, the finding may be of substantial public health relevance.

Is age at menopause increasing across Europe? : results on age at menopause and determinants from two population-based studies

Objective: To investigate the variability and determinants of menopause age in two European cohort studies, the European Respiratory Health Survey and the Swiss Air Pollution and Lung Disease in Adults Cohort. Methods: Age at menopause was estimated in 5,288 women, aged 30 to 60 years, randomly selected in nine European countries between 1998 and 2002. Determinants of natural and surgically induced menopause were investigated by Cox regression and heterogeneity by meta-analysis. Follicle-stimulating hormone and luteinizing hormone levels were assessed in a subsample. Results: A quarter of the women were postmenopausal by age 50.8 years. Median age of natural menopause was 54 years. Hormone levels were within expected ranges for premenopausal and postmenopausal women. Surgically induced menopause was highly prevalent (22%-47%), associated with earlier timing of menopause. Determinants of earlier menopause were current smoking (hazard ratio [HR], 1.59; 95% CI, 1.27-1.98), body mass index greater than 30 kg/m2 (HR, 1.32; 95%, CI, 1.02-1.70), and low physical activity (HR, 1.37; 95%, CI, 1.12-1.67). The determinant for later menopause was multiparity (HR, 0.74; 95% CI, 0.62-0.89). Predictors were similar for naturally and surgically induced menopause. Oral contraceptive use yielded heterogeneous effects on timing of menopause. Later birth was associated with later menopause (HR, 0.934; 95% CI, 0.91-0.96). This evidence of a secular trend is heterogeneous across countries. Conclusions: Age at menopause varies across Europe, shifting toward higher ages. This secular trend seems paradoxical because several adult determinants, that is, overweight, smoking, sedentarity, and nulliparity, associated with early menopause are on the rise in Europe. The heterogeneity of the secular trend suggests additional country-specific factors not included in the study, such as improved childhood nutrition and health, that have an influence on reproductive aging.

Prioritised research agenda for prevention and control of chronic respiratory diseases

The 2008–2013 World Health Organization (WHO) action plan on noncommunicable diseases (NCDs) includes chronic respiratory diseases as one of its four priorities. Major chronic respiratory diseases (CRDs) include asthma and rhinitis, chronic obstructive pulmonary disease, occupational lung diseases, sleep-disordered breathing, pulmonary hypertension, bronchiectiasis and pulmonary interstitial diseases. A billion people suffer from chronic respiratory diseases, the majority being in developing countries. CRDs have major adverse effects on the life and disability of patients. Effective intervention plans can prevent and control CRDs, thus reducing morbidity and mortality. A prioritised research agenda should encapsulate all of these considerations in the frame of the global fight against NCDs. This requires both CRD-targeted interventions and transverse NCD programmes which include CRDs, with emphasis on health promotion and disease prevention.

Transportation noise and blood pressure in a population-based sample of adults

Background: There is some evidence for an association between traffic noise and ischemic heart disease; however, associations with blood pressure have been inconsistent, and little is known about health effects of railway noise. Objectives: We aimed to investigate the effects of railway and traffic noise exposure on blood pressure; a secondary aim was to address potentially susceptible subpopulations. Methods: We performed adjusted linear regression analyses using data from 6,450 participants of the second survey of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA 2) to estimate the associations of daytime and nighttime railway and traffic noise (A-weighted decibels) with systolic blood pressure (SBP) and diastolic blood pressure (DBP; millimeters of mercury). Noise data were provided by the Federal Office for the Environment. Stratified analyses by self-reported hypertension, cardiovascular disease (CVD), and diabetes were performed. Results: Mean noise exposure during the day and night was 51 dB(A) and 39 dB(A) for traffic noise, respectively, and 19 dB(A) and 17 dB(A) for railway noise. Adjusted regression models yielded significant effect estimates for a 10 dB(A) increase in railway noise during the night [SBP β = 0.84; 95% confidence interval (CI): 0.22, 1.46; DBP β = 0.44; 95% CI: 0.06, 0.81] and day (SBP β = 0.60; 95% CI: 0.07, 1.13). Additional adjustment for nitrogen dioxide left effect estimates almost unchanged. Stronger associations were estimated for participants with chronic disease. Significant associations with traffic noise were seen only among participants with diabetes. Conclusion: We found evidence of an adverse effect of railway noise on blood pressure in this cohort population. Traffic noise was associated with higher blood pressure only in diabetics, possibly due to low exposure levels. The study results imply more severe health effects by transportation noise in vulnerable populations, such as adults with hypertension, diabetes, or CVD.

