Proposal of a radiation-free screening protocol for early detection of interstitial lung involvement in seropositive and ACPA-positive rheumatoid arthritis.

Background: Seropositive rheumatoid arthritis (RA) is associated with significant cardiovascular and pulmonary morbidity. However, screening for early detection of pulmonary involvement especially interstitial lung disease (ILD) is not established in RA.

Methods: We propose a non-invasive radiation-free approach to screen for interstitial lung involvement (ILI) by means of pulmonary function tests (PFT) and pleuro-pulmonary transthoracic ultrasound (LUS) with additional cardiopulmonary exercise tests (CPET) with ECG, and echocardiography.

[Diagnostics of Interstitial Lung Diseases - Practical Instructions with a Focus on Rheumatologic Systemic Diseases].

Interstitial lung diseases (ILD) are etiologically heterogeneous with unknown and known causes like rheumatologic systemic diseases differing in their therapeutic and prognostic consequences. In consensus between pulmonologists, rheumatologists, radiologists, and pathologists, we developed practical instructions for ILD diagnosis in rheumatologic systemic diseases, in particular because ILD can present in early stages of rheumatic systemic diseases. ILD diagnosis is based on clinical assessment results including a detailed medical history, physical examination, focused laboratory tests, radiology with a high-resolution computed tomography, lung function, and histopathology also to differentiate it from cardiac and infection associated lung diseases.

Bronchoscopic Probe-Based Confocal Laser Endomicroscopy to Diagnose Diffuse Parenchymal Lung Diseases.

Background: Diagnosis of diffuse parenchymal lung disease (DPLD) is based on clinical evaluation, radiological imaging and histology. However, additional techniques are warranted to improve diagnosis.

Aims And Objective: Probe based confocal laser endomicroscopy (pCLE) allows real time in vivo visualisation of the alveolar compartment during bronchoscopy based on autofluorescence of elastic fibres.

Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers.

The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types.

Automated evaluation of probe-based confocal laser endomicroscopy in the lung.

Rationale: Probe-based confocal endomicroscopy provides real time videos of autoflourescent elastin structures within the alveoli. With it, multiple changes in the elastin structure due to different diffuse parenchymal lung diseases have previously been described. However, these evaluations have mainly relied on qualitative evaluation by the examiner and manually selected parts post-examination.

Screening for Bronchoscopic Lung Volume Reduction: Reasons for Not Receiving Interventional Treatment.

Background: Evidence for bronchoscopic lung volume reduction (BLVR) is based on phase 2 studies and small randomized controlled trials with in- and exclusion criteria defining a therapeutic window and contraindications. Little is known about the applicability in routine clinical practice.

Aim: Which percentage of patients with severe emphysema referred to a specialized treatment center for BLVR is ultimately suitable for interventional bronchoscopic treatment? What is the relevance of the different contraindications?

Methods: Retrospective evaluation of emphysema patients referred to Asklepios Fachkliniken Munich-Gauting for BLVR between January 2014 and June 2015.

Pulmonary hypertension due to lung diseases: Updated recommendations from the Cologne Consensus Conference 2018.

The 2015 European Guidelines on Pulmonary Hypertension did not only cover pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase‑5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH.

Daily Chronic Intermittent Hypobaric Hypoxia Does Not Induce Chronic Increase in Pulmonary Arterial Pressure Assessed by Echocardiography.

Chronic hypoxia causes pulmonary vascular remodeling resulting in persistently increased pulmonary arterial pressures (PAP) even after return to normoxia. Recently, interest in chronic intermittent hypobaric hypoxia (CIHH) was raised because it occurs in subjects working at high altitude (HA) but living in lowland. However, effects of daily CIHH on PAP are unknown.

Pulmonary CCR2CD4 T cells are immune regulatory and attenuate lung fibrosis development.

Background: Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2CD4 T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 cell populations might either increase or decrease disease pathogenesis depending on their subtype.

Objective: To investigate the role of CCR2CD4 T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis.

Inspiratory capacity is not altered in operable chronic thromboembolic pulmonary hypertension.

Pathological alterations of inspiratory capacity (IC) have been observed in pulmonary hypertension. However, the clinical significance of IC in operable chronic thromboembolic pulmonary hypertension (CTEPH) without other pulmonary diseases remains unknown. CTEPH patients scheduled for pulmonary endarterectomy were prospectively screened.

Collapse phenomenon during Chartis collateral ventilation assessment.

Chartis is increasingly used for bronchoscopic assessment of collateral ventilation before endobronchial valve (EBV) treatment for severe emphysema. Its prognostic value is, however, limited by the airway collapse phenomenon. The frequency and clinical significance of the collapse phenomenon remain largely unknown.

The prognostic relevance of oxygen uptake in inoperable chronic thromboembolic pulmonary hypertension.

Background: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) present with a decreased oxygen uptake, however, the prognostic relevance of oxygen uptake (VO ) in inoperable CTEPH is unknown.

Methods: Patients with inoperable CTEPH were retrospectively analyzed. All patients were assessed by means of right heart catheterisation and cardio pulmonary exercise testing in semisupine position with a 30 Watt increment step-protocol.

The H2S-generating enzymes cystathionine β-synthase and cystathionine γ-lyase play a role in vascular development during normal lung alveolarization.

