Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae. METHODS: In this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed. RESULTS: Twelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V'O2) considered within normal limits (median peak predicted O2 uptake (V'O2) of 98% [87.2-106.3]). Length of ICU stay remained an independent predictor of V'O2. More than half of the patients with a normal peak predicted V'O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21-0.32] at anaerobic threshold (AT) and 0.29 [0.25-0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2-44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = - 0.15; p = 0.01). CONCLUSIONS: Twelve months after severe COVID-19 pneumonia, most of the patients had a peak V'O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea. TRIAL REGISTRATION: NCT04519320 (19/08/2020).

Concurrence of 1- and 3-Min Sit-to-Stand Tests with the 6-Min Walk Test in Idiopathic Pulmonary Fibrosis.

BACKGROUND: In idiopathic pulmonary fibrosis (IPF), some physiological parameters measured during a 6-min walk test (6-MWT) impart reliable prognostic information. Sit-to-stand tests (STSTs) are field exercise tests that are easier to implement than the 6-MWT in daily practice. OBJECTIVES: The aims of the study were to test the reproducibility and compare 2 STSTs (the 1-min STST [1-STST] and the semi-paced 3-min chair rise test [3-CRT]) in IPF, and to determine if selected physiological parameters (speed of displacement and changes in pulse oxygen saturation [SpO2]) are interchangeable between the STSTs and the 6-MWT. METHODS: Thirty-three patients with stable IPF were studied in 3 French expert centers. To test reproducibility, intra-class correlations (ICCs) of parameters measured during tests performed 7-14 days apart were calculated. To test interchangeability, the agreement and correlation of physiological responses measured during STSTs and during 6-MWT were studied. RESULTS: Vertical displacements and changes in SpO2 during both STSTs were reproducible, with ICCs ranging from 0.78 [0.63-0.87] to 0.95 [0.92-0.97]. Vertical displacements during 1-STST and 3-CRT were correlated with 6-MWT distance (correlation coefficients (r) of 0.72 and 0.77, respectively; p < 0.001). Similarly, correlations were found between changes in SpO2 measured during the 2 STSTs and the 6-MWT, with coefficients ranging from 0.73 to 0.91 (p < 0.001). Distance walked and SpO2 during 6-MWT were well estimated from vertical displacement and SpO2 during the 2 STSTs, respectively. CONCLUSION: The correlations found between the 2 STSTs and the 6-MWT suggest that STSTs may be of interest to assess displacement and exercise-induced changes in SpO2 in IPF patients.

Cardiorespiratory and Autonomic Nervous System Responses to Prolonged Eccentric Cycling.

Offering large muscle benefits despite low metabolic demand, continuous eccentric exercise appears to be an interesting alternative to concentric exercise. Nevertheless, further knowledge is needed about prolonged eccentric exercise. This work sought to investigate the cardiovascular responses to prolonged constant-load eccentric compared to concentric cycling. Ten healthy males performed two 45-min exercise sessions of either concentric or eccentric cycling separated by a month and matched for heart rate during the first 5 min of exercise. Cardiorespiratory, autonomic nervous system and vascular responses were assessed at rest, and during exercise and recovery. During cycling, oxygen uptake, cardiac output and systolic blood pressure were similar but heart rate and diastolic blood pressure were greater whereas stroke volume was lower during eccentric than concentric cycling (118±21 vs. 104±10 bpm; 77±9 vs. 65±8 mmHg; 122±12 vs. 135±13 mL). Baroreflex and noradrenaline concentration were altered during eccentric cycling, and after eccentric exercise, vascular tone was greater than after concentric cycling. We observed increased cardiovascular strain and altered baroreflex activity during eccentric compared with concentric exercise, suggesting eccentric cycling triggers greater sympathetic activity.

Muscle Oxygenation Responses to Low-intensity Steady Rate Concentric and Eccentric Cycling.

Muscle deoxygenation responses provide information about the training impulse of an exercise session enabling adaptation to be predicted. Our aim was to investigate muscle oxygenation profiles during prolonged low-intensity eccentric and concentric cycling. Twelve healthy men performed two 45-min exercise sessions of concentric (CON) and eccentric (ECC) cycling, matched for the same heart rate at the start of each session. Mechanical power output during ECC was ~2.5 times that of CON (210±40 W vs. 82±16 W). Oxygen uptake, blood lactate, cardiac output and systolic arterial pressure responses did not differ between exercises. Heart rate was similar at 5 min of each exercise bout but progressively increased during ECC and was higher at 15, 30 and 45 min of ECC compared to CON (+10 bpm), with a trend for a lower stroke volume. Diastolic and mean blood pressures were higher during ECC. No significant differences were observed in muscle oxygenation profiles. Muscle oxygenation responses during prolonged low-intensity exercise were not affected by the type of muscle action at the same metabolic demand and cardiac output.

Smoking habits in French farmers: a cross-sectional study.

