Determinants of change in airway reactivity over 11 years in the SAPALDIA population study.

We investigated determinants of change in bronchial reactivity in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), a population-based cohort with wide age range (29-72 yrs at follow-up). The role of sex, age, atopic status, smoking and body mass index (BMI) on percentage change in bronchial reactivity slope from the baseline value was analysed in 3,005 participants with methacholine tests in 1991 and 2002, and complete covariate data. Slope was defined as percentage decline in forced expiratory volume in 1 s from its maximal value per micromole of methacholine. Bronchial hyperreactivity prevalence fell from 14.3 to 12.5% during follow-up. Baseline age was nonlinearly associated with change in reactivity slope: participants aged <50 yrs experienced a decline and those above an increase during follow-up. Atopy was not associated with change, but accentuated the age pattern (p-value for interaction = 0.038). Smoking significantly increased slope by 21.2%, as did weight gain (2.7% increase per BMI unit). Compared with persistent smokers, those who ceased smoking before baseline or during follow-up experienced a significant decrease in slope (-27.7 and -23.9%, respectively). Differing, but not statistically different, age relationships and effect sizes for smoking and BMI between sexes were found. Mean bronchial reactivity increases after 50 yrs of age, possibly due to airway remodelling or ventilation-perfusion disturbances related to cumulative lifetime exposures.

Longitudinal change of prebronchodilator spirometric obstruction and health outcomes: results from the SAPALDIA cohort.

BACKGROUND: Understanding the prognostic meaning of early stages of chronic obstructive pulmonary disease (COPD) in the general population is relevant for discussions about underdiagnosis. To date, COPD prevalence and incidence have often been estimated using prebrochodilation spirometry instead of postbronchodilation spirometry. In the SAPALDIA (Swiss Study on Air Pollution and Lung Disease in Adults) cohort, time course, clinical relevance and determinants of severity stages of obstruction were investigated using prebronchodilator spirometry. METHODS: Incident obstruction was defined as an FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >or=0.70 at baseline and <0.70 at follow-up, and non-persistence was defined inversely. Determinants were assessed in 5490 adults with spirometry and respiratory symptom data in 1991 and 2002 using Poisson regression controlling for self-declared asthma and wheezing. Change in obstruction severity (defined analogously to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification) over 11 years was related to shortness of breath and health service utilisation for respiratory problems by logistic models. RESULTS: The incidence rate of obstruction was 14.2 cases/1000 person years. 20.9% of obstructive cases (n = 113/540) were non-persistent. Age, smoking, chronic bronchitis and non-current asthma were determinants of incidence. After adjustment for asthma, only progressive stage I or persistent stage II obstruction was associated with shortness of breath (OR 1.71, 95% CI 0.83 to 3.54; OR 3.11, 95% CI 1.50 to 6.42, respectively) and health service utilisation for respiratory problems (OR 2.49, 95% CI 1.02 to 6.10; OR 4.17 95% CI 1.91 to 9.13, respectively) at follow-up. CONCLUSIONS: The observed non-persistence of obstruction suggests that prebronchodilation spirometry, as used in epidemiological studies, might misclassify COPD. Future epidemiological studies should consider both prebronchodilation and postbronchodilation measurements and take specific clinical factors related to asthma and COPD into consideration for estimation of disease burden and prediction of health outcomes.

Health-related quality of life in Swiss adolescents with asthma. Validation of the AAQOL-D and comparison with Australian adolescents.

