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Search Results (1,218)

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13 pages, 2232 KiB  
Article
Artificial Intelligence-Assisted Lung Perfusion Quantification from Spectral CT Iodine Map in Pulmonary Embolism
by Reza Piri, Parisa Seyedhosseini, Samir Jawad, Emilie Sonne-Holm, Camilla Stedstrup Mosgaard, Ekim Seven, Kristian Eskesen, Ole Peter Kristiansen, Søren Fanø, Mathias Greve Lindholm, Lia E. Bang, Jørn Carlsen, Anna Kalhauge, Lars Lönn, Jesper Kjærgaard and Peter Sommer Ulriksen
Diagnostics 2025, 15(15), 1963; https://doi.org/10.3390/diagnostics15151963 - 5 Aug 2025
Abstract
Introduction: This study evaluated the performance of automated dual-energy computed tomography (DECT)-based quantification of perfusion defects (PDs) in acute pulmonary embolism and examined its correlation with clinical parameters. Methods: We retrospectively analyzed data from 171 patients treated for moderate-to-severe acute pulmonary [...] Read more.
Introduction: This study evaluated the performance of automated dual-energy computed tomography (DECT)-based quantification of perfusion defects (PDs) in acute pulmonary embolism and examined its correlation with clinical parameters. Methods: We retrospectively analyzed data from 171 patients treated for moderate-to-severe acute pulmonary embolism, who underwent DECT imaging at two separate time points. PDs were quantified using a fully automated AI-based segmentation method that relied exclusively on iodine perfusion maps. This was compared with a semi-automatic clinician-guided segmentation, where radiologists manually adjusted thresholds to eliminate artifacts. Clinical variables including the Miller obstruction score, right-to-left ventricular diameter ratio, oxygen saturation, and patient-reported symptoms were also collected. Results: The semiautomatic method demonstrated stronger correlations with embolic burden (Miller score; r = 0.4, p < 0.001 at follow-up) and a negative correlation with oxygen saturation (r = −0.2, p = 0.04). In contrast, the fully automated AI-based quantification consistently produced lower PD values and demonstrated weaker associations with clinical parameters. Conclusions: Semiautomatic quantification of PDs currently provides superior accuracy and clinical relevance for evaluating lung PDs in acute pulmonary embolism. Future multimodal AI models that incorporate both anatomical and clinical data may further enhance diagnostic precision. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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15 pages, 258 KiB  
Article
The Pulmonary Manifestation of Mastocytosis: Experiences of the National Reference Centre of Excellence
by Marlena Sztormowska, Aleksandra Górska, Maciej Piskunowicz, Lucyna Górska, Wojciech Nazar, Marta Chełmińska, Krzysztof Kuziemski, Ewa Jassem and Marek Niedoszytko
J. Clin. Med. 2025, 14(15), 5455; https://doi.org/10.3390/jcm14155455 - 3 Aug 2025
Viewed by 129
Abstract
Background: Patients with mastocytosis may present with exacerbated respiratory symptoms and lung diseases resulting from mast cell mediator release. However, their prevalence and severity level remain under debate. The study aims to analyze the prevalence of respiratory symptoms and the usefulness of lung [...] Read more.
