Search Results (3,735)

Accurate diagnosis of PM and precise histologic subtyping are critical for optimal therapeutic decision-making, as treatment strategies—including chemotherapy, immunotherapy, or multimodality approaches—are largely subtype-dependent. Because of the several-decade latency between fiber inhalation and symptom onset, many cases are diagnosed at an advanced stage, when patients are already in poor clinical condition. As observed across multiple solid malignancies, earlier-stage diagnosis is associated with improved prognosis and expanded therapeutic options. However, the rarity of PM, the absence of validated screening strategies, and its nonspecific clinical and radiologic presentation—often mimicking both benign and metastatic pleural conditions, frequently result in diagnostic delay. Furthermore, the lack of pathognomonic histopathologic markers further complicates timely and definitive diagnosis. This review aims to delineate the epidemiologic, clinical, radiologic, and pathologic barriers that hinder accurate and early detection of PM. Current clinical evidence points to an urgent need to develop novel, validated biomarkers in PM, which will require a multidisciplinary approach. Full article

Background: Targeted therapies directed against oncogenic drivers have substantially improved outcomes for patients with epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Despite high initial response rates, most patients ultimately develop acquired resistance to tyrosine kinase inhibitors (TKIs), reflecting complex biological adaptations under therapeutic pressure. Methods: This narrative review synthesizes experimental, translational, and clinical studies examining how environmental and occupational respiratory exposures may influence resistance mechanisms in EGFR- and ALK-driven NSCLC. The review emphasizes exposure-associated signaling plasticity, inflammatory microenvironmental modulation, metabolic reprogramming, and pharmacokinetic alterations. Results: Recent evidence suggests that respiratory exposures, including cigarette smoke, air pollution, diesel exhaust, and occupational inhalational toxicants, can modulate oncogenic signaling networks relevant to resistance to targeted therapies. These mechanisms include aberrant EGFR activation, bypass signaling through the mesenchymal–epithelial transition receptor (MET) and SRC pathways, epithelial–mesenchymal transition (EMT), adaptive kinome remodeling, and exposure-associated inflammatory signaling, all of which may influence tumor evolution and therapeutic response. Conclusions: This review introduces a novel exposome-driven conceptual framework integrating environmental exposures with signaling plasticity and resistance evolution in oncogene-driven NSCLC. These findings support the concept that the respiratory exposome may represent an underrecognized modifier of targeted therapy response. Incorporating structured exposure assessment into precision oncology approaches may refine risk stratification and inform exposure-aware therapeutic strategies. Full article

X-linked dystrophin-deficient muscular dystrophy (DD-MD) is an uncommon neuromuscular disorder in cats. We described an adult male cat with chronic tongue protrusion, dysphagia, muscle hypertrophy, and a history of rhabdomyolysis associated with anesthesia. Clinical pathology revealed markedly increased CK activity, muscle histopathology demonstrated a dystrophic phenotype, and an absence of dystrophin protein was confirmed by immunofluorescent staining. Whole genome sequencing identified two potential disease-causing variants, including a new missense variant in the DMD gene (c.2207T>C; p.Gln736Arg), which was considered causative of the clinical phenotype. A second variant in the CLIC2 gene was also detected but was considered unlikely to cause myopathic signs. The clinical course remained stable over 1.5 years with supportive management and dietary modification, and no further episodes of rhabdomyolysis occurred. This case expands the known spectrum of feline DMD variants and highlights the value of genetic testing combined with muscle histopathology for diagnosing chronic presentations of MD. Avoidance of inhalant anesthetics may be important in managing affected cats due to the risk of acute muscle injury. Full article

