Progressive pulmonary fibrosis in patients with connective tissue disease-associated interstitial lung disease: An explorative study.

Objectives: The aim of this study was to identify differences and similarities between connective tissue disease (CTD) patients with and without progressive pulmonary fibrosis (PPF) by applying the new guidelines. Patients and methods: Patient characteristics and disease courses from medical records of 50 CTD-associated Interstitial lung disease (ILD) patients (33 females, 17 males; mean age: 60.1±12.9 years) were longitudinally studied between January 2018 and May 2022. Respiratory involvement in CTD patients was described, and differences in CTD patients who developed PPF compared to those who did not were identified by the 2022 ATS (American Thoracic Society)/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT (Asociación Latinoamericana de Thórax) Guidelines on Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis in Adults. Results: In the majority (74%) of patients, CTD was diagnosed before ILD onset. Nonspecific interstitial pneumonia was the most common high resolution computer tomography pattern, followed by the usual interstitial pneumonia pattern. On pulmonary function test, 38% had a restrictive pattern at baseline. Patients without PPF tended to have worse lung function at baseline and increased macrophage count in bronchoalveolar lavage than patients with PPF. Conclusion: In patients without PPF, disease progression may be missed, resulting in inadequate management. Interdisciplinary management of patients with CTD with the participation of pulmonologists and precise lung function diagnostics is recommended.

[Medical societies in Germany call for a ban on flavors in e-cigarettes - A Position Paper of the German Respiratory Society (DGP) in cooperation with other professional associations and organizations]. / Medizinische Fachgesellschaften fordern ein Verbot von Aromen in E-Zigaretten.

E-cigarettes are primarily used by teenagers and young adults. Flavors in e-cigarettes increase their attractiveness and encourage young people and adults to start using them. This exposes young people in particular to the risk of nicotine addiction and various toxic substances from the aerosol of e-cigarettes. There are indications that various flavors in e-cigarettes are harmful to health, although toxicological studies are still lacking for the majority of flavors. There is a need for independent scientific investigations in this area. The scientific societies involved are calling for a ban on flavors in e-cigarettes, a ban on disposable e-cigarettes, effective regulation of the sale of e-cigarettes and effective control and implementation of the provisions for the protection of minors.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society and the European Society of Intensive Care Medicine. Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society (ERS) and the European Society of Intensive Care Medicine (ESICM). Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Deventilation Syndrome in COPD Patients Receiving Long-Term Home Noninvasive Ventilation: A Systematic Scoping Review.

The treatment of patients with COPD and chronic hypercapnic respiratory failure using noninvasive ventilation (NIV) is well established. A "deventilation syndrome" (DVS) has been described as acute dyspnea after cessation of NIV therapy. A systematic scoping review reporting according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) searching Embase was conducted in September 2021. A final manual search followed in February 2023. Literature synthesis was blinded using Rayyan by three different reviewers. A total of 2,009 studies were screened. Five studies met the eligibility criteria. Four articles presented original data. Three articles examined potential treatment options. Three studies were prospective; none were randomized. A total of 122 patients were included. DVS was defined differently in all studies. Seventy-four patients were identified to suffer from DVS (48 controls). Patients were evaluated by blood gas analysis, transcutaneous TcCO2 measurement, spirometry, whole-body plethysmography, respiratory muscle assessments, diaphragmatic electromyography, ultrasound, 6-min walk test, polysomnography, and questionnaires. Treatment approaches studied were minimization of "patient-ventilator asynchrony" (PVA) and use of pursed- lip breathing ventilation. Pathophysiological mechanisms discussed were PVA, high inspiratory positive airway pressure, hyperinflation, respiratory muscle impairment, and increased respiratory rates. Compared with controls, patients with DVS appeared to suffer from more severe airway obstruction, hyperinflation, and PaCO2 retention; worse exercise test scores; and poorer quality of life. The available evidence does not allow for definite conclusions about pathophysiological mechanisms, ethology, or therapeutic options. Future studies should focus on a consistent definition and possible pathomechanisms.

Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review.

This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting Focal adhesion kinase (FAK) and the Transforming Growth Factor ß (TGF-ß) pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, ß-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

GLI-12 Reference Values versus Fixed 0.7 Ratio for the Detection of Airflow Obstruction in the Presence of Lung Hyperinflation.

