Expedition 5300: limits of human adaptations in the highest city in the world.

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2500 m throughout the world. Among them, 50 000 live in the world's highest city, La Rinconada, located at 5000-5300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to investigate the physiological adaptations and altitude-related health issues in this unique population. Dwellers from La Rinconada have very high haemoglobin concentration (20.3 ± 2.4 g/dL; n = 57) and those with chronic mountain sickness (CMS) exhibit even higher concentrations (23.1 ± 1.7 g/dL; n = 150). These values are associated with large total haemoglobin mass and blood volume, without an associated iron deficit. These changes in intravascular volumes lead to a substantial increase in blood viscosity, which is even larger in CMS patients. Despite these large haematological changes, 24 h blood pressure monitoring is essentially normal in La Rinconada, but some results suggest impaired vascular reactivity. Echocardiography revealed large right heart dilatation and high pulmonary arterial pressure as well as left ventricle concentric remodelling and grade I diastolic dysfunction. These changes in heart dimension and function tend to be more severe in highlanders with CMS. Polygraphy evaluations revealed a large reduction in nocturnal pulse oxygen saturation (median SpO2  = 79%), which is even more severe in CMS patients who also tended to show a higher oxygen desaturation index. The population of La Rinconada offers a unique opportunity to investigate the human responses to chronic severe hypoxia, at an altitude that is probably close to the maximum altitude human beings can permanently tolerate without presenting major health issues.

Mechanisms relating to sleeping position to the endotypes of sleep disordered breathing.

PURPOSE: Obstructive sleep apnea (OSA) severity varies considerably depending on the body position during sleep in certain subjects. Such variability may be underpinned by specific, body position-related changes in OSA pathophysiological determinants, or endotypes. Also head position relative to trunk may influence OSA endotypes. However, no studies to our knowledge have reviewed the endotype variations according to head or body position up to now. RECENT FINDINGS: Several findings illustrate that supine OSA is mostly attributable to unfavorable upper airway anatomy compared to lateral position. However, a reduced lung volume, with consequent ventilatory instability (or elevated loop gain), may also play a role. Furthermore, preliminary findings suggest that prone and reclined positions may have a beneficial effect on collapsibility and loop gain. SUMMARY: Sleeping supine induces many unfavorable pathophysiological changes, especially in certain predisposed OSA patients. Little is known on the influence of other sleep positions on key endotypic traits.

Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population.

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.

Effects of short-term exposure to particulate matter on emergency department admission and hospitalization for asthma exacerbations in Brescia district.

BACKGROUND: Rising pollution plays a crucial role in worsening several respiratory diseases. Particulate Matter (PM)-induced asthma exacerbations are one of the most dangerous events. OBJECTIVES: To assess the correlation between progressive particulate matter short-term exposure and asthma exacerbations, we investigated the role of PM levels on Emergency Department (ED) admissions and hospitalizations for these events in Brescia, an important industrial city located in northern Italy with high yearly levels of air pollution. METHODS: We analyzed 1050 clinical records of ED admissions for suspected asthma exacerbation, starting from January 2014 to December 2017. Daily PM levels were collected from the Environmental Protection Regional Agency. We performed a time-series analysis using a Poisson regression model with single and multiple day-lag. Results were expressed as Relative Risk (RR) and Excess of Relative Risk (ERR) of severe asthma exacerbation over a 10 µg/m3 increase in PM10 and PM2.5 concentration. RESULTS: We selected and focused our analysis on 543 admissions for indisputable asthma exacerbation in ED and hospital. The time-series study showed an increase of the RR (CI95%) for asthma exacerbation-related ED admissions of 1.24 with an ERR of 24.2% for PM2.5 at lag0-1 (p < 0.05). We also estimated for PM2.5 a RR (CI95%) of 1.12 with an ERR of 12.5% at lag0-5 (p ≤ 0.05). Again, for PM2.5, an increase of the RR (CI95%) for asthma exacerbation-related hospitalizations of 1.31 with an ERR of 30.7% at lag0-1 (p < 0.05) has been documented. These findings were confirmed and even reinforced considering only the population living in the city. CONCLUSIONS: Short-term PM exposure, especially for PM2.5, plays a critical role in inducing asthma exacerbation events leading to ED admission or hospitalization.

