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8 pages, 1275 KB  
Case Report
Mixed Infectious–Immune Pneumonitis Associated with PD-L1 Blockade: A Case of Durvalumab-Induced Lung Injury Complicated by Human Metapneumovirus Infection
by Luca Pipitò, Chiara Vincenza Mazzola, Ilenia Giacchino, Riccardo De Rosa, Carola Maria Gagliardo, Alessio Giuseppe Lipari, Paola Monte, Federica Furia, Erika Mannino, Rosaria Pecoraro, Nicola Scichilone and Antonio Cascio
J. Clin. Med. 2026, 15(1), 251; https://doi.org/10.3390/jcm15010251 - 29 Dec 2025
Viewed by 326
Abstract
Background: Durvalumab, a PD-L1 inhibitor used as consolidation therapy after chemoradiation in unresectable stage III non–small cell lung cancer (NSCLC), can induce immune-related adverse events, among which immune-mediated pneumonitis represents one of the most severe. Differentiating checkpoint inhibitor pneumonitis (CIP) from infectious pneumonia [...] Read more.
Background: Durvalumab, a PD-L1 inhibitor used as consolidation therapy after chemoradiation in unresectable stage III non–small cell lung cancer (NSCLC), can induce immune-related adverse events, among which immune-mediated pneumonitis represents one of the most severe. Differentiating checkpoint inhibitor pneumonitis (CIP) from infectious pneumonia is challenging due to overlapping clinical and radiologic findings. Case presentation: We describe a 67-year-old woman with stage III lung adenocarcinoma treated with chemotherapy, radiotherapy, and durvalumab, who presented with progressive dyspnea and extensive bilateral ground-glass opacities on CT imaging. Laboratory tests revealed leukopenia and elevated inflammatory markers. Despite broad-spectrum antibiotic and antiviral therapy, her condition worsened, requiring high-flow nasal cannula oxygen therapy. Multiplex molecular testing on sputum identified human metapneumovirus (HMPV), while blood cultures and urinary antigens for Streptococcus pneumoniae and Legionella pneumophila were negative. A pulmonology consultation raised suspicion for severe durvalumab-induced pneumonitis exacerbated by viral infection. High-dose methylprednisolone (2 mg/kg/day) followed by a four-week taper led to gradual clinical and radiologic resolution. Durvalumab was permanently discontinued. Discussion: To our knowledge, this is the first reported case of HMPV-associated pneumonitis in a patient receiving durvalumab. This case highlights the potential synergistic interplay between viral infection and immune checkpoint blockade, resulting in severe lung injury. Comprehensive microbiologic evaluation, including molecular diagnostics, is essential to guide therapy and distinguish infectious from immune-mediated causes. Conclusions: Early recognition of mixed infectious and immune-mediated pneumonitis, and timely corticosteroid therapy are critical to achieving favorable outcomes and preventing irreversible pulmonary damage. Full article
(This article belongs to the Section Infectious Diseases)
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25 pages, 5270 KB  
Article
Ceragenins in Combination with Ivacaftor Prevent the Formation of Biofilm by Bacteria That Cause Rhinosinusitis
by Szczepan Kaliniak, Piotr Deptuła, Jakub Spałek, Mariusz Sawieljew, Sylwia Chmielewska-Deptuła, Tamara Daniluk, Agata Lesiak, Bonita Durnaś, Paul B. Savage, Ewelina Piktel, Robert Bucki and Sławomir Okła
Pharmaceutics 2026, 18(1), 1; https://doi.org/10.3390/pharmaceutics18010001 - 19 Dec 2025
Viewed by 348
Abstract
Background/Objectives: Ceragenins (CSAs) maintain strong antibacterial activity even in cystic fibrosis (CF) sputum. Ivacaftor (IVA), a CF transmembrane regulator modulator, provides significant clinical benefits in CF therapy. Based on these properties, we hypothesized that the combination of CSAs and IVA, due to their [...] Read more.
