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Review
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Cristina Maria Radu

,

Irena Nedelea

,

Vlad Andrei Ardelean

,

Adriana Parau

,

Milena Adina Man

Abstract: Background: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary antibody deficiency, associated with recurrent infections, immune dysregulation, and non-infectious complications. Amyloidosis is a rare but severe complication with pulmonary involvement being exceptional. Objective: To review reported cases of amyloidosis complicating CVID and present a unique case of pulmonary involvement. Methods: A literature research identified observational studies and case reports linking amyloidosis with CVID. Additionally, we describe a patient with CVID complicated by pulmonary and gastrointestinal amyloidosis. Results: Fifteen cases were identified, mostly amyloid A (AA) with multiple organ involvement. Only one case of pulmonary amyloidosis was reported. To date, no cases of pulmonary light-chain amyloidosis (AL) have been described in CVID patients without an underlying plasma cell dyscrasia. Our patient initially presented with AA amyloidosis but evolved to systemic AL type with rapid progression and fatal outcome despite therapy. Conclusions: Amyloidosis should be considered in CVID patients with atypical symptoms. Accurate amyloid typing is essential as treatment differs between AA and AL types. Early recognition may improve outcomes.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Caroline Braschel

,

Hannah Fabikan

,

Vania Mikaela Rodriguez

,

Maximilian Hochmair

,

Oliver Illini

,

Leyla Ay

,

Christoph Weinlinger

,

Julie Krainer-Jacobs

,

Nino Müser

,

Arschang Valipour

+1 authors

Abstract: Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence EGFR mutations was 11% (145 out of 1,267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4-24.9) and 14.2 months (95% CI: 7.4-20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, EGFR common mutation subtype (HR = 3.71 95%CI: 1.23 – 11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18-21. Conclusion: The results underscore the prognostic role of distinct EGFR genotypes and the urgency to determine the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mu-tations and the resulting need for further research to investigate alternative treatment options.
Review
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Martina Mazzoni

,

Sonia Lomuscio

,

Adriano La Vecchia

,

Rosamaria Terracciano

,

Fabio Antonelli

,

Pierluigi Vuilleumier

,

Annalisa Allegorico

Abstract: Background: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders characterized by variable degrees of inflammation and fibrosis affecting the pulmonary interstitium. Advances in molecular biology and genetics have greatly expanded our understanding of ILD pathogenesis, revealing novel mechanisms and supporting the development of precision medicine approaches. Genetic insights: Genetic factors play a pivotal role in ILD heterogeneity, influencing disease onset, severity, and progression. To date, more than 30 genes with different inheritance patterns (autosomal dominant, recessive, or X-linked) have been associated to ILDs. These genes are primarily involved in surfactant metabolism, telomere mainte-nance, immune regulation, and epithelial repair. Recent evidence also implicates genes encoding aminoacyl-tRNA synthetases. This review summarises the main genetic al-terations underlying ILD pathogenesis and discusses their impact on diagnostic and therapeutic approaches, highlighting how identification of disease-causing variants can improve diagnostic accuracy, refine prognostic assessment, and inform recurrence risk. Methods: A narrative review was conducted through targeted PubMed and Embase searches using disease- and gene-related keywords. Eligible publications included narrative and systematic reviews, meta-analyses, case series, prospective studies, society guidelines, and peer-reviewed editorials. Conclusions: This synthesis brings together the latest genetic insights into pediatric ILDs and their clinical implications. Integrating genomic data into clinical practice may enable earlier diagnosis, tailored follow-up, individualized therapeutic strategies, and more informed genetic counseling. Collectively, these advances hold promise for better out-comes in children affected by ILDs.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Quan Vu Tran Thien

