Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis and the role of biomarkers.

Abstract

Idiopathic pulmonary fibrosis (IPF) patients report fatigue, possibly reflecting sleep disturbance, but little is known about sleep-related changes. We compared ventilation and gas exchange during sleep and exercise in a cohort of IPF patients, and evaluated associations with selected biological markers. Twenty stable IPF patients (aged 67.9 ± 12.3 [SD]) underwent overnight polysomnography following an acclimatization night. Cardiopulmonary exercise testing was performed and inflammatory markers measured including TNF-α, IL-6, CXCL8, C-C motif ligand 18 (CCL-18) and C-reactive protein (CRP) RESULTS: Nine patients had sleep-disordered breathing (SDB) with an apnea-hypopnea frequency (AHI) ≥ 5/h, but only two had Epworth sleepiness score ≥ 10, thus having an obstructive sleep apnea syndrome. Sleep quality was poor. Transcutaneous carbon dioxide tension (PtcCO2) rose by 2.56 ± 1.59 kPa overnight (P = 0.001), suggesting hypoventilation. Oxygen saturation (SaO2) was lower during sleep than exercise (P < 0.01), and exercise variables correlated with resting pulmonary function. CCL-18 and CRP levels were elevated and correlated with PtcCO2 rise during sleep (P < 0.05). CCL-18 negatively correlated with diffusion capacity of carbon monoxide (DLCO), arterial oxygen (PaO2) and mean arterial carbon dioxide (PaCO2) (P < 0.05) and CRP negatively correlated with DLCO, PaO2, sleep SaO2 and oxygen uptake (VO2) during exercise (P < 0.05). IPF patients desaturate more during sleep than exercise; thus, nocturnal pulse oxymetry could be included in clinical assessment. CCL-18 and CRP levels correlate with physiological markers of fibrosis.