Inspiratory Muscle Dysfunction Mediates and Predicts a Disease Continuum of Hypercapnic Failure in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Advanced chronic obstructive pulmonary disease (COPD) is associated with chronic hypercapnic failure. The present work aimed to comprehensively investigate inspiratory muscle function as a potential key determinant of hypercapnic respiratory failure in patients with COPD. METHODS: Prospective patient recruitment encompassed 61 stable subjects with COPD across different stages of respiratory failure, ranging from normocapnia to isolated nighttime hypercapnia and daytime hypercapnia. Arterialized blood gas analyses and overnight transcutaneous capnometry were used for patient stratification. Assessment of respiratory muscle function encompassed body plethysmography, maximum inspiratory pressure (MIP), diaphragm ultrasound, and transdiaphragmatic pressure recordings following cervical magnetic stimulation of the phrenic nerves (twPdi) and a maximum sniff manoeuvre (Sniff Pdi). RESULTS: Twenty patients showed no hypercapnia, 10 had isolated nocturnal hypercapnia, and 31 had daytime hypercapnia. Body plethysmography clearly distinguished patients with and without hypercapnia but did not discriminate patients with isolated nocturnal hypercapnia from those with daytime hypercapnia. In contrast to ultrasound parameters and transdiaphragmatic pressures, only MIP reflected the extent of hypercapnia across all three stages. MIP values below -48 cmH2O predicted nocturnal hypercapnia (area under the curve = 0.733, p = 0.052). CONCLUSION: In COPD, inspiratory muscle dysfunction contributes to progressive hypercapnic failure. In contrast to invasive tests of diaphragm strength only MIP fully reflects the pathophysiological continuum of hypercapnic failure and predicts isolated nocturnal hypercapnia.

[Prognostic factors in an individualised approach to non-pharmacological therapy of COVID-19: from oxygen and mechanical ventilation to extracorporeal membrane oxygenation]. / Prognostische Faktoren bei einem schrittweisen Ansatz zur nicht-pharmakologischen Therapie von Sauerstoff und mechanischer Beatmung bis hin zur extrakorporalen Membranoxygenierung bei COVID-19.

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.

Analysis of an Individualised Stepwise Approach to Non-Pharmacological Therapy in COVID-19.

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.

Interaction of panic and episodic breathlessness among patients with life-limiting diseases: a cross-sectional study.

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.

Decannulation/Weaning Potential and Success in Home Intensive Care.

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.

Sleep-related breathing disorders in idiopathic pulmonary fibrosis are frequent and may be associated with pulmonary vascular involvement.

PURPOSE: Sleep-related breathing disorders (SRBD) may be associated with a worse prognosis in idiopathic pulmonary fibrosis (IPF). However, the prevalence of sleep disorders in IPF and the pathophysiological link between SRBD and IPF is unclear. PATIENTS AND METHODS: In this prospective trial, consecutive patients with stable IPF underwent polysomnography and cardiopulmonary exercise testing. Epworth sleepiness scale, Regensburg insomnia scale, and Pittsburgh sleep quality index were evaluated. Exclusion criteria were oxygen supplementation therapy, lung emphysema, and heart failure. For pairwise comparison of categorical data, the two-proportion z-test was applied. Correlation between continuous variables was assessed via the Pearson correlation coefficient. Patients without and with SRBD were compared. To find predictors for SRBD in IPF, multivariable logistic regression was applied. RESULTS: A total of 74 IPF patients were evaluated and 45 patients (11 female, median age 74 years, forced vital capacity 71.3%, DLCO 53.9%) were analyzed. Any kind of sleep disorder was found in 89% of patients. SRBD was present in 49% (81% obstructive sleep apnea, 19% central sleep apnea), insomnia in 40%, and periodic leg movements in 47% of subjects. The SRBD subgroup presented with a significantly lower performance (workload(peak)%pred 86.5 vs. 101.0 (p = 0.036); V'O2(AT) 618.5 ml/min vs. 774.0 ml/min (p = 0.043)) and exhibited a significantly higher V'E/V'CO2(peak) of 43.0 l/l vs. 38.5 l/l (p = 0.037). In search of predictors for SRBD by logistic regression, workload(peak)%pred was identified as a significant variable (p = 0.033). CONCLUSIONS: SRBD is frequent in IPF. Pulmonary vascular limitations may represent the pathophysiological link between IPF and SRBD. Workload(peak)%pred may be an independent risk factor for the occurrence of SRBD.

Profiles and treatment patterns of patients with pulmonary arterial hypertension on monotherapy at experienced centres.

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.

Initial Proportion and Dynamic of B.1.1.7 SARS-CoV-2 in a Large City in the West of Germany.

Rationale: Several mutational variants of SARS-CoV-2 have been identified in the past months with increasing prevalence worldwide. Some variants, such as B.1.1.7, are of high relevance due to increased transmissibility, facilitating virus spread and calling for stricter containment measures. Objectives: The aim of this study was to examine proportion and dynamic of B.1.1.7 in SARS-CoV-2-positive samples in a large city in the west of Germany. Methods: Consecutive SARS-CoV-2-positive samples from a local outpatient clinic, obtained over a period of 4 weeks (mid-January to mid-February 2021), were examined for the presence of the variant B.1.1.7. The size of B.1.1.7 infection clusters was compared with non-B.1.1.7 clusters. The transmissibility of SARS-CoV-2 variant B.1.1.7 was described based on corresponding cases of an infection cluster in a local child daycare centre. Results: Among 226 SARS-CoV-2-positive cases, B.1.1.7 was detected in 74 subjects (33%). The 7-day moving mean of the B.1.1.7 proportion started at 20% and reached 50% only 3 weeks later. B.1.1.7 clusters comprised 10.7 ± 12.1 persons per cluster, while non-B.1.1.7 clusters were considerably smaller (5.1 ± 5.8). One specific B.1.1.7 infection cluster in a 40-children daycare centre started with one teacher leading to 11 infected children and 8 infections among teachers. The infection spread to 6 families and one other daycare centre, with a total 43 SARS-CoV-2-positive subjects. Conclusions: We found a rapid increase in the SARS-CoV-2 variant B.1.1.7 with larger infection clusters than non-B.1.1.7. These results suggested a rapid increase in the B.1.1.7 proportion and a renewed increase in the total number of SARS-CoV-2 infections for the time following the analysed period. Considering the rapid emergence and spread of viral variants, close monitoring of mutation events is essential. Therefore, routine whole-genome sequencing appears to be useful in addition to searching for known mutations.

