Azithromycin for prevention of exacerbations of COPD
Open accessAbstract
BACKGROUND: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS: A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). 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±12.8 vs. 0.6±11.4, P=0.004); 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). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS: 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 a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The intervention most consistently proven to decrease exacerbation frequency in COPD, cystic fibrosis, and bronchiectasis is azithromycin.
“The intervention most consistently proven to decrease exacerbation frequency (in COPD,143 cystic fibrosis144 and bronchiectasis145) is azithromycin, a macrolide antibiotic.”
From The microbiome and critical illness (2016) · cites this paper as [143]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1994) · doi:10.1201/9780429246593 · Cited by 40,500 · see citing works
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1993) · doi:10.1007/978-1-4899-4541-9 · Cited by 21,230 · see citing works
Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease
CALVERLEY, P. M. A., Anderson, J. A., Celli, B. R., Ferguson, G. T., Jenkins, C. R., Jones, P., Yates, J., & Vestbo, J. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa063070 · Cited by 3,233 · see citing works
The St George's Respiratory Questionnaire
Jones, P., Quirk, F. H., & Baveystock, C. M. (1991) · Respiratory Medicine · doi:10.1016/s0954-6111(06)80166-6 · Cited by 2,729 · see citing works
Chronic Obstructive Pulmonary Disease
Flavin, K., Morkane, C. M., & Marsh, S. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108233712.025 · Cited by 2,694 · see citing works
Effect of Exacerbation on Quality of Life in Patients with Chronic Obstructive Pulmonary Disease
SEEMUNGAL, T. A. R., Donaldson, G. C., Paul, E. A., Bestall, J., Jeffries, D. J., & Wedzicha, J. A. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.5.9709032 · Cited by 2,291 · see citing works
Donaldson, G. C. (2002) · Thorax · doi:10.1136/thorax.57.10.847 · Cited by 2,249 · see citing works
A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease
Tashkin, D. P., Celli, B. R., Senn, S. J., Burkhart, D., Kesten, S., Menjoge, S., & Decramer, M. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0805800 · Cited by 2,182 · see citing works
Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease
Soler‐Cataluña, J. J. (2005) · Thorax · doi:10.1136/thx.2005.040527 · Cited by 1,931 · see citing works
Chronic Obstructive Pulmonary Disease Surveillance—United States, 1971–2000
Mannino, D. M., Homa, D. M., Akinbami, L. J., Ford, E. S., & Redd, S. C. (2002) · Respiratory Care · doi:10.1177/002013240204701009 · Cited by 1,293 · see citing works
Calverley, P. M. A., PAUWELS, R. A., Vestbo, J., Jones, P., Pride, N. B., Gulsvik, A., Anderson, J. A., & Maden, C. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12459-2 · Cited by 1,217 · see citing works
Szafrański, W., Cukier, A., Ramírez, A. S., Menga, G., Sansores, R. H., Nahabedian, S., Peterson, S., & Olsson, H. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00031402 · Cited by 883 · see citing works
A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease
Casaburi, R. H., Mahler, D. A., Jones, P., Wanner, A., Pedro, G. S. S., ZuWallack, R., Menjoge, S., Serby, C. W., & Witek, T. J. (2002) · European Respiratory Journal · doi:10.1183/09031936.02.00269802 · Cited by 881 · see citing works
Self-citationImproved health outcomes in patients with COPD during 1 yr's treatment with tiotropium
Vincken, W., van Noord, J. A., Greefhorst, A. P. M., Bantje, T. A., Kesten, S., Korducki, L., & Cornelissen, P. J. G. (2002) · European Respiratory Journal · doi:10.1183/09031936.02.00238702 · Cited by 735 · see citing works
Patel, I. S. (2002) · Thorax · doi:10.1136/thorax.57.9.759 · Cited by 689 · see citing works
Aaron, S. D., Vandemheen, K. L., Fergusson, D. A., Maltais, F., Bourbeau, J., Goldstein, R. S., Balter, M. S., O'Donnell, D., McIvor, A., Sharma, S., et al. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-8-200704170-00152 · Cited by 643 · see citing works
Kanner, R. E., Anthonisen, N. R., & Connett, J. E. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.3.2010017 · Cited by 585 · see citing works
Self-citationEfficacy of Salmeterol Xinafoate in the Treatment of COPD