The Chinese giant salamander (Andrias davidianus) is a nationally protected species in China, and its respiratory behavior serves as a key indicator of its physiological state, health status, and biological rhythm. However, research on intelligent monitoring of its respiratory behavior remains limited due to several challenges, including the species’ nocturnal habits, resulting in low image contrast and poor quality in dark environments; extremely subtle breathing movements; and high-cost manual annotation, leading to a scarcity of high-quality annotated visual data. These factors severely constrain the application of deep learning techniques in this field. To support research on respiratory behavior monitoring in the Chinese giant salamander, this study constructs and releases the CGS-BR dataset, which is the first vision-based dataset dedicated specifically to respiratory behavior detection in this species. The dataset was collected under controlled simulated breeding conditions and consists of 1732 images extracted from 215 high-definition video clips. Following a standardized procedure, each complete respiratory cycle is manually annotated into four stages: head-up, diving, exhalation, and inhalation. To validate the effectiveness of this dataset, this study selects YOLOv8n as the baseline model, which balances detection accuracy, speed, and parameter count, enabling efficient giant salamander respiratory detection under limited resources. By comparing it with several representative models, we provide a reliable evaluation of the dataset’s applicability. CGS-BR aims to provide fundamental data support for research on respiratory monitoring in the Chinese giant salamander, laying the foundation for subsequent applications in conservation management, captive breeding, health monitoring, and early disease warning. Full article

Background/Objectives: Cannabidiol (CBD) has emerged as a potential therapeutic agent for respiratory disorders, including asthma and chronic obstructive pulmonary disease. However, its clinical translation via pulmonary delivery is limited by poor aqueous solubility, chemical instability, and low local bioavailability. This study aimed to develop and optimize a sodium stearate (NaSt)-based spray-dried dry powder inhaler (DPI) formulation to enhance the aerosol performance, dissolution, and storage stability of CBD. Methods: CBD microparticles were prepared by spray drying using NaSt as the primary excipient. The feed preparation method, spray-drying parameters, and CBD:NaSt ratios were systematically optimized. The resulting powders were evaluated for aerodynamic properties using cascade impaction, dissolution behavior in simulated lung fluid, solid-state characteristics, and accelerated stability under stress conditions. Results: The optimized formulation, SD-4, a spray-dried CBD:NaSt formulation prepared at a 20:80 weight ratio using Process B, demonstrated excellent aerosolization performance, with a fine particle fraction (FPF) exceeding 50% and a mass median aerodynamic diameter (MMAD) of 5.08 ± 0.1 μm. Dissolution testing revealed more than a three-fold increase in drug release compared with raw CBD, attributed to amorphous dispersion within the NaSt matrix and surfactant-induced micellization. Accelerated stability studies confirmed improved retention of the amorphous state and drug content, while antioxidant incorporation further reduced oxidative degradation. Conclusions: The NaSt-based spray-dried formulation significantly improved aerosol deposition efficiency, dissolution rate, and physicochemical stability of CBD. This formulation strategy may provide a promising platform for pulmonary delivery of poorly water-soluble compounds. Full article

Background: Inhaled therapy is the mainstay of asthma management, yet many patients are prescribed pressurized metered-dose inhalers (pMDIs) with valved holding chambers (VHCs) based on a presumed low inspiratory capacity, often without objective measurement. The USE-DPI study aimed to determine how many of these patients can generate sufficient peak inspiratory flow (PIF) to use a dry powder inhaler (DPI). Methods: This multicenter, observational, cross-sectional study included 346 patients with asthma treated with pMDI and VHC. PIF was measured using the In-Check Dial at two resistance settings (R2 and R4). The primary outcome was the proportion of patients achieving PIF ≥ 30 L/min. Results: Almost all patients reached the 30 L/min threshold (99.4% at R2 and 98.7% at R4). Using a higher threshold of 60 L/min (R2), 76.1% met this criterion. Lower PIF (<60 L/min) was associated with older age, reduced lung function (FEV1 ≤ 80% predicted), and poorer asthma control. No significant variables were associated with failure to reach 30 L/min. Conclusions: Most patients using pMDI with VHC can generate sufficient inspiratory flow for medium- to high-resistance DPIs. Objective PIF assessment may help guide inhaler selection, although its clinical impact requires further study. Full article

