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Abstract Objective Progressive immunodeficiency associated with HIV-infection leads to a progressive course of liver disease in HIV/HCV-co-infected patients. Highly active antiretroviral therapy (HAART) efficiently restores and preserves immune functions and has recently been demonstrated to also result in reduced liver-related mortality in HIV/HCV-co-infected patients. Methods To analyse differences in current liver fibrosis as a possible effect of HAART on fibrosis progression we assessed hepatic fibrosis by transient elastography in a cross-sectional comparison between HCV-mono-infected and HIV/HCV-co-infected patients presenting at our outpatient department in 2007. Results Overall, we did not find any difference in the distribution of liver stiffness between mono- (n = 84) and double-infected (n = 57) patients (14.4 kPa (10.8 - 18.2) versus 12.4 kPa (9.1 - 16.1), mean (95%-CI)). However, in the 8 HIV+ patients with CD4 counts < 200/μl liver stiffness was markedly greater (18.4 kPa (0.8 - 36.0)) than in HIV+ patients with preserved immunity (11.5 kPa (8.4 - 15.0)). Conclusions These findings are in line with other data that show an improved prognosis of chronic hepatitis C in HIV+ patients under effective HAART, and may be a hint that fibrosis progression in well-treated HIV+ patients will no longer be different from that in HCV-mono-infected patients.

Background: Our centre followed a stepwise approach in the nonpharmacological treatment of respiratory failure in COVID-19 in accordance with German national guidelines, escalating non-invasive measures before invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyse this individualized approach to non-pharmacologic therapy in terms of patient characteristics and clinical features that may help predict more severe disease, particularly the need for intensive care., Method: This retrospective single-centre study of COVID-19 inpatients between March 2020 and December 2021 analysed anthropometric data, non-pharmacological maximum therapy and survival status via a manual medical file review., Results: Of 1052 COVID-19-related admissions, 835 patients were included in the analysis cohort (54% male, median 58 years); 34% (n=284) received no therapy, 40% (n=337) conventional oxygen therapy (COT), 3% (n=22) high flow nasal cannula (NHFC), 9% (n=73) continuous positive airway pressure (CPAP), 7% (n=56) non-invasive ventilation (NIV), 4% (n=34) intermittent mandatory ventilation (IMV), and 3% (n=29) extracorporeal membrane oxygenation (ECMO). Of 551 patients treated with at least COT, 12.3% required intubation. A total of 183 patients required ICU treatment, and 106 (13%) died. 25 (74%) IMV patients and 23 (79%) ECMO patients died. Arterial hypertension, diabetes and dyslipidemia was more prevalent in non-survivors. Binary logistic analysis revealed the following risk factors for increased mortality: an oxygen supplementation of ≥2 L/min at baseline (OR 6.96 [4.01-12.08]), age (OR 1.09 [1.05-1.14]), and male sex (OR 2.23 [0.79-6.31])., Conclusion: The physician's immediate clinical decision to provide oxygen therapy, along with other recognized risk factors, plays an important role in predicting the severity of the disease course and thus aiding in the management of COVID-19., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Episodic breathlessness is often accompanied by panic. A vicious cycle of breathlessness-panic-breathlessness leads to emergencies with severe breathlessness and/or fear of dying. However, the interaction between episodic breathlessness and panic is poorly understood. Thus, the aim is a better understanding of the interaction between panic and episodic breathlessness to develop appropriate support for patients suffering from this symptom., Methods: Patients suffering from episodic breathlessness due to life-limiting diseases answered questions on the characteristics of episodic breathlessness and panic-spectrum psychopathology, including underlying mechanisms. Using the Patient Health Questionnaire and the Structured Clinical Interview for DSM-IV Diagnoses (SCID), patients were screened for panic disorder. An open-ended question captured the patients' descriptions of panic during breathlessness episodes., Results: Forty-six patients [52% women, mean age =66 years; standard deviation (SD) 7.3 years] provided information: 61% suffered from panic during the entire breathlessness episode, 39% experienced panic in every episode, and 25% were diagnosed with panic disorder. Exploratory data analysis was conducted. Patients with high scores in breathlessness catastrophizing thoughts experienced more panic in a breathlessness episode (P<0.001) and considered themselves more panic than low-scorers (P=0.024). There was a significant indirect effect of episodic breathlessness intensity on the panic experienced in an episode, and this effect was mediated by catastrophizing thoughts regarding breathlessness (b=0.164; 95% CI: 0.105, 0.222). Patients described in the open-ended question experiencing only panic or breathlessness, or a combination of both. Some patients managed to differentiate panic from episodic breathlessness, and used strategies to avoid panic in an episode., Conclusions: Research on treatment options for episodic breathlessness should not only focus on panic in breathlessness episodes, but also on underlying mechanisms such as catastrophizing thoughts, as they aggravate the burden.

