Otto Brändli

Self-administration and interviewer-administration of the German Chronic Respiratory Questionnaire: instrument development and assessment of validity and reliability in two randomised studies

BackgroundAssessment of health-related quality of life (HRQL) is important in patients with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD in Germany, Switzerland and Austria there is no validated disease-specific instrument available. The objective of this study was to translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely used respiratory HRQL questionnaires, into German, develop an interviewer- and self-administered version including both standardised and individualised dyspnoea questions, and validate these versions in two randomised studies.MethodsWe recruited three groups of patients with COPD in Switzerland, Germany and Austria. The 44 patients of the first group completed the CRQ during pilot testing to adapt the CRQ to German-speaking patients. We then recruited 80 patients participating in pulmonary rehabilitation programs to assess internal consistency reliability and cross-sectional validity of the CRQ. The third group consisted of 38 patients with stable COPD without an intervention to assess test-retest reliability. To compare the interviewer- and self-administered versions, we randomised patients in groups 2 and 3 to the interviewer- or self-administered CRQ. Patients completed both the standardised and individualised dyspnoea questions.ResultsFor both administration formats and all domains, we found good internal consistency reliability (Crohnbachs alpha between 0.73 and 0.89). Cross-sectional validity tended to be better for the standardised compared to the individualised dyspnoea questions and cross-sectional validity was slightly better for the self-administered format. Test-retest reliability was good for both the interviewer-administered CRQ (intraclass correlation coefficients for different domains between 0.81 and 0.95) and the self-administered format (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person variability was responsible for the higher test-retest reliability of the interviewer-administered format while between person variability was similar for both formats.ConclusionsInvestigators in German-speaking countries can choose between valid and reliable self-and interviewer-administered CRQ formats.

Preliminary validation of PRISM (Pictorial Representation of Illness and Self Measure) - a brief method to assess suffering.

Background: Alleviation of suffering is widely acknowledged as one of the main goals of medicine. However, no measure to assess this crucial aspect of illness has been developed to date. Aims: To validate PRISM (Pictorial Representation of Illness and Self-Measure) as a simple quantitative method of assessing the perceived burden of suffering due to illness. Methods: Validity and reliability studies to date have involved over 700 patients with a variety of chronic physical illnesses. Results: Reliability of PRISM is good (test-retest reliability r = 0.95; p ≤ 0.001, interrater reliability r = 0.79; p ≤ 0.001). Qualitative data indicate that the interpretation of the PRISM task is not only consistent among patients, but also consistent with that expected from existing literature on suffering. As expected, PRISM shows strong correlations with psychological variables (notably depression and coping resilience) and also correlates with SF-36 subscale scores. Prospective longitudinal data demonstrate that PRISM is sensitive to therapeutic change. It is very acceptable to patients and takes less than 5 min to administer. Conclusion: In the absence of a ‘gold standard’ measure of suffering, our validation data must be interpreted with caution. However, the performance of PRISM is entirely consistent with what would be expected of a measure of suffering, based on current published work.

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.

Associations between lung function and estimated average exposure to NO2 in eight areas of Switzerland

