Search Results (325)

Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies. Full article

Background and Objectives: Nintedanib is indicated for progressive pulmonary fibrosis (PPF) based on clinical trial results. The primary objectives of this study were to evaluate the effectiveness of nintedanib on forced vital capacity (FVC) and diffusing lung capacity for CO (DLCO) after one year of treatment, and to compare the annual rate of decline (“slope”) for FVC, DLCO and 6 minute walking distance (6MWD) with the year prior to treatment. The secondary objectives were antifibrotic safety, tolerability, adverse events, immunosuppressant use, dyspnoea and survival. Materials and Methods: This study was a single-centre, retrospective, observational cohort study that included consecutive patients with PPF treated with nintedanib. Results: Fifty-five patients with non-IPF fibrotic ILD initiated nintedanib due to fibrosis progression. Most patients (63.4%) stabilised/improved FVC after 1 year of treatment, and 82.5% stabilised/improved DLCO. The “slope” of FVC and DLCO was reduced after 1 year of treatment compared to the year before initiation, although the difference was not statistically significant: FVC slope was +0.61% in the year after initiation vs. −2.3% in the year prior (mean change: 2.94%, 95%CI [−4.74, 10.62]); DLCO slope was −3.8% after treatment vs. −7% before initiation (mean change: 3.24%, 95%CI [−7.43, 13.92]). Dyspnoea improved in 23.2% of patients. A reduction in immunosuppressant use was observed after nintedanib initiation. Forty-one patients (74.5%) experienced at least one side effect: diarrhoea (60%), hepatotoxicity (23.6%), or asthenia (12.7%). Fifteen patients required permanent or temporary treatment discontinuation. Conclusions: In our real-world PPF cohort, most patients showed FVC and/or DLCO stabilisation or improvement after one year of nintedanib treatment. A non-significant reduction in the rate of FVC decline after one year of treatment was also observed, as was a reduction in symptom severity in our real-life PPF cohort. Full article

A 40-year-old man with complex congenital heart disease (double-inlet left ventricle with transposition of the great arteries), previously treated with a Blalock–Taussig shunt in infancy and a modified Fontan procedure (including superior vena cava-to-pulmonary artery anastomosis, atriopulmonary connection, and tricuspid valve closure with a Dacron patch), presented to the emergency department with worsening dyspnea and hypoxemia (SpO₂ < 80%). Echocardiography suggested a shunt through the tricuspid patch, possibly related to prior atrial flutter ablation. Cardiac catheterization confirmed an approximately 10 mm fenestration in the calcified patch causing a significant bidirectional shunt, along with two fistulae between the innominate vein and the left atrium. The fenestration was successfully closed using a septal occluder via right femoral venous access under transesophageal echocardiographic guidance. The venous collaterals were occluded with vascular plugs via right femoral and left brachial approaches. Technical success of the closure of the intracardiac and the venous shunts was confirmed angiographically at the end of the procedure. Oxygen saturation improved immediately from 72% to 91% and remained stable at the 2-year follow-up. Similarly, NYHA functional class improved from IV to II and episodes of tachycardia became less frequent and better tolerated, with sustained benefit throughout follow-up. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (F-ILD) are characterised by progressive loss of lung function, worsening symptoms, and poor prognosis. Current antifibrotic therapies slow disease progression but do not arrest or reverse fibrosis and are frequently associated with adverse effects. Senicapoc, a selective KCa3.1 channel inhibitor, has shown antifibrotic effects in preclinical models, human lung myofibroblasts, and ex vivo human lung tissue. This study aims to determine whether senicapoc reduces the rate of decline in forced vital capacity (FVC) over 26 weeks, compared with placebo, in patients with IPF or other progressive F-ILD, while also characterising safety and tolerability. Methods: This is an investigator-initiated, prospective, randomised, double-blind, placebo-controlled, multicentre phase II trial. Adults with IPF or other F-ILD with documented progression despite optimised antifibrotic management according to standard care and individual tolerability will be randomised 1:1 to receive senicapoc 30 mg once daily or a matching placebo for 26 weeks in addition to standard care. The primary outcome is the rate of decline in FVC over 26 weeks. Secondary outcomes include changes in diffusion capacity, 6 min walk distance, dyspnoea, health-related quality of life, adverse events, and senicapoc plasma concentrations, with mortality and exacerbations assessed as exploratory outcomes. The planned sample size is 140 participants. The primary analysis will be conducted in the intention-to-treat population using a linear mixed-effects model for repeated measurements. Results: No results are available, as this article describes the study protocol. Conclusions: This study will provide proof of concept for the efficacy, safety, and tolerability of senicapoc in progressive fibrotic interstitial lung disease. If successful, it will support further clinical development of KCa3.1 inhibition as a novel antifibrotic strategy. Full article