PRINCIPLES: The Adolescent Asthma Quality of Life Questionnaire (AAQOL) is the only asthma-specific quality-of-life questionnaire to date for use specifically in adolescents. The aim of this study was translation of the AAQOL into German, revalidation of the German version (AAQOL-D) and comparison of health-related quality of life (HRQOL) in Swiss and Australian adolescents. METHODS: 60 adolescents with frequent episodic or persistent asthma aged 12-17 years were recruited. The standardised method consisted of (1) translation of the AAQOL; (2) additional item selection via semistructured interviews (n = 11); (3) item reduction and re-validation (n = 56). For item reduction the clinical impact method was applied. RESULTS: The same 32 items were identified as relevant for the AAQOL-D as in the original version (AAQOL). Internal consistency for the 6 dimensions and the total score was high (alpha = 0.76-0.87). Despite consideration of psychosocial aspects relevant to adolescents, high correlation with the Pediatric Asthma Quality of Life Questionnaire was confirmed for the AAQOL-D (rho = 0.85; p <0.0001). Correlation with a health status thermometer consisted in rho = 0.74 (p <0.0001). There was moderate correlation with clinical parameters of asthma severity (rho = 0.51-0.73; p < or = 0.0002), not however with frequency of medication (rho = 0.22; p = 0.13). Comparison of Swiss and Australian adolescents showed that Swiss adolescents were more bothered by cigarette smoke and the need to avoid places where cigarettes were smoked. CONCLUSIONS: The AAQOL-D is a valid multidimensional instrument in German for assessing HRQOL of adolescents with asthma. HRQOL of Swiss adolescents with asthma may be enhanced by implementing non-smoking policies promoting smoke-free environments.

Competition performance and basal nocturnal catecholamine excretion in cross-country skiers.

UNLABELLED: Objective techniques to determine whether an athlete is optimally prepared for a competition are virtually nonexistent. Preparedness for sports competition is commonly judged through the experience of the athletes and their coaches. Evidence from overtraining studies suggests that catecholamine (Cat) excretion rates may correlate with performance in athletes. PURPOSE: We therefore attempted to determine whether a relationship existed between performances of world-class cross-country skiers and basal nocturnal Cat excretion (BNCE). METHOD: During the Cross-Country Skiing World Championships, we determined BNCE in nine cross-country skiers of the Swiss national team by measuring free Cat concentration (dopamine = D, norepinephrine = NE, epinephrine = E) in morning urine samples, using high performance liquid chromatography. Expert judgments of competition performance (ECP) were assessed by two experienced professional coaches of the national team by using an 11-step scale. RESULTS: The BNCE correlated significantly with ECP in cross-country skiers (r2 = 0.84 and P < for NE; r2 = 0.86 and P < 0.001 for D). Athletes who had their best absolute competition results (ACR) showed the highest NE and D concentrations. CONCLUSION: These data suggest that competitive cross-country skiers with higher D and NE excretion may reach better competition levels compared with those with lower levels. Measures of BNCE provide objective information about competition performance, which may benefit athletes in their precompetition preparation.

CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils.

CD137 (ILA / 4-1BB) is a member of the TNF / NGF receptor family, and has previously been suggested to be involved in T cell activation and differentiation. Here, we demonstrate that blood neutrophils from control individuals and patients with cystic fibrosis express CD137 mRNA and surface protein. In contrast, lung neutrophils derived from patients with cystic fibrosis did not express detectable CD137 levels. Such CD137-deficient neutrophils could also be generated from normal neutrophils by TNF-alpha stimulation in vitro. TNF-alpha was found to be highly expressed in epithelial cells from cystic fibrosis but not normal lungs, suggesting that TNF-alpha might account for reduced neutrophil CD137 levels under inflammatory conditions in vivo. To investigate whether CD137 is involved in the regulation of apoptosis, neutrophils were activated with functional anti-CD137 antibody in the presence or absence of different neutrophil survival factors in vitro. Activation of CD137 abrogated GM-CSF-mediated anti-apoptosis in normal but not in CD137-deficient neutrophils. Moreover, G-CSF- and IFN-gamma-mediated neutrophil anti-apoptosis was not affected by anti-CD137 antibody treatment. In conclusion, these data suggest that CD137 activation may limit GM-CSF-mediated anti-apoptosis of neutrophils. The absence of this anti-inflammatory mechanism in inflammatory responses might be associated with massive neutrophil accumulation and consequent tissue damage.

Vagal activity and airway response to ipratropium bromide before and after exercise in ambient and cold conditions in healthy cross-country runners.

