Changes in cardiopulmonary exercise capacity and limitations 3-12 months after COVID-19.

RATIONALE: To describe cardiopulmonary function during exercise 12 months after hospital discharge for coronavirus disease 2019 (COVID-19), assess the change from 3 to 12 months, and compare the results with matched controls without COVID-19. METHODS: In this prospective, longitudinal, multicentre cohort study, hospitalised COVID-19 patients were examined using a cardiopulmonary exercise test (CPET) 3 and 12 months after discharge. At 3 months, 180 performed a successful CPET, and 177 did so at 12 months (mean age 59.3 years, 85 females). The COVID-19 patients were compared with controls without COVID-19 matched for age, sex, body mass index and comorbidity. Main outcome was peak oxygen uptake (V'O2  peak). RESULTS: Exercise intolerance (V'O2  peak <80% predicted) was observed in 23% of patients at 12 months, related to circulatory (28%), ventilatory (17%) and other limitations including deconditioning and dysfunctional breathing (55%). Estimated mean difference between 3 and 12 months showed significant increases in V'O2  peak % pred (5.0 percentage points (pp), 95% CI 3.1-6.9 pp; p<0.001), V'O2  peak·kg-1 % pred (3.4 pp, 95% CI 1.6-5.1 pp; p<0.001) and oxygen pulse % pred (4.6 pp, 95% CI 2.5-6.8 pp; p<0.001). V'O2  peak was 2440 mL·min-1 in COVID-19 patients compared to 2972 mL·min-1 in matched controls. CONCLUSIONS: 1 year after hospital discharge for COVID-19, the majority (77%), had normal exercise capacity. Only every fourth had exercise intolerance and in these circulatory limiting factors were more common than ventilator factors. Deconditioning was common. V'O2  peak and oxygen pulse improved significantly from 3 months.

Cardiopulmonary exercise capacity and limitations 3†months after COVID-19 hospitalisation.

BACKGROUND: This study aimed to describe cardiopulmonary function during exercise 3 months after hospital discharge for COVID-19 and compare groups according to dyspnoea and intensive care unit (ICU) stay. METHODS: Participants with COVID-19 discharged from five large Norwegian hospitals were consecutively invited to a multicentre, prospective cohort study. In total, 156 participants (mean age 56.2 years, 60 females) were examined with a cardiopulmonary exercise test (CPET) 3 months after discharge and compared with a reference population. Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. RESULTS: Peak oxygen uptake (V'O2  peak) <80% predicted was observed in 31% (n=49). Ventilatory efficiency was reduced in 15% (n=24), while breathing reserve <15% was observed in 16% (n=25). Oxygen pulse <80% predicted was found in 18% (n=28). Dyspnoea (mMRC ≥1) was reported by 47% (n=59). These participants had similar V'O2  peak (p=0.10) but lower mean±sd V'O2  peak·kg-1 % predicted compared with participants without dyspnoea (mMRC 0) (76±16% versus 89±18%; p=0.009) due to higher body mass index (p=0.03). For ICU- versus non-ICU-treated participants, mean±sd V'O2  peak % predicted was 82±15% and 90±17% (p=0.004), respectively. Ventilation, breathing reserve and ventilatory efficiency were similar between the ICU and non-ICU groups. CONCLUSIONS: One-third of participants experienced V'O2  peak <80% predicted 3 months after hospital discharge for COVID-19. Dyspnoeic participants were characterised by lower exercise capacity due to obesity and lower ventilatory efficiency. Ventilation and ventilatory efficiency were similar between ICU- and non-ICU-treated participants.

Lung function and peak oxygen uptake in chronic obstructive pulmonary disease phenotypes with and without emphysema.