Background: Early intubation versus use of conventional or high-flow nasal cannula oxygen therapy (COT/HFNC), continuous positive airway pressure (CPAP), and non-invasive ventilation (NIV) has been debated throughout the COVID-19 pandemic. Our centre followed a stepwise approach, in concordance with German national guidelines, escalating non-invasive modalities prior to invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO), rather than early or late intubation., Objectives: The aims of the study were to investigate the real-life usage of these modalities and analyse patient characteristics and survival., Method: A retrospective monocentric observation was conducted of all consecutive COVID-19 hospital admissions between March 2020 and December 2021 at a university-affiliated pulmonary centre in Germany. Anthropometric data, therapy, and survival status were descriptively analysed., Results: From 1,052 COVID-19-related admissions, 835 patients were included (54% male, median 58 years). Maximum therapy was as follows: 34% (n = 284) no therapy, 40% (n = 337) COT, 3% (n = 22) HFNC, 9% (n = 73) CPAP, 7% (n = 56) NIV, 4% (n = 34) IMV, and 3% (n = 29) ECMO. Of 551 patients treated with at least COT, 12.3% required intubation. Overall, 183 patients required intensive unit care, and 106 (13%) died. Of the 68 patients who received IMV/ECMO, 48 died (74%). The strategy for non-pharmacological therapy was individual but remained consistent throughout the studied period., Conclusions: This study provides valuable insight into COVID-19 care in Germany and shows how the majority of patients could be treated with the maximum treatment required according to disease severity following the national algorithm. Escalation of therapy modality is interlinked with disease severity and thus associated with mortality., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The number of patients receiving home long-term ventilation has risen considerably in recent decades owing to medical advancements. Experts believe that the potential for ventilator weaning or tracheostoma removal is currently insufficiently exploited., Objective: The objective of this study was to investigate the characteristics, prognosis, and decannulation/weaning potential of patients under home intensive care., Methods: In this retrospective analysis of 607 patients on home intensive care, decannulation/weaning status and survival were documented for a 2-year period after initial assessment. At the time of hospital discharge, when clinicians had deemed the weaning process concluded, an independent expert noninvasively assessed the long-term decannulation/weaning. Comparative analyses based on specific criteria, such as ventilation and decannulation/weaning status, age, and underlying diseases, were performed. Potential predictors of survival were identified via multivariable logistic regression., Results: Eighteen percent of patients were decannulated/weaned within 2 years after hospital discharge and had better mean survival than patients not decannulated/weaned (552 vs. 420 days, p < 0.001). More than half of these patients were identified to have decannulation/weaning potential based on the assessment of the independent expert. Patients with neuromuscular and neurological diseases had the best survival (546 and 501 days), patients with postsurgical conditions and cardiological diseases the worst (346 and 323 days). Underlying disease and decannulation/weaning status were significant predictors of 2-year survival., Conclusion: Successful decannulation/weaning of patients on long-term home intensive care is associated with better survival. Even in the absence of decannulation/weaning potential at the time of hospital discharge, patients may develop decannulation/weaning potential over time, which should therefore be assessed repeatedly., (© 2022 S. Karger AG, Basel.)

