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. 2008 Jul 17;2008:1508.

Bronchitis (acute)

Peter Wark 1
PMCID: PMC2907939  PMID: 19445737

Abstract

Introduction

Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens. The role of smoking or of environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear. A third of people may have longer-term symptoms or recurrence.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute bronchitis in people without chronic respiratory disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin [with or without clavulanic acid], cephalosporins, or macrolides), antihistamines, antitussives, beta2 agonists (inhaled or oral), cephalosporins, expectorants, and analgesics.

Key Points

Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK.

  • The causes are usually considered to be infective, but only around half of people have identifiable pathogens.

  • The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.

  • A third of people may have longer-term symptoms or recurrence.

Antibiotics have only a modest effect on the duration of cough compared with placebo, and increase the risks of adverse effects and drug resistance.

  • We don't know for sure whether any one antibiotic regimen is superior to the others.

  • There is no evidence to support the use of broad-spectrum antibiotics, such as quinolones or amoxicillin-clavulanic acid (co-amoxiclav), over amoxicillin alone in acute bronchitis.

  • It has not been shown that smokers are more likely to benefit from antibiotics than non-smokers.

  • We found insufficient evidence on the use of extract of ivy and thyme as a cough expectorant.

We don't know whether analgesics, antihistamines, antitussives, inhaled or oral beta2 agonists, or expectorants improve symptoms of acute bronchitis compared with placebo, as few good-quality studies have been found.

About this condition

Definition

Acute bronchitis is a transient inflammation of the trachea and major bronchi. Clinically, it is diagnosed on the basis of cough and occasionally sputum, dyspnoea, and wheeze. This review is limited to episodes of acute bronchitis in people (smokers and non-smokers) with no pre-existing respiratory disease (such as a pre-existing diagnosis of asthma or chronic bronchitis, evidence of fixed airflow obstruction, or both) and excluding those with clinical or radiographic evidence of pneumonia. However, the reliance on a clinical definition for acute bronchitis implies that people with conditions such as transient/mild asthma or mild chronic obstructive pulmonary disease may have been recruited in some of the reported studies.

Incidence/ Prevalence

Acute bronchitis affects 44/1000 adults (age over 16 years) each year in the UK, with 82% of episodes occurring in autumn or winter. One survey found that acute bronchitis was the fifth most common reason for people of any age to present to a general practitioner in Australia.

Aetiology/ Risk factors

Infection is believed to be the trigger for acute bronchitis. However, pathogens have been identified in less than 55% of people. Community studies that attempted to isolate pathogens from the sputum of people with acute bronchitis found viruses in 8-23% of people, typical bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) in 45%, and atypical bacteria (Mycobacterium pneumoniae, Chlamydia pneumoniae, Bordetella pertussis) in 0-25%. It is unclear whether smoking affects the risk for developing acute bronchitis.

Prognosis

Acute bronchitis is regarded as a mild, self-limiting illness, but there are limited data on prognosis and rates of complications, such as chronic cough or progression to chronic bronchitis or pneumonia. One prospective longitudinal study reviewed 653 previously well adults who presented to suburban general practices over a 12-month period with symptoms of acute lower respiratory tract infection. It found that, within the first month of the illness, 20% of people re-presented to their general practitioner with persistent or recurrent symptoms, mostly persistent cough. The no-treatment control group of one RCT (212 people; about 16% took antibiotics outside of the study protocol) found that participants had at least a slight problem with cough for a mean of 11.4 days, with "moderately bad" cough lasting for a mean of 5.7 days. Another prospective study of 138 previously well adults found that 34% had symptoms consistent with either chronic bronchitis or asthma 3 years after initial presentation with acute bronchitis. It is also unclear whether acute bronchitis plays a causal role in the progression to chronic bronchitis, or is simply a marker of predisposition to chronic lung disease. Although smoking has been identified as the most important risk factor for chronic bronchitis, it is unclear whether the inflammatory effects of cigarette smoke and infection causing acute bronchitis have additive effects in leading to chronic inflammatory airway changes. In children, exposure to parental environmental tobacco smoke is associated with an increase in risk for community lower respiratory tract infection in children aged 0-2 years, and an increase in symptoms of cough and phlegm in those aged 5-16 years.

Aims of intervention

To improve symptoms associated with acute bronchitis; to reduce complications, with minimal adverse effects.

Outcomes

Symptom severity: duration of symptoms, particularly cough, sputum production, and fever; limitation of activities; clinical improvement. Complications of acute bronchitis: especially chronic cough, pneumonia, and chronic bronchitis. Quality-of life. Adverse effects.

Methods

BMJ Clinical Evidence search and appraisal September 2007. The following databases were used to identify studies for this review: Medline 1966 to September 2007, Embase 1980 to September 2007, and The Cochrane Database of Systematic Reviews 2007, Issue 2. Additional searches were carried out using the following websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE clinical guidelines. Abstracts of the studies retrieved were assessed independently by two information specialists using predetermined criteria to identify relevant studies. We included people of any age or sex with acute bronchitis. We excluded trials conducted in people who had chronic respiratory disease or other acute respiratory diseases. We excluded non-systematic reviews, non-randomised trials, and RCTs that were not double blinded, comprised fewer than 20 people, or were of less than 4 days' treatment duration or had less than 2 weeks' duration of follow-up. We did not exclude studies based on loss to follow-up. We excluded all studies described as "open", "open label", or "single blinded". Where systematic reviews were being regularly updated, we only included the most updated version of the review, and made note of previous versions if the conclusions had altered. Where there was more than one systematic review about an option, both reviews were examined and their results commented on. Consideration was given to the quality of the review in terms of its methods of inclusion, its assessment of the literature (published and non-published), and any potential conflicts of interest. If one systematic review was felt to be outdated and a more recent version existed, or new RCTs had emerged that were felt to alter the conclusions of the review, then this was reported and a decision made to include or exclude the review. A regular surveillance protocol is used to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are continually added to the chapter as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table.

