【每日动态】抗生素和NSAID对急性支气管炎的咳嗽无效
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Respiratory tract infections exert asignificant burden on society through resultant school and employment absencesand demand on primary care services. Most episodes are caused by respiratoryviruses such as rhinovirus. Not only are there no effective antiviral drugsavailable to treat such infections, but our ability to manage their symptoms,especially cough, remains poor. Antibiotics are widely prescribed for acutebronchitis in primary care settings, even though their use demonstratesnegligible effects on illness duration and correlates poorly with the presenceof bacterial infection.1 ,2 Ineffectiveantibiotic use results in unnecessary cost and exposure for patients, and leadsto greater bacterial resistance to antibiotics. Llor and colleagues hypothesisethat airway inflammation in acute bronchitis may respond to non-steroidalanti-inflammatory drugs (NSAIDs). Although one study found no evidence thatthey reduce the duration of cough in the common cold,3 NSAIDsare often used for symptomatic benefits. A robust study to assess their effecton cough symptoms has not previously been reported. This study took the novelstep of comparing the effect of NSAIDs against the broad-spectrum antibioticco-amoxiclav and placebo.
Method
This was a single-blind,placebo-controlled, parallel group study conducted in nine primary care centresin Spain. The study assessed acute bronchitis, defined as a respiratoryinfection of less than 1week in duration with cough, discoloured sputum and at least oneother lower respiratory tract symptom, such as breathlessness, wheezing andchest pain and/or discomfort. Patients were aged 18–70years. The key exclusion criteriaincluded the presence of radiologically confirmed pneumonia; ‘severe illness’,according to the predefined clinical criteria; and a significant comorbidity(including asthma, chronic obstructive pulmonary disease andimmunosuppression). Patients were randomised to thrice-daily treatment groupsof either amoxicillin-clavulanic acid 500/125mg, ibuprofen 600mg or placebo for 10days. Patients were blind to the intervention. The primary outcomewas the number of days following randomisation that cough was still recorded bythe patient on a daily diary card. The power calculation determined aclinically significant change in the cough duration as a difference of 2days from placebo.
Findings
A total of 416 patients were randomisedinto the three treatment arms. Fifty-six per cent were women, while the meanage was 45.1years (withSD of 14.3). The overall mean duration of cough was 10days (95% CI 9 to 11). The meanduration for the ibuprofen group was 9days (95% CI 8 to 10), versus 11days for co-amoxiclav (95% CI 10 to 12) and 11 for placebo (95% CI 8to 14). A logrank test result was 0.25.
The overall absence of clear benefit wassimilar across adjusted models and various secondary outcomes, includingoverall symptom duration and a measure of ‘clinical success’. Adverse eventswere significantly more common in the antibiotic group (12%) compared with theibuprofen arm (5%) and patients receiving placebo (3%; p=0.008).
Commentary
This study adds to the weight of evidenceagainst using antibiotics for self-limiting acute bronchitis and also providesevidence that the use of NSAIDs will not reduce the duration of cough in thiscondition.
The most important limitation is theexclusion of patients with comorbidities, those aged over 70 and those inresidential care—groups presenting commonly and in whom, perhaps, any benefitmight be greatest. The usefulness of the complete absence of cough as theprimary endpoint is questionable. The duration of symptoms is likely importantto patients but a reduction in symptom intensity might also allow an earlierreturn to usual activity. Assessing symptoms is challenging, with overallburden representing a complex composite of severity and duration. Perhaps,also, the treatment was started too late; there was a 4-day average delaybetween the symptom onset and the start of therapy. Moreover, the authors notethat NSAIDs may be prescribed to reduce other symptoms such as chestdiscomfort—the decision not to collect data examining this perhaps represents amissed opportunity.
The study was single-blind, therefore theinvestigators were aware of the treatment allocation. This reflected theexpense of manufacturing identical preparations in investigator-led studies anddoes not appear to have led to bias, given the similar outcomes betweentreatment arms.
In conclusion, it is clear that antibioticsand NSAIDs should not be used routinely to treat cough in acute bronchitis inpatients under the age of 70 without comorbidity. That is not to downplay theimportance of such circumstances; there remains a real and urgent need todevelop effective therapies to reduce the burden of acute bronchitis and otherviral infections of the respiratory tract.
Method
This was a single-blind,placebo-controlled, parallel group study conducted in nine primary care centresin Spain. The study assessed acute bronchitis, defined as a respiratoryinfection of less than 1week in duration with cough, discoloured sputum and at least oneother lower respiratory tract symptom, such as breathlessness, wheezing andchest pain and/or discomfort. Patients were aged 18–70years. The key exclusion criteriaincluded the presence of radiologically confirmed pneumonia; ‘severe illness’,according to the predefined clinical criteria; and a significant comorbidity(including asthma, chronic obstructive pulmonary disease andimmunosuppression). Patients were randomised to thrice-daily treatment groupsof either amoxicillin-clavulanic acid 500/125mg, ibuprofen 600mg or placebo for 10days. Patients were blind to the intervention. The primary outcomewas the number of days following randomisation that cough was still recorded bythe patient on a daily diary card. The power calculation determined aclinically significant change in the cough duration as a difference of 2days from placebo.
Findings
A total of 416 patients were randomisedinto the three treatment arms. Fifty-six per cent were women, while the meanage was 45.1years (withSD of 14.3). The overall mean duration of cough was 10days (95% CI 9 to 11). The meanduration for the ibuprofen group was 9days (95% CI 8 to 10), versus 11days for co-amoxiclav (95% CI 10 to 12) and 11 for placebo (95% CI 8to 14). A logrank test result was 0.25.
The overall absence of clear benefit wassimilar across adjusted models and various secondary outcomes, includingoverall symptom duration and a measure of ‘clinical success’. Adverse eventswere significantly more common in the antibiotic group (12%) compared with theibuprofen arm (5%) and patients receiving placebo (3%; p=0.008).
Commentary
This study adds to the weight of evidenceagainst using antibiotics for self-limiting acute bronchitis and also providesevidence that the use of NSAIDs will not reduce the duration of cough in thiscondition.
The most important limitation is theexclusion of patients with comorbidities, those aged over 70 and those inresidential care—groups presenting commonly and in whom, perhaps, any benefitmight be greatest. The usefulness of the complete absence of cough as theprimary endpoint is questionable. The duration of symptoms is likely importantto patients but a reduction in symptom intensity might also allow an earlierreturn to usual activity. Assessing symptoms is challenging, with overallburden representing a complex composite of severity and duration. Perhaps,also, the treatment was started too late; there was a 4-day average delaybetween the symptom onset and the start of therapy. Moreover, the authors notethat NSAIDs may be prescribed to reduce other symptoms such as chestdiscomfort—the decision not to collect data examining this perhaps represents amissed opportunity.
The study was single-blind, therefore theinvestigators were aware of the treatment allocation. This reflected theexpense of manufacturing identical preparations in investigator-led studies anddoes not appear to have led to bias, given the similar outcomes betweentreatment arms.
In conclusion, it is clear that antibioticsand NSAIDs should not be used routinely to treat cough in acute bronchitis inpatients under the age of 70 without comorbidity. That is not to downplay theimportance of such circumstances; there remains a real and urgent need todevelop effective therapies to reduce the burden of acute bronchitis and otherviral infections of the respiratory tract.
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