,

Tho Nguyen Van

,

Quyen Thi Le Pham

,

Linh Duong Thi Chuc

,

Cong Nguyen Hai

,

Tuan Tran Trong Anh

,

Khai Ho Quoc

,

Huong Hoang Thi Lan

,

Lan Le Thi Tuyet

Abstract: Background/Objectives: Asthma action plans (AAP) are recommended for patients’ self-management of asthma and should be adapted countries’ situation. This study aimed to develop expert consensus on the optimal structure and content and action of asthma action plans for Vietnamese settings to ensure feasibility, acceptance and implementation. Methods: A Delphi consensus conducted over two rounds. The proposed items were evaluated by a Vietnamese panel of pulmonologists, allergist, tuberculosis/lung disease specialists and general practitioners. Structured online questionnaires with 5-point Likert scales were used. Consensus was defined as >80% agreement and < 10% strong disagreement. Results: 26 and 21 participants completed round 1 and round 2, respectively. 4-zone of AAP was preferred (42.3%) over 3-zone (38.5%) or 2-zone (19.2%). AAP should include some key statements for asthma, symptoms for self-monitoring, objective asthma control questionnaire, actions for changes of maintenance medication and instructions in emergency situations. AAP zones should be classified on symptom frequency and severity. Patient actions should be tailored to their treatment regimen (MART or ICS/LABA + SABA). APP might not include peak expiratory flow monitoring and oral corticosteroid self-administration for both MART and ICS/LABA + SABA regimen, and might not add SABA together with ICS dose escalation for ICS/LABA + SABA regimen. Conclusions: This study established an expert consensus on fundamental AAP structural elements and actions for the Vietnamese. The failure to achieve consensus on PEF monitoring tools and OCS for self-management of asthma exacerbation reflects concerns about medication abuse, especially in Vietnam healthcare settings.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Lanre Peter Daodu

,

Yogini Raste

,

Judith E. Allgrove

,

Francesca I.F. Arrigoni

,

Reem Kayyali

Abstract: Background: Pulmonary impairments have been identified as some of the most complex and debilitating post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID. This study identified and characterised the specific forms of pulmonary impairments detected using pulmonary function tests (PFT), chest X-rays (CXR), and CT scans in patients with long COVID symptoms. Methods: We conducted a single-centre retrospective study to evaluate 60 patients with long COVID who underwent pulmonary function tests (PFTs), chest X-rays (CXRs), and computed tomography (CT) scans. Pulmonary function in long COVID patients was assessed using defined thresholds for key test parameters, enabling categorisation into normal, restrictive, obstructive, and mixed lung-function patterns. We applied exact binomial (Clopper–Pearson) 95% confidence intervals to calculate the proportions of patients falling below the defined thresholds. We also assessed the relationship among spirometric indices, lung volumes, and diffusion capacity (DLCO) using scatter plots with corresponding linear regression. The findings from the CXRs and CT scans were categorised, and their prevalence was calculated. Results: A total of 60 patients with long COVID symptoms (mean age 60 ± 13 years; 57% female) were evaluated. The cohort was ethnically diverse and predominantly non-smokers, with a mean BMI of 32.4 ± 6.3 kg/m². Pulmonary function testing revealed that most patients had preserved spirometry, with mean FEV1 and FVC above 90% predicted. However, a significant proportion exhibited reductions in lung volumes, with total lung capacity (TLC) decreasing in 35%, and diffusion capacity (TLCO) decreasing in 75%. Lung function pattern analysis showed 88% of patients had normal function, while 12% displayed a restrictive pattern; no obstructive or mixed patterns were observed. Radiographic assessment revealed that 58% of chest X-rays were normal, whereas CT scans showed ground-glass opacities in 65% and fibrotic changes in 55% of patients, along with findings such as atelectasis, air trapping, and bronchial wall thickening. Conclusion This study reveals that long COVID is marked by preserved spirometry yet significant alveolar gas exchange impairment, with frequent diffusion deficits, fibrotic changes, and ground-glass opacities indicating persistent parenchymal and microvascular injury. These findings highlight the need for ongoing research and multidisciplinary management to address the enduring impact of chronic pulmonary dysfunction.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Hamza Ogun

,

Esat Hayat

,

Nuran Gökbulut

,

Merve Yüzbaşıoğlu

,

Abdullah Kansu

,

Ömer Faruk Özer

,

Deniz Kara

,

Fatmanur Okyaltırık

Abstract:

