Withdrawal of inhaled corticosteroids from COPD patients with mild or moderate airflow limitation in primary care: feasibility trial reveals high prevalence of suspected undiagnosed asthma

Problem

Higher-dosage inhaled corticosteroids (ICS) are frequently prescribed outside guidelines to COPD patients with mild or moderate airflow limitation (FEV1 (forced expiratory volume in one second) ≥50% predicted) and low exacerbation risk, despite little evidence of benefit and risk of adverse effects.This trial aimed to explore the feasibility of withdrawing higher-dosage ICS therapy from eligible COPD patients with mild or moderate airflow limitation in primary care.

Approach

This was an open, feasibility trial in primary care. Outcome measures included the prevalence of suitable participants, the accuracy of their identification and their willingness to accept open randomisation to discontinue ICS therapy for up to six months with monitoring at baseline, three and six months.

Findings

392 (13%) of 2967 COPD patients from 20 primary care practices (209,618 total population) were identified as potentially eligible for ICS withdrawal by algorithm search of electronic records. Following individual record review, 243 (62%) of these were deemed ineligible because of (a) one severe or two moderate COPD exacerbations in the previous year (86, 22%); (b) severe airflow limitation (65, 17%); (c) asthma (15, 4%); (d) active cancer, dementia, palliative care, drug or alcohol dependence or being housebound (77, 20%). The remainder (149) were invited for assessment. 61 attended and all agreed to randomisation to ICS withdrawal or usual care. At baseline assessment, 10 exhibited significant reversibility at spirometry testing (FEV1 reversibility >12% and 200ml) which was a safety exclusion criterion, 2 had suffered two or more moderate COPD exacerbations, identifiable at interview only, in the prior year, 7 had severe airflow limitation and 2 had normal spirometry. 40 were randomised. Over the ensuing 6 months, 1 patient died of a cause unrelated to the study and another was lost to follow up. 18 (45%) of the 38 (10 withdrawal, 8 usual care) exhibited previously undocumented evidence of FEV1 variability consistent with asthma. This was supported by significant associations in the ICS withdrawal group between FEV1 variability and elevated fractional exhaled nitric oxide (FeNO) (p=0.04), history of atopy (p=0.01), elevated symptom score (p=0.04) and poorer quality of life (p=0.04).

Consequences

Open, randomised allocation of eligible patients to withdrawal of ICS therapy or usual care was acceptable. Retention at follow-up for 6 months was excellent. Identification of COPD patients with mild or moderate airflow limitation suitable for a trial of withdrawal of higher-dosage ICS therapy was difficult because of poor recording of suitability criteria (undocumented exacerbations and unreliable lung function). Nearly 50% of eligible participants with no previously recorded evidence of bronchodilator reversibility or past history of asthma demonstrated FEV1 variability suggestive of it. Primary care teams should be aware of the possibility of previously undiagnosed asthma being uncovered in significant numbers of COPD patients whose treatment is reviewed.