BACKGROUND: Farmers are exposed to multiple air contaminants that may interact with tobacco smoking in the development of respiratory diseases. Farmers are currently considered to smoke less than non-farmers, but precise data in different categories of age and farming activities are lacking. METHODS: Smoking habits were studied in a cross-sectional study involving 4105 farmers and 996 non-farming controls aged 40-74 years in 9 French departments between October 2012 and May 2013. Three age groups were defined (40-54, 55-64 and 65-74years). Farmers were divided into four activity groups, namely cattle breeders, livestock farmers working in confined spaces, crop farmers and others. Smoking prevalence was compared between farmers and controls, and odds ratios (ORs) for smoking adjusted for age were calculated. RESULTS: The adjusted OR for ever-smoking was lower among farmers than among non-farmers in all age categories, but the ORs for current smoking were similar in farmers and controls. Smoking prevalence varied according to the type of farming activity, and was lower than in non-farming controls only among cattle breeders and confined livestock farmers. In farmers, the proportion of smokers was higher in the youngest age categories compared with the older age classes. CONCLUSIONS: Our results confirm that the prevalence of ever-smokers is lower in farmers than in non-farmers. Nevertheless, our data show that active smoking prevalence is similar in farmers and in non-farmers. This suggests that farmers, just like non-farmers, should be targeted by primary prevention campaigns against smoking.

Effects of long-acting bronchodilators on cardiac autonomic control in COPD.

INTRODUCTION: Several studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting ß2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved. METHODS: We performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial - NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a predictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test). RESULTS: 34 patients attended four visits to receive either tiotropium 18µg, glycopyrronium 44µg, indacaterol 150 µg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate compared to placebo. No significant differences were observed for HRV and BRS between active drugs and placebo in supine position or after passive rising. CONCLUSION: We did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.

Result of one-year, prospective follow-up of intensive care unit survivors after SARS-CoV-2 pneumonia.

INTRODUCTION: Survivors of viral ARDS are at risk of long-term physical, functional and neuropsychological complications resulting from the lung injury itself, but also from potential multiorgan dysfunction, and the long stay in the intensive care unit (ICU). Recovery profiles after severe SARS-CoV-2 pneumonia in intensive care unit survivors have yet to be clearly defined. MATERIAL AND METHODS: The goal of this single-center, prospective, observational study was to systematically evaluate pulmonary and extrapulmonary function at 12 months after a stay in the ICU, in a prospectively identified cohort of patients who survived SARS-CoV-2 pneumonia. Eligible patients were assessed at 3, 6 and 12 months after onset of SARS-CoV-2. Patients underwent physical examination, pulmonary function testing, chest computed tomography (CT) scan, a standardized six-minute walk test with continuous oximetry, overnight home respiratory polygraphy and have completed quality of life questionnaire. The primary endpoint was alteration of the alveolar-capillary barrier compared to reference values as measured by DLCO, at 12 months after onset of SARS-CoV-2 symptoms. RESULTS: In total, 85 patients (median age 68.4 years, (interquartile range [IQR] = 60.1-72.9 years), 78.8% male) participated in the trial. The median length of hospital stay was 44 days (IQR: 20-60) including 17 days in ICU (IQR: 11-26). Pulmonary function tests were completed at 3 months (n = 85), 6 months (n = 80), and 12 months (n = 73) after onset of symptoms. Most patients showed an improvement in DLCO at each timepoint (3, 6, and 12 months). All patients who normalized their DLCO did not subsequently deteriorate, except one. Chest CT scans were abnormal in 77 patients (96.3%) at 3 months and although the proportion was the same at 12 months, but patterns have changed. CONCLUSION: We report the results of a comprehensive evaluation of 85 patients admitted to the ICU for SARS-CoV-2, at one-year follow-up after symptom onset. We show that most patients had an improvement in DLCO at each timepoint. TRIAL REGISTRATION: Clinical trial registration number: NCT04519320.

Prevalence and Characteristics of Sleep Apnea in Intensive Care Unit Survivors After SARS-CoV-2 Pneumonia.

Background: Sleep apnea (SA) was reported as possibly exacerbating symptoms of COVID-19, a disease induced by SARS-CoV-2 virus. The same comorbidities are common with both pathologies. This study aimed to estimate the prevalence, characteristics of SA and variation in AHI three months after severe COVID-19 requiring intensive care unit (ICU) admission. Methods: A prospective cohort of patients admitted to ICU for severe COVID-19 underwent an overnight home polygraphy 3 months after onset of symptoms, as part of a comprehensive follow-up program (pulmonary function tests, 6-minute walk tests and chest CT-scan). Patients with an apnea hypopnea index (AHI) ≥5 were considered as having SA. We performed a comparative descriptive analysis of 2 subgroups according to the existence, severity of SA and indication for effective SA treatment: patients with absent or mild SA (AHI <15) vs patients with moderate to severe SA (AHI ≥15). Results: Among 68 patients included, 62 (91%) had known comorbidities (34 hypertension, 21 obesity, 20 dyslipidemia, 16 type 2 diabetes). It has been observed a preexisting SA for 13 patients (19.1%). At 3 months, 62 patients (91%) had SA with 85.5% of obstructive events. Twenty-four patients had no or a mild SA (AHI <15) and 44 had moderate to severe SA (AHI ≥15). Ischemic heart disease exclusively affected the moderate to severe SA group. Except for thoracic CT-scan which revealed less honeycomb lesions, COVID-19 symptoms were more severe in the group with moderate to severe SA, requiring a longer curarization, more prone position sessions and more frequent tracheotomy. Conclusion: SA involved 91% of patients in our population at 3 months of severe COVID-19 and was mainly obstructive type. Although SA might be a risk factor as well as consequences of ICU care in severe COVID-19 infection, our results underline the importance of sleep explorations after an ICU stay for this disease.

