ORIGINAL RESEARCH
Michal Shani, MD, MPH; Sophia Eilat-Tsanani, MD; Doron Comaneshter, PhD; Michael J. Segel, MD
Corresponding Author: Michal Shani, MD, MPH; Department of Family Medicine The Faculty of Medical and Health Sciences, Tel Aviv University; Department of Family Medicine Central District, Clalit Health Service.
Email: michal.shani@gmail.com
DOI: 10.3122/jabfm.2025.250341R1
Keywords: Chronic Obstructive Pulmonary Disease, Inhalers, Israel, Patient Adherence, Primary Health Care, Retrospective Studies
Dates: Submitted: 08-27-2025; Revised: 12-27-2025; Accepted: 02-02-2026
Status: In Press.
BACKGROUND: Inhalers containing bronchodilators and corticosteroids are the cornerstone of COPD pharmacotherapy. Adherence to prescribed medication is critical to successful management. We studied inhaler adherence in a large cohort of COPD patients in Israel, to assess the effect of specific inhaler devices and medications on adherence.
METHODS: We performed a retrospective cohort study in Clalit Health Service (CHS), an HMO serving >50% of the population of Israel. CHS members aged 40-80 years with a diagnosis of COPD, who filled ≥1 prescription/year 2017-2019 (regular users) for at least one inhaler containing long-acting beta-adrenergics (LABA), long-acting anti-muscarinics (LAMA) and/or inhaled corticosteroids (ICS), were included. Filled monthly prescriptions were used as a proxy for actual medication use. The primary endpoint was the proportion of adherent users (purchase of ≥7 inhalers/yr in 2018).
RESULTS: 20,413 COPD patients (age 68.4±7.1 yrs. 58% men, 87% ever smokers) were identified. Of 11,422 regular inhaler purchasers (56% of total), only 6,771 (59%) were adherent. Increasing age, male gender, better socio-economic status and smoking history were significant predictors of good adherence. Good adherence was more common for inhalers including LAMA. There were significant differences in adherence between inhaler devices. Adherence to once-daily inhalers appeared to be better than twice daily inhalers. Patients with good adherence were more likely to experience exacerbations, to be hospitalized and to die.
CONCLUSIONS: Adherence to inhalers in COPD patients was related to drug class, inhaler device and recommended frequency of use. Adherence was associated with worse outcomes, suggesting sicker patients are more adherent.