Increased versus stable doses of inhaled steroids for exacerbations of chronic asthma in adults and children: Update
Authors: E Flemyng , D Mitchell 
Published: November 2023

Abstract
Rationale
Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned.
Objectives
To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma.
Search methods
We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021.
Eligibility criteria
Parallel and cross-over blinded randomised controlled trials (RCTs)
Outcomes
Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation.
Risk of bias
We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials.
Synthesis methods
We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods.
Included studies
We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data.
Synthesis of results
People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias.
Authors' conclusions
Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated.
Funding
This Cochrane Review had no dedicated funding.
Registration
Protocol (2009): doi.org/10.1002/14651858.CD007524
Original review (2010): doi.org/10.1002/14651858.CD007524.pub3
Review update (2014): doi.org/10.1002/14651858.CD007524.pub4