A modified Delphi exercise in physician-perceived risk factors for drug-induced pneumotoxicity in patients with rheumatological disease.

BACKGROUND: Drugs used to treat rheumatic disease are associated with pneumotoxicity (drug-induced lung disease), but little is known about associated risk factors. AIM: To determine expert physician-perceived risk factors for developing pneumotoxicity in patients with rheumatologic conditions. METHODS: A modified international 3-tier Delphi exercise was performed. Tier 1 determined patient and drug variables that physicians perceive to be risk factors. Tier 2 determined degree of risk associated with the Tier-1 derived variables. Tier 3 aimed to internally validate and stratify exemplar cases into risk categories. RESULTS: 134 pulmonologists and 49 rheumatologists responded to Tier 1;157 physicians completed all tiers. Perceived risk factors included: drug type; history of previous pneumotoxicity; age; smoking; underlying rheumatic disease type and activity; renal function; pulmonary hypertension; left ventricular failure;presence, nature, severity and progression of pre-existing interstitial lung disease. Tier 2 data stratified these variables into risk profiles e.g. never versus current smoking was perceived as low and high risk respectively. An example of perceived high risk resulting from Tier 3 is a 75-year-old current smoker with high-activity rheumatoid arthritis (RA) with severe, progressive ILD being started on methotrexate. A perceived low risk is a 75-year-old currentsmoker with moderate-activity RA and emphysema with no cardiac or renal disease and no pre-existing ILD being started on rituximab. A risk prediction scoring tool is being developed to be used in validation studies. CONCLUSION: This modified Delphi exercise defined and stratified the perceived risk factors for developing pneumotoxicity. Age, current smoking, high underlying rheumatological disease activity, HRCT definite UIP and honeycombing, severity and progression of pre-existing ILD were perceived to be the highest risk-factors.

[Outpatient exercise training for chronic lung disease - for whom, how and why?] / Lungensport: Für wen, wie und warum?

There is a legal entitlement to participate in outpatient exercise groups in accordance with the German Social Code (Book IX) which regulates and facilitates prescriptions for patients with chronic respiratory diseases. A medical examination with specific inclusion and exclusion criteria prior to admission to an exercise group ensures safe participation.Traditional outpatient exercise groups are conducted in face-to-face groups for 60 to 90 minutes, once a week, with structured warm-up, main and cool-down phases. In addition, since the coronavirus pandemic, the introduction of online exercise groups via videoconferencing has enabled flexible participation (even without a prescription). To date, more than 11,000 German patients have participated in online exercise groups since 2021.Scientific evidence confirms the significant benefits of regular exercise, such as improved physical performance and reduced breathlessness. The psychosocial benefits and the promotion of self-efficacy are additionally supported by the supervision of a specialized trainer. Regular exercise (e.g. in outpatient exercise groups) is an inexpensive and very effective form of therapy to improve the quality of life of people with chronic respiratory diseases.

Nuts and bolts of lung ultrasound: utility, scanning techniques, protocols, and findings in common pathologies.

Point of Care ultrasound (POCUS) of the lungs, also known as lung ultrasound (LUS), has emerged as a technique that allows for the diagnosis of many respiratory pathologies with greater accuracy and speed compared to conventional techniques such as chest x-ray and auscultation. The goal of this narrative review is to provide a simple and practical approach to LUS for critical care, pulmonary, and anesthesia providers, as well as respiratory therapists and other health care providers to be able to implement this technique into their clinical practice. In this review, we will discuss the basic physics of LUS, provide a hands-on scanning technique, describe LUS findings seen in normal and pathological conditions (such as mainstem intubation, pneumothorax, atelectasis, pneumonia, aspiration, COPD exacerbation, cardiogenic pulmonary edema, ARDS, and pleural effusion) and also review the training necessary to achieve competence in LUS.

Risk of pulmonary complications after video-assisted thoracoscopic pulmonary resection in children.

