Asthma research in 2025 further advanced a multidimensional view of asthma, integrating disease trajectory, exacerbation risk, structural airway changes, comorbidities, and treatment responsiveness. In mild asthma, studies published in 2025 further reinforced the importance of anti-inflammatory reliever strategies over SABA-only treatment by supporting timely inhaled corticosteroid delivery at symptom worsening to reduce exacerbation risk, particularly in adults and adolescents, while providing emerging but still nuanced evidence in child. In severe asthma, the therapeutic focus expanded beyond exacerbation reduction towards disease modification, including oral corticosteroid sparing, improvement or normalisation of lung function, reduction of mucus plugging, and attainment of clinical remission. Clinical remission became more clearly defined and increasingly positioned as a treatment target and research endpoint, supported by emerging consensus definitions, real-world data, and analyses of biologic trials. Real-world asthma management increasingly emphasised implementation, including treatable-traits-based care, biomarker-informed stratification, digital inhaler technologies, and approaches to persistent ethnic, social, and age-related inequities in outcomes. Advances in pathobiology highlighted the central role of the airway epithelium, inflammatory cellular ecosystems, microbiome-associated endotypes, mucus-plug biology, and early-life origins of airway remodelling in shaping asthma heterogeneity and progression.
Obesity is increasingly encountered among patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory or cardiac failure. It alters respiratory and cardiovascular physiology and drug pharmacokinetics and introduces technical and logistical challenges that may complicate patient selection, ECMO initiation, cannulation, anticoagulation, and monitoring. This review summarizes current evidence regarding the epidemiology, physiological implications, outcomes, and management of obesity in patients supported with veno-venous (VV) or veno-arterial (VA) ECMO. Available evidence, largely retrospective and based on body mass index classifications, suggests that obesity should not be considered a contraindication to VV-ECMO, with outcomes comparable to or potentially better than those of patients without obesity. However, obesity-related respiratory mechanics may exaggerate the apparent severity of lung injury, emphasizing the need for optimized conventional ARDS management, including appropriate ventilatory strategies and prone positioning, before ECMO initiation. In contrast, outcomes during VA-ECMO are more heterogeneous, particularly in extracorporeal cardiopulmonary resuscitation (ECPR), and may be influenced by patient selection, comorbidities, and timing of support. Obesity also creates important technical challenges requiring individualized cannulation, anticoagulation, and perfusion strategies. Obesity alone should not preclude access to ECMO, particularly VV-ECMO. Successful management requires anticipation of obesity-related challenges, appropriate infrastructure, and structured multidisciplinary protocols. Further prospective studies are needed to clarify obesity-specific risks, optimize management strategies, and evaluate long-term outcomes.
Long-term real-world outcomes of edoxaban in chronic thromboembolic pulmonary hypertension (CTEPH) remain incompletely characterized despite emerging evidence, including the KABUKI randomized trial. To evaluate long-term effectiveness and safety of edoxaban in patients with CTEPH using a nationwide registry. We analyzed the CTEPH AC Registry, a multicenter prospective observational cohort. Patients with CTEPH receiving edoxaban at registration were included. The primary effectiveness endpoint was morbidity and mortality events, a composite of all-cause death, lung transplantation, rescue pulmonary endarterectomy or balloon pulmonary angioplasty, ≥15% decline in 6-minute walk distance with worsening World Health Organization functional class, or symptomatic venous thromboembolism. The primary safety endpoint was clinically relevant bleeding according to International Society on Thrombosis and Haemostasis criteria. Among 408 patients, median follow-up was 552 days. The cumulative incidence of morbidity and mortality events was 4.7%, 10.0%, and 14.1% at 1, 3, and 5 years, respectively. The cumulative incidence of clinically relevant bleeding was 3.2%, 4.8%, and 5.6%, respectively, and major bleeding occurred in 2.4% at 5 years. Symptomatic venous thromboembolism occurred in 1.5% at 5 years. Outcomes were broadly consistent across reperfusion history, World Health Organization functional class, edoxaban dose, and renal function strata. In this Japanese nationwide registry, long-term edoxaban therapy was associated with sustained clinical stability in patients with CTEPH. No clear late-emerging safety signal was observed, but extrapolation beyond Japan requires caution, particularly in patients with different body size, renal function, or concomitant medication profiles.
