Advances in Respiratory Medicine

16 pages, 1765 KB

Open AccessArticle

Cryptic Circulation and Co-Infections of Endemic Human Coronaviruses During the First Years of the COVID-19 Pandemic in Brazil

by Ana Karolina Mendes Moreno, Rajiv Gandhi Gopalsamy, Lucas Alves da Mota Santana, Marina dos Santos Barreto, Pedro Henrique Macedo Moura, Deise Maria Rego Rodrigues Silva, Túlio César Rodrigues Leite, Camila de Paula Dias, Breno de Melo Silva, Lysandro Pinto Borges and Ricardo Lemes Gonçalves

Adv. Respir. Med. 2025, 93(6), 55; https://doi.org/10.3390/arm93060055 - 5 Dec 2025

Abstract

During the COVID-19 pandemic, the global focus on SARS-CoV-2 overshadowed the epidemiology of other respiratory pathogens. This study aimed to characterize the circulation of endemic human coronaviruses (HCoVs) in Brazil. We retrospectively analyzed results from 22,472 PCR tests for HCoVs (from 5183 patients) [...] Read more.

During the COVID-19 pandemic, the global focus on SARS-CoV-2 overshadowed the epidemiology of other respiratory pathogens. This study aimed to characterize the circulation of endemic human coronaviruses (HCoVs) in Brazil. We retrospectively analyzed results from 22,472 PCR tests for HCoVs (from 5183 patients) and 601,278 tests for SARS-CoV-2 (from 475,856 patients) between November 2019 and June 2021. HCoVs were detected in 160 patients (3.09%), with HCoV-NL63 as the most frequent species. HCoV circulation was intermittent, with positivity peaks up to 4% but also periods of up to six months with an absence of detections in 2020, contrasting with the sustained high positivity of SARS-CoV-2 (22.37%). Co-infections were frequent: 26.25% of HCoV-positive patients were co-infected with at least one other respiratory pathogen, most commonly Rhinovirus/Enterovirus, and cases involving up to five pathogens were observed, seven patients had co-infections between HCoVs and SARS-CoV-2. These findings reveal the persistent, often cryptic, circulation of HCoVs during the pandemic and highlight their role as key components in complex multi-pathogen infections. This underscores the critical importance of implementing comprehensive molecular diagnostic panels in routine respiratory surveillance to ensure accurate etiology, guide appropriate clinical management, and fully assess the public health burden of non-SARS-CoV-2 coronaviruses. Full article

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18 pages, 1064 KB

Open AccessArticle

Prevalence of Urinary Tract Cancer in Patients with Obstructive Sleep Apnea: Data from the Vercelli Registry

by Beatrice Ragnoli, Patrizia Pochetti, Fausto Chiazza, Carlotta Bertelegni, Danila Azzolina and Mario Malerba

Adv. Respir. Med. 2025, 93(6), 54; https://doi.org/10.3390/arm93060054 - 27 Nov 2025

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Abstract

Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting [...] Read more.

Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting hypoxia-sensitive urinary tract tissues. This study aimed to assess the prevalence of different cancer types among patients with concurrent OSA and malignancy and to characterize the clinical profiles of those with urinary tract cancer. Methods: We retrospectively analyzed 50 patients with both OSA and cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. Results: Among the cohort (70% males) of OSA-cancer patients, urinary tract cancers were the most frequent (34%), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and other cancers (2%); 10% had multiple cancer sites. Patients with urinary tract cancer were mainly male (88%, p = 0.0043) and displayed better respiratory indices, frequent hypertension, and higher C-PAP adherence. Conclusions: These findings suggest a possible link between OSA-related hypoxia and carcinogenesis in urinary tract tissues and support increased clinical surveillance and further research to determine potential protective effects of C-PAP therapy. Full article

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12 pages, 641 KB

Open AccessArticle

Effectiveness and Safety of Glycopyrronium–Formoterol–Budesonide Triple Therapy in Chronic Obstructive Pulmonary Disease (AIR-FORCE): An Open-Label Multi-Centric Phase 4 Study

by Anjali R. Nath, Adesh Kumar, Amit Suresh Bhate, Bharat Mehrotra, Deependra Kumar Rai, Vijay Kumar Barge, Divya Bhojwani, Sagar Bhagat, Sumit Bhushan, Saiprasad Patil and Hanmant Barkate

Adv. Respir. Med. 2025, 93(6), 53; https://doi.org/10.3390/arm93060053 - 25 Nov 2025

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Abstract

Chronic obstructive pulmonary disease (COPD) is a major health burden in India with limited real-world data on triple inhaler therapy. This prospective, open-label, multi-center, single-arm, phase 4 study (October 2023–August 2024) assessed the effectiveness and safety of glycopyrronium/formoterol fumarate/budesonide (GFB) triple therapy, administered [...] Read more.

