Search

Background and objective: The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory efficiency (increased ventilatory requirement for CO2 clearance [V˙E/V˙CO2]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DLCO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. Methods: In this retrospective analysis, we compared V˙E/V˙CO2, dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DLCO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the

ABSTRACT Background and objective Frailty is the age-related accumulation of deficits that decrease the ability to respond to biological stress. Patients with fibrotic interstitial lung disease ( ILD) may be frail due to consequences of ILD, age, co-morbidities and adverse effects of pharmacotherapies. The objective of this study was to examine the prevalence and predictors of frailty in fibrotic ILD. Methods Fibrotic ILD patients were recruited from a specialized clinic. Patients with ILD secondary to a systemic disease were excluded. Frailty was determined using the Frailty Index based on the presence or absence of multiple deficits, including co-morbidities, symptoms and functional limitations. The Frailty Index was based on the proportion of deficits present, with frailty defined as a score >0.21. Cronbach's alpha was used to estimate the internal consistency of the Frailty Index. Dyspnoea was measured using the University of California San Diego Shortness of Breath Questionnaire. Multivariate analysis was used to determine independent predictors of frailty. Results The definition of frailty was met in 50% of the 129 patients. Cronbach's alpha for the Frailty Index was 0.87. The Frailty Index was associated with forced vital capacity ( FVC), forced expiratory volume in 1 s ( FEV1 ), diffusion capacity of the lung for carbon monoxide ( DLCO ), ILD-gender, age and physiology ( GAP) index, composite physiologic index and dyspnoea score. Dyspnoea severity was the strongest unadjusted predictor (r = 0.65, P < 0.001) and only independent predictor of the Frailty Index (0.034 increase in Frailty Index per 10-point increase in dyspnoea score; R2 = 0.37; P < 0.001). Conclusion Frailty is highly prevalent and is strongly and independently associated with dyspnoea severity, demonstrating that dyspnoea is a more important determinant of frailty than pulmonary function. [ABSTRACT FROM AUTHOR]

• Resting lung function tests underestimate physiologic impairment during exercise in interstitial lung disease. • Exertional dyspnea in interstitial lung disease is highly correlated with increased inspiratory neural drive. • Inhaled nebulized fentanyl did not reduced dyspnea or inspiratory neural drive compared to placebo. • Novel treatments for exertional dyspnea in interstitial lung disease are needed. Exertional dyspnea in interstitial lung disease (ILD) remains difficult to manage despite advances in disease-targeted therapies. Pulmonary opioid receptors present a potential therapeutic target for nebulized fentanyl to provide dyspnea relief. ILD patients were characterized with reference to healthy volunteers. A randomized, double-blind, placebo-controlled crossover comparison of 100 mcg nebulized fentanyl vs placebo on dyspnea intensity and inspiratory neural drive (IND) during constant work rate (CWR) cycle exercise was performed in 21 ILD patients. Dyspnea intensity in ILD increased in association with an increase in IND (diaphragm activation) from a high resting value of 16.66 ± 6.52 %–60.04 ± 12.52 % of maximum (r = 0.798, p < 0.001). At isotime during CWR exercise, Borg dyspnea intensity ratings with fentanyl vs placebo were 4.1 ± 1.2 vs 3.8 ± 1.2, respectively (p = 0.174), and IND responses were also similar. IND rose sharply during constant work rate exercise in association with dyspnea intensity in mild to moderate ILD but was not different after nebulized fentanyl compared with placebo. [ABSTRACT FROM AUTHOR]

Fatigue is a common, debilitating, and poorly understood symptom post-COVID-19. We sought to better characterize differences in those with and without post-COVID-19 fatigue using cardiopulmonary exercise testing. Despite elevated dyspnoea intensity ratings, V̇O 2 peak (ml/kg/min) was the only significant difference in the physiological responses to exercise (19.9 ± 7.1 fatigue vs. 24.4 ± 6.7 ml/kg/min non-fatigue, p = 0.04). Consistent with previous findings, we also observed a higher psychological burden in those with fatigue in the context of similar resting cardiopulmonary function. Our findings suggest that lower cardiorespiratory fitness and/or psychological factors may contribute to post-COVID-19 fatigue symptomology. Further research is needed for rehabilitation and symptom management following SARS-CoV-2 infection. • Peak ⩒O 2 (ml/kg/min) is lower in survivors with post-COVID-19 fatigue vs. without. • Dyspnoea is elevated during exercise in COVID-19 survivors with fatigue vs. without. • Higher psychological burden may contribute to post-COVID-19 fatigue symptomology. [ABSTRACT FROM AUTHOR]

The functional disturbances driving "out-of-proportion" dyspnoea in patients with fibrosing interstitial lung disease (f -ILD) showing only mild restrictive abnormalities remain poorly understood. Eighteen patients (10 with idiopathic pulmonary fibrosis) showing preserved spirometry and mildly reduced total lung capacity (≥70% predicted) and 18 controls underwent an incremental cardiopulmonary exercise test with measurements of operating lung volumes and Borg dyspnoea scores. Patients' lower exercise tolerance was associated with higher ventilation (V̇ E)/carbon dioxide (V̇CO 2) compared with controls (V̇ E /V̇CO 2 nadir=35 ± 3 versus 29 ± 2; p < 0.001). Patients showed higher tidal volume/inspiratory capacity and lower inspiratory reserve volume at a given exercise intensity, reporting higher dyspnoea scores as a function of both work rate and V̇ E. Steeper dyspnoea-work rate slopes were associated with lower lung diffusing capacity, higher V̇ E /V̇CO 2 , and lower peak O 2 uptake (p < 0.05). Heightened ventilatory demands in the setting of progressively lower capacity for tidal volume expansion on exertion largely explain higher-than-expected dyspnoea in f -ILD patients with largely preserved dynamic and "static" lung volumes at rest. • The physiological abnormalities driving "out-of-proportion" dyspnea in mild f -ILD remain unclear. • Despite normal spirometry and total lung capacity typically above 70% predicted, patients showed moderate impairment in DL CO • Exertional dyspnea was related to heightened ventilatory demands and progressively lower capacity for tidal volume expansion • Exertional dyspnea and exercise intolerance were associated with lower DL CO , excess ventilation, and inspiratory constraints • These findings can causally link mild f -ILD to "out-of-proportion" dyspnoea, exposing potential therapeutic targets [ABSTRACT FROM AUTHOR]