Introduction: Airflow obstruction (AO) is evidenced by reduced forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) with the threshold for diagnosis often being set at <0.7. However, currently the ATS/ERS standards for interpretation of lung function tests recommend the lower limit of normal (LLN), calculated by reference equations of the Global Lung Initiative from 2012 (GLI-12), as a threshold for AO diagnosis. The present study aims to investigate phenotypes, with focus on hyperinflation, which influence AO prevalence defined by FEV1/FVC < LLN when compared to the fixed 0.7 threshold. Methods: Data from 3,875 lung function tests (56.4% men, aged 18-95) including 3,824 body plethysmography recordings performed from July 2021 to June 2022 were analysed. The difference between both classifiers was quantified, before and after stratification by sex, age, and hyperinflation. Results: AO diagnosis was significantly less frequent with the LLN threshold (18.2%) compared to the fixed threshold (28.0%) (p < 0.001) with discordance rate of 10.5%. In the presence of mild or moderate hyperinflation, there was substantial agreement (Cohen's kappa: 0.616, 0.718) between the classifiers compared to near perfect agreement in the presence of severe hyperinflation (Cohen's kappa: 0.896). In addition, subgroup analysis after stratification for sex, age, and hyperinflation showed significant differences between both classifiers. Conclusion: The importance of using the LLN threshold instead of the fixed 0.7 threshold for the diagnosis of AO is highlighted. When using the fixed threshold AO, misdiagnosis was more common in the presence of mild to moderate hyperinflation.

RSV vaccination strategies for high-risk patients 2023: a collaborative position paper by leading German medical societies and organizations.

Respiratory syncytial virus (RSV) inflicts severe illness and courses of infections not only in neonates, infants, and young children, but also causes significant morbidity and mortality in older adults and in people with immunosuppression, hemato-oncologic disease, chronic lung disease, or cardiovascular disease. In June and August 2023, effective vaccines against RSV were approved for the first time by the European Medicines Agency (EMA) for the EU. The respective pivotal studies showed a very high efficacy of the vaccine in preventing severe RSV-associated respiratory infections. At this point, use of the respective vaccines is restricted to persons aged 60 years or older, according to the registration studies. We therefore recommend use of the vaccination in persons aged 60 years or older. In addition, we recommend use of the vaccination in adults of any age with severe pulmonary or cardiovascular pre-existing conditions, as well as in adults with significant immune compromise, after individual consultation with the treating physician. Cost coverage can be applied for individually with the responsible health insurance company.

[Pulmonary involvement in idiopathic inflammatory myopathies]. / Pulmonale Beteiligung bei idiopathischen inflammatorischen Myopathien.

Idiopathic inflammatory myopathies are rare systemic diseases with different types of pulmonary manifestations depending on the underlying aetiology; here, interstitial lung diseases (ILD) are the most frequently found patterns depending on the underlying disorder. There is a lack of sufficient prospective studies on this heterogeneous group of patients, particularly in case of ILD being involved. The diagnosis is based upon guideline recommendations for ILD and requires a multidisciplinary discussion within a team with specific expertise in this field. Myositis specific antibodies and myositis associated antibodies form an essential part of the diagnostic tools and may also be associated with a certain phenotype or disease progression. Anti-t-RNA-synthetase antibodies (Anti-ARS) and anti-melanoma differentiation-associated gene 5 antibodies (MDA5) play an important clinical role for treatment the estimation of response and prognosis. The most common ILD patterns are nonspecific interstitial pneumonia (NSIP) and organising pneumonia (OP) or a mixed pattern of both. Treatment is based on systemic steroids and early initiation of other immunosuppressant drugs. Evidence for this is, however, sparse, since most of the studies having investigated treatment modalities are of retrospective nature, even though some new prospective data may be useful for the establishment of treatment pathways in the future.

Ambulatory Long-Term Oxygen Therapy in Patients with Severe COPD: A Randomized Crossover Trial to Compare Constant-Minute-Volume and Constant-Bolus Systems.

