Abstract/Text
CONTEXT: Antibiotic use is associated with increased rates of antibiotic-resistant organisms. A previous study has shown that colds, upper respiratory tract infections, and bronchitis account for nearly one third of all antibiotic prescribing by ambulatory care physicians. How frequently antibiotics are prescribed for these conditions and for and by whom is not known.
OBJECTIVES: To measure antibiotic prescription rates and to identify predictors of antibiotic use for adults diagnosed as having colds, upper respiratory tract infections, and bronchitis in the United States.
DESIGN: Sample survey of practicing physicians participating in the National Ambulatory Medical Care Survey, 1992.
SETTING: Office-based physician practices.
SUBJECTS: Physicians (n=1529) completing patient record forms for adult office visits (n=28787).
MAIN OUTCOME MEASURES: Antibiotic prescriptions for colds, upper respiratory tract infections, and bronchitis.
RESULTS: Office visits for colds, upper respiratory tract infections, and bronchitis resulted in approximately 12 million antibiotic prescriptions, accounting for 21% of all antibiotic prescriptions to adults in 1992. A total of 51 % of patients diagnosed as having colds, 52% of patients diagnosed as having upper respiratory tract infections, and 66% of patients diagnosed as having bronchitis were treated with antibiotics. Female sex (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.05-2.62) and rural practice location (OR, 2.25; 95% CI, 1.33-3.80) were associated with greater antibiotic prescription rates, whereas black race (OR, 0.44; 95% CI, 0.21-0.93) was associated with lower antibiotic prescription rates. Patient age, Hispanic ethnicity, geographic region, physician specialty, and payment sources were not associated with antibiotic prescription rates in the bivariate analysis. Multivariate logistic regression analysis identified only rural practice location (adjusted OR, 2.58; 95% CI, 1.39-4.76) to be independently associated with more frequent antibiotic prescriptions for colds, upper respiratory tract infections, and bronchitis.
CONCLUSION: Although antibiotics have little or no benefit for colds, upper respiratory tract infections, or bronchitis, these conditions account for a sizable proportion of total antibiotic prescriptions for adults by office-based physicians in the United States. Overuse of antibiotics is widespread across geographical areas, medical specialties, and payment sources. Therefore, effective strategies for changing prescribing behavior for these conditions will need to be broad based.
Abstract/Text
The following principles of appropriate antibiotic use for adults with acute bronchitis apply to immunocompetent adults without complicating comorbid conditions, such as chronic lung or heart disease. The evaluation of adults with an acute cough illness or a presumptive diagnosis of uncomplicated acute bronchitis should focus on ruling out serious illness, particularly pneumonia. In healthy, nonelderly adults, pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds, and chest radiography is usually not indicated. In patients with cough lasting 3 weeks or longer, chest radiography may be warranted in the absence of other known causes. Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough. If pertussis infection is suspected (an unusual circumstance), a diagnostic test should be performed and antimicrobial therapy initiated. Patient satisfaction with care for acute bronchitis depends most on physician--patient communication rather than on antibiotic treatment.
Andrew Bush, Anne H Thomson
Acute bronchiolitis.
BMJ. 2007 Nov 17;335(7628):1037-41. doi: 10.1136/bmj.39374.600081.AD.
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Abstract/Text
BACKGROUND: The reliability of chest physical examination and the degree of agreement among examiners in diagnosing pneumonia based on these findings are largely unknown.
OBJECTIVES: To determine the accuracy of various physical examination maneuvers in diagnosing pneumonia and to compare the interobserver reliability of the maneuvers among 3 examiners.
METHODS: Fifty-two male patients presenting to the emergency department of a university-affiliated Veterans Affairs medical center with symptoms of lower respiratory tract infection (cough and change in sputum) were prospectively examined. A comprehensive lung physical examination was performed sequentially by 3 physicians who were blind to clinical history, laboratory findings, and x-ray results. Examination findings by lung site and whether the examiner diagnosed pneumonia were recorded on a standard form. Chest x-ray films were read by a radiologist.
RESULTS: Twenty-four patients had pneumonia confirmed by chest x-ray films. Twenty-eight patients did not have pneumonia. Abnormal lung sounds were common in both groups; the most frequently detected were rales in the upright seated position and bronchial breath sounds. Relatively high agreement among examiners (kappa approximately 0.5) occurred for rales in the lateral decubitus position and for wheezes. The 3 examiners' clinical diagnosis of pneumonia had a sensitivity of 47% to 69% and specificity of 58% to 75%.
