Search Results (3,803)

Objective: To delineate the demographic, clinical, and radiological features of immunocompetent patients with pulmonary cryptococcosis (PC) who test negative for serum cryptococcal antigen (CrAg), a subgroup that poses a diagnostic challenge. Methods: Participants were stratified into CrAg-positive (n = 128) and CrAg-negative (n = 71) cohorts. Comparative analyses were performed on clinical presentation, chest computed tomography (CT) imaging features, and laboratory parameters. Results: Patients with false-negative CrAg results were more likely to be asymptomatic (46.5% vs. 20.3% in the CrAg-positive group; p < 0.05). Their chest CT scans typically revealed solitary pulmonary nodules, frequently unilateral and located in the right lung, with a notable absence of pleural effusion or lymphadenopathy. Laboratory findings in the CrAg-negative group were characterized by a lower neutrophil ratio and erythrocyte sedimentation rate. Furthermore, higher CrAg titers were significantly correlated with the presence of respiratory symptoms, specific CT signs (e.g., air bronchogram, lymphadenopathy), and elevated systemic inflammatory markers. Conclusions: False-negative serum CrAg in immunocompetent PC patients is characterized by an asymptomatic presentation and a solitary nodule on imaging, with normal laboratory parameters. CrAg titers may reflect disease severity and warrant prospective evaluation as a potential biomarker for guiding antifungal therapy. Full article

Background/Objectives: This study aimed to compare structural and functional parameters between chronic obstructive pulmonary disease (COPD) patients and healthy controls, assess associations with pulmonary function, and identify factors independently associated with COPD status. Methods: A cross-sectional study was conducted in 89 participants (COPD: n = 45; controls: n = 44). Structural parameters included forward shoulder posture (FSP), scapular rotation, scapular distance (SD), and pectoralis minor index, measured bilaterally. Functional parameters included maximum inspiratory and expiratory pressures (MIP/MEP), chest expansion at three thoracic levels, spinal angles, and spirometry (%FVC, %FEV1, FEV1/FVC, FEF_25–75%, PEFR). Univariate and stepwise multivariate logistic regression identified variables independently associated with COPD. Results: COPD patients were older and exhibited lower anthropometric measures. Scapular rotation was greater in COPD (p < 0.05 bilaterally), while SD was significantly reduced (p < 0.001 bilaterally). MIP, MEP, and chest expansion at all three levels were significantly impaired in COPD (p < 0.05). All spirometric parameters were markedly lower in COPD (all p < 0.001). SD was positively associated with spirometric indices on both sides (p < 0.01). FSP was inversely associated with MIP, MEP, and chest expansion (p < 0.05). In multivariate logistic regression, age (OR 1.280, p = 0.018), %FVC (OR 0.875, p = 0.029), and FEF_25–75% (OR 0.909, p < 0.001) were independently associated with COPD status. Conclusions: Patients with COPD demonstrated reduced SD and increased scapular rotation. SD was significantly associated with pulmonary function, whereas FEF_25–75% and %FVC emerged as independently associated variables of COPD status. Collectively, these findings underscore the clinical relevance of integrating targeted scapulothoracic and respiratory rehabilitation strategies to optimize functional outcomes and support overall respiratory health and well-being. Full article

High-throughput metagenomic sequencing and advances in mucosal immunology have refuted the traditional physiological concept of a sterile respiratory tract. The oral cavity has been recognized as a dynamic determinant of systemic health. As in other parts of the body, recent studies also suggest that pulmonary health may be linked to oral health. Under eubiotic conditions, the oral microbiome maintains local immunological homeostasis and colonization resistance. Oral dysbiosis, characterized by sequential shifts in microbial communities and the proliferation of the pathogenic red complex (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia), induces a state of chronic systemic inflammation, potentially involved in an infectious axis between the oral cavity and the lung. This review evaluates the tripartite systemic pathways of metastatic infection, metastatic injury, and metastatic inflammation that govern the translocation of oral pathobionts and their bioactive components, including lipopolysaccharides, outer membrane vesicles, and matrix metalloproteinases, to the lower respiratory tract via microaspiration and hematogenous circulation. The clinical implications across the chronic respiratory disease spectrum are examined, with a focus on how deficits in oral microbial diversity influence chronic obstructive pulmonary disease (COPD) pathogenesis, modulate the pulmonary virome and mycobiome, and stimulate maladaptive trained immunity. Furthermore, the contribution of biological aging is assessed, highlighting the roles of immunosenescence, inflammaging, and physiological reflex decline within the broader mucosal continuum. Finally, the clinical translation of this axis is analyzed, emphasizing the integration of saliva-based point-of-care nano-theranostics, metatranscriptomic profiling, and targeted interventions—such as professional oral biofilm management in intensive care settings and precision microbiome engineering—to preserve respiratory function and restore immune homeostasis. Full article

