Undiagnosed Chronic Obstructive Pulmonary Disease Contributes to the Burden of Health Care Use. Data from the CanCOLD Study.

RATIONALE: Chronic obstructive pulmonary disease (COPD) remains undiagnosed in many individuals with persistent airflow limitation. These individuals may be susceptible to exacerbation-like respiratory events that consume health care resources. OBJECTIVES: To compare exacerbation-like respiratory events, event prevalence, and differences in the odds of using medication and/or health services between subjects with diagnosed and undiagnosed COPD. METHODS: Subjects sampled from the general population participating in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study, with at least 12 months of exacerbation-event follow-up who were classified as having physician-diagnosed or undiagnosed COPD were assessed. Exacerbation-like respiratory events were captured using a questionnaire administered every 3 months. MEASUREMENTS AND MAIN RESULTS: A total of 355 subjects were undiagnosed and 150 were diagnosed with COPD. Undiagnosed subjects were less symptomatic and functionally impaired, had been prescribed fewer respiratory medications, and had better health status. The incidence of reported exacerbation-like events was higher in diagnosed subjects and increased in both groups with the severity of airflow obstruction. Although subjects with diagnosed COPD were more often prescribed medication for exacerbation events, health service use for exacerbation events was similar in both groups. CONCLUSIONS: Most subjects with COPD in Canada remain undiagnosed. These subjects are less symptomatic and impaired, which may partly explain lack of diagnosis. Although patients with undiagnosed COPD experience fewer exacerbations than those with diagnosed COPD, they use a similar amount of health services for exacerbation events; thus, the overall health system burden of exacerbations in those with undiagnosed COPD is considerable.

Vastus lateralis Na(+)-K(+)-ATPase activity, protein, and isoform distribution in chronic obstructive pulmonary disease.

In this study we investigate the hypothesis that protein abundance, isoform distribution, and maximal catalytic activity of sodium-potassium-adenosine triphosphatase (Na(+)-K(+)-ATPase) would be altered in muscle of patients with moderate to severe chronic obstructive pulmonary disease (COPD). Tissue samples were obtained from the vastus lateralis of 10 patients with COPD (mean +/- SE: age = 67 +/- 2.9 years; FEV1 = 39 +/- 5.5%) and 10 healthy, matched controls (CON: age = 68 +/- 2 years; FEV1 = 114 +/- 4.2%). The samples were assessed for maximal catalytic activity (Vmax) of the enzyme using the K(+)-stimulated 3-O-methylfluorescein-phosphatase (3-O-MFPase) assay, enzyme abundance using the [3H]-ouabain assay, and isoform content of both alpha (alpha1, alpha2, alpha3) and beta (beta1, beta2, beta3) using Western blot techniques. A 19.4% lower (P < 0.05) Vmax was observed in COPD compared with CON (90.7 +/- 6.7 vs. 73.1 +/- 4.7 nmol x mg protein(-1) h(-1)). No differences between groups were observed for pump concentration (259 +/- 15 vs. 243 +/- 17 pmol x g wet weight). For the isoforms, alpha1 was decreased by 28% (P < 0.05), and alpha2 was increased by 12% (P < 0.05) in COPD compared with CON. No differences between groups were observed for alpha3 or for the beta isoforms. We conclude that moderate COPD compromises Vmax, which occurs in the absence of changes in pump abundance. The reduction in Vmax could be due to a shift in isoform expression (alpha1, alpha2), alterations in intrinsic regulation, or to structural changes in the enzyme. The changes observed in the catalytic activity of the pump could have major effects on membrane excitability and fatigability, which are typically compromised in COPD.

Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease.

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity (V(max)) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 +/- 4 yr; FEV(1)/FVC = 44 +/- 3%, where FEV(1) is forced expiratory volume in 1 s and FVC is forced vital capacity; means +/- SE) and nine healthy age-matched controls (age 68 +/- 2 yr; FEV(1)/FVC = 75 +/- 2%). Compared with control, the COPD patients displayed lower (P < 0.05) V(max) (mol.kg protein(-1).h(-1)) for cytochrome c oxidase (COX; 21.2 +/- 2.0 vs. 28.7 +/- 2.2) and 3-hydroxyacyl-CoA dehydrogenase (HADH; 2.54 +/- 0.14 vs. 3.74 +/- 0.12) but not citrate synthase (CS; 2.20 +/- 0.16 vs. 3.19 +/- 0.5). While no differences between groups were observed in V(max) for creatine phosphokinase, phosphorylase (PHOSPH), phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase (HEX) was elevated in COPD (P < 0.05). Enzyme activity ratios were higher (P < 0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/HADH in COPD compared with control. It is concluded that COPD patients exhibit a reduced potential for both the electron transport system and fat oxidation and an increased potential for glucose phosphorylation while the potential for glycogenolysis and glycolysis remains normal. A comparison of enzyme ratios indicated greater potentials for glucose phosphorylation relative to the citric acid cycle and the electron transport chain and glycogenolysis and glycolysis relative to beta-oxidation.