Lung Ultrasound in Patients With SARS-COV-2 Pneumonia: Correlations With Chest Computed Tomography, Respiratory Impairment, and Inflammatory Cascade.

OBJECTIVES: Lung ultrasound (LUS) might be comparable to chest computed tomography (CT) in detecting parenchymal and pleural pathology, and in monitoring interstitial lung disease. We aimed to describe LUS characteristics of patients during the hospitalization for COVID-19 pneumonia, and to compare the extent of lung involvement at LUS and chest-CT with inflammatory response and the severity of respiration impairment. METHODS: During a 2-week period, we performed LUS and chest CT in hospitalized patients affected by COVID-19 pneumonia. Dosages of high sensitivity C-reactive protein (HS-CRP), d-dimer, and interleukin-6 (IL-6) were also obtained. The index of lung function (P/F ratio) was calculated from the blood gas test. LUS and CT scoring were assessed using previously validated scores. RESULTS: Twenty-six consecutive patients (3 women) underwent LUS 34 ± 14 days from the early symptoms. Among them, 21 underwent CT on the same day of LUS. A fair association was found between LUS and CT scores (R = 0.45, P = .049), which became stronger if the B-lines score on LUS was not considered (R = 0.57, P = .024). LUS B-lines score correlated with IL-6 levels (R = 0.75, P = .011), and the number of involved lung segments detected by LUS correlated with the P/F ratio (R = 0.60, P = .019) but not with HS-CRP and d-Dimer levels. No correlations were found between CT scores and inflammations markers or P/F. CONCLUSION: In patients with COVID-19 pneumonia, LUS was correlated with both the extent of the inflammatory response and the P/F ratio.

Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is highly prevalent with numerous deleterious effects on neurocognitive and cardiovascular health. It is characterized by collapse of the upper airway during sleep, due to the decrease in both basal and compensatory UA muscle activities. However, the leading treatment, continuous positive airway pressure, is often poorly tolerated. This review presents latest works focusing on novel interventions targeting upper airway muscles to alleviate OSA severity. RECENT FINDINGS: In the last years, researchers have focused on the development of alternative treatment strategies targeting UA muscle activation, including pharmacological and nonpharmacological interventions. SUMMARY: Among the nonpharmacological treatments, hypoglossal nerve stimulation aims to increase upper airway muscle phasic activity during sleep through electrical stimulation, while myofunctional therapy improves the activity and coordination of upper airway dilator muscles.Regarding OSA pharmacotherapy, recent findings strongly suggest that selective norepinephrine reuptake inhibitors such as atomoxetine and reboxetine, when administered with antimuscarinics such as oxybutynin, can alleviate OSA in most patients increasing pharyngeal dilator muscles activity during sleep. New combinations of norepinephrine reuptake inhibitors and antimuscarinics have further been explored with variable success and animal models showed that leptin, thyrothropin releasing hormone analogues and gene therapy hold potential for the future of OSA pharmacotherapy.

Breath-holding as a novel approach to risk stratification in COVID-19.

BACKGROUND: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). METHODS: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. RESULTS: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. CONCLUSIONS: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.

Investigating the Link between Alpha-1 Antitrypsin Deficiency and Abdominal Aortic Aneurysms.

