Faculty Bibliography

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.

Many studies have demonstrated an association of both a sedentary lifestyle and a high body mass index (BMI) with greater risk for cardiovascular disease. Within the prospective SAPALDIA cohort (Swiss cohort Study on Air Pollution and Lung Diseases in Adults), we investigated whether regular exercise was protective against reduced heart rate variability (HRV), a clinically relevant predictor of cardiovascular morbidity and mortality, and whether adverse effects of obesity and weight gain on HRV were modified by regular exercise. Twenty-four-hour electrocardiograms were recorded in 1,712 randomly selected SAPALDIA participants aged >or=50, for whom BMI was assessed in the years 1991 and 2001-2003. Other examinations included an interview investigating health status (especially respiratory and cardiovascular health and health relevant behaviours including physical activity) and measurements of blood pressure, body height and weight. The association between regular physical activity and HRV and interactions with BMI and BMI change was assessed in multivariable linear regression analyses. Compared to sedentary obese subjects, SDNN (standard deviation of all RR intervals) was 14% (95% CI: 8-20%) higher in sedentary normal weight subjects; 19% (CI: 12-27%) higher in normal weight subjects exercising regularly >or=2 h/week; and 19% (CI: 11-28%) higher in obese subjects exercising regularly >or=2 h/week. Compared with sedentary subjects who gained weight, those who gained weight but did exercise regularly had a 13% higher SDNN (CI: 7-20%). Regular physical exercise has strong beneficial effects on cardiac autonomic nervous function and thus appears to offset the negative effect of obesity on HRV.

BACKGROUND: Individuals with severe deficiency in serum alpha(1)-antitrypsin (AAT) concentrations are at high risk for developing chronic obstructive pulmonary disease (COPD), whereas those carrying the PI*MZ genotype are at slightly increased risk. Testing appropriate subgroups of the population for AAT deficiency (AATD) is therefore an important aspect of COPD prevention and timely treatment. We decided to perform an exhaustive investigation of SERPINA1 gene variants in individuals from the general population with a moderately reduced serum AAT concentration, because such information is currently unavailable. METHODS: We determined the Z and S alleles of 1399 individuals enrolled in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) with serum AAT concentrations < or = 1.13 g/L and submitted 423 of these samples for complete exon 2-->5 sequencing. RESULTS: We found that 900 of 1399 samples (64%), carried the normal PI*MM genotype, whereas 499 samples (36%) carried at least 1 SERPINA1 deficiency variant. In the subpopulations in which AAT concentrations ranged from > 1.03 to < or = 1.13 and from > 0.93 to < or = 1.03 g/L, individuals with the PI*MM genotype represented the majority (86.5% and 53.8%, respectively). The PI*MS genotype was predominant (54.9%) in the AAT range of 0.83 to 0.93 g/L, whereas PI*MZ represented 76.4% in the AAT range of > 0.73 to < or = 0.83 g/L. CONCLUSIONS: This analysis provided a detailed molecular definition of intermediate AATD, which would be helpful in the diagnostic setting.

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. METHODS: In 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels < or = 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. RESULTS: Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p < 0.001), that disappeared after adjustment for CRP (p = 0.28). In addition, the AAT and FEV1 association was modified by gender, menopausal status in women, and smoking. CONCLUSION: The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.

The need for updated spirometric reference values to be used on European populations is widely acknowledged, especially for subjects aged >70 yrs. Their reference values are generally based on extrapolations. The aim of the present study was to calculate reference values for lung function screening of healthy, never-smoking adults aged 18-80 yrs and to compare them with the most widely used reference equations. Results of screening spirometry of 8,684 healthy, never-smoking adults were used to calculate mean values and fifth percentiles of lung function variables. The European Community of Coal and Steel (ECCS) reference equations underestimate forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). For example, in 50-yr-old males (height 175 cm), lower limits of normal for FEV(1) are underestimated by 198 mL, and for FVC by 210 mL. In 50-yr-old females (height 165 cm), lower limits of normal for FEV(1) are underestimated by 191 mL, and for FVC by 270 mL. The decline of FVC in elderly subjects is steeper than predicted by the ECCS. Reference equations derived from spirometry data locally collected in a practical setting by well-trained personnel might be more appropriate for everyday use than generally used equations based on data from scientific studies in the distant past.