Background: Patients with mastocytosis may present with exacerbated respiratory symptoms and lung diseases resulting from mast cell mediator release. However, their prevalence and severity level remain under debate. The study aims to analyze the prevalence of respiratory symptoms and the usefulness of lung function tests like spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) of the chest in mastocytosis patients presenting with dyspnea, cough, and exercise intolerance. Methods: We included 104 patients with mastocytosis and 71 healthy controls. Data collection encompassed patient interview, clinical examination, spirometry, DLCO, and chest HRCT. Diagnosis of mastocytosis included bone marrow biopsies and serum tryptase measurements. Results: Compared to controls, patients with mastocytosis exhibited significantly lower values in FEV1/VC ratio, absolute DLCO/VA, predicted DLCO/VA, absolute DLCOcSB, and predicted DLCOcSB (p < 0.001). Commonly reported respiratory symptoms included dyspnea (36.5%), chest tightness (22.1%), and wheezing (9.6%). Airway obstruction was identified in 7.7% of patients; however, it appeared to be independent of the mastocytosis subtype. A decreased DLCO/VA ratio was observed in 4.8% of patients, but HRCT did not reveal any evidence of underlying lung disease. Conclusions: Mastocytosis appears to be a risk factor for the occurrence and exacerbation of respiratory symptoms. However, airway obstruction and impairment of the alveolar–capillary membrane seem to occur independently of the clinical subtype of mastocytosis. Additionally, the causal relationship between pulmonary involvement, mast cell infiltration of the alveolar–capillary membrane, and the systemic circulation of mast cell mediators remains unclear and requires further research. Full article
(This article belongs to the Section Respiratory Medicine)
23 pages, 1337 KiB  
Review
Balancing Innovation and Safety: Prediction, Prevention, and Management of Pneumonitis in Lung Cancer Patients Receiving Novel Anti-Cancer Agents
by Sarah Liu, Daniel Wang, Andrew Robinson, Mihaela Mates, Yuchen Li, Negar Chooback, Pierre-Olivier Gaudreau, Geneviève C. Digby, Andrea S. Fung and Sofia Genta
Cancers 2025, 17(15), 2522; https://doi.org/10.3390/cancers17152522 - 30 Jul 2025
Viewed by 315
Abstract
Pneumonitis is characterized as inflammation of the lung parenchyma, and a potential adverse effect of several anti-cancer therapies. Diagnosing pneumonitis can be particularly challenging in lung cancer patients due to inherent similarities in symptoms and radiological presentation associated with pneumonitis, as well as [...] Read more.
Pneumonitis is characterized as inflammation of the lung parenchyma, and a potential adverse effect of several anti-cancer therapies. Diagnosing pneumonitis can be particularly challenging in lung cancer patients due to inherent similarities in symptoms and radiological presentation associated with pneumonitis, as well as other common conditions such as infection or disease progression. Furthermore, many lung cancer patients have underlying pulmonary conditions that might render them more susceptible to severe or fatal outcomes from pneumonitis. Novel anti-cancer agents, such as antibody–drug conjugates (ADCs) and bispecific antibodies (BsAbs), are being incorporated into the treatment of lung cancer; therefore, understanding the risk and mechanisms underlying the potential development of pneumonitis with these new therapies is important to ensure continuous improvements in patient care. This narrative review provides an overview of the incidence of pneumonitis observed with novel anti-cancer agents, characterizes potential pathophysiological mechanisms underlying pneumonitis risk and emerging predictive biomarkers, highlights management strategies, and explores future directions for minimizing the risk of pneumonitis for lung cancer patients. Full article
(This article belongs to the Special Issue Cancer Immunotherapy in Clinical and Translational Research)
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13 pages, 1017 KiB  
Article
Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis
by Ionut-Valentin Stanciu, Ariadna-Petronela Fildan, Adrian Cosmin Ilie, Cristian Oancea, Livia Stanga, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Doina-Ecaterina Tofolean, Ionela Preotesoiu, Viorica Zamfir and Elena Dantes
J. Clin. Med. 2025, 14(15), 5327; https://doi.org/10.3390/jcm14155327 - 28 Jul 2025
Viewed by 291
Abstract
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised [...] Read more.
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL−1 vs. 16.2 pg mL−1; p = 0.009) and IL-1β (5.34 pg mL−1 vs. 3.67 pg mL−1; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL−1) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL−1 rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m−2) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article
(This article belongs to the Section Infectious Diseases)
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8 pages, 855 KiB  
Case Report
Severe Malaria Due to Plasmodium falciparum in an Immunocompetent Young Adult: Rapid Progression to Multiorgan Failure
by Valeria Sanclemente-Cardoza, Harold Andrés Payán-Salcedo and Jose Luis Estela-Zape
Life 2025, 15(8), 1201; https://doi.org/10.3390/life15081201 - 28 Jul 2025
Viewed by 273
Abstract
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation [...] Read more.
