Asthma and COPD are 2 of the more common ailments responsible for patients presenting to an Emergency Department with complaints of shortness of breath. Last week, we met as a residency and, led by Dr. Lauren Titone, Dr. Walker Plash, and Dr. Rob Thompson, discussed some newer literature for the treatment of these often intertwined conditions. Take a listen to the podcast below to hear our thoughts and read the summary below for the breakdown.
The Reduce Trial
Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. JAMA 2013;309(21):2223–9.
This trial sought to answer the following question: In patients with acute COPD exacerbations is a five day course of steroids non-inferior to a 14 day course of steroids at preventing repeat exacerbations?
It is a multicenter, double-blind, randomized, non-inferiority study performed at 5 teaching hospitals in Switzerland. The authors enrolled 314 patients age >40 with FEV1/FVC ratios <70% and a > 20 smoking pack year history. Patients received either a traditional course of 14 days (without taper) or an experimental 5 day course of steroids. Patients were given 40mg IV of methylprednisolone in the ED followed by 40mg of prednisone or placebo. All participants were also given standard bronchodilator treatments, 7 days of antibiotics and 6 months of tiotropium plus a combination inhaled glucocorticoid/long acting beta agonist. The primary outcome was re-exacerbation requiring contact with a physician within a 6 month follow up period. They powered this non-inferiority study to allow for a 15% increase in treatment failure in exchange for the shorter course of steroids.
The results showed that 5 days of glucocorticoid therapy was non-inferior to 14 days with a HR of 0.95. Secondary outcomes showed that the 5 day group had a shorter hospital stay by 1 day but there were no significant differences in mortality, need for NIPPV or intubation or glucocorticoid side effects. The latter point was somewhat surprising however the authors postulated that 6 months of follow up may not be an appropriate time course to see a difference. Some limitations include the somewhat intensive treatment both groups received (inhaled steroids, antibiotics etc) and that the study was not powered for superiority. This was a very sick patient population, with 83% of patients defined as GOLD criteria 3 or 4 and only about 8% of participants discharged from the ED. We felt that these patients were on the whole somewhat sicker than what we see in our shop however given that 5 days remained non-inferior despite this severity, these data could be extrapolated to our patient population. While most of our providers are prescribing 5 day courses already this paper gave us a good evidence based foundation as to the efficacy of our practice.
Summary by Dr. Lauren Titone
Single Dose Dexamethasone in Asthma?
MD MWR, MD BL, BS MR, PharmD JL, MS HJAM. A Randomized Controlled Noninferiority Trial of Single Dose ofOral Dexamethasone Versus 5 Days of Oral Prednisone in Acute Adult Asthma. Annals of Emergency Medicine 2016;68(5):608–13.
This was a single center, prospective, randomized, triple blinded non-inferiority trial of a single dose of oral dexamethasone vs 5 days of oral prednisone in acute adult asthma exacerbations.
The respiratory therapists screened and enrolled patients who were 18-55 years old, had a history of asthma, and required more than 1 albuterol treatment. The excluded anyone if they did not have a working telephone number, or were less than <18 and >55, pregnant, allergic to corticosteroids, use of corticosteroids 2 weeks before, history of chronic respiratory disease, pulmonary fibrosis, HIV/AIDS, CHF, or DM. They also excluded anyone with active varicella or TB, and anyone requiring immediate airway intervention (NIPPV or Intubation). The patients received 1 dose of 12mg of Dexamethasone and 4 placebo tablets or 1 dose of 60mg Prednisone and 4 additional 60mg prednisone tablets. 465 patients were enrolled, but only 375 were analyzed secondary to need for admission or loss of follow up. The primary outcome was need for a repeat visit in 2 weeks for worsening or persistent asthma symptoms. The secondary outcomes were side effects of the glucocorticoids and current asthma symptoms. The followed up with patients via telephone at 2 weeks.
They found a 2.3% difference between the 2 groups that favored the prednisone group. The 95% CI was (-4.1 to 8.6) which was greater than the preset 8% non-inferiority limit. Therefore, dexamethasone was found to be NOT non-inferior to 5 days of prednisone. This study is not going to lead to an earth shattering practice changes, but I think it supports using a single dose of dexamethasone, for acute adult asthma exacerbations, in patients where compliance is a concern.
Summary by Dr. Rob Thompson
Do All Admitted COPD Patients Need Antibiotics?
Rothberg MB. Antibiotic Therapy and Treatment Failure in Patients Hospitalized for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. JAMA 2010;303(20):2035–42.
This was a retrospective multi-center cohort study of patients admitted for an acute exacerbation of COPD with admission to 313 hospitals in the US participating in a healthcare utilization database comparing administration of antibiotics in the first two days vs later antibiotic administration or no antibiotic administration.
Primary outcome was treatment failure (defined as initiation of mechanical intubation after day 2, in-hospital mortality, or readmission for acute COPD exacerbation within 30 days of discharge). Secondary outcomes included hospital cost, length of stay, allergic reactions, antibiotic associated diarrhea, and readmission for diarrhea or C. difficile within 30 days of discharge.
Primary outcome showed a decrease in treatment failure for groups treated with early antibiotics, with an odds ratio of 0.87 for covariate adjusted analysis. Early antibiotics did show a slight increase in c. difficile diarrhea as well as readmission with diarrhea. It also showed a slight increase in length of stay and cost in the covariate adjusted group (OR 1.03 for both). There were a few issues with this study, mostly that it was a retrospective review and limited by using an administrative database. Despite these limitations, it was a robust retrospective review.
We took away that, in patients with acute COPD exacerbations, it is reasonable to give antibiotics even in patients without pneumonia. It is likely to be of more benefit in sicker patients, and future studies are likely to be geared towards predicting who needs antibiotics and who does not in acute COPD exacerbations. Until these future studies are performed or a prospective study shows contrary information, we will likely treat all of our admitted patients with COPD with antibiotics.
Summary by Dr. Walker Plash