CONCLUSIONS: The degree of interobserver agreement was highly variable for different physical examination findings. The most valuable examination maneuvers in detecting pneumonia were unilateral rales and rales in the lateral decubitus position. The traditional chest physical examination is not sufficiently accurate on its own to confirm or exclude the diagnosis of pneumonia.
Abstract/Text
BACKGROUND: Acute bronchitis is a common clinical problem that causes considerable morbidity and presents both diagnostic and treatment dilemmas for the physician. An evaluation of all published randomized controlled trials of antibiotics in the treatment of acute bronchitis was conducted to (1) quantitatively assess methodologic rigor, (2) determine if effectiveness of antimicrobial therapy is known, and (3) analyze strengths and weaknesses of randomized controlled trials in family practice settings.
METHODS: A scoring system for the evaluation of randomized controlled trials was adapted for this study. Four raters, who were blinded to which journals published the studies and the type of antibiotic used in each study, assessed the six-randomized clinical trials for treatment of bronchitis identified through a literature search. The trials were rated according to criteria that measured internal validity.
RESULTS: Scores for internal validity ranged from 65.5 to 102.5 points with a maximum possible score of 120 points (54.6% to 85.4%). The two trials with the highest scores assessed doxycycline and showed no benefit from use of this antibiotic. Single trials that studied erythromycin and trimethoprim-sulfamethoxazole showed improvement in outcome from use of these drugs; however, of the six trials, these two studies ranked fourth and fifth for internal validity. Low scores resulted from small sample size, possible contamination with other treatment measures, and poor assessment of subjects' compliance with antibiotic regimen.
CONCLUSIONS: An evaluation of the current literature does not support antibiotic treatment for acute bronchitis. Further studies of this common illness are indicated. It is hoped that this critical review of randomized control trials will prove useful in the planning of future studies, in placing greater emphasis on methodologic rigor, and in giving greater consideration to the practical constraints of research in the family practice setting.
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BACKGROUND: Most clinicians prescribe antibiotics for acute bronchitis in spite of recommendations against this practice. Because the results of individual clinical trials have been mixed, we conducted a meta-analysis to determine whether antibiotics are effective treatment for acute bronchitis.
METHODS: We conducted a comprehensive search to identify all trials in which patients who had a diagnosis of acute bronchitis were randomly assigned to treatment with an antibiotic or placebo. Patient-oriented outcomes of importance that were reported in at least 3 studies were quantitatively summarized.
RESULTS: Nine studies met the inclusion criteria, but not all trials provided data for each outcome. Patients given antibiotics were less likely to have a cough (relative risk [RR] = 0.69; 95% confidence interval [CI], 0.49 -0.98) and be considered unimproved (RR = 0.51; 95% CI, 0.30-0.88) at a follow-up visit; but they were not less likely to have a productive cough (RR = 0.79; 95% CI, 0.60-1.03), activity limitations (RR = 0.59; 95% CI, 0.24-1.44), or feel ill (RR = 0.70; 95% CI, 0.31-1.58). Antibiotic-treated patients had a slightly shorter duration of productive cough (weighted mean difference [WMD] = -0.56 days; 95% CI, -1.09 to -0.04), but not of overall cough (WMD = -0.94; 95% CI, -2.08 to 0.21) or activity limitations (WMD = -0.49; 95% CI, -1.07 to 0.10). Patients treated with antibiotics did not report significantly more adverse effects (RR = 1.47; 95% CI, 0.82-2.65).
CONCLUSIONS: Antibiotics may be modestly effective for a minority of patients with acute bronchitis. It is not clear which patient subgroups might benefit, and the failure of some studies to report negative findings may have resulted in overestimates of the benefits of antibiotics. Antibiotics are not necessary for every patient with acute bronchitis.
Abstract/Text
OBJECTIVES: People with acute bronchitis may show little evidence of bacterial infection. If effective, antibiotics could shorten the course of the disease. However, if they are not effective, the risk of antibiotic resistance may be increased. The objective of this review was to assess the effects of antibiotic treatment in patients with a clinical diagnosis of acute bronchitis.
SEARCH STRATEGY: The authors searched MEDLINE, Embase, reference lists of articles, personal collections up to 1996 and Sci-search from 1989 to 1996.
SELECTION CRITERIA: Randomized trials comparing any antibiotic therapy with placebo in acute bronchitis.
DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial quality.
PRIMARY RESULTS: The results of eight trials involving 750 patients from eight years of age to 65 and older and including smokers and nonsmokers were included. The quality of the trials was variable. A variety of outcome measures was assessed. In many cases, only outcomes that showed a statistically significant difference between groups were reported. Overall, patients taking antibiotics had slightly better outcomes than those taking placebo. They were less likely to report feeling unwell at a follow-up visit (odds ratio, 0.42; 95 percent confidence interval [CI] 0.22 to 0.82), to show no improvement on physician assessment (odds ratio, 0.43; CI, 0.23 to 0.79) or to have abnormal lung findings (odds ratio, 0.33; CI, 0.13 to 0.86), and had a more rapid return to work or usual activities (weighted mean difference, 0.7 days earlier; CI, 0.2 to 1.3). Antibiotic-treated patients reported significantly more adverse effects (odds ratio, 1.64; CI, 1.05 to 2.57), such as nausea, vomiting, headache, skin rash or vaginitis.
REVIEWERS' CONCLUSIONS: Antibiotics appear to have a modest beneficial effect in the treatment of acute bronchitis, with a correspondingly small risk of adverse effects. The benefits of antibiotics may be overestimated in this analysis because of the tendency of published reports to include complete data only on outcomes found to be statistically significant.
Abstract/Text
CONTEXT: The emergence and spread of antibiotic-resistant Streptococcus pneumoniae in US communities is due, in part, to the excessive use of antibiotics for acute respiratory tract infections.
OBJECTIVE: To decrease total antibiotic use for uncomplicated acute bronchitis in adults.
DESIGN: Prospective, nonrandomized controlled trial, including baseline (November 1996-February 1997) and study (November 1997-February 1998) periods.
SETTING: Four selected primary care practices belonging to a group-model health maintenance organization in the Denver, Colo, metropolitan area.
PARTICIPANTS: Consecutive adults diagnosed as having uncomplicated acute bronchitis. A total of 2462 adults were included at baseline and 2027 adults were included in the study. Clinicians included 56 physicians, 28 physician assistants or nurse practitioners, and 9 registered nurses.
INTERVENTION: The full intervention site received household and office-based patient educational materials, as well as a clinician intervention consisting of education, practice-profiling, and academic detailing. A limited intervention site received only office-based educational materials, and control sites provided usual care.
MAIN OUTCOME MEASURE: Antibiotic prescriptions for uncomplicated acute bronchitis during baseline and study periods.
RESULTS: Antibiotic prescription rates for uncomplicated acute bronchitis were similar at all 4 sites during the baseline period. During the study period, there was a substantial decline in antibiotic prescription rates at the full intervention site (from 74% to 48% [P = .003]), but not at the control and limited intervention sites (78% to 76% [P = .81] and 82% to 77% [P = .68], respectively). Compared with control sites, changes in nonantibiotic prescriptions (inhaled bronchodilators, cough suppressants, and analgesics) were not significantly different for intervention sites. Return office visits (within 30 days of the incident visit) for bronchitis or pneumonia did not change significantly for any of the sites.
CONCLUSIONS: Antibiotic treatment of adults diagnosed as having uncomplicated acute bronchitis can be safely reduced using a combination of patient and clinician interventions.
Abstract/Text
AIMS: To understand which clinical criteria physicians use to diagnose pneumonia compared to bronchitis and upper respiratory tract infection (URTI).
METHODS: Retrospective chart review of adults diagnosed with pneumonia, bronchitis, or URTI.
RESULTS: Logistic regression analysis identified rales, a temperature > 100 degrees F (37.8 degrees C), chest pain, dyspnoea, rhonchi, heart rate, respiratory rate, and rhinorrhoea, as the best explanation for the variation in diagnosis of pneumonia compared to either of the alternative diagnoses (R2 = 59.3), with rales and a temperature > 100 degrees F explaining 30% of the variation. Rales, chest pain, and a temperature > 100 degrees F best predicted the ordering of a chest x-ray (R2 = 20.0). However, 35% (59/175) of patients diagnosed with pneumonia had a negative chest x-ray. Abnormal breath sounds were the best predictors for prescribing antibiotics (R2 = 38%). A significant number of patients with acute bronchitis (93% excluding sinusitis) and URTI (42%) were given antibiotics.
CONCLUSIONS: The presence of abnormal breath sounds and a temperature > 100 degrees F were the best predictors of a diagnosis of pneumonia.