Aims: Guideline recommendations highlight the critical role of combination therapy for the treatment of pulmonary arterial hypertension (PAH). Conversely, registry data demonstrate that a considerable number of PAH patients remain on monotherapy. The reasons for this discrepancy remain elusive. The aim of this study was to assess the patient profiles, treatment patterns, and disease characteristics of patients diagnosed with PAH who were kept on monotherapy at experienced pulmonary hypertension (PH) centres and to capture potential reasons for monotherapy., Methods and Results: We analysed the patient profiles of 182 patients on monotherapy with PAH-targeted drugs, managed at experienced PH expert centres (Cologne, Giessen, Heidelberg, and Dresden). Patients were identified based on their latest follow-up visit and analysed retrospectively from the time of PAH diagnosis to last follow-up. Patients were dichotomized by age, and patient characteristics, treatment patterns, response to therapy, change in risk status, and drug tolerability were recorded during the course of their disease. Patients' mean age was 69.1 ± 13.1 years at the most recent follow-up (Key Time Point 1) and 64.5 ± 14.9 years at the time of diagnosis (Key Time Point 2). The mean time on monotherapy was 60.7 ± 53.8 months; 35.7/64.3% of patients were male/female. The majority (66.5%) had idiopathic PAH, followed by PAH associated with connective tissue disease (17.0%) and portopulmonary PH (8.2%). Among patients on monotherapy, there were five main clusters: (i) patients with failed escalation attempts mostly because of intolerability (26.9%); (ii) low risk on monotherapy, favourable response, and no reason for escalation (24.2%); (iii) patients with mild PAH (36.3%); (iv) elderly patients with PAH and multiple co-morbidities (38.5%); and (v) patients with associated forms of PAH where the level of evidence for combination therapies is considered low (16.5%). There were substantial differences between patients above or below the median age (68 years). The most frequently used monotherapy for PAH was phosphodiesterase type 5 inhibitors (75.3%)., Conclusions: A considerable number of PAH patients are on monotherapy at large PH expert centres, characterized by specific reasons that justify this kind of treatment. Nevertheless, as comprehensive treatment strategies have shown improved long-term outcomes even in mildly symptomatic patients, each case of monotherapy should be justified., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Context: Episodic breathlessness is characterized by increased breathlessness intensity, and it is burdensome for patients. A vicious cycle of breathlessness-anxiety/panic-breathlessness leads to emergencies that can rarely be alleviated by drugs. Non-pharmacological interventions seem to be beneficial: Can a brief cognitive and behavioral intervention help patients to better manage episodic breathlessness?, Objectives: To evaluate the feasibility, safety, acceptability, and potential effects of a brief cognitive and behavioral intervention for the management of episodic breathlessness., Methods: Between February 2019 and February 2020, 49 patients with life-limiting diseases suffering from episodic breathlessness were enrolled in the single-arm phase II study. The baseline assessment was followed by the one- to two-hour intervention. In weeks two, four, and six after the intervention, the outcomes (main outcome of potential effects: mastery of breathlessness) were assessed, and in week six, a qualitative interview, and the final assessment took place. A mixed-methods approach was used to evaluate mainly the feasibility, including interviewing informal carers., Results: 46/49 patients (24 female; 36 with COPD; mean age: 66.0 years) participated in the baseline assessment, 38 attended the intervention, 32 completed the final assessment, and 22 were interviewed. Study procedures and the intervention were feasible and mainly well accepted and patients did not experience burdens caused by it (28/32). In the interviews, patients described a positive change in their competencies in managing episodic breathlessness and feelings of anxiety during the episode. Mastery of breathlessness improved after the intervention., Conclusion: The brief cognitive and behavioral intervention and the study procedures are feasible, safe, and well accepted. We can describe a change for better management of episodic breathlessness in patients after the intervention, still, this needs to be evaluated in a Phase III trial for inclusion in the management of episodic breathlessness., (Copyright © 2022. Published by Elsevier Inc.)