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article
(This article belongs to the Section Medical Research)
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20 pages, 4051 KiB  
Review
Right Heart Evaluation: A Tough Challenge for Clinicians
by Martina Pucci, Luca Maria Capece, Mariateresa Pontoriero, Daniele Paoletta, Marina Iacono, Francesca La Rocca, Roberto Luise and Roberta Esposito
Life 2025, 15(8), 1194; https://doi.org/10.3390/life15081194 - 27 Jul 2025
Viewed by 328
Abstract
The right heart–pulmonary circulation unit (RH-PCU) constitutes an integrated anatomo-functional system characterized by high-volume blood flow, low intravascular pressure, and minimal pulmonary vascular resistance. The RH-PCU dysfunction is a challenge for clinicians, as it can result from numerous pathological conditions, each with different [...] Read more.
The right heart–pulmonary circulation unit (RH-PCU) constitutes an integrated anatomo-functional system characterized by high-volume blood flow, low intravascular pressure, and minimal pulmonary vascular resistance. The RH-PCU dysfunction is a challenge for clinicians, as it can result from numerous pathological conditions, each with different clinical presentations. The pathophysiological changes underlying the hemodynamic alterations in the pressure and volume affecting the right ventricle can lead the patient to present with the primary symptom: dyspnea. We review the clinical presentation, the laboratory test, and the role of multimodality imaging in the evaluation of the disfunction of the RHPCU, including echocardiography, stress echocardiography, computed tomography, magnetic resonance imaging, nuclear imaging, and invasive pressure measurement through catheterization. We therefore aimed to describe the various diagnostic options available to clinicians, evaluating their effectiveness and limitations of use. Full article
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19 pages, 1135 KiB  
Article
Can Lung Ultrasound Act as a Diagnosis and Monitoring Tool in Children with Community Acquired Pneumonia? Correlation with Risk Factors, Clinical Indicators and Biologic Results
by Raluca Isac, Alexandra-Monica Cugerian-Ratiu, Andrada-Mara Micsescu-Olah, Alexandra Daniela Bodescu, Laura-Adelina Vlad, Anca Mirela Zaroniu, Mihai Gafencu and Gabriela Doros
J. Clin. Med. 2025, 14(15), 5304; https://doi.org/10.3390/jcm14155304 - 27 Jul 2025
Viewed by 421
Abstract
Background: Community-acquired pneumonia (CAP) is the leading cause of mortality in children from middle- to low-income countries; diagnosing CAP includes clinical evaluation, laboratory testing and pulmonary imaging. Lung ultrasound (LUS) is a sensitive, accessible, non-invasive, non-radiant method for accurately evaluating the lung involvement [...] Read more.
Background: Community-acquired pneumonia (CAP) is the leading cause of mortality in children from middle- to low-income countries; diagnosing CAP includes clinical evaluation, laboratory testing and pulmonary imaging. Lung ultrasound (LUS) is a sensitive, accessible, non-invasive, non-radiant method for accurately evaluating the lung involvement in acute diseases. Whether LUS findings can be correlated with CAP’s severity or sepsis risk remains debatable. This study aimed to increase the importance of LUS in diagnosing and monitoring CAP. We analyzed 102 children aged 1 month up to 18 years, hospital admitted with CAP. Mean age was 5.71 ± 4.85 years. Underweight was encountered in 44.11% of children, especially below 5 years, while overweight was encountered in 11.36% of older children and adolescents. Patients with CAP presented with fever (79.41%), cough (97.05%), tachypnea (18.62%), respiratory failure symptoms (20.58%), chest pain (12.74%) or poor feeding. Despite the fact that 21.56% had clinically occult CAP and six patients (5.88%) experienced radiologically occult pneumonia, CAP diagnosis was established based on anomalies detected using LUS. Conclusions: Detailed clinical examination with abnormal/modified breath sounds and/or tachypnea is suggestive of acute pneumonia. LUS is a sensitive diagnostic tool. A future perspective of including LUS in the diagnosis algorithm of CAP should be taken into consideration. Full article
(This article belongs to the Special Issue Clinical Updates in Lung Ultrasound)
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13 pages, 1542 KiB  
Case Report
Reclassification of Seronegative Rheumatoid Arthritis as Anti-PL-12 Antisynthetase Syndrome with Interstitial Lung Disease and Joint Involvement–Case Report
by Diana Elena Cosău, Alexandru Dan Costache, Irina Iuliana Costache Enache, Ionela Lăcrămioara Șerban, Luiza Andreea Petrariu, Cristina Pomîrleanu, Mara Russu, Vladia Lăpuște and Codrina Ancuța
Reports 2025, 8(3), 123; https://doi.org/10.3390/reports8030123 - 26 Jul 2025
Viewed by 372
Abstract
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include [...] Read more.