Lorne A Becker, Jeffrey Hom, Miguel Villasis-Keever, Johannes C van der Wouden
Beta2-agonists for acute bronchitis.
Cochrane Database Syst Rev. 2011 Jul 6;(7):CD001726. doi: 10.1002/14651858.CD001726.pub4. Epub 2011 Jul 6.
Abstract/Text
BACKGROUND: There are no clearly effective treatments for the cough of acute bronchitis. Beta2-agonists are often prescribed, perhaps because clinicians suspect many patients also have reversible airflow restriction contributing to the symptoms.
OBJECTIVES: To determine whether beta2-agonists improve acute bronchitis symptoms in patients with no underlying pulmonary disease.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2011, issue 1 which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to February week 1, 2011) and EMBASE (1974 to February 2011).
SELECTION CRITERIA: Randomised controlled trials (RCTs) in which patients (adults, or children over two years of age) with acute bronchitis or acute cough and without known pulmonary disease were allocated to beta2-agonist versus placebo, no treatment or alternative treatment.
DATA COLLECTION AND ANALYSIS: Three review authors independently selected outcomes and extracted data while blinded to study results. Two review authors independently assessed each trial for risk of bias. We analysed trials in children and adults separately.
MAIN RESULTS: Two trials in children (n = 109) with no evidence of airway obstruction did not find any benefits from oral beta2-agonists. Five trials in adults (n = 418) had mixed results but overall summary statistics did not reveal any significant benefits from oral (three trials) nor inhaled (two trials) beta2-agonists. There were no significant differences in daily cough scores nor in the percentage of adults still coughing after seven days (control group 73%; risk ratio (RR) 0.77, 95% confidence interval (CI) 0.54 to 1.09). in one trial, subgroups with evidence of airflow limitation had lower symptom scores if given beta2-agonists. The trials that noted quicker resolution of cough with beta2-agonists were those with a higher proportion of wheezing patients at baseline. Adults given beta2-agonists were more likely to report tremor, shakiness or nervousness (RR 7.94, 95% CI 1.17 to 53.94; number needed to treat to harm (NNTH) 2.3).
AUTHORS' CONCLUSIONS: There is no evidence to support the use of beta2-agonists in children with acute cough who do not have evidence of airflow obstruction. There is also little evidence that the routine use of beta2-agonists is helpful for adults with acute cough. These agents may reduce symptoms, including cough, in people with evidence of airflow obstruction. However, this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with their use.
Abstract/Text
OBJECTIVE: Our goal was to determine whether beta2-agonists improve the symptoms of acute bronchitis or acute cough in patients who do not have underlying pulmonary disease.
STUDY DESIGN: We performed a systematic review including meta-analysis.
DATA SOURCES: We included randomized controlled trials comparing beta2-agonists with placebo or alternative therapies identified from the Cochrane Library, MEDLINE, EMBASE, conference proceedings, Science Citation Index, the System for Information on Grey Literature in Europe, and letters to manufacturers of beta2-agonists.
OUTCOMES MEASURED: We measured duration, persistence, severity or frequency of cough, productive cough, and night cough; duration of activity limitations; and adverse effects.
RESULTS: Two trials in children with cough and no obvious airway obstruction did not find any benefits from beta2-agonists. Five trials in adults with cough and with or without airway obstruction had mixed results, but summary statistics did not reveal any significant benefits from beta2-agonists. Studies that enrolled more wheezing patients were more likely to show benefits from beta2-agonists, and in one study only patients with evidence of airflow limitation were more likely to benefit. Patients given beta2-agonists were more likely to report tremor, shakiness, or nervousness than those in the control groups.
CONCLUSIONS: There is no evidence to support using beta2-agonists in children with acute cough and no evidence of airflow obstruction. There is little evidence that the routine use of beta2-agonists for adults with acute cough is helpful. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction, but this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.
Abstract/Text
BACKGROUND: Beta-agonist agents have been used for bronchospasm and cough in a variety of settings. We sought to evaluate the efficacy of oral albuterol for acute cough in ambulatory adults.
METHODS: We performed a prospective, randomized, controlled, double-blind clinical trial comparing albuterol 4 mg by mouth three times daily for 7 days with placebo in 104 adults. Subjects had cough of less than 4 weeks' duration and no evidence of pneumonia, asthma, or chronic obstructive pulmonary disease. All subjects were enrolled at the walk-in clinic of a rural academic medical center.