Background/Objectives: Ceragenins (CSAs) maintain strong antibacterial activity even in cystic fibrosis (CF) sputum. Ivacaftor (IVA), a CF transmembrane regulator modulator, provides significant clinical benefits in CF therapy. Based on these properties, we hypothesized that the combination of CSAs and IVA, due to their antibacterial and biofilm-penetrating abilities, may also be beneficial in the treatment of chronic rhinosinusitis (CRS), including CRS in CF patients. Notably, the physicochemical properties of biofilms in chronic rhinosinusitis (CRS) resemble those in CF sputum. Methods: We determined the minimal inhibitory and bactericidal concentrations (MIC and MBC) and the fractional inhibitory concentration index (FICI) for ceragenins (CSA-13, CSA-44, CSA-131), ivacaftor (IVA), selected conventional antibiotics, and their combinations against both reference and clinical strains. Bacterial viability within biofilms was also evaluated following exposure to these agents. Atomic force microscopy (AFM) was used to analyze the morphology and nanomechanical properties of Staphylococcus aureus and Pseudomonas aeruginosa. In addition, rheological measurements of Pseudomonas aeruginosa biofilms treated with CSAs combined with IVA were performed using a rotational rheometer. Results: The tested agents demonstrated anti-biofilm activity against bacterial strains associated with CRS development. IVA enhanced the anti-biofilm effects of both CSAs and tested antibiotics. CSAs exhibited low MIC and MBC values, confirming their efficacy against tested pathogens. AFM showed that CSA-44, IVA, vancomycin, and their combinations altered the nanomechanical properties of Pseudomonas aeruginosa and Staphylococcus aureus cells. Interestingly, the addition of IVA induced aggregation of S. aureus cells. CSAs reduced the stiffness of P. aeruginosa biofilms, and co-treatment with IVA resulted in a further decrease in biofilm stiffness. Conclusions: These findings indicate that ceragenins, particularly in combination with ivacaftor, represent a promising therapeutic strategy for challenging chronic infections caused by the studied bacteria. This supports further research aimed at developing new treatment methods for CRS. Full article
(This article belongs to the Section Drug Targeting and Design)
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15 pages, 1036 KB  
Article
Sputum Exosomal microRNAs as Non-Invasive Biomarkers in COPD: A Cross-Sectional Study
by Ourania S. Kotsiou, Irene Tsilioni, Aikaterini Tsingene, Aikaterini Katsanaki, Nikolaos A. A. Balatsos, Erasmia Rouka, Zoe Daniil and Konstantinos I. Gourgoulianis
Biomedicines 2025, 13(12), 3027; https://doi.org/10.3390/biomedicines13123027 - 10 Dec 2025
Viewed by 347
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition marked by airway inflammation, airflow limitation, and structural remodeling. Exosomal microRNAs (exo-miRNAs) are stable, cell-free biomarkers reflecting airway molecular changes. While serum and BALF exosomal miRNAs have been examined, sputum-derived profiles remain underexplored. [...] Read more.
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition marked by airway inflammation, airflow limitation, and structural remodeling. Exosomal microRNAs (exo-miRNAs) are stable, cell-free biomarkers reflecting airway molecular changes. While serum and BALF exosomal miRNAs have been examined, sputum-derived profiles remain underexplored. Methods: Induced sputum was collected from 20 clinically stable COPD patients and 10 age-matched healthy controls. Exosomes were isolated by polymer-based precipitation and verified by transmission electron microscopy and Western blotting for CD9 and CD81. Nine candidate miRNAs (miR-21, miR-155, miR-34a, miR-126, miR-210, miR-146a, miR-199a-5p, miR-223, miR-1246) were quantified by RT-qPCR. Group comparisons used the Mann–Whitney U test, correlations Pearson’s r, and diagnostic accuracy ROC analysis. Results: Sputum-derived exosomes displayed characteristic morphology and canonical protein markers. COPD patients showed significant dysregulation of exosomal miRNAs, including upregulation of miR-21 (fold change = 3.4; 95% CI: 0.12–0.64 vs. 0.18–0.22; p < 0.001) and miR-223 (fold change = 2.1; 95% CI: 0.00–3.79 vs. 0.86–1.22; p = 0.004), and downregulation of miR-155 (fold change = 0.35; 95% CI: 0.43–0.67 vs. 0.86–1.22; p = 0.002), miR-126 (fold change = 0.42; 95% CI: 0.30–0.39 vs. 0.80–1.42; p = 0.009), and miR-146a (fold change = 0.28; 95% CI: 0.49–1.12 vs. 0.87–1.35; p = 0.006). miR-21 correlated with symptom burden (CAT; r = 0.445; p = 0.049). Among individual biomarkers, miR-155 exhibited the best diagnostic performance for COPD detection (AUC = 0.730; 95% CI: 0.53–0.93), which further improved when combined with miR-126 and miR-146a (AUC = 0.841; 95% CI: 0.69–0.98). For disease stratification, miR-126 most effectively discriminated mild from moderate-to-severe COPD (AUC = 0.728; 95% CI: 0.50–0.96). These results indicate that sputum-derived exosomal miRNAs—particularly miR-155, miR-126, and miR-146a—may serve as promising non-invasive biomarkers for COPD diagnosis and clinical phenotyping. Conclusions: Sputum exosomal miRNAs reveal a distinct COPD-specific signature reflecting inflammation, impaired repair, and immune dysregulation. Composite panels incorporating miR-155, miR-126, and miR-146a enhance diagnostic accuracy and could be integrated into non-invasive workflows for COPD detection and staging. Full article
(This article belongs to the Special Issue Advanced Research in Pulmonary Pathophysiology)
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13 pages, 270 KB  
Article
Asthma-Associated COPD Etiotype: Clinical Features and Inflammatory Patterns in Biological Samples
by Camyla Fernandez de Farias, José Baddini-Martinez, Ana Luisa Godoy Fernandes, Maria Marta Amorim, Michel Dracoulakis, Maria Amélia Santos, Lilian Ballini Caetano and Fernando Sergio Leitão Filho
J. Pers. Med. 2025, 15(12), 615; https://doi.org/10.3390/jpm15120615 - 10 Dec 2025
Viewed by 352
Abstract
Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recognizes asthma as a potential causal pathway for chronic obstructive pulmonary disease, referred to as the COPD-A etiotype. However, the clinical and inflammatory characteristics of this phenotype remain poorly defined. Objectives: [...] Read more.
Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recognizes asthma as a potential causal pathway for chronic obstructive pulmonary disease, referred to as the COPD-A etiotype. However, the clinical and inflammatory characteristics of this phenotype remain poorly defined. Objectives: This study aimed to characterize clinical traits and cytokine profiles in stable asthmatics exhibiting persistent airflow limitation compatible with COPD-A. Methods: In this cross-sectional study, 94 stable asthmatic patients (71.3% female; age = 54.0 ± 15.6 years) without relevant smoking or environmental exposures were evaluated. COPD-A was defined by a post-bronchodilator FEV1/FVC ratio < 0.70. Asthma control (ACQ, ACT), quality of life (AQLQ), and lung function were assessed. Levels of IL-5, IL-8, IL-13, IL-17A, IL-17F, IL-25, IL-33, and TNF were quantified in nasal lavage, induced sputum, and blood samples. Results: Among the participants, 42 (44.7%) fulfilled COPD-A criteria. Compared with non-COPD-A subjects, those with COPD-A were older (60.5 vs. 48.7 years; p < 0.001) and had longer disease duration (39.8 vs. 30.1 years; p < 0.001), lower post-bronchodilator FEV1% predicted (68.1 vs. 87.1%; p < 0.001), and poorer asthma control (ACQ = 1.00 vs. 0.64; p = 0.003). Cytokine levels were comparable between groups except for higher IL-8 concentrations in induced sputum of COPD-A subjects (7.66 vs. 2.51 pg/mL; p = 0.024). Sputum IL-8 ≥ 3.096 pg/mL independently predicted COPD-A (aOR = 12.82; p = 0.023). Conclusions: Over 40% of non-smoking asthmatics exhibited persistent airflow limitation consistent with COPD-A. Elevated sputum IL-8 levels may be a potential biomarker of this etiotype. Full article
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21 pages, 869 KB  
Review
Tracing Microplastics in the Human Body: From Detection to Disease Mechanisms
by Stefana Anastasia Talau, Mihaela Chialda, Cristian Ichim, Horatiu Dura and Ciprian Tanasescu
Diagnostics 2025, 15(23), 2971; https://doi.org/10.3390/diagnostics15232971 - 23 Nov 2025
Viewed by 1036
Abstract
Microplastics (MPs), defined as plastic particles < 5 mm diameter, have become a growing public health concern. First identified in the aquatic environment in 2004 and later in air samples in 2015, airborne MPs display wide variations in shape and size, with fibres [...] Read more.
Microplastics (MPs), defined as plastic particles < 5 mm diameter, have become a growing public health concern. First identified in the aquatic environment in 2004 and later in air samples in 2015, airborne MPs display wide variations in shape and size, with fibres being the most common. These physical characteristics, together with others such as median aerodynamic diameter, influence how deeply they penetrate and where they deposit within the respiratory tract. Recent studies have confirmed the presence of MPs in nasal lavage fluid, bronchoalveolar lavage fluid, sputum, pleural fluid and lung tissue samples, with higher concentrations observed in older individuals, smokers and those with occupational exposure. Multiple polymer types have been identified, most frequently polypropylene, polyethylene and polyester. Experimental models demonstrate that MPs can induce inflammation, oxidative stress, mitochondrial dysfunction, microbiota alterations, fibrosis and carcinogenic changes, with toxicity generally increasing as particle size decreases. Despite the growing evidence of plastic toxicity, only a limited number of studies have examined MPs’ influence on the respiratory system, focusing mostly on polyester spheres, rather than fibres, which dominate real-world exposure. Current findings suggest MPs contribute to several pathophysiological processes and may play a role in respiratory disease. However, further research is needed to clarify the underlying mechanisms, long-term consequences and clinical relevance of these emerging pollutants. Full article
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16 pages, 1814 KB  
Article
A Treatment-Resistant Severe Asthma Phenotype with Dysregulated Hippo Pathway as Shown by Sputum Transcriptomics and Proteomics
by Emília Ma. Medeiros de Andrade Belitardo, Paula C. Almeida, Flávia A. Sena, Eduardo S. Silva, Danilo J. P. G. Rocha, Juliana Mendonça, Carina S. Pinheiro, Peter Briza, Fatima Ferreira, Lúcio R. Queiroz, Eric R. G. R. Aguiar, Álvaro A. Cruz, Luis G. C. Pacheco and Neuza M. Alcantara-Neves
Allergies 2025, 5(4), 38; https://doi.org/10.3390/allergies5040038 - 3 Nov 2025
Viewed by 787
Abstract
Severe asthma is a heterogeneous condition often resistant to conventional corticosteroid therapy, necessitating the identification of novel biomarkers and therapeutic targets. This study investigates immunological, transcriptional, and proteomic biomarkers in severe asthma patients from the Brazilian ProAR cohort. Cytokines were measured using a [...] Read more.