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are major risk factors for lung cancer and other diseases, acting through the aryl hydrocarbon receptor (AHR). Alveolar macrophages (AMs) help regulate the lung microenvironment by responding to inhaled toxicants and resident microbiota. Although small extracellular vesicles (sEVs, aka exosomes) released by AMs mediate intercellular communication and immune responses, the influence of lung microbiota on sEV biogenesis and the mechanisms underlying sEV dysregulation during PAH exposure remain unknown. Here, we investigated the interplay between AMs, B[a]P, and lung microbiota, focusing on sEV-associated miRNAs (exo-miRNAs). Murine AMs (MH-S) were exposed to varying B[a]P concentrations in the presence or absence of murine lung microbiota with or without an AHR antagonist. sEVs from each condition were characterized and profiled for miRNA. Distinct miRNA signatures emerged: high-dose B[a]P enriched miRNAs linked to cancer progression, whereas lung microbiota alone or with low-dose B[a]P induced tumor-suppressor miRNAs that limit proliferation and metastasis and promote apoptosis, an effect enhanced by AHR antagonism. Lung microbiota appeared to counteract high-dose B[a]P by modulating tumor-suppressive exo-miRNAs. This study demonstrates that lung microbiota-induced exo-miRNAs critically shape AM-derived sEV-miRNA signaling during PAH exposure. The identified exosomal miRNAs could serve as important exposure biomarkers and therapeutic targets for mitigating B[a]P-induced toxicity and cancer development. Full article

Per- and polyfluoroalkyl substances (PFAS) are highly stable and persistent environmental contaminants. Their exceptional chemical stability prevents natural breakdown, leading to global distribution and bioaccumulation in aquatic organisms. Long-chain PFAS, such as perfluorooctane sulfonic acid (PFOS), tend to accumulate in the liver, kidneys, and muscle tissues, whereas short-chain PFAS remain largely dissolved in water and show lower accumulation. Freshwater fish generally contain higher PFAS levels than marine fish, with concentrations varying according to species, habitat, trophic level, contamination site, and other factors. Human exposure primarily occurs through the consumption of contaminated fish and seafood, as well as through drinking water, inhalation, and skin contact. Such exposure is associated with immunosuppression, high cholesterol, hormonal disruption, cancer, and other health risks. Regulatory limits exist for four PFAS compounds, while many others, including emerging compounds, remain unregulated. This review synthesizes the current knowledge on the global distribution of PFAS across various fish species, analytical approaches including sample preparation (e.g., SPE, QuEChERS) and instrumental techniques (e.g., LC-MS/MS, HRMS), human dietary exposure, and the related health risks. By integrating environmental distribution, bioaccumulation, analytical challenges, and health issues, this review provides an up-to-date perspective on PFAS in fish and emphasizes the need for ongoing monitoring and stricter regulatory frameworks to ensure food safety and protect both human health and ecosystems. Full article

The continuous accumulation of micro- and nanoplastics in the human living environment and their deposition in various organs of the body have become a global public health concern with the widespread use of plastic products. This review summarizes the main categories of micro- and nanoplastics entering the body through dietary intake and air inhalation, based on human exposure pathways. By integrating existing literature data, this review estimates the daily intake and excretion of micro- and nanoplastics in humans, summarizes evidence regarding their potential deposition patterns in blood cells and hematopoietic-related organs, mainly inferred from animal and in vitro studies, and discusses the possible impacts of such deposition on hematopoietic function. Furthermore, the toxic effects and potential hazards of micro- and nanoplastics on the human hematopoietic system at both cellular and animal levels, along with the underlying molecular mechanisms, are comprehensively reviewed. From the dual perspectives of environmental governance and bodily protection, exploratory research ideas are proposed, including biodegradation strategies and the application of medicinal and edible homologous substances. This review aims to provide insights for reducing the risk of hematopoietic system diseases and preventing harm caused by micro- and nanoplastics to the human body in the future. Full article

This review summarizes innovative co-formulation strategies for non-marketed dry powder inhalers (DPIs), enabling the simultaneous pulmonary delivery of multiple active pharmaceutical ingredients (APIs). Key approaches include co-amorphous systems (COAMS) and co-crystals, which combine two APIs into a single particle, improving aerodynamic properties, solubility, dissolution, and patient compliance while reducing manufacturing complexity. Core–shell microparticles, produced via spray drying, allow spatial separation and controlled release of APIs, minimizing drug–drug interactions and enabling tailored pharmacokinetics. Co-spray drying of dual APIs can yield particles with superior aerosolization and stability, though examples remain limited. Nanoparticle-based systems offer enhanced lung deposition and cellular uptake but face challenges in device compatibility, scalability, and regulatory approval. Each technology presents unique advantages and limitations regarding manufacturability, dose flexibility, and clinical translation. This review also highlights advances in in vitro toxicity testing, including air–liquid interface cultures, organoids, lung-on-chip models, and precision-cut lung slices, which are increasingly important as alternatives to animal studies. The importance of using an aerosol exposure system for the testing is highlighted. Ultimately, the choice of co-formulation platform should balance scientific innovation with practical considerations of manufacturing and regulatory requirements to maximize therapeutic benefit and commercial viability for future DPI combination products. Full article