Chronic obstructive pulmonary disease (COPD) is a major health burden in India with limited real-world data on triple inhaler therapy. This prospective, open-label, multi-center, single-arm, phase 4 study (October 2023–August 2024) assessed the effectiveness and safety of glycopyrronium/formoterol fumarate/budesonide (GFB) triple therapy, administered as metered-dose inhaler (MDI) or dry-powder inhaler (DPI), in Indian COPD patients. Symptomatic patients aged ≥40 years with minimum one exacerbation in the past year and receiving dual or monotherapy were included. GFB was delivered as MDI or DPI based on physician and patient preference. Primary outcomes were changes from baseline in trough forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), and modified medical research council (mMRC) score over 24 weeks, with assessment of exacerbations, hospitalizations, rescue medication use, and safety. In 184 patients (70.65% male, mean age 53.7 years), GFB significantly improved FEV₁, FVC, and mMRC scores. Eleven mild exacerbations were reported without hospitalization; 17.39% used rescue salbutamol largely in the first 4 weeks. GFB was well tolerated, with mild-to-moderate adverse events in 14.67%, and outcomes were comparable between MDI and DPI. Our findings support GFB as safe and effective treatment in real-world COPD management. Full article

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12 pages, 479 KB

Open AccessFeature PaperArticle

Preoperative Six-Minute Walking Distance as a Predictor of Postoperative Complications in Patients Undergoing Lobectomy for Non-Small-Cell Lung Cancer

by Naoki Maki, Takahiro Yanagihara, Ashoka Indranatha Wijesinghe, Kazuto Sugai, Tomoyuki Kawamura, Yusuke Saeki, Shinsuke Kitazawa, Naohiro Kobayashi, Shinji Kikuchi, Yukinobu Goto, Harumi Sakamoto, Keisuke Taniguchi, Hideo Ichimura and Yukio Sato

Adv. Respir. Med. 2025, 93(6), 52; https://doi.org/10.3390/arm93060052 - 24 Nov 2025

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Abstract

Introduction: Minimally invasive video-assisted thoracic surgery (VATS) for lung cancer has become a widely used approach. However, postoperative pulmonary complications (PCs) such as pneumonia, atelectasis, and lung fistula remain significant challenges, particularly in older adult patients with multiple comorbidities. The 6-minute walk test [...] Read more.

Introduction: Minimally invasive video-assisted thoracic surgery (VATS) for lung cancer has become a widely used approach. However, postoperative pulmonary complications (PCs) such as pneumonia, atelectasis, and lung fistula remain significant challenges, particularly in older adult patients with multiple comorbidities. The 6-minute walk test (6MWT) has been suggested as a predictor of postoperative outcomes in various surgical settings, but its relationship with postoperative complications following VATS lobectomy for lung cancer has not been thoroughly explored. The aim of this study was to determine if preoperative 6MWD predicted the occurrence of 30-day PCs among patients undergoing VATS lobectomy for non-small-cell lung cancer. Methods: This retrospective study examined 66 patients who underwent VATS lobectomy for lung cancer. Participants were categorized into two groups: those with postoperative pulmonary complications (n = 11) and those without (n = 55). The research period was from January to September 2022. The preoperative 6MWT distance, along with other clinical and demographic factors, was assessed to determine its predictive value for postoperative complications. Multivariate logistic regression analysis was performed to identify significant predictors. Results: The study found that preoperative 6MWT ≤ 450 m was a significant predictor of postoperative pulmonary complications (odds ratio: 5.674, 95% CI: 1.206–26.684, p = 0.028). Conclusions: The preoperative 6MWT distance is a useful predictor of postoperative pulmonary complications in patients undergoing VATS lobectomy for lung cancer. Patients with a 6MWT ≤ 450 m may be at higher risk for complications such as pneumonia, atelectasis, and lung fistula. Incorporating preoperative 6MWT as a risk stratification tool could help guide clinical decisions and rehabilitation efforts to improve postoperative outcomes in this patient population. Full article

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37 pages, 1479 KB

Open AccessReview

A Unified Map of Airway Interactions: Secretome and Mechanotransduction Loops from Development to Disease

by Crizaldy Tugade and Jopeth Ramis

Adv. Respir. Med. 2025, 93(6), 51; https://doi.org/10.3390/arm93060051 - 12 Nov 2025

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Abstract

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory [...] Read more.

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements. Full article

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9 pages, 243 KB

Open AccessArticle

Unraveling the Complexities of Hypersensitivity Pneumonitis with Autoimmune Features: A Retrospective Analysis

by Joana Lourenço, Sofia Castro, David Barros Coelho, André Terras Alexandre, Natália Melo, Patrícia Caetano Mota, Hélder Novais Bastos, André Carvalho and António Morais

Adv. Respir. Med. 2025, 93(6), 50; https://doi.org/10.3390/arm93060050 - 7 Nov 2025

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Abstract

Background: Some hypersensitivity pneumonitis (HP) patients exhibit autoimmune features (HPAF). This study compared outcomes of HPAF and HP without autoimmune features, focusing on progressive pulmonary fibrosis (PPF) and response to immunosuppression. Methods: A retrospective cohort study included HP patients from a single center. [...] Read more.