GRADE evaluation of interventions for bronchitis (acute)

Important outcomes Symptom severity (for example, cough, global symptoms, limitation of activities, clinical assessment), quality of life, complications of acute bronchitis, adverse effects
Number of studies (participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of treatments for acute bronchitis in people without chronic respiratory disease?
at least 5 (at least 916) Symptom severity Any antibiotic v placebo 4 0 0 –1 0 Moderate Directness point deducted for use of subjective/surrogate outcomes
5 (378) Symptom severity Macrolides v placebo 4 -2 0 -2 0 Very low Quality points deducted for poor follow up in some RCTs and small RCTs unlikely to have power to find significant difference between groups. Directness points deducted for use of subjective/surrogate outcomes and no clinical outcomes reported in 1 RCT
1 (220) Quality of life Macrolides v placebo 4 0 0 -1 0 Moderate Directness point deducted for small number of comparators
5 (620) Symptom severity Tetracyclins v placebo 4 0 0 -2 0 Low Directness points deducted for use of subjective/surrogate outcomes and limited outcomes reported in 1 RCT
1 (340) Symptom severity Cephalosporins v placebo 4 0 0 -2 0 Low Directness point deducted for limited number of outcomes and comparators
1 (135) Symptom severity Penicillins v placebo 4 –1 0 -1 0 Low Quality point deducted for sparse data. Directness point deducted for unclear outcome
1 (67) Symptom severity Trimethoprim-sulfamethoxazole v placebo 4 –1 0 -2 0 Very low Quality point deducted for sparse data. Directness points deducted for subjective/surrogate outcome and restricted range of outcomes
1 (296) Symptom severity Amoxicillin v cephalosparins 4 0 0 -1 0 Moderate Directness point deducted for small number of comparators
1 (196) Symptom severity Amoxicillin v macrolides 4 –1 0 -2 0 Very low Quality point deducted for sparse data. Directness points deducted for small number of comparators and use of composite outcome
1 (214) Symptom severity Macrolides v each other 4 0 0 -1 0 Moderate Directness points deducted for small number of comparators
3 (927) Symptom severity Cephalosporins v each other 4 0 0 -1 0 Moderate Directness point deducted for use of unclear outcomes
1 (100) Symptom severity Antihistamines v placebo 4 –1 0 -1 0 Low Quality point deducted for sparse data. Directness point deducted for small number of comparators
2 (132) Symptom severity Dextromethorphan v placebo in children 4 –2 0 -1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for use of unclear outcome
2 (at least 81) Symptom severity Codeine v placebo in adults 4 –1 0 -2 0 Very low Quality point deducted for incomplete reporting of results. Directness points deducted for short follow up in 1 RCT, use of subjective outcome, and unclear scoring system for outcome measurement
1 (108) Symptom severity Moguisteine v placebo in adults 4 –1 0 -1 0 Low Quality point deducted for sparse data. Directness point deducted for unclear clinical importance
1 (108) Adverse effects Moguisteine v placebo in adults 4 -1 0 0 0 Moderate Quality point deducted for sparse data
at least 3 (at least 220) Symptom severity Inhaled beta2 agonists v placebo 4 –1 0 -1 0 Low Quality point deducted for combining data for both oral and inhaled beta2 agonists. Directness point deducted for use of subjective/surrogate outcome
1 (73) Adverse effects Inhaled beta2 agonists v placebo 4 –1 0 0 +2 High Quality point deducted for sparse data. Effect size points added for RR above 5
3 (263) Symptom severity Oral beta2 agonists v placebo 4 0 0 -2 0 Low Directness point deducted for sub-group analysis (children, adults) and use of subjective/surrogate outcome
2 (212 ) Adverse effects Oral beta2 agonists v placebo 4 0 0 -1 0 Moderate Directness point deducted for sub-group analysis (children, adults)
1 (34) Symptom severity Oral beta2 agonists v antibiotics 4 –1 0 -2 +1 Low Quality point deducted for sparse data. Directness points deducted for small number of comparators and restricted outcomes reported. Effect size point added for RR less than 0.5
1 (363) Symptom severity Expectorant v placebo 4 -1 0 -1 0 Low Quality point deducted for incomplete reporting of results. Directness point deducted for small number of comparators and use of subjective outcome
2 (812) Symptom severity Amoxicillin–clavulanic acid v cephalosporins 4 0 0 -1 0 Moderate Directness point deducted for small number of comparators
2 (635) Adverse effects Amoxicillin–clavulanic acid v cecephalosporins 4 -1 0 0 0 Moderate Quality point deducted for incomplete reporting of results
Open in a new tab

Type of evidence: 4 = RCT. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio

Glossary

High-quality evidence

Further research is very unlikely to change our confidence in the estimate of effect.

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Asthma

Asthma and other wheezing disorders of childhood

Chronic obstructive pulmonary disease

Upper respiratory tract infection

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2008 Jul 17;2008:1508.

Antibiotics versus placebo and versus other treatments

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Any antibiotic compared with placebo: Antibiotics (analysed as a group) seem to be more effective than placebo at decreasing the proportion of people with cough, night cough, or with no improvement (measured by physician's global assessment) at 1-2 weeks, and also seem to be more effective at reducing the duration of cough or productive cough, but we don't know about days with impared activities or "feeling ill" ( moderate-quality evidence ). Macrolides compared with placebo: We don't know whether erythromycin or azithromycin are more effective than placebo at improving outcomes (including cough, general symptoms, impaired activities, clinical improvement) in people aged 8-65 years or over ( very low-quality evidence ). Tetracyclins compared with placebo: Doxycyline may be more effective than placebo at decreasing the proportion of people with cough at follow up, but we don't know about other symptoms such as productive cough, night cough, people feeling ill, having impaired activities, or not improving clinically. We don't know whether demeclocycline is more effective than placebo at reducing the proportion of people with a productive cough ( low-quality evidence ). Cephalosporins compared with placebo: Cefuroxime may be more effective than placebo at decreasing the proportion of people with night cough (low-quality evidence). Penicillins compared with placebo: Amoxicillin–clavulanic acid (co-amoxiclav) may be no more effective at reducing the proportion of people with persistent or worsening symptoms (not further defined) at 5-7 days (low-quality evidence). Trimethoprim–sulfamethoxazole compared with placebo: We don't know whether trimethoprim–sulfamethoxazole is more effective than placebo at reducing the proportion of people with limitations in work or activities (very low-quality evidence). Antibiotics compared with oral beta2 agonists: Erythromycin may be less effective than oral salbutamol at reducing the proportion of adults with a cough at 7 days, but we don't know about other symptoms (low-quality evidence). QUALITY OF LIFE Macrolides compared with placebo: Azithromycin seems to be no more effective than placebo at improving quality of life scores at 3-7 days in people aged 18-88 years (moderate-quality evidence). NOTE Antibiotics are associated with adverse events such as nausea, vomiting, rash, headache, and vaginitis. Widespread antibiotic use may lead to bacterial resistance to antibiotics.

