Mid-term pulmonary sequelae after hospitalisation for COVID-19: The French SISCOVID cohort.

BACKGROUND: Even though COVID-19 clinical features, pathogenesis, complications, and therapeutic options have been largely described in the literature, long-term consequences in patients remain poorly known. METHODS: The French, multicentre, non-interventional SISCOVID study evaluated lung impairment three (M3) and six months (M6) after hospital discharge in patients recovered from COVID-19. Evaluation was based on clinical examination, pulmonary function tests, and chest computed tomography (CT-scan). RESULTS: Of the 320 included patients (mean age: 61 years; men: 64.1%), 205 had had a severe form of COVID-19, being hospitalised in an intensive care unit (ICU), and requiring high flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation. At M6, 54.1% of included patients had persistent dyspnoea (mMRC score ≥1), 20.1% severe impairment in gas diffusing capacity (DLCO <60% pred.), 21.6% restrictive ventilatory pattern (total lung capacity <80% pred.), and 40% a fibrotic-like pattern at CT-scan. Fibrotic-like pattern and restrictive ventilatory pattern were significantly more frequent in patients recovered from severe than non-severe COVID-19. Improved functional and radiological outcomes were observed between M3 and M6. At M6, age was an independent risk factor for severe DLco impairment and fibrotic-like pattern and severe COVID-19 form was independent risk factor for restrictive ventilatory profile and fibrotic-like pattern. CONCLUSION: Six months after discharge, patients hospitalised for COVID-19, especially those recovered from a severe form of COVID-19, frequently presented persistent dyspnoea, lung function impairment, and persistent fibrotic-like pattern, confirming the need for long-term post-discharge follow-up in these patients and for further studies to better understand long-term COVID-19 lung impairment.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

The Importance of Apneic Events in Obstructive Sleep Apnea Associated with Acute Coronary Syndrome.

BACKGROUND: Obstructive sleep apnea (OSA) is a potential cardiovascular risk factor. However, there is currently no prominent screening strategy for its diagnosis in patients with acute coronary syndrome (ACS). The aim of this study was to establish the impact of apneic events in case of OSA associated with ACS. METHODS: Between January 1st and June 30th, fifty-three subjects with ACS (first acute myocardial infarction) were prospectively evaluated for OSA. Each patient was evaluated by polysomnography (PSG) two months after the ACS. RESULTS: Mean age of 59±9,6 years, 81,1% males, BMI at 28,5±4,2 kg/m2, neck circumference of 42,5±12,6 cm, and waist circumference os 102,5±16,5 cm. The majority of patients (73,6%) had moderate to severe OSA (apnea-hypopnea index (AHI) ≥ 15/h and arousal index ≥ 10/h). We defined the apneic coefficient (AC) as the ratio between apnea index (AI) and AHI. We chose as cut-off the median value of apnea coefficient in our population which was at 37%. The patients with a higher AC (AC ≥ 37% versus AC < 37%) had higher levels of Troponin-I (63,4±63,2 versus 29,7±36,1 ng/mL, p=0,016), higher levels of NT-proBNP (1879,8±2141,8 versus 480±621,3 pg/mL, p=0,001), higher SYNTAX score (15,8±11,5 versus 10,2±5,9, p=0,049), and lower left ventricle ejection fraction (LVEF 53,3±11,4 versus 59,4±6,4%, p=0,023) and were more likely to have a STEMI (21 patients (77,7%) vesus 14 patients (53,8%), p=0,031). CONCLUSION: An apneic coefficient (AI/AHI) ≥ 37% is correlated with more severe cardiac impairment, as well as higher hypoxemia and arousal index.

Hemodynamic profile of pulmonary hypertension (PH) in ARDS.

Acute respiratory distress syndrome (ARDS) is a diffuse lung injury that leads to a severe acute respiratory failure. Traditional diagnostic criteria for pulmonary hypertension (PH), in this situation, may be unreliable due to the effects of positive pressure ventilation and vasoactive agents. The aim of this study is to describe the hemodynamic characteristics of PH secondary to ARDS, in relation with respiratory parameters. We assessed the hemodynamic, respiratory function, and ventilator parameters in a cohort of 38 individuals with ARDS-associated PH defined by mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Individual characteristics: PaO2/FiO2 = 110 ± 60 mmHg, alveolar-arterial oxygen gradient (A-aO2) = 549 ± 148.9 mmHg, positive end-expiratory pressure (PEEP) = 8.7 ± 3.5 cmH2O, pulmonary static compliance (Cstat) = 30 ± 12.1 L*cmH2O-1, mPAP = 35.4 ±6.6 mmHg, pulmonary artery wedge pressure (PAWP) = 15.6 ± 5.5 mmHg, cardiac index (CI) = 3.4 ± 1.2 L/min/m2, pulmonary vascular resistance (PVR) = 3.3 ± 1.6 Wood units (WU), right atrial pressure (RAP) = 13.4 ± 5.4 mmHg, diastolic pulmonary gradient (DPG) = 12.6 ± 6.5 mmHg, and trans-pulmonary gradient (TPG) = 19.7 ± 7.7 mmHg. The composite marker-DPG >7 mmHg and PVR > 3 WU-is associated with lower CI ( P = 0.016), higher mPAP ( P = 0.003), and lower pulmonary static compliance ( P = 0.028). We confirmed a poor prognosis of ARDS associated with PH, with a 50% survival rate after 17 days. We observed that the survival rate at 28 days was better in the case of improvement in the PaO2/FiO2 ratio in the first 24 h (log rank P = 0.003). ARDS associated with PH is a severe condition with a very poor survival rate. The composite marker DPG > 7 mmHg and PVR > 3 WU seemed to better describe the hemodynamic and respiratory dysfunction. The improvement in PaO2/FiO2 ratio in the first 24 h defined a better survival in our cohort of patients.