BACKGROUND: Alpha-1-Antitrypsin (AAT) is one of the major plasmatic protease inhibitors. In the last decade, an association between Alpha-1-Antitrypsin Deficiency (AATD) and Abdominal Aortic Aneurysms (AAA) has been hypothesized. Multiple factors may be involved in AAA's etiopathogenesis, and an underlying structural defect of the extracellular matrix (ECM) is always present. AATD could be a reasonable risk factor for AAA because it is related to protease/antiprotease imbalance and enhanced ECM degradation of the vessel wall. METHODS: We performed genotyping of 138 patients hospitalized in the Vascular Surgery Division of the ASST-Spedali Civili di Brescia, Italy, for nontraumatic rupture of AAA. The second purpose was to observe the distribution of main nongenetic risk factors for AAA between patients with and without AATD. RESULTS: Out of 138 patients, 22 were found with AATD: 16 MS, 1 SS, 3 MZ, and 2 with a new rare AAT variant. When compared to the general Italian population, our cohort's frequency of deficient S allele was significantly higher (7.8 vs. 2.2% respectively, P < 0.01), whereas the deficient Z allele was similar (1.1 vs. 1.3% respectively, P > 0.05). Although we found no differences in age, gender, hypertension, diabetes, and smoke habits between AAA patients with and without AATD, hyperlipidemia was significantly less frequent in patients with AATD (46.4 vs. 12.5% respectively, P < 0.05). CONCLUSIONS: In our AAA patients' cohort, the S allele frequency was higher than in the general Italian population. Our results support the hypothesis that AATD might be a risk factor for AAA.

Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis.

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment.The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of -2.09 (95% CI -2.78- -1.40) mmHg for systolic BP and -1.92 (95% CI -2.40- -1.43) mmHg for diastolic BP and -1.27 (95% CI -2.34- -0.20) mmHg for systolic BP and -1.11 (95% CI -1.82- -0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP -2.93 mmHg), with uncontrolled BP at baseline (systolic BP -4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP -7.57 mmHg).Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.

Effect of Ultrafiltration on Sleep Apnea and Cardiac Function in End-Stage Renal Disease.

RATIONALE: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration. METHODS: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. -Results: Fifteen subjects had baseline measurements, of which 7 had an AHI <15 (no-sleep-apnea group) and 8 had an AHI ≥15 (sleep-apnea group). At baseline, there was no overnight change in the LVEF in either the no-sleep-apnea group or the sleep-apnea group. In the no-sleep-apnea group, there was also no overnight change in MPI, IVCT/ET and IVRT/ET. However, in the sleep-apnea group there were overnight increases in MPI, IVCT/ET and IVRT/ET (p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished. CONCLUSIONS: In ESRD, cardiac function deteriorates overnight in those with sleep apnea, but not in those without sleep apnea. This overnight deterioration in the sleep-apnea group may be at least partially due to sleep apnea, since attenuation of sleep apnea by UF was accompanied by elimination of this deleterious overnight effect.

Evening sock marks as an adjunct to the clinical prediction of obstructive sleep apnea.

STUDY OBJECTIVES: Fluid overload shifting from the legs to the upper airway during sleep promotes obstructive sleep apnea (OSA) and interventions targeting fluid attenuate OSA. Fluid shift has been previously measured by bioelectrical impedance, a complex and time-consuming technique not applicable in the daily clinical settings. The aim of this study is to evaluate the presence of clinically detectable fluid overload and shift and its association with OSA. METHODS: Patients undergoing sleep study for suspected OSA were asked to report the presence of 11 signs/symptoms associated to excessive accumulation of fluid in different parts of the body at different times of the day. RESULTS: Among 392 patients (male: 53%, median [interquartile range] age: 56 years [1], body mass index, BMI: 29 kg/m2 [2]) included in the study, 135 (34%) had moderate-to-severe OSA (apnea hypopnea index, AHI ≥ 15). Daytime fluid accumulation and nocturnal fluid shift, clinically detectable by patient-reported "evening sock marks," "heavy legs during the day," and "morning stuffed nose," were prevalent in the entire population (46%, 43%, and 33%, respectively). In multivariate analysis, evening sock marks was an independent correlate of having an AHI ≥ 15, together with male sex, older age, and self-reported snoring and apneas. CONCLUSIONS: Clinically detectable fluid overload and shift are prevalent in patients addressed for suspected OSA, and evening sock marks, a marker for leg swelling, is an independent correlate of moderate-to-severe OSA. This sign might contribute to OSA diagnosis and identification of patients likely to be treated by interventions targeting fluid overload and shift.