Benefits

Any antibiotic versus placebo:

We found one systematic review, which compared antibiotics versus placebo (search date 2004, 13 RCTs; 1914 people aged 8–65 years and over, including smokers but excluding people with chronic bronchitis). Acute bronchitis was defined by cough, sputum production, or physician diagnosis. The antibiotics used were doxycycline (4 RCTs), erythromycin (4 RCTs), azithromycin (1 RCT), cefuroxime (1 RCT), amoxicillin–clavulanic acid (co-amoxiclav; 1 RCT), trimethoprim–sulphamethoxazole (TMP-SMX, co-trimoxazole; 1 RCT), and demeclocycline (1 RCT). The review found that antibiotics modestly (but significantly) improved most outcomes compared with placebo. It found that antibiotics significantly reduced the proportion of people with cough at 1–2 weeks compared with placebo (people with cough: 4 RCTs; 47/143 [33%] with antibiotics v 67/132 [51%] with placebo; RR 0.64, 95% CI 0.49 to 0.85). It also found that antibiotics significantly reduced the mean number of days with reported cough compared with placebo (5 RCTs; WMD –0.58 days, 95% CI –1.16 days to –0.01 days). Antibiotics significantly reduced the proportion of people with night cough at 1–2 weeks compared with placebo (people with night cough: 4 RCTs; 80/271 [30%] with antibiotics v 119/167 [71%]; RR 0.67, 95% CI 0.54 to 0.83). People receiving antibiotics were also significantly more likely to have improved at 1–2 weeks, as judged by their physician's global assessment (people judged not to have improved: 5 RCTs; 32/413 [8%] with antibiotics v 71/503 [14%] with placebo; RR 0.44, 95% CI 0.30 to 0.65). People receiving antibiotics had fewer mean days with impaired activities and days feeling ill compared with people not receiving antibiotics, although the difference between groups did not quite reach significance (impaired activities: 5 RCTs, 393 people, WMD –0.48 days, 95% CI –0.96 days to +0.01 days; days feeling ill: 4 RCTs, 435 people, WMD –0.58 days, 95% CI –1.16 days to +0.00 days). The review found that antibiotics modestly (but significantly) reduced the duration of productive cough compared with placebo (5 RCTs, 535 people; WMD –0.52 days, 95% CI –1.03 days to –0.01 days). The clinical importance of this result is unclear. For analyses of specific types of antibiotic versus placebo, see below.

Amoxicillin versus placebo:

We found one systematic review (search date 2004), which identified no RCTs comparing amoxicillin versus placebo.

Macrolides versus placebo:

We found one systematic review (search date 2004), which identified four RCTs of erythromycin and one RCT of azithromycin (see table 1 ). The review did not perform a meta-analysis of macrolides versus placebo. In the review, participants were aged 8–65 years and over, and included smokers but excluded people with chronic bronchitis. Acute bronchitis was defined by cough, sputum production, or physician diagnosis. One RCT identified by the review (91 people aged at least 8 years) found a significant reduction in the mean number of days of impaired activities with erythromycin compared with placebo. However, none of the four RCTs identified by the review found significant differences between erythromycin and placebo in: the number of people with cough, night cough, productive cough, limitation in work/activities, or abnormal lung examination; the proportion of people who had not improved clinically at follow-up; and the mean number of days of cough, productive cough, or feeling ill. Similarly, the RCT of azithromycin found no significant difference between azithromycin and vitamin C (placebo) in the proportion of people with impaired activities at 1 week. The original report of this RCT also reported on quality of life, and found no significant difference in health-related quality of life at days 3 and 7 between azithromycin and vitamin C.

Table 1.

Double blind RCTs of antibiotics compared with placebo.

