Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults
Bibliographic record
Abstract
BACKGROUND: Consensus statements recommend the addition of long-acting inhaled beta2-agonists only in asthmatic patients who are inadequately controlled on inhaled corticosteroids. OBJECTIVES: To compare the efficacy of initiating anti-inflammatory therapy using the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS+LABA) as compared to inhaled corticosteroids alone (ICS alone) in steroid-naive children and adults with persistent asthma. SEARCH STRATEGY: We identified randomised controlled trials (RCTs) through electronic database searches (Cochrane Airways Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL) until April 2004, bibliographies of identified RCTs and correspondence with manufacturers. SELECTION CRITERIA: RCTs comparing the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS + LABA) to inhaled corticosteroids (ICS) alone in steroid-naive children and adults with asthma. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by each reviewer for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of asthma exacerbations requiring systemic corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptoms, use of other measures of asthma control, adverse events, and withdrawal rates. MAIN RESULTS: Eighteen trials met the inclusion criteria; nine (totaling 1061 adults) contributed sufficient data to be analysed. Baseline forced expiratory volume in one minute (FEV1) was less than 80% predicted value in four trials and equal to or greater than 80% in five trials. The long-acting beta2-agonists (LABA) formoterol (N=2) or salmeterol (N=7) were added to a dose of at least 800 microg/day of beclomethasone dipropionate (BDP) equivalent of inhaled corticosteroids (ICS) in three trials and to at least 400 microg/day in the six remaining trials. Treatment with ICS plus LABA was not associated with a lower risk of exacerbations requiring oral corticosteroids than ICS alone (relative risk (RR) 1.2; 95% confidence interval (CI) 0.8 to 1.9). FEV1 improved significantly with LABA (weighted mean difference (WMD) 210 ml; 95% CI 120 to 300), as did symptom-free days (WMD 10.74%; 95% CI 1.86 to 19.62), but the change in use of rescue fast-acting beta2-agonists was not significantly different between the groups (WMD -0.4 puff/day, 95% CI -0.9 to 0.1). There was no significant group difference in adverse events (RR 1.1; 95% CI 0.8 to 1.5), withdrawals (RR 0.9; 95% CI 0.6 to 1.2), or withdrawals due to poor asthma control (RR 1.3; 95% CI 0.5 to 3.4). AUTHORS' CONCLUSIONS: In steroid-naive patients with mild to moderate airway obstruction, the initiation of inhaled corticosteroids in combination with long-acting beta2-agonists does not significantly reduce the rate of exacerbations over that achieved with inhaled corticosteroids alone; it does improve lung function and symptom-free days but does not reduce rescue beta2-agonist use as compared to inhaled steroids alone. Both options appear safe. There is insufficient evidence at present to recommend use of combination therapy rather than ICS alone as a first-line treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.009 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.021 | 0.004 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".