Lymphangioleiomyomatosis (LAM) is typically recognized by diffuse, bilateral, thin-walled pulmonary cysts on high-resolution computed tomography. However, atypical presentations dominated by lymphatic manifestations and chylous pulmonary congestion may delay diagnosis. We report a 44-year-old woman with progressive exertional dyspnea and recurrent nontraumatic chylothorax. A contrast-enhanced chest and abdominopelvic CT in 2018 had shown multiple extrapulmonary cystic lymphatic lesions involving the mediastinal, retroperitoneal, and bilateral iliac vascular regions, while no obvious pulmonary abnormality was reported. In 2021, imaging showed bilateral pleural effusions, ascites, posterior-predominant patchy pulmonary opacities suggestive of chylous or lymphatic pulmonary congestion, and persistent extrapulmonary cystic lymphatic lesions. Classic diffuse thin-walled pulmonary cysts were not the dominant initial imaging feature. Her history of uterine perivascular epithelioid cell tumor of uncertain malignant potential further complicated the differential diagnosis. Transbronchial cryobiopsy showed enlarged airspaces with spindle-cell proliferation along the walls of enlarged airspaces and focal perivascular distribution. Immunohistochemistry demonstrated positivity for HMB45, smooth muscle actin, and desmin. Serum vascular endothelial growth factor-D was markedly elevated at 5337 pg/mL, supporting sporadic LAM with lymphatic involvement. After sirolimus treatment, the patient remained clinically stable, and imaging showed partial resolution of pulmonary opacities and pleural abnormalities, together with marked reduction of pelvic extrapulmonary cystic lymphatic lesions. Long-term follow-up CT showed several subtle posterior air-containing structures or pulmonary cystic airspace-like changes, some of which could represent small airways or terminal bronchioles rather than definite LAM-related cystic airspaces. The imaging pattern did not evolve into classic diffuse cystic LAM. This case expands the recognized radiological spectrum of LAM and highlights that LAM should be considered when chylous pulmonary congestion and extrapulmonary cystic lymphatic lesions predominate despite nonclassic pulmonary cystic findings.
Asthma is a common chronic inflammatory airway disease with diverse clinical manifestations, among which cough is one of the most significant and complex symptoms. Cough not only impacts patients’ quality of life but also significantly influences the diagnosis and management of asthma. In recent years, with advancements in molecular biology and immunology, researchers have progressively uncovered multiple phenotypes of cough in asthma and their corresponding endotypic mechanisms, encompassing the activation of immune cells, the release of inflammatory mediators, and the role of airway neural regulation, among other aspects. However, challenges remain in standardizing the classification of cough phenotypes and establishing precise diagnostic and therapeutic pathways. This article systematically reviews the latest research progress on the phenotypes and endotypes of cough in asthma. It focuses on elucidating the immune-inflammatory and neural regulatory mechanisms, integrating the latest advancements in clinical diagnostic and therapeutic strategies. The aim is to provide theoretical support and practical guidance for the precision medicine of asthmatic cough, thereby promoting in-depth exploration and clinical application in this field.
This narrative synthesis proposes a hypothesis-generating, phenotype-stratified management algorithm for refractory GERC based on available evidence and clinical experience; prospective multicenter validation is needed to confirm its generalizability and long-term clinical efficacy. Gastroesophageal reflux-induced cough (GERC) accounts for 10–21% of chronic cough cases, with up to 43–75% presenting without typical heartburn or regurgitation. Current diagnostic frameworks lack translation into mechanism-specific treatment algorithms, leaving clinicians with empirical trial-and-error when standard acid suppression fails. This synthesis integrates six objective diagnostic metrics—acid exposure time, non-acid reflux episodes, cough-specific symptom association probability, post-reflux swallow-induced peristaltic wave index, mean nocturnal baseline impedance, and lower esophageal sphincter dual-defect—to classify four mechanistically distinct phenotypes (Types A–D), each matched to targeted therapy based on a comprehensive narrative synthesis of published therapeutic trials. The following response rates are derived from previously published historical cohorts and are not original data from the present study. In published historical cohorts, phenotype-matched therapy was associated with superior outcomes: Type B (clearance failure/non-acid) achieved 81.5% response with prokinetic combination versus 5.3% with escalated proton pump inhibitor monotherapy; Type C (structural dual-defect) attained 92% proton pump inhibitor-free status at 5 years post-fundoplication; Type D (cough hypersensitivity) showed 72% cough improvement with transoral incisionless fundoplication in cough-predominant patients; Type A (acid-dominant) received optimized potassium-competitive acid blocker suppression as the reference pathway. Structured deprescribing minimized polypharmacy for responders, while salvage pathways prioritized surgery for mechanical phenotypes. This phenotype-driven algorithm provides a mechanism-informed framework for managing refractory GERC, translating objective diagnostic metrics into targeted therapeutic escalation. Prospective validation is warranted to confirm improved clinical outcomes and cost-effectiveness.
