Adverse Outcomes Associated With Inhaled Corticosteroid Use in Individuals With Chronic Obstructive Pulmonary Disease

Dear Editor,

We have read with great interest the recent article by Pace et al. (1) addressing the adverse outcomes associated with long-term inhaled corticosteroid (ICS) use in patients with chronic obstructive pulmonary disease (COPD). Their findings, derived from extensive electronic health record data, offer robust evidence about the increased risk of serious long-term complications, including diabetes mellitus type 2, cataracts, osteoporosis, pneumonia, and non-traumatic fractures. As family physician researchers from Spain, we would like to reflect on the implications of these well-known findings from the perspective of primary care practice and existing clinical guidelines, particularly focusing on the Spanish National Guideline (2).

In Spain, GesEPOC provides specific criteria for initiating and maintaining ICS treatment in COPD, emphasizing the use of ICS only in patients who experience frequent exacerbations (≥2 exacerbations per year or one hospitalization due to COPD exacerbation), particularly those with high blood eosinophil counts (>300 cells/µL), or with clinical features suggesting asthma-COPD overlap syndrome (3). Despite these clear indications, we frequently observe in daily practice that ICS prescriptions are more generalized and sometimes do not strictly follow these evidence-based recommendations. This discrepancy may partly arise from therapeutic inertia or a lack of updated knowledge among clinicians regarding ICS indications.

The results presented by Pace et al. strongly reinforce the necessity for primary care professionals to adhere closely to current guidelines, highlighting that non-indicated ICS treatments might be causing preventable harm. Their research methodology, including a rigorous propensity matching and clear delineation of long-term vs. short-term ICS exposure, lends considerable strength and validity to their conclusions, thus underlining the urgency of reevaluating ICS use in our clinical practice.

In our experience, another critical barrier in appropriately prescribing ICS according to guidelines is the limited access to certain clinical parameters, notably eosinophil counts, in primary care settings in Spain. While GesEPOC clearly stipulates the need for eosinophil counts to stratify treatment (3), such data are often unavailable or inconsistently measured in routine practice, making accurate clinical decisions challenging. Enhancing the accessibility and routine inclusion of eosinophil counts in primary care settings could significantly align clinical practice with guideline recommendations, potentially reducing unnecessary ICS exposure and associated risks.

Another aspect worth emphasizing is the importance of regularly reviewing and reassessing COPD management strategies. Pace et al. demonstrate clearly that prolonged ICS use, beyond two years, significantly elevates the risk of adverse outcomes. Consistent with GesEPOC's recommendation for periodic reassessment of treatment efficacy and safety, we argue for the systematic implementation of structured reviews at the primary care level, ideally annually. Such reviews would allow clinicians to withdraw unnecessary ICS therapy safely, particularly in patients with stable COPD without exacerbations and without significant eosinophilia. Recent studies such as the WISDOM trial (4) support safe ICS withdrawal in appropriately selected patients, further advocating for the necessity of routine medication reassessment.

The role of primary care nurses also emerges as a critical element in managing COPD treatments effectively. Nursing professionals in Spanish primary care often assume responsibility for patient education, including inhaler technique and medication adherence assessments. Strengthening nursing roles through dedicated respiratory training could enhance early detection of inappropriate ICS use, improve inhalation techniques, and reinforce patient self-management practices. Evidence consistently shows that structured nurse-led interventions significantly improve COPD outcomes (5), suggesting this as an effective strategy to minimize long-term ICS exposure risks.

Moreover, coordination between primary and specialist care, specifically pulmonology services, needs improvement. Frequently, ICS therapy initiated in specialized settings continues indefinitely upon the patient's return to primary care, often without a clear reassessment plan. Enhanced communication channels and shared decision-making protocols between primary care and pulmonology departments could optimize COPD management, preventing prolonged unnecessary ICS exposure and thereby reducing the adverse outcomes identified by Pace et al.

We also wish to highlight the ethical considerations regarding patient safety in prescribing ICS. As physicians, we have an ethical duty to minimize harm; thus, we must carefully weigh the benefits and risks of prolonged ICS use, particularly in the context of multimorbidity frequently encountered in elderly COPD patients. The findings of Pace et al. offer compelling evidence that, without clear indication, ICS therapy contributes to avoidable chronic conditions like diabetes and osteoporosis, thus raising significant ethical and safety concerns.

Finally, differences between the recommendations of GesEPOC and international guidelines such as the Global Initiative for Chronic Obstructive Lung Disease (6), could introduce confusion and inconsistency in clinical decisions. GOLD recommendations are broadly consistent with GesEPOC but differ slightly in treatment algorithms and patient stratification details. Clarifying these discrepancies through consensus documents or joint guidelines could substantially enhance clinical decision-making confidence among primary care providers, promoting safer and more appropriate ICS use.

In conclusion, we sincerely thank Pace and colleagues for highlighting critical evidence concerning ICS-associated risks in COPD. Their robust methodology and clear outcomes strongly align with our practical observations and challenges in primary care. Reinforcing adherence to current guidelines, enhancing nurse involvement, improving diagnostic parameter accessibility, fostering primary-specialist collaboration, and addressing ethical implications in COPD management represent actionable strategies to translate these findings into safer, evidence-based clinical practice.

REFERENCES:

1. Pace WD, Callen E, Gaona-Villarreal G, Shaikh A, Yawn BP. Adverse Outcomes Associated With Inhaled Corticosteroid Use in Individuals With Chronic Obstructive Pulmonary Disease. Ann Fam Med. 2025 Mar 1;23(2):127–35.

2. Sociedad Española de Neumología y Cirugía Torácica. Actualización 2021 de la Guía Española de la EPOC (GesEPOC). [cited 2025 Apr 17]. GUÍA Española de la EPOC (GesEPOC). Available from: https://gesepocsepar.com/#contenido

3. Miravitlles M, Calle M, Molina J, Almagro P, Gómez JT, Trigueros JA, et al. Actualización 2021 de la Guía Española de la EPOC (GesEPOC). Tratamiento farmacológico de la EPOC estable. Arch Bronconeumol. 2022 Jan 1;58(1):69–81.

4. Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, et al. Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD. N Engl J Med. 2014 Oct 2;371(14):1285–94.

5. Jolly K, Sidhu MS, Bates E, Majothi S, Sitch A, Bayliss S, et al. Systematic review of the effectiveness of community-based self-management interventions among primary care COPD patients. Npj Prim Care Respir Med. 2018 Nov 23;28(1):1–8.

6. Sharma M, Joshi S, Banjade P, Ghamande SA, Surani S. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines Reviewed. [cited 2025 Apr 17]; Available from: https://openrespiratorymedicinejournal.com/VOLUME/18/ELOCATOR/e187430642...