Abstract and Introduction
Abstract
Background: It is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF.
Methods: We used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007 to 2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date.
Results: Out of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24–0.75), p = 0.003) and all-cause mortality (HR 0.49, 95% CI 0.30–0.80), p = 0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with > = 1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15–0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19–0.94) in the year prior to the index date, which reflect sicker subgroups of persons.
Conclusions: Undergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.
Introduction
Idiopathic pulmonary fibrosis (IPF) is the most common fibrotic lung disease and its prevalence may be increasing.[1,2] IPF is generally a progressive disease, with a median survival from diagnosis of 2–3 years.[3,4] Acute respiratory deteriorations occur in IPF, due to a known cause (like respiratory tract infection) or due to an unknown cause (termed ‘acute exacerbations’).[3,4] Acute exacerbations are the leading cause of hospitalization in IPF.[5,6] Recently introduced anti-fibrotic drug therapies for IPF are successful in slowing disease progression, but are not curative.[7,8] Although lung transplantation is a definite treatment for IPF, availability is limited to a small percentage of individuals due to limited organ supply.[9]
Sleep breathing disorders, including obstructive sleep apnea (OSA)[10–16] and sustained nocturnal hypoxemia,[11,17] are commonly encountered in IPF. In advanced IPF, hypoventilation may also occur, but the prevalence of this sleep breathing disorder in IPF is not well-known. Untreated sleep breathing disorders may worsen IPF through several mechanisms. First, chronic, intermittent hypoxemia has been shown in animal models to promote pulmonary fibrosis through oxidative and inflammatory pathways.[18,19] Second, repetitive forced inspirations against a closed glottis, which occurs in OSA, may cause recurrent tractional injury to peripheral lung tissue, which may in turn promote pulmonary fibrosis.[20] Third, gastroesophageal reflux, which can be induced by OSA,[21] may lead to the development or progression of IPF.[22,23] Finally, untreated OSA may contribute to complications of pulmonary arterial hypertension,[24] the presence of which is associated with increased mortality in IPF.[25] Although sleep breathing disorders may theoretically worsen IPF, there is a paucity of published literature on whether diagnosing and treating sleep breathing disorders in the setting of IPF influences health outcomes. Two small, observational studies involving individuals with newly-diagnosed IPF and moderate-to-severe OSA showed that those adherent with positive airway pressure (PAP) therapy had significantly better survival than those that were non-adherent,[14,15] but that there was no improvement in exacerbations necessitating hospitalization.[14] A final observational study involving individuals with a variety of forms of interstitial lung disease (only 32.5% of whom had IPF) found no improvement in all-cause mortality or progression-free survival among those with OSA versus no OSA, nor among those with OSA adherent with PAP compared to those with OSA and not using PAP.[26] However, in the subset of individuals with interstitial lung disease requiring supplemental oxygen, adherence to PAP therapy for OSA was associated with significantly better progression-free survival.[26] The need for further research to clarify the importance of diagnosing and treating sleep breathing disorders in IPF has been advocated by international IPF guidelines.[3]
In Ontario, Canada, sleep breathing disorders are diagnosed solely via laboratory-based polysomnography (PSG), with testing mandated prior to the initiation of appropriate treatments. Therefore, we considered PSG receipt a surrogate marker for the diagnosis and treatment of sleep breathing disorder for the purposes of this study. The objective of our study was to evaluate the association between receipt of PSG and respiratory-related hospitalization and mortality among individuals with IPF. Our hypothesis was that individuals with IPF that undergo PSG (a proxy marker for the diagnosis and treatment of sleep breathing disorder) will have reduced respiratory-related hospitalization and mortality than those that do not undergo such testing. Our work was intended to be hypothesis-generating.