• Kay Wang, Silvana Bettiol, Matthew J Thompson, Nia W Roberts, Rafael Perera, Carl J Heneghan, and Anthony Harnden.
• Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, Oxon, UK, OX2 6GG.
• Cochrane Db Syst Rev. 2014 Sep 22; 2014 (9): CD003257CD003257.

BackgroundAround 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).ObjectivesTo assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.Search MethodsWe updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE 2014, Issue 2), accessed from The Cochrane Library, MEDLINE (1950 to 30 January 2014), EMBASE (1980 to 30 January 2014), AMED (1985 to 30 January 2014), CINAHL (1980 to 30 January 2014) and LILACS (30 January 2014). We searched Current Controlled Trials to identify trials in progress.Selection CriteriaWe selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.Data Collection And AnalysisTwo review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated searches in 2012 and 2014. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. Main ResultsWe included 12 trials of varying sample sizes (N = 9 to 135), mainly from high-income countries, including a total of 578 participants. Ten trials recruited children (N = 448 participants). Two trials recruited adolescents and adults (N = 130 participants). We considered only three trials to be of high methodological quality (one trial each of diphenhydramine, pertussis immunoglobulin and montelukast). Included studies did not show a statistically significant benefit for any of the interventions. Only six trials, including a total of 196 participants, reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) -4.7 to 8.5 (N = 49 participants from one trial). One trial on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02, N = 47 participants) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4, N = 46 participants). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4, N = 11 participants from one trial) and salbutamol showed no change in coughing paroxysms per day (MD -0.2; 95% CI -4.1 to 3.7, N = 42 participants from two trials). Only one trial comparing pertussis immunoglobulin versus placebo (N = 47 participants) reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site).Authors' ConclusionsThere is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough. More high-quality trials are needed to assess the effectiveness of potential antitussive treatments in patients with whooping cough.

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