Withdrawal of long-term epoprostenol therapy in pulmonary arterial hypertension (PAH).

Once initiated for pulmonary arterial hypertension (PAH), epoprostenol treatment usually needs to be delivered for an indefinite duration. It is possible that some participants could be transitioned from epoprostenol to oral therapies. We retrospectively evaluated eight PAH participants transitioned from epoprostenol to PAH oral drugs. The criteria for epoprostenol withdrawal were: (1) persistent improvement of clinic and hemodynamic status; (2) stable dose of epoprostenol for the last three months; and (3) the participant's preference for oral therapy after evaluation of risk-benefit. We evaluated the clinical, functional, and hemodynamic status at baseline, at withdrawal, and after the transition to oral PAH therapy. The transition was completed in all eight participants. Four participants had a complete successful transition (CT) with a stable clinical and hemodynamic course and four participants had a partial successful transition (PT) remaining stable clinically, with a mild hemodynamic worsening, but without need to re-initiate epoprostenol therapy. The four CT participants were treated with epoprostenol for a shorter period of time (CT group: 35 ± 30 versus PT group: 79 ± 49 months, P = 0.08). Mean epoprostenol dosage was lower in the CT group (CT group: 15 ± 1.5 ng/kg/min versus PT group: 24 ± 11 ng/kg/min, P = 0.09). Safe withdrawal of epoprostenol treatment and transition to oral PAH therapy was possible in a small and highly selected group of participants. The majority of these participants had a porto-pulmonary PAH or PAH associated to HIV infection.

Pulmonary Arterial Hypertension-Specific Drug Therapy in COPD Patients with Severe Pulmonary Hypertension and Mild-to-Moderate Airflow Limitation.

BACKGROUND: Patients with severe pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD) present a poor outcome. Specific PH treatment could improve the clinical and hemodynamic status of these patients but may worsen arterial blood gases. OBJECTIVES: Our study retrospectively included 28 patients with severe precapillary PH (mean pulmonary arterial pressure >35 mm Hg) associated with mild-to-moderate COPD [forced expiratory volume in 1 s (FEV1) >50% predicted]. All patients underwent specific pulmonary arterial hypertension (PAH) treatment as mono-, bi- or triple therapy. METHODS: Our single-center study was conducted based on retrospective data of 537 right heart catheterizations (RHCs) performed on patients with COPD from January 2004 to June 2014. An echocardiography, comprehensive blood tests, pulmonary function tests, and a high-resolution computed tomography were performed before the RHCs. All patients underwent RHC with a Swan-Ganz catheter. RESULTS: Compared to baseline, patients treated with specific PAH drugs showed a significant increase in cardiac index at long term (2.5 ± 0.7 liters/min/m2 at baseline vs. 3.2 ± 0.6 liters/min/m2 at 6/12 months; p = 0.003) as well as a decrease in pulmonary vascular resistance in the long term (8.4 ± 4.2 Wood units at baseline vs. 5 ± 1.7 Wood units at 6/12 months; p = 0.008). There was a slight decrease in arterial oxygen tension (PaO2) after 3 months of treatment (-2.4 ± 7.21 mm Hg; p = 0.066). During a median follow-up of 3 years, 12 patients (42.8%) died (including all causes of death). CONCLUSIONS: This preliminary report suggests that the use of specific PH therapy in severe PH associated with mild-to-moderate COPD can improve pulmonary hemodynamic parameters, with worsening of PaO2, which had no clinical significance and did not lead to specific PAH therapy withdrawal in any patient.