Severe asthma is a heterogeneous condition often resistant to conventional corticosteroid therapy, necessitating the identification of novel biomarkers and therapeutic targets. This study investigates immunological, transcriptional, and proteomic biomarkers in severe asthma patients from the Brazilian ProAR cohort. Cytokines were measured using a multiplex technology and the differential sputum cell count was performed by cytospin preparations. Sputum transcriptomics was performed by RNA-seq using Ion S5 next-generation sequencing platform. The proteomic study of sputum was performed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) using Q Exactive Orbitrap technology. Compared to mild-to-moderate asthma (MMA) and treatment-controlled severe asthma (SAC), the treatment-resistant severe asthma (SAR) group exhibited increased sputum neutrophilia, eosinophilia, and elevated IL-6 and TNF levels, correlating with impaired lung function. Transcriptomic and proteomic analyses revealed a Th2-independent molecular signature characterized by downregulation of the Hippo signaling pathway and upregulation of JAK–STAT inflammatory cascades. Distinctive microRNA profiles suggest regulatory involvement in inflammatory and proliferative processes. These findings align with prior studies, reinforcing the presence of an IL-6- and TNF-high severe asthma phenotype across diverse populations. Our results highlight key inflammatory pathways that may underlie corticosteroid resistance, offering potential targets for personalized therapeutic interventions in severe asthma. Full article
(This article belongs to the Section Asthma/Respiratory)
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13 pages, 451 KB  
Article
Evaluation of Performance of C-Reactive Protein (CRP) and Interferon-Gamma-Inducible Protein 10 (IP-10) as Screening for Active Tuberculosis
by Rotimi Samuel Owolabi, Russel Dacombe, Konstantina Kontogianni, Olusegun M. Akinwande, Lovett Lawson and Luis E. Cuevas
Trop. Med. Infect. Dis. 2025, 10(11), 306; https://doi.org/10.3390/tropicalmed10110306 - 27 Oct 2025
Viewed by 989
Abstract
Background: Most of the currently approved TB diagnostics are sputum-based. However, due to unusual clinical presentations of TB among HIV patients, they may not have TB symptoms and be able to produce sputum. Hence, these diagnostics may not be able to detect as [...] Read more.
Background: Most of the currently approved TB diagnostics are sputum-based. However, due to unusual clinical presentations of TB among HIV patients, they may not have TB symptoms and be able to produce sputum. Hence, these diagnostics may not be able to detect as many TB cases as possible among these patients. Therefore, this study assessed the performance of C-reactive protein (CRP) and interferon-gamma-inducible protein 10 (IP-10) as a screening tool for TB. Methods: This prospective study was conducted by consecutively recruiting patients with TB symptoms, collecting their sputum and blood samples, using sputum culture as the reference standard, and determining the best cut-off point of serum levels of CRP and IP-10 (separately and in combination) for TB diagnosis. Findings: CRP and IP-10 were measured in 408 patients with TB symptoms, of which 21% had culture-confirmed TB. CRP’s sensitivity and specificity were (91.4% and 33.2%), (95.3% and 42.6%) and (84.8% and 22.1%) for the whole study population, HIV-negative and HIV-positive patients, respectively. The sensitivity and specificity of IP-10 were (87.3% and 40.9%), (87.5% and 50.3%) and (79.4% and 47.2%) for the patients’ categories, respectively. Combination of CRP and IP-10 slightly improved the performance of the biomarkers among HIV-negative patients, with sensitivity of 97.5% and specificity of 43.3%. Interpretation: Though CRP and IP-10 performed better in HIV-negative patients than among people living with HIV (PLHIV), the performance of the biomarkers is lower than what is recommended by the WHO (sensitivity ≥ 90% and specificity ≥ 70%) for a TB screening tool. Hence, there is a need for better non-sputum-based TB diagnostics. Full article
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23 pages, 993 KB  
Review
Neutrophilic Asthma—From Mechanisms to New Perspectives of Therapy
by Ilona Iwaszko, Krzysztof Specjalski, Marta Chełmińska and Marek Niedoszytko
J. Clin. Med. 2025, 14(20), 7137; https://doi.org/10.3390/jcm14207137 - 10 Oct 2025
Viewed by 2457
Abstract
Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from >40% to >76%) with low eosinophils (<2%). The prevalence of NA [...] Read more.
Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from >40% to >76%) with low eosinophils (<2%). The prevalence of NA ranges from 16% to 28% of the adult asthma population depending on the definitions and study methods applied. A clinical picture of NA is characterized by late onset of symptoms, higher exacerbation rate, lower level of symptoms control, and poorer response to steroids compared to eosinophilic phenotype. Comorbidities such as obesity and GERD as well as the influence of environmental factors (air pollution, smoking, bacterial infections) contribute to the development and severe course of the disease. NA is T2-low disease with predominantly Th1/Th17-type inflammation. Neutrophils are key cells responsible for initiating and sustaining inflammation. In addition to their primary functions like phagocytosis, degranulation, and NETosis, neutrophils release several pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF) and chemokines (CXCL-1, -2, -8, -9, -10) responsible for the recruitment of other neutrophils or T cells. Increasing knowledge about the biology of neutrophiles and their role in asthma results in new potential therapies that could improve control of NA, particularly new biologicals targeting Th1/Th17-related cytokines. In this review, we discuss the prevalence, mechanisms, and clinical features of neutrophilic asthma. Furthermore, current therapeutic options and some promising perspectives for the near future are presented. Full article
(This article belongs to the Special Issue Advances in Asthma: 2nd Edition)
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13 pages, 1896 KB  
Systematic Review
Pneumocystis jirovecii Pneumonia Diagnosis with Oropharyngeal Wash PCR in Immunocompromised Patients—A Systematic Review
by Vasco Salgado Costa, José Pedro Cidade, Inês Medeiros, Pedro Fidalgo, Hugo Moreira, Teresa Miranda and Pedro Póvoa
J. Clin. Med. 2025, 14(18), 6572; https://doi.org/10.3390/jcm14186572 - 18 Sep 2025
Viewed by 1943
Abstract
Background/Objectives:  Pneumocystis jirovecii pneumonia (PJP) remains a major cause of morbidity and mortality in immunocompromised patients. Bronchoalveolar lavage (BAL) is the diagnostic gold standard but is invasive and often impractical in critically ill patients. Oropharyngeal wash (OW) polymerase chain reaction (PCR) offers [...] Read more.
Background/Objectives:  Pneumocystis jirovecii pneumonia (PJP) remains a major cause of morbidity and mortality in immunocompromised patients. Bronchoalveolar lavage (BAL) is the diagnostic gold standard but is invasive and often impractical in critically ill patients. Oropharyngeal wash (OW) polymerase chain reaction (PCR) offers a rapid, non-invasive alternative. We performed a systematic review focusing on this respiratory sample’s diagnostic accuracy and clinical utility. Methods: We searched PubMed, Scopus, Web of Science, Cochrane Library, and clinical trial registries including ClinicalTrials.gov and MedRxiv for studies of PCR-based P. jirovecii detection in OW samples from immunocompromised adults, using BAL or induced sputum as reference standards. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Quality was assessed with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and pooled sensitivity/specificity were estimated using a bivariate random-effects model. Results: Twelve studies (n = 633; 346 confirmed PJP cases) met the inclusion criteria. Most cohorts were human immunodeficiency virus (HIV)-positive. Pooled sensitivity was 68.3% (95% CI: 59.2–75.9) and specificity 91.8% (95% CI: 85.9–95.3); the area under the summary receiver operating characteristic curve (AUC) was 0.887. Diagnostic yield improved with pre-sample cough induction, 60-s gargling, early sampling before extended therapy, and higher fungal loads. Risk of bias was low, and no significant publication bias was detected. Conclusions: OW-based PCR delivers high specificity and moderate sensitivity for PJP diagnosis, offering a safe, scalable, and patient-friendly alternative when invasive testing is unfeasible. Optimizing collection protocols and expanding evaluation to non-HIV immunosuppressed populations could enhance its role as an early screening tool, enabling faster treatment decisions and reducing unnecessary antimicrobial exposure. Full article
(This article belongs to the Special Issue Clinical Advances in Critical Care Medicine)
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6 pages, 1522 KB  
Case Report
Lymphomatoid Granulomatosis and Tuberculosis, Coincidence or Cohabitation—A Case Report
by Nicolas Giachetti, Sarah Bellal, Marianne Schwarz, Jérôme Paillassa, Aline Clavert, Mathilde Hunault-Berger and Firas Safa
Lymphatics 2025, 3(3), 28; https://doi.org/10.3390/lymphatics3030028 - 15 Sep 2025
Viewed by 651
Abstract
Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV-induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size, being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible. Although pathogenesis is not [...] Read more.
Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV-induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size, being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis. Case presentation: An 80-year-old female patient presented to the emergency unit for steadily increasing dyspnea, with workup revealing bilateral pulmonary nodules and mediastinal lymph node enlargement on chest imaging. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined with azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade 2 LYG. Treatment with corticosteroids and weekly rituximab was initiated, leading to rapid improvement of respiratory symptoms. After the second dose of rituximab, sputum cultures that were initially collected were found to be positive for Mycobacterium tuberculosis. Rituximab was suspended, and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both tuberculosis and LYG, with at least a partial remission of the latter. Conclusions: Our case highlights the importance of a complete diagnostic workup when a diagnosis of LYG is made, to avoid missing a concomitant pulmonary disease, such as tuberculosis, even when definite pathologic and clinical features of the former are present. Full article
(This article belongs to the Special Issue Indolent Lymphomas and Lymphoreticular Proliferative Diseases)
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17 pages, 6558 KB  
Article
Multi-Omics Reveals Aberrant Phenotypes of Respiratory Microbiome and Phospholipidomics Associated with Asthma-Related Inflammation
by Huan Liu, Zemin Li, Xu Zhang, Jiang-Chao Zhao, Jianmin Chai and Chun Chang
Microorganisms 2025, 13(8), 1761; https://doi.org/10.3390/microorganisms13081761 - 28 Jul 2025
Viewed by 1165
Abstract
Respiratory microbiota and lipids are closely associated with airway inflammation. This study aimed to analyze the correlations among the respiratory microbiome, the airway glycerophospholipid–sphingolipid profiles, and airway inflammation in patients with asthma. We conducted a cross-sectional study involving 61 patients with asthma and [...] Read more.
Respiratory microbiota and lipids are closely associated with airway inflammation. This study aimed to analyze the correlations among the respiratory microbiome, the airway glycerophospholipid–sphingolipid profiles, and airway inflammation in patients with asthma. We conducted a cross-sectional study involving 61 patients with asthma and 17 healthy controls. Targeted phospholipidomics was performed on exhaled breath condensate (EBC) samples, and microbial composition was analyzed via the 16S rDNA sequencing of induced sputum. Asthma patients exhibited significant alterations in the EBC lipid profiles, with reduced levels of multiple ceramides (Cer) and glycerophospholipids, including phosphatidylethanolamine (PE) and phosphatidylcholine (PC), compared with healthy controls. These lipids were inversely correlated with the sputum interleukin-4 (IL-4) levels. Microbiome analysis revealed an increased abundance of Leptotrichia and Parasutterella in asthma patients, both positively associated with IL-4. Correlation analysis highlighted a potential interaction network involving PA, PE, ceramides, Streptococcus, Corynebacterium, Parasutterella, and Leptotrichia. Specific alterations in airway microbiota and phospholipid metabolism are associated with asthma-related inflammation, supporting the concept of a microbiota–phospholipid–immune axis and providing potential targets for future mechanistic and therapeutic studies. Full article
(This article belongs to the Section Microbiomes)
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14 pages, 655 KB  
Article
Risk Factors and Biomarkers for Pulmonary Toxicities Associated with Immune Checkpoint Inhibitors
by Efraim Guzel, Ismail Hanta, Oya Baydar Toprak, Okan Gurbuz, Burak Mete and Ertugrul Bayram
Medicina 2025, 61(7), 1258; https://doi.org/10.3390/medicina61071258 - 11 Jul 2025
Cited by 1 | Viewed by 1168
Abstract
Background and Objectives: Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking agents in cancer therapy; however, their immune-related adverse effects, especially pulmonary toxicity, significantly limit their use. This study aimed to determine the incidence and risk factors associated with ICI-induced pulmonary toxicity. [...] Read more.