Severity stages of obesity-related breathing disorders - a cross-sectional cohort study.

INTRODUCTION: There is a general underappreciation of the spectrum of obesity-related breathing disorders and their consequences. We therefore compared characteristics of obese patients with eucapnic obstructive sleep apnea (OSA), OSA with obesity-related sleep hypoventilation (ORSH) or obesity hypoventilation syndrome (OHS) to identify the major determinants of hypoventilation. PATIENTS AND METHODS: In this prospective, diagnostic study (NCT04570540), obese patients with OSA, ORSH or OHS were characterized applying polysomnography with transcutaneous capnometry, blood gas analyses, bodyplethysmography and measurement of hypercapnic ventilatory response (HCVR). Pathophysiological variables known to contribute to hypoventilation and differing significantly between the groups were specified as potential independent variables in a multivariable logistic regression to identify major determinants of hypoventilation. RESULTS: Twenty, 43 and 19 patients were in the OSA, ORSH and OHS group, respectively. BMI was significantly lower in OSA as compared to OHS. The extent of SRBD was significantly higher in OHS as compared to OSA or ORSH. Patients with ORSH or OHS showed a significantly decreased forced expiratory volume in 1 s and forced vital capacity compared to OSA. HCVR was significantly lower in OHS and identified as the major determinant of hypoventilation in a multivariable logistic regression (Nagelkerke R2 = 0.346, p = 0.050, odds ratio (95%-confidence interval) 0.129 (0.017-1.004)). CONCLUSION: Although there were differences in BMI, respiratory mechanics and severity of upper airway obstruction between groups, our data support HCVR as the major determinant of obesity-associated hypoventilation.

Hypoglossal nerve stimulation for obstructive sleep apnea: updated position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery.

Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize the complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions, whereat, minimal reporting standards to document outcome and usage are recommended.

Only I Know Now, of Course, How to Deal With it, or Better to Deal With it: A Mixed Methods Phase II Study of a Cognitive and Behavioral Intervention for the Management of Episodic Breathlessness.

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.

European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea.

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.

Respiratory Muscle Function Tests and Diaphragm Ultrasound Predict Nocturnal Hypoventilation in Slowly Progressive Myopathies.

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 ptcCO2 ≥ 50 mmHg for ≥ 30 min or increase in ptcCO2 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.

Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing.

Rationale: Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. Objectives: Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. Methods: From five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs. Measurements and Main Results: A total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93]. Conclusions: Using nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea.

Technical Innovations in Pneumology: E-Health, Screening, Diagnostics, and Therapy.

At the 2020 "Luftschlösser" (castles in the air) conference, experts from a wide range of pneumological fields discussed technical innovations in pneumology, which can be seen in many different areas of the field, including e-health, screening, diagnostics, and therapy. They contribute to substantial advancements ranging from the innovative use of diagnostic tools to novel treatments for chronic lung diseases. Artificial intelligence enables broader screening, which can be expected to have beneficial effects on disease progression and overall prognosis. There is still a high demand for clinical trials to investigate the usefulness and risk-benefit ratio. Open questions remain especially about the quality and utility of medical apps in an inadequately regulated market. This article weighs the pros and cons of technical innovations in specific subspecialties of pneumology based on the lively exchange of ideas among various pneumological experts.

Sleep-Disordered Breathing and Nocturnal Hypoxemia in Precapillary Pulmonary Hypertension: Prevalence, Pathophysiological Determinants, and Clinical Consequences.

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.

High sensitivity of PD-L1 analysis from pleural effusion in nonsmall cell lung cancer.

Background: Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) immune checkpoint inhibitors have been approved for monotherapy of metastatic nonsmall cell lung cancer (mNSCLC) depending on tumour cells' PD-L1 expression. Pleural effusion is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from pleural effusion samples is unclear. Aim: The aim of the study was to analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of pleural effusion in NSCLC as compared to immunohistochemistry of pleural biopsies. Patients and Methods: Fifty consecutive subjects (17 female, median age 72.5 years, seven never-smokers) were enrolled in this prospective controlled two-centre study. Inclusion criteria were pleural effusion, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, and written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, and positive and negative predictive value was performed for PD-L1 detection from pleural effusion. Results: 50 subjects underwent pleural puncture and thoracoscopy. Pathological diagnoses were lung cancer (48), lymphoma (1) and mesothelioma (1). Sensitivity, specificity, positive predictive value and negative predictive value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% CI 46-100%), 63% (36-84%), 45% (18-75%) and 100% (66-100%), and with expression ≥1% defined as positive 86% (56-97%), 43% (12-80%), 75% (47-92%) and 60% (17-93%). Conclusion: PD-L1 analysis in tumour-positive pleural effusion samples shows a very high sensitivity and negative predictive value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negative predictive value, making other invasive procedures necessary (NCT02855281).

Evaluation of a multicomponent grading system for obstructive sleep apnoea: the Baveno classification.

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.