RESULTS: There was no significant difference between treated and control subjects in any measure of efficacy including cough severity score, reduction in sleepless nights, utilization of health care, or return to full activity. There were significantly more reports of "shakiness" and "nervousness" among albuterol-treated subjects than among controls.
CONCLUSIONS: Oral albuterol should not be used in unselected patients with acute, nonspecific cough.
Abstract/Text
STUDY OBJECTIVE: The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies.
STUDY DESIGN: The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period.
SETTING: One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies.
PATIENTS: Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis.
MEASUREMENTS AND RESULTS: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo.
CONCLUSION: The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI.
Abstract/Text
Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection. It is the most common lower respiratory infection in this age group. It is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, increased mucus production, and bronchospasm. The American Academy of Pediatrics convened a committee composed of primary care physicians and specialists in the fields of pulmonology, infectious disease, emergency medicine, epidemiology, and medical informatics. The committee partnered with the Agency for Healthcare Research and Quality and the RTI International-University of North Carolina Evidence-Based Practice Center to develop a comprehensive review of the evidence-based literature related to the diagnosis, management, and prevention of bronchiolitis. The resulting evidence report and other sources of data were used to formulate clinical practice guideline recommendations. This guideline addresses the diagnosis of bronchiolitis as well as various therapeutic interventions including bronchodilators, corticosteroids, antiviral and antibacterial agents, hydration, chest physiotherapy, and oxygen. Recommendations are made for prevention of respiratory syncytial virus infection with palivizumab and the control of nosocomial spread of infection. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent comprehensive peer review before it was approved by the American Academy of Pediatrics. This clinical practice guideline is not intended as a sole source of guidance in the management of children with bronchiolitis. Rather, it is intended to assist clinicians in decision-making. It is not intended to replace clinical judgment or establish a protocol for the care of all children with this condition. These recommendations may not provide the only appropriate approach to the management of children with bronchiolitis.
Anne M Gadomski, Melissa Brower
Bronchodilators for bronchiolitis.
Cochrane Database Syst Rev. 2010 Dec 8;(12):CD001266. doi: 10.1002/14651858.CD001266.pub2. Epub 2010 Dec 8.
Abstract/Text
BACKGROUND: Bronchiolitis is an acute, viral lower respiratory tract infection affecting infants and often treated with bronchodilators.
OBJECTIVES: To assess the effects of bronchodilators on clinical outcomes in infants with acute bronchiolitis.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1) which contains the Acute Respiratory Infections Group's Specialized Register, MEDLINE (1966 to March week 2 2010) and EMBASE (2003 to March 2010).
SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing bronchodilators (other than epinephrine) with placebo for bronchiolitis.
DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data. Unpublished data were obtained from trial authors.
MAIN RESULTS: We included 28 trials (1912 infants) with bronchiolitis. In 10 inpatient and 10 outpatient studies, oxygen saturation did not improve with bronchodilators (mean difference (MD) -0.45, 95% confidence interval (CI) -0.96 to 0.05, n = 1182). Outpatient bronchodilator treatment did not reduce the rate of hospitalization (12% in bronchodilator group versus 16% in placebo, odds ratio (OR) 0.78, 95% CI 0.47 to 1.29, n = 650). Inpatient bronchodilator treatment did not reduce the duration of hospitalization (MD 0.06, 95% CI -0.27 to 0.39, n = 349). In seven inpatient and eight outpatient studies, average clinical score decreased slightly with bronchodilators (standardized mean difference (SMD) -0.37, 95% CI -0.62 to -0.13, n = 1006).Oximetry and clinical score outcomes showed significant heterogeneity. Including only studies at low risk of bias significantly reduced heterogeneity measures for oximetry (I(2) statistic = 17%) and average clinical score (I(2) statistic = 26%), while having little impact on the overall effect size of oximetry (MD -0.38, 95% CI -0.75 to 0.00, P = 0.05) and average clinical score (SMD -0.26, 95% CI -0.44 to -0.08, P = 0.005).Effect estimates for outpatients were slightly larger than for inpatients for oximetry (outpatients MD -0.57, 95% CI -1.13 to 0.00 versus inpatients MD -0.29, 95% CI -1.10 to 0.51) and average clinical score (outpatients SMD -0.49, 95% CI -0.86 to -0.11 versus inpatients SMD -0.20, 95% CI -0.43 to 0.03). Adverse effects included tachycardia and tremors.