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article
(This article belongs to the Section Critical Care/Emergency Medicine/Pulmonary)
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14 pages, 487 KiB  
Article
Sex-Based Differences in Clinical Presentation, Management, and Outcomes in Patients Hospitalized with Pulmonary Embolism: A Retrospective Cohort Study
by Benjamin Troxler, Maria Boesing, Cedrine Kueng, Fabienne Jaun, Joerg Daniel Leuppi and Giorgia Lüthi-Corridori
J. Clin. Med. 2025, 14(15), 5287; https://doi.org/10.3390/jcm14155287 - 26 Jul 2025
Viewed by 264
Abstract
Background/Objectives: Pulmonary embolism (PE) remains a major cause of morbidity and mortality. Despite advances in care, its nonspecific symptoms pose diagnostic and therapeutic challenges. Emerging evidence suggests sex-based differences in PE presentation, management, and outcomes, yet real-world data from European settings remain [...] Read more.
Background/Objectives: Pulmonary embolism (PE) remains a major cause of morbidity and mortality. Despite advances in care, its nonspecific symptoms pose diagnostic and therapeutic challenges. Emerging evidence suggests sex-based differences in PE presentation, management, and outcomes, yet real-world data from European settings remain scarce. This study aimed to investigate sex differences in clinical presentation, diagnostic workup, therapeutic interventions, and outcomes among hospitalized PE patients. Methods: We conducted a retrospective cohort study including all adult patients (≥18 years) admitted with a main diagnosis of acute PE at the Cantonal Hospital Baselland between January 2018 and December 2020. Data were extracted from electronic medical records and included demographics, comorbidities, symptoms, diagnostics, treatments, and outcomes. Sex-based comparisons were performed using univariate analyses. Results: Among 197 patients, 54% were women. Compared to men, women were more often admitted by ambulance (42% n = 45 vs. 24% n = 22, p = 0.009), had more frequent tachycardia (38% n = 41 vs. 23% n = 21, p = 0.024), and received lysis therapy more often (10% n = 11 vs. 2% n = 2, p = 0.023). DVT was more frequently diagnosed in women when sonography was performed (82% n = 49 vs. 64% n = 34, p = 0.035). Men had higher rates of B symptoms, smoking, and family history of PE. Women had longer hospital stays and were more frequently discharged to rehabilitation facilities. No sex differences were found in in-hospital mortality, 6-month rehospitalization, or adherence to diagnostic guidelines. Conclusions: This study reveals sex-based differences in PE presentation and management, suggesting potential disparities in care pathways. Further research is needed to promote equitable, personalized treatment strategies. Full article
(This article belongs to the Special Issue Pulmonary Embolism: Clinical Advances and Future Opportunities)
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10 pages, 232 KiB  
Article
Long-Term Pulmonary Function in Healthcare Workers: A Spirometric Evaluation Three Years Post-COVID-19 Pandemic
by Lorenzo Ippoliti, Luca Coppeta, Giuseppe Bizzarro, Cristiana Ferrari, Andrea Mazza, Agostino Paolino, Claudia Salvi, Laura Angelini, Cristina Brugaletta, Matteo Pasanisi, Antonio Pietroiusti and Andrea Magrini
Biomedicines 2025, 13(8), 1809; https://doi.org/10.3390/biomedicines13081809 - 24 Jul 2025
Viewed by 246
Abstract
Background: The long-term impact of SARS-CoV-2 infection on pulmonary function remains insufficiently characterised, particularly among individuals who have experienced mild or asymptomatic disease. This study aimed to assess spirometric changes over a three-year period and evaluate potential associations with demographic and clinical [...] Read more.