Environmental exposure to particulate matter, including PM_2.5 and engineered nanomaterials, is a major global health concern. Although acute toxic effects have been widely documented, new evidence suggests that the retained particle burden arising from incomplete clearance, tissue retention, and redistribution plays a key role in long-term health outcomes. This review synthesizes knowledge on particle accumulation at multiple biological levels. It examines how particles are retained in pulmonary and lymphoid tissues, their uptake by immune cells, and their sequestration within organelles, particularly the endo-lysosomal system. The mechanisms by which lysosomal dysfunction can cause mitochondrial stress, redox and metabolic disturbances, and impaired autophagy are also discussed. These disruptions can alter the status of immune cells and disturb immune homeostasis. This review also examines how immune perturbation from accumulation may contribute to chronic lung diseases. Understanding these mechanisms explains the persistent health effects associated with low-dose exposure and supports more effective risk assessment and prevention. Full article

Background: The breathing cycle consists of abdominal breathing (AB), for which the diaphragm is responsible, and thoracic breathing (TB), generated by the intercostal muscles. Contraction of the two portions of the diaphragm accounts for 80% percent of inspiration. While bilateral diaphragmatic paralysis causes severe shortness of breath, hemidiaphragm paralysis (HDP) gives fewer symptoms at rest, making it difficult to recognize and diagnose. Because this condition is rare, little is known regarding its consequences on breathing efficiency. Hypothesis: Based on previous studies, we hypothesized that body positions substantially affect the efficiency of breathing in a patient with unilateral hemidiaphragm paralysis and the corresponding physiological parameters. Aims: To measure and compare the amplitudes of abdominal and chest movements in different body positions in an individual with HDP and measure parameters indicating breathing efficiency. Patient and Methods: The patient had HDP due to iatrogenic phrenic nerve injury. Changes in the circumference of the abdomen and chest were measured during inhalation and exhalation with respiratory plethysmography belts (placed on standardized reproducible positions on the chest and abdomen) in different body positions: sitting (SI), standing (ST), lying (SU) and prone (PR). Breathing frequency was calculated, and blood oxygen saturation (SpO₂) was measured with a pulse oximeter. Results: The percentage (%) contributions of abdominal breathing were SI: 16.0; ST: 50.3; SU: −53.5; PR: 1.1. A negative sign shows paradoxical breathing. Blood oxygen saturation (SpO₂) in the four positions was SI: 93%; ST: 93%; SU: 82%; and PR: 82%, whereas the respiratory rate (1/min) was SI:19.4; ST: 15.0; SU: 37.5; PR: 35.9. Conclusions: Body position markedly influences the relative contributions of abdominal and thoracic breathing and overall respiratory efficiency in patients with hemidiaphragm paralysis; abdominal breathing in the supine and prone positions is greatly reduced leading to decreased blood oxygen saturation, a compensatory increase in respiratory rate, and severe dyspnea even at rest. Full article

Background/Objectives: Therapeutic adherence to asthma and COPD medications remains worryingly low and varies widely across patient groups, underscoring persistent challenges in chronic respiratory care. The aim of this nationwide study is to quantify real-world adherence and to identify its demographic and clinical determinants using the Belgian health care claims database of the National Institute for Health and Disability Insurance (NIHDI). Methods: Adherence was assessed using the Continuous Multiple Interval Measure of Medication Availability (CMA) among patients treated between 2020 and 2023. Mixed-effects logistic regression was applied to identify determinants of adherence. Results: Only 30.5% of patients achieved good adherence (CMA ≥ 0.8). Adherence varied substantially across pharmacological classes, ranging from 8.1% for inhaled corticosteroids to 66.4% for triple therapy. Age emerged as a major determinant, with adherence increasing steadily across age groups: only 4.0% of children and 15.7% of adolescents reached good adherence, compared with progressively higher rates in adults. Mixed-effects logistic regression confirmed age, sex, and pharmacological class as robust predictors of adherence. Conclusions: These findings highlight the magnitude of the therapeutic adherence gap in chronic respiratory diseases and clearly identify children, adolescents, and ICS or LABA + ICS users as the highest-risk groups. Recognizing these profiles has direct implications for clinical practice, as it provides concrete targets for future patient-centered interventions and guideline-concordant adherence-enhancing strategies. Full article