Vitamin A plays an important role in multiple homeostatic functions such as vision, immunity, epithelial cell integrity and differentiation, cell signaling, pulmonary function, reproduction, growth, and development. Vitamin A deficiency was described in people with cystic fibrosis (pwCF) due to a multitude of causes, such as suboptimally managed exocrine pancreatic insufficiency, advanced cystic fibrosis-related liver disease (aCFLD), and a history of intestinal resection, and is generally rare in contemporary practice. Apart from true vitamin A deficiency, low vitamin A levels may also be noted in various inflammatory states, as vitamin A is a negative acute-phase reactant. In the current era of cystic fibrosis (CF) transmembrane-conductance regulator (CFTR)-directed therapies, there is a paradigm shift in vitamin A status, with deficiency statuses becoming rarer, and instead higher serum vitamin levels (in some cases, even in the hypervitaminosis range) are increasingly reported. People with aCFLD, renal insufficiency, post-lung transplantation, and pregnancy are prone to vitamin A toxicity. Hence, CF clinicians should be proactive in evaluating these abnormalities and proficient in managing both deficiency and toxicity, as both these conditions can be associated with adverse outcomes. In this review, we detailed the basics of vitamin A metabolism, manifestations of both vitamin A deficiency and excess, and their clinical implications in pwCF. Full article

Our earlier studies have revealed the beneficial impact of vitamin D3 (VD3) metabolites on the development of pulmonary fibrosis in a murine model of hypersensitivity pneumonitis (HP). Despite the discovery of the great antifibrotic potential of both the bioactive form of VD3, 1,25(OH)₂-VD3 and its direct precursor, 25(OH)-VD3, study designs based on the co-administration of VD3-metabolites and fibrosis-inducers do not reflect the clinical situation. Thus, the presented study aims to examine the effectiveness of therapeutic interventions based on the mentioned inhalations, initiated during the acute phase of HP at the first signs of pulmonary fibrosis. The research was performed using VD3-deficient mice with HP, while VD3-sufficient mice were used as the main control. The data were collected after 28 days of daily exposure of the mice to a fibrosis-inducer (an antigen of Pantoea agglomerans, a well-known etiological factor in HP), with 25(OH)-VD3 or 1,25(OH)₂-VD3 administered daily during the last 14 days of the experiment. The effect of the intervention was monitored by whole-body plethysmography, histological assessment, flow cytometry, RealTime-PCR, and ELISA. Treatment with VD3 metabolites initiated during the acute phase of HP alleviated the disease courses and restored respiratory function, thanks to inhibition of pathological extracellular matrix deposition, immune-cell infiltration of lung parenchyma, profibrotic cytokine production, and EMT progression. Despite the discovery of the beneficial features of the investigated VD3-based therapies, none of them caused full recovery in mice with HP. Nevertheless, after verification in additional animal models and a deeper understanding of the underlying molecular mechanisms, the identified beneficial features of the investigated metabolites have the potential to serve as a foundation for future therapies for HP fibrosis. Full article

Background: Pulmonary fibrosis is a chronic and progressive disease characterized by excessive deposition of extracellular matrix and scarring of lung tissue, resulting in a gradual decline in respiratory function. Despite advances in understanding its pathogenesis, effective therapeutic options remain limited. This study aimed to evaluate the antifibrotic effects of concentrated polyphenolic extracts obtained from bilberry (Vaccinium uliginosum), cranberry (Vaccinium oxycoccos), and lingonberry (Vaccinium vitis-idaea) in a bleomycin-induced rat model of pulmonary fibrosis. Methods: Pulmonary fibrosis was induced in rats through the intratracheal administration of bleomycin. Beginning seven days after fibrosis induction, concentrated polyphenolic extracts from the three Vaccinium species were administered orally for 14 consecutive days. Lung histomorphology, inflammatory cell infiltration, collagen composition, and hemorheological parameters were subsequently evaluated. Results: Treatment with the berry polyphenolic extracts reduced the severity of bleomycin-induced pulmonary fibrosis and decreased inflammatory cell infiltration in lung tissue. The extracts also influenced collagen remodeling, promoting a relative predominance of immature type III collagen over mature type I collagen. Furthermore, bleomycin-induced pulmonary fibrosis was accompanied by increased blood viscosity, whereas treatment with the polyphenolic extracts partially normalized the altered hemorheological parameters. Conclusions: Concentrated polyphenolic extracts derived from Vaccinium species demonstrated antifibrotic, anti-inflammatory, and hemorheological effects in experimental pulmonary fibrosis. These findings support further investigation of their underlying molecular mechanisms and potential translational applications studies. Full article