Postural respiratory-related cortical activation and rostral fluid shift in awake healthy humans.

NEW FINDINGS: What is the central question of this study? Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects? What is the main finding and its importance? Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. ABSTRACT: Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre-inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory-related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty-four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory-related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis.

Obstructive sleep apnea and chronic kidney disease.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease (CKD). The relationship between OSA and CKD is likely to be bi-directional. On one hand, the presence of OSA leads to intermittent hypoxia, sympathetic nervous system activity, and hypertension, all of which may have deleterious effects on kidney function. On the other hand, in patients with end-stage renal disease (ESRD), intensification of renal replacement therapy has been shown to attenuate sleep apnea severity, suggesting that the renal disease itself contributes to the pathogenesis of OSA. The present review describes our current understanding of the bi-directional relationship between OSA and CKD. RECENT FINDINGS: Studies suggest that the presence of OSA and nocturnal hypoxia may lead to worsening of kidney function. One potential mechanism is activation of the renin-angiotensin system by OSA, an effect which may be attenuated by CPAP therapy. In ESRD, fluid overload plays an important role in the pathogenesis of OSA and fluid removal by ultrafiltration leads to marked improvements in sleep apnea severity. SUMMARY: OSA is associated with accelerated loss of kidney function. In patients with ESRD, fluid overload plays an important role in the pathogenesis of OSA.

The effect of fluid overload on sleep apnoea severity in haemodialysis patients.

As in heart failure, obstructive and central sleep apnoea (OSA and CSA, respectively) are common in end-stage renal disease. Fluid overload characterises end-stage renal disease and heart failure, and in heart failure plays a role in the pathogenesis of OSA and CSA. We postulated that in end-stage renal disease patients, those with sleep apnoea would have greater fluid volume overload than those without.End-stage renal disease patients on thrice-weekly haemodialysis underwent overnight polysomnography on a nondialysis day to determine their apnoea-hypopnoea index (AHI). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance.28 patients had an AHI ≥15 (sleep apnoea group; OSA:CSA 21:7) and 12 had an AHI <15 (no sleep apnoea group). Total body extracellular fluid volume was 2.6 L greater in the sleep apnoea group than in the no sleep apnoea group (p=0.006). Neck, thorax, and leg fluid volumes were also greater in the sleep apnoea than the no sleep apnoea group (p<0.05), despite no difference in body mass index (p=0.165).These findings support a role for fluid overload in the pathogenesis of both OSA and CSA in end-stage renal disease.

Cardiac Sympathetic Hyperactivity in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in 0.5-1% of the general population. Both OSA and COPD are associated with increased sympathetic nervous activity, and patients affected by both disorders have higher risk for increased morbidity and mortality as compared with patients with COPD or OSA alone. We tested the hypothesis that patients with COPD and OSA (Overlap syndrome) have higher sympathetic and lower parasympathetic modulation of heart rate variability (HRV) in comparison with patients suffering from COPD or OSA alone. HRV indices in the frequency domain were evaluated from daytime electrocardiographic recordings in 14 patients with both severe OSA (apnea-hypopnea index ≥ 30) and mild-to-moderate COPD and compared with those with OSA (n = 24) or COPD (n = 16) alone. We found that, in the Overlap syndrome group, high-frequency (HF, 0.4-0.15 Hz) power was significantly lower (0.18 nu vs 0.34 nu in OSA and 0.44 nu in COPD patients, p < 0.01) and low-frequency (LF, 0.15-0.05 Hz) power was significantly greater (0.82 nu vs 0.66 nu in OSA and 0.57 nu in COPD patients, p < 0.01) compared with COPD and OSA groups. Patients with both OSA and COPD had higher LF/HF ratio as compared with patients in OSA and COPD groups (4.5 [5.9] vs 1.9 [2.6] and 1.3 [1.3], respectively, p < 0.01). For the Overlap syndrome group, there was a significant direct relationship between LF/HF ratio and residual volume (r2 = 0.62, p = 0.007). These findings show that patients with both OSA and COPD have higher sympathetic modulation of heart rate compared with those with OSA or COPD alone. Furthermore, the findings provide a potential mechanism for the increased morbidity and mortality reported in patients suffering from both disorders, suggesting new therapeutic perspectives in Overlap syndrome.

