Background and objective: In obstructive sleep apnoea (OSA), intermittent hypoxia (IH) compromises immune surveillance through the upregulation of the programmed cell death-1 (PD-1) receptor and its ligand (PD-L1). Because the risk of OSA-related cancer depends on age, we assessed PD-L1/PD-1 expression in middle-aged and older patients with OSA as well as in a murine model. Methods: PD-L1 expression was studied in 41 patients with severe OSA and 40 healthy volunteers (HV), divided into two groups (≤55 and >55 years of age). We used flow cytometry, quantitative PCR (qPCR) and ELISA to determine PD-L1 expression on monocytes and plasma PD-L1 protein levels. Moreover, we analysed PD-L1 expression on an in vivo IH model with old and young mice. Results: In subjects up to 55 years of age, severe OSA increased PD-L1 surface protein and mRNA level expression on monocytes and soluble-PD-L1 protein concentration in plasma compared to HV. PD-L1 and hypoxia-induced factor (HIF)-1α expression correlated with age in HV, whereas in patients with OSA there was a negative relationship. In the mice exposed to IH, PD-L1 expression on F4/80+ splenocytes was also only increased in young animals. HIF-1α expression was significantly higher in patients with OSA than in HV in subjects up to 55 years of age, while PD-L1 expression in monocytes was related to HIF-1α expression in young patients with OSA. Conclusion: PD-L1 upregulation in patients with OSA as a consequence of HIF-1α activation occurs mainly in young patients. In older patients with OSA, upregulation was not detected, possibly due to impaired oxygen sensitivity.
RESULTS
Study subjectsForty-one patients with severe OSA were prospectively recruited, including 21 young patients (age < 55 years)Respirology (2019) 24, 684-692Age-dependent PD-L1 upregulation in OSA † † P < 0.01 versus HV younger than 55 years. ‡ ‡ P < 0.01 versus HV older than 55 years. § § P < 0.05 versus patients with OSA older than 55 years. AHI, apnoea-hypopnoea index; FEV 1 , forced expiratory volume at 1 s; FVC, forced vital capacity; HDL, high-density lipoprotein; HV, healthy volunteer; LDL, low-density lipoprotein; OSA, obstructive sleep apnoea; SpO 2 , oxyhaemoglobin saturation.
IntroductionAir pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis.ObjectiveIn this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.MethodsWe conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home.ResultsThe increase in average values of CO [OR 1.62 (1.11–2.36) and OR 1.84 (1.1–3.06)], NO2 [OR 1.64 (1.01–2.66)], and NOx [OR 1.11 (1–1.23) and OR 1.19 (1.03–1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients.ConclusionAir pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.
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