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains an important cause of morbidity and mortality in systemic sclerosis. Mycophenolate mofetil (MMF) is widely used as first-line immunosuppressive therapy; however, real-world descriptions of pulmonary functional and radiologic evolution during MMF therapy remain limited, particularly according to high-resolution computed tomography (HRCT) pattern. Objectives: To descriptively evaluate pulmonary function evolution, radiologic findings, and safety outcomes in patients with SSc-ILD treated with MMF in routine clinical practice, with exploratory analyses according to HRCT pattern and subsequent antifibrotic use. Materials and Methods: We conducted a retrospective single-center study including 20 patients with SSc-ILD treated with MMF. Clinical, functional (forced vital capacity [FVC]; diffusing capacity for carbon monoxide [DLCO]), and radiologic (HRCT Warrick score) parameters were assessed at baseline, 6 months, and 12 months. Patients were stratified according to nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) patterns. Statistical analyses were exploratory and descriptive. Results: Pulmonary function remained overall stable during follow-up under MMF therapy, while DLCO improvement was observed at 6 months and remained stable at 12 months. Radiologic progression appeared more limited in patients with NSIP pattern, whereas patients with UIP pattern generally exhibited more frequent radiologic progression during follow-up. Patients who subsequently received nintedanib generally presented with UIP-pattern disease, lower baseline DLCO values, and more advanced pulmonary involvement. MMF was generally well tolerated, with treatment discontinuation due to adverse events observed in a single patient. Conclusions: This small retrospective real-world case series describes pulmonary functional and radiologic evolution in patients with SSc-ILD treated with MMF in routine clinical practice. Overall functional stabilization was observed during follow-up, while radiologic progression was more frequently observed in patients with UIP-pattern disease and more advanced baseline pulmonary involvement. Because of the exploratory descriptive design and limited sample size, these observations should be interpreted cautiously and considered hypothesis-generating only. Further prospective studies with standardized radiologic assessment are required. Full article

Background: The increased detection of small peripheral non-small-cell lung cancers through screening programs has renewed interest in parenchyma-sparing sublobar resection as an alternative to lobectomy. While oncologic non-inferiority has been established, the functional impact of sublobar resection remains a key consideration. Methods: We reviewed evidence from landmark randomized controlled trials, recent meta-analyses, observational studies, and updated clinical practice guidelines. Results: In the CALGB 140503 trial, sublobar resection demonstrated only a modest 2-percentage-point advantage in preserved FEV1 and FVC at 6 months compared with lobectomy, a difference considered clinically marginal in patients with normal baseline pulmonary function. A meta-analysis of five randomized controlled trials confirmed that sublobar resection was associated with significantly less reduction in postoperative lung function. A retrospective study demonstrated that segmentectomy preserved FEV1 at 84.2% of preoperative values versus 69.9% after lobectomy at one year, with particular benefit observed in elderly patients and those with COPD. Volumetric analyses showed greater contralateral compensatory lung expansion after lobectomy, partially offsetting functional differences. Notably, patient-reported outcomes, including physical function, dyspnea, and cough scores, showed no significant differences between groups up to two years postoperatively. The ERS/ESTS 2025 guideline noted that segmentectomy is associated with reduced long-term dyspnea deterioration and may improve patients’ ability to tolerate subsequent treatments. Conclusions: Sublobar resection offers a statistically significant but modest advantage in spirometric lung function preservation over lobectomy for early-stage NSCLC. This benefit may be most clinically relevant in patients with compromised baseline pulmonary function, COPD, or a potential need for future treatments. Full article