Background and Objectives: Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking agents in cancer therapy; however, their immune-related adverse effects, especially pulmonary toxicity, significantly limit their use. This study aimed to determine the incidence and risk factors associated with ICI-induced pulmonary toxicity. Materials and Methods: We conducted a prospective observational study involving 126 patients aged ≥18 years with malignancies treated with ICIs between April 2022 and April 2024. Patients were followed every six months over a two-year period. Clinical, laboratory, and radiological data were collected to assess pulmonary toxicity. Results: The mean age of our patients was 62.93 ± 12.94 years, and 81% were male. The ICI-related pulmonary toxicity rate was 16.7%, and the all-cause mortality rate was 68.3%. In the analysis, the conditions associated with pulmonary toxicity were the type of malignancy, the presence of lung cancer, COPD, long-term ICI use, dyspnea, cough and sputum, the pre-ICI lung nodule mass, and high blood monocyte levels. Our regression analysis results for the determination of risk factors showed a 7.70-fold increase in the presence of cough symptoms, a 4.57-fold increase in the presence of COPD, a 0.998-fold increase for every 1 unit decrease in lymphocyte count, and an 11.75-fold increase in risk for a monocyte count of 130 or less. Conclusions: Our study’s findings suggest that patients with identifiable risk factors for pulmonary toxicity should undergo closer monitoring and early diagnostic evaluation during ICI therapy to reduce morbidity and mortality. Full article
(This article belongs to the Section Oncology)
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15 pages, 1420 KB  
Review
How Effectively Can Oxidative Stress and Inflammation Be Reversed When CFTR Function Is Pharmacologically Improved?
by Valeria Rachela Villella, Alice Castaldo, Filippo Scialò and Giuseppe Castaldo
Antioxidants 2025, 14(3), 310; https://doi.org/10.3390/antiox14030310 - 4 Mar 2025
Cited by 3 | Viewed by 2160
Abstract
A critical challenge in the age of advanced modulator therapies is to understand and determine how effectively chronic oxidative stress and oxidative stress-induced inflammation can be reversed and physiological balance restored when CFTR function is pharmacologically improved. The triple therapy with elexacaftor–tezacaftor–ivacaftor (ETI) [...] Read more.
A critical challenge in the age of advanced modulator therapies is to understand and determine how effectively chronic oxidative stress and oxidative stress-induced inflammation can be reversed and physiological balance restored when CFTR function is pharmacologically improved. The triple therapy with elexacaftor–tezacaftor–ivacaftor (ETI) suggests that CFTR activity in individuals with at least one F508del mutation can be partially restored to about 50% of normal levels. Although incomplete, the partial recovery of CFTR function has been shown to drastically lower sputum pathogen content, enhance microbiome diversity, and lower inflammation markers within the first year of treatment in adolescents and adults with cystic fibrosis. However, despite these advancements, residual airway infection, oxidative stress and inflammation persist, with levels similar to other chronic lung conditions, like non-CF bronchiectasis. This persistence highlights the necessity for innovative antioxidant and anti-inflammatory treatments, in particular for individuals with advanced lung disease. To address this issue, emerging multi-omics technologies offer valuable tools to investigate the impact of modulator therapies on various molecular pathways. By analyzing changes in gene expression, epigenetic modifications, protein profiles and metabolic processes in airway-derived samples, it could be possible to uncover the mechanisms driving persistent oxidative stress and inflammation. These insights could pave the way for identifying new therapeutic targets to fully restore airway health and overall physiological balance. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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10 pages, 356 KB  
Article
Clinical Utility of Induced Sputum and Bronchoalveolar Lavage Cultures in Diagnosing Nontuberculous Mycobacterial Pulmonary Disease
by Maria Angela Licata, Paola Mencarini, Annelisa Mastrobattista, Serena Maria Carli, Carlotta Cerva, Silvia Mosti, Raffaella Libertone, Alberto Zolezzi, Pietro Vittozzi, Carla Nisii, Antonio Mazzarelli, Angela Cannas, Assunta Navarra, Stefania Ianniello, Rocco Trisolini, Delia Goletti, Fabrizio Palmieri and Gina Gualano
Pathogens 2024, 13(12), 1064; https://doi.org/10.3390/pathogens13121064 - 3 Dec 2024
Cited by 4 | Viewed by 2820
Abstract
Diagnosing non-tuberculous mycobacterial pulmonary disease (NTM-PD) in patients unable to produce sputum spontaneously requires invasive procedures to obtain valid respiratory specimens. In this retrospective study, we evaluated the results of microbiological tests performed on respiratory samples of 132 patients affected by NTM-PD. In [...] Read more.
