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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 11823

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Dr. Diego Bagnasco

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1. Respiratory and Allergy Clinic, Department of Internal Medicine (DIMI), University of Genoa, 16132 Genoa, Italy
2. IRCCS Policlinico San Martino, 16132 Genoa, Italy
Interests: asthma; severe asthma; lung disease; lung physiopathology; T2 inflammation; rhinosinusitis; nasal polyps
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Special Issue Information

Dear Colleagues,

This compilation of articles under the Special Issue titled "New Insights in Respiratory Diseases" will serve as a vital contribution to the scientific community by advancing our understanding of respiratory pathophysiology and therapeutic intervention strategies, particularly in asthma, COPD, and bronchiectasis. Contributions to this collection of valuable work will allow researchers and clinicians to share novel findings and critical analyses that challenge conventional paradigms and highlight emerging trends in the diagnosis, treatment, and management of respiratory disorders. Detailed scientific manuscripts foster interdisciplinary collaboration and cultivate a robust framework for the integration of basic science, clinical data, and translational research. High-quality manuscripts play an essential role in elucidating the complex mechanisms underlying respiratory conditions, from chronic obstructive pulmonary disease to bronchiectasis. By disseminating data-driven evidence and systematic reviews, these manuscripts contribute to the optimization of patient care and the refinement of clinical guidelines. Each contribution not only documents current advancements but also identifies knowledge gaps that warrant further investigation, thereby stimulating future research directions. Furthermore, authors are instrumental in providing critical insights into the molecular, cellular, and genetic determinants of respiratory diseases. Their work supports the development of innovative diagnostic tools and personalized therapies that address patient-specific needs. The peer-reviewed nature of these articles ensures that findings meet rigorous scientific standards, thereby enhancing the credibility of the conclusions drawn. Ultimately, the aggregation of well-researched articles within this collection empowers healthcare professionals to make informed decisions, encourages the adaptation of best practices in clinical settings, and drives progress towards improved respiratory health outcomes.

Dr. Diego Bagnasco
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

asthma
COPD
bronchiectasis
genetic
therapeutics

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Related Special Issue

New Insights in Respiratory Diseases (2nd Edition) in Biomedicines (3 articles)

Published Papers (9 papers)

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Editorial

Jump to: Research, Review

4 pages, 541 KB

Open AccessEditorial

New Insights in Respiratory Diseases

by Diego Bagnasco and Benedetta Bondi

Biomedicines 2026, 14(2), 427; https://doi.org/10.3390/biomedicines14020427 - 13 Feb 2026

Viewed by 643

Abstract

In recent years, pulmonology has undergone a profound transformation, perhaps the most significant since the birth of modern respiratory medicine [...] Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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Research

Jump to: Editorial, Review

14 pages, 810 KB

Open AccessArticle

Baseline Composite Score for 12-Month Clinical Remission in Biologic-Treated Severe Asthma: Development of the Base4Score

by Juan Luis García-Rivero, Adil Hannaoui Anaaoui, Abel Pallarés-Sanmartín, Marina Blanco-Aparicio, Raquel García-Hernáez, Victoria García-Gallardo Sanz, Uxío Calvo-Álvarez, Luis Carazo-Fernández, Tamara Hermida-Valverde, Silvia Dorronsoro, Inés Carrascosa-Anguiano, Ignacio Lobato Astiárraga, Idania de los Santos, Ana Isabel Enríquez Rodríguez, Luis Pérez de Llano, Pablo Álvarez Vega, Beatriz Abascal-Bolado and Miguel Santibañez

Biomedicines 2026, 14(4), 747; https://doi.org/10.3390/biomedicines14040747 - 25 Mar 2026