Mahler, D. A., Donohue, J. F., Barbee, R. A., Goldman, M. D., Gross, N. J., Wisniewski, M., Yancey, S. W., Zakes, B. A., RICKARD, K. A., & Anderson, W. H. (1999) · CHEST Journal · doi:10.1378/chest.115.4.957 · Cited by 508 · see citing works
Seemungal, T., Wilkinson, T. M. A., Hurst, J. R., Perera, W. R., Sapsford, R. J., & Wedzicha, J. A. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200801-145oc · Cited by 442 · see citing works
Niewoehner, D. E., Rice, K. L., Côté, C., et al. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-143-5-200509060-00007 · Cited by 436 · see citing works
Self-citationBrusasco, V. (2005) · Thorax · doi:10.1136/thx.2005.brusascolett · Cited by 431 · see citing works
Brusasco, V. (2003) · Thorax · doi:10.1136/thorax.58.5.399 · Cited by 408 · see citing works
Welte, T., Miravitlles, M., Hernandez, P., Eriksson, G., Peterson, S., Polanowski, T., & Kessler, R. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200904-0492oc · Cited by 406 · see citing works
Contemporary Management of Chronic Obstructive Pulmonary Disease
Sin, D. D., McAlister, F. A., Man, S. F. P., & Anthonisen, N. R. (2003) · JAMA · doi:10.1001/jama.290.17.2301 · Cited by 400 · see citing works
Self-citationSaiman, L. M. (2010) · JAMA · doi:10.1001/jama.2010.563 · Cited by 326 · see citing works
The costs of exacerbations in chronic obstructive pulmonary disease (COPD)
Andersson, F., Borg, S., Jansson, S., Jonsson, A.-C., Ericsson, Å., Prütz, C., Rönmark, E., & Lundbäck, B. (2002) · Respiratory Medicine · doi:10.1053/rmed.2002.1334 · Cited by 298 · see citing works
Design and Analysis of Group Sequential Tests Based on the Type I Error Spending Rate Function
Kim, K., & DeMets, D. L. (1987) · Biometrika · doi:10.1093/biomet/74.1.149 · Cited by 295 · see citing works
The Costs of Treating COPD in the United States
Strassels, S. A., Smith, D. H., Sullivan, S. D., et al. (2001) · CHEST Journal · doi:10.1378/chest.119.2.344 · Cited by 289 · see citing works
The Most Expensive Medical Conditions In America
Druss, B. G., Marcus, S. C., Olfson, M., & Pincus, H. A. (2002) · Health Affairs · doi:10.1377/hlthaff.21.4.105 · Cited by 236 · see citing works
Lindenauer, P. K., Pekow, P. S., Gao, S., Crawford, A. S., Gutiérrez, B., & Benjamin, E. M. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-144-12-200606200-00006 · Cited by 190 · see citing works
Erythromycin and Common Cold in COPD
Suzuki, T., Yanai, M., Yamaya, M., Satoh‐Nakagawa, T., Sekizawa, K., Ishida, S., & Sasaki, H. (2001) · CHEST Journal · doi:10.1378/chest.120.3.730 · Cited by 168 · see citing works
Role of macrolide therapy in chronic obstructive pulmonary disease
Martínez, F. J. (2008) · International Journal of COPD · doi:10.2147/copd.s681 · Cited by 122 · see citing works
He, Z., Ou, L.-M., Zhang, J., Bai, J., Liu, G., Li, M., Deng, J., MacNee, W., & Zhong, X. (2010) · Respiration · doi:10.1159/000321374 · Cited by 121 · see citing works
with chronic obstructive pulmonary disease Severe acute exacerbations and mortality in patients
Ochando, R., Soler‐Cataluña, J. J., Martínez‐García, M. Á., Sánchez, P. R., Salcedo, E., & Navarro, M. (2006) · Cited by 103 · see citing works
Phaff, S. J., Tiddens, H. A. W. M., Verbrugh, H. A., et al. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl014 · Cited by 102 · see citing works
The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD
Banerjee, D., Khair, O. A., & Honeybourne, D. (2004) · Respiratory Medicine · doi:10.1016/j.rmed.2004.06.009 · Cited by 93 · see citing works
Direct Costs of COPD in the U.S.: An Analysis of Medical Expenditure Panel Survey (MEPS) Data
Miller, J. D., Foster, T. S., Boulanger, L., et al. (2005) · COPD Journal of Chronic Obstructive Pulmonary Disease · doi:10.1080/15412550500218221 · Cited by 88 · see citing works
Long-term azithromycin use in patients with chronic obstructive pulmonary disease and tracheostomy
Blasi, F., Bonardi, D. R., Aliberti, S., et al. (2009) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2009.12.002 · Cited by 81 · see citing works
Yamaya, M., Azuma, A., Tanaka, H., et al. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.01725.x · Cited by 36 · see citing works
Tsai, C., Sobrino, J. A., & Camargo, C. A. (2008) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.2008.00284.x · Cited by 33 · see citing works
Gómez, J., Baños, V., Simarro, E., et al. (2000) · PubMed · Cited by 32 · see citing works