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear-nose-throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes., Competing Interests: Conflicts of Interest: W. Randerath reports personal fees received from Weinmann, Heinen & Löwenstein, Resmed, Inspire, Philips Respironics, and Bioprojet, outside the submitted work. Conflicts of interest: J. Verbraecken reports receiving payments to institution for lectures, presentations, speakers bureaus, manuscript writing or educational events from SomnoMed and Inspire Medical Systems, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for ResMed Narval, payments to institution, outside the submitted work. Conflicts of interest: C.A.L. de Raaff has nothing to disclose. Conflicts of interest: J. Heder reports grants received from ResMed, outside the submitted work. Lecture fees from Bayer Pharma and Jazz Pharmaceuticals outside the submitted work. Patent filed and granted for Pharmacological therapy in OSA. Participation on a data safety monitoring board or advisory board for DSMB. Conflicts of interest: S. Herkenrath has nothing to disclose. Conflicts of interest: W. Hohenhorst has nothing to disclose. Conflicts of interest: T. Jakob has nothing to disclose. Conflicts of interest: O. Marrone has nothing to disclose. Conflicts of interest: M. Marklund has nothing to disclose. Conflicts of interest: W.T. McNicholas has nothing to disclose. Conflicts of interest: R.L. Morgan has nothing to disclose. Conflicts of interest: J-L. Pépin reports grants and research funds from (payments made to the institutions) Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire, outside the submitted work. Consulting fees from: Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed, and Sefam, outside the submitted work. Conflicts of interest: S. Schiza has nothing to disclose. Conflicts of interest: N. Skoetz reports support for the present manuscript from the European Respiratory Society. Personal payments received from Cochrane outside the submitted work. Conflicts of interest: D. Smyth has nothing to disclose. Conflicts of interest: J. Steier reports receiving grants from the British Lung Foundation, outside the submitted work. Payments of honoraria received from Jazz Pharmaceuticals and Sanofi. Named inventor on pending patent WO2016124739A1. President of the British Sleep Society. Conflicts of interest: T. Tonia acts as an ERS methodologist. Conflicts of interest: W. Trzepizur has nothing to disclose. Conflicts of interest: P-H. van Mechelen has nothing to disclose. Conflicts of interest: P. Wijkstra has nothing to disclose., (Copyright ©The authors 2021.)

Introduction: In slowly progressive myopathies, diaphragm weakness early manifests through sleep-related hypoventilation as reflected by nocturnal hypercapnia. This study investigated whether daytime tests of respiratory muscle function and diaphragm ultrasound predict hypercapnia during sleep. Methods: Twenty-seven patients with genetic myopathies (myotonic dystrophy type 1 and 2, late-onset Pompe disease, facioscapulohumeral dystrophy; 48 ± 11 years) underwent overnight transcutaneous capnometry, spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Results: Sixteen out of 27 patients showed nocturnal hypercapnia (peak p tc CO 2 ≥ 50 mmHg for ≥ 30 min or increase in p tc CO 2 by 10 mmHg or more from the baseline value). In these patients, forced vital capacity (FVC; % predicted) and maximum inspiratory pressure (MIP; % of lower limit or normal or LLN) were significantly reduced compared to normocapnic individuals. Nocturnal hypercapnia was predicted by reduction in FVC of <60% [sensitivity, 1.0; area under the curve (AUC), 0.82] and MIP (%LLN) <120% (sensitivity, 0.83; AUC, 0.84), the latter reflecting that in patients with neuromuscular disease, pretest likelihood of abnormality is per se higher than in healthy subjects. Diaphragm excursion velocity during a sniff maneuver excluded nocturnal hypercapnia with high sensitivity (0.90) using a cutoff of 8.0 cm/s. Conclusion: In slowly progressive myopathies, nocturnal hypercapnia is predicted by FVC <60% or MIP <120% (LLN). As a novelty, nocturnal hypercapnia can be excluded with acceptable sensitivity by diaphragm excursion velocity >8.0 cm/s on diaphragm ultrasound., Competing Interests: JS has been supported by the Else-Kröner-Fresenius Stiftung (Grant SP A109) and by the Kommission für Innovative Medizinische Forschung an der Medizinischen Fakultät Muenster (IMF Grant SP 11 18 15), Deutsche-Herzstiftung (DHS Grant SP 01/09), Scuola Superiore Sant‘Anna Pisa, Italy (Ph.D. Programme Translational Medicine), and Chiesi and Boehringer Ingelheim outside this work. MB has been supported by Loewenstein Medical outside this work. PY and MB have received speaker honoraria and travel grants from Sanofi Genzyme, Sanofi-Aventis, UCB, and Loewenstein Medical. WR has received travel grants and speaker honoraria from Loewenstein Medical, Philips Respironics, Novartis, Inspire, and Boehringer Ingelheim. H-JK was supported by Deutsche Forschungsgemeinschaft (DFG) outside this work and received travel grants and/or speaking fees from Actelion, Bayer, GlaxoSmithKline, MSD Sharp & Dohme, and Pfizer Deutschland. MD reports to have received travel grants and/or speaking fees and/or fees for consulting from Actelion, Astra Zeneca, Bayer, Berlin Chemie, Boehringer, Chiesi, Hamilton, Loewenstein Medical, Intermune, Linde, Novartis, Pfizer, Philips Respironics, ResMed, Roche and Weinmann. The remaining 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 Spiesshoefer, Lutter, Kabitz, Henke, Herkenrath, Randerath, Young, Dreher, Görlich and Boentert.)

Background: In precapillary pulmonary hypertension (PH), nasal high flow therapy (NHF) may favorably alter sympathovagal balance (SVB) and sleep-related breathing through washout of anatomical dead space and alleviation of obstructive sleep apnea (OSA) due to generation of positive airway pressure., Objectives: To investigate the effects of NHF on SVB, sleep, and OSA in patients with PH, and compare them with those of positive airway pressure therapy (PAP)., Methods: Twelve patients with PH (Nice class I or IV) and confirmed OSA underwent full polysomnography, and noninvasive monitoring of SVB parameters (spectral analysis of heart rate, diastolic blood pressure variability). Study nights were randomly split into four 2-h segments with no treatment, PAP, NHF 20 L/min, or NHF 50 L/min. In-depth SVB analysis was conducted on 10-min epochs during daytime and stable N2 sleep at nighttime., Results: At daytime and compared with no treatment, NHF20 and NHF50 were associated with a flow-dependent increase in peripheral oxygen saturation but a shift in SVB towards increased sympathetic drive. At nighttime, NHF20 was associated with increased parasympathetic drive and improvements in sleep efficiency, but did not alter OSA severity. NHF50 was poorly tolerated. PAP therapy improved OSA but had heterogenous effects on SVB and neutral effects on sleep outcomes. Hemodynamic effects were neutral for all interventions., Conclusions: In sleeping PH patients with OSA NHF20 but not NHF50 leads to decreased sympathetic drive likely due to washout of anatomical dead space. NHF was not effective in lowering the apnea-hypopnoea index and NHF50 was poorly tolerated.

