April, 2011 Pulmonary Journal Club

Calverly P, Rabe K, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374:685-94. (Click here for PDF version of article)

Reference as: Mathew M, Hurley J. April, 2011 pulmonary journal club. Southwest J Pulm Crit Care 2011;2:58. (Click here for PDF version of journal club)

The use of phosphodiesterase inhibitors in COPD is not a noveau concept. Since their introduction in the early 1970's its role in COPD has been tangental. Nonselective phosphodiesterase inhibitors such as aminophylline and theophylline showed efficacy as bronchodilators and anti-inflammatories. The nonselective PDE inhibitors fell out of favor due to its side effect profile and narrow therapeutic index. With the approval of roflumilast by the Federal Drug Administration, we reviewed the study by Calverly et al. which reviewed two trials of roflumilast as a selective PDE4 inhibitor and its capacity to improve lung function and reduce COPD exacerbations. The two studies were large multicenter double blinded placebo controlled trials which followed patients over 52 weeks.  Patients with severe COPD were divided into two subsets; a placebo group and a roflumilast treatment group. Primary endpoints were a change in FEV1 and number of COPD exacerbations. The results showed patients on roflumilast had a slight statistically significant improvement in lung function with an increase in prebronchodilator FEV1 of 40ml. The study also showed a reduction in COPD exacerbations by 17% in the treatment arm. Main side effects were severe nausea, vomiting, diarrhea and an average weight loss of 4.2 kg when compared to placebo. The main limitation of this study is that it failed to show that medication related improvements were anything more than a bronchodilator effect. A cost analysis would also have been helpful.

Overall, Roflumilast as a new selective PDE4 inhibitor does show some mild improvement in lung function and reduction in COPD exacerbations. However, the benefits are small and cost may be a factor. Its main role may be limited to very severe COPD patients with cardiac disease and a BMI greater than 30.  

Manoj Mathew, MD, FCCP, MCCM

Jessica Hurley, MD

February 2011 Pulmonary Journal Club

Rice KL, Dewan N, Bloomfield HE, Grill J, Schult TM, Nelson DB, Kumari S, Thomas M, Geist LJ, Beaner C, Caldwell M, Niewoehner DE. Disease Management Program for Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial. Am J Respir Crit Care Med 2010;182:890-6. (Click here for abstract).

Reference as: Park K. February 2011 Pulmonary Journal Club. Southwest J Pulm Crit Care 2011;2:25-26. (Click here for PDF version)

The authors investigated the effect of disease management on chronic obstructive pulmonary disease admissions and emergency room visits. The study was designed as a randomized, controlled trial at five VA medical centers.  The study included high risk COPD patients defined as hospital admission or ED visit for COPD, home oxygen or systemic corticosteroid use for COPD within one year. 

The no intervention group received usual care.  The intervention group received a 1 to 1.5 hour session usually ran by a respiratory care therapist.  The session included education on COPD, smoking cessation, use of inhalers, appropriate vaccines and an action plan.  Patients were educated on early detection and treatment of their disease.  They were also followed up with monthly phone calls.

743 patients were randomized and followed for one year.  VA electronic records were used to follow patients.  Hospital admissions and ED visits outside VA system were reported by the patients.

There was statistically significant 41% decrease in the primary outcome at the end of one year.  All cause hospitalization and ED visits were also decreased by 28% (p<0.05).

This study demonstrates that a relatively simple intervention for disease management can improve hospital admission and ED visits.  Although there is a question of how COPD exacerbations were defined; the potential over use of medication; and whether the intervention is cost effective, this study lends credence to the concept that patient education may have a positive effect in severe COPD.

Prepared by Kevin Park, MD

Click here for accompanying Editorial.

December 2010 Pulmonary Journal Club

Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease (COPD). New Engl J Med 2010;363:1128-38.  

Reference as: Luedy HW, Mathew M. December 2010 pulmonary journal club: Susceptibility to exacerbation in chronic obstructive pulmonary disease (COPD). Southwest J Pulm Crit Care 2010;1:21. (Click here for PDF version)

   This large, observational cohort study tested the hypothesis that there is a frequent-exacerbation phenotype in COPD.  2138 pts were followed for 3 years. The frequency of exacerbations, defined as the prescription of antibiotics, steroids, or both, was noted.  The results demonstrate that the greatest predictor of COPD exacerbations was a previous exacerbation.  The authors noted that patients who experience two or more exacerbations in a year were likely to continue to have frequent exacerbations and this was independent of disease severity.  This was an important study in several regards. First, it shows that collecting data from large COPD sample sizes are possible, which in turn may yield further speciation on what constitutes an exacerbation.  Second, several intangible factors may play a role in exacerbations but these factors remain unknown.  Although the study demonstrates that patients that have COPD exacerbations will likely have more, how this can be modified is unknown.

Prepared by Henry W. Luedy, MD and  Manoj Mathew, MD