BACKGROUND: Postoperative pulmonary complications (PPCs) are associated with high mortality and morbidity rates. Children are more susceptible to PPCs owing to smaller functional residual capacity and greater closing volume. Risk factors of PPCs in children undergoing lung resection remain unclear. METHODS: This retrospective study enrolled children who underwent video-assisted thoracoscopic surgery between January 2018 and February 2023. The primary outcome was PPC occurrence. Multivariate logistic regression was used to analyze risk factors for PPCs. RESULTS: Overall, 640 children were analyzed; their median age was 7 (interquartile range: 5-11) months, and the median tidal volume was 7.66 (6.59-8.49) mL/kg. One hundred and seventeen (18.3%) developed PPCs. PPCs were independently associated with male sex (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.17-2.88; P=0.008), longer OLV duration (OR, 1.01; 95% CI, 1.0-1.01; P=0.001), and less surgeon's experience (OR, 1.67; 95% CI, 1.03-2.7; P=0.036). When low-tidal-volume cutoff was defined as <8 mL/kg, PEEP level was a protective factor for PPCs (OR, 0.83; 95% CI, 0.69-1.00; P=0.046). Additionally, PPCs were associated with increased hospital stay (P<0.001). CONCLUSIONS: Male sex, longer OLV duration, less surgeon's experience, and lower PEEP were risk factors of PPCs in children undergoing video-assisted thoracoscopic surgery. Our findings may serve as targets for prospective studies investigating specific ventilation strategies for children.

Microbiome and metabolome patterns after lung transplantation reflect underlying disease and chronic lung allograft dysfunction.

BACKGROUND: Progression of chronic lung disease may lead to the requirement for lung transplant (LTx). Despite improvements in short-term survival after LTx, chronic lung allograft dysfunction (CLAD) remains a critical challenge for long-term survival. This study investigates the molecular and microbial relationships between underlying lung disease and the development of CLAD in bronchoalveolar lavage fluid (BALF) from subjects post-LTx, which is crucial for tailoring treatment strategies specific to allograft dysfunctions. METHODS: Paired 16S rRNA gene amplicon sequencing and untargeted LC-MS/MS metabolomics were performed on 856 BALF samples collected over 10 years from LTx recipients (n = 195) with alpha-1-antitrypsin disease (AATD, n = 23), cystic fibrosis (CF, n = 47), chronic obstructive pulmonary disease (COPD, n = 78), or pulmonary fibrosis (PF, n = 47). Data were analyzed using random forest (RF) machine learning and multivariate statistics for associations with underlying disease and CLAD development. RESULTS: The BALF microbiome and metabolome after LTx differed significantly according to the underlying disease state (PERMANOVA, p = 0.001), with CF and AATD demonstrating distinct microbiome and metabolome profiles, respectively. Uniqueness in CF was mainly driven by Pseudomonas abundance and its metabolites, whereas AATD had elevated levels of phenylalanine and a lack of shared metabolites with the other underlying diseases. BALF microbiome and metabolome composition were also distinct between those who did or did not develop CLAD during the sample collection period (PERMANOVA, p = 0.001). An increase in the average abundance of Veillonella (AATD, COPD) and Streptococcus (CF, PF) was associated with CLAD development, and decreases in the abundance of phenylalanine-derivative alkaloids (CF, COPD) and glycerophosphorylcholines (CF, COPD, PF) were signatures of the CLAD metabolome. Although the relative abundance of Pseudomonas was not associated with CLAD, the abundance of its virulence metabolites, including siderophores, quorum-sensing quinolones, and phenazines, were elevated in those with CF who developed CLAD. There was a positive correlation between the abundance of these molecules and the abundance of Pseudomonas in the microbiome, but there was no correlation between their abundance and the time in which BALF samples were collected post-LTx. CONCLUSIONS: The BALF microbiome and metabolome after LTx are particularly distinct in those with underlying CF and AATD. These data reflect those who developed CLAD, with increased virulence metabolite production from Pseudomonas, an aspect of CF CLAD cases. These findings shed light on disease-specific microbial and metabolic signatures in LTx recipients, offering valuable insights into the underlying causes of allograft rejection. Video Abstract.

Implementation of spirometry screening for post-tuberculosis lung disease (PTLD) among adolescents and adults enrolled within the National Tuberculosis Control Program of Carmelo Hospital in Chókwè District, Mozambique: A hybrid type III effectiveness-implementation study protocol.

