Luc Burdet

Oxygen saturation during daily activities in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) frequently develop nocturnal oxygen desturation because of alveolar hypoventilation, worsening of ventilation-perfusion mismatch, and sometimes obstructive sleep apnoeas. In contrast, little is known about their oxygen status during the various activities of daily life. The aim of this study was to compare the oxygen saturation profile during day and night, and to assess the influence of different daily activities in COPD. During a rehabilitation programme, we studied 30 patients with moderate-to-severe COPD (median forced expiratory volume in one second (FEV1) 37% of predicted), without marked hypoxaemia (median arterial oxygen tension (Pa,O2) 9.1 kPa). Arterial oxygen saturation (Sa,O2) was assessed by pulse oximetry during night (8 h) and day (10.5 h). The mean and minimal Sa,O2 were calculated, and desaturations were defined as Sa,O2 falls > 4%.h-1. Daily activities were identified by the patients as resting, eating, washing, nebulization therapy and walking. Mean Sa,O2 was lower during the night (88%) than during the day (89%). In contrast, minimal Sa,O2 was lower during the day (69%) than during the night (72%), and the number of desaturations was higher during the day (8.6 desaturations.h-1) than during the night (6.8 desaturations.h-1). Mean Sa,O2 was 88% during walking, which was lower than during resting (90%), nebulization (90%), and meals (89%). The number of desaturations was higher during walking (13.1 desaturations.h-1), washing (12.6 desaturations.h-1), and eating (9.2 desaturations.h-1) than during resting (5.3 desaturations.h-1). We conclude that daily activities, such as walking, washing and eating, are associated with transient oxygen desaturation in patients with moderate-to-severe chronic obstructive pulmonary disease, even without marked resting hypoxaemia.

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.

Prevalence of airflow obstruction in smokers and never-smokers in Switzerland

The aim of the present study was to measure age-specific prevalence of airflow obstruction in Switzerland in smokers and never-smokers using pulmonary function tests and respiratory symptoms from 6,126 subjects participating in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults. The lower limit of normal of the forced expiratory volume in 1 s/forced vital capacity ratio was used to define airflow obstruction. Severity of airflow obstruction was graded according to the recommendations of the Global Initiative for Chronic Obstructive Lung Disease. Prevalence of airflow obstruction ranged from 2.5% in subjects aged 30–39 yrs to 8.0% in those aged ≥70 yrs. In multivariate analysis, age (OR 2.8, ≥70 yrs versus 30–39 yrs), smoking (OR 1.8) and asthma (OR 6.7) were associated with airflow obstruction. Never-smokers constituted 29.3% of subjects with airflow obstruction. Never-smokers with airflow obstruction were younger, more likely to be male and reported asthma more frequently than obstructive smokers. Obstructive smokers and never-smokers had similar level of symptoms and quality of life impairment. The prevalence of airflow obstruction in Switzerland is similar to other developed countries. Never-smokers account for a third of the prevalence, which is higher proportion than elsewhere. Airflow obstruction in never-smokers deserves attention because of its frequency and its similar health impact to that in smokers.

Body composition by X-ray absorptiometry and bioelectrical impedance in chronic respiratory insufficiency patients

Nutrition assessment is important during chronic respiratory insufficiency to evaluate the level of malnutrition or obesity and should include body composition measurements. The appreciation of fat-free and fat reserves in patients with chronic respiratory insufficiency can aid in designing an adapted nutritional support, e.g., nutritional support in malnutrition and food restriction in obesity. The purpose of the present study was to cross-validate fat-free and fat mass obtained by various bioelectric impedance (BIA) formulas with the fat-free and fat mass measured by dual-energy X-ray absorptiometry (DXA) and determine the formulas that are best suited to predict the fat-free and fat mass for a group of patients with severe chronic respiratory insufficiency. Seventy-five patients (15 women and 60 men) with chronic obstructive and restrictive respiratory insufficiency aged 45-86 y were included in this study. Body composition was calculated according to 13 different BIA formulas for women and 12 for men and compared with DXA. Because of the variability, calculated as 2 standard deviations, of +/- 5.0 kg fat-free mass for women and +/- 6.4 kg for men for the best predictive formula, the use of the various existing BIA formulas was considered not clinically relevant. Therefore disease-specific formulas for patients with chronic respiratory insufficiency should be developed to improve the prediction of fat-free and fat mass by BIA in these patients.

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.

Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years

Objectives Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. Methods Spirometry data from two time points (follow-up time 9–11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28–73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. Results Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. Conclusion Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.

Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are frequently malnourished and have increased resting energy expenditure (REE). An increase in the work of breathing is generally considered to be the main cause of this hypermetabolism, but other factors may also be implicated. Bronchodilators may decrease the work of breathing by reducing airway obstruction, but beta 2 adrenergic agents have a thermogenic effect. The aim of this study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD. METHODS: Thirteen patients (10 men) of mean (SD) age 68.3 (7.3) years and forced expiratory volume in one second (FEV1) 39.0 (17.0)% predicted were studied on three consecutive days. The REE was measured by indirect calorimetry at 30, 60, 120, and 180 minutes after double blind nebulisation of either salbutamol, ipratropium bromide, or placebo in random order. RESULTS: FEV1 increased both after salbutamol and after ipratropium. The difference in the mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI +104 to +295). The difference in mean response between ipratropium and placebo was +78 ml (95% CI +2 to +160). REE increased after salbutamol but was not changed after ipratropium. The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI +2.2 to +7.4). Heart rate increased after salbutamol but not after ipratropium. The difference in the mean response between salbutamol and placebo was +5.5 beats/ min (95% CI +2.6 to +8.4). CONCLUSION: Salbutamol, but not ipratropium bromide, induces a sustained increase in the REE of patients with COPD despite a reduction in airway obstruction.

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.

Particulate matter and subclinical atherosclerosis : associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study

Background: Subclinical atherosclerosis has been associated with long-term exposure to particulate matter (PM), but the relevance of particle size and sources of exposure remains unclear. Objectives: We investigated the association of long-term exposure to PM10 (≤ 10 μm), PM2.5 (≤ 2.5 μm: total mass, vehicular, and crustal sources), and ultrafine particles [UFP < 0.1 μm: particle number concentration (PNC) and lung-deposited surface area (LDSA)] with carotid intima-media thickness (CIMT). Methods: We used data from 1,503 participants ≥ 50 years old who participated in the third examination of the Swiss SAPALDIA cohort. Exposures were obtained from dispersion models and land-use regression models. Covariate information, including previous cardiovascular risk factors, was obtained from the second and third SAPALDIA examinations. Results: The adjusted percent difference in CIMT associated with an exposure contrast between the 10th and 90th percentile was 1.58% (95% CI: –0.30, 3.47%) for PM10, 2.10% (95% CI: 0.04, 4.16%) for PM2.5, 1.67% (95% CI: –0.13, 3.48%) for the vehicular source of PM2.5, –0.58% (95% CI: –3.95, 2.79%) for the crustal source of PM2.5, 2.06% (95% CI: 0.03, 4.10%) for PNC, and 2.32% (95% CI: 0.23, 4.40%) for LDSA. Stronger associations were observed among diabetics, subjects with low-educational level, and those at higher cardiovascular risk. Conclusions: CIMT was associated with exposure to PM10, PM2.5, and UFP. The PM2.5 source-specific analysis showed a positive association for the vehicular source but not for the crustal source. Although the effects of PNC and LDSA were similar in magnitude, two-pollutant and residual-based models suggested that LDSA may be a better marker for the health relevance of UFP. Citation: Aguilera I, Dratva J, Caviezel S, Burdet L, de Groot E, Ducret-Stich RE, Eeftens M, Keidel D, Meier R, Perez L, Rothe T, Schaffner E, Schmit-Trucksäss A, Tsai MY, Schindler C, Künzli N, Probst-Hensch N. 2016. Particulate matter and subclinical atherosclerosis: associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study. Environ Health Perspect 124:1700–1706; http://dx.doi.org/10.1289/EHP161

Validity and reliability of a French version of the MRF-28 health-related quality of life questionnaire.

Background: Evaluation of health-related quality of life (HRQL) in chronic respiratory failure (CRF) is an important issue for evaluating the impact of treatment. Objectives: To elaborate a French version of the Maugeri Foundation Respiratory Failure Questionnaire (MRF-28) disease-specific HRQL questionnaire and determine its validity and reliability in patients with CRF treated by home mechanical ventilation (HMV). Methods: Forward- and back-translation of the MRF-28 questionnaire; the final version was submitted to 81 patients treated with HMV for CRF, simultaneously with the St. George’s Respiratory Questionnaire (SGRQ), the Short Form 36 (SF-36), and the Hospital Anxiety and Depression scale (HAD). Validity was determined by correlation with previously validated HRQL scores and recorded physiological parameters. Reliability was evaluated by assessing internal consistency and test-retest stability of the MRF-28 scores. Results: The French version of the MRF-28 and its subscores (‘daily activity’, ‘cognitive function’, and ‘invalidity’) were highly significantly correlated with subscores of the SGRQ, the SF-36 and the HAD. Both the MRF-28 and the SGRQ were correlated only with age and the 6-min walk test. The MRF-28 showed high test-retest reliability after 2 weeks (r2 = 0.80, p < 0.0001) and high internal consistency (Crohnbachs’ α coefficient: 0.91). Conclusion: The French version of the MRF-28 is a valid and reliable disease-specific questionnaire for assessing HRQL in patients with CRF.