Mirabegron, a β3-adrenoceptor agonist used for treating overactive bladder, has recently been identified in pharmacovigilance analyses as a potential signal for drug-induced myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although detailed clinical reports are lacking. We herein describe a patient who developed MPO-ANCA-positive vasculitis approximately 1 year after mirabegron initiation. The patient presented with inflammatory symptoms, elevated MPO-ANCA and C-reactive protein levels, and hematuria, with an improvement following drug discontinuation, thus allowing for the withdrawal of immunosuppressive therapy within 1 year. Causality was assessed as "probable/likely" using the WHO-UMC system. This case highlights the importance of early recognition and prompt drug withdrawal in cases of drug-induced AAV.
Prospective real-world data on remission rates in patients with severe eosinophilic asthma (SEA) treated with benralizumab for more than 1 year are currently lacking. Here we investigate the long-term effectiveness of benralizumab treatment over 2 years on symptom control, clinical outcomes, and remission rates in real-world patients with SEA. XALOC-2 is a prospective, observational real-world study in adults with SEA in Belgium, Canada, Germany, and Switzerland. Three-component clinical remission (3-CR; defined as the absence of exacerbations and oral corticosteroid use [over a 12-month period], and the presence of good asthma control [asthma control questionnaire (ACQ) thresholds of ≤0.75 or <1.5]), was assessed at Weeks 0/56/112. Among the 534 patients analyzed, median (interquartile range [IQR]) age at benralizumab treatment initiation was 58.0 (48.0-66.0) years; 76.3% had adult-onset asthma, and 49.3% were female. The median (IQR) ACQ score decreased from 3.0 (2.2-3.8) at baseline to 1.2 (0.6-2.3) at Week 56 and remained stable at Week 112 (1.2 [0.5-2.2]). When using the strictest ACQ threshold (≤0.75), the proportion of patients with 3-CR at Week 56 (27%) remained nearly unchanged at Week 122 (25%). A similar stability of 3-CR was observed when using the less strict ACQ threshold (<1.5): 42% at Week 56 and 41% at Week 112. Real-world patients with SEA showed early and sustained disease control and sustained remission rates after 2 years of benralizumab treatment. Even with the strictest ACQ threshold for asthma control, more than one-quarter of patients were in remission after 2 years of benralizumab.
Objective: Pembrolizumab monotherapy is an anti-PD-1 immunotherapy that is approved as a first-line treatment for non-small cell lung cancer (NSCLC) patients with high PD-L1 expression (≥50%). However, approximately 55% of these patients do not respond. Early identification of likely non-responders is critical to enable timely transition to alternative treatments. Materials: This study analyzed a retrospective cohort of NSCLC patients treated with first-line PD-L1 monotherapy, divided into a discovery training set (n: 97; 27 non-responders) and a preliminary test set (n: 17; 9 non-responders). Treatment response was assessed using baseline and follow-up CT scans in accordance with the response evaluation criteria in solid tumors (RECIST v1.1). Methods: Our objective was to extract deep learning (DL) features from the two groups of patients and apply transfer learning techniques to identify patients at risk of progression on pembrolizumab monotherapy. A nonparametric statistical test (Mann-Whitney U) was employed to rank the discriminative power of the 128 features from these training groups. Two types of support vector machine (SVM-RBF and SVM-Polynomial) classifiers were employed to investigate the discriminating power of the highest-ranked features as measured by F1 score and AUC values over ROC curves at the three levels of the data (slice, lesion, and patient) with and without clinical descriptors. Results: SVM-RBF performed best when trained on the 10 highest-ranked DL features and five clinical descriptors, achieving AUC of 0.742 (CI 95% 0.47-1.00), SN of 88.9%, SP of 75% and F1 score of 84.2% on preliminary test set patients, whereas an AUC of 0.902 ± 0.031, SN of 81.5%, SP of 81.4% and F1 score of 71% were observed for the discovery training set. Conclusions: Integrating CT-based DL features with clinical descriptors demonstrated balanced performance, offering a promising tool to identify patients at risk of progression on pembrolizumab monotherapy to support first-line treatment decisions in PD-L1-high NSCLC.