BACKGROUND: Despite receiving adequate treatment, many tuberculosis (TB) survivors are left with post-tuberculosis complications, possibly due to lung tissue damage incurred during the active period of the disease. Current TB programs worldwide deliver quality care throughout the course of active TB treatment, yet often fail to provide organized follow-up once treatment ends. Post-tuberculosis lung disease (PTLD) is a prominent, yet underrecognized cause of chronic lung disease, managed similarly to chronic respiratory diseases with pharmacotherapy and/or personalized pulmonary rehabilitation interventions. Basic pulmonary rehabilitation packages for people finishing TB treatment are still lacking in low- and middle-income countries (LMICs). We offer a study protocol to evaluate the implementation of spirometry and symptom screening for PTLD among people who have completed TB treatment in a rural district in Mozambique. METHODS: The overall objective of this study is to evaluate the introduction of a new screening program that utilizes symptom screening and spirometry for diagnosing PTLD among adolescents and adults that have completed TB treatment. This research protocol consists of three complementary components: 1) assessing the prevalence of PTLD among patients enrolled in the National TB Control Program (NTCP) at Carmelo Hospital (CHC) in Chókwè District, Mozambique; 2) evaluating anticipated implementation outcomes through the identification of the site-, provider-, and individual-level determinants that either facilitate or hinder the successful adoption, implementation, and maintenance of the spirometry screening program, and 3) evaluating the real-time implementation outcomes/processes in order to provide practical evidence-based key indicators of successful implementation of the spirometry screening program. DISCUSSION: Providing well-organized, evidence-based care for individuals with a history of TB who are experiencing symptoms of PTLD can relieve chronic respiratory issues, enhance quality of life, and potentially lower the risk of further pulmonary infections, including recurrent TB. However, there is a significant gap in the literature regarding the implementation of best practices of HIV and TB health services delivery. Addressing this gap could assist Mozambique in improving diagnosis, treatment, and continuity of care for people formerly living with TB. The insights from this study will help decision-makers improve spirometry screening coverage, enhance intervention effectiveness, and translate our findings to evidence-based programming. TRIAL REGISTRATION: ISRCTN92021748 retrospectively registered.

Nontuberculous Mycobacterial Pulmonary Disease: Patients, Principles, and Prospects.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in incidence globally and challenging to manage. The 2020 multisociety treatment guideline and the 2022 consensus recommendations provide comprehensive evidence-based guides to manage pulmonary diseases caused by the most common NTM. However, with >190 different NTM species that may require different multidrug regimens for treatment, the breadth and complexity of NTM-PD remain daunting for both patients and clinicians. In this narrative review, we aim to distill this broad, complex field into principles applicable to most NTM species and highlight important nuances, specifically elaborating on the presentation, diagnosis, principles of patient-centered care, principles of pathogen-directed therapy, and prospects of NTM-PD.

Computer-aided diagnosis of cystic lung diseases using CT scans and deep learning.

BACKGROUND: Auxiliary diagnosis of different types of cystic lung diseases (CLDs) is important in the clinic and is instrumental in facilitating early and specific treatments. Current clinical methods heavily depend on accumulated experience, restricting their applicability in regions with less developed medical resources. Thus, how to realize the computer-aided diagnosis of CLDs is of great clinical value. PURPOSE: This work proposed a deep learning-based method for automatically segmenting the lung parenchyma in computed tomography (CT) slice images and accurately diagnosing the CLDs using CT scans. METHODS: A two-stage deep learning method was proposed for the automatic classification of normal cases and five different CLDs using CT scans. Lung parenchyma segmentation is the foundation of CT image analysis and auxiliary diagnosis. To meet the requirements of different sizes of the lung parenchyma, an adaptive region-growing and improved U-Net model was employed for mask acquisition and automatic segmentation. The former was achieved by a self-designed adaptive seed point selection method based on similarity measurement, and the latter introduced multiscale input and multichannel output into the original U-Net model and effectively achieved the lightweight design by adjusting the structure and parameters. After that, the middle 30 consecutive CT slice images of each sample were segmented to obtain lung parenchyma, which was employed for training and testing the proposed multichannel parallel input recursive MLP-Mixer network (MPIRMNet) model, achieving the computer-aided diagnosis of CLDs. RESULTS: A total of 4718 and 16 290 CT slice images collected from 543 patients were employed to validate the proposed segmentation and classification methods, respectively. Experimental results showed that the improved U-Net model can accurately segment the lung parenchyma in CT slice images, with the Dice, precision, volumetric overlap error, and relative volume difference of 0.96 ± 0.01, 0.93 ± 0.04, 0.05 ± 0.02, and 0.05 ± 0.03, respectively. Meanwhile, the proposed MPIRMNet model achieved appreciable classification effect for normal cases and different CLDs, with the accuracy, sensitivity, specificity, and F1 score of 0.8823 ± 0.0324, 0.8897 ± 0.0325, 0.9746 ± 0.0078, and 0.8831 ± 0.0334, respectively. Compared with classical machine learning and convolutional neural networks-based methods for this task, the proposed classification method had a preferable performance, with a significant improvement of accuracy of 10.74%. CONCLUSIONS: The work introduced a two-stage deep learning method, which can achieve the segmentation of lung parenchyma and the classification of CLDs. Compared to previous diagnostic tasks targeting single CLD, this work can achieve various CLDs' diagnosis in the early stage, thereby achieving targeted treatment and increasing the potential and value of clinical applications.