Viewed by 596

Abstract

Background: Clinical remission has become a realistic treatment goal in severe asthma, but current evidence mostly reports global remission rates without accounting for baseline disease burden. No simple tool exists to quantify baseline severity and estimate an individual patient’s probability of achieving remission under biologic therapy. Methods: This prospective observational study included 93 adults with severe asthma initiating tezepelumab across 14 specialised severe asthma units in Spain. Four baseline domains—poor symptom control (ACT < 20), ≥1 severe exacerbation in the previous 12 months, maintenance oral corticosteroid (OCS) use, and FEV₁ < 80% predicted—were used to construct an empirically weighted composite score (Base4Score) based on the inverse probability of correcting each abnormal domain at 12 months. Strict clinical remission at 12 months was defined as ACT ≥ 20, no severe exacerbations, no maintenance OCS, and FEV₁ ≥ 80%. Logistic regression was used to assess the association between the score and non-remission, adjusting for age, sex, smoking status, T2 phenotype, and biologic-naive status. Results: Of 93 treated patients, 81 had complete baseline data for Base4Score derivation and 77 had complete 12-month data for strict clinical remission analysis. Strict clinical remission was achieved in 16/77 patients (20.8%). Remission rates decreased across increasing baseline score strata: 40.0% for scores < 5, 17.6% for scores 5 to <9, and 12.5% for scores ≥ 9 (linear p-trend = 0.022). Each 1-point increase in the continuous Base4Score was associated with higher adjusted odds of non-remission (OR 1.22; 95% CI 1.00–1.49; p = 0.047), and patients with scores ≥ 9 had approximately sevenfold higher adjusted odds of non-remission than those with scores < 5 (OR 6.77; 95% CI 1.40–32.84; p = 0.018). Conclusions: The Base4Score is a simple, empirically derived baseline severity index that predicts 12-month strict clinical remission in severe asthma treated with tezepelumab. If externally validated, it could help personalise expectations, optimise timing of biologic initiation and guide treat-to-target strategies in severe asthma. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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22 pages, 800 KB

Open AccessArticle

The Influence of Smoking on Respiratory Function in Medical Students at the University of Medicine, Pharmacy, Science and Technology of Târgu-Mureș

by Edith-Simona Ianosi, Renata-Ingrid Ianosi, Hajnal Finta, Raul-Alexandru Lefter, Anca Meda Văsieșiu, Dragoș Huțanu and Maria-Beatrice Ianosi

Biomedicines 2026, 14(1), 164; https://doi.org/10.3390/biomedicines14010164 - 13 Jan 2026

Cited by 3 | Viewed by 976

Abstract

Background: Cigarette smoking remains one of the most important preventable causes of respiratory morbidity, exerting detrimental effects even in young adults. Medical students represent a particularly relevant population, as the lifestyle habits they adopt during their training years may influence both their personal health and professional credibility. Methods: We conducted a cross-sectional analysis of 264 medical students from the University of Medicine, Pharmacology, Science and Technology of Târgu-Mures, aged 18–30 years, stratified according to smoking status, type of tobacco product used, and lifestyle characteristics (athletic vs. sedentary). Standardized spirometry was performed to assess FVC, FEV₁, FEV₁/FVC ratio, PEF, and small airway flow parameters (MEF₂₅, MEF₅₀, MEF₇₅). Statistical comparisons between groups were performed using t-tests, Mann–Whitney U tests, chi-square tests, and correlation analyses, with p < 0.05 considered statistically significant. Results: Smokers demonstrated significantly lower values for FEV₁, PEF, and MEF parameters compared with non-smokers, confirming early functional impairment of both large and small airways. Within the smoking group, users of e-cigarettes or heated tobacco products exhibited more favorable FEV₁ and small airway flow values than conventional cigarette smokers. However, differences in FVC were less pronounced. Significantly, athletes consistently outperformed their sedentary peers across all respiratory parameters, regardless of smoking status, with markedly higher FEV₁, FVC, and MEF values and a lower prevalence of obstructive patterns. Cumulative smoking exposure (pack-years) was inversely associated with small airway function, whereas higher levels of physical activity were independently linked to a pronounced protective effect. Conclusions: Even in early adulthood, smoking is related to measurable declines in lung function, particularly affecting small airway dynamics. Although alternative products may appear less harmful than conventional cigarettes, they cannot be considered risk-free. Conversely, regular physical activity demonstrated a protective association in the case–control analysis, attenuating functional decline and supporting the preservation of long-term respiratory health. These findings underscore the importance of integrated prevention strategies in medical universities, combining smoking cessation initiatives with the systematic promotion of physical activity to safeguard the health of future physicians and reinforce their role as credible health advocates. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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17 pages, 1777 KB

