Lung function and respiratory symptoms in a 1-year randomized smoking cessation trial of varenicline in COPD patients.

Respir Med. 2011 Nov;105(11):1682-90

Authors: Tashkin DP, Rennard S, Taylor Hays J, Lawrence D, Marton JP, Lee TC

Abstract
There are few data concerning changes in lung function and respiratory symptoms in smokers with chronic obstructive pulmonary disease (COPD) weeks to months after quitting smoking. We examined serial changes in spirometry and Clinical COPD Questionnaire (CCQ) scores (measuring respiratory symptoms and health-related quality of life) in COPD participants by smoking status during a smoking cessation trial. In this randomized, double-blind trial, smokers with mild-to-moderate COPD were treated with varenicline 1 mg b.i.d. or placebo for 12 weeks and followed to Week 52. Primary endpoints of abstinence were previously reported. Secondary endpoints were mean changes from baseline in post-bronchodilator forced expired volume in 1 s (FEV(1)) and CCQ scores. Change from baseline in post-bronchodilator FEV(1) was significantly improved in continuous abstainers (121.8 mL) vs. continuous smokers (37.9 mL) at Week 12 (P = 0.0069), but not at Weeks 24 or 52. Mean change from baseline at Week 12 in CCQ Total Score was significantly better in continuous abstainers (-1.04) vs. continuous smokers (-0.53; P < 0.0001): this improvement was sustained at Weeks 24 and 52. In a 1-year cessation trial of smokers with COPD, continuous abstinence compared with continuous smoking significantly improved post-bronchodilator FEV(1) at Week 12 (although the difference narrowed subsequently) and CCQ Total Scores at Week 12, with sustained improvement thereafter. (Trial registry: http://www.clinicaltrials.gov; trial identifier: NCT00285012).

PMID: 21621992 [PubMed - indexed for MEDLINE]

Impaired adrenergic- and corticotropic-axis outflow during exercise in chronic obstructive pulmonary disease.

Metabolism. 2011 Nov;60(11):1521-9

Authors: Iranmanesh A, Rochester DF, Liu J, Veldhuis JD

Abstract
Exercise stimulates coordinated release of the sympathoadrenal hormones adrenocorticotropic hormone (ACTH), cortisol, norepinephrine (NE), and epinephrine (Epi). The study hypothesis was that chronic obstructive pulmonary disease (COPD) is marked by heightened sympathoadrenal outflow at comparable relative workloads. The location of the study was at a clinical research unit. Eight healthy men and 9 men with stable COPD (forced expiratory volume at 1 second <75% predicted) were studied. Volunteers rested (baseline) or exercised at individual submaximal (35% ± 5%) or maximal oxygen consumption. Blood was sampled every 2 minutes for 40 minutes concurrently. Two-way analysis of covariance was applied to examine group (healthy/COPD) and exercise (3 levels) effects on ACTH, cortisol, NE, and Epi release and regularity (estimable by approximate entropy). The timing of peak hormone concentrations was Epi, 14 minutes; NE, 16 minutes; ACTH, 22 minutes; and cortisol, 34 minutes in both cohorts. Type of exercise regimen influenced all 4 hormones (each P < .001), and subject group (control vs COPD) affected cortisol (P < .001) and Epi (P = .048) responses. Exercise regimen and group together controlled ACTH, cortisol, and Epi (each P < .001), but not NE, responses. In particular, endocrine responses were attenuated in COPD compared with control subjects. Approximate entropy analysis also identified loss of maximal exercise-induced ACTH-secretory regularity in COPD patients (P = .042). These outcomes demonstrate impaired rather than augmented exercise-associated sympathocorticotropic-axis outflow in patients with COPD even when outcomes are normalized to maximal oxygen consumption, suggesting that factors other than fitness are at work.

PMID: 21632072 [PubMed - indexed for MEDLINE]

The health, activity, dyspnea, obstruction, age, and hospitalization: prognostic score for stable COPD patients.

Respir Med. 2011 Nov;105(11):1662-70

Authors: Esteban C, Quintana JM, Aburto M, Moraza J, Arostegui I, España PP, Aizpiri S, Capelastegui A

Abstract
Multidimensional instruments for determining the severity and prognosis of chronic obstructive pulmonary disease (COPD) must be used in daily clinical practice. Objective: To develop and validate a new COPD severity score using variables readily obtained in clinical practice and to compare its predictive capacity with that of other multidimensional indexes. Data collected from a prospective cohort of 611 stable COPD patients were used to derive a clinical prediction rule that was later validated in a separate prospective cohort of 348 patients. In the multivariate analyses, six independent predictive factors were correlated with overall and respiratory mortality: health status, physical activity, dyspnea, airway obstruction (FEV(1)), age, and hospitalizations for COPD exacerbations in the previous two years. These create the HADO-AH score. Based on the β parameter obtained in the multivariate model, a score was assigned to each predictive variable. The area under the curve for 5-year mortality was 0.79 (95% CI, 0.74-0.83) in the derivation cohort and 0.76 (95% CI, 0.71-0.81) in the validation cohort. The HADO-AH score was a significantly better predictor of mortality than the HADO-score and the Body-mass index, Obstruction, Dyspnea, Exercise-index were statistically significant (p < 0.0004 and p = 0.021, respectively), but was similar to the Age, Dyspnea, and Obstruction-index (p = 0.345). The HADO-AH score provides estimates of all-cause and respiratory mortality that are equal to, or better than, those of other multidimensional instruments. Because it uses only easily accessible measures, it could be useful at all levels of care.

PMID: 21703842 [PubMed - indexed for MEDLINE]