The prevention of COPD exacerbations by salmeterol/fluticasone propionate or tiotropium bromide.

Rationale: Exacerbations are key drivers of morbidity and mortality in chronicobstructive pulmonary disease (COPD).Objectives: We compared the relative efficacy of the long-acting inhaledbronchodilator/anti-inflammatory combination (salmeterol/fluticasone propionate) 50/500mcg bd and the long-acting bronchodilator (tiotropium) 18mcg od in preventing exacerbations and related outcomes in moderate severe COPD Methods: 1323 patients (mean age 64yr, forced expiratory volume in 1sec 39 per cent predicted) were randomized in 2-year, double blind, double-dummy, parallel study.Measurements and Main Results: Primary endpoint was healthcare utilization exacerbation rate. Other endpoints included health status measured by St. Georges Respiratory Questionnaire (SGRQ), mortality, adverse events and study withdrawal.Probability of withdrawing from the study was 29 per cent greater with tiotropium than salmeterol/fluticasone propionate (p=0.005). The modelled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio 0.967 [95 per cent CI: 0.836 to 1.119]; p=0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionateversus tiotropium (difference 2.1 units, 95 per cent CI: 0.1 to 4.0, p=0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3 per cent of patients in this group died compared to 38 (6 per cent) in the tiotropium group (p=0.032). Morepneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (p=0.008).Conclusions: We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate treated patients.

Early therapy improves outcomes of exacerbations of Chronic Obstructive Pulmonary Disease

Treatment of chronic obstructive pulmonary disease (COPD) exacerbations improves outcomes; however, responses to treatment are variable, and patients with COPD often delay presentation or fail to seek therapy. The impact on exacerbation outcomes, hospitalization, and health status of delaying or failing to seek treatment is poorly understood. We studied between 1996 and 2002 a cohort of 128 patients with COPD, mean (SD) FEV1 of 1.07 (0.43) L. Patients recorded respiratory symptoms daily and reported exacerbations to the outpatient-based study team or to their primary care physician; 1,099 exacerbations were recorded by the patients, of which 658 were reported to a physician. The time between exacerbation onset and treatment was a median (interquartile range) of 3.69 (2.0–5.57) days, and the exacerbation recovery time was 10.7 (7.0–14.0) days. Earlier treatment was associated with a faster recovery (regression coefficient 0.42 days/day delay) (confidence interval, 0.19–0.65; p < 0.001). Patients who reported a higher proportion of exacerbations for treatment had better health-related quality of life than those patients with more untreated exacerbations (rho = –0.22, p = 0.018). Failure to report exacerbations was associated with an increased risk of emergency hospitalization (rho = 0.21, p = 0.04). Patient recognition of exacerbation symptoms and prompt treatment improves exacerbation recovery, reduces risks of hospitalization, and is associated with a better health-related quality of life

Airway and systemic inflammation and decline in lung function in patients with COPD

Study objective: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline FEV. Patient and design: a cohort of 148 COPD patients (100 men) was monitored daily for a median 2.9 years (interquartile range [IQR], 2.1 to 4.8). At recruitment median age was 68.5 years (IQR, 62.5 to 73.6) and FEV as percentage of predicted (FEV percent Pred) was 38.5 percent (IQR, 27.7 to 50.3). Results: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR 1.48 to 3.96) and FEV declined by 40.2 mL/yr or as FEV percent Pred by 1.5 percent/yr. Concerning inflammatory markers, sputum interlukin (IL)-6 rose by 9 pg/mL, sputum neutrophil count rose by 1.64 x 10,000,000 cells per gram sputum per year, and plasma fibrinogen rose by 0.10 g/L/yr (all p, 0.05). Patients with frequent exacerbations (less than or equal to 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p= 0.046, n= 130) and 29.5 pg/mL/yr (p< 0.001, n=98), respectively, compared to patients with infrequent exacerbations (<2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV percentPred decline of 0.97 percent/yr (p=0.001 and .40 percent/yr (p=0.014). respectively. Conclusions: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function (AU)