OBJECTIVE: To determine whether the variability in the effect of ipratropium bromide on the bronchial response to exercise among endurance athletes depends on their vagal activity. The hypothesis was that this would be the case. DESIGN: Participants served as their own controls in a double-blind, repeated-measures investigation. SETTING: Climatic chamber in an exercise laboratory. PARTICIPANTS: Six well-trained healthy adult cross-country runners (three women and three men). INTERVENTIONS: Four exercise provocation tests at ambient temperature of 22 or -5 degrees C after inhalation of ipratropium bromide or placebo. MAIN OUTCOME MEASURES: Vagal activity was assessed in each visit by a 4-second cycling test; airway response to exercise was measured by periodic pulmonary function testing. RESULTS: With ipratropium bromide, forced expiratory volume in 1 second (FEV1) increased by 5.3+/-1.4% at 22 degrees C and by 7.5+/-1.5% at -5 degrees C. The beneficial response of the large airways to ipratropium bromide versus placebo was positively related to vagal activity for FEV1 at -5 degrees C, for peak expiratory flow (PEF) at -5 degrees C, and for PEF at 22 degrees C. CONCLUSION: The findings suggest that the beneficial large-airways response to ipratropium bromide may be related to vagal activity. CLINICAL RELEVANCE: Information about vagal activity may help to determine whether an athlete is a suitable candidate for treatment with ipratropium bromide. This may offer more therapeutic possibilities, especially for those individuals who have a high vagal activity, such as endurance athletes.

The anaerobic threshold in cystic fibrosis: comparison of V-slope method, lactate turn points, and Conconi test.

Physical exercise can improve sputum clearance in patients with cystic fibrosis (CF). To set up individual training protocols it is desirable to know the anaerobic threshold (AT). Established methods such as blood lactate measurements and ergometry can only be performed in specialized centers. Conconi showed that the heart rate threshold (HRT), i.e., the deflection point from the linear relationship between work load and heart rate, correlated significantly with the AT in healthy adults. To assess the reliability of the HRT in CF, we performed ergometry in 32 CF patients (mean age, 21.0 +/- 5.5 years; mean Shwachman score, 77.8 +/- 12.0) according to the Conconi protocol. The HRT was compared with the aerobic threshold (AeT) as determined by the V-slope method and with two turn points in the lactate performance curve (LTP1, LTP2). An HRT could be obtained in only 17 of the 32 patients (53%). In these 17 patients there was a significant correlation between HRT and the other thresholds, but the absolute values for the AT differed considerably: The mean HRT was 132% higher than the AeT according to Beaver, 107% higher than LTP1, and 19% higher than LTP2. Exercise protocols that rely solely on the HRT in CF will lead to excessive exertion during exercise training programs in these patients. According to these results the HRT of Conconi is not a suitable method to determine appropriate exercise levels in CF training programs and might even be harmful in CF patients. These results also indicate the need to test the reliability of a diagnostic procedure that has been developed only for healthy people.

[Acute deterioration of the CO diffusion capacity following exposure to ski-wax vapors]. / Akute Verschlechterung der CO-Diffusionskapazität nach Exposition mit Skiwachsdämpfen.

In cross country skiing use of hot wax is of importance. 90% of the active swiss cross country skiers have their own, self maintained equipment. Long unprotected exposure to hot wax fumes may cause disturbance of lung function. To examine short lasting disturbance in pulmonary function, CO-diffusion capacity and dynamic and static lung volumes in five healthy human subjects after exposure for one hour to hot wax (containing Paraffin and Cera-F) were determined. The subjects complained about burning eyes and tears, sore throat and coughing. Immediately after exposure all subjects showed a significant decrease of the CO-diffusion capacity of 10.6% (SEM 3.9), related to the ventilated alveolar space (DCOSB/VA). Maximal decrease of 13.6% (SEM 2.4) was after 90 min. After 24 hours the reduction persisted with 9.4% (SEM 2.1). The dynamic and static lung volumes remained unchanged. In summary a reduction of the CO-diffusion capacity after inhalative hot wax exposure was observed for at least 24 hours.