Unrecognised asthma in mild or moderate COPD on higher-dose inhaled steroids: action needed
Problem
Higher-dose inhaled corticosteroids (ICS) are prescribed frequently by GPs, outside COPD guidelines, to patients with mild or moderate airflow limitation. Evidence suggests these are rarely indicated and risk important side-effects. We assessed the implications and opportunities of withdrawal by GPs of ICS prescribed outside guidelines in COPD patients with mild or moderate airflow limitation.
Approach
COPD patients with mild or moderate airflow limitation, with no history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations or of asthma, and using ICS (dose >400mcg beclomethasone diproprionate - BDP/day equivalent), were recruited by their GPs to undergo ICS withdrawal. The electronic records of potential participants, identified by algorithm assessment, were reviewed followed by clinical assessment of those eligible. Participants were randomised to withdrawal from higher-dose ICS. Impact of withdrawal was assessed through measures of lung function (forced expiratory volume in the first second – FEV1), quality of life (COPD Assessment Test – CAT), exacerbations, and cellular and molecular biomarkers. Measures were repeated at 3 and 6 months.
Findings
392 (13%) patients with mild or moderate airflow limitation were identified for higher-dose ICS withdrawal from a COPD population of 2967. On individual record review, 15 (5%) of those identified had prior evidence of asthma. A further 228 (58%) were excluded for other reasons. 149 eligible patients were invited for clinical assessment. 61 attended. All agreed to randomisation for ICS withdrawal. Eleven (18%) had new evidence of asthma on assessment (FEV1 variability > 12% and >200ml). 40 were randomised to ICS withdrawal or maintenance of whom 18 (45%) had new evidence of asthma after repeated spirometric assessment over six months; 10 (25%) were in the withdrawal group and 8 (20%) in the maintenance group. Worsening symptom burden (increase of ≥+2 in CAT score) was seen after withdrawal of ICS in those with FEV1 variability consistent with a diagnosis of asthma. The presence of a Th2 (asthma-like) inflammatory response in the patients with FEV1 variability was seen in: significant association between FEV1 variability and raised fractional exhaled nitric oxide (FENO) levels (p=0.009); significant association between FEV1 variability and a combination of raised FENO and symptom burden (p=0.005); and significant association between FEV1 variability and a combination of blood eosinophil count and symptom burden (0.005).
Consequences
Withdrawal of higher-dose ICS prescribed outside guidelines for COPD is feasible and acceptable. A high proportion of these patients had features consistent with a diagnosis of asthma. We recommend that general practices actively assess patients with COPD with mild or moderate airflow limitation on higher-dose ICS (dose >400mcg BDP equivalent) to identify those with airflow variability suggestive of asthma. Adoption of an asthma treatment strategy recommended by the asthma guidelines should be considered in these patients.