Tidal changes in esophageal pressure (ΔPes) are used as a surrogate for pleural pressure changes (ΔPpl) to assess chest wall mechanics. The Baydur ratio evaluates pressure transmission and guides catheter positioning. The effects of correcting ΔPes using the Baydur ratio on the accuracy of ΔPpl estimation and its dependence on ventilation mode, spontaneous inspiratory effort, and body position, remain unclear. In ten pigs, ΔPpl was measured using intrapleural balloon catheters, while Pes was recorded at three esophageal locations in supine and prone positions. Animals underwent controlled and assisted ventilation. Baydur ratios were derived during assisted ventilation and from external chest compressions during controlled ventilation. ΔPes before and after correction was compared with ΔPpl using mixed-effects models and Bland-Altman analysis. Additionally, we quantified the proportion of values with (ΔPes-ΔPpl) ≤ 1 cmH₂O. During assisted ventilation, ΔPes showed good agreement with posterior ΔPpl. Baydur correction improved scaling and association (slope 0.76 vs 0.50; r 0.81 vs 0.79, p<0.01) and increased values within ±1 cmH₂O from 29% to 45% when the Baydur ratio fell outside the accepted range. During controlled ventilation, ΔPes showed weaker association and wider limits of agreement, without improvement after correction. Similar patterns were observed in prone position. ΔPes more accurately reflected posterior ΔPpl during assisted ventilation. Baydur correction improves scaling and association, particularly when the Baydur ratio falls outside the accepted range, but does not improve and may worsen agreement during controlled ventilation.
Cystic fibrosis (CF) is a rare autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although relatively common in Caucasian populations, CF is rare in China, where it frequently presents with non-specific respiratory symptoms, leading to delayed diagnosis and frequent coinfections with multidrug-resistant pathogens. A 21-year-old man presented with a 6-year history of recurrent productive cough and intermittent fever over the past 6 months. Imaging revealed bronchiectasis with evidence of infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid identified Staphylococcus aureus and Mycobacterium abscessus. Further investigations revealed pancreatic lipomatosis, congenital absence of seminal vesicles, and fat-soluble vitamin deficiencies. CF diagnosis was confirmed by elevated sweat chloride concentration (88 mmol/L) and biallelic CFTR mutations. Clinical stability was achieved through a quadruple antimycobacterial regimen (linezolid, moxifloxacin, azithromycin, and minocycline) combined with systemic supportive care. CFTR modulator therapy was deferred due to limited access and financial constraints. We report a case of CF in a Chinese patient presenting with nontuberculous mycobacterial infection, a condition rarely documented in East Asian populations. We provide a review of the relevant literature, aiming to emphasize the importance of early recognition of CF, personalized antimicrobial strategies, and improved access to essential medications.
Optimal corticosteroid treatment duration for immune checkpoint inhibitor-related pneumonitis remains uncertain. No randomized trials have addressed this issue. To determine whether a 3-week corticosteroid taper is noninferior to the guideline-recommended 6-week taper for short-term treatment success in patients with mild (Common Terminology Criteria for Adverse Events Grade 1-2) immune-related pneumonitis. Patients with mild immune-related pneumonitis were assigned to either a 3-week or 6-week corticosteroid regimen. The primary endpoint was the treatment success rate at 8 weeks, defined as resting room-air SpO2 ≥ 90% without steroid escalation or prolongation due to pneumonitis worsening. Overall, 106 patients were randomized (median age, 72 years; Grade 2, 73%). Treatment success rates were 66.7% and 85.2% in the 3- and 6-week groups, respectively, which did not demonstrate noninferiority (difference: -18.5 percentage points [80% confidence interval: -29.0% to - 7.9%] P = .621) of the 3-week regimen. A predefined exploratory analysis indicated superiority of the 6-week regimen (P = .013). Grade ≥ 3 adverse events occurred in 12% and 24% of the 3- and 6-week groups, respectively; however, all were manageable with clinical interventions. The total quality of life mean change using the King's Brief Interstitial Lung Disease score from baseline was 4.78 and 6.28 in the 3- and 6-week groups, respectively (between-group difference: -1.50 percentage points; 95% confidence interval: -5.91 to 2.91). Overall survival was comparable between the groups (hazard ratio: 1.03; 95% confidence interval: 0.46-2.29; P = .95). This study establishes the 6-week corticosteroid regimen as an evidence-based standard for treating ICI-related pneumonitis.