Background: Some hypersensitivity pneumonitis (HP) patients exhibit autoimmune features (HPAF). This study compared outcomes of HPAF and HP without autoimmune features, focusing on progressive pulmonary fibrosis (PPF) and response to immunosuppression. Methods: A retrospective cohort study included HP patients from a single center. HPAF was defined as HP overlapping with autoimmune disease or presenting autoimmune markers/symptoms not fulfilling connective tissue disease criteria. A control HP group without autoimmune features was randomly selected. Demographics, autoimmune profiles, and outcomes over two years were analyzed. Results: 103 patients were included (52 HPAF; 51 HP). In HPAF, the most common autoimmune diseases were rheumatoid arthritis (9.6%), while 57.7% had isolated autoimmune serology. Groups showed no baseline differences in demographics, exposures, smoking, or lung function. Fibrotic disease on high-resolution CT at diagnosis was less frequent in HPAF (71.2% vs. 88.2%; p = 0.031). At two-year follow-up, survival, transplantation, and PPF prevalence were similar. HPAF patients received immunosuppression less often (69.2% vs. 86.3%; p = 0.038). Among patients under immunosuppression, PPF was significantly lower in HPAF group (8.6% vs. 29.5%; p = 0.021). Conclusions: Within two years post-diagnosis, HPAF and HP had comparable overall outcomes. However, under immunosuppression, HPAF patients had significantly lower odds of developing PPF (adjusted OR 0.08; 95% CI 0.008–0.816; p = 0.033) compared to HP patients, suggesting a more favorable treatment response. Full article

18 pages, 5513 KB

Open AccessArticle

A Plant-Based Diet Alleviates Molecular Pulmonary Abnormalities in Hypertension

by Rami Salim Najjar, Jaishree Jagirdar and Andrew T. Gewirtz

Adv. Respir. Med. 2025, 93(6), 49; https://doi.org/10.3390/arm93060049 - 4 Nov 2025

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Abstract

Background: Essential hypertension is associated with an increased risk of pulmonary hypertension (PH). PH is diagnosed more frequently in females. Little is known about the effects of a plant-based diet (PBD) in improving lung abnormalities in PH. Methods: We compared 28- [...] Read more.

Background: Essential hypertension is associated with an increased risk of pulmonary hypertension (PH). PH is diagnosed more frequently in females. Little is known about the effects of a plant-based diet (PBD) in improving lung abnormalities in PH. Methods: We compared 28- and 40-week-old female normotensive Wistar Kyoto and spontaneously hypertensive rats (SHR), maintained from the age of 4 weeks on a control refined diet or a PBD, comprising 28% fruits, vegetables, nuts and legumes. A subset of control SHRs were switched to the PBD at 28 weeks of age. Lungs were taken for protein and histological analysis. Results: Relative to WKYs, SHRs consuming the control diet exhibited decreased lung endothelial nitric oxide synthase (eNOS). PBD consumption by SHRs prevented and reversed this phenotype. Expression of E-cadherin was also reduced in SHRs. This reduction was attenuated by PBD consumption treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the lung was increased in SHRs and attenuated by PBD. The expression of activated transforming growth factor (TGF)-β1 was also attenuated by a PBD. Conclusions: The PBD favorably mediated hypertension-induced pulmonary molecular abnormalities in lung endothelium, epithelial junction and pro-fibrotic signaling. Future studies should assess the effects of a PBD in improving PH and lung function. Full article

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17 pages, 895 KB

Open AccessReview

Pulmonary Veno-Occlusive Disease: A Comprehensive Review of Diagnostic Challenges, Therapeutic Limitations, and Evolving Management

by Brian Foster, Sikandar Khan, Ana Suarez Gonzalez and Samantha Gillenwater

Adv. Respir. Med. 2025, 93(6), 48; https://doi.org/10.3390/arm93060048 - 31 Oct 2025

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Abstract

Pulmonary veno-occlusive disease (PVOD) is a rare and under-recognized cause of pulmonary hypertension. It is characterized by fibrotic obstruction of small pulmonary veins and venules. Its clinical presentation closely mimics pulmonary arterial hypertension (PAH), leading to frequent misdiagnosis, delayed recognition, and potentially harmful [...] Read more.

Pulmonary veno-occlusive disease (PVOD) is a rare and under-recognized cause of pulmonary hypertension. It is characterized by fibrotic obstruction of small pulmonary veins and venules. Its clinical presentation closely mimics pulmonary arterial hypertension (PAH), leading to frequent misdiagnosis, delayed recognition, and potentially harmful exposure to PAH-specific vasodilator therapy. This review aims to synthesize our evolving understanding of PVOD, discussing its etiologies, role of genetic underpinnings, histopathologic features, pathophysiology, clinical presentation, and characteristic imaging findings. It then discusses management strategies emphasizing early recognition, supportive care, avoidance of inappropriate PAH therapies due to poor response, and timely referral for lung transplantation. Despite advances in identification and management, PVOD remains a fatal condition with a median survival of less than two years, underscoring the importance of early recognition and multidisciplinary care. Full article

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Adv. Respir. Med., Volume 93, Issue 6 (December 2025) – 8 articles

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