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Loop Gain (LG), a concept borrowed from engineering used to describe the stability of electrical circuits under negative feedback, has emerged as a crucial pathophysiological trait in sleep respiratory disorders. In simple terms, LG measures how the respiratory control system reacts to changes in breathing. A high LG suggests that minor disturbances in breathing prompt exaggerated responses, potentially leading to instability and oscillations in respiratory patterns. Conversely, a low LG implies that the system responds more gently to disturbances, resulting in stable and well-regulated breathing. However, understanding the concept of loop gain presents challenges due to its dynamic nature across various sleep respiratory disorders, sleep stages, positions, and interactions with other pathophysiological traits. Recent efforts have aimed to identify a non-invasive method for assessing LG, with some evidence suggesting that information regarding pathophysiological traits can be extracted from polysomnography. There exists a clinical imperative for physician to unravel the intricacies of LG when managing Obstructive Sleep Apnea (OSA) patients, because LG abnormalities delineate a distinct pathophysiological phenotype of OSA. Specifically, certain patients exhibit a high LG as the primary factor driving sleep apnea, influencing treatment outcomes. For instance, individuals with high LG may respond differently to therapies such as continuous positive airway pressure (CPAP) or oral appliances compared to those with normal LG, or they can be treated with specific drugs or combination therapies. Thus, understanding LG becomes paramount for precise assessment of OSA patients and is fundamental for optimizing a personalized and effective treatment approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: OSAS is a syndrome that often presents clinically differently between men and women. The aim of this study was to assess the clinical presentation, nocturnal home sleep cardiorespiratory monitoring and therapeutic adherence to CPAP in both sexes to identify the most frequent patterns., Methods: Data from the first visit, the nocturnal home sleep cardiorespiratory monitoring and follow-up visit of 74 OSA patients were collected. Exclusion criteria included other respiratory and/or neuromuscular diseases (including Obesity hypoventilation syndrome) and other non-respiratory sleep disorders., Results: Men were older and had a higher supine AHI and ODI compared to women. In addition, BMI and age correlated positively with AHI in males. Women had a higher hypopneas frequency and better therapeutic adherence to CPAP., Conclusions: Men were associated with a higher AHI when sleeping in the supine position and this may be useful to look for new therapeutic options in combination with or as an alternative to CPAP. BMI correlated positively with AHI in men and this should be considered to stimulate weight loss as the main treatment to reduce the number of apneas/hypopneas, as men also had less therapeutic adherence to CPAP in our study. Females presented a significantly higher frequency of hypopneas than men, as well as a lower number of desaturation events per hour (ODI): these differences in the nocturnal home sleep cardiorespiratory monitoring could reflect different pathophysiological mechanisms of OSAS onset between the two sexes, which should be investigated in future scientific studies., (© 2024. The Author(s).)

Transbronchial lung cryobiopsy (TBCB) is a reliable method for obtaining histopathological findings in interstitial lung diseases. TBCB is traditionally performed during rigid bronchoscopy, positioning an endobronchial balloon blocker to facilitate bleeding management. Therefore, it can be challenging to implement in Centers without access to anesthesiologic support or dedicated beds for endoscopic procedures. We present a series of 11 patients who underwent 12 TBCBs using a flexible bronchoscope and a 5 Fr endobronchial blocker passing through an uncuffed endotracheal tube, under moderate sedation and spontaneous breathing. All procedures were carried out in an endoscopy suite, using fluoroscopy guidance but without requiring anesthesiologic assistance. TBCB was feasible in all cases, and it demonstrated similar or improved diagnostic yield (90.1%) and safety compared to rigid bronchoscopy. In 1 case, it was successfully repeated due to an inconclusive histological definition at the first attempt. The size of the samples was consistent with the literature, as it was the incidence of pneumothorax (16.6%). Four cases of moderate bleeding and 4 cases of severe bleeding were managed without further complications. To our knowledge, this is the first description of a technique allowing to perform TBCB through an artificial airway without need for either rigid bronchoscopy or general anesthesia. We believe this technique could make TBCB faster, cost-effective, and feasible even in resource-limited settings without compromising on safety. However, further studies are needed to validate these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Obstructive sleep apnea syndrome (OSAS) and asthma are two diseases with a high epidemiological impact that may often coexist. Both diseases have underlying pathogenic mechanisms (chronic inflammation, genetic predisposition, etc.); it is still unclear whether or not their coexistence is due to a specific pathophysiological factor. In the literature, the pathogenesis of OSAS has four pathophysiological traits: one or more anatomical predisposing factors, a low arousal threshold (low AT), high loop gain, and poor muscle responsiveness. In this study, we hypothesized that a low AT is a common pathophysiological factor in OSAS and asthma., Methods: A retrospective study of patients attending the Pulmonology Unit of the University Hospital of Trieste was carried out. Low AT was predicted on the bases of the following polysomnography features, as previously shown by Edwards et al.: an AHI of < 30 events/h, a nadir SpO2 of > 82.5%, and a hypopnea fraction of total respiratory events of > 58.3%., Results: Thirty-five patients with asthma and OSAS and 36 with OSAS alone were included in the study. Low AT was present in 71% of patients affected by asthma and OSAS (25 patients out of 35) versus 31% (11 patients out of 36) of patients affected by OSAS alone with a statistically significant difference (p = 0.002) between the two groups. Stratifying for BMI and OSAS severity, the difference between groups remained statistically significant., Conclusions: This is the first study to describe specific polysomnographic characteristics of patients affected by asthma and OSAS. A low AT may well be the pathophysiological factor common to the two diseases. If confirmed by other studies, this finding could lead to the presence of asthma and OSAS in the same individual being considered a syndrome with a common pathophysiological factor., (© 2022. The Author(s).)

Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking., Methods: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction ( P aO 2 / F IO 2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14., Results: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO 2 / F IO 2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points., Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia., Competing Interests: Conflict of interest: F. Salton, P. Confalonieri, S. Centanni, M. Mondoni, N. Petrosillo, D. Lacedonia, A. Voza, N. Carpenè, M. Montico, N. Reccardini, G.U. Meduri, B. Ruaro and M. Confalonieri have no conflicts of interest to disclose. P. Bonfanti received personal fees from ViiV Healthcare, Gilead, Janssen, Merck and Pfizer, not related to this work. G. Lapadula received personal fees from ViiV Healthcare and Pfizer, not related to this work., (Copyright ©The authors 2023.)

Introduction: The treatment of choice for obstructive sleep apnea syndrome (OSAS) is continuous positive airway pressure (CPAP). However, CPAP is usually poorly tolerated and mandibular advancement devices (MADs) are an alternative innovative therapeutic approach. Uncertainty still remains as to the most suitable candidates for MAD. Herein, it is hypothesized that the presence of low arousal threshold (low ArTH) could be predictive of MAD treatment failure. Methods: A total of 32 consecutive patients, with OSAS of any severity, who preferred an alternate therapy to CPAP, were treated with a tailored MAD aimed at obtaining 50% of their maximal mandibular advancement. Treatment response after 6 months of therapy was defined as AHI < 5 events per hour or a reduction of AHI ≥ 50% from baseline. Low ArTH was predicted based on the following polysomnography features, as previously shown by Edwards et al.: an AHI of 82.5% and a hypopnea fraction of total respiratory events of >58.3%. Results: There were 25 (78.1%) responders (p-value < 0.01) at 6 months. Thirteen patients (40.6%) in the non-severe group reached AHI lower than 5 events per hour. MAD treatment significantly reduced the median AHI in all patients from a median value of 22.5 to 6.5 (74.7% of reduction, p-value < 0.001). The mandibular advancement device reduced AHI, whatever the disease severity. A significant higher reduction of Delta AHI, after 6 months of treatment, was found for patients without low ArTH. Conclusions: Low ArTH at baseline was associated with a poorer response to MAD treatment and a lower AHI reduction at 6 months. A non-invasive assessment of Low ArTH can be performed through the Edwards’ score, which could help to identify an endotype with a lower predicted response to oral appliances in a clinical setting.

Obstructive sleep apnea syndrome (OSAS) is characterized by symptoms and signs of more than 5 apneas per hour (AHI) at polysomnography or 15 or more apneas per hour without symptoms. In this review, the focus will be a subgroup of patients: adult non-obese subjects with OSA and their specific features. In non-obese OSA patients (patients with BMI < 30 kg/m 2 ), there are specific polysomnographic features which reflect specific pathophysiological traits. Previous authors identified an anatomical factor (cranial anatomical factors, retrognatia, etc.) in OSA non-obese. We have hypothesized that in this subgroup of patients, there could be a non-anatomical pathological prevalent trait. Little evidence exists regarding the role of low arousal threshold. This factor could explain the difficulty in treating OSA in non-obese patients and emphasizes the importance of a specific therapeutic approach for each patient., (© 2021. The Author(s).)

Laser speckle contrast analysis (LASCA) is a non-contact technique able to quantify peripheral blood perfusion (PBP) over large skin areas. LASCA has been used to study hand PBP in several clinical conditions. These include systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) and LASCA showed that PBP was significantly lower in these conditions than in healthy subjects (HS). Moreover, it has been demonstrated that LASCA is a safe technique also able to monitor digital ulcer perfusion and their evolution in SSc patients, during systemic and local treatment. The use of LASCA, coupled with reactivity tests is commonplace in the field of microvascular function research. Post-occlusive hyperemia reactivity (POHR) and local thermal hyperemia, associated with laser techniques are reliable tests in the evaluation of perfusion in SSc patients. Other studies used laser speckled techniques, together with acetylcholine and sodium nitroprusside iontophoresis, as specific tests of endothelium function. In conclusion, LASCA is a safe, non-contact reliable instrument for the quantification of PBP at skin level and can also be associated with reactivity tests to monitor disease progression and response to treatment in different connective tissue diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ruaro, Bruni, Wade, Baratella, Confalonieri, Antonaglia, Geri, Biolo, Confalonieri and Salton.)

Background: Obstructive sleep apnea syndrome (OSAS) has emerged as a risk factor for cardiovascular disease. A prothrombotic state may affect coagulation and participate in the atherosclerotic process in subjects with OSAS. These alterations in coagulation seem to involve the plasminogen activation system. We evaluated the imbalances of the plasminogen activation system related to OSAS, and we assessed the effects of CPAP on the plasminogen activation system., Methods: Thirty-nine subjects were submitted to a home-based cardiorespiratory sleep study, and 14 healthy subjects (apnea-hypopnea index < 5) were used as controls. Serum levels of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and active transforming growth factor-β (TGF-β) were measured. These molecules were reassessed in only 17 of the subjects after 1 month of CPAP., Results: PAI-1 and tPA were significantly higher in the subjects with OSAS compared with the controls, whereas TGF-β and uPA levels were lower. PAI-1 showed a significant positive correlation with the apnea-hypopnea index, percentage of time spent at O2 saturation < 90%, and oxygen desaturation index, whereas TGF-β was inversely related to all 3 of these parameters. After the CPAP therapy, PAI-1 significantly decreased, whereas TGF-β showed a significant increase, although the values did not reach those of the controls. uPA and tPA did not show significant differences after the treatment., Conclusions: Our results suggest an imbalance of fibrinolysis related to OSAS and an improvement of the prothrombotic state after the CPAP treatment., (Copyright © 2015 by Daedalus Enterprises.)