Background/Objectives: Obstructive sleep apnea (OSA) diagnosis relies primarily on the apnea-hypopnea index (AHI), which measures event frequency but not duration. This study aimed to evaluate the diagnostic and classificatory potential of apnea and hypopnea duration (AHD) and oxidative stress markers in OSA. Methods: This case-control study included 47 patients with newly diagnosed OSA and 12 healthy controls. Participants underwent polysomnography and oxidative stress assessment through measurement of total-thiol, native-thiol, disulfide, myeloperoxidase, paraoxonase, catalase, malate dehydrogenase, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). The patient group was classified and compared based on OSA severity. Results: Total AHD of the severe OSA group was significantly longer than both other groups (p < 0.001). TAS levels of both OSA groups were significantly lower compared to controls (p = 0.006). TAS demonstrated moderate correlations with polysomnography parameters. A total AHD value of >12 min discriminated OSA with 100% sensitivity and specificity. A total AHD value of >80 min distinguished severe OSA with 100% sensitivity and 97.22% specificity. Conclusions: Total AHD is a valuable parameter for OSA diagnosis and severity classification, demonstrating superior discriminatory performance compared to the widely-used AHI. Although TAS was associated with OSA presence, oxidative stress parameters have limited utility for assessing OSA severity.

Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Melissa Skibba

,

Allan R Brasier

Abstract: Respiratory syncytial virus (RSV), a member of genus Orthopneumovirus, is an etiological agent in infant lower respiratory tract infections (LRTIs) producing substantial global morbidity. Here, secretoglobin (Scgb1a1)-derived progenitors play a primary role in triggering innate, inflammatory, and cell state transitions in response to RSV LRTIs. Whether RSV activation of innate signaling in this epithelial sentinel population leads to chronic airway disease is unknown. To understand the role of innate signaling in Scgb1a1-derived progenitors, a model of RSV-post viral disease (PVLD) was developed and studied in the presence or absence of RelA conditional knockout (CKO). In wild type mice, we observed persistence of atypical, differentiation intermediate, alveolar type 2 (aAT2) cells characterized by tumor protein 63 (Trp63), Aquaporin-3 (Aqp3) and Itgb4 expression. Mechanistically, we found the formation of aAT2 population was prevented by RelA CKO. Lineage tracing using Scgb1a1 CreERTM X mTmG mice demonstrated that the Scgb1a1+ populations were precursors to the aAT2 population. Single-cell RNA sequencing (scRNA-seq) showed that RSV-PVLD coordinately upregulates Nuclear Receptor Subfamily 1 Group D (Nr1d1/2), Clock and Basic Helix-Loop-Helix ARNT Like 1 (Bmal) both in the aAT2 cell and its Pdgfra+-mesenchymal niche in a RelA-dependent manner. Systematic analysis of intercellular epithelial-mesenchymal communication in the scRNA-Seq data showed that the clock-dysregulated epithelial-mesenchymal niche produces aberrant Angptl4 expression. We conclude that RSV-PVLD is mediated, at least in part, by RelA signaling in Scgb1a1-derived epithelial progenitors dysregulating an aAT2-PDGFRa epithelial-mesenchymal niche associated with persistent RSV replication, ANGPTL4 signaling and inflammatory clock expression.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Olga L. Voronina

,

Natalia N. Ryzhova

,

Marina S. Kunda

,

Ekaterina I. Ermolova

,

Elena L. Amelina

,

Rezuan U. Kagazezhev

,

Alexander L. Gintsburg

Abstract:

Chronic lung infection with Pseudomonadota (PCH) in patients with cystic fibrosis (pwCF) is difficult to eradicate. CFTR modulators have a potential role in the prevention of airway infections, but their ability to eradicate chronic infection remains to be investigated. The aim of our study was to evaluate the impact of combination (antibacterial (AT) and modulator (MT)) therapy on the lung microbiome composition (LMC) in the pwCF cohort. The microbiome of sputum samples longitudinally collected from Russian adult pwCF chronically infected with Pseudomonadota CF pathogens (PCH) was analyzed. MT resulted in a trend of bacterial load reduction. LMC did not undergo significant changes in PCH pwCF receiving MT for less than three years. Two-component MT resulted in a temporary decrease in the proportion of the CF pathogen only when combined with a course of AT. Three-component MT has been successful in inducing favorable microbiome changes (with abundance and diversity of anaerobic taxa) over a period of more than 3 years, but not for all cases of Burkholderiales infection. Respiratory system damaged by bronchiectasis is susceptible to new infections, so patient management requires constant monitoring of the LMC and replenishment of the therapeutic landscape with both new modulators and new antibacterial drugs.

Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Hong Jie Bian

,

Qin Hua Zhao

,

Feng Ling Ju

,

Lan Wang

,

Yu Pei Han

,

Hong Ling Qiu

,

Ci Jun Luo

,

Pei Gang

,

Ke Li

,

Xu Meng Ding

Abstract:

Background: The Right Ventricular Free Wall Longitudinal Strain/Pulmonary Arterial Systolic Pressure (RVFWLS/PASP) ratio is a novel echocardiographic parameter for assessing right ventricular–pulmonary artery (RV-PA) coupling. Its prognostic role in patients with pulmonary arterial hypertension (PAH) remains poorly defined. This study aimed to explore the prognostic value of RVFWLS/PASP in PAH. Methods: A retrospective cohort study was conducted involving patients with PAH at Shanghai Pulmonary Hospital and Nanyang Second People's Hospital from December 2009 to October 2024.The RVFWLS/PASP ratio is calculated, where the numerator (RVFWLS) is derived using speckle tracking echocardiography, and the denominator (PASP) is estimated based on the tricuspid regurgitation velocity. The primary endpoint was event-free survival, with events defined as all-cause mortality, lung transplantation, rehospitalization for right heart failure, or escalation of targeted therapy due to clinical deterioration. Cox regression analysis was used to identify and validate RVFWLS/PASP characteristics in patients with different outcomes. Kaplan-Meier survival analysis was employed to evaluate the additive value of RVFWLS/PASP to previously established risk models. Results: A total of 216 adult PAH patients were enrolled. The median follow-up time was 31 months. The survival rate of patients in the lower RVFWLS/PASP group was significantly worse than those in the higher RVFWLS/PASP group (Log-rank P <0.05). Multivariate Cox regression demonstrated that after adjusting for other prognostic factors,RVFWLS/PASP ratio (HR = 0.20, 95% CI: 0.04-0.92, p = 0.039) and CTD-PH diagnosis (HR = 2.09, 95% CI: 1.36-3.22, p < 0.001) remained independent predictors of adverse clinical events. RVFWLS/PASP enabled further risk stratification of patients classified as low-risk by established models. Conclusion: The echocardiographic parameter RVFWLS/PASP serves as an independent determinant of long-term prognosis in patients with PAH, indicating that improved RV-PA coupling is significantly associated with better clinical outcomes. RVFWLS/PASP provides incremental value for risk stratification and may demonstrate heterogeneous utility across different clinical subgroups.

Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Jovana Maskovic Pekmezovic

,

Jelena Cvejic

,

Ivana Sekulovic Radovanovic

,

Ivana Buha

,

Dragana Maric

Abstract:

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive condition and a leading cause of morbidity and mortality worldwide. The rate of forced expiratory volume in one second (FEV1) decline is a key prognostic marker. This study aimed to evaluate the impact of demographic, clinical, and therapeutic factors, including respiratory muscle strength and inhaled corticosteroid (ICS) use, on FEV1 decline.Methods: A prospective study was conducted in 2019 at the Clinic for Pulmonology, Clinical Center of Serbia. Fifty patients with stable COPD underwent spirometry, body plethysmography, respiratory muscle strength testing, and laboratory analyses. Demo-graphic and clinical data were collected via questionnaire. All assessments were repeated after six months of regular inhalation therapy.Results: Significant reductions were observed in FEV1, FVC, TLC, PImax, and PEmax. Lower baseline respiratory muscle strength predicted a faster FEV1 decline. Patients in GOLD stage 2 and those with greater hyperinflation exhibited accelerated functional deterioration. Therapy type affected selected parameters: LABA/ICS and LAMA/LABA/ICS regimens significantly reduced residual volume, but not the rate of FEV1 decline. Higher eosinophil counts were associated with a slower reduction in FEV1, suggesting a potential protective effect of ICS.Conclusion: Respiratory muscle strength, hyperinflation, and eosinophil count represent important predictors of COPD progression. Incorporating these parameters into diagnostic and therapeutic algorithms may improve early risk stratification and support indi-vidualized treatment strategies.

Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Benedetta Bondi

,

Martina Buscema

,

Federico Di Marco

,

Carlo Conti

,

Andrea Caviglia

,

Lorenzo Fucci

,

Anna Maria Riccio

,

Marcello Mincarini

,

Martina Ottoni

,

Fulvio Braido

+2 authors

Abstract: The diagnosis and management of UAD require an integrated, multidisciplinary approach. Diagnostic strategies combine clinical evaluation, imaging (CT), allergy testing, biomarker measurement (such as FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, IOS) to phenotype the disease. Therapeutic management is stratified and aims to control inflammation and symptoms in both compartments. Cornerstones include topical corticosteroids (intranasal and inhaled) and saline irrigations. For severe forms, especially T2-high, targeted biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP) have revolutionized treatment, reducing dependence on oral corticosteroids and the need for surgical interventions (like endoscopic sinus surgery, ESS). Adopting a "treatable traits" approach is emerging as a key strategy for precision medicine in UAD.
Review
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Chai Jin Lim

,

Yousef Shahin

Abstract: Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular connections between the pulmonary arteries and veins, often leading to significant clinical complications such as hypoxemia, paradoxical embolism, and brain abscesses. Embolisation has become the primary therapeutic modality for managing symptomatic PAVMs, with advancements in both technique and technology improving patient outcomes. This review explores the latest innovations in embolisation therapies for PAVMs, emphasizing emerging techniques, devices, and strategies that have refined treatment efficacy and safety. Recent progress includes the introduction of precisely targeted embolisation techniques, such as cone-beam computed tomography (CBCT) guidance and three-dimensional imaging, enabling more accurate identification and treatment of complex, multiple, or peripheral lesions. Additionally, vascular plugs and microcoils have demonstrated superior performance in terms of lower recurrence rates and more complete occlusion of feeding vessels compared to traditional devices. The use of endovascular navigation systems has further enhanced procedural success, allowing for better catheter manipulation in challenging anatomical conditions. Advancements in patient selection and pre-procedural planning, driven by enhanced imaging modalities such as CT pulmonary angiography (CTPA) and contrast-enhanced ultrasound, have led to improved outcomes and reduced complications. Moreover, personalized approaches, including consideration of patient-specific risk factors like comorbidities and lesion location, are becoming integral to optimizing treatment protocols. While the benefits of embolisation are well-documented, ongoing research continues to explore the long-term outcomes, including post-embolisation pulmonary function, recurrence rates, and quality of life improvements. This review highlights the evolving landscape of embolisation for PAVMs and underscores the importance of continued innovation in enhancing treatment strategies and patient care. This review aims to explore the ongoing advancements in embolisation techniques for PAVMs, emphasising the critical role of innovation in improving therapeutic approaches and patient outcomes.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Latika Giri

,

Pradeep Raj Regmi

,

Ghanshyam Gurung

,

Grusha Gurung

,

Shova Aryal

,

Sagar Mandal

,

Samyam Giri

,

Sahadev Chaulagain

,

Sandip Acharya

,

Muhammad Umair

Abstract: Background: Chest radiography is the most widely used diagnostic imaging modality. Yet its interpretation is challenged by limited radiology workforce, especially in low- and middle-income countries (LMICs). The interpretation is both time consuming and error-prone in high volume settings. Artificial Intelligence (AI) systems trained on public data may lack generalizability to multi-view, real-world, local images. Deep learning tools have the potential to augment radiologists by providing real-time decision support by overcoming these. Objective: We evaluated the diagnostic accuracy of a deep learning-based convolutional neural network (CNN) trained on multi-view, hybrid (public and local datasets) for detecting thoracic abnormalities in chest radiographs of adults presenting to a tertiary hospital. Methods: A CNN was pretrained on large public datasets (VinBig, NIH) and fine-tuned on adult chest radiographs both frontal [posteroanterior (PA) and anteroposterior (AP)] from Tribhuvan University Teaching Hospital TUTH, Nepal. The dataset included emergency (ER), ICU, and outpatient (OPD) radiographs. Data augmentation simulated poor-quality images and artifacts (ECG wires, text labels, rotation, low exposure). Fourteen thoracic pathologies were annotated by 3 radiologists. Bounding boxes were refined using Weighted Boxes Fusion (WBF) and displayed in 14 unique colors for interpretability. The system was evaluated on a held-out test set (N=522) against radiologist consensus. Primary outcomes included AUC, sensitivity, specificity, mean average precision (mAP), and reporting time. Deployment feasibility was tested on Picture Archiving and Communication System (PACS) and in offline standalone mode. Results: The CNN achieved an overall AUC of 0.86 across 14 abnormalities, with 68% sensitivity,99% specificity, and 0.93 mAP. Colored bounding boxes improved clarity when multiple pathologies co-occurred (e.g., cardiomegaly with effusion). The system performed effectively on PA, AP, and lateral views, including poor-quality ER/ICU images. Deployment testing confirmed seamless PACS integration and offline functionality. Conclusion: The CNN trained on adult CXRs performed reliably in detecting key thoracic findings across varied clinical settings. Its robustness to image quality, integration of multiple views and visualization capabilities suggest it could serve as a useful aid for triage and diagnosis.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Ruba Abdulrazaq Ebzee