Background: The long-term impact of SARS-CoV-2 infection on pulmonary function remains insufficiently characterised, particularly among individuals who have experienced mild or asymptomatic disease. This study aimed to assess spirometric changes over a three-year period and evaluate potential associations with demographic and clinical variables. Methods: We retrospectively analysed spirometry data from 103 healthcare workers (HCWs) who underwent pulmonary function tests at three time points: before the pandemic (Time 0), one year post-pandemic (Time 1), and two years post-pandemic (Time 2). Linear regression models were employed to evaluate the impact of various factors, including age, BMI, gender, smoking status, history of SARS-CoV-2 infection, vaccination status prior to infection, and the number of infections, on changes in FVC and FEV1. Results: A statistically significant decrease in both FVC and FEV1 were observed at Time 1 and Time 2 compared to baseline (p < 0.05). Smoking habits were significantly associated with a greater decline in both FVC and FEV1. Multiple infections were associated with larger reductions in FVC at Time 1. No significant associations were found with age, gender, BMI, or vaccination status. Even in the absence of severe symptoms of the disease, healthcare workers exhibited a measurable decline in pulmonary function over time. Smoking and reinfection emerged as relevant factors associated with reduced lung capacity. Conclusions: These findings emphasise the need for ongoing respiratory monitoring in occupational settings and the importance of targeted preventive measures. Full article
27 pages, 1201 KiB  
Review
Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients
by Aitor Gonzaga, Gema Martinez-Navarrete, Loreto Macia, Marga Anton-Bonete, Gladys Cahuana, Juan R. Tejedo, Vanessa Zorrilla-Muñoz, Eduardo Fernandez-Jover, Etelvina Andreu, Cristina Eguizabal, Antonio Pérez-Martínez, Carlos Solano, Luis Manuel Hernández-Blasco and Bernat Soria
Biomedicines 2025, 13(8), 1801; https://doi.org/10.3390/biomedicines13081801 - 23 Jul 2025
Viewed by 457
Abstract
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). [...] Read more.
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article
(This article belongs to the Section Gene and Cell Therapy)
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9 pages, 418 KiB  
Review
The Occult Cascade That Leads to CTEPH
by Charli Fox and Lavannya M. Pandit
BioChem 2025, 5(3), 22; https://doi.org/10.3390/biochem5030022 - 23 Jul 2025
Viewed by 191
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, [...] Read more.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article
(This article belongs to the Special Issue Feature Papers in BioChem, 2nd Edition)
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18 pages, 386 KiB  
Review
Role of Non-Invasive Ventilation in Elderly Patients: Therapeutic Opportunity or Medical Futility? An Updated Narrative Review
by Francesca Sangiovanni, Giulia Sartori, Nadia Castaldo, Alberto Fantin and Ernesto Crisafulli
Medicina 2025, 61(7), 1288; https://doi.org/10.3390/medicina61071288 - 17 Jul 2025
Viewed by 438
Abstract
Background and Objectives: Acute respiratory failure (ARF) represents an increasingly relevant clinical challenge in older subjects due to population aging and the high prevalence of cardiopulmonary comorbidities. Non-invasive ventilation (NIV), developed as continuous positive airway pressure (CPAP) or bilevel positive airway pressure [...] Read more.
