A recent cross-sectional study examined how nocturnal gastroesophageal reflux disease (GERD) and sleep-disordered breathing (SDB) were associated with patient-reported outcomes and physiologic measures in idiopathic pulmonary fibrosis (IPF).
Although GERD and OSA are recognized comorbidities in IPF, their overlapping effects—particularly during sleep—remain poorly defined. A team of investigators from the University of Wisconsin sought to clarify these relationships by evaluating nocturnal GERD symptoms, polysomnography‑defined sleep abnormalities, and clinical outcomes in a well‑characterized IPF cohort. The results were recently reported in the Canadian Respiratory Journal.1
The exploratory study enrolled 24 adults with IPF receiving stable antifibrotic therapy. Participants completed validated questionnaires, pulmonary function testing, 6‑minute walk distance testing, and overnight in‑laboratory polysomnography. GERD was assessed using documented clinical diagnoses and the Nocturnal Gastroesophageal Reflux Disease Symptom Severity and Impact Questionnaire (N‑GSSIQ).1
“Disentangling the impact of nocturnal GERD from that of OSA is inherently challenging, as GERD and OSA frequently coexist, and daytime symptoms such as cough and fatigue are also common manifestations of IPF,” said Mihaela Teodorescu, MD, Professor of Medicine, University of Wisconsin (UW) School of Medicine and Public Health.
Despite this overlap, the study revealed a distinct divergence in the impact of these conditions.
The findings suggest that nocturnal GERD is an important correlate of patient‑reported outcomes, said Dr. Teodorescu, speaking on behalf of her UW team, including Stephen Halliday, MD, a pulmonologist at UW Health and Associate Professor of Medicine, UW School of Medicine and Public Health; and Braden Ellis, a UW honorary fellow and medical student at Tulane University.
“Higher N‑GSSIQ scores, reflecting greater nocturnal GERD severity, were associated with increased daytime fatigue, impaired sleep quality, diminished social and emotional functioning, and greater pain burden,” she said.
In contrast, OSA severity was more closely linked to objective physiologic impairment.
“Although OSA did not consistently correlate with subjective fatigue in our cohort, it was significantly associated with impaired gas exchange and reduced exercise capacity, as measured by 6‑minute walk distance,” Dr. Teodorescu said.
These findings suggest that GERD and OSA were associated with different dimensions of IPF morbidity.
Clinically diagnosed GERD was present in 71% of participants, nearly all of whom were receiving acid‑suppressive therapy. Nevertheless, N‑GSSIQ scores revealed substantial residual nocturnal GERD burden. Although a GERD diagnosis alone was not associated with worse symptoms or pulmonary physiology, higher nocturnal symptom scores were consistently linked to worse patient‑reported outcomes.
“What was unexpected, however, was the residual nocturnal GERD burden and its association with periodic limb movement and sleep disturbance—an effect that differs from the traditional symptom pattern attributed to acid reflux alone,” Ellis said. “These findings raise the possibility that the residual reflux may potentially be nonacidic in nature and impact sleep differently. Further investigation using advanced diagnostic modalities is needed to better characterize the nature of residual nocturnal reflux, clarify its impact on sleep, and determine whether it influences IPF progression.”
Polysomnography demonstrated substantial sleep disruption across the cohort, including reduced sleep efficiency and altered sleep architecture. GERD was associated with these abnormalities. Patients with GERD exhibited more stage N2 sleep, less rapid eye movement sleep, and a higher periodic limb movement index (PLMI). Increasing nocturnal GERD severity correlated with higher PLMI.
“The only polysomnographic correlate we identified was a higher PLMI, raising the possibility that nocturnal GERD-related discomfort or, alternatively, the effects of GERD therapy on iron absorption may contribute to periodic limb movements and subsequent sleep disruption,” Dr. Teodorescu said, observing an association previously described in the general population.
Sleep‑disordered breathing was strikingly prevalent. Based on the apnea-hypopnea index (AHI), 79% of participants met the criteria for OSA, with most cases being moderate to severe. More than half had not been previously diagnosed.
“Awareness among both providers and patients of the high prevalence of OSA and IPF overlap, coupled with early recognition, represents the critical first step,” Dr. Teodorescu said, given the potential association with worse physiology.
Unlike in the general population, commonly used OSA screening questionnaires may perform poorly in IPF because these symptoms are multifactorial, arising from the underlying lung disease itself, comorbid GERD, mood disorders, and other contributors independent of OSA, she added.
The authors also noted that defining OSA based on AHI alone and relying on home testing methodologies may underestimate disease burden in this population.
“From our perspective, the first and most promising intervention is increased recognition of the impacts of GERD and OSA on [quality of life and physiology for patients with IPF],” Dr. Halliday said. While CPAP remains the first‑line therapy for OSA and symptomatic GERD is often treated with acid-suppressive therapy, the investigators highlighted the need to explore additional strategies, including treatments for nonacid reflux and alternatives to CPAP such as mandibular advancement or nerve stimulation.
Together, the findings support thorough evaluation of sleep‑related comorbidities in IPF to identify potentially modifiable contributors to symptoms and physiologic impairment that may otherwise be missed.
References
1. Ellis B, Morris D, Peterson A, et al. Gastroesophageal reflux, sleep-disordered breathing, and outcomes in patients with idiopathic pulmonary fibrosis. Can Respir J. 2025;2025:4228567. doi:10.1155/carj/4228567
