Tools for Practice


#329 Coughing up the evidence: Bronchodilators or inhaled steroids for post-infectious cough


CLINICAL QUESTION
Do bronchodilators or inhaled corticosteroids (ICS) improve post-infectious cough in adults without asthma?

BOTTOM LINE
Data is very limited with only two ICS randomized controlled trials (RCTs) (163 patients) and one bronchodilator RCT (92 patients). For adults, post-infectious cough scores may improve ~50% on placebo and ~5-10% more with ICS over 2 weeks. Ipratropium/salbutamol may resolve cough in more patients than placebo at day 10 (69% versus 37%) but most patients (>80%, regardless of treatment) will have cough resolution by day 20.


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EVIDENCE
  • Differences statistically significant unless noted.
  • ICS versus placebo:
    • Four systematic reviews of treatments for persistent cough (4-9 RCTs, 335-750 patients): Interpretation limited by inclusion of RCTs with acute (<3 weeks)1,2 and chronic (>8 weeks)2,3 cough, and multiple drug classes.4  
      • Most useful systematic review2 (2 RCTs, 163 patients), mostly subacute cough (3-8 weeks):
        • ICS 0.42 (standard mean difference) better than placebo. In clinical terms, placebo improved cough scores at ~2 weeks by ~50-56% and ICS improves ~2-13% more.
        • Largest RCT5 (133 patients) also reported:
          • Additional outcomes (days off work, nocturnal awakenings, adverse effects): No difference.
          • Proportion of non-smokers with >50% cough improvement: 81% versus 54% (placebo), number needed to treat (NNT)=4.
            • No improvement among smokers.
          • Limitations: Not all patients had post-infectious cough; study industry funded.
        • Bronchodilators versus placebo:
          • One RCT6 of 92 patients (cough duration 3-4 weeks): Combination of nebulized salbutamol/ipratropium versus placebo.
            • Proportion with ongoing cough at day 10: 37% versus 69% placebo, NNT=3.
            • No difference at day 20 (both >80% resolved).
            • Limitations: Small studies; non-validated cough scores; multiple outcomes.
Context
  • Post-infectious cough is a cough persisting 3-8 weeks after an acute respiratory illness.7
  • One RCT8 compared beclomethasone and placebo in 72 patients with prolonged acute cough (10 days-3 weeks), so likely not true post-infectious (subacute) cough.
    • ICS improved 3 of 6 outcomes over placebo on device-measured cough, but no difference in patient-reported symptoms.
  • Guidelines suggest considering a trial of inhaled ipratropium or, if refractory, inhaled corticosteroids.9
  • RCTs above did not include patients with COVID-19.
December 11, 2022

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Author(s):

  • Emelie Braschi MD CCFP PhD
  • G. Michael Allan MD CCFP
  • Samantha Moe PharmD

1. El-Gohary M, Hay AD, Coventry P, et al. Family Practice 2013; 30: 492-500.

2. Lee SE, Lee JH, Kim HJ, et al. Allergy Asthma Immunol Res 2019; 11(6): 856-70.

3. Johnstone KJ, Chang AB, Fong KM, et al. Cochrane Database Syst Rev. 2013 Mar 28; (3):CD009305.

4. Speich B, Thomer A, Aghlmandi S, et al. Br J Gen Pract. 2018; 68(675):e694-e702.

5. Ponsioen BP, Hop WCJ, Vermue NA, et al. Eur Respir J 2005; 25 (1): 147-52.

6. Zanasi A, Lecchi M, Del Forno M, et al. Pulm Pharmacol Ther 2014; 29: 224-32.

7. Irwin RS, French CL, Chang AB, et al. Chest 2018; 153(10): 196-209.

8. Gillissen A, Richter A, Oster H. J Physiol Pharmacol 2007; 58 (Suppl 5 Pt 1):223-32.

9. Irwin RS, Baumann MH, Bolser DC, et al. Chest 2006; 129(1 Suppl):1S-23S.

Authors do not have any conflicts of interest to declare.