Open AccessArticle

Assessing the Heterogeneous Treatment Effects of Glucocorticoids in Infants and Toddlers with Severe Pneumonia

by Zhoumeng Ying, Haiyan Ge, Wei Han, Ge Hu, Zhenchen Zhu, Jinhua Wang, Lan Song, Dong Qu and Zhengyu Jin

Biomedicines 2025, 13(10), 2333; https://doi.org/10.3390/biomedicines13102333 - 24 Sep 2025

Cited by 2 | Viewed by 1530

Abstract

Background: Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalizations and a risk factor for chronic respiratory conditions. Glucocorticoids (GCs) are used as adjunctive therapy to reduce inflammation, but their efficacy in infants and toddlers remains unclear. Method: A retrospective study of 1116 infants and toddlers with severe CAP was conducted, using causal forest to estimate individual treatment effects (ITEs), with the duration of intensive care unit (ICU) stay as the outcome. Patients were stratified based on ITEs to investigate the heterogeneous treatment effect (HTE) and identify responders. Generalized linear models validated the HTE across subclasses, followed by comparative analyses to characterize responders. Variable importance was assessed using the causal model, and Shapley additive explanations (SHAP) quantified each variable’s contribution to the ITE. Analysis was also performed in mechanically ventilated patients (MV group). Results: GCs demonstrated significant HTE. Older patients and those with elevated inflammation markers showed better responses, whereas no such benefit was observed in respiratory syncytial virus-infected patients. These subgroups experienced shorter ICU stays both in the whole cohort (β = −0.16, p < 0.001) and MV group (β = −0.34, p < 0.001), and shorter ventilation duration was observed in the MV group (β = −0.35, p < 0.001). Age and the anion gap were key predictors of ITEs. SHAP analysis revealed a positive correlation between age and GC effectiveness. Conclusions: Significant heterogeneity in GC treatment effects exists among infants and toddlers with severe CAP, highlighting the need for optimization of GC use in this population. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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13 pages, 459 KB

Open AccessArticle

The Impact of Pulmonary Hypertension on Hospitalization Risk in Adults with Respiratory Syncytial Virus Infection

by Mayuri Mudgal, Aseem Rai Bhatnagar, Aneesh Kumar Vasudevan, Ajeetha Priya Gajendiran, Venkatesh Gondhi, Swetha Balaji, Shanjai Krishnan Murugan and Kulothungan Gunasekaran

Biomedicines 2025, 13(9), 2272; https://doi.org/10.3390/biomedicines13092272 - 16 Sep 2025