Pulmonary arterial hypertension (PAH), a major subtype of pulmonary hypertension (PH), is a significant human pulmonary disease whose pathogenic mechanisms remain incompletely understood. Conventional animal models for PAH induction often fail to fully replicate the entire disease progression, making it difficult to trace the initial causes, key pathogenic events, and early disease mechanisms. We propose an evidence-based hypothesis that Broiler Ascites Syndrome (BAS) exhibits high similarity to human pulmonary arterial hypertension in terms of pathogenic triggers and molecular pathology, suggesting its potential as a spontaneous animal model for PAH research. This review systematically summarizes the pathogenic mechanisms and disease-inducing factors of BAS, analyzing its pathobiological commonalities with PAH. We demonstrate shared features in pulmonary vascular remodeling mechanisms, including cellular dysfunction, tissue fibrosis, and immune dysregulation. Furthermore, consistent reactive mechanisms are observed across different types of PAH-related studies and corresponding poultry research. This collective evidence supports the feasibility of utilizing BAS as a spontaneous animal model for PAH investigation. By comparing the pathogenic mechanisms of BAS and PAH, this work provides novel insights for developing animal models in PAH research. If validated, this model could address limitations of existing models regarding hypoxia tolerance, and right heart remodeling. Full article

Background: Diets composed of various components have been shown to influence inflammatory diseases such as asthma. While most studies have focused on fiber-rich diets to investigate their effects on the immune system and, consequently, on asthma, little is known about the impact of sugar-rich diets, particularly when such diets are consumed over short periods of time. Methods: To investigate the short-term effects of a sugar-rich diet on allergic airway inflammation, A/J mice were fed either a standard diet or a sugar-enriched diet and subsequently sensitized and challenged with ovalbumin or PBS. Airway inflammation was assessed by bronchoalveolar lavage (BAL) cell analysis, including eosinophil counts and cytokine levels (IL-4, TNF-α, IL-33), and by lung histology (H&E for inflammatory infiltrate and PAS for mucus). Serum IgE levels were also measured. In addition, glucose tolerance, visceral and subcutaneous adipose tissue mass, and inflammatory markers in visceral adipose tissue were evaluated. Results: Short-term consumption of a sugar-rich diet induced glucose intolerance and expansion of adipose tissue, particularly visceral fat, independent of ovalbumin sensitization. Gonadal adipose tissue analysis revealed a shift toward M1 macrophage polarization, characterized by elevated TNF-α, IL-6, and IL-1β, increased leptin levels, and reduced adiponectin. In OVA-sensitized mice, the sugar-rich diet significantly exacerbated eosinophil infiltration in BAL, increased IL-4, TNF-α, and IL-33, and enhanced PAS-positive mucus accumulation and inflammatory infiltrates in the lung. Moreover, total serum IgE was significantly higher in allergic mice fed the sugar-rich diet compared with allergic mice on the standard diet. Importantly, in non-sensitized mice fed the sugar-rich diet, no pulmonary inflammation was detected by BAL, demonstrating that HSD alone does not induce asthma but amplifies allergic responses when sensitization is present. Conclusions: Our findings demonstrate that short-term consumption of a sugar-rich diet is sufficient to exacerbate, but not initiate, allergic pulmonary inflammation. From a translational perspective, reducing dietary sugar intake may represent a valuable adjuvant strategy in the management of allergic asthma. Full article

Background/Objectives: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is linked to substantial morbidity and mortality. While nintedanib (NTB) slows lung function decline in progressive pulmonary fibrosis (PPF), real-world data—particularly regarding radiographic outcomes—remain limited. We aimed to evaluate the real-world effectiveness and tolerability of antifibrotic therapy—predominantly NTB—on radiographic and functional outcomes in a Hungarian CTD-ILD cohort. Methods: We conducted a retrospective observational cohort study including 72 patients with progressive CTD-ILD who initiated antifibrotic therapy at two Hungarian tertiary centers between January 2021 and June 2025. The primary endpoint was the proportion of patients without significant radiographic progression at 6–12 months, based on blinded assessment of paired high-resolution computed tomography (HRCT) scans by two thoracic radiologists. Secondary endpoints included changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) at 6 and 12 months, safety and tolerability, and correlations between lung function and disease-related factors. Results: The cohort comprised systemic sclerosis–ILD (n = 25), rheumatoid arthritis–ILD (n = 23), and other CTD-ILD (n = 24). Radiographic stability was observed in 65.8–78.9% of patients, with improvement most commonly seen in ground-glass opacities, while traction bronchiectasis remained largely unchanged. Radiographic disease extent showed the strongest inverse correlation with baseline FVC and DLCO (p < 0.05). Significant improvements in FVC and DLCO were observed at 6 and 12 months (p < 0.001). Antifibrotic therapy was well tolerated, including in combination with immunosuppressive treatment. Conclusions: These real-world data support the effectiveness and safety of NTB in PPF–CTD-ILD and highlight radiologic disease burden as a key determinant of functional impairment. Full article