Background and Methods: Constant-minute-volume and constant-bolus devices serve as two different means of portable oxygen conservation. A prospective randomised crossover study was conducted in COPD GOLD IV patients to investigate the effect of these two devices on dyspnea, oxygenation and 6-minute walking test (6MWT) distance. The primary endpoint was the final operating level required (operating level range 1-5 for both devices) by either device to meet the success criteria for mobile oxygen therapy, as outlined in the British Thoracic Society guidelines (SpO2 ≥90% throughout 6MWT; ≥10% increase in walking distance from baseline; improvement in BORG of at least 1 point from baseline). Results: Twenty-five patients were enrolled in the study and randomly assigned to one of two sequences involving the use of each type of portable oxygen conservation device. 14 female, 67.9 years (±7.8); FEV1: 27.3%pred. (±8.4); PaO2 at rest without oxygen: 50.3mmHg (±5.9). For both systems, 24/25 patients (96%) were successfully recruited. The mean operating-level difference when success criteria were met was -0.58 in favor of the constant bolus device (95% CI: -0.88 to -0.28, P <0.001). Secondary endpoints (walking distance, respiratory rate and BORG dyspnea) showed no statistically significant or clinically relevant differences. An algorithm created especially for this study showed a high success rate in terms of titration for the required operating level. Conclusion: Both portable oxygen-conserving devices met the success criteria in 96% of patients in the 6MWT when they were titrated to the correct level. The constant-bolus device required a significantly lower operating level to achieve the success criteria, hereby reducing energy consumption. Individual titration of the respective device is recommended, which can be facilitated by the novel titration algorithm described here.

[Non-invasive Mechanical Ventilation in Acute Respiratory Failure. Clinical Practice Guidelines - on behalf of the German Society of Pneumology and Ventilatory Medicine]. / S2k-Leitlinie Nichtinvasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

Adherence enhancing interventions for pharmacological and oxygen therapy in patients with COPD: protocol for a systematic review and component network meta-analyses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by hyperinflation and expiratory airflow limitation due to long-term exposure to irritants. The variety and complexity of COPD treatment and the possible added comorbidities may make the patients find it difficult to cope with the required medications. That is why supporting patients' adherence is critical because not taking medications correctly increases the risk of complications and creates an additional financial burden. A range of interventions aiming to improve patient adherence were used, and most of them are complex since they involve a mix of elements. Furthermore, despite the variety of available tools, assessing adherence is challenging because clinicians usually do not get a concrete judgement if their patients followed their treatment plan reliably. We aim to evaluate the effectiveness of adherence-enhancing interventions for COPD patients, explore which intervention (component) works for which patients and check the factors influencing the implementation and participant responses. METHODS: We will perform a comprehensive literature search (Medline, Embase, Cochrane Library, trial registries) without restrictions on language and publication status, and we will include all controlled studies investigating the effect of adherence-enhancing intervention on patients with COPD. We plan to involve COPD patients in the systematic review development through two patient interviews (one before and one after the systematic review). Two reviewers will perform the screening, data extraction and risk of bias (ROB) assessment. For ROB, we will use ROB 2.0 to assess randomised controlled trials, and ROBINS-I to assess non-randomised studies. We will perform pair-wise random-effects meta-analyses and component network meta-analyses to identify the most effective components and combinations of components. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. To determine the degree of complexity, we will use the iCAT_SR checklist, and then, following a logical model, we will group the interventions according to prespecified criteria. DISCUSSION: This systematic review aims to point out the most effective and implementable adherence-enhancing interventions by using methods for synthesising evidence on complex interventions and involving COPD patients all along with the review process. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022353977.

Clinical and imaging factors that can predict contagiousness of pulmonary tuberculosis.