In this paper, we present results from the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults) regarding associations between lung function [forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)], as assessed during the cross-sectional study in 1991, and average levels of NO2 exposure within the eight study communities. We distinguished average home outdoor exposure and average personal exposure to NO2 and obtained exposure estimates by computing regional averages of passive sampler measurements performed by a random subsample of SAPALDIA participants in 1993. Previous analyses had revealed associations between average lung function and average air pollution levels between communities. The present results show that such associations may also be seen within communities: a 10-μg per m3 increase in average home outdoor and personal exposure to NO2 between zones of residence of the same community was associated with a change in average FVC by −0.59% [95% confidence limits (CL) = 0.01, −1.19] and −0.74% (95% CL = −0.07, −1.41), respectively. These values, however, are smaller than the ones found for the corresponding associations between study communities: −1.67% (95% CL = −1.01, −2.33) and −2.93% (95% CL = −2.11, −3.75), respectively. The different magnitudes of these two types of associations might be explained by differences in spatial variation between various components of air pollution. (Epidemiology 1998;9:405–411)A common strategy for modeling dose-response in epidemiology is to transform ordered exposures and covariates into sets of dichotomous indicator variables (that is, to factor the variables). Factoring tends to increase estimation variance, but it also tends to decrease bias and thus may increase or decrease total accuracy. We conducted a simulation study to examine the impact of factoring on the accuracy of rate estimation. Factored and unfactored Poisson regression models were fit to follow-up study datasets that were randomly generated from 37,500 population model forms that ranged from subadditive to supramultiplicative. In the situations we examined, factoring sometimes substantially improved accuracy relative to fitting the corresponding unfactored model, sometimes substantially decreased accuracy, and sometimes made little difference. The difference in accuracy between factored and unfactored models depended in a complicated fashion on the difference between the true and fitted model forms, the strength of exposure and covariate effects in the population, and the study size. It may be difficult in practice to predict when factoring is increasing or decreasing accuracy. We recommend, therefore, that the strategy of factoring variables be supplemented with other strategies for modeling dose-response.

SERPINA1 Gene Variants in Individuals from the General Population with Reduced α1-Antitrypsin Concentrations

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.

Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study

BackgroundThe aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women.MethodsIn a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18 – 60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years.ResultsIn both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC<0.70 compared to other women (-39.4 vs -12.2 mL/yr per pack per day, p < 0.002).ConclusionThere are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

Re-estimated equations for 5th percentiles of lung function variables

In 1996 we published reference equations for the 5th percentiles of lung function parameters (FVC, FEV1, PEF, FEF25, FEF50, FEF75, FEF25–75, FEV1/FVC) as a function of age and height.1 These reference values were derived from the subsample of the Swiss SAPALDIA study population consisting of never smokers without respiratory symptoms (1267 men and 1890 women aged between 18 and 60 years). In the meantime our German colleagues have applied extrapolations of the 5th percentile curves to men aged between 60 and 70 years2 and have found that for some of the lung function parameters—for example, FEV1—the 5th percentiles appeared to get too close to the mean at age 70 (fig 1). Figure 1 Mean and 5th percentile of FEV1 in men …

Circulating alpha1-antitrypsin in the general population: Determinants and association with lung function

BackgroundSevere 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.MethodsIn 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels ≤ 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.ResultsFemale 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.ConclusionThe results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.

Early versus late pulmonary rehabilitation in chronic obstructive pulmonary disease patients with acute exacerbations: a randomized trial.

Background: Around the world, the timing of referral of chronic obstructive pulmonary disease (COPD) patients for pulmonary rehabilitation differs from immediately after exacerbation (early) to later on when patients are in a stable state (late). There are no trials comparing the different time points of referral for pulmonary rehabilitation. Objectives: Our aim was to compare the effects of early and late pulmonary rehabilitation on exacerbation rates and health-related quality of life (HRQOL) in COPD patients with exacerbations. Methods: We randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages II–IV) with a recent exacerbation to early (within 2 weeks) or late pulmonary rehabilitation (starting 6 months after randomization and in a stable state). The primary outcome was the exacerbation rate over 18 months, and secondary outcomes included HRQOL and mortality. We used multivariate analyses and an intention-to-treat analysis approach. Results: We randomized 36 patients to pulmonary rehabilitation. On average, patients with early rehabilitation (n = 19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43–1.63; p = 0.60). Over the 18-month period, patients with late rehabilitation experienced more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74 and on the Medical Research Council dyspnea scale 0.37), but neither these differences nor any difference in HRQOL domains reached statistical significance. Conclusions: We did not find any statistically significant differences between early and late pulmonary rehabilitation. However, our trial indicates that early rehabilitation may lead to faster recovery of HRQOL after exacerbations compared to rehabilitation later on when patients are in a stable state.

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 FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio ≥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.