2011 Literature Review: COPD

April 2011

Radiographic emphysema correlated with low bone mineral density: COPD's systemic inflammatory effects are postulated to negatively impact bone turnover. After looking at CT scans, PFTs, and steroid history in 190 current and former smokers, Bon et al found visual emphysema on chest CT was highly correlated with osteopenia/osteoporosis, with an odds ratio of 2.55 that was independent of airflow limitation, age, sex, inhaled/oral steroid use, and current smoking status. AJRCCM 2011;183:885-890.
COPD in never-smokers: BOLD unravels some of the mystery. Never-smokers make up >25% of the people with COPD in some studies. Who are these people? The BOLD study gathered data from 14 countries (in the U.S., Europe, Turkey, China, South Africa, Philippines and Australia), including spirometry and questionnaires on environmental exposures and symptoms from 10,000 people. Of the 4,291 never-smokers, 4% had ATS-defined COPD (5.6% by GOLD). Impressively, these never-smokers comprised 20% of the moderate-to-severe (GOLD II+) COPD cases, and 81% of them were undiagnosed. More than two-thirds were women.
They had a 72% rate of respiratory symptoms (compared to 44% for never-smokers without COPD), and they were more likely to report 10 years of exposure to indoor fires (22% vs 15%) and/or organic dusts in the workplace (19% vs 10%) than unobstructed never-smokers. COPD rates in never-smokers were highest in Australia (7.5%) and Poland (9%), and lowest in the U.S. (3.5%). A collective of drug companies are funding this ongoing study that could guide public health efforts (and drug marketing). CHEST 2011;139:752-763.

Natural history of nonspecific pulmonary function tests: Iyer et al re-checked PFTs on 1,284 people with nonspecific results (low FEV1 or FVC but normal TLC and FEV1/FVC ratio), at a median of 3 years after the abnormal test. 64% continued to have the nonspecific result; 16% had restriction; 15% had obstruction; 2% had a mixed pattern; 3% were normal. They recommend changing the current guidelines that label these people as having obstruction. CHEST 2011;139:878-886.

March 2011

CAGE MATCH: Tiotropium vs. Salmeterol ... scorecard: time-to-COPD exacerbation (POET-COPD trial):  Who's the best bronchodilator on the block? In 725 centers, in 25 countries, among COPD'ers with FEV1<=70% (moderate-or-worse) and an exacerbation in the past year, after using tiotropium or salmeterol (double-dummy) for 1 year, the winner is.... Tiotropium! Probably! With a time-to-first-exacerbation of 187 vs. 145 days -- but only in the quartile of study patients having the earliest exacerbations. That sounded confusing to us too. Only 36% of patients had an exacerbation during the year, so this is really an analysis of the first 1,844 to have exacerbations of the original 7,376 patients (if our math is right -- they don't provide this number). That said, tiotropium won hands down, with a small/modest benefit that was not apparently influenced by glucocorticoid use, drug discontinuation or other confounders. In absolute terms, tiotropium prevented 0.08 more exacerbations per patient per year (0.64 vs. 0.72) than did salmeterol, especially severe exacerbations (number needed to treat for one year to prevent an additional exacerbation = 13)No difference in adverse events. Boehringer Ingelheim was heavily involved in the design and controlled the statistical analysis of the study.  NEJM 2011;364:1093-1103. RANDOMIZED TRIAL (n=7,376).

Chantix worked in people with mild to moderate COPD: Tashkin et al randomized 504 patients at 27 centers with COPD and FEV1 > 49% to varenicline or placebo for 12 weeks, with 52 weeks follow up. Abstinence rate (carbon monoxide-confirmed) was 42% vs 9% in weeks 9 - 12 (1' endpoint), and 19% vs. 6% in weeks 9 - 52 (p<0.0001). And even better, no one killed themselves!  CHEST 2011;139:591-599. 

February 2011

Once-daily indacaterol as effective as salmeterol bid for COPD
The once-daily beta-agonist was better than placebo and at least as good as twice-daily salmeterol, as measured by the SGRQTDI, and FEV1 after 12 weeks. The drug previously matched up well against tiotropium. Indacaterol is available in Europe, but not in the U.S. ERJ 2011;37:273-279. RANDOMIZED TRIAL (n=838). 

NOTE: In March 2011, an FDA advisory panel voted to approve indacaterol for U.S. use.

Long-term oxygen therapy: Christopher KL & Porte P, CHEST 2011;139:430-440. REVIEW

Transtracheal oxygen therapy: Christopher KL, Schwartz MD, CHEST 2011;139. REVIEW

Inspiratory muscle training in COPD: Gosselink R, ERJ 2011;37:416-425. REVIEW

January 2011 was not reviewed.