Previous studies of associations of forced expiratory lung volume in one second (FEV1) with peak oxygen uptake (VO2peak) in chronic obstructive pulmonary disease (COPD) have not taken sex, age and height related variance of dynamic lung volumes into account. Nor have such demographic spread of spirometric measures been considered in studies comparing VO2peak between COPD phenotypes characterized by degree of emphysema. We aimed to assess the association of FEV1Z-score with VO2peak in COPD (n = 186) and investigate whether this association differs between emphysema (E-COPD) and non-emphysema (NE-COPD) phenotypes. Corresponding assessments using standardized percent predicted FEV1 (ppFEV1) were performed for comparison. Additionally, phenotype related differences in VO2peak were compared using FEV1Z-score and ppFEV1 as alternative expressions of FEV1. E-COPD and NE-COPD were defined by transfer factor of the lung for carbon monoxide below and above lower limits of normal (LLN), respectively. The associations were assessed in linear regression models. One unit reduction in FEV1Z-score was associated with 1.9 (95% CI 1.4, 2.5) ml/kg/min lower VO2peak. In stratified analyses, corresponding estimates were 2.2 (95% CI 1.4, 2.9) and 1.2 (95% CI 0.2, 2.2) ml/kg/min lower VO2peak in E-COPD and NE-COPD, respectively. The association did not differ statistically by COPD phenotype (p-value for interaction = 0.153). Similar estimates were obtained in analyses using standardized ppFEV1. Compared to NE-COPD, VO2peak was 2.2 (95% CI 0.8, 3.6) and 2.1 (95% CI 0.8, 3.5) ml/kg/min lower in E-COPD when adjusted for FEV1Z-score and ppFEV1, respectively. In COPD, FEV1Z-score is positively associated with VO2peak. This association was stronger in E-COPD but did not differ statistically by phenotype. Both the association of FEV1 with VO2peak and the difference in VO2peak comparing COPD phenotypes seems independent of sex, age and height related variance in FEV1. Mechanisms leading to reduction in FEV1 may contribute to lower VO2peak in E-COPD.

The association between normal lung function and peak oxygen uptake in patients with exercise intolerance and coronary artery disease.

In coronary artery disease (CAD), exercise intolerance with reduced oxygen uptake at peak exercise (VO2peak) is assumed to primarily reflect cardiovascular limitation. However, oxygen transport and utilization depends on an integrated organ response, to which the normal pulmonary system may influence overall capacity. This study aimed to investigate the associations between normal values of lung function measures and VO2peak in patients with exercise intolerance and CAD. We hypothesized that forced expiratory lung volume in one second (FEV1), transfer factor of the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA) above lower limits of normal (LLN) are associated with VO2peak in these patients. We assessed patients with established CAD (n = 93; 21 women) referred for evaluation due to exercise intolerance from primary care to a private specialist clinic in Norway. Lung function tests and cardiopulmonary exercise testing (CPET) were performed. Z-scores of FEV1, FEV1/forced vital capacity (FVC), TLCO and TLCO/VA were calculated using the Global Lung Function Initiative (GLI) software and LLN was defined as the fifth percentile (z = -1.645). Non-obstructive patients, defined by both FEV1 and FEV1/FVC above LLN, were assessed. The associations of FEV1Z-score, TLCOZ-score and TLCO/VAZ-score above LLN with VO2peak were investigated using linear regression models. Mean VO2peak ± standard deviation (SD) was 23.8 ± 6.4 ml/kg/min in men and 19.7 ± 4.4 ml/kg/min in women. On average, one SD increase in FEV1, TLCO and TLCO/VA were associated with 1.4 (95% CI 0.2, 2.6), 2.6 (95% CI 1.2, 4.0) and 1.3 (95% CI 0.2, 2.5) ml/kg/min higher VO2peak, respectively. In non-obstructive patients with exercise intolerance and CAD, FEV1, TLCO and TLCO/VA above LLN are positively associated with VO2peak. This may imply a clinically significant influence of normal lung function on exercise capacity in these patients.

Comparison of Mitochondrial Respiration in M. triceps brachii and M. vastus lateralis Between Elite Cross-Country Skiers and Physically Active Controls.