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People with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) experience chronic breathlessness and reduced quality of life (QOL). Specialised singing programs for people with lung disease may improve QOL and symptoms. A randomised controlled trial conducted in Australia to determine the feasibility and effectiveness of 12 weeks of online, guided group singing on QOL (primary outcome, as measured by SF36), as compared to usual care in people with COPD or ILD. anxiety, depression, dyspnoea and loneliness. Intervention effectiveness was assessed using mixed effects linear regression. One hundred and one participants were randomised (50 singing, 51 control; 64 COPD, 37 ILD; mean age 69.6 years; 74% women; 42% mMRC = 2, 58% mMRC ≥ 3). The results of the primary endpoint were a mean treatment effect (MTE) of singing of 2.5 points (95% CI -1.9 to 6.8; p = 0.266) on SF-36 mental health score (MCS) and 2.6 points (95% CI -0.9 to 6.1; p = 0.138) on the physical component score (PCS), neither of which were statistically or clinically significant. In the per-protocol analysis, significant improvement in MCS was detected in participants who attended 8 or more sessions (MTE:4.8; 95% CI 0.1 to 9.5; p = 0.047). No significant effects on secondary outcomes were detected. No adverse events were reported. This RCT demonstrated that online group singing is a feasible intervention for people with COPD or ILD and breathlessness. Although the intention-to-treat analysis did not demonstrate effectiveness, per-protocol analyses suggest that singing may improve mental health components of QOL in people with COPD or ILD.
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Lung cancer screening is now widely adopted across healthcare systems. Screening typically occurs in asymptomatic individuals. As symptoms of lung cancer overlap with those of chronic conditions, defining asymptomatic screening is challenging. This study outlines the frequency of symptomatic participants in a lung cancer screening trial. How common are respiratory and red flag symptoms in lung cancer screening participants and how do these symptoms impact screening outcomes? SUMMIT is a prospective observational cohort study to assess the implementation of Low-Dose Computed Tomography (LDCT) screening for lung cancer. Baseline clinical assessments collected self-reported symptoms, medical history, demographics, and spirometry. Haemoptysis (in last year) and unintentional weight loss (≥5kg in 3 months) were classified as red flag symptoms, and cough (acute: onset less than six weeks, or chronic: >6 weeks) and dyspnoea (modified Medical Research Council scale≥1) classified as non-specific symptoms. Lung cancer diagnoses within one year were ascertained. Multivariable logistic regression was used to assess associations between symptoms and lung cancer. Among 13,035 participants eligible for a baseline LDCT 76% (N=9,859) reported at least one symptom. Cough was present in 36% (N=4,707) and 66% of participants reported dyspnoea. Only 6% of participants reported red flag symptoms, including hemoptysis and weight loss. The presence of any of these symptoms was associated with higher likelihood of lung cancer diagnosis in the year following assessment (OR 1.45, p=0.03, adjusted for other baseline factors). Symptoms are commonly reported in those undergoing lung cancer screening and those with symptoms are more likely to be diagnosed with lung cancer.