,

Ibrahim Yusuf Abubeker

,

Ahmed Aboughalia

,

Mohammed I Danjuma

Abstract: BackgroundDespite Immune checkpoint inhibitors (ICPIs) transformation of lung cancer treatment, pneumonitis remains a potentially serious immune-related adverse event. In this review we conducted a network meta-analysis (NMA) to quantify the exact burden of pneumonitis risk across multiple ICPIs analogs.MethodsWe searched the following data bases PubMed, Embase, Scopus MEDLINE and Cochrane data base of systematic reviews as well as gray literature google scholars for eligible studies reporting on the prevalence of pneumonitis following immune check points inhibitors exposures. 29 studies enrolling 15,271 patients with non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC), analyzing both monotherapy and combination regimens satisfied inclusion criteria included in the review. Pairwise and network meta-analyses were performed to estimate pooled odds ratios (ORs) for pneumonitis, using placebo as the common comparator. Sensitivity analyses assessed the impact of study quality and combination therapies.ResultsPembrolizumab was associated with a significantly increased risk of pneumonitis compared to placebo (odds ratio [OR] = 2.67, 95% confidence interval [CI]: 1.70–4.17), with similar elevated risk observed for sugemalimab (odds ratio [OR] = 2.45, 95% confidence interval [CI]: 1.52–3.95). Nivolumab showed a nonsignificant but elevated estimate (odds Ratio [OR] = 2.69, 95% confidence interval [CI]: 0.64–11.35). Atezolizumab and ipilimumab demonstrated modest or uncertain risk. Heterogeneity was low (I² = 12%), and results were robust to sensitivity analyses. Higher pneumonitis rates were observed in combination regimens.ConclusionOur analysis demonstrates that pneumonitis risk varies among ICPIs, with pembrolizumab and sugemalimab showing the highest odds. Although the absolute incidence is low, the potential severity of pneumonitis warrants vigilant monitoring. These results should guide clinicians in risk stratification, treatment planning, and support and support the development of standardized reporting criteria and further comparative research.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Ramakanth Pata