BACKGROUND: Knowledge on predicting pulmonary tuberculosis (PTB) contagiosity in the hospital admission setting is limited. The objective was to assess clinical and radiological criteria to predict PTB contagiosity. METHODS: Retrospective analysis of 7 clinical, 4 chest X-ray (CXR) and 5 computed tomography (CT) signs in 299 PTB patients admitted to an urban tertiary hospital from 2008 to 2016. If the acid fact bacilli stain was positive (AFB+) on admission, the case was considered high contagiosity. RESULTS: Best predictors for high PTB contagiosity (AFB+) were haemoptysis (OR 4.33), cough (3.00), weight loss (2.96), cavitation in CT (2.75), cavitation in CXR (2.55), tree-in-bud-sign in CT (2.12), German residency of the patient (1.89), and abnormal auscultation findings (1.83). A previous TB infection reduced the risk of contagiosity statistically (0.40). Radiographic infiltrates, miliary picture, and pleural effusion were not helpful in predicting high or low contagiosity. 34% of all patients were clinically asymptomatic (20% of the highly contagious group, 50% of the low contagious group). CONCLUSION: Haemoptysis, cough and weight loss as well as cavitation and tree-in-bud sign in CXR/CT can be helpful to predict PTB contagiosity and to improve PTB management.

Costs of Weaning Failure: A Prospective, Multicentre, Controlled, Non-Randomised, Interventional Study on Economic Implications for the German Health Care System.

BACKGROUND: Intensive care patients with respiratory failure often need invasive mechanical ventilation (IMV). With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV rises as well. Up to 85% of these patients have no access to a certified weaning centre. Their medical care is associated with impaired quality of life and high costs for the German health care system. OBJECTIVES: This study examined the weaning outcome of patients in certified weaning centres after a primarily unsuccessful weaning attempt in order to calculate saving expenses compared to patients on long-term IMV in an outpatient setting. METHODS: In this multicentre, controlled, non-randomised, interventional, prospective study, 61 patients (16 from out-of-hospital long-term IMV, 49 from other hospitals) were referred to a certified weaning centre for a second weaning phase. The incurred costs after 1 year of the latter were compared to insurance claim data of patients who were discharged from an acute hospital stay to receive IMV in an outpatient setting. RESULTS: In the intervention group, 50 patients (82%) could be completely weaned or partially weaned using non-invasive ventilation, thus not needing IMV any longer. The costs per patient for weaning and out-of-hospital care in the intervention group were EUR 114,877.08, and the costs in the comparison cohort were EUR 234,442.62. CONCLUSIONS: Early transfer to a certified weaning centre can increase weaning success and reduce total costs by approximately EUR 120,000 per patient in the first year. Given the existing structural prerequisites in Germany, every patient should have access to a weaning centre before being transferred to long-term IMV, from a medical and health economical point of view.

[Neuralgic amyotrophy: a common cause of unilateral and bilateral diaphragmatic pareses]. / Die neuralgische Amyotrophie: eine häufige Ursache uni- oder bilateraler Zwerchfellparesen.

There are several causes for unilateral or bilateral diaphragmatic paresis. The most common cause is an (intraoperative) injury to the phrenic nerve.However, in up to 20% of cases, no explanation can be found despite extensive workup. Neuralgic amyotrophy (NA, also known as Parsonage-Turner syndrome) is a common underdiagnosed multifocal autoimmune-inflammatory disease that predominantly affects proximal nerve segments of the upper extremities. Classic symptoms include acute onset of severe pain in the shoulder girdle with delayed onset of paresis of the shoulder and arm muscles. In at least 7% of cases, the phrenic nerve is also affected. Based on the annual incidence of NA of 1:1000, the entity as a cause of diaphragmatic dysfunction is probably not as uncommon as previously thought. However, clinical experience shows that this diagnosis is often not considered, and diaphragmatic paresis gets wrongly classified as idiopathic.This is particularly disastrous because in the early stage of NA, medical therapy with corticosteroids is mostly not considered and the possibility that surgical repair of the diaphragm may be performed prematurely, given that the condition may resolve spontaneously many months after symptom onset.The aim of the present article is to raise awareness of the entity of NA as a cause of diaphragmatic paresis and to establish a standardized approach to diagnosis and treatment.

Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD). Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO2, PaO2, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate. Results: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO2 was greater with higher baseline PaCO2. NIV intensity per se was not associated with improved PaCO2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO2. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found. Conclusion: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO2, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy. (AU)

[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

The use of digital web-based video training for correct inhalation technique during the COVID-19 pandemic.

Scientifically validated web-based training videos for proper inhalation technique were increasingly used by an international audience during the pandemic. Translations into additional languages would support a larger patient population. https://bit.ly/3lYQwsD.