Background/Objectives: Since 2015, pulmonary arterial hypertension (PAH)-specific medications have been fully reimbursed in Lithuania. To describe the current situation of PAH treatment in the country and to determine survival during different PAH treatment regimens. Methods: The data from the Institute of Hygiene and the State Data Agency of Lithuania cases with administrative codes I27.0 and I27.8 have been evaluated. Results: In 2025, 225 confirmed cases of PAH were treated with PAH-specific medications in two PH centers. At least one PAH-specific medication was prescribed to 163 (72.4%) female and 62 (27.6%) male patients. Among these, 96 (42.7%) received sildenafil monotherapy, 82 (36.4%) received a combination of sildenafil and an ERA, 36 (16.0%) were on triple PAH-specific therapy (including selexipag or treprostinil), and 11 (4.9%) received other regimens due to specific medical considerations. The age of adults treated with sildenafil monotherapy vs. other therapies was 63.9 ± 14.8 (n = 117) and 51.5 ± 17.3 (n = 116) years, respectively (p < 0.05). A total of 191 PAH patients who received targeted therapy died during the observational period 2017–2025. Of these, 105 received monotherapy, 57 sildenafil and endothelin receptor antagonist and 29 triple therapies (treprostinil [n = 19], selexipag [n = 6], or inhaled iloprost [n = 4] were prescribed as the third drug). Patients who died and received triple therapy were younger than those on mono- and dual therapy (age at diagnosis 45.0 ± 21.6, 67.2 ± 14.7 and 61.6 ± 16.3 years, respectively, p < 0.01). Survival was longer in patients on dual therapy compared with monotherapy (43.1 ± 28.1 vs. 31.7 ± 25.0 months, p = 0.04), and the longest was in those receiving triple therapy (59.9 ± 29.4 months; p < 0.05). Conclusions: The availability of reimbursed medications dramatically increased the number of treated PAH cases in Lithuania. In 2025, most of the PAH patients received sildenafil monotherapy. Patients treated with sildenafil only were significantly older than the rest of cohort. In the survival analysis, combination PAH therapies were more often prescribed to younger patients and were associated with longer duration of life than monotherapy. Full article

Background: CD8A-related CD8α deficiency (Immunodeficiency 116) is a rare autosomal recessive primary immunodeficiency disease characterized by absent CD8⁺ T cells and variable sinopulmonary disease. Case Presentation: A seven-year-old boy from a consanguineous family was referred for chronic wet cough and “uncontrolled asthma” despite being prescribed high-dose inhaled corticosteroids and montelukast. He was hospitalized seven times over a two-year period for presumed asthma exacerbations complicated by pneumonia. An examination revealed bilateral crackles without wheezing. Throat culture tested positive for Haemophilus influenzae. CT imaging showed signs of chronic rhinosinusitis (maxillary mucosal thickening) and chronic airway disease with bronchiectatic changes. The patient’s immunoglobulin levels were within normal ranges for his age group. Flow cytometry revealed profound CD8⁺ T-cell lymphopenia (CD8⁺ 0.21%; 11 cells/µL; near-absent after excluding dual-positive cells) with expansion of CD3⁺CD4⁻CD8⁻ T cells (29.5%). CD8A gene sequencing identified a novel homozygous nonsense variant NM_001768.7:c.319C>T (p.Arg107Ter; GRCh38: chr2:86790412G>A), consistent with loss of CD8α and secondary loss of CD8β surface expression. A literature review identified three previously reported symptomatic patients (and two asymptomatic sisters in the first family), all with recurrent respiratory infections and variable structural lung disease. Conclusions: This case highlights CD8A deficiency as a rare mimic of pediatric asthma and expands the genotype spectrum with a truncating CD8A variant. Early lymphocyte immunophenotyping in children with recurrent sinopulmonary infections may prevent delayed diagnosis and progressive airway damage. Full article