New findings on pathophysiology, epidemiology, and outcome have raised concerns on the relevance of the apnoea-hypopnoea index (AHI) in the classification of obstructive sleep apnoea (OSA) severity. Recently, a multicomponent grading system decision integrating symptomatology and comorbidities (Baveno classification), was proposed to characterise OSA and to guide therapeutic decisions. We evaluated whether this system reflects the OSA population, whether it translates into differences in outcomes, and whether the addition of AHI improves the scheme. A total of 14 499 OSA patients from the European Sleep Apnoea Database cohort were analysed. The groups were homogeneously distributed and were found to clearly stratify the population with respect to baseline parameters. Differences in sleepiness and blood pressure between the groups were analysed in a subgroup of patients after 24-36 months of treatment. Group A (minor symptoms and comorbidities) did not demonstrate any effect of treatment on outcome. However, groups B (severe symptoms, minor comorbidities), C (minor symptoms, severe comorbidities) and D (severe symptoms and comorbidities) were associated with improvement in either or both parameters with treatment. The AHI is an essential prerequisite of the diagnosis; however, adding the AHI did not improve the classification. Rather, it was inferior with respect to guiding the treatment decision. Thus, the Baveno classification allows a better stratification of the OSA population and may provide a better guidance for therapeutic decisions in OSA., Competing Interests: Conflict of interest: W.J. Randerath reports speaking fees and travel grants from Philips Respironics, Heinen und Löwenstein, ResMed, Bioprojet, Bayer Vital and Vanda Pharma outside the submitted work. Conflict of interest: S. Herkenrath has nothing to disclose. Conflict of interest: M. Treml has nothing to disclose. Conflict of interest: L. Grote reports grants from Bayer, the Philips Respironics Foundation and the ResMed Foundation for the ESADA network during the conduct of the study; and nonfinancial and other support from Itamar Medical, ResMed, Philips, AstraZeneca and Breas outside the submitted work. In addition, L. Grote has a patent on sleep apnoea therapy licensed. Conflict of interest: J. Hedner reports grants from Bayer AG, the European Respiratory Society (for database maintenance) and Desitin GmbH outside the submitted work; in addition, J. Hedner has a patent issued on pharmacological therapy of OSA. Conflict of interest: M.R. Bonsignore has nothing to disclose. Conflict of interest: J.L. Pépin grants and research funds from the Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, ResMed, and Vitalaire; and fees from Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz Pharmaceutical, Night Balance, Philips and ResMed. Conflict of interest: S. Ryan has nothing to disclose. Conflict of interest: S. Schiza has nothing to disclose. Conflict of interest: J. Verbraecken reports an educational grant and an advisory board fee from ResMed; a consultancy fee from Philips; lecture fees from Sanofi and Agfa-Gevaert; an educational grant and an advisory board fee from Bioprojet; an educational grant from and study participation for Jazz Pharmaceutics; an educational grant from AirLiquide; a lecture fee from Springer; an educational grant from Westfalen Medical; an educational grant and a lecture fee from SomnoMed; educational grants from Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance and Heinen & Löwenstein; lecture fees from AstraZeneca; and educational grants from Accuramed, Bekaert Deslee Academy and UCB Pharma, all outside the submitted work. Conflict of interest: W.T. McNicholas has nothing to disclose. Conflict of interest: A. Pataka has nothing to disclose. Conflict of interest: P. Sliwinski has nothing to disclose. Conflict of interest: Ö.K. Basoglu has nothing to disclose., (Copyright ©The authors 2021.)

Background and Objective: The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood., Methods: Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34)., Results: Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to <15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO2] <90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO2, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = -0.39; p = 0.03) and end-systolic (r = -0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO2 but not with measures of OSA severity or daytime clinical variables., Conclusion: OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH., (© 2021 S. Karger AG, Basel.)