Impact of road traffic noise annoyance on health-related quality of life: results from a population-based study

PurposeTo estimate the impact of traffic-related noise annoyance on health-related quality of life (HrQoL) in a population-based study and potential effect modification by gender.MethodsThe study included 5,021 participants of the Swiss Cohort Study of Air Pollution and Lung Disease in Adults second survey. The association between traffic-related noise annoyance, measured on an 11-point scale, and HrQoL, based on SF-36 scores, was investigated by multivariate regression analysis. Effect sizes were calculated, and interactions by gender and chronic disease status examined.ResultsThirteen percentage of the study population reported high annoyance due to traffic. Women were more likely to report high noise annoyance (adjOR 1.23; 95%CI 1.01–1.48). Except for general health, all SF-36 scores showed a significant negative association with noise annoyance. The respective effect sizes ranged between 0.13 and 0.54. Significant effect modification by gender and chronic disease status was present in specific SF-36 domains.ConclusionThis paper presents first evidence of an inverse relationship of noise annoyance and HrQoL in a general population. Although the estimated effects are small to moderate for individuals, they may add up to a relevant public health impact.

Ambient air pollution and adult asthma incidence in six European cohorts (ESCAPE)

BACKGROUND Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. OBJECTIVE We aimed to investigate the association between air pollution and adult onset asthma. METHODS Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect. RESULTS In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 μg/m3; p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 μg/m3; p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 μg/m3), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 μg/m3), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10-5/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles × meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 μg/m3). CONCLUSIONS Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed.

Improvements in PM10 Exposure and Reduced Rates of Respiratory Symptoms in a Cohort of Swiss Adults (SAPALDIA)

RATIONALE Reductions in mortality following improvements in air quality were documented by several studies, and our group found, in an earlier analysis, that decreasing particulate levels attenuate lung function decline in adults. OBJECTIVES We investigated whether decreases in particulates with an aerodynamic diameter of less than 10 microm (PM10) were associated with lower rates of reporting respiratory symptoms (i.e., decreased morbidity) on follow-up. METHODS The present analysis includes 7,019 subjects who underwent detailed baseline examinations in 1991 and a follow-up interview in 2002. Each subject was assigned model-based estimates of average PM10 during the 12 months preceding each health assessment and the difference was used as the exposure variable of interest (DeltaPM10). Analyses were stratified by symptom status at baseline and associations between DeltaPM10 and change in symptom status during follow-up were adjusted for important baseline characteristics, smoking status at follow-up, and season. We then estimated adjusted odds ratios for symptoms at follow-up and numbers of symptomatic cases prevented due to the observed reductions in PM10. MEASUREMENTS AND MAIN RESULTS Residential exposure to PM10 was lower in 2002 than in 1991 (mean decline 6.2 microg/m3; SD = 3.9 microg/m3). Estimated benefits (per 10,000 persons) attributable to the observed changes in PM10-levels were: 259 (95% confidence interval [CI]: 102-416) fewer subjects with regular cough, 179 (95% CI, 30-328) fewer subjects with chronic cough or phlegm and 137 (95% CI, 9-266) fewer subjects with wheezing and breathlessness. CONCLUSIONS Reductions in particle levels in Switzerland over the 11-year follow-up period had a beneficial effect on respiratory symptoms among adults.