Ventilatory adaptation during eccentric cycling in patients with severe COPD: Potential implications for exercise training.

INTRODUCTION: Eccentric (ECC) cycling is viewed as an alternative to concentric (CON) cycling for exercise training in patients with severe COPD as it induces a much lower ventilatory demand for a given mechanical load than CON cycling. However, a more hyperpneic breathing pattern (i.e., higher fB and lower tidal volume (VT)) during ECC than during CON has been reported in healthy subjects. RESEARCH QUESTION: Do patients with severe COPD develop a more hyperpneic breathing pattern during ECC than during CON cycling, and is it associated with differences in dynamic hyperinflation, ventilatory efficiency and cardiometabolic adaptation? METHODS: Fourteen patients with severe COPD performed incremental CON and ECC cardiopulmonary exercise tests (CPET). Several physiological parameters including VT, fB, inspiratory capacity (IC) and oxygen consumption (V̇O2) were recorded at each workload increment during CPET. RESULTS: At the highest identical minute ventilation (V̇E) achieved during ECC and CON (28.6 ± 4.6 L.min-1), VT was lower (1010 ± 218 vs. 1100 ± 233 mL; p = 0.02), fB was higher (29.0 ± 5.1 vs. 27.0 ± 5.5 min-1; p = 0.03), IC(% baseline) was lower (84 ± 10 vs. 78 ± 9; p < 0.01) and markers of ventilatory efficiency were poorer during ECC than during CON. Similar results were found at the highest identical V̇O2 achieved during ECC and CON. CONCLUSION: The finding of a more hyperpneic ventilatory pattern during ECC cycling together with a lower IC and a poorer ventilatory efficiency suggests that ECC exercise training should be decided with caution in patients with severe COPD.

Divergent endothelial function but similar platelet microvesicle responses following eccentric and concentric cycling at a similar aerobic power output.

Endothelial function and microvesicle concentration changes after acute bouts of continuous eccentric exercise have not been assessed previously nor compared with concentric exercise at similar aerobic power outputs. This method of training may be useful among some clinical populations, but acute responses are not well described. As such, 12 healthy males completed 2 experimental sessions of either 45 min of eccentric or concentric cycling at a matched aerobic power output below the ventilatory threshold. Brachial artery vascular function was assessed throughout 5 min of forearm ischemia and 3 min thereafter, before and at 5 and 40 min of recovery following each exercise session [flow-mediated dilation (FMD)]. Venous blood samples were acquired before each vascular function assessment. FMD significantly decreased after eccentric cycling by 40 min of recovery (P < 0.05), but was unaltered after concentric exercise. No differences in peak hyperemic blood flow velocity occurred neither between modalities nor at any time point (P > 0.05). Platelet-derived microvesicles increased by ~20% after both exercise modalities (P < 0.05) while endothelial-derived microvesicles were unchanged (P > 0.05). Moderate relationships with cardiac output, a surrogate for shear stress, and norepinephrine were apparent (P < 0.05), but there were no relationships with inflammatory or acute phase proteins. In summary, eccentric endurance exercise induced macrovascular endothelial dysfunction; however, endothelial activation determined by endothelial microvesicles did not occur suggesting that this modality may induce oxidative stress but no significant endothelial damage. In addition, the increase in platelet microvesicle concentrations may induce beneficial microvascular adaptations as suggested by previous research.NEW & NOTEWORTHY Continuous eccentric cycling exercise induces substantial skeletal muscle, tendon, and bone strain providing a potentially beneficial stimulus among clinical populations. This modality also induces temporary endothelial dysfunction but no apparent damage or activation of the endothelium indicated by microvesicle production, whereas proangiogenic platelet microvesicles are released similarly following both concentric and eccentric cycling and may relate to the shear stress and catecholamine response to exercise.

Similar substrate oxidation rates in concentric and eccentric cycling matched for aerobic power output.

This study investigated substrate oxidation in concentric and eccentric cycling matched for aerobic power output in the postprandial state. Energy expenditure, respiratory exchange ratio, and fat and carbohydrate oxidation rates were measured at rest and after 15, 30, and 45 min of eccentric and concentric cycling in 12 men. Absolute and relative aerobic power output and energy expenditure were similar during concentric and eccentric exercise. No effect of exercise modality was observed for substrate metabolism.