RATIONALE: The main purposes of this study were to compare mitochondrial respiration in M. triceps brachii and M. vastus lateralis between elite cross-country (XC) skiers and physically active controls (CON), and to explore the associations between mitochondrial respiration in these muscles and peak oxygen uptake ( V ˙ O2peak) in arm- and leg-dominant exercise modes. METHODS: Thirteen male elite XC skiers (age: 25 ± 4; peak oxygen uptake ( V ˙ O2peak): 75.5 ± 4.2 mL⋅kg-1⋅min-1) and twelve CON (age: 26 ± 3; V ˙ O2peak: 57.2 ± 6.4 mL⋅kg-1⋅min-1) had microbiopsies taken from M. vastus lateralis and M. triceps brachii, which were analyzed for various measures of mitochondrial respiration using high-resolution respirometry. Thereafter, all participants tested V ˙ O2peak in both running (RUN) and upper body poling (UBP). RESULTS: XC skiers had generally higher mitochondrial respiration in M. triceps brachii compared to CON (P < 0.001), whereas no significant group-differences in mitochondrial respiration in M. vastus lateralis were revealed. XC skiers had higher mitochondrial respiration in M. triceps brachii compared to M. vastus lateralis (P = 0.005-0.058), whereas in CON, most mitochondrial respiration measures were higher in M. vastus lateralis than in M. triceps brachii (P < 0.01). When all athletes were pooled, there was a strong positive correlation between V ˙ O2peak in UBP and mitochondrial respiration in M. triceps brachii on several measures (P < 0.01), whereas no correlation was found for RUN. CONCLUSION: The higher mitochondrial respiration found in M. triceps brachii compared to M. vastus lateralis among our elite XC skiers demonstrates the potential for the arm muscles to adapt to aerobic endurance training. The opposite pattern found in CON, clearly showed lower mitochondrial respiration in M. triceps brachii compared to XC skiers, whereas respiration in M. vastus lateralis did not differ between groups. The strong positive correlation between mitochondrial respiration in M. triceps brachii and V ˙ O2peak in UBP indicate that arm muscles' respiratory function may be a limiting factor for V ˙ O2peak in arm-dominant exercise modes.

The association between dynamic lung volume and peak oxygen uptake in a healthy general population: the HUNT study.

BACKGROUND: Although dynamic lung volume is not considered a limiting factor of peak oxygen uptake (VO2peak) in healthy subjects, an association between forced expiratory lung volume in one second (FEV1) and VO2peak has been reported in a healthy population aged 69 - 77 years. We hypothesized that a corresponding association could be found in a healthy general population including young and middle-aged subjects. METHODS: In a population-based study in Norway, we investigated the association between FEV1 above the lower limit of normal (LLN) and VO2peak using linear regression and assessed the ventilatory reserve (VR) in healthy subjects aged 20 - 79 years (n = 741). RESULTS: On average, one standard deviation (SD) increase in FEV1 was associated with 1.2 ml/kg/min (95% CI 0.7 - 1.6) higher VO2peak. The association did not differ statistically by sex (p-value for interaction = 0.16) and was similar (0.9 ml/kg/min, 95% CI 0.2 - 1.5) in a sensitivity analysis including only never-smokers (n = 376). In subjects below and above 45 years of age, corresponding estimates were 1.2 ml/kg/min (95% CI 0.5 - 1.8) and 1.2 ml/kg/min (95% CI 0.5 - 1.9), respectively. Preserved VR (≥ 20%) was observed in 66.6% of men and 86.4% of women. CONCLUSIONS: Normal dynamic lung volume, defined as FEV1 above LLN, was positively associated with VO2peak in both men and women, in never-smokers and in subjects below and above 45 years of age. The majority of subjects had preserved VR, and the results suggest that FEV1 within normal limits may influence VO2peak in healthy subjects even when no ventilatory limitation to exercise is evident.