AUTHORS' CONCLUSIONS: Bronchodilators do not improve oxygen saturation, do not reduce hospital admission after outpatient treatment, do not shorten the duration of hospitalization and do not reduce the time to resolution of illness at home. The small improvements in clinical scores for outpatients must be weighed against the costs and adverse effects of bronchodilators.
Abstract/Text
OBJECTIVE: To evaluate the efficacy of beta2-agonists in bronchiolitis.
DESIGN: Critical review and meta-analysis of randomized controlled trials of inhaled beta2-agonists.
RESULTS: Three inpatient and five outpatient studies were identified. Inpatient studies (82 patients) were characterized by wide variability in therapeutic regimens and measurement of outcomes. Several problems were identified in the selection and specification of patients, such as failure to assess the prestudy duration of illness or to exclude patients already taking bronchodilators. Meta-analysis was not possible for inpatient trials due to the great variability in study outcomes, timing of outcome assessment, and drug regimens. Results of inpatient trials were contradictory: one found significant reductions in the clinical score and a shorter hospital stay with treatment, whereas two others found only significant oxygen desaturations. Outpatient studies (251 patients) examined immediate changes in physiologic measures and clinical scores after two treatments, but have not examined the effects of the longer-term regimen customarily used by clinicians. Meta-analysis revealed that short-term beta2-agonist therapy had no impact on the hospitalization rate or respiratory rate, and had a statistically significant but clinically insignificant impact on oxygen saturation and heart rate. The diversity of scoring systems precluded pooling of clinical score data.
CONCLUSIONS: Despite eight clinical trials, conclusive evidence for the efficacy of beta2-agonist therapy for bronchiolitis remains unavailable. Well-designed inpatient trials are needed. Meta-analysis of outpatient studies does not support the use of beta2-agonist therapy for bronchiolitis, but investigators have not studied the outcomes and the long-term outpatient regimen customarily used by clinicians.
Abstract/Text
OBJECTIVE: To examine the efficacy of albuterol (0.15 mg/kg per dose) in the management of bronchiolitis.
DESIGN: Randomized, double-blind, placebo-controlled outpatient clinical trial utilizing four study groups: neubulized albuterol, nebulized saline, oral albuterol, and oral placebo.
SETTING: Pediatric emergency department and outpatient clinic at University of Maryland in Baltimore.
PATIENTS: Eighty-eight infants (median age 5.5 months) being treated for their first episode of wheezing were randomly assigned to nebulized albuterol (n = 22), nebulized saline (n = 23), oral albuterol (n = 19), oral placebo (n = 24).
INTERVENTIONS: The nebulized groups received two nebulizations 30 minutes apart, whereas the oral groups received one oral dose.
MAIN OUTCOME MEASURES: Respiratory and heart rates, clinical score, oxygen saturation (Spo2), and the infant's state, ie, asleep, awake, or feeding, were recorded at baseline and at 30 and 60 minutes after treatment.
RESULTS: Randomization produced equivalent groups in terms of demographics and baseline measures. There were no statistically significant differences in any outcomes among the four treatments, except for oral albuterol, which produced an increase in heart rate (15 beats per minute, P = .005). No differences in the need for additional treatment or hospitalization were observed. Change in the state of the infant during the trial had significant effects on respiratory rate and clinical score.
CONCLUSIONS: Albuterol is as effective as oral placebo in the management of bronchiolitis. Past studies supporting the use of albuterol did not control for effects of change in state of the infant and did not use a truly inactive placebo group. This study underscores the importance of these design components in measuring the efficacy of albuterol in infants.
Howard M Corneli, Joseph J Zorc, Prashant Mahajan, Prashant Majahan, Kathy N Shaw, Richard Holubkov, Scott D Reeves, Richard M Ruddy, Baqir Malik, Kyle A Nelson, Joan S Bregstein, Kathleen M Brown, Matthew N Denenberg, Kathleen A Lillis, Lynn Babcock Cimpello, James W Tsung, Dominic A Borgialli, Marc N Baskin, Getachew Teshome, Mitchell A Goldstein, David Monroe, J Michael Dean, Nathan Kuppermann, Bronchiolitis Study Group of the Pediatric Emergency Care Applied Research Network (PECARN)
A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis.
N Engl J Med. 2007 Jul 26;357(4):331-9. doi: 10.1056/NEJMoa071255.