Background: The optimal intraoperative positive end-expiratory pressure (PEEP) obtained by titrating to the lowest tolerable fraction of inspired oxygen (FiO₂) has been proposed recently; however, whether its performance in obtaining optimal PEEP is comparable to that from electrical impedance tomography (EIT) titration remains unknown. Methods: Ninety-three adult patients undergoing robotic-assisted laparoscopic prostatectomy under general anesthesia were enrolled in this study. They underwent the determination of optimal PEEP obtained either by titrating to the lowest tolerable FiO₂ (PEEP_O2) or using EIT (PEEP_EIT). The primary endpoint was intraoperative optimal PEEP values. Secondary endpoints included pre-extubation arterial oxygen partial pressure (PaO₂)/FiO₂, intraoperative mean arterial blood pressure (MAP), the incidence of hypoxemia in the postanesthesia care unit (PACU), and postoperative pulmonary complications (PPCs) up to discharge from hospital. Results: Group PEEP_O2 (n = 47) exhibited a higher optimal PEEP compared to Group PEEP_EIT (n = 46) [Median (IQR): 18 (16–18 cmH₂O) vs. 16 (14–16 cmH₂O), p < 0.001]. Pre-extubation PaO₂/FiO₂ was higher in Group PEEP_O2 (510.5 ± 80.0 vs. 471.8 ± 69.0 mmHg, p = 0.015), while lung dynamic compliance (41.1 ± 7.7 vs. 37.3 ± 6.4 mL cmH₂O⁻¹, p = 0.011) and static compliance (36.4 ± 5.8 vs. 33.6 ± 5.5 mL cmH₂O⁻¹, p = 0.017) were also higher in Group PEEP_O2. Additionally, driving pressure (11.0 ± 2.0 vs. 12.1 ± 1.9 cmH₂O, p = 0.006) was lower in Group PEEP_O2. There were no significant differences in intraoperative MAP and the incidences of PACU hypoxemia and PPCs between the two groups. Conclusions: The optimal PEEP obtained by titrating to the lowest tolerable FiO₂ is a clinically acceptable alternative of that obtained using EIT. Therefore, this technique could be a viable alternative to EIT for obtaining optimal PEEP. Full article

Background/Objectives: Right vertical infra-axillary thoracotomy to repair ventricular septal defects (VSDs) and atrial septal defects (ASDs) is less invasive than conventional surgical repair via median sternotomy. However, right vertical infra-axillary thoracotomy (RVIAT) may result in unilateral lung injury, a serious postoperative complication requiring extracorporeal circulation and unilateral lung collapse. The aim of this study was to evaluate whether repeated lung recruitment provides enhanced respiratory compliance and lung oxygenation in children who have undergone right vertical infra-axillary thoracotomy (RVIAT) to correct a congenital heart defect. Methods: Eligible participants were children with a common congenital heart defect corrected via RVIAT. Seventy-seven children were randomly classified into two groups. In group A (n = 39), an alveolar recruitment maneuver (ARM) was performed immediately after cardiopulmonary bypass. Children in group C (n = 38) did not receive any additional interventions during surgery. Results: The ARM group tolerated open lung ventilation without significant hemodynamic instability. Compared to controls, intraoperative PaO₂, PaO₂/FiO₂ and lung compliance (Com_dyn) improved in group A (p < 0.05), who also showed a significantly lower IL-6 (p < 0.05). In addition, group A had a lower incidence of lung injury and lung atelectasis than Group C at specific post CPB time points. Conclusions: Our findings provide some indication that the application of ARM could effectively improve the oxygenation profile, reduce postoperative pulmonary complications, and attenuate the postoperative inflammatory response in children with a common congenital heart defect corrected via the RVIAT technique. Full article