Background: In lung transplant recipients (LTRs), restrictive ventilation disorder may be present due to respiratory muscle dysfunction that may reduce exercise capacity. This might be mediated by pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)., Objective: We investigated lung respiratory muscle function as well as circulating pro-inflammatory cytokines and exercise capacity in LTRs., Methods: Fifteen LTRs (6 female, age 56 ± 14 years, 63 ± 45 months post-transplantation) and 15 healthy controls matched for age, sex, and body mass index underwent spirometry, measurement of mouth occlusion pressures, diaphragm ultrasound, and recording of twitch transdiaphragmatic (twPdi) and gastric pressures (twPgas) following magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots. Exercise capacity was quantified using the 6-min walking distance (6MWD). Plasma IL-6 and TNF-α were measured using enzyme-linked immunosorbent assays., Results: Compared with controls, patients had lower values for forced vital capacity (FVC; 81 ± 30 vs.109 ± 18% predicted, p = 0.01), maximum expiratory pressure (100 ± 21 vs.127 ± 17 cm H2O, p = 0.04), diaphragm thickening ratio (2.2 ± 0.4 vs. 3.0 ± 1.1, p = 0.01), and twPdi (10.4 ± 3.5 vs. 17.6 ± 6.7 cm H2O, p = 0.01). In LTRs, elevation of TNF-α was related to lung function (13 ± 3 vs. 11 ± 2 pg/mL in patients with FVC ≤80 vs. >80% predicted; p < 0.05), and lung function (forced expiratory volume after 1 s) was closely associated with diaphragm thickening ratio (r = 0.81; p < 0.01) and 6MWD (r = 0.63; p = 0.02)., Conclusion: There is marked restrictive ventilation disorder and respiratory muscle weakness in LTRs, especially inspiratory muscle weakness with diaphragm dysfunction. Lung function impairment relates to elevated levels of circulating TNF-α and diaphragm dysfunction and is associated with exercise intolerance., (© 2020 S. Karger AG, Basel.)

The pathophysiology of respiratory muscle weakness in myotonic dystrophy type 1 (DM1) remains incompletely understood. 21 adult patients with DM1 (11 men, 42 ± 13 years) and 21 healthy matched controls underwent spirometry, manometry, and diaphragm ultrasound. In addition, surface electromyography of the diaphragm and the obliquus abdominis muscle was performed following cortical and posterior cervical magnetic stimulation (CMS) of the phrenic nerves or magnetic stimulation of the lower thoracic nerve roots. Magnetic stimulation was combined with invasive recording of the twitch transdiaphragmatic and gastric pressure (twPdi and twPgas) in 10 subjects per group. The following parameters were reduced in DM1 patients compared to control subjects: maximum inspiratory pressure (MIP; 40.3 ± 19.2 vs. 95.8 ± 28.5 cmH 2 O, p < 0.01), diaphragm thickening ratio (DTR; 2.0 ± 0.4 vs. 2.7 ± 0.6, p < 0.01), twPdi following CMS (10.8 ± 8.3 vs. 21.4 ± 10.1 cmH2O, p = 0.03), and amplitude of diaphragm compound muscle action potentials (0.10 ± 0.25 vs. 0.46 ± 0.35 mV; p = 0.04). MIP and DTR were significantly correlated with the muscular impairment rating scale (MIRS) score. Maximum expiratory pressure (MEP) was reduced in DM1 patients compared to controls (41.3 ± 13.4 vs. 133.8 ± 28.0 cmH2O, p < 0.01) and showed negative correlation with the MIRS score. Pgas following a maximum cough was markedly lower in patients than in controls (71.9 ± 43.2 vs. 102.4 ± 35.5 cmH 2 O) but without statistical significance (p = 0.06). In DM1, respiratory muscle weakness relates to clinical disease severity and involves inspiratory and probably expiratory muscle strength. Axonal phrenic nerve pathology may contribute to diaphragm dysfunction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Reference values derived from existing diaphragm ultrasound protocols are inconsistent, and the association between sonographic measures of diaphragm function and volitional tests of respiratory muscle strength is still ambiguous., Objective: To propose a standardized and comprehensive protocol for diaphragm ultrasound in order to determine lower limits of normal (LLN) for both diaphragm excursion and thickness in healthy subjects and to explore the association between volitional tests of respiratory muscle strength and diaphragm ultrasound parameters., Methods: Seventy healthy adult subjects (25 men, 45 women; age 34 ± 13 years) underwent spirometric lung function testing, determination of maximal inspiratory and expiratory pressure along with ultrasound evaluation of diaphragm excursion and thickness during tidal breathing, deep breathing, and maximum voluntary sniff. Excursion data were collected for amplitude and velocity of diaphragm displacement. Diaphragm thickness was measured in the zone of apposition at total lung capacity (TLC) and functional residual capacity (FRC). All participants underwent invasive measurement of transdiaphragmatic pressure (Pdi) during different voluntary breathing maneuvers., Results: Ultrasound data were successfully obtained in all participants (procedure duration 12 ± 3 min). LLNs (defined as the 5th percentile) for diaphragm excursion were as follows: (a) during tidal breathing: 1.2 cm (males; M) and 1.2 cm (females; F) for amplitude, and 0.8 cm/s (M) and 0.8 cm/s (F) for velocity, (b) during maximum voluntary sniff: 2.0 cm (M) and 1.5 cm (F) for amplitude, and 6.7 (M) cm/s and 5.2 cm/s (F) for velocity, and (c) at TLC: 7.9 cm (M) and 6.4 cm (F) for amplitude. LLN for diaphragm thickness was 0.17 cm (M) and 0.15 cm (F) at FRC, and 0.46 cm (M) and 0.35 cm (F) at TLC. Values for males were consistently higher than for females, independent of age. LLN for diaphragmatic thickening ratio was 2.2 with no difference between genders. LLN for invasively measured Pdi during different breathing maneuvers are presented. Voluntary Pdi showed only weak correlation with both diaphragm excursion velocity and amplitude during forced inspiration., Conclusions: Diaphragm ultrasound is an easy-to-perform and reproducible diagnostic tool for noninvasive assessment of diaphragm excursion and thickness. It supplements but does not replace respiratory muscle strength testing., (© 2020 S. Karger AG, Basel.)

Introduction: The purpose of this study was to comprehensively evaluate respiratory muscle function in adults with facioscapulohumeral muscular dystrophy (FSHD)., Methods: Fourteen patients with FSHD (9 men, 53 ± 16 years of age) and 14 matched controls underwent spirometry, diaphragm ultrasound, and measurement of twitch gastric and transdiaphragmatic pressures (twPgas and twPdi; n = 10) after magnetic stimulation of the lower thoracic nerve roots and the phrenic nerves. The latter was combined with recording of diaphragm compound muscle action potentials (CMAPs; n = 14)., Results: The following parameters were significantly lower in patients vs controls: forced vital capacity (FVC); maximum inspiratory and expiratory pressure; peak cough flow; diaphragm excursion amplitude; and thickening ratio on ultrasound, twPdi (11 ± 5 vs 20 ± 6 cmH 2 O) and twPgas (7 ± 3 vs 25 ± 20 cmH 2 O). Diaphragm CMAP showed no group differences. FVC correlated inversely with the clinical severity scale score (r = -0.63, P = .02)., Discussion: In FSHD, respiratory muscle weakness involves both the diaphragm and the expiratory abdominal muscles., (© 2019 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.)

It is unclear whether there are cardiopulmonary exercise testing (CPET) parameters which may indicate poor prognosis in the early course of fibrosing interstitial lung disease. 27 untreated consecutive subjects (13 idiopathic non-specific interstitial pneumonia (iNSIP), 14 idiopathic pulmonary fibrosis (IPF); 19 male; age 69 ± 10 years) were enrolled in this observational pilot study. Subjects underwent routine pulmonary function testing and CPET. Statistically, the t test and the Mann-Whitney-U test were applied in the presence of normal and non-normal distribution (according to Shapiro-Wilk), respectively. Analyzing the whole cohort, only mild functional impairments were determined. Comparison of iNSIP and IPF groups detected significant differences for the CPET parameters V'O 2 Peak[%pred] (p = 0.011), V'O 2 /kgPeak (p = 0.033), Watt[%pred] (p = 0.048), V'E/V'CO 2 (Rest: p = 0.016; AT: p = 0.011; Peak: p = 0.019; Slope: p = 0.040), V'E/V'O 2 (Rest: p = 0.033 AT: p = 0.014; Peak: p = 0.035). CPET parameters may indicate IPF-specific impairments even in mild disease. It may be hypothesized that these parameters are early biomarkers of poor prognosis.