Pulmonary Lymphatics History, Anatomy, and Pathophysiology: Emerging Knowledge and a Look to the Future.

Central lymphatic disorders of the lung have not received intense investigation. Lymphatic system physiology is presented in the context of historical developments and basic lung lymphatic anatomy is reviewed followed by emerging characteristics of primary and secondary pathophysiological disturbances of lymphatic involvement in a number of pulmonary diseases including Gorham-Stout disease, pulmonary edema and infections and inflammatory conditions including lymphangioleiomyomatosis (LAM). The future includes potential molecular targeting of lymphangiogenesis or lymphatic vessels for interventional occlusion. This article is an amalgamation of presentations at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease and as part of a Special Symposium on the Lymphatic system of the Heart and Lung in Health and Disease at the 26th International Congress of Lymphology meeting held in Barcelona, Spain, September 2017, which has been updated to 2024.

Alpha 1 antitrypsin augmentation for alpha 1 antitrypsin deficiency associated lung disease.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of alpha 1 antitrypsin augmentation therapy on respiratory disease in people with alpha 1 antitrypsin deficiency.

Comparative analysis of non-tuberculous mycobacterial lung disease and lung colonization: a case-control study.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are common opportunistic pathogens, and the most common infection site is lung. NTM are found commonly in the environment. Many patients have NTM lung colonization (NTM-Col). NTM lung disease (NTM-LD) have no specific sympotms, though it is hard to differentiate NTM-LD and NTM-Col under this circumstance. The aim of this study is to explore the differences between NTM-LD and NTM-Col for future clinical diagnosis and treatment. METHODS: We retrospectively enrolled patients who had a history of NTM isolated from respiratory specimens in Peking Union Medical College Hospital (PUMCH) from January 1st, 2013 to December 31st, 2022. Patients were classified into NTM-LD group and NTM-Col group. Demographic characteristics, clinical manifestations, laboratory tests and imaging findings of the two groups were compared. Comparative analysis was also performed in peripheral blood lymphocyte subsets among three groups. RESULTS: A total of 127 NTM-LD patients and 37 NTM-Col patients were enrolled. Proportion of patients with bronchiectasis was higher in NTM-LD group than in NTM-Col group (P = 0.026). Predominant NTM isolates were Mycobacterium avium complex (MAC). NTM-LD group had a higher proportion of Mycobacterium intracellulare (P = 0.004). CD4+ T cells counts was lower in NTM-LD group (P = 0.041) than in NTM-Col group. Imaging finding of bronchiectasis (P = 0.006) was higher in NTM-LD group than in NTM-Col group. Imaging findings of bronchiectasis (OR = 6.282, P = 0.016), and CD4+ T cell count (OR = 0.997, P = 0.012) were independent associated factors for differential diagnosis between NTM-LD and NTM-Col. CONCLUSION: NTM isolates from both NTM-LD and NTM-Col patients were predominantly MAC, with a higher Mycobacterium intracellulare isolation rate in NTM-LD group. Imaging findings of bronchiectasis and lower peripheral blood CD4+ T cell count may be helpful to separate the diagnosis of NTM-LD from NTM-Col.

Drosophila melanogaster as an Alternative Model to Higher Organisms for In Vivo Lung Research.

COPD and asthma are lung diseases that cause considerable burden to more than 800 million people worldwide. As both lung diseases are so far incurable, it is mandatory to understand the mechanisms underlying disease development and progression for developing novel therapeutic approaches. Exposures to environmental cues such as cigarette smoke in earliest life are known to increase disease risks in the individual's own future. To explore the pathomechanisms leading to later airway disease, mammalian models are instrumental. However, such in vivo experiments are time-consuming and burdensome for the animals, which applies in particular to transgenerational studies. Along this line, the fruit fly Drosophila melanogaster comes with several advantages for research in this field. The short lifespan facilitates transgenerational studies. A high number of evolutionary conserved signaling pathways, together with a large toolbox for tissue-specific gene modification, has the potential to identify novel target genes involved in disease development. A well-defined airway microbiome could help to untangle interactions between disease development and microbiome composition. In the following article, Drosophila melanogaster is therefore presented and discussed as an alternative in vivo model to investigate airway diseases that can complement and/or replace models in higher organisms.