Acute hypoxemic and hypercapnic respiratory failure are among the most common reasons for ICU admission and need for invasive mechanical ventilation. Noninvasive respiratory support (NIRS) strategies-including high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP)-may prevent intubation, improve outcomes, and reduce ICU utilization. However, there is uncertainty regarding optimal patient and modality selection, resulting in variable implementation. There are no clinical practice guidelines comprehensively addressing the use of the different noninvasive respiratory support strategies across the spectrum of acute respiratory failure. To update and develop new evidence-based clinical practice recommendations informing noninvasive respiratory support use, including HFNC, NIV and CPAP, in adults with acute respiratory failure. A multidisciplinary panel used the GRADE approach to address four PICO questions related to the use of NIRS for hypoxemic and hypercapnic respiratory failure, preoxygenation for intubation, and post-extubation respiratory support. Recommendations were informed by several systematic reviews and network meta-analyses. The panel made a strong recommendation for HFNC and a conditional recommendation for NIV or CPAP for adults with acute hypoxemic respiratory failure with close monitoring for the need for escalation of respiratory support, based primarily on effects on need for intubation. For acute hypercapnic respiratory failure, the panel made a strong recommendation for NIV to reduce mortality and need for invasive mechanical ventilation, and a conditional recommendation for HFNC only in patients with less severe hypercapnia and with mild acidemia (eg, pH > 7.25), provided that close monitoring and prompt escalation to NIV are available. The panel made a strong recommendation for HFNC or NIV for preoxygenation prior to endotracheal intubation to prevent peri-intubation hypoxemia. The panel also issued a risk-based recommendation, suggesting HFNC for low-risk patients and NIV for high-risk patients to reduce the need for re-intubation following extubation after critical illness. Noninvasive respiratory support strategies are effective in improving outcomes in a range of clinical scenarios. We provide evidence-based recommendations, which can be further informed by patient risk, institutional capacity, and interface tolerance.
Managing central nervous system (CNS) metastases of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer can be challenging if dose-limiting toxicities prevent adequate drug exposure. We report the case of a 70-year-old woman with a suprasellar metastasis abutting the optic chiasm for whom radiotherapy was contraindicated. Although treatment with 80 mg osimertinib once daily was begun, recurrent grade 3 neutropenia required a dose reduction to 40 mg every other day. During alternate-day dosing, the suprasellar lesion progressed despite continued control of extracranial disease, threatening the patient's vision. To enhance exposure of the CNS to osimertinib, its dosage was escalated to 40 mg once daily supported by granulocyte colony-stimulating factor (filgrastim). This strategy successfully led to tumor regression and maintained disease control without unmanageable toxicity. This case suggests that dose reduction can weaken the effect of osimertinib on the CNS and that maintaining dose intensity using granulocyte colony-stimulating factor support is a viable and effective strategy for controlling CNS lesions in eloquent areas when local therapy is contraindicated.
Genetic cardiomyopathies commonly cause end-stage heart failure, yet genetic testing is inconsistently applied in heart transplant recipients. Identifying pathogenic/likely pathogenic (P/LP) variants clarifies etiology and informs familial risk, but data on diagnostic yield are limited. We performed a meta-analysis to quantify genetic testing yield in heart transplant recipients and implications for cascade testing. MEDLINE and Embase were searched for studies examining cardiomyopathy-focused genetic testing in heart transplant recipients. Pooled P/LP cardiomyopathy variant yields were estimated using random-effects models, stratified by cardiomyopathy phenotype. Cascade testing outcomes were summarized. Eleven studies met inclusion criteria. Overall, 32% (95% CI: 21-46%) of heart transplant recipients carried a P/LP variant. Yield was highest in non-ischemic cardiomyopathy (34%, 95% CI: 24-47%) and non-ischemic dilated cardiomyopathy cohorts (29%, 95% CI: 12-54%), and lowest in ischemic cardiomyopathy cohorts (8%, 95% CI: 4-18%). Heterogeneity ranged from I2 35% to 92%. Among studies reporting cascade testing outcomes, 52-92% of families underwent testing; 30-40% of relatives had P/LP variants, 15-69% of which demonstrated a phenotypic CM. While exact estimates should be interpreted cautiously given heterogeneity across cohorts, the consistency of findings suggests meaningful clinical relevance. Cardiomyopathy-focused genetic testing identifies P/LP variants in many heart transplant recipients, with important implications for cascade testing, supporting integration of cardiomyopathy-related genetic evaluation into heart transplant programs.