The gasotransmitter hydrogen sulfide (H2S) is emerging as a mediator of lung physiology and disease. Recent studies revealed that H2S administration limited perturbations to lung structure in experimental animal models of bronchopulmonary dysplasia (BPD), partially restoring alveolarization, limiting pulmonary hypertension, limiting inflammation, and promoting epithelial repair. No studies have addressed roles for endogenous H2S in lung development.

Carcinoid tumours of the lung and the 'PEPPS' approach: evaluation of preoperative bronchoscopic tumour debulking as preparation for subsequent parenchyma-sparing surgery.

Background: Preoperative bronchoscopic tumour ablation has been suggested as a beneficial treatment for bronchopulmonary carcinoid tumours, although data regarding its effects and long-term outcome are lacking.

Methods: In our case-matched cohort study with 208 patients with bronchopulmonary carcinoid tumours we investigated the role of preoperative bronchoscopic interventions before subsequent surgery and analysed the safety of this Procedure of Endobronchial Preparation for Parenchyma-sparing Surgery (PEPPS) based on metastasis and recurrence rates as well as survival data from 1991 to 2010. The subsequent surgery was classified into parenchyma-sparing procedures and classical lobectomies, bilobectomies and pneumonectomies.

Sildenafil versus nitric oxide for acute vasodilator testing in pulmonary arterial hypertension.

Vasoreactivity testing with inhaled NO is recommended for pulmonary arterial hypertension (PAH) because of its therapeutic and prognostic value. Sildenafil has acute pulmonary vasodilating properties, but its diagnostic and prognostic impact in PAH is unknown. Our objective was to compare acute vasodilating responses to sildenafil and those to NO during right heart catheterization and also their prognostic values in patients with PAH.

Acute hemodynamic effects of nebulized iloprost via the I-neb Adaptive Aerosol Delivery system in pulmonary hypertension.

Inhaled iloprost has proven to be an effective therapy in patients with pulmonary hypertension (PH). However, the acute hemodynamic effect of nebulized iloprost delivered via the I-neb Adaptive Aerosol Delivery (AAD) system remains unclear and needs to be assessed. In this study, 126 patients with PH were classified according to current guidelines (59, 34, 29, and 4 patients in groups 1/1', 3, 4, and 5, respectively; 20 patients had idiopathic pulmonary arterial hypertension [iPAH]), were randomly assigned to inhale iloprost 2.

Poor sleep quality is associated with exercise limitation in precapillary pulmonary hypertension.

Background: Patients with precapillary pulmonary hypertension (PH) have been reported to suffer from poor sleep quality, however, if this is related to physical exercise performance has not yet been thoroughly investigated.

Methods: Clinically stable out-patients with idiopathic pulmonary arterial hypertension (IPAH, n = 52) and chronic thromboembolic PH (CTEPH, n = 64) in NYHA classes II and III were prospectively enrolled. 54 healthy volunteers matched for anthropometric variables served as a control group.

The prognostic significance of inspiratory capacity in pulmonary arterial hypertension.

Background: Patients with pulmonary arterial hypertension (PAH) present with an altered inspiratory capacity (IC) reflecting dynamic hyperinflation (DH) that leads to mechanical constraints and excessive ventilatory demand, particularly during exercise, resulting in exertional dyspnea.

Objectives: Assessment of the long-term consequences of altered IC and DH in PAH.

Methods: 50 patients with newly diagnosed PAH were prospectively recruited.

Lysyl oxidases play a causal role in vascular remodeling in clinical and experimental pulmonary arterial hypertension.

Objective: Pulmonary vascular remodeling, the pathological hallmark of pulmonary arterial hypertension, is attributed to proliferation, apoptosis resistance, and migration of vascular cells. A role of dysregulated matrix cross-linking and stability as a pathogenic mechanism has received little attention. We aimed to assess whether matrix cross-linking enzymes played a causal role in experimental pulmonary hypertension (PH).

Endobronchial therapy with a thulium fiber laser (1940 nm).

Background: Nd:YAG laser (1064 nm) is standard in bronchology. The thulium fiber laser (1940 nm) has a nearly 1000-fold increased absorption in water, enabling precise tissue ablation with a small margin of coagulation, whereas 1064-nm laser light penetrates deeper into tissue with less controllable effects.

Objectives: To assess the safety, feasibility, and versatility of endobronchial thulium laser therapy in an observational cohort study.

Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-β signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts.

Glucocorticoids represent the mainstay therapy for many lung diseases, providing outstanding management of asthma but performing surprisingly poorly in patients with acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung fibrosis, and blunted lung development associated with bronchopulmonary dysplasia in preterm infants. TGF-β is a pathogenic mediator of all four of these diseases, prompting us to explore glucocorticoid/TGF-β signaling cross-talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide, and fluticasone, potentiated TGF-β signaling by the Acvrl1/Smad1/5/8 signaling axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well as primary lung fibroblasts, smooth muscle cells, and endothelial cells.

Sleep apnea in precapillary pulmonary hypertension.

Objectives: Pilot studies have described the occurrence of sleep apnea in patients with precapillary pulmonary hypertension (PH). However, there are no data on the prevalence of sleep-related breathing disorders in larger patient cohorts with PH.

Methods: 169 patients with a diagnosis of PH confirmed by right heart catheterisation and clinically stable in NYHA classes II or III were prospectively investigated by polygraphy (n = 105 females, mean age: 61.