Diagnosing non-tuberculous mycobacterial pulmonary disease (NTM-PD) in patients unable to produce sputum spontaneously requires invasive procedures to obtain valid respiratory specimens. In this retrospective study, we evaluated the results of microbiological tests performed on respiratory samples of 132 patients affected by NTM-PD. In the diagnostic workout, 98 patients performed both induced sputum (IS) and bronchoalveolar lavage (BAL) and were enrolled in our study. A total of 93 out of 98 BAL samples (95%) were culture-positive for mycobacteria, whereas only 67/153 (44%) induced sputum cultures were positive for NTM (p < 0.001). Molecular identification of NTM with real-time polymerase chain reaction (PCR) was positive in 48/64 BAL (75%) and in 47/139 (34%) IS samples (p < 0.001). Patients affected by nodular-bronchiectatic form were 65/98 (66%): BAL culture was positive in 95% of cases (62/65 BAL), while only 30/99 IS cultures were positive (30%; p < 0.001). PCR was positive in 76% of BAL samples examined (26/34) and in 26% of the IS samples (24 out of 91) (p < 0.001). Among 33 patients with a fibro-cavitary radiological pattern, 65% of IS (35/54) were culture-positive for NTM, whereas 94% of cases (31/33) had a positive culture for NTM from BAL (p = 0.002). PCR was positive in 73% of BAL samples tested (22/30) and 48% of IS samples tested (23/48) (p = 0.031). Our results confirm BAL mycobacterial culture as the gold standard for the diagnosis of pulmonary mycobacteriosis. FBS with BAL should be performed in every patient with a strong suspicion of NTM-PD, if other respiratory samples are repeatedly negative. Sputum induction is a useful technique to obtain valid respiratory samples when patients are unable to produce spontaneous sputum, especially in the outpatient setting. However, during the diagnostic workup of NTM-PD, we should not forget that PCR and mycobacterial culture of induced sputum have a lower yield than when performed on BAL, especially in the nodular-bronchiectatic form of the disease. Full article
(This article belongs to the Section Bacterial Pathogens)
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Article
Prognostic Factors in Severe Eosinophilic Asthma in a Pediatric Population: A Prospective Cohort Study in Spain
by Clara Padró-Casas, María Basagaña, María del Mar Martínez-Colls, Ignasi García-Olivé, Carlos Pollan Guisasola, Aina Teniente-Serra, Eva Martínez-Cáceres, José Tomás Navarro and Carlos Martínez-Rivera
J. Clin. Med. 2024, 13(23), 7202; https://doi.org/10.3390/jcm13237202 - 27 Nov 2024
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Abstract
Background/Objectives: The objective of this study was to provide real-world data on prognostic factors in children with severe eosinophilic asthma and to assess biomarkers of outcome. Methods: Fifty-nine children (aged 6–17 years) were included in a prospective cohort attended in a [...] Read more.
Background/Objectives: The objective of this study was to provide real-world data on prognostic factors in children with severe eosinophilic asthma and to assess biomarkers of outcome. Methods: Fifty-nine children (aged 6–17 years) were included in a prospective cohort attended in a Severe Asthma Unit of a tertiary care teaching hospital in Badalona (Barcelona, Spain) and visited at baseline and at 1-year follow-up. Study variables included asthma control using the Asthma Control Test (ACT), forced expiratory volume in one second (FEV1), exacerbation episodes, fractional exhaled nitric oxide (FeNO), and inflammatory biomarkers (blood tests, sputum cells, immunoallergic tests, and levels of cytokines and effector cells in blood and sputum). Results: There were 36 boys and 23 girls, with a mean (SD) age of 11.9 (2.8) years. Uncontrolled severe asthma was diagnosed in 83.1% of cases, with poor symptom control (ACT score < 20) in 52.5%, obstructive pattern (FEV1 < 80% predicted) in 35.6%, and more than one exacerbation in the previous year in 30.5%. The mean duration of asthma was 9.2 (3.6) years. Positive prick tests were recorded in 55 patients, with polysensitization in 6. The mean percentage of sputum eosinophils was 2.5% (3.1%), and the mean eosinophil blood count 543.4 (427.7) cells/µL. Ten patients (32%) showed sputum eosinophilia (>3% eosinophils). Sputum eosinophils did not correlate with blood eosinophils, FeNO, and serum periostin. At 12 months, 13 (22%) children had uncontrolled asthma and 46 (78%) had controlled asthma. Variables significantly associated with uncontrolled asthma were duration of asthma (OR = 1.23, 95% CI 1.01–1.49, p = 0.04) and an ACT score < 20 (OR = 0.80, 95% CI 0.69–0.93, p = 0.004). Lower serum levels of IL-9 appeared to be related with uncontrolled asthma, but statistical significance was not reached. Conclusions: Pediatric severe eosinophilic asthma showed a predominant allergic phenotype with symptomatic disease as a main contributor of uncontrolled asthma at 1 year. Predictive biomarkers of outcome were not identified. Further studies are needed to confirm the present findings especially considering additional variables for a better phenotypic characterization of severe eosinophilic asthma in children and to study in-depth the role of inflammatory biomarkers. Full article
(This article belongs to the Special Issue Clinical Management of Children and Adolescents with Asthma)
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