Pulmonary fibrosis is a progressive interstitial lung disease characterized by persistent alveolar epithelial injury, aberrant repair, and excessive extracellular matrix deposition. Increasing evidence indicates that disease progression is closely associated with alveolar type II (AT2) cell dysfunction, impaired AT2-to-AT1 differentiation, and the persistence of transitional epithelial populations, including KRT8⁺ intermediate populations. Because the formation and resolution of these transitional epithelial populations require dynamic regulation of stress-responsive transcripts and differentiation-associated RNA programs, they provide a biologically relevant context for investigating RNA modification-mediated post-transcriptional regulation. RNA modifications have emerged as post-transcriptional regulatory layers that modulate RNA stability, processing, translation efficiency, and stress-response gene expression, thereby influencing epithelial stress adaptation and repair-related state transitions. Among these modifications, N6-methyladenosine (m6A) is the best-characterized layer, with evidence linking it to epithelial injury responses, senescence-associated transcript remodeling, and differentiation impairment. In contrast, non-m6A modifications, including m5C, m1A, m7G, pseudouridine (Ψ), and A-to-I RNA editing, remain emerging regulatory layers with limited AT2 cell-specific functional validation. This review summarizes current evidence connecting RNA modifications with alveolar epithelial injury, transitional-state persistence, epithelial–mesenchymal communication, and fibrotic remodeling. Rather than interpreting RNA modifications as isolated pathogenic drivers, we highlight their context-dependent roles in RNA fate control, epithelial stress adaptation, and aberrant repair in pulmonary fibrosis. Full article

Trained immunity (TI) represents a form of immune memory in innate immune cells, driven by sustained epigenetic and metabolic reprogramming that potentiates innate immune responses. Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by persistent alveolar injury and pathological tissue remodeling. Given the central role of macrophages in IPF pathogenesis, we hypothesized that inducing TI could functionally reprogram these cells and attenuate fibrosis. In a murine model of pulmonary fibrosis induced by bleomycin, prior induction of TI via β-glucan enhanced autophagic activity in macrophages and reduced pathological collagen deposition. This trained response restricted bleomycin-triggered mitochondrial DNA release and suppressed the mitochondrial apoptosis pathway, thereby promoting macrophage survival. The protective effects were diminished by administration of the AMPK inhibitor Compound C. Our findings indicate that TI promotes mitophagy correlating with the AMPK-ULK1 signaling axis, thereby reducing alveolar macrophage apoptosis and uncovering a potential therapeutic strategy for pulmonary fibrosis. Full article

India has one of the highest public health burdens attributable to air pollution globally. Despite national air quality regulations and control policies, improvements in air quality have been limited, restricting opportunities to evaluate the health benefits of cleaner air under real-world conditions. COVID-19 lockdowns substantially reduced air pollution in India’s megacities, creating a natural experiment for assessing pollution-attributable health benefits. Using ambient PM_2.5 concentration data from United States Embassy and Consulate monitors in Chennai, Hyderabad, Kolkata, Mumbai, and New Delhi during the 2020 and 2021 lockdowns, and World Health Organization AirQ+ software, we estimated the short- and long-term health benefits of maintaining lockdown-related improvements in air quality. PM_2.5 reductions ranging from 28–77% during the first lockdown, if sustained long term, would lead to about 42,778 fewer premature deaths in the short term and 132,000 fewer annual avoidable deaths from all causes under the modeled scenario across the five cities. We also estimated annual reductions of 11,100 deaths from chronic obstructive pulmonary disease, 3900 from lung cancer, 5500 from ischaemic heart disease, 3900 from stroke, and 1240 from acute lower respiratory infection. These findings support stronger air quality standards, emission controls, and policy enforcement to reduce air pollution-related mortality in Indian megacities. Full article