Cited by 1 | Viewed by 1377

Abstract

Background/Objectives: Respiratory syncytial virus (RSV) infection can lead to significant complications, particularly among those with underlying cardiovascular and pulmonary complications. Patients with pulmonary hypertension (PH) are susceptible to clinical deterioration triggered by respiratory infections due to their limited cardiopulmonary reserve. This study aimed to assess the risk of hospitalization in RSV-infected adults with and without PH. Methods: We conducted a retrospective cohort study using the research network TriNetX to assess the risk of hospitalization in a cohort of patients with RSV infection, comparing those with and without PH. Propensity score matching was performed for demographic variables and RSV risk factors between the two cohorts. The risk of hospitalization was expressed as an adjusted odds ratio (aOR) with a 95% confidence interval (CI). Results: There were 193,256 patients in the RSV with PH cohort and 2,843,714 in the RSV without PH cohort (all aged >18 years). The mean age of the RSV with PH cohort was 68.2 ± 15.3 years, 50.6% were females, 64% were white, and 64.2% were group 2 PH. The RSV with PH cohort was at an increased risk of hospitalization (aOR 1.89, 95% CI 1.87–1.92, p-value 0.02). There was a significant risk (aOR 1.29, 95% CI 1.27–1.32) for the composite outcome of hospitalization-related complications between the two cohorts. Comorbid conditions (diabetes, cardiovascular disease, chronic lung disease, and chronic kidney disease) increased the risk of hospitalization in the RSV with PH group, with the biggest effect noted with underlying cardiovascular disease. Similarly, those with group 2 PH had a higher risk of hospitalization compared to the other PH groups. Remarkably, all PH groups demonstrated increased hospitalization risk compared to the RSV without PH cohort. Conclusions: We found that patients >18 years of age with PH and RSV infection were at an increased risk of hospitalization, with subsequently higher rates of RSV-infection-related complications. All PH groups had a higher hospitalization risk compared to the RSV without PH cohort, likely denoting PH as an independent risk factor for worse RSV-infection-related outcomes. RSV vaccination, therefore, may benefit all age groups of patients with PH. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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19 pages, 2154 KB

Open AccessArticle

Association of LPCAT1*rs9728 Variant with Reduced Susceptibility to Neonatal Respiratory Distress Syndrome

by Shimaa Dorgham, Sohier Yahia, Doaa Shahin, Ahmad M. Eita, Eman A. Toraih and Rami M. Elshazli

Biomedicines 2025, 13(9), 2237; https://doi.org/10.3390/biomedicines13092237 - 11 Sep 2025

Cited by 1 | Viewed by 1496

Abstract

Background/Objectives: Neonatal respiratory distress syndrome (NRDS) is a heterogenous respiratory illness that mainly affects preterm neonates. It is characterized by insufficient production of pulmonary surfactant and impaired lung compliance. The lysophosphatidylcholine acyltransferase 1 (LPCAT1) enzyme has a crucial function in lipid remodeling through the conversion of lysophosphatidylcholine to phosphatidylcholine, the major component of pulmonary surfactant. In this research, we aimed to investigate the association of the LPCAT1*rs9728 variant with NRDS susceptibility using hereditary analysis and bioinformatic approaches. Methods: The LPCAT1 (rs9728; c.*1668T>C) variant was characterized among 100 preterm neonates with RDS and 100 non-RDS neonates utilizing the TaqMan SNP genotyping assay. Logistic regression analysis was performed to identify the risk factors of respiratory distress syndrome. The functional mechanism of the LPCAT1 gene was elucidated using bioinformatic approaches. Results: The LPCAT1*rs9728 C/C genotype was significantly associated with a 78% reduced risk of NRDS (OR = 0.22, p = 0.027), although the minor C allele did not attain a significant finding (OR = 0.83, p = 0.416). Apgar score and Silverman–Andersen respiratory severity score (RSS) were statistically significant with prematurity classes (p < 0.05). Additionally, gestational age and birth weight were considered independent risk factors in the progression of RDS among preterm neonates. Conclusions: This research exhibited a significant difference between the LPCAT1 (rs9728; c.*1668T>C) variant and reduced risk against the development of RDS among preterm neonates. The rs9728*C/C genotype revealed a significant association with decreased risk of NRDS compared to non-RDS neonates. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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22 pages, 9750 KB

Open AccessArticle

SIK2 Drives Pulmonary Fibrosis by Enhancing Fibroblast Glycolysis and Activation

by Jianhan He, Ruihan Dong, Huihui Yue, Fengqin Zhang, Xinran Dou, Xuan Li, Hui Li and Huilan Zhang