Bickerstaff's brainstem encephalitis (BBE) is an autoimmune disorder typically localized to the brainstem. While cortical involvement is rare, severe cases presenting with decorticate posturing and profound consciousness disturbance can mask typical clinical features, making early diagnosis challenging. A 22-year-old woman developed progressive numbness in her limbs and lips, visual impairment, and impaired consciousness 13 days after an episode of gastroenteritis. Upon admission, she exhibited a Japan Coma Scale score of III-200, decorticate posturing, absent brainstem reflexes, and hyperreflexia. Cerebrospinal fluid analysis revealed pleocytosis and elevated protein levels. Although contrast-enhanced MRI showed only faint enhancement along the leptomeninges of the cerebral cortex and midbrain, acute-phase 123I-IMP cerebral blood flow (CBF) single photon emission computed tomography (SPECT) demonstrated diffuse cortical hypoperfusion and paradoxical hyperperfusion in the bilateral basal ganglia. Furthermore, multiple autoantibodies associated with autoimmune encephalitis and demyelinating diseases-including anti-NMDAR, LGI1, CASPR2, AMPAR, GABABR, DPPX, GlyR, mGluR5, MOG, and AQP4 antibodies-were all negative in both serum and cerebrospinal fluid. Following aggressive immunotherapy, her consciousness improved rapidly. It was only during this recovery phase that the classic BBE triad of total ophthalmoplegia and ataxia became apparent, which had been masked by the initial severe consciousness disturbance. The diagnosis of BBE was retrospectively confirmed based on this clinical evolution and the high titers of serum anti-GQ1b and anti-GT1a IgG antibodies. Follow-up SPECT confirmed the normalization of CBF, correlating with her clinical recovery. This case demonstrates that cerebral perfusion SPECT is capable of detecting reversible dysfunction within the cortex and basal ganglia in BBE. It highlights the importance of considering BBE even in atypical cases with predominant cortical symptoms, where the diagnosis may only become clear through clinical evolution and ancillary functional imaging.
Post-bronchoscopy infections are usually bacterial, whereas procedure-associated endobronchial dissemination of Mycobacterium tuberculosis is rarely reported. A 52-year-old woman with poorly controlled diabetes (HbA1c 13.8%) had a 19-mm left upper-lobe nodule radiologically suspicious for lung cancer. Because tissue confirmation was required and tuberculosis remained in the differential diagnosis (positive T-SPOT.TB on admission), endobronchial ultrasonography with a guide sheath (EBUS-GS)-guided transbronchial biopsy was performed under airborne precautions. Bronchial lavage smear and loop-mediated isothermal amplification were positive for M. tuberculosis, and histology showed extensive caseous necrosis with numerous acid-fast bacilli, consistent with a tuberculoma. Two days later, she developed a 39°C fever with rapid cavitation of the primary lesion and new ipsilateral tree-in-bud opacities. No bacterial pathogens other than M. tuberculosis were identified despite empirical ceftriaxone. Standard antituberculosis therapy led to clinical and radiological improvement.
Lung-protective ventilation is the current standard for mechanical ventilation of patients with acute respiratory distress syndrome (ARDS). Traditionally, this approach has focused on the controlled phase of mechanical ventilation, but emerging data suggest that how patients are managed during assisted ventilation may also impact clinical outcomes. Experimental and observational clinical data indicate that excessive respiratory effort may further damage already injured lungs and may also lead to diaphragm myotrauma. Conversely, insufficient effort and prolonged passive ventilation are associated with diaphragm atrophy and dysfunction. Recent non-invasive techniques to monitor respiratory drive and effort at the bedside have facilitated the development of a new strategy to protect both the lungs and the diaphragm. The lung- and diaphragm-protective (LDP) ventilation framework highlights the need to better integrate ventilation and sedation strategies to facilitate timely and safe spontaneous breathing. This new paradigm has driven the development of emerging supportive and therapeutic modalities, such as diaphragm neurostimulation and partial neuromuscular blockade. Clinical trials are needed to evaluate the impact of LDP strategies on patient-centered outcomes, using designs that account for the possibility of heterogeneity of treatment effect in the ARDS population. In this review, we summarize the physiological background for the LDP framework, as well as the current clinical evidence evaluating this strategy.
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