Background: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating skeletal muscle weakness and fatigue, leading to reduced functional independence and impaired quality of life (QoL). Although exercise has historically been discouraged due to concerns about symptom exacerbation, emerging evidence suggest that structured exercise programs may be safe and beneficial in clinically stable patients. This systematic review critically evaluates current evidence on exercise and physical activity interventions in MG, focusing on effectiveness, safety, and impact on functional outcomes, fatigue, and QoL. Materials and Methods: A systematic review was conducted following PRISMA guidelines. Searches were performed in PubMed, Web of Science, Google Scholar, Scopus and ScienceDirect for studies published between 2015 and 2025. Keywords included MG, physical activity, aerobic training, resistance training, and respiratory muscle training. Methodological quality was assessed using the Downs and Black checklist. Results: Eight controlled studies met the inclusion criteria, encompassing aerobic, resistance, combined, and respiratory muscle training interventions. Sample sizes ranged from small pilot studies to moderate-size randomized controlled trials. Overall, exercise interventions were well tolerated, with no evidence of sustained symptoms exacerbation. Aerobic and combined programs consistently improved functional capacity, muscle strength, and activities of daily living. Respiratory muscle training demonstrated improvements in pulmonary function and inspiratory muscle strength, although findings were more heterogeneous. Study quality ranged from poor to excellent, with common limitations including small sample size, short follow-up duration, and heterogeneity in exercise programs. Conclusions: Current evidence supports the safety and potential efficacy of individualized, symptom-guided exercise interventions in clinically stable MG. Regular physical activity exercise may reduce secondary deconditioning, improve functional outcomes, and enhance QoL. However, larger, high-quality randomized controlled trials with standardized programs and longer follow-up periods are required to strengthen clinical recommendations and clarify long-term effects. Full article

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article

Postoperative respiratory failure (PRF) remains a pervasive clinical challenge that substantially contributes to perioperative morbidity, mortality, and prolonged ICU stay. Although conventional oxygen therapy is often sufficient, a significant subset of high-risk patients requires escalation to advanced non-invasive support to avoid reintubation and invasive mechanical ventilation. Evidence from recent randomized trials, including the 2025 RENOVATE and Goret et al. studies, indicates that both non-invasive ventilation (NIV) and high-flow nasal oxygen (HFNO) reduce postoperative pulmonary complications and reintubation in selected high-risk populations. While NIV is preferred for hypercapnic ventilatory failure and is commonly used in selected high-risk cardiac surgery patients, HFNO offers comparable outcomes in pure hypoxemic failure with the added benefits of superior patient tolerance and a lower incidence of interface-related complications. Effective PRF management necessitates an individualized, physiology-based approach. By implementing a phenotype-driven algorithm that aligns device mechanics with the dominant pathophysiology, such as atelectasis versus pump failure, clinicians can optimize patient outcomes while minimizing the specific risks associated with delayed intubation. Full article

Background: Nanostructured, rod-shaped microparticles represent a promising drug delivery platform for the pulmonary delivery and targeting of alveolar macrophages by exploiting the aerodynamic advantages of fiber-like geometries. These microrods feature a hierarchical architecture, designed for potential macromolecular payloads, and silica (SiO₂)-based systems have previously been shown to successfully deliver oligonucleotides in vitro. However, current microrod systems mainly rely on nanoparticulate SiO₂-based frameworks with limited biodegradability and lack a specific escape mechanism to the cytosol. Therefore, a nanostructured calcium phosphate (CaP) framework is proposed as a biodegradable and resorbable alternative, featuring pH-responsive dissolution under endolysosomal conditions. Methods and Results: This study presents the fabrication of nanostructured, rod-shaped calcium phosphate microparticles and discusses their suitability as a potential pulmonary drug delivery platform. The particles feature dissolution-driven disintegration in acidic and ion-rich environments relevant to phagolysosomes. In addition, the particles exhibited a favorable acute cytotoxicity profile in the murine alveolar macrophage cell line MH-S compared with their SiO₂-based counterparts. Comparative RNA-seq analysis of MH-S exposed to the particles indicates a mild transcriptomic response, while canonical signatures of classical or alternative macrophage activation programs were not observed, supporting a generally well-tolerated exposure profile of the carrier. Conclusions: Together, these findings establish key prerequisites for employing calcium phosphate microrods as a biodegradable pulmonary carrier platform in subsequent studies incorporating therapeutic cargos. Full article