Calverley, P. M., PAUWELS, R. A., & Vestbo, J. (2003) · Ghent University Academic Bibliography (Ghent University) · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Vogelmeier, C. F., Criner, G. J., Martinez, F. J., Anzueto, A., Barnes, P. J., Bourbeau, J., Celli, B. R., Chen, R., Decramer, M., Fabbri, L. M., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201701-0218pp · Cited by 3,187 · see citing works
Self-citationFokkens, W. J., Lund, V. J., Mullol, J., Bachert, C., Alobid, I., Baroody, F., Cohen, N., Cervin, A., Douglas, R., Gevaert, P., et al. (2012) · Rhinology journal · doi:10.4193/rhino12.000 · Cited by 2,387 · see citing works
International Consensus Statement on Allergy and Rhinology: Rhinosinusitis
Orlandi, R. R., Kingdom, T. T., Hwang, P. H., Smith, T. L., Alt, J. A., Baroody, F. M., Batra, P. S., Bernal‐Sprekelsen, M., Bhattacharyya, N., Chandra, R. K., et al. (2016) · International Forum of Allergy & Rhinology · doi:10.1002/alr.21695 · Cited by 892 · see citing works
Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hockey, H., Milne, D., Fergusson, W., Tuffery, C., Sexton, P., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60953-2 · Cited by 600 · see citing works
The role of the microbiome in exacerbations of chronic lung diseases
Dickson, R. P., Martinez, F. J., & Huffnagle, G. B. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61136-3 · Cited by 495 · see citing works
Self-citationSegal, L. N., Alekseyenko, A. V., Clemente, J. C., Kulkarni, R., Wu, B., Chen, H., Berger, K. I., Goldring, R. M., Rom, W. N., Blaser, M. J., et al. (2013) · Microbiome · doi:10.1186/2049-2618-1-19 · Cited by 482 · see citing works
The microbiome and critical illness
Dickson, R. P. (2016) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00427-0 · Cited by 460 · see citing works
Gut-Lung Axis: The Microbial Contributions and Clinical Implications
He, Y., Wen, Q., Yao, F., Xu, D., Huang, Y., & Wang, J. (2017) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2016.1176988 · Cited by 301 · see citing works
Larsen, J. M., Musavian, H. S., Butt, T. M., Ingvorsen, C., Thysen, A. H., & Brix, S. (2015) · Immunology · doi:10.1111/imm.12376 · Cited by 200 · see citing works
Health Coaching and Chronic Obstructive Pulmonary Disease Rehospitalization: A Randomized Study
Benzo, R., Vickers, K., Novotny, P. J., Tucker, S., Hoult, J., Neuenfeldt, P., Connett, J., Lorig, K., & McEvoy, C. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2503oc · Cited by 176 · see citing works
Self-citation
- Authors
- Albert, R. K., Connett, J., Bailey, W. C., Casaburi, R., Cooper, J. A. D., Criner, G. J., Curtis, J. L., Dransfield, M. T., Han, M. K., Lazarus, S. C., Make, B., Marchetti, N., Martinez, F. J., Madinger, N. E., McEvoy, C., Niewoehner, D. E., Porsasz, J., Price, C. S., Reilly, J., Scanlon, P. D., Sciurba, F. C., Scharf, S. M., Washko, G. R., Woodruff, P. G., & Anthonisen, N. R.
- Affiliations
- Denver Health Medical Center (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-08-25
- Volume
- 365
- Issue
- 8
- Pages
- 689-698
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3220999
- OpenAlex
- W2096373158
- Cited by
- 1,226
- References
- 43
- Citations by year
- 2026: 41 · 2025: 51 · 2024: 67 · 2023: 60 · 2022: 55 · 2021: 72 · 2020: 66 · 2019: 91 · 2018: 84 · 2017: 96 · 2016: 84 · 2015: 114 · 2014: 118 · 2013: 121 · 2012: 91
- FWCI
- 91.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1k23hl089353-01a1)
- National Heart, Lung, and Blood Institute (U10HL074418, U10HL074407, K23 HL-089353, U10HL074431, HL074422, HL074409, U10HL074424, HL074439, U10HL074422, HL 074428, U10HL074416, U10HL074409, HL074418, HL074407, U10HL074439, U10HL074441, HL074408, U10HL074428, HL074441, U10HL074408)
- National Center for Research Resources (M01RR000056, M01RR000051, M01RR016500, M01RR002635, M01RR000425)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Keywords
- azithromycin, chronic obstructive pulmonary disease, COPD exacerbations, macrolide antibiotics, exacerbation prevention, St George's Respiratory Questionnaire, quality of life, hearing loss, QT prolongation, adverse effects, risk stratification, usual care
- MeSH terms
- Aged, Anti-Bacterial Agents, Bacterial Infections, Female, Humans, Male, Middle Aged, Nasopharynx, Prospective Studies, Treatment Outcome, Azithromycin, Macrolides, Drug Resistance, Bacterial, Pulmonary Disease, Chronic Obstructive
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
