[Skip to Content]
[Skip to Content Landing]

Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract InfectionA Randomized Clinical Trial

Educational Objective
To learn the effects of oral corticosteroids in patients with acute lower respiratory tract infection.
1 Credit CME
Key Points

Question  Does a moderate dose of oral corticosteroid reduce the duration or severity of acute lower respiratory tract infection in adults without asthma presenting to primary care?

Findings  In this randomized trial of 401 adults with symptoms of acute lower respiratory tract infection, treatment with oral prednisolone, 40 mg/d for 5 days, compared with placebo did not significantly reduce the median duration of moderately bad or worse cough (5 days in each group) or the mean severity of symptoms between days 2 and 4 (1.99 vs 2.16 points out of 6).

Meaning  These findings do not support the use of oral steroids for the treatment of acute lower respiratory tract infection in the absence of asthma.


Importance  Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence.

Objective  To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma.

Design, Setting, and Participants  Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years.

Interventions  Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days.

Main Outcomes and Measures  The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events.

Results  Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, −0.20; 95% CI, −0.40 to 0.00; P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events.

Conclusions and Relevance  Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity.

Trial Registration  ISRCTN.com Identifier: ISRCTN57309858

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Corresponding Author: Alastair D. Hay, FRCGP, Centre for Academic Primary Care, NIHR School for Primary Care Research, Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Rd, Clifton, Bristol BS8 2PS, England (alastair.hay@bristol.ac.uk).

Accepted for Publication: July 21, 2017.

Author Contributions: Dr Brookes had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hay, Little, Harnden, Thompson, Wang, Kendrick, Brookes, May, Carroll, El-Gohary, Moore.

Acquisition, analysis, or interpretation of data: Harnden, Wang, Kendrick, Orton, Brookes, Young, May, Hollinghurst, Carroll, Downing, Timmins, Lafond, Moore.

Drafting of the manuscript: Hay, Kendrick, Orton, Brookes, Young, Downing, Timmins, Lafond, El-Gohary, Moore.

Critical revision of the manuscript for important intellectual content: Hay, Little, Harnden, Thompson, Wang, Kendrick, Orton, Brookes, Young, May, Hollinghurst, Carroll, Lafond, Moore.

Statistical analysis: Brookes, Young, May.

Obtained funding: Hay, Little, Harnden, Wang, Kendrick, Orton, Moore.

Administrative, technical, or material support: Thompson, Orton, Downing, Timmins, Lafond, Moore.

Supervision: Hay, Little, Harnden, Wang, Kendrick, Brookes, May, Hollinghurst, Lafond.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Thompson reports that he has received funding from Alere Inc to conduct research on C-reactive protein point-of-care tests, has received funding from Roche Molecular Diagnostics for consultancy work, and is a cofounder of Phoresa Inc, which is developing point-of-care tests for primary care. No other disclosures were reported.

Funding/Support: This article presents independent research funded by the National Institute for Health Research (NIHR) School for Primary Care Research (grant reference 117a). Dr Hay is funded by an NIHR Research Professorship (NIHR-RP-02-12-012). The study sponsor was the University of Bristol.

Role of the Funder/Sponsor: Neither the funder nor the sponsor had no involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Disclaimer: The views expressed herein are those of the authors and not necessarily those of the NIHR, the National Health Service, or the UK Department of Health.

Additional Contributions: We thank the participants, the recruiting primary care sites, the NIHR Clinical Research Network, and all members of the OSAC team. We also thank the members of the trial steering committee (who provided independent supervision on behalf of the funder and sponsor) and the data monitoring committee (who oversaw safety), the Nottingham University Hospitals NHS Trust pharmacy, and the University Hospitals Bristol NHS Foundation Trust. We thank Mark Ebell, MD, University of Georgia, who (without compensation) conducted a secondary data analysis to estimate the use of oral prednisolone for acute lower respiratory tract infection using administrative data from the southeastern United States.

