BRONCHITIS




























ARTIC PC trial - Amoxicillin vs Placebo for Bronchitis in Children, Lancet (2021) [PubMed abstract]
  • The ARTIC PC trial enrolled 432 children with symptoms consistent with acute bronchitis
Main inclusion criteria
  • Age 6 months - 12 years
  • Acute cough as predominant symptom
  • Symptoms less than 21 days
  • Presence of shortness of breath, sputum, or pain
Main exclusion criteria
  • Non-infectious cause
  • Likely viral cause (e.g. croup)
  • Immunocompromised
  • Pneumonia likely or severely ill
Baseline characteristics
  • Average age 3.2 years
  • History of asthma - 10%
  • Abnormal chest exam - 35%
  • Sputum or chest rattle - 76%
  • Fever during illness - 78%
  • Shortness of breath - 46%
  • Tachypnea - 14%
Randomized treatment groups
  • Group 1 (221 patients): Amoxicillin 50 mg/kg/day in 3 divided doses for 7 days
  • Group 2 (211 patients): Placebo
Primary outcome: Duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved
Results

Duration: 28 days
Outcome Amoxicillin Placebo Comparisons
Primary outcome 5 6 HR 1.13, 95%CI [0.90 to 1.42]
Return for new or worsening symptoms 30% 38% RR 0.80, 95%CI [0.58 to 1.05]
  • In subgroup analyses that looked at patients with abnormal chest signs (e.g. wheeze, crackles) (N=106), sputum (N=239), fever (N=246), or shortness of breath (N=148), there was no significant difference between the groups.
  • Side effects were similar between groups

Findings: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.
Augmentin® vs Ibuprofen vs Placebo for Acute Bronchitis, BMJ (2013) [PubMed abstract]
  • A study published in the BMJ randomized 416 patients with acute bronchitis to augmentin, ibuprofen, or placebo
Main inclusion criteria
  • Respiratory infection for < 1 week with cough as the predominant feature
  • Discolored sputum
  • At least one of the following: dyspnea, wheezing, chest discomfort, or chest pain
Main exclusion criteria
  • Use of antibiotic, anti-inflammatory, or corticosteroid in previous two weeks
  • Respiratory rate > 25 breaths per minute
  • Heart rate > 120 bpm
  • History of asthma or COPD
  • Pneumonia on X-ray
Baseline characteristics
  • Average age 45 years
  • Current smoker - 39% | Former smoker - 15%
  • Reported dyspnea - 34%
  • Wheezing on exam - 30%
  • Average number of days with cough at randomization - 4
Randomized treatment groups
  • Group 1 (137 patients) - Augmentin® 500/125 mg 3 times a day for 10 days
  • Group 2 (136 patients) - Ibuprofen 600 mg 3 times a day for 10 days
  • Group 3 (143 patients) - Placebo
  • Symptomatic treatment except for antibiotics and NSAIDs were allowed
Primary outcome: Number of days with frequent cough after the first visit as recorded in the patient's symptom diary
Results

Duration: 30 days
Outcome Augmentin Ibuprofen Placebo Comparisons
Primary outcome (# of days with frequent cough) 11 9 11 p=0.25
Cure or improvement at end of treatment 78% 86% 86% p=0.13
  • The overall mean duration of cough was 14.6 days
  • Adverse events, typically GI related, were more common in the Augmentin group (12%) than the ibuprofen (5%) and placebo (3%) groups (p=0.008)

Findings: No significant differences were observed in the number of days with cough between patients with uncomplicated acute bronchitis and discolored sputum treated with ibuprofen, Augmentin, or placebo
Amoxicillin vs Placebo for Acute Bronchitis, Lancet Infectious Disease (2013) [PubMed abstract]
  • A study published in Lancet Infectious Disease randomized 2061 patients with bronchitis to amoxicillin or placebo
Main inclusion criteria
  • Acute cough (≤ 28 days) or lower-respiratory tract infection considered most probable diagnosis
Main exclusion criteria
  • Focal chest signs (focal crepitations, bronchial breathing) and systemic features (high fever, vomiting, severe diarrhea)
  • Cough thought to be of noninfectious cause (e.g. PE, reflux, allergies)
Baseline characteristics
  • Average age 49 years
  • Present or past smoker - 53%
  • COPD or asthma - 15%
  • Sputum production - 79%
  • Discolored sputum - 49%
Randomized treatment groups
  • Group 1 (1038 patients) - Amoxicillin 1000 mg 3 times a day for 7 days
  • Group 2 (1023 patients) - Placebo for 7 days
Primary outcome: Number of days with symptoms rated by patients as “moderately bad” or worse after initial presentation
Results

Duration: 28 days
Outcome Amoxicillin Placebo Comparisons
Primary outcome (median # of days) 6 7 HR 1.06, 95%CI [0.96 - 1.18] p=0.23
Worsening of illness during follow-up 15.9% 19.3% OR 0.79, 95%CI [0.63 - 0.99] p=0.043
Nausea, rash, or diarrhea 28.7% 24% p=0.025

Findings: When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms.

Azithromycin (Z-pak®) vs Vitamin C for Acute Bronchitis, Lancet (2002) [PubMed abstract]
  • A study published in the Lancet randomized 220 patients with acute bronchitis to a Z-pak or Vitamin C
Main inclusion criteria
  • Cough for 2 - 14 days with or without sputum production
  • Diagnosed with acute bronchitis by physician
Main exclusion criteria
  • History of COPD or asthma
  • Current treatment with bronchodilators or glucocorticoids
  • Temp > 102°
  • Respiratory rate ≥ 25 breaths/minute
  • Infiltrates on chest X-ray
Baseline characteristics
  • Average age 46 years
  • Median number of days with cough - 5
  • Wheezing on exam - 12%
  • Current smoker - 36%
Randomized treatment groups
  • Group 1 (112 patients) - Azithromycin 500 mg X 1 day, then 250 mg a day for 4 days (Z-Pak®)
  • Group 2 (108 patients) - Vitamin C 500 mg X 1 day, then 250 mg a day for 4 days
  • All participants were also given an albuterol inhaler to use as needed for cough. No other medications were allowed.
Primary outcome: Health-related quality of life on day 7 of follow-up. Health-related quality of life was measured on 4 domains: symptom effects on daily activities, coughing and shortness of breath, general symptoms, and emotional functioning
Results

Duration: 7 days
  • Primary outcome (Day 7): There was no significant difference between the two groups in any of the 4 domains
  • Primary outcome (Day 3): There was no significant difference between the two groups in any of the 4 domains
  • There was no significant difference between the two groups in the frequency of adverse events

Findings: Azithromycin is no better than low-dose Vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder



Prednisolone vs Placebo in Nonasthmatic Adults with Bronchitis, JAMA (2017) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=401, length = 28 days) in nonasthmatic adults diagnosed with acute bronchitis
  • Treatment: Prednisolone 40 mg once daily for 5 days vs Placebo
  • Primary outcome: Duration of moderately bad or worse cough
  • Results:
    • Primary outcome (median days): Prednisolone - 5 days, Placebo - 5 days (p=0.36)
    • Of note, 47% of patients had wheezing at baseline and 70% reported shortness of breath
  • Findings: 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.