,

Joanna Kristeva

,

Mallory Illies

,

Justin Stocks

Abstract: Background: Pulmonary hypertension (PH) is a frequent and serious complication of advanced chronic obstructive pulmonary disease (COPD) and is associated with poor prognosis and limited treatment options. Current management focuses on optimizing COPD care, while the role of pulmonary vasodilators remains controversial. Ensifentrine, a dual phosphodiesterase (PDE) 3/4 inhibitor with bronchodilatory and anti-inflammatory properties, may offer therapeutic benefit in COPD-associated PH. Objective: To retrospectively evaluate the effects of 6 months of nebulized ensifentrine on pulmonary hemodynamics and functional outcomes in patients with severe COPD and associated pre-capillary PH. Methods: We conducted a single-center, retrospective chart review of patients with GOLD stage III and IV COPD and confirmed pre-capillary PH (mean pulmonary artery pressure [mPAP] ≥20 mmHg, pulmonary vascular resistance [PVR] > 2 Wood Units, pulmonary capillary wedge pressure ≤15 mmHg). Five patients treated with nebulized ensifentrine (3 mg twice daily) between September 2024 and May 2025 were analyzed. Hemodynamics via right heart catheterization (RHC) and 6-minute walk distance (6MWD) were assessed at baseline and at 6 months. Results: The cohort (mean age 76 years, 60% male, mean FEV₁ 33.4% predicted) demonstrated severe emphysema and PH (baseline mPAP 53.2 mmHg, PVR 9.5 WU, cardiac index 2.5 L/min/m²). After 6 months, mean changes were: mPAP: decrease by 1.6 mmHg Cardiac index: increase by 0.1 L/min/m² PVR: decrease by 1.0 WU 6MWD: Improved by 31 m
mMRC dyspnea score improved from 3.6 to 3.2, CAT score from 23 to 21.6, and DLCO increased modestly (29%→31.2% predicted). No adverse events, exacerbations, or hospitalizations were observed during this period. The combination of ensifentrine with roflumilast was well tolerated. Conclusions: In this retrospective study, ensifentrine was safe and associated with modest improvements in pulmonary hemodynamics and functional status in severe COPD with pre-capillary PH. These preliminary findings warrant confirmation in larger, prospective controlled trials.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Xin-Yi Feng

,

Fei-Yao Wang

,

Si-Yu Jiang

,

Li-Heng Wang

,

Xin-Yue Chen

,

Shi-Bo Tang

,

Fan Yang

,

Rui Li

Abstract:

Objective: To determine whether deep-learning–derived quantitative HRCT parameters, combined with clinical characteristics, can predict in-hospital adverse outcomes and long-term reinfection in patients with COVID-19 pneumonia. Methods: We retrospectively analyzed 236 RT-PCR–confirmed patients who underwent HRCT between November 2022 and January 2023 at the Affiliated Hospital of North Sichuan Medical College. Pulmonary inflammatory regions were automatically segmented, and quantitative metrics—including opacity score, lesion volume and percentage, high-attenuation lesion volume and percentage, and mean total-lung attenuation—were extracted using an artificial-intelligence pneumonia analysis prototype (Siemens Healthineers, Erlangen, Germany). Optimal thresholds derived from receiver-operating-characteristic curves for the composite endpoint of intensive-care-unit admission or all-cause death were applied to stratify patients. Cox proportional-hazards models were used to identify independent predictors of adverse outcomes and subsequent SARS-CoV-2 reinfection. Results: Adverse outcomes occurred in 16.1% of patients. Higher opacity scores, larger lesion burdens, greater proportions of high-attenuation opacities, and higher mean lung attenuation were all associated with poorer outcomes (all P < 0.05). After adjusting for age and chronic obstructive pulmonary disease, an opacity score ≥ 5.5 (HR = 3.02), lesion percentage ≥ 18.85% (HR = 2.33), and mean attenuation ≥ −662.4 HU (HR = 2.20) remained independent predictors. During a median follow-up of 603 days, opacity score ≥ 5.5 (HR = 5.32), high-attenuation volume ≥ 140.37 ml (HR = 3.81), and high-attenuation percentage ≥ 4.94% (HR = 3.39) independently predicted reinfection (all P ≤ 0.027). Conclusions: Deep-learning–based quantitative HRCT metrics provide incremental prognostic information for risk stratification of both acute adverse outcomes and long-term reinfection among COVID-19 patient.

Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Maria Caridad Mata

,

Ignacio Español

,

Arantxa Gelabert

,

Jesus Aibar

,

Nuria Albacar

,

Elena Sandoval

,

Pedro Castro

,

Sònia Jiménez

,

Jeisson Osorio

,

Jorge Moisés

Abstract: High-risk pulmonary embolism (PE) is a life-threatening condition characterized by he-modynamic instability, often leading to catastrophic outcomes such as cardiac arrest and cardiogenic shock. We conducted a retrospective analysis of patients diagnosed with high-risk PE at a single tertiary center between 2018 and 2024. Catastrophic PE was de-fined as high-risk PE with hemodynamic collapse, including cardiac arrest and/or the requirement for high-dose vasopressors. Data on clinical characteristics, treatments, and outcomes were analyzed. Catastrophic PE accounted for 59% of cases. Systemic throm-bolysis was the most frequent reperfusion strategy (67%), while catheter-directed therapies (35.4%) and VA-ECMO (11.4%) were used selectively. Despite aggressive management, catastrophic PE exhibited significantly higher mortality rates at 7 days (40%) and 30 days (49%) compared to non-catastrophic cases (9% and 12.5%, respectively). These patients also showed higher rates of multiorgan failure and required more invasive support. This study underscores the importance of early recognition and tailored treatment strategies for catastrophic PE, highlighting its distinct clinical presentation and worse outcomes compared to non-catastrophic high-risk PE. Further research is essential to refine treatment protocols and improve survival in this critically ill population, emphasizing the utility of a standardized classification to enhance clinical management and research consistency.
Concept Paper
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Abhishek Kumar