Biomedicines 2025, 13(8), 1919; https://doi.org/10.3390/biomedicines13081919 - 6 Aug 2025

Cited by 2 | Viewed by 2104

Abstract

Background: Pulmonary fibrosis (PF), the end-stage manifestation of interstitial lung disease, is defined by excessive extracellular matrix deposition and alveolar destruction. Activated fibroblasts, the primary matrix producers, rely heavily on dysregulated glucose metabolism for their activation. While Salt Inducible Kinase 2 (SIK2) regulates glycolytic pathways in oncogenesis, its specific contributions to fibroblast activation and therapeutic potential in PF pathogenesis remain undefined. This study elucidates the functional role of SIK2 in PF and assesses its viability as a therapeutic target. Methods: SIK2 expression/localization in fibrosis was assessed by Western blot and immunofluorescence. Fibroblast-specific Sik2 KO mice evaluated effects on bleomycin-induced fibrosis. SIK2’s role in fibroblast activation and glucose metabolism impact (enzyme expression, metabolism assays, metabolites) were tested. SIK2 inhibitors were screened and evaluated therapeutically in fibrosis models. Results: It demonstrated significant SIK2 upregulation, specifically within activated fibroblasts of fibrotic lungs from both PF patients and murine models. Functional assays demonstrated that SIK2 is crucial for fibroblast activation, proliferation, and migration. Mechanistically, SIK2 enhances fibroblast glucose metabolism by increasing the expression of glycolysis-related enzymes. Additionally, this study demonstrated that the SIK2 inhibitor YKL06-061 effectively inhibited PF in both bleomycin and FITC-induced PF mouse models with the preliminary safety profile. Furthermore, we identified a novel therapeutic application for the clinically approved drug fostamatinib, demonstrating it inhibits fibroblast activation via SIK2 targeting and alleviates PF in mice. Conclusions: Our findings highlight SIK2 as a promising therapeutic target and provide compelling preclinical evidence for two distinct anti-fibrotic strategies with significant potential for future PF treatment. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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12 pages, 676 KB

Open AccessArticle

Challenges Pertaining to the Optimization of Therapy and the Management of Asthma—Results from the 2023 EU-LAMA Survey

by Michał Panek, Robab Breyer-Kohansal, Paschalis Steiropoulos, Peter Kopač, Monika Knopczyk, Tomasz Dębowski, Christer Janson and Maciej Kupczyk

Biomedicines 2025, 13(8), 1877; https://doi.org/10.3390/biomedicines13081877 - 1 Aug 2025

Cited by 1 | Viewed by 1255

Abstract

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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Review

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24 pages, 3975 KB

Open AccessReview

Percolation Forces in Lung Inflammation: Determining the Path to Emphysema or Fibrosis

by Jerome Cantor

Biomedicines 2026, 14(2), 281; https://doi.org/10.3390/biomedicines14020281 - 27 Jan 2026

Cited by 1 | Viewed by 741

Abstract

The dichotomous outcomes of chronic lung inflammation, represented by either pulmonary emphysema or interstitial fibrosis, involve poorly understood overlapping mechanisms. Recent insights from network theory suggest that percolation phenomena, coupled with the dynamics of extracellular matrix crosslinking, play an important role in determining these divergent pathological trajectories. This review examines how critical percolation thresholds at which local damage or repair transitions to system-wide structural failure or rigidification determine the changes in lung tissue during chronic inflammation. We examine the mechanisms of collagen and elastin crosslinking, the feedback loops that amplify initial perturbations, and the threshold behaviors that push inflamed lung tissue toward either emphysematous destruction or fibrotic consolidation. Understanding these percolation-dependent transitions provides new insights into why similar inflammatory insults can produce opposite structural outcomes and suggests novel therapeutic strategies targeting the crosslinking mechanisms that underlie these critical transitions. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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