Ref Intervention (length of treatment) Number of people (age) Outcomes Absolute figures for treatment v placebo Difference between treatment and placebo (95% CI)
Erythromycin (7 days) 52 adults (18–65 years) Proportion of people • not improved clinically 5/26 v 10/24 RR 0.46 (0.18 to 1.16)
        • with adverse effects 5/26 v 9/24 RR 0.51 (0.20 to 1.32)
Erythromycin (10 days) 63 adults (18 years and over) Proportion of people • with cough 14/23 v 18/22 RR 0.74 (0.51 to 1.09)
        • with night cough 7/21 v 14/24 RR 0.57 (0.29 to 1.14)
        • with productive cough 13/23 v 14/22 RR 0.89 (0.55 to 1.43)
        • with limitations in work/activities 1/20 v 3/23 RR 0.38 (0.04 to 3.40)
        • with abnormal lung exam at follow-up 0/23 v 6/22 RR 0.07 (0 to 1.24)
        • with adverse effects 4/31 v 0/26 RR 7.59 (0.43 to 134.81)
Erythromycin (10 days) 23 adults (18–65 years) Proportion of people • with cough 8/11 v 6/9 RR 1.09 (0.61 to 1.96)
        • with night cough 2/10 v 2/8 RR 0.80 (0.14 to 4.49)
        • with productive cough 9/11 v 6/9 RR 1.23 (0.72 to 2.10)
        • with abnormal lung exam at follow-up 7/14 v 5/9 RR 0.90 (0.41 to 1.97)
        • with adverse effects 3/14 v 2/9 RR 0.96 (0.2 to 4.69)
Erythromycin (10 days) 91 people (8 years and over) Proportion of people • with productive cough 28/41 v 27/31 RR 0.78 (0.61 to 1.01)
      Mean number of days • of cough 8.76 v 8.94 WMD –0.18 (–3.95 to +0.59)
        • of productive cough 6.34 v 5.76 WMD +0.58 (–2.03 to +3.19)
        • of impaired activities 0.75 v 2.16 WMD –1.41 (–2.57 to –0.25)*
        • of feeling ill 3.92 v 3.67 WMD +0.25 (–2.09 to +2.59)
      Proportion of people • with adverse effects 18/49 v 6/42 RR 2.57 (1.12 to 5.88)*
Azithromycin 220 adults (18–88 years) Proportion of people • with impaired activities 11/97 v 10/92 RR 1.04 (0.47 to 2.34)
        • with adverse effects 24/97 v 19/92 RR 1.20 (0.71 to 2.04)
      Difference in scores • quality of life at day 3 1.4 v 1.7 WMD +0.3 (–0.03 to +0.55
        • quality of life at day 7 0.9 v 0.9 WMD +0.03 (–0.20 to +0.26
Doxycycline (7 days) 39 people (12 years and over) Mean number of days • of cough 9.4 v 10.8 WMD –1.4 (–3.33 to +0.53)
        • of productive cough 8.5 v 10.4 WMD –1.9 (–3.96 to +0.16)
        • of impaired activities 3.4 v 3.9 WMD –0.5 (–1.95 to +0.95)
Doxycycline (10 days) 212 people (14 years and over) Number of people • with productive cough 30/104 v 32/103 RR 0.93 (0.61 to 1.41)
        • not improved clinically 3/106 v 7/103 RR 0.42 (0.11 to 1.57)
      Mean number of days • of cough 6.4 v 6.3 WMD +0.1 (–0.67 to +0.87)
        • of productive cough 4.7 v 5.3 WMD –0.6 (–1.43 to +0.23)
        • of impaired activities 6.2 v 6.2 WMD 0 (–1.22 to +1.22)
        • of feeling ill 3.8 v 4.4 WMD –0.60 (–1.33 to +0.13)
      Proportion of people • with adverse effects 12/104 v 11/106 RR 1.11 (0.51 to 2.41)
Doxycycline (10 days) 158 adults (18 years and over) Proportion of people • with cough 15/70 v 26/67 RR 0.55 (0.32 to 0.95)*
        • with night cough 8/69 v 7/66 RR 1.09 (0.42 to 2.85)
        • with productive cough 13/69 v 14/67 RR 0.90 (0.46 to 1.77)
        • with limitations in work/activities 6/67 v 9/65 RR 0.65 (0.24 to 1.71)
        • not improved clinically 9/73 v 17/72 RR 0.53 (0.25 to 1.09)
        • with abnormal lung exams 5/70 v 8/67 RR 0.60 (0.21 to 1.74)
      Mean number of days • of cough 4.7 v 6.2 WMD –1.50 (–2.50 to –0.46)*
        • of productive cough 2.8 v 3.3 WMD –0.5 (–1.4 to +0.4)
        • of impaired activities 1.6 v 2.5 WMD –0.90 (–1.86 to +0.06)
        • of feeling ill 4.3 v 5.1 WMD –0.8 (–1.88 to +0.28)
      Proportion of people • with adverse effects 15/78 v 9/80 RR 1.71 (0.80 to 3.67)
Doxycycline (7 days) 74 adults (21–65 years) Proportion of people • with cough 10/39 v 17/34 RR 0.51 (0.27 to 0.96)*
        • with productive cough 2/37 v 3/32 RR 0.58 (0.10 to 3.24)
        • with limitations in work/activities 0/36 v 0/30 Not estimable
        • not improved clinically 2/37 v 1/32 RR 1.73 (0.16 to 18.20)
        • with abnormal lung exams 0/36 v 2/29 RR 0.16 (0.01 to 3.25)
      Mean number of days • of cough 7.97 v 10.41 WMD –2.44 (–6.17 to +1.29)
        • of productive cough 2.03 v 2.19 WMD –0.16 (–1.34 to +1.02)
        • of impaired activities 2.25 v 2.07 WMD +0.18 (–0.7 to +1.06)
        • of feeling ill 20.1 v 18.5 WMD +1.60 (–4.2 to +7.4)
Demeclocycline 164 adults Proportion of people • with productive cough 40/81 v 33/83 RR 1.24, 95% CI 0.88 to 1.75
Trimethoprim–sulfamethoxazole (7 days) 67 people (14 years and over) Proportion of people • with limitations in work/activities 5/19 v 12/29 RR 0.64 (0.27 to 1.52)
        • with adverse effects 3/25 v 1/29 RR 3.48 (0.39 to 31.38)
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Ref, reference; * significant difference between treatment and control group.

Tetracyclines versus placebo:

We found one systematic review (search date 2004), which identified four RCTs comparing doxycycline versus placebo, and one RCT comparing demeclocycline versus placebo (see table 1 ). The review did not perform a meta-analysis of tetracyclines versus placebo. Participants were aged 8–65 years and over and included smokers but excluded people with chronic bronchitis. Acute bronchitis was defined by cough, sputum production, or physician diagnosis. Two of the RCTs identified by the review found that doxycycline significantly reduced the number of people with cough at follow-up compared with placebo. One RCT found that doxycycline significantly reduced the mean number of days of cough compared with placebo. None of the RCTs found significant effects of doxycycline compared with placebo on: the number of people with productive cough, night cough, limitation in work/activities, abnormal lung examination; proportion of people who had not improved clinically at follow-up; or mean number of days with productive cough, or feeling ill. The RCT of demeclocycline found no significant difference in the proportion of people with productive cough between demeclocycline and placebo.

Cephalosporins versus placebo:

We found one systematic review (search date 2004), which identified one RCT comparing cefuroxime versus placebo. It found that cefuroxime significantly improved night cough compared with placebo (proportion with cough: 63/171 [37%] with antibiotics v 96/169 [57%] with placebo; RR 0.65, 95% CI 0.51 to 0.82).

Penicillins versus placebo:

We found one systematic review (search date 2004), which identified one RCT comparing amoxicillin–clavulanic acid (co-amoxiclav) versus placebo. It found no significant difference between amoxicillin–clavulanic acid and placebo in the proportion of people who had persistent or worsened symptoms at 5–7 days (30/67 [45%] with antibiotics v 30/68 [44%] with placebo; RR 1.03, 95% CI 0.82 to 1.29).

Trimethoprim–sulfamethoxazole (TMP-SMX, co-trimoxazole) versus placebo:

We found one systematic review (search date 2004), which identified one RCT comparing TMP-SMX versus placebo (see table 1 ). It found no significant difference in the proportion of people with limitations in work or activities at follow-up between TMP-SMX and placebo.

Antibiotics versus inhaled or oral beta2 agonists:

See benefits of oral beta2 agonists and of inhaled beta2 agonists.

