In patients with fibrotic interstitial lung disease, nocturnal hypoxemia is associated with poor clinical outcomes, according to results of a prospective observational cohort study.
While both obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are known to be common in patients with fibrotic interstitial lung disease (F-ILD), how they affect disease outcomes has remained unclear, Katherine J. Myall, MBChB, and colleagues reported in their published study. They noted that deposition of extracellular matrix within the lung parenchyma found in F-ILD is associated with restrictive lung disease and impaired gas exchange leading to progressive breathlessness and exercise intolerance and ultimately respiratory failure.
Prior research has suggested that sleep architecture is disrupted in F-ILD, with nocturnal desaturations from relative hypoventilation during rapid-eye movement sleep and higher incidence of OSA. While disrupted sleep architecture has been associated with poorer outcomes including worse survival, the relationship between sleep and F-ILD is not well understood, especially whether either total time spent in sleep with hypoxemia or repeated desaturations and arousals seen in OSA might promote disease progression, the researchers wrote.
They conducted a prospective observational cohort study among 102 idiopathic pulmonary fibrosis patients without daytime hypoxemia (74.5% male; age 73.0 years), among whom 91.1% and 31.4% had nocturnal hypoxemia (NH) and obstructive sleep apnea (OSA), respectively. There were no significant differences between those with and without NH or OSA at baseline. The study’s primary outcome measure was change in King’s Brief Interstitial Lung Disease questionnaire (KBILD) at 12 months from baseline. The secondary outcome measures were annualized change in forced vital capacity (FVC), transfer factor for carbon monoxide (TLCO), and mortality at 12 months.
Mortality association?
The analysis showed NH was associated with a more rapid decline in both quality of life (KBILD change –11.3 in the NH group vs. –6.7 in those without NH, P = .005) and higher all-cause mortality at 1 year (hazard ratio [HR], 8.21; 95% confidence interval [CI], 2.40-28.1, P < .001). There was no increased risk of death in patients with OSA compared with those without (HR, 2.78; 95% CI 0.85-9.12, P = .19), and OSA in the absence of NH was not associated with worsening of KBILD scores (P = .30). Analysis of findings did not reveal any relationship between disease severity and sleep characteristics.
“This suggests that the excess mortality demonstrated in earlier studies of patients with OSA may be related to prolonged hypoxemia rather than sleep disruption or the other deleterious physiological effects of OSA, such as sympathetic excitation,” noted Dr. Myall and colleagues. Underscoring that the current study is the first to elucidate the contribution of prolonged NH to disease progression and death in this population, they added that since the central process in the development of idiopathic pulmonary fibrosis is thought to be one of repeated or sustained lung injury, one hypothesis is that prolonged hypoxia of the alveolar epithelium due to prolonged nocturnal hypoxemia may be the source of this insult.
“These data provide support for screening for nocturnal hypoxemia, as well as obstructive sleep apnea in patients with F-ILD to allow early identification of these potentially modifiable conditions. Trials of CPAP and nocturnal oxygen therapy would offer a potential intervention to correct prolonged nocturnal hypoxemia, offering the potential to improve quality of life and survival for patients who otherwise have limited treatment options,” the researchers concluded.
A possible limitations of the study was the fact that patients were offered referral for CPAP therapy, and were used in the analysis only if they elected not to commence therapy. This may have introduced a bias, although there was no statistically significant difference between patients who opted to be referred and those who did not, according to the authors.
Dr. Myall reported having no conflicts of interest to declare.