Background and Clinical Significance: Pulmonary disease caused by nontuberculous mycobacteria (NTM) represents an important diagnostic challenge in tuberculosis-endemic settings because its clinical, radiological, and microbiological features may overlap with those of pulmonary tuberculosis (TB). Accurate distinction between these conditions is essential to avoid diagnostic delay and inappropriate treatment. Case Presentation: We present two cases that illustrate the heterogeneity of imaging patterns associated with NTM disease. The first case involved a 55-year-old woman with previously treated pulmonary tuberculosis who presented with chronic productive cough, recurrent mild hemoptysis, and progressive nodular-bronchiectatic and cavitary abnormalities. Mycobacterium avium was repeatedly isolated from independently collected respiratory specimens and identified using a line probe assay (LPA). The second case involved a 65-year-old man with severe chronic obstructive pulmonary disease (COPD), bronchiectasis, previous tuberculosis, and extensive bilateral fibrocavitary lung disease. Respiratory specimens were acid-fast bacilli-positive, whereas GeneXpert MTB/RIF repeatedly failed to detect the Mycobacterium tuberculosis complex. Repeated cultures identified Mycobacterium xenopi, including isolates from two sputum specimens and one bronchial aspirate. Treatment was subsequently adapted according to species identification and multidisciplinary assessment. These cases illustrate two major phenotypes of pulmonary NTM disease: nodular-bronchiectatic disease caused by M. avium and fibrocavitary disease caused by M. xenopi. They emphasize that persistent acid-fast bacilli (AFB) positivity with negative GeneXpert MTB/RIF results should prompt consideration of NTM alongside other differential diagnoses, followed by mycobacterial culture and species-level identification. Conclusions: The diagnosis of pulmonary NTM disease requires integration of clinical manifestations, radiological evolution, and repeated microbiological confirmation. Early species identification, multidisciplinary treatment selection, and close follow-up may reduce diagnostic delays and support appropriate individualized management. Full article

Understanding how clinical pathways evolve over time is essential for characterizing care processes. It also helps identify potential shifts in diagnostic and organizational practices. This study provides a descriptive analysis of patient trajectories for four major respiratory conditions: lung cancer, interstitial fibrosis, chronic obstructive pulmonary disease (COPD), and pneumonia. Trajectories were compared between a pre-COVID-19 period (2018–2019) and a COVID-19 period (2020–2022) in a specialized hospital. Using process mining applied to administrative event logs, we examined three aspects of care: the structure and sequencing of activities, the timing of transitions between care encounters, and imaging timeliness. The analysis spanned inpatient, emergency department, and outpatient settings. Indicators of care duration and transition timing revealed heterogeneous temporal patterns. Several conditions showed shorter intervals in the COVID-19 period, whereas others varied little. Activity-level analyses complemented these findings. Process maps indicated stable structural components in many pathways, together with differences in timing and execution. In the emergency department, care shifted toward bedside radiography, whereas CT chest volumes remained relatively stable across periods and settings. Imaging timeliness stayed consistently high in the emergency department and relatively stable for most inpatient conditions. Outcome-related indicators, including 30-day readmission and prolonged care trajectories, showed only modest differences between periods. Overall, the study demonstrates the value of process mining for describing real-world clinical pathways and identifying temporal variations in care. These results provide a foundation for future work that integrates richer clinical information and analytical approaches capable of assessing causal relationships. Full article

Background: Although diagnosis of pulmonary nontuberculous mycobacterial (NTM) disease typically relies on bronchoscopic sampling, microbiologic testing, and histopathologic evaluation, definitive diagnosis is often difficult. This study investigated whether cytokine profiling of bronchoalveolar lavage (BAL) fluid can help differentiate NTM pulmonary disease (NTM-PD) from other diffuse lung disorders. Methods: From January 2023 to July 2025, we prospectively evaluated 50 patients presenting with undiagnosed micronodular or diffuse pulmonary opacities. BAL fluid was collected during bronchoscopy and analyzed for cytokines and related biomarkers. Eleven patients were clinically diagnosed with NTM-PD based on American Thoracic Society/Infectious Diseases Society of America criteria. Cytokine and cellular profiles were compared between patients with NTM-PD and those with other diffuse lung disorders. A secondary analysis compared infectious granulomatous disease (NTM-PD; n = 11) with noninfectious granulomatous disease (e.g., sarcoidosis; n = 8). Results: BAL fluid from patients with NTM-PD showed significantly higher levels of interleukin-8 (IL-8), interleukin-13 (IL-13), YKL-40, and neutrophils compared to those with other diffuse lung disorders. In subgroup analysis, IL-8, IL-13, and neutrophil proportions remained significantly elevated in infectious granulomatous NTM-PD compared with noninfectious granulomatous disorders. Conclusions: NTM-PD is associated with a distinct BAL cytokine profile characterized by elevated IL-8, IL-13, YKL-40, and neutrophil proportions. Full article