Harms

Any antibiotics versus placebo:

In the systematic review, more people taking antibiotics than placebo had adverse effects, including nausea, vomiting, headache, skin rash, and vaginitis, but the difference between groups did not reach significance (9 RCTs; 105/595 [18%] with antibiotics v 85/580 [15%] with placebo; RR 1.22, 95% CI 0.94 to 1.58).

Amoxicillin versus placebo:

We found no RCTs.

Macrolides versus placebo:

One RCT included in the review found that significantly more people had adverse effects with erythromycin compared with placebo (see table 1 ). The other four RCTs included in the review found no significant difference in adverse effects between erythromycin or azithromycin and placebo.

Tetracyclines versus placebo:

One RCT included in the systematic review found no significant difference in adverse effects between doxycycline and placebo.(see table 1 ). The other RCTs identified by the review gave no information on adverse effects.

Cephalosporins versus placebo:

The RCT found no significant difference between cefuroxime and placebo in the proportion of people with adverse effects 24/171 [14%] with antibiotics v 28/172 [16%] with placebo; RR 0.86, 95% CI 0.52 to 1.42).

Penicillins versus placebo:

The RCT identified by the review gave no information on adverse effects.

Antibiotics versus inhaled or oral beta2 agonists:

See harms of oral beta2 agonists and of inhaled beta2 agonists.

Comment

Clinical guide:

Physicians may be more likely to prescribe antibiotics for smokers with acute bronchitis than for non-smokers (90% in smokers v 75% in non-smokers; P less than 0.05). However, seven of the trials included in the systematic review found that smoking status did not affect response to antibiotics. All of the RCTs mentioned above diagnosed acute bronchitis on clinical grounds, and commenced treatment independently of sputum culture results. It may be that isolation of a single organism on sputum culture could better identify people with a bacterial cause for their bronchitis, and thus identify a group which is more likely to benefit from antimicrobial therapy. However, sputum cultures are not generally used in the context of acute bronchitis. Relying on a clinical diagnosis of acute bronchitis is necessary, but the RCTs are likely to have included participants with a broad spectrum of illness. The RCTs did not differentiate on the basis of severity or duration of symptoms, and it is even possible that some people had mild pneumonia, because chest radiographs were not done universally to exclude this. Therefore, it is possible that a more severe subgroup exists, in which the benefit from antibiotics would be clearer. The systematic review found that, to prevent one person from having a cough at follow-up, the number needed to treat would be 6 (95% CI 3 to 14). Given that treatment leads to a mean reduction in symptoms of less than 1 day compared with placebo, it is likely that this is of limited clinical relevance in most people, who will spontaneously improve anyway, albeit slightly more slowly. By contrast, to see improvement in symptoms severe enough to limit work or activities caused by cough following acute bronchitis, the number needed to treat is 20 (95% CI 14 to 23). Conversely, the risk of antibiotics for acute bronchitis leading to an adverse event meant that the number needed to harm was similar, at 33 (95% CI 21 to 35). In addition, the potential small individual benefit from antibiotics must be weighed against the risk to the community effect that more widespread antibiotic use may increase bacterial resistance. There is no evidence to support the use of broad-spectrum antibiotics such as quinolones or amoxicillin–clavulanic acid (co-amoxiclav) in people with acute bronchitis.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Antibiotics versus each other

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Amoxicillin compared with cephalosporins: Amoxicillin and cefuroxime (a cephalosporin) seem to be equally effective at increasing clinical cure rates at 10 days from the start of treatment in adults with clinically diagnosed acute bronchitis ( moderate quality evidence ). Amoxicillin compared with macrolides: We don't know whether amoxicillin is more effective than roxithromycin (a macrolide) at increasing the proportion of people with physician assessed improvement or cure in adults with clinically diagnosed acute bronchitis ( very low-quality evidence ). Macrolides compared with each other: Azithromycin and clarithromycin seem to be equally effective at increasing clinical cure rates or at reducing relapse rates at 6-7 days in adults with clinically diagnosed acute bronchitis (moderate-quality evidence). Cephalosporins compared with each other: We don't know whether cephalosporins differ in their effectiveness at improving cure rates or satisfactory clinical outcomes (not further defined) in people with clinically diagnosed acute bronchitis (moderate-quality evidence). NOTE Widespread antibiotic use may lead to bacterial resistance to antibiotics.

Benefits

We found no systematic review.

Amoxicillin versus cephalosporins:

We found one RCT (296 adults with clinically diagnosed acute bronchitis and no pre-existing lung disease) comparing amoxicillin 250 mg three times daily versus cefuroxime 250 mg twice daily for 7 days. It found no significant difference in clinical cure rates at 72 hours post-treatment between amoxicillin and cefuroxime (123/153 [80%] with amoxicillin v 109/143 [76%] with cefuroxime; P = 0.8).

Amoxicillin versus macrolides:

We found one RCT (196 adults with clinically diagnosed acute bronchitis and no pre-existing lung disease) comparing amoxicillin 500 mg three times daily versus roxithromycin 150 mg once daily for 10 days. It found no significant difference between amoxicillin and roxithromycin in the proportion of people with physician-assessed improvement or cure (89/96 [93%] with roxithromycin v 88/96 [92%] with amoxicillin; P = 0.8).

Macrolides versus each other:

We found one RCT (214 adults with clinically diagnosed acute bronchitis and no pre-existing lung disease) comparing azithromycin 500 mg once daily for 2 days, then 250 mg once daily for 3 days versus clarithromycin 250 mg once daily for 5 days. It found no significant difference between azithromycin and clarithromycin in clinical cure rates or relapse rates after 6–7 days (cure rate: 55/103 [53%] with azithromycin v 70/108 [65%] with clarithromycin, P = 0.4; relapse rate: 2/95 [2%] with azithromycin v 1/101 [1%] with clarithromycin, P = 0.5).