Background and Objectives: Acute respiratory failure (ARF) represents an increasingly relevant clinical challenge in older subjects due to population aging and the high prevalence of cardiopulmonary comorbidities. Non-invasive ventilation (NIV), developed as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP), has become a first-line treatment in various forms of ARF, including acute cardiogenic pulmonary oedema (ACPE) and acute exacerbations of COPD (AECOPD), offering several clinical advantages. In this context, the limited evidence on the efficacy of NIV in older patients leaves considerable uncertainty as to whether it constitutes a valid therapeutic option or represents medical futility in these patients. Materials and Methods: This narrative review explores the use of NIV and its outcomes in four key clinical scenarios in the elderly: ARF due to ACPE, AECOPD, community-acquired pneumonia (CAP), and palliative/end-of-life care. Results: Strong evidence supports NIV use with improved outcomes in ACPE and AECOPD, even in older populations. Conversely, data on its use in pneumonia are inconclusive, with potential harm if applied inappropriately. In palliative care, NIV can help relieve symptoms, but if not used appropriately, it may extend suffering. Conclusions: Age alone does not appear to be a sufficient factor to determine whether or not to use NIV; it becomes relevant only when considered in conjunction with the purpose of its use and the patient’s clinical history and condition. Data remain limited and often conflicting, particularly when investigating the elderly population and patients with a “do not intubate” (DNI) order. There is a need for additional research on these patients, focusing on long-term outcomes and quality of life. Full article
(This article belongs to the Section Pulmonology)
13 pages, 1916 KiB  
Case Report
Beyond Comorbidity: Pulmonary Adenocarcinoma in a Patient with Rheumatoid Arthritis—A Case Report and Literature Review
by Ancuța-Alina Constantin, Mihai Alexandru Arghir, Dana Avasilcăi and Florin-Dumitru Mihălțan
Life 2025, 15(7), 1118; https://doi.org/10.3390/life15071118 - 17 Jul 2025
Viewed by 355
Abstract
Lung cancer is one of the most common and deadly forms of cancer worldwide, despite sustained efforts to encourage smoking cessation and raise awareness of the risk factors. In Romania, lung cancer is a significant health challenge, being the leading cause of death [...] Read more.
Lung cancer is one of the most common and deadly forms of cancer worldwide, despite sustained efforts to encourage smoking cessation and raise awareness of the risk factors. In Romania, lung cancer is a significant health challenge, being the leading cause of death caused by cancer, especially amongst men. The incidence of lung cancer in connective tissue disease (CTD) varies in different studies from 4.5% in rheumatoid arthritis (RA), to 4.4% in polymyositis or dermatomyositis, and up to 11.1% in systemic sclerosis. However, older studies have shown an increased risk of cancer in patients with rheumatoid arthritis (RA), ranging from 10% to 30% compared to the general population, particularly in those undergoing methotrexate therapy. Rheumatoid arthritis affects approximately 40 per 100,000 people annually worldwide, with a three- to four-fold higher incidence in women. Non-small cell lung cancer (NSCLC), the most common lung cancer subtype, has been linked to RA, yet the association remains poorly defined, with limited insight into the underlying molecular mechanisms. We present the case of a 61-year-old male with a 49-pack-year smoking history and a known diagnosis of rheumatoid arthritis, currently managed with methotrexate therapy. He was admitted for evaluation due to a progressive decline in general condition, characterized by worsening dyspnea and chest pain, symptoms that had been longstanding but had markedly exacerbated over the past two weeks. Based on a chest CT performed prior to the patient’s admission to our clinic, subsequent diagnostic investigations established the diagnosis of pulmonary adenocarcinoma. The diagnostic process proved to be particularly challenging due to the presence of multiple comorbidities, which significantly impacted both the diagnostic approach and the overall clinical trajectory. Full article
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Article
Cytokine Profiles of Bronchoalveolar Lavage in Patients with Interstitial Lung Diseases and Non-Allergic Asthma
by Dana Greif Lenarčič, Urska Bidovec Stojković, Pia Kristanc, Peter Kopač, Mateja Marc Malovrh, Izidor Kern, Katarina Osolnik and Peter Korošec
Int. J. Mol. Sci. 2025, 26(14), 6831; https://doi.org/10.3390/ijms26146831 - 16 Jul 2025
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Abstract
Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated [...] Read more.
Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article
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