Effectiveness of Antitussives, Anticholinergics and Honey Versus Usual Care in Adults With Acute Bronchitis.

Despite the frequent use of therapies in acute bronchitis, encouraged by the over-the-counter availability in pharmacies, the evidence of their benefit is scarce, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of 3 symptomatic therapies (dextromethorphan, ipratropium and honey) associated with usual care and the usual care in adults with acute bronchitis. This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than three weeks as the main symptom, scoring ≥ 4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, usual care + dextromethorphan 30 mg t.i.d., usual care + ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or usual care + 30 mg (a spoonful) of honey t.i.d., all taken for up to 14 days. The exclusion criteria will be: pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs, admitted to a long-term residence, or inability to give informed consent. Sample: 668 patients. The primary outcome will be the number of days with moderate-severe cough in the intention-to-treat (ITT) population, i.e., the number of days from the randomisation visit until the last day the patient scores three or more in either daytime or nocturnal cough in the symptom diary. All patients will be given a symptom diary to be self-administered while symptoms are present. A second visit will be scheduled at day 2-3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called six weeks after the baseline visit.

Inclusion criteria

• age 18 years or older, and
• symptoms of acute bronchitis with cough starting within 3 weeks before study inclusion, and
• patients who score ≥ 4 in either the daytime and/or nocturnal cough on a 7-point Likert scale, and
• patients who consent to participate.

Exclusion criteria

• suspected pneumonia; if the professional suspects pneumonia, a chest X-ray will be recommended and the patient will be randomized if this diagnosis is discarded; or
• criteria for hospital admission (impaired consciousness, respiratory rate > 30 breaths/minute, pulse > 125 beats/minute, systolic blood pressure <90 mm Hg or diastolic blood pressure <60 mm Hg, temperature > 104°F or oxygen saturation <92%)
• pregnancy or breast feeding
• baseline respiratory disease such as chronic obstructive pulmonary disease, asthma, tuberculosis or bronchiectasis
• associated significant comorbidity, such as moderate-severe heart failure, dementia, acute myocardial infarction/recent cerebral vascular accident (< 3 months), severe liver failure, severe renal failure
• immunosuppression, such as chronic infection by HIV, transplanted, neutropenic, or patients receiving immunosuppressive treatment
• active neoplasm
• terminal illness
• history of intolerance or allergy to any of the study treatments
• patients in whom, in the opinion of the investigator, treatment with dextromethorphan, ipratropium bromide or honey is contraindicated
• patients living in long-term institutions
• difficulty in conducting scheduled follow-up visits