Cephalosporins versus each other:

We found three RCTs. The first RCT (537 people aged at least 12 years with clinically diagnosed acute bronchitis and no pre-existing lung disease) compared three interventions: cefuroxime 250 mg twice daily for 5 days, cefuroxime 250 mg twice daily for 10 days, and amoxicillin 500 mg plus clavulanic acid 125 mg three times daily for 10 days. It found no significant difference between 5 and 10 days of cefuroxime in cure rates 1–3 days after completing treatment (84/177 [48%] with cefuroxime for 5 days v 100/177 [57%] with cefuroxime for 10 days; P = 0.41). The second RCT (465 children aged below 12 years with clinically diagnosed acute bronchitis and no pre-existing lung disease) compared cefuroxime 250 mg twice daily versus cefixime 400 mg once daily for 10 days. It found no significant difference in clinical outcome between cefuroxime and cefixime after 14 days (proportion with satisfactory clinical outcome, as assessed by the treating general practitioner: 130/148 [88%] with cefuroxime v 217/238 [91%] with cefixime; P = 0.8). It was not clear how “satisfactory clinical outcome” was defined. The third RCT (196 elderly people with clinically diagnosed acute purulent bronchitis and no pre-existing lung disease) comparing cefuroxime 250 mg twice daily versus cefpodoxime 200 mg twice daily for 5 days, found no significant difference in physician-rated satisfactory clinical response after 10 days between cefuroxime and cefpodoxime (86/95 [91%] with cefuroxime v 87/92 [95%] with cefpodoxime; P = 0.76). It was not clear how “satisfactory clinical response” was defined.

Cephalosporins versus amoxicillin–clavulanic acid (co-amoxiclav):

See benefits of amoxicillin–clavulanic acid (co-amoxiclav) versus cephalosprins.

Harms

Amoxicillin versus cephalosporins:

The RCT gave no information on adverse effects.

Amoxicillin versus macrolides:

The RCT gave no information on adverse effects.

Macrolides versus each other:

The RCT found no significant difference between azithromycin and clarithromycin in adverse effects (17/105 [16%] with azithromycin v 13/109 [12%] with clarithromycin; P = 0.56).

Cephalosporins versus each other:

The first RCT found no significant differences in adverse effects between 5 and 10 day regimens of cefuroxime (AR for at least 1 treatment-related adverse event: 23% with 5 days' treatment v 23% with 10 days' treatment; P = 1.00). The second RCT, which compared cefuroxime versus cefixime, gave no information on adverse effects. The third RCT found that the rate of adverse effects was similar with cefuroxime and cefpodoxime (4/95 [4%] with cefuroxime v 6/92 [7%] with cefpodoxime; CI not reported).

Cephalosporins versus amoxicillin–clavulanic acid (co-amoxiclav):

See harms of amoxicillin–clavulanic acid (co-amoxiclav) versus cephalosprins.

Comment

See comment on amoxicillin–clavulanic acid, andclinical guide on antibiotics versus placebo and other treatments.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Antihistamines

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Compared with placebo: Terfenadine may be no more effective than placebo at reducing mean cough scores at 4 days in adult non-smokers with acute bronchitis ( low-quality evidence ).

Benefits

We found one systematic review of non-prescription medications in people with acute bronchitis (search date 2004). The review identified one RCT (100 adult non-smokers) that met our inclusion criteria. It compared terfenadine 100 mg twice daily versus placebo for 4 or 5 days. It found no significant difference in mean cough score at day 4 between terfenadine and placebo (mean cough score [range 0–3, higher scores indicating worse cough]: 0.80 with terfenadine v 0.65 with placebo; P = 0.35).

Harms

The RCT reported a low incidence of adverse effects, but did not specify them.

Comment

Clinical guide:

The systematic review stated that it examined the effects of treatments in people with “upper respiratory tract infection” rather than “acute bronchitis”. However, the clinical criteria used to define this population were consistent with the definition of acute bronchitis used in this review.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Antitussives

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Dextromethorpan compared with placebo in children: Dextromethorphan may be no more effective than placebo at reducing mean cough scores or at improving "general condition" (not further defined) at 1-3 days in children ( very low-quality evidence ). Codeine compared with placebo in adults: Codeine may be no more effective than placebo at reducing cough severity scores at 90 minutes and 5 days in adults (very low-quality evidence). Moguisteine compared with placebo in adults: Moguisteine may be modestly more effective at reducing mean cough severity scores in adults ( low-quality evidence ). ADVERSE EFFECTS Moguisteine compared with placebo in adults: Moguisteine may be associated with an increase in nausea, vomiting, and abdominal pain compared with placebo in adults ( moderate quality evidence ).

Benefits

Dextromethropan compared with placebo in children:

We found two systematic reviews (search dates 2004, and 2003; see comment below). The first review compared non-prescription medications versus placebo in children with acute cough. It identified one RCT (57 children) that met our inclusion criteria. The RCT compared three treatments at bedtime for 3 nights: dextromethorphan 15 mg once daily, codeine 10 mg once daily, and placebo. It found no significant difference between treatments in mean cough score after 3 days (reduction in mean cough score [range 0–4, higher score indicating more severe cough]: 2.1 with dextromethorphan v 2.2 with codeine v 2.2 with placebo; dextromethorphan v placebo, P = 0.4; codeine v placebo, P = 0.7). The second review compared beta2 agonists versus placebo in children with acute bronchitis, and identified one additional RCT (75 children with acute bronchitis or acute cough), which included an antitussive treatment arm. The RCT compared three treatments: dextromethorphan (7.5 mg once daily for children aged under 7 years and 15 mg once daily for children 7 years and over), dextromethorphan plus salbutamol (albuterol 1 mg once daily for children aged under 7 years and 2 mg once daily for children 7 years and over), and placebo once daily for 3 days. It found no significant difference between dextromethorphan and placebo in cough symptoms at 1, 2, or 3 days, or in general condition (mean cough score, day 1: 1.30 with dextromethorphan v 1.44 with placebo; day 2: 0.93 with dextromethorphan v 1.06 with placebo; day 3: 0.60 with dextromethorphan v 0.76 with placebo; differences reported as non-significant for all days, P values not reported; mean general condition score, day 1: 1.00 with dextromethorphan v 1.40 with placebo; day 2: 1.48 with dextromethorphan v 1.64 with placebo; day 3: 2.00 with dextromethorphan v 2.08 with placebo; difference reported as non-significant for all days, P values not reported). More than half of the people reported some or marked relief from the medication (16/24 [67%] with dextromethorphan v 19/26 [73%] with placebo) but the differences between the groups were reported as non-significant.