Background Pulmonary arterial hypertension (PAH) is a progressive disease that affects the central nervous system. The cardiopulmonary-brain axis hypothesis links right ventricular dysfunction to cerebral hypoperfusion, yet the association between regional cerebral blood flow (CBF) alterations, right heart dysfunction, and the clinical utility of CBF for risk stratification remains poorly understood. Objectives To investigate the association between CBF and right heart dysfunction in patients with PAH, and to evaluate the potential of CBF as a non-invasive biomarker for risk stratification. Design Cross-sectional, retrospective study. Methods Thirty PAH patients and 51 age- and sex-matched healthy controls (HCs) were retrospectively identified. Brain MRI data, including 3D arterial spin labeling (ASL) at 3.0 T for CBF quantification were analyzed. For the PAH cohort, clinical assessment included right heart catheterization (RHC) and transthoracic echocardiography (TTE) to evaluate the structure of the right ventricle (RV) and hemodynamics. Patients were stratified into low and intermediate/high-risk groups according to the 2022 ESC/ERS guidelines. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory value of CBF for risk stratification. Generalized Linear Models were applied to analyze associations between CBF, cardiac and hemodynamic parameters, and neuropsychological metrics. Results Compared with HCs, PAH patients exhibited significant regional hypoperfusion, predominantly in the right hippocampus, frontal gyri, and insula. Regional CBF values correlated inversely with RV area (systolic RV area and right caudate: r = -0.569, P = 0.006, systolic RV area and right thalamus: r = -0.587, P = 0.004, diastolic RV area and right caudate: r = -0.513, P = 0.012, diastolic RV area and right thalamus: r = -0.545, P = 0.007) and septal thickness (right superior frontal gyrus: r = -0.528, P = 0.015, left anterior cingulate: r = -0.495, P = 0.024). Notably, intermediate/high-risk patients demonstrated significantly lower CBF compared to low-risk patients, particularly in the parietal and frontal cortices. ROC analysis indicated that regional CBF, in addition to patient sex and age, could distinguish intermediate/high-risk patients from low-risk patients (right superior frontal region: AUC = 0.793, Sensitivity = 71%). Additionally, reduced CBF in the insula was associated with lower Mini-Mental State Examination (MMSE) scores. Conclusion This study demonstrates that cerebral hypoperfusion in PAH is closely associated with right ventricular dysfunction and disease severity. ASL-derived CBF holds promise as a non-invasive biomarker to refine risk stratification, offering novel insights into the cardiopulmonary-brain interaction.
Background Sodium−glucose cotransporter−2 inhibitors (SGLT2 inhibitors) confer broad cardiovascular benefits, but their role in pulmonary arterial hypertension (PAH) remains unclear. Objective To investigate the potential therapeutic role of SGLT2 inhibitors in PAH by evaluating their longitudinal association, including improvement in risk profile, functional status, and ventricular coupling. Design Multicenter retrospective longitudinal pilot study. Methods Adults with Group 1 PAH confirmed by right heart catheterization were followed and categorized by exposure to SGLT2 inhibitors. Time-to-clinical improvement was assessed using Cox proportional hazard models adjusted for age, gender, PAH etiology, pulmonary vascular resistance, and baseline risk profile. Two predefined endpoints were evaluated: (1) improvement by ≥ 1 category in a four-level risk stratification, and (2) achievement of a low-risk profile. Longitudinal changes in functional, biomarkers, and echocardiographic measures were analyzed using linear mixed-effects models adjusting for relevant covariates. Results Among 83 patients with PAH, 43 received SGLT2 inhibitors. SGLT2 inhibitor use was independently associated with a higher rate of improvement by ≥ 1 risk category (hazard ratio [HR] 2.21, 95%CI 1.06−4.63; p = 0.034) and a higher likelihood of achieving a low risk profile (HR 2.62, 95% CI 1.02−6.76; p = 0.045). Longitudinal improvement was observed across the cohort in six-minute walk distance, Borg dyspnea score, B-type natriuretic peptide (BNP) levels, and composite risk score (all p <0.001), with SGLT2 inhibitor use associated with greater improvement in persistently lower log-BNP levels during follow-up (p = 0.007). Echocardiographic demonstrated reductions in pulmonary artery systolic pressure and improvement in RV-pulmonary artery coupling over time. Conclusion In this real-world cohort, SGLT2 inhibitor use was associated with a higher likelihood of clinical improvement and achieving a low-risk profile in PAH, alongside favorable longitudinal changes in biomarkers and hemodynamics. Prospective randomized trials are warranted.
Exacerbations of chronic obstructive pulmonary disease (COPD) are significantly associated with poor prognosis and impose a