Use of artificial intelligence-powered ECG to differentiate between cardiac and pulmonary pathologies in patients with acute dyspnoea in the emergency department.

BACKGROUND: Acute dyspnoea is common in acute care settings. However, identifying the origin of dyspnoea in the emergency department (ED) is often challenging. We aimed to investigate whether our artificial intelligence (AI)-powered ECG analysis reliably distinguishes between the causes of dyspnoea and evaluate its potential as a clinical triage tool for comparing conventional heart failure diagnostic processes using natriuretic peptides. METHODS: A retrospective analysis was conducted using an AI-based ECG algorithm on patients ≥18 years old presenting with dyspnoea at the ED from February 2006 to September 2023. Patients were categorised into cardiac or pulmonary origin groups based on initial admission. The performance of an AI-ECG using a transformer neural network algorithm was assessed to analyse standard 12-lead ECGs for accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Additionally, we compared the diagnostic efficacy of AI-ECG models with N-terminal probrain natriuretic peptide (NT-proBNP) levels to identify cardiac origins. RESULTS: Among the 3105 patients included in the study, 1197 had cardiac-origin dyspnoea. The AI-ECG model demonstrated an AUC of 0.938 and 88.1% accuracy for cardiac-origin dyspnoea. The sensitivity, specificity and positive and negative predictive values were 93.0%, 79.5%, 89.0% and 86.4%, respectively. The F1 score was 0.828. AI-ECG demonstrated superior diagnostic performance in identifying cardiac-origin dyspnoea compared with NT-proBNP. True cardiac origin was confirmed in 96 patients in a sensitivity analysis of 129 patients with a high probability of cardiac origin initially misdiagnosed as pulmonary origin predicted by AI-ECG. CONCLUSIONS: AI-ECG demonstrated superior diagnostic accuracy over NT-proBNP and showed promise as a clinical triage tool. It is a potentially valuable tool for identifying the origin of dyspnoea in emergency settings and supporting decision-making.

Thoracic ultrasound: a review of the state-of-the-art.

Thoracic ultrasound (TUS) is a tool that has become increasingly essential in the daily practice of thoracic medicine. Driven by the need to assess patients during the COVID-19 pandemic, there has been an increase in the use of point-of-care TUS, which has demonstrated several benefits, either as a complement to clinical decision-making for diagnosis or as a real-time guide for procedures, whether as a predictor or measure of treatment response. Here, we present a review of TUS, based on the most recent scientific evidence, from equipment and techniques to the fundamentals of pulmonary ultrasound, describing normal and pathological findings, as well as focusing on the management of lung disease and guidance for invasive thoracic procedures at the bedside. Finally, we highlight areas of perspective and potential lines of research to maintain interest in this valuable tool, in order to improve the diagnostic process and expand the treatment arsenal.

Drug-induced lung disease: a narrative review.

Drug-induced lung disease (DILD) encompasses a broad, highly heterogeneous group of conditions that may occur as a result of exposure to numerous agents, such as antineoplastic drugs, conventional or biological disease-modifying antirheumatic drugs, antiarrhythmics, and antibiotics. Between 3% and 5% of prevalent cases of interstitial lung diseases are reported as DILDs. The pathogenesis of lung injury in DILD is variable, multifactorial, and often unknown. Acute presentation is the most common, can occur from days to months after the start of treatment, and ranges from asymptomatic to acute respiratory failure. The CT patterns are varied and include ground-glass opacities, organizing pneumonia, and diffuse alveolar damage. Notably, there are no clinical manifestations or CT patterns specific to DILD, which makes the diagnosis quite challenging and necessitates a high index of suspicion, as well as the exclusion of alternative causes such as infection, cardiac-related pulmonary edema, exacerbation of a preexisting ILD, and neoplastic lung involvement. Discontinuation of the offending medication constitutes the cornerstone of treatment, and corticosteroid treatment is usually necessary after the onset of clinical manifestations. The prognosis varies widely, with high mortality rates in severe cases. A history of medications related to pulmonary toxicity in patients with new-onset respiratory symptoms should prompt consideration of DILD as a potential underlying cause.