Zoonotic bacterial pathogens are transmitted through various routes and are traditionally associated with acute febrile illnesses that may include pulmonary complications. However, in some survivors, the disease extends beyond the acute phase, leading to the remodeling of pulmonary architecture and driving progressive fibrosis. Although no direct cases have been reported, these pathogens may plausibly predispose injured lungs to carcinogenesis, similar to the well-recognized phenomenon of tuberculosis-associated scar cancer. As such long-term sequelae remain largely overlooked in current clinical practice, their potential contribution to fibrotic and malignant lung disease represents a critical and underexplored knowledge gap. This review proposes a unified mechanistic framework linking acute pathogen-mediated alveolar damage to chronic pulmonary fibrosis and subsequent lung carcinogenesis. We delineate four convergent biological pillars driving this continuum: (1) pathogen persistence establishing chronic Interleukin-1β (IL-1β)/Tumor necrosis factor-α (TNF-α)-mediated inflammation; (2) sustained TGF-β signaling and mechanotransduction driving progressive extracellular matrix remodeling; (3) unresolved reactive oxygen species (ROS) generation causing profound oxidative DNA damage; and (4) aberrant epithelial–mesenchymal transition (EMT) that perpetuates fibrosis and generates pre-malignant cell populations. Together, these sequelae alter lung biomechanics, suppress local immune surveillance, and create a mutagenic environment that is highly conductive to malignant transformation. Although direct epidemiological data remain emerging, the significant mechanistic overlap with idiopathic pulmonary fibrosis (IPF) presents a compelling rationale for shared oncogenic risk. We advocate for a paradigm shift in clinical practice, emphasizing the potential value of long-term surveillance for survivors of severe pulmonary infections. By integrating infectious diseases, pulmonology, and oncology, this framework highlights a neglected cause of fibrotic lung disease and establishes a foundation for future translational research. Full article

Pulmonary involvement in primary Sjögren’s syndrome (pSS) is common and exhibits significant clinical heterogeneity, particularly in cases where interstitial lung disease (pSS-ILD) develops. Reported variability in prevalence, radiologic phenotypes, and clinical outcomes indicates both underlying biological diversity and differences in classification criteria, case ascertainment, and diagnostic approaches. Pulmonary manifestations may be subclinical, and early interstitial abnormalities are frequently undetected due to the limited sensitivity of chest radiography. Presentations such as ILD-first or non-sicca onset, seronegative disease, and coexisting or mimicking conditions, including lymphoproliferative disorders and amyloidosis, increase the difficulty of diagnosis. High-resolution computed tomography (HRCT) demonstrates a wide range of patterns, including inflammatory, fibrotic, and mixed phenotypes, which often overlap and change over time. Reliance on pattern-based categorization may not adequately reflect the underlying pathobiology; for example, those with usual interstitial pneumonia (UIP)-like morphology have significant prognostic implications within the pSS spectrum. A structured, multidomain assessment that integrates symptoms, pulmonary function, and HRCT findings, ideally inside a multidisciplinary discussion (MDD), may boost diagnostic accuracy and risk stratification. Nevertheless, heterogeneity in definitions and reporting continues to impede comparability across patient cohorts. Additional research is necessary to standardize phenotyping frameworks and identify predictors of disease progression to inform individualized diagnostic and management strategies. Full article

Pulmonary Hypertension (PH) in patients with Interstitial Lung Disease (ILD) is a critical, yet underrecognized, complication that affects patients’ quality of life and increases mortality. Emerging evidence further suggests that PH-ILD is not merely a consequence of hypoxia and parenchymal fibrosis, as the severity of pulmonary vascular disease often correlates poorly with the extent of fibrotic lung involvement, indicating more complex underlying pathophysiological mechanisms. Diagnosis requires a high index of suspicion when symptoms appear “disproportionate” to the degree of parenchymal lung disease. Key indicators include diffusing capacity for carbon monoxide (DLCO) < 45%, a forced vital capacity to diffusing capacity for carbon monoxide ratio (FVC/DLCO) > 1.6, and radiological findings of increased pulmonary artery diameter. While echocardiography and circulating biomarkers serve as useful screening tools, right heart catheterization remains the gold standard for definitive diagnosis. Early identification is essential for risk stratification, lung transplant evaluation, and determining eligibility for targeted pharmacological interventions, as this group of patients remains one of the most therapeutically challenging forms of pulmonary vascular disease. Ongoing research and advances in diagnostic tools are increasingly focused on refining phenotypic classification, identifying valuable biomarkers, and elucidating molecular drivers that may enable personalized treatment strategies in this heterogeneous patient group. Full article