,

Amit Kumar Singh

,

Hridayesh Prakash

Abstract: Mycobacterium tuberculosis is responsible for Tuberculosis disease in human which possess major challenge to health care system. This is due to complex architecture of this pathogen which enables to thrive and encounter hostile micromilieu which is customized to kill the pathogen. The mycobacterial cell envelope is enriched with lipoglycans like lipoarabinomannan (LAM) which orchestrate the interaction of pathogen with host cell. LAM is structurally diverse and displayed on membrane as mannose-capped LAM (ManLAM) and phosphatidylinositol LAM (PI-LAM). Each of these is endowed with different immunomodulatory activities in host. ManLAM inhibits pro-inflammatory programming by tweaking the production of IL-10, inhibiting the budding of phagosomes into lysosomes and favours persistence of the bacteria. In contrast, PI-LAM triggers pro-inflammatory response and augment autophagy in host. LAM offer intrinsic resistance in pathogen toward oxidative stress, ferroptosis and cathepsin-dependent phagosome maturation. LAM-directed IL-10–producing B cells contribute to the virulence and therapeutic challenge. In view of above, LAM is therefore a distinctive target for mitigating mycobacterial "yardstick" of pathogenesis and drug resistance. Developing LAM based approach may offer impactful outcome not only in prognosis and also developing effective host-directed therapy strategies.
Article
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Beatrice Ragnoli

,

Patrizia Pochetti

,

Fausto Chiazza

,

Carlotta Bertelegni

,

Danila Azzolina

,

Mario Malerba

Abstract: Obstructive Sleep Apnea (OSA) is associated with several comorbidities, including renal dysfunction, which may improve with C-PAP therapy. Sleep fragmentation and nocturnal hypoxia in OSA have been hypothesized to contribute to carcinogenesis, particularly affecting hypoxia-sensitive urinary tract cells. The aim of the present study was to assess cancer prevalence in OSA patients and explore clinical profiles of those with urinary tract cancer. We retrospectively analyzed 50 OSA patients with cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. 70% of patients were male. Among OSA-cancer patients, 34% had urinary tract cancer (88% males, p&lt;0.05), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and others (2%). 10% had multiple cancer sites. Hierarchical clustering revealed a distinct profile: urinary tract cancer associated with better respiratory indices, frequent hypertension and higher C-PAP compliance. Our findings show a higher prevalence of urinary tract cancer in male OSA patients, suggesting a possible link between OSA-related hypoxia and carcinogenesis. This supports increased clinical surveillance and further research into whether OSA is a modifiable cancer risk factor. PAP therapy may offer protective benefits.
Review
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Jerome Cantor

Abstract: Pulmonary emphysema is a progressive and debilitating lung disease characterized by the destruction of alveolar walls and enlargement of airspaces, resulting in impaired gas exchange and reduced lung function. Central to this pathology is the degradation of the extracellular matrix (ECM), particularly the elastic fiber network containing elastin protein responsible for storing and releasing the energy that expels air from the lung. Both intrinsic and extrinsic mechanical stress play a pivotal role in ECM remodeling, influencing elastin degradation and the structural integrity of alveolar walls. This paper explores the interactions between mechanical forces and ECM components, emphasizing the role of increased elastin crosslinking in the pathogenesis and progression of emphysema. The molecular mechanisms responsible for this process are described in the context of emergent phenomena associated with alveolar wall distension and rupture, including the role of diagnostic biomarkers in the early detection of elastic fiber injury that may facilitate timely therapeutic interventions designed to preserve ECM integrity and improve patient outcomes.

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