[Metabolic profile in obese patients with obstructive sleep apnea. A comparison between patients with insulin resistance and with insulin sensitivity]. / Profilul metabolic al pacientilor cu sindrom de apnee obstructiva în somn si obezitate. Comparatie între pacienti cu insulinorezistenta si pacienti cu insulinosensibilitate.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) may induce metabolic abnormalities through intermittent hypoxemia and simpathetic activation. It is difficult to demonstrate an independent role of OSAS in the occurrence of metabolic abnormalities, as obesity represents an important risk factor for both OSAS and metabolic abnormalities. AIM: to assess the relations between insulin resistance (IR), insulin sensitivity (IS), OSAS severity and nocturnal oxyhaemoglobin levels in obese, nondiabetic patients with daytime sleepiness. MATERIAL AND METHODS: We evaluated 99 consecutive, obese, nondiabetic patients (fasting glycemia < 126 mg/dL, no hypoglycemic or hypolipemiant medication) diagnosed with OSAS (AHI > 5/hour and daytime sleepiness) by an ambulatory six channel cardio-respiratory polygraphy. Hight, weight serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) levels were evaluated. Correlations between Apneea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), average and lowest oxyhaemoglobin saturation (SaO), body mass index (BMI) and insulin resistance or sensitivity were assesed. IR was defined as a TG/ HDL-Cratio > 3, and insulin sensitivity (IS) as a TG/HDL-C ratio < 2. RESULTS: 64 patients (out of 99) had lR and 18 IS. In the IR group (44 men and 20 women), the mean age was 52 +/- 10.6 years, mean BMI: 38.54 +/- 6.67 Kg/m2 (30-60), TG/HDL-C:5, 27 +/- 2.03 (3.02-11.1), mean AHI: 49.65 +/- 25.55/hour (7-110), mean ODI: 4769 +/- 24.95/hour (4-98), mean average SaO2 89.42 +/- 4.6 and mean lowest SaO2 68.4% +/- 13.8% (32-88%). 48 patients had severe, 7 moderate and 9 mild OSAS. In the IS group (10 men and 8 women), the mean age was 58.4 +/- 8.2years, mean BMI: 35.4 +/- 4.29 Kg/m2 (30-46), TG/ HDL-C: 1.64 +/- 0.29 (1.13-1.95), mean AHI: 45.8 +/- 30.3/hour (9-131), mean ODI: 39.9 +/- 32.2/hour (2-133), mean average SaO2 90.8 +/- 8.2 (81-95) and mean lowest SaO2: 74% +/- 10.8% (52-87%). 12 patients had severe, 3 moderate and 3 mild OSAS. Insulin sensitivity positively correlated with mean average SaO2 (r: 0.49; p: 0.037) and negatively with ODI (r: - 0,56; p: 0.014). Insulin resistance negatively correlated with mean lowest SaO2 (r: -0,25; p: 0.045). Mean lowest SaO2 values were significant lower in patients with IR than in those with IS (p: 0.042). No statistically significant difference was found for BMI, AHI or ODI between IR and IS patients. CONCLUSIONS: nocturnal oxyhaemoglobin levels rather than OSAS severity (expressed as AHI or ODI) may be involved in the occurrence of metabolic abnormalities in obese nondiabetic patients. Preserving insulin sensitivity is more likely when oxyhaemoglobin levels are higher and ODI is lower. Mean lowest nocturnal SaO2 levels seems to be independently involved in the development of insulin resistance as no statistically significant differences were found for BMI between the two groups.

The role of overnight pulse-oximetry in recognition of obstructive sleep apnea syndrome in morbidly obese and non obese patients.

MATERIAL AND METHODS: We prospectively evaluated 199 individuals with high pre-test clinical suspicion of OSAS. Of these, 123 patients were morbidly obese (Group A) and 76 were non-obese (Group B). We performed six channel cardio-respiratory polygraphy and assessed the correlation between the Desaturation Index (DI) and the Apnea Hypopnea Index (AHI) for both groups. RESULTS: In group A: 116 patients (94.3%) were diagnosed with OSAS (AHI>5/hour); mean age: 59.4±10.9 years; mean BMI: 44.8±4.9 kg/m(2). The mean DI was 47.2±27.6/hour and the mean AHI: 46.5±27.6/hour. Mean average SaO2 was 88.5±6.3 %. In group B, 65 patients (85.52%) were diagnosed with SAS; mean age: 51.2 ± 12.7 years; mean BMI: 27.24±2.2 kg/m(2).The mean DI was 23.12 ± 18.35/hour and the mean AHI: 28.8 ± 18.5/hour. Mean average SaO2 was 93.7±2.07 %.A significant positive correlation (correlation index rA = 0.863 and rB= 0.877) was found between DI and AHI in both groups (p<0.001). CONCLUSION: Assessment of the Desaturation Index by nocturnal pulse-oximetry maintains its utility as a screening method for OSAS in both obese and non-obese patients with high clinical pre-test suspicion, despite the fact that the basal nocturnal saturation was found to be lower in group A.

[Devices used in non-invasive ventilation for obstructive sleep apnea associating COPD and/or morbid obesity]. / Dispozitive utilizate în ventilatia non-invaziva in Sindromul de Apnee în Somn, care asociaza BPOC si/sau obezitate morbida.

Obstructive Sleep Apnea (OSA), COPD and morbid obesity are three medical conditions with increasing prevalence, and their association is not rare in clinical practice. Whereas CPAP remains the gold standard therapy of severe symptomatic OSA, non-invasive ventilation, often requiring additional oxygen therapy, could be necessary to achieve a satisfactory arterial oxyhaemoglobin saturation and carbon dioxide level, and is used on a long term basis for patients with OSA and COPD/morbid obesity. Thus, non-invasive ventilation is intended to increase the minute ventilation, and the devices used could achieve this either by providing a targeted volume as a result ofa pressure (barometric devices), or an actual volume (volumetric devices). In this paper are described the basic mechanisms, operating principle, the advantages and limitations of the most used devices for this kind of patients, in ambulatory settings.