Home-based exercise program for people with residual disability following hospitalization for COVID-19: Randomized control trial.

BACKGROUND: The best exercise program for individuals with effort intolerance or hypoxia at rest and/or during exercise post-COVID-19 treatment who have already had in-hospital rehabilitation remains unknown. OBJECTIVE: We evaluated the efficacy of a home-based rehabilitation exercise program intervention that included teleconsultations with a specialist nurse. METHODS: This was a multicenter randomized controlled trial for individuals who had been diagnosed with, and treated for, COVID-19. Despite inpatient rehabilitation they still had effort intolerance; this was defined as being a) only able to walk <70 % of the predicted distance during the six-minute walking test (6MWT) and/or b) oxygen desaturation all day long/during effort. The primary outcome was effort tolerance, as evaluated by the 6MWT. Secondary outcomes were dyspnea, fatigue, spirometry, respiratory muscle evaluations, and oxygenation. The Intervention group performed 4 weeks of a self-directed exercise program with bi-weekly physiotherapist video calls; the Control group participated in physical activity howsoever they wished. Exercises were divided into 4 intensity levels according to disability and oxygen desaturation. The program progressively increased from low (walking, free-body exercise, sit-to-stand, and balance exercises) to high (speed walking with a pedometer, cycle ergometer, and strengthening exercises). RESULTS: We included 79 participants: 40 in the Intervention and 39 in the Control group. Mean (SD) age was 67.1 (10.3) years; 72 % (n = 57) were male. No intergroup differences in effort tolerance were found [Intervention 77.6 (75.4)m vs Control 49.5 (73.3)m (p = 0.109)]. Participants with 6MWT distance results < lower limit of normality values showed best improvements in mean (SD) effort tolerance: Intervention, 120.1 (75.8)m vs Control, 59.1 (75.6)m (p = 0.035). After 2 months, mean (SD) 6MWT distances in the 2 groups were similar: Intervention, 475.9 (82.4)m vs Control, 469.2 (118.9)m (p = 0.807). CONCLUSIONS: In individuals with residual disability post-COVID-19 and after inpatient rehabilitation, a home-based exercise program with teleconsultation significantly improves effort tolerance but only for people who had severe effort intolerance at baseline. DATABASE REGISTRATION: ClinicalTrials.gov number, NCT04821934.

Pharmacotherapy for obstructive sleep apnea: targeting specific pathophysiological traits.

INTRODUCTION: The pathophysiology of obstructive sleep apnea (OSA) is multi-factorial and complex. Varying OSA's pathophysiological traits have been identified, including pharyngeal collapsibility, upper airway muscle reactivity, arousal threshold, and regulation of the ventilatory drive. Being CPAP of difficult tolerance and other interventions reserved to specific subpopulations new pharmacological treatments for OSA might be resolutive. AREAS COVERED: Several existing and newly developed pharmacological drugs can impact one or more endotypes and could therefore be proposed as treatment options for sleep disordered breathing. With this review we will explore different pathophysiological traits as new targets for OSA therapy. This review will summarize the most promising pharmacological treatment for OSA accordingly with their mechanisms of action on upper airway collapsibility, muscle responsiveness, arousal threshold, and loop gain. EXPERT OPINION: Only understanding the pathophysiological traits causing OSA in each patient and placing the disease in the framework of patient comorbidities, we will be able to evolve interventions toward OSA. The development of new drug's combinations will permit different approaches and different choices beside conventional treatments. In the next future, we hope that sleep specialists will select the treatment for a specific patient on the base of its pathophysiology, defining a precision medicine for OSA.