Abstract/Text
BACKGROUND: Bronchiolitis, the most common infection of the lower respiratory tract in infants, is a leading cause of hospitalization in childhood. Corticosteroids are commonly used to treat bronchiolitis, but evidence of their effectiveness is limited.
METHODS: We conducted a double-blind, randomized trial comparing a single dose of oral dexamethasone (1 mg per kilogram of body weight) with placebo in 600 children (age range, 2 to 12 months) with a first episode of wheezing diagnosed in the emergency department as moderate-to-severe bronchiolitis (defined by a Respiratory Distress Assessment Instrument score > or =6). We enrolled patients at 20 emergency departments during the months of November through April over a 3-year period. The primary outcome was hospital admission after 4 hours of emergency department observation. The secondary outcome was the Respiratory Assessment Change Score (RACS). We also evaluated later outcomes: length of hospital stay, later medical visits or admissions, and adverse events.
RESULTS: Baseline characteristics were similar in the two groups. The admission rate was 39.7% for children assigned to dexamethasone, as compared with 41.0% for those assigned to placebo (absolute difference, -1.3%; 95% confidence interval [CI], -9.2 to 6.5). Both groups had respiratory improvement during observation; the mean 4-hour RACS was -5.3 for dexamethasone, as compared with -4.8 for placebo (absolute difference, -0.5; 95% CI, -1.3 to 0.3). Multivariate adjustment did not significantly alter the results, nor were differences detected in later outcomes.
CONCLUSIONS: In infants with acute moderate-to-severe bronchiolitis who were treated in the emergency department, a single dose of 1 mg of oral dexamethasone per kilogram did not significantly alter the rate of hospital admission, the respiratory status after 4 hours of observation, or later outcomes. (ClinicalTrials.gov number, NCT00119002 [ClinicalTrials.gov].).
Copyright 2007 Massachusetts Medical Society.
Abstract/Text
BACKGROUND AND OBJECTIVE: The management of bronchiolitis is still controversial and to the best of our knowledge, no clinical trial with oral corticosteroids in outpatients has been carried out in developing countries. The objective was to compare the efficacy of a single dose of oral dexamethasone in infants with moderate to severe bronchiolitis presenting to an emergency department.
MATERIAL AND METHODS: A randomised, double-blind, placebo-controlled trial was conducted in Paraguay. At baseline, respiratory distress assessment instrument (RDAI), heart and respiratory rates, and transcutaneous haemoglobin oxygen saturation (SpO(2)) were recorded. Children received either a single dose of dexamethasone (0.5 mg/kg) or placebo; and then both groups received two nebulisations with adrenaline. Respiratory status was recorded again after the 1st and 4th hours. The primary outcome was RDAI improvement at the 4th hour; and the secondary was the hospital admission rate.
RESULTS: During 5 months, 80 (33.3 %) out of 240 infants who consulted with acute respiratory illness fulfilled the inclusion criteria. During the trial 15 were excluded, therefore, 65 infants (33 in the dexamethasone vs. 32 in the placebo group) finished the study. Baseline characteristics and respiratory status were similar between groups. There were no differences in RDAI, heart and respiratory rate and SpO(2) between groups after the 1st and 4th hours. The hospitalisation rate was similar between groups (21 % vs. 25 %, p = 0.9, respectively), independently of the virus identified.
CONCLUSIONS: Infants with moderate-severe bronchiolitis who were treated with a single dose of dexamethasone did not significantly alter the rate of hospitalisation or respiratory status.
Tom Jefferson, Carlo Di Pietrantonj, Alessandro Rivetti, Ghada A Bawazeer, Lubna A Al-Ansary, Eliana Ferroni
Vaccines for preventing influenza in healthy adults.
Cochrane Database Syst Rev. 2010 Jul 7;(7):CD001269. doi: 10.1002/14651858.CD001269.pub4. Epub 2010 Jul 7.
Abstract/Text
BACKGROUND: Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.
OBJECTIVES: Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010, issue 2), MEDLINE (January 1966 to June 2010) and EMBASE (1990 to June 2010).
SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally-occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data.
MAIN RESULTS: We included 50 reports. Forty (59 sub-studies) were clinical trials of over 70,000 people. Eight were comparative non-RCTs and assessed serious harms. Two were reports of harms which could not be introduced in the data analysis. In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barré Syndrome per million vaccinations. The harms evidence base is limited.
AUTHORS' CONCLUSIONS: Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.WARNING: This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.