National Institute for Health and Clinical Excellence. Respiratory tract infections: prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. July 2008. https://www.nice.org.uk/guidance/cg69. Accessed August 1, 2017.
Fleming-Dutra  KE, Hersh  AL, Shapiro  DJ,  et al.  Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011.  JAMA. 2016;315(17):1864-1873.PubMedGoogle ScholarCrossref
Butler  CC, Hood  K, Verheij  T,  et al.  Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries.  BMJ. 2009;338:b2242.PubMedGoogle ScholarCrossref
Little  P, Stuart  B, Moore  M,  et al; GRACE Consortium.  Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial.  Lancet Infect Dis. 2013;13(2):123-129.PubMedGoogle ScholarCrossref
Gonzales  R, Malone  DC, Maselli  JH, Sande  MA.  Excessive antibiotic use for acute respiratory infections in the United States.  Clin Infect Dis. 2001;33(6):757-762.PubMedGoogle ScholarCrossref
Morice  AH, McGarvey  L, Pavord  I; British Thoracic Society Cough Guideline Group.  Recommendations for the management of cough in adults.  Thorax. 2006;61(suppl 1):i1-i24. PubMedGoogle ScholarCrossref
World Health Organization.  Antimicrobial Resistance: Global Report on Surveillance. Geneva, Switzerland: World Health Organization; 2014.
Public Health England. English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) 2010 to 2014. November 2015. https://www.gov.uk/mwg-internal/de5fs23hu73ds/progress?id=Lpkkp2P0R21gtGdImtDUQvQucNAADvg1F4z_9merBkU,&dl. Accessed July 27, 2017.
Costelloe  C, Metcalfe  C, Lovering  A, Mant  D, Hay  AD.  Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis.  BMJ. 2010;340:c2096.PubMedGoogle ScholarCrossref
White House. National Strategy for Combating Antibiotic-Resistant Bacteria. September 2014. https://www.cdc.gov/drugresistance/pdf/executive-order_ar.pdf. Accessed July 27, 2017.
Department of Health. UK Five Year Antimicrobial Resistance Strategy 2013 to 2018. September 2013. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/244058/20130902_UK_5_year_AMR_strategy.pdf. Accessed July 27, 2017.
Bardin  PG, Fraenkel  DJ, Sanderson  G, Lampe  F, Holgate  ST.  Lower airways inflammatory response during rhinovirus colds.  Int Arch Allergy Immunol. 1995;107(1-3):127-129.PubMedGoogle ScholarCrossref
Gonzales  R, Sande  MA.  Uncomplicated acute bronchitis.  Ann Intern Med. 2000;133(12):981-991.PubMedGoogle ScholarCrossref
Ebell  MHR, Radke  T.  Antibiotic use for viral acute respiratory tract infections remains common.  Am J Manag Care. 2015;21(10):e567-e575.PubMedGoogle Scholar
El-Gohary  M, Hay  AD, Coventry  P, Moore  M, Stuart  B, Little  P.  Corticosteroids for acute and subacute cough following respiratory tract infection: a systematic review.  Fam Pract. 2013;30(5):492-500.PubMedGoogle ScholarCrossref
Office for National Statistics. National population projections, 2012-based reference volume: series PP2. March 28, 2014. http://webarchive.nationalarchives.gov.uk/20160106063015/http://www.ons.gov.uk/ons/rel/npp/national-population-projections/2012-based-reference-volume--series-pp2/index.html. Accessed July 27, 2017.
British Thoracic Network/Scottish Intercollegiate Guidelines Network.  British Guideline on the Management of Asthma: A National Clinical Guideline. Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network; 2016.
Watson  L, Little  P, Moore  M, Warner  G, Williamson  I.  Validation study of a diary for use in acute lower respiratory tract infection.  Fam Pract. 2001;18(5):553-554.PubMedGoogle ScholarCrossref
Little  P, Rumsby  K, Kelly  J,  et al.  Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.  JAMA. 2005;293(24):3029-3035.PubMedGoogle ScholarCrossref
Stata [computer program]. Version 13. College Station, TX: Stata Corp; 2013.
Schoenfeld  D.  Chi-squared goodness-of-fit tests for the proportional hazards regression model.  Biometrika. 1980;67(1):145-153.Google ScholarCrossref
Altman  DG, Andersen  PK.  Calculating the number needed to treat for trials where the outcome is time to an event.  BMJ. 1999;319(7223):1492-1495.PubMedGoogle ScholarCrossref
Welch  C, Bartlett  J, Petersen  I.  Application of multiple imputation using the two-fold fully conditional specification algorithm in longitudinal clinical data.  Stata J. 2014;14(2):418-431.PubMedGoogle Scholar
Rubin  D.  Inference and missing data.  Biometrika. 1976;63(3):581-592.Google ScholarCrossref
Matthews  JN, Altman  DG, Campbell  MJ, Royston  P.  Analysis of serial measurements in medical research.  BMJ. 1990;300(6719):230-235.PubMedGoogle ScholarCrossref
Hayward  G, Heneghan  C, Perera  R, Thompson  M.  Intranasal corticosteroids in management of acute sinusitis: a systematic review and meta-analysis.  Ann Fam Med. 2012;10(3):241-249.PubMedGoogle ScholarCrossref
Venekamp  RP, Bonten  MJ, Rovers  MM, Verheij  TJ, Sachs  AP.  Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial.  CMAJ. 2012;184(14):E751-E757.PubMedGoogle ScholarCrossref
Siemieniuk  RA, Meade  MO, Alonso-Coello  P,  et al.  Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis.  Ann Intern Med. 2015;163(7):519-528.PubMedGoogle ScholarCrossref
Russell  K, Wiebe  N, Saenz  A,  et al.  Glucocorticoids for croup.  Cochrane Database Syst Rev. 2004;(1):CD001955.PubMedGoogle Scholar
Zalmanovici  A, Yaphe  J.  Steroids for acute sinusitis.  Cochrane Database Syst Rev. 2007;(2):CD005149.PubMedGoogle Scholar
Hayward  G, Thompson  M, Heneghan  C, Perera  R, Del Mar  C, Glasziou  P.  Corticosteroids for pain relief in sore throat: systematic review and meta-analysis.  BMJ. 2009;339:b2976.PubMedGoogle ScholarCrossref
Bafadhel  M, McKenna  S, Terry  S,  et al.  Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial.  Am J Respir Crit Care Med. 2012;186(1):48-55.PubMedGoogle ScholarCrossref
Bjermer  L, Alving  K, Diamant  Z,  et al.  Current evidence and future research needs for FeNO measurement in respiratory diseases.  Respir Med. 2014;108(6):830-841.PubMedGoogle ScholarCrossref
Beale  J, Jayaraman  A, Jackson  DJ,  et al.  Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation.  Sci Transl Med. 2014;6(256):256ra134.PubMedGoogle ScholarCrossref
Sullivan  FM, Swan  IRC, Donnan  PT,  et al.  Early treatment with prednisolone or acyclovir in Bell’s palsy.  N Engl J Med. 2007;357(16):1598-1607.PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity


My Saved Searches

You currently have no searches saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
State Requirements