Codeine compared with placebo in adults:

We found one systematic review (search date 2004, 2 RCTs meeting our inclusion criteria; see comment below) The first RCT identified by the review (81 adults) compared codeine 30 mg four times daily for 4 days versus placebo. It found no significant difference between codeine and placebo in mean cough severity score (higher score indicates worse cough, scale end points unclear) over a 5-day period (mean cough severity score: 17.2 with codeine v 18.0 with placebo; P = 0.5). The second RCT identified by the review found no significant difference between codeine 30 mg single dose and placebo in subjective cough severity score at 90 minutes after treatment (subjective score on a five-point rating scale reduced from 2.0 to 1.0 in both groups (P = 0.8) .

Moguisteine compared with placebo in adults:

One RCT (108 adults) identified by the review compared moguisteine 200 mg three times daily for 5 days versus placebo. It found that moguisteine modestly reduced cough severity score compared with placebo (mean difference in cough score on a scale of 0–9 [higher score indicating more-severe cough]: 0.5; P less than 0.05).

Harms

Dextromethropan compared with placebo in children:

In the RCT identified by the first review, no additional adverse effects were recorded with treatment compared with placebo (the event rates for each group were not reported). The RCT identified by the second review found a low incidence of serious adverse effects in all treatment groups, and no significant difference between the dextromethorphan and placebo groups (children with serious adverse effects: 3/24 [13%] with dextromethorphan v 1/26 [4%] with placebo; difference reported as non-significant, P value not reported).

Codeine compared with placebo in adults:

The RCTs identified by the review gave no information on adverse effects.

Moguisteine compared with placebo in adults:

The RCT found that moguisteine increased nausea, vomiting, and abdominal pain compared with placebo (13/58 [22%] with moguisteine v 5/58 [9%] with placebo; P less than 0.05).

Comment

Clinical guide:

Four of the six RCTs in adults identified by the first systematic review were excluded because the treatment duration was less than 4 days. The first systematic review stated that it examined the effects of treatments in people with “upper respiratory tract infection” rather than “acute bronchitis”. However, the clinical criteria used to define this population were consistent with the definition of acute bronchitis used in this review. Moguisteine is available without prescription only in the UK. The first systematic review (search date 2004) identified 24 RCTs of various non-prescription medications: nine of these RCTs were wholly or partly funded by the pharmaceutical industry; six of these nine RCTs found positive results, whereas only three out of 12 independent RCTs demonstrated a positive result.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Beta2 agonists (inhaled)

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Compared with placebo: We don't know whether inhaled beta 2 agonists are more effective at reducing the proportion of adults with cough at 7 days or in increasing the proportion of people able to work at 4 days ( low-quality evidence ). ADVERSE EFFECTS Compared with placebo: Inhaled beta 2 agonists are associated with an increase in shaking and tremor in adults compared with placebo ( high-quality evidence ). NOTE We found no direct results about inhaled beta 2 agonists in the treatment of children with acute bronchitis.

Benefits

We found one systematic review (search date 2000; 2 RCTs of inhaled beta2 agonists in 125 adults, both smokers and non-smokers, with acute bronchitis or acute cough). People with pre-existing lung disease, with another acute respiratory disorder, or aged under 24 months were excluded.

Inhaled beta2 agonists versus placebo:

The review meta-analysis combined results for oral and inhaled beta2 agonists (salbutamol and fenoterol) versus placebo in adults and found no significant difference in the proportion of adults with cough after 7 days (3 RCTs, 220 adults: 119 people in 2 RCTs of inhaled beta2 agonists, and 101 people in 1 RCT of oral beta2 agonists; 70/110 [64%] with beta2 agonists v 78/110 [71%] with placebo; RR 0.86, 95% CI 0.63 to 1.18). Similarly, it found no significant difference in the proportion of adults unable to work after 4 days of treatment between oral or inhaled beta2 agonists and placebo (2 RCTs, 149 adults: 43 people in 1 RCT of inhaled beta2 agonists, and 103 people in 1 RCT of oral beta2 agonists; 22/76 [29%] with beta2 agonists v 23/76 [30%] with placebo; RR 0.82, 95% CI 0.28 to 2.34). It identified no RCTs assessing inhaled beta2 agonists in children.

Inhaled beta2 agonists versus antibiotics:

The systematic review identified no RCTs in children or adults.

Harms

Inhaled beta2 agonists versus placebo:

The systematic review found that, in adults, shaking and tremor were significantly more frequently associated with inhaled beta2 agonists than with placebo (1 RCT, 73 adults: 18/37 [49%] with beta2 agonists v 0/36 [0%] with placebo; RR 36.0, 95% CI 2.3 to 576.3).

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Beta2 agonists (oral)

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Compared with placebo: Oral salbutamol may be no more effective than placebo at reducing the proportion of adults and children with cough, or in reducing the proportion of adults unable to work after 4 days ( low-quality evidence ). Compared with antibiotics: Oral salbutamol may be more effective than erythromycin at reducing the proportion of adults with cough at 7 days, but we don't know about other symptoms (low-quality evidence). ADVERSE EFFECTS Compared with placebo: Oral beta 2 agonists are associated with an increase in shaking and tremor in adults compared with placebo ( moderate-quality evidence ).

Benefits

We found one systematic review (search date 2000; 2 RCTs in 109 children and 3 RCTs in 292 adults, both smokers and non-smokers, with acute bronchitis or acute cough). People with pre-existing lung disease, with another acute respiratory disorder, or aged under 24 months were excluded. Two RCTs had more than two study arms. Results from children and adults were analysed separately.

Oral beta2 agonists versus placebo:

The review found no significant difference between an oral beta2 agonist (salbutamol [albuterol]) and placebo in the proportion of children with cough after 7 days (1 RCT, 59 children: 11/30 [37%] with beta2 agonist v 12/29 [41%] with placebo; RR 0.89, 95% CI 0.47 to 1.65). The review found no significant difference between and oral beta2 agonist and placebo in the proportion of adults with cough after 7 days (1 RCT, 101 adults: 39/50 [78%] with oral beta2 agonist v 37/50 [74%] with placebo; RR 1.08, 95% CI 0.86 to 1.35). It also found no significant difference in the proportion of adults unable to work after 4 days of treatment (1 RCT, 103 adults: 17/53 [32%] with oral beta2 agonist v 12/50 [24%] with placebo; RR 1.34, 95% CI 0.71 to 2.51).

