Dataset Information

Six years progression of exercise capacity in subjects with mild to moderate airflow obstruction, smoking and never smoking controls.

ABSTRACT: BACKGROUND:Exercise capacity is an important feature in patients with COPD. Its impairment drives disability and dependency for daily activities performance. This study evaluated the six years change in exercise capacity in subjects with airflow obstruction and compared this to subjects without airflow obstruction, with and without a smoking history. METHODS:Cardiopulmonary exercise tests (CPET) were repeatedly performed during a six years follow up period. Peak oxygen uptake (VO2peak), work rate (WRpeak), heart rate (HRpeak), minute ventilation (VEpeak), respiratory exchange ratio (RERpeak) and ventilatory reserve (VE/MVV) were collected as effort dependent outcomes. The slopes of oxygen uptake, ventilatory and mechanical efficiency (OUES, ?VE/?VCO2 and ?VO2/?WR) were collected as effort independent outcomes. RESULTS:One hundred and thirty-eight subjects were included. Thirty-eight presented airflow obstruction (63±6 years, 74% men, FEV1 90±15%pred), 44 had a smoking history but no airflow obstruction (61±5 years, 61% men, FEV1 105±15%pred) and 56 had never smoked (61±7 years, 57% men, FEV1 117±18%pred). At baseline, the airflow obstruction group had slightly worse exercise capacity in comparison to the never smoking control group, in absolute terms and expressed as percentage of the predicted value (VO2peak = 27±5 versus 32±8 ml/min/kg, p<0.01; 112±29 versus 130±33%pred, p = 0.04). Most exercise variables showed a statistically significant yearly deterioration, with exception of VE/MVV, ?VE/?VCO2 and ?VO2/?WR. The yearly decline in VO2peak and OUES was not faster in subjects with airflow obstruction than in smoking and never smoking controls (VO2peak -67 (9) versus -76 (9) ml/min, p = 0.44 and versus -58 (9), p = 0.47; OUES -32 (11) versus -68 (10), p = 0.03 and versus -68 (13), p = 0.03). CONCLUSIONS:With exception of VO2peak, effort dependent variables deteriorated faster in subjects with airflow obstruction compared to never smoking controls. The deterioration of effort independent variables, however, was not accelerated in the airflow obstruction group compared to controls.

SUBMITTER: Rodrigues FM

PROVIDER: S-EPMC6306213 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Six years progression of exercise capacity in subjects with mild to moderate airflow obstruction, smoking and never smoking controls.

Rodrigues Fernanda Machado FM Loeckx Matthias M Hornikx Miek M Van Remoortel Hans H Louvaris Zafeiris Z Demeyer Heleen H Janssens Wim W Troosters Thierry T

PloS one 20181226 12

<h4>Background</h4>Exercise capacity is an important feature in patients with COPD. Its impairment drives disability and dependency for daily activities performance. This study evaluated the six years change in exercise capacity in subjects with airflow obstruction and compared this to subjects without airflow obstruction, with and without a smoking history.<h4>Methods</h4>Cardiopulmonary exercise tests (CPET) were repeatedly performed during a six years follow up period. Peak oxygen uptake (VO2 ...[more]

PMID: 30586370

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Project description:BackgroundPatients with COPD need to cope with a disabling disease, which leads to health status impairment.AimTo investigate the long term change of health status in subjects with mild to moderate airflow obstruction and to compare this to subjects without airflow obstruction, with and without a smoking history. Second, to investigate the factors potentially associated to rapid health status decline in our total cohort.MethodsTwo hundred and one subjects were included. Generic [Short form 36 health survey (SF36) and EuroQol - 5 dimensions (EQ-5D)] and disease specific [Clinical COPD questionnaire (CCQ) and COPD Assessment Test (CAT)] health status questionnaires were regularly repeated over a six years period. Other functional outcomes comprised measures of lung function, physical fitness, physical activity and emotional state.ResultsOn average, health status decline did not differ between groups with the exception of the EQ-5D index, which deteriorated faster in subjects with airflow obstruction compared to the never smoking control group [- 0.018(0.008) versus 0.00006(0.003), p = 0.03]. Subjects presenting at least one exacerbation had faster rate of deterioration measured with CAT [0.91(0.21) versus - 0.26(0.25), p < 0.01]. Characteristics of the fast declining group were older age, worse lung function, physical fitness, physical activity and disease specific baseline health status. Subjects with airflow obstruction had a 2.5 (95% CI 1.36-4.71) higher risk of presenting fast overall health status decline. Fast overall decline was associated with the presence of acute exacerbation(s) (44% of the subjects with exacerbation(s) versus 17% of subjects without exacerbation, p = 0.03). Changes in fat free mass, functional exercise capacity and in symptoms of anxiety and depression correlated weakly to changes in health status measured with all questionnaires.ConclusionSubjects with mild airflow obstruction present a significant deterioration of health status, which is generally not much faster compared to smoking and never smoking controls. Subjects with fast decline in overall health status are older and more likely to have airflow obstruction, acute respiratory exacerbation(s), reduced physical fitness, physical activity and impaired COPD specific health status at baseline.Trial registrationNCT01314807 - retrospectively registered on March 2011.

Project description:Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We hypothesised that these "resistant smokers" may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re-sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the "resistant smokers" and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.34 × 10(-4)) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke.

Dataset Information

Six years progression of exercise capacity in subjects with mild to moderate airflow obstruction, smoking and never smoking controls.

Publications

Six years progression of exercise capacity in subjects with mild to moderate airflow obstruction, smoking and never smoking controls.

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