The Association of Exhaled Nitric Oxide Level With Respiratory Muscle Strength, Pulmonary Function, Exercise Capacity, Sleep Quality, Functional Status, and Health-Related Quality of Life in Patients With Pulmonary Arterial Hypertension

Abstract

Abstract RATIONALE: Considering that nitric oxide is a significant pathophysiological mediator of pulmonary hypertension for maintaining vascular health, the aim of this study was to investigate the relationship between fractional exhaled nitric oxide (FENO) level and respiratory muscle strength, pulmonary function, exercise capacity, sleep quality, functional status, and health-related quality of life (HRQoL) in patients with pulmonary arterial hypertension (PAH). METHODS: Clinically and hemodynamically stable 48 PAH patients (idiopathic n=22, associated with congenital heart disease n=26) under PAH-specific therapy for a minimum of 3 months, between the ages 20-74 (mean [SD] age: 48.4 [12.1] years) and with the World Health Organization (WHO) functional class I to III participated in the study. Online measurement of FENO was performed using a portable electrochemical analyzer, with a constant expiratory flow rate of 0.05 L/second. Respiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) through a mouth pressure meter. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and peak expiratory flow (PEF) values were measured with a spirometer. Exercise capacity was evaluated by measuring 6-minute walk distance (6MWD) with 6-minute walk test. Sleep quality was assessed with Pittsburgh Sleep Quality Index (PSQI). Functional status was determined by using WHO functional classification. HRQoL was assessed with emPHasis-10, a disease-specific questionnaire. Spearman correlation analysis was used for statistical data analyses. RESULTS: Mean FENO level of the patients was 12,4±3,3 parts per billion. There was a statistically significant positive correlation between FENO and MIP (r=,399, p=0,005), MEP (r=,494, p=0,000), FEV1 (r=,407, p=0,004), FVC (r=,435, p=0,002), PEF (r=,322, p=0,026), 6MWD (r=,691, p=0,000). Higher FENO values were also statistically associated with improved WHO functional class (r=-,648, p=0,000), PSQI global score (r=-,703, p=0,000) and emPHasis-10 score (r=-,407, p=0,004). However, no significant correlation was found between FENO level and FEV1/FVC ratio (r=0.121, p=0.411). CONCLUSION: This study, conducted on PAH patients, demonstrated that FENO level was strongly associated with exercise capacity, functional classification, sleep quality and that there was a moderate correlation between FENO level and respiratory muscle strength, HRQoL, and pulmonary function except FEV1/FVC ratio. Therefore, monitoring FENO levels for the evaluation and management of pulmonary hypertension in clinical practice may be useful.