31. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. May 3, 2019─The antibiotic azithromycin may reduce treatment failure in patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (COPD), according to a randomized, controlled trial published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine. Erythromycin and common cold in COPD. Among patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (COPD), 49% of those who received adjunct therapy with azithromycin had COPD treatment failure by three months versus 60% of those who did not. Azithromycin Appears to Reduce Treatment Failure in Severe, Acute COPD Exacerbations May 3, 2019─The antibiotic azithromycin may reduce treatment failure in patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (COPD), according to a randomized, controlled trial published online in the American Thoracic Society’s American Journal of Respiratory and Critical … Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. Am J Respir Crit Care Med 1998;157:1418-1422, 7. — both in Minnesota; the Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh (F.C.S. The data were analyzed by the second author, who is a statistician, together with the first author. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in … Our results should be applied only to patients with COPD who either require supplemental oxygen or have had acute exacerbations and who do not have resting tachycardia or prolongation of the QTc interval, are not taking medications associated with QTc prolongation, and do not have hearing abnormalities that place them below the 95th percentile of patients of similar age. Proportion of Participants Free from Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) for 1 Year, According to Study Group. Mortality among those in the azithromycin group was half of the placebo group: 2 percent vs. 4 percent. Since approximately 80% of our participants were taking inhaled glucocorticoids with or without long-acting beta2-agonists or long-acting muscarinic antagonists throughout the study, the ability of azithromycin to decrease the frequency of acute exacerbations would seem to be additive to these other therapies. The patients were randomly assigned to treatment with azithromycin (n = 147) or placebo (n = 154) within 48 hours of admission. Sputum samples are preferred for the assessment of bacterial colonization. He ZY, Ou LM, Zhang JQ, et al. Azithromycin for prevention of exacerbations of COPD Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in … ), Acute exacerbations of chronic obstructive pulmonary disease (COPD) result in frequent visits to physicians' offices and emergency rooms and numerous hospitalizations and days lost from work; they also account for a substantial percentage of the cost of treating COPD.1-5 Patients who have acute exacerbations of COPD, as compared with patients with COPD who do not have acute exacerbations, have an increased risk of death, a more rapid decline in lung function, and reduced quality of life.6-11 Although inhaled glucocorticoids, long-acting beta2-agonists, and long-acting muscarinic antagonists reduce the frequency of acute exacerbations of COPD,12-24 patients receiving all three of these medications may still have as many as 1.4 acute exacerbations, on average, each year.23. Mahler DA, Donohue JF, Barbee RA, et al. The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.1 vs. 0.6±11.4, P=0.006); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Azithromycin is generally first-line, if the patient hasn't been exposed to it recently (don't worry, it doesn't cause Torsade de Pointes). — all in Denver; the Division of Biostatistics, School of Public Health (J.C.), and the Department of Medicine (D.E.N., J.R.), University of Minnesota, and the Division of Pulmonary Medicine, Medicine Service, Minneapolis Veterans Affairs (VA) Medical Center (D.E.N., J.R.) — both in Minneapolis; the Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham (W.C.B., J.A.D.C., M.T.D. Sin DD, McAlister FA, Man SFP, Anthonisen NR. Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Supported by grants (U10 HL074407, U10 HL074408, U10 HL074409, U10 HL074416, U10 HL074418, U10 HL074422, U10 HL074424, U10 HL074428, U10 HL074431, U10 HL074439, and U10 HL074441) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. The effect of azithromycin on the secondary outcomes is summarized in Table 2. FEV1 denotes forced expiratory volume in 1 second, and FVC forced vital capacity. ), 34. The content of this site is intended for health care professionals. 6. ); the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston (G.R.W. Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Gomez J, Banos V, Simarro E, et al. All the authors made the decision to submit the manuscript for publication. Direct costs of COPD in the U.S.: an analysis of Medical Expenditure Panel Survey (MEPS) data. Maintenance treatment with azithromycin significantly decreased the exacerbation rate compared with placebo and should therefore be considered for use in patients with COPD who have the frequent exacerbator phenotype and are refractory to standard care. Rates of Acute Exacerbations of Chronic Obstructive Pulmonary Disease per Person-Year, According to Study Group. MMWR Surveill Summ 2002;51:1-16, 9. 2011;365:689-98). Phaff SJ, Tiddens HA, Verbrugh HA, Ott A. Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. Efron B, Tibshirani RJ. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. Banerjee D, Khair OA, Honeybourne D. The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD. Nasopharyngeal swabs were obtained at 85% and 84% of the clinic visits attended by participants in the azithromycin group and placebo group, respectively. Patel and colleagues39 found that 52% of patients with frequent acute exacerbations of COPD had induced sputum that was most commonly colonized with Haemophilus influenzae, S. pneumoniae, H. parainfluenzae, and Moraxella catarrhalis. Macrolide antibiotics have immunomodulatory, antiinflammatory, and antibacterial effects. These episodes are usually associated with a sense of distress, and the effects are more severe than the symptom… Patients in the azithromycin arm of the study received 500 mg/day for three days while hospitalized, and then received 250 mg twice weekly for three months once they left the hospital. JAMA 2003;290:2301-2312, 25. Pulm Pharmacol Ther 2010;3:200-207, 32. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. A small but significant between-group difference was observed in the mean age-adjusted hearing thresholds for the four sound frequencies from enrollment to month 3, with patients in the azithromycin group having more pronounced hearing decrements (see Section F in the Supplementary Appendix). Thorax 2005;60:925-931, 12. In addition, it should be recognized that the long-term effects of this treatment on microbial resistance in the community are not known. Seemungal TAR, Wilkinson TMA, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Jones PW, Quirk FH, Baveystock CM. Bootstrap methods were used to compute confidence intervals for median times to the first exacerbation and for the difference in median times between the two groups.35 The rates of acute exacerbations of COPD were determined by dividing the number of acute exacerbations by the person-years of follow-up and were compared with the use of both Poisson and negative binomial analyses. // 450 msec), the use of medications that prolong the QTc interval or are associated with torsades de pointes (with the exception of amiodarone),33 and hearing impairment documented by audiometric testing. The American Thoracic Society improves global health by advancing research, patient care, and public health in pulmonary disease, critical illness, and sleep disorders. 1. Despite this, we found no evidence suggesting that colonization increased the incidence of acute exacerbations of COPD or pneumonia, consistent with prior observations in patients with cystic fibrosis.37,38 Although we saw no adverse cardiac effects of azithromycin, risk factors for the prolongation of the QTc interval were assessed before enrollment and participants who were thought to be at risk were excluded. The rate of death from respiratory causes was 2% and 1% in the two groups, respectively (P=0.48). Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Druss BG, Marcus SC, Olfson M, Pincus HA. Biometrika 1987;74:149-154, 37. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Ann Intern Med 2005;143:317-326, 20. The COPD Clinical Research Network is supported by a Cooperative Agreement from the Division of Lung Diseases of the NHLBI. Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery. Address reprint requests to Dr. Albert at Denver Health, 777 Bannock St., MC 4000, Denver, CO 80204-4507, or at [email protected]. Half the patients were given azithromycin, the other half a placebo, in addition to the medicines their physicians would normally prescribe to resolve the exacerbation. The affiliations of the authors are listed in the Appendix. These benefits appeared more pronounced among non-smokers. ), and the Pulmonary Section, Birmingham VA Medical Center (J.A.D.C., M.T.D.) Contemporary management of chronic obstructive pulmonary disease: scientific review. Niewoehner DE, Rice K, Cote C, et al. Although this intervention could change microbial resistance patterns, the effect of this change is not known. Because the researchers did not reach their goal of 500 participants, the trial was underpowered to demonstrate statistical significance of its primary endpoint: time to treatment failure. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. Current smokers experienced little or no benefit from low-dose azithromycin. Because most COPD patients who experience an acute exacerbation are already in treatment, researchers wanted to replicate that real-world scenario. Polypill with or without Aspirin in Persons without Cardiovascular Disease, Case 2-2021: A 26-Year-Old Pregnant Woman with Ventricular Tachycardia and Shock, Post-Transcriptional Genetic Silencing of, http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm. All the authors assume responsibility for the data and analyses and vouch for the fidelity of the study to the protocol. The antibiotic azithromycin may reduce treatment failure in patients hospitalized for an acute exacerbation of COPD, according to a randomized, controlled trial published online in the American Journal of Respiratory and Critical Care Medicine.. Cultures from 68% of the participants in the azithromycin group and 70% in the placebo group who were not colonized with selected respiratory pathogens at the time of enrollment but who became colonized during the course of the study were available for susceptibility testing (P=0.76), and the incidence of resistance to macrolides was 81% and 41% in the two groups, respectively (P<0.001) (Section G in the Supplementary Appendix). // ]]> Which Genes for Hereditary Breast Cancer? This decrease was accompanied by a decrease in the incidence of colonization with selected respiratory pathogens and improved quality of life, but also an increase in the incidence of colonization with macrolide-resistant organisms and an excess rate of hearing decrements of approximately 5%. Hearing was assessed by means of audiometry at the time of enrollment and at 3 and 12 months, or whenever a patient reported worsening hearing or tinnitus. Cultures from 56% of the participants in the azithromycin group and 59% in the placebo group who had selected respiratory pathogens cultured from their nasopharyngeal swabs at the time of enrollment were available for susceptibility testing (P=0.68); the remaining cultures were not tested because of protocol errors. Chest 2001;119:344-352, 2. COPD (exacerbation/lung attack)? The effect of azithromycin on the secondary outcomes is summarized in. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Kim K, DeMets DL. Azithromycin for Prevention of COPD Exacerbations. The protocol was designed by the first author and was modified on the basis of input from the remaining authors. Accordingly, the data were analyzed with the use of group sequential testing36 that allowed “spending” a little of the alpha at each interim analysis such that, at the end of the study, the total type I error did not exceed 0.05. The authors' affiliations are as follows: the Medicine Service, Denver Health and Department of Medicine (R.K.A., C.S.P. Macrolide antibiotics have immunomodulatory, antiinflammatory, and antibacterial effects. Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). This study was funded by the Flemish Government Agency for Innovation by Science and Technology (FWO Vlaanderen), the Belgium Respiratory Society and TEVA, Belgium. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. DOI: 10.1056/NEJMoa1104623, Tap into groundbreaking research and clinically relevant insights. The total SGRQ scores recorded at 1 year decreased a mean (±SD) of 2.8±12.1 units in the azithromycin group, as compared with a mean of 0.6±11.4 units in the placebo group (P=0.006) (see Section C in the Supplementary Appendix for individual scale scores). Ann Intern Med 2007;146:545-555, 24. The date of each acute exacerbation was taken as the date treatment was prescribed. Effect of Treatment for Chronic Obstructive Pulmonary Disease (COPD) on Hospitalization Rates, Emergency Department or Urgent Care Visits, and Unscheduled Office Visits. 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