Oral beta2 agonists versus antibiotics:

The systematic review identified one small RCT, which compared an oral beta2 agonist (salbutamol [albuterol]) versus oral erythromycin for 7 days in 34 adults. It found that oral salbutamol significantly reduced the proportion of adults with cough after 7 days compared with erythromycin (7/17 [41%] with oral salbutamol v 15/17 [88%] with erythromycin; RR 0.47, 95% CI 0.26 to 0.85). The review identified no RCTs comparing oral beta2 agonists versus antibiotics in children.

Harms

Oral beta2 agonists versus placebo:

The systematic review found that, in children, shaking and tremor were more frequently associated with oral beta2 agonists than with placebo, although the increase did not reach significance (2 RCTs, 108 children: 6/55 [11%] with beta2 agonists v 0/53 [0%] with placebo; RR 10.7, 95% CI 0.6 to 184.3). The systematic review found that, in adults, shaking and tremor were significantly more frequently associated with oral beta2 agonists than with placebo (1 RCT, 104 adults: 34/51 [67%] with beta2 agonists v 12/53 [23%] with placebo; RR 2.94, 95% CI 1.73 to 5.02).

Oral beta2 agonists versus antibiotics:

The RCT identified by the review found that tremor and shaking were more frequently associated with oral beta2 agonist compared with erythromycin, although the difference was not significant (6/17 [35%] with beta2 agonist v 0/17 [0%] with erythromycin; RR 13.0, 95% CI 0.8 to 214.0).

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Expectorants

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Compared with placebo: Oral thyme–ivy syrup expectorant may be more effective than placebo at reducing cough frequency (subjectively measured) and symptoms (measured by Bronchitis Severity Score) at 9 days in adults ( low-quality evidence ).

Benefits

We found one systematic review (search date 2004) of non-prescription medications for acute cough in people with acute bronchitis, which found no RCTs evaluating the effect of expectorants in people with acute bronchitis.We found one subsequent RCT (363 adults with acute bronchitis) which compared an oral thyme–ivy syrup (Bronchipret Saft) versus placebo with a 9-day follow-up period.The primary outcomes were cough frequency (assessed by subjective counting of coughing fits during the day) and symptoms (measured by Bronchitis Severity Score [BSS]). The RCT found that the thyme–ivy combination significantly reduced cough frequency (78% reduction with thyme-ivy v 56% reduction with placebo, P less than 0.001) and significantly decreased symptoms (results presented graphically, P less than 0.001) compared with placebo at day 9 follow-up.

Harms

The subsequent RCT reported similar rates of adverse effects for thyme–ivy syrup compared with placebo (7/183 [4%] with thyme–ivy syrup v 8/179 [5%] with placebo) .

Comment

The systematic review stated that it examined the effects of treatments in people with “upper respiratory tract infection” rather than “acute bronchitis”. However, the clinical criteria used to define this population were consistent with the definition of acute bronchitis used in this review. In the subsequent RCT the study population was defined as people with acute bronchitis and productive cough and, although chest radiographs were not done, the participants' characteristics are consistent with a diagnosis of acute bronchitis, and not of mild acute pneumonia.

Substantive changes

Expectorants One RCT added comparing a combination of thyme, herb, and ivy leaves versus placebo. The RCT found that the combination of thyme, herb, and ivy leaves reduced cough frequency and symptoms at 9 days. Categorisation unchanged (Unknown effectiveness) as there remain insufficient data about expectorants as a class to fully assess their effects.

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Amoxicillin–clavulanic acid (co-amoxiclav) versus cephalosporins

Summary

SYMPTOM SEVERITY (FOR EXAMPLE, COUGH, GLOBAL SYMPTOMS, LIMITATION OF ACTIVITIES, CLINICAL IMPROVEMENT) Compared with cephalosporins: Amoxicillin–clavulanic acid (co-amoxiclav) and cefuroxime seem to be qually effective at increasing clinical cure rates and self-reported clinical improvement ( moderate-quality evidence ). ADVERSE EFFECTS Compared with cephalosporins: Amoxicillin–clavulanic acid seems to be associated with more gastrointestinal adverse effects than cefuroxime (moderate-quality evidence).

Benefits

We found no systematic review. We found two RCTs. The first RCT (312 adults with clinically diagnosed acute bronchitis and no pre-existing lung disease) compared amoxicillin 875 mg plus clavulanic acid 125 mg twice daily for 5 days versus cefuroxime 250 mg twice daily. It found no significant difference between amoxicillin–clavulanic acid (co-amoxiclav) and cefuroxime in self-reported clinical improvement at 10–14 days (128/142 [90%] with amoxicillin–clavulanic acid v 114/133 [86%] with cefuroxime; P = 0.27). The second RCT (537 people aged 12 years and over with clinically diagnosed acute bronchitis and no pre-existing lung disease) compared three interventions: amoxicillin 500 mg plus clavulanic acid 125 mg three times daily for 10 days; cefuroxime 250 mg twice daily for 5 days; and cefuroxime 250 mg twice daily for 10 days. It found no significant difference in cure rates 1–3 days after completing treatment between amoxicillin–clavulanic acid and cefuroxime (116/183 [63%] with amoxicillin–clavulanic acid v 84/177 [48%] with cefuroxime for 5 days, P = 0.91; 116/183 [63%] with amoxicillin–clavulanic acid v 100/177 [57%] with cefuroxime for 10 days, P = 0.45).

Harms

The first RCT found that amoxicillin–clavulanic acid (co-amoxiclav) was associated with more adverse effects than cefuroxime (45/142 [32%] with amoxicillin–clavulanic acid v 16/133 [12%] with cefuroxime; P = 0.001). Most of the adverse effects were gastrointestinal. The second RCT found that a significantly higher proportion of people had gastrointestinal symptoms with amoxicillin–clavulanic acid than with cefuroxime (67/183 [37%] with amoxicillin–clavulanic acid v 26/177 [15%] with cefuroxime for 5 days; P less than 0.01).

Comment

Amoxicillin–clavulanic acid (co-amoxiclav) did not seem to offer additional benefits over cefuroxime, and was associated with more adverse effects. There is no evidence to support the use of broad-spectrum antibiotics such as amoxicillin–clavulanic acid in people with acute bronchitis. See also clinical guide in antibiotics versus placebo and other treatments.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Jul 17;2008:1508.

Analgesics

Summary

We found no direct information from RCTs about the effects of analgesics in people with acute bronchitis.

Benefits

We found no RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Analgesics New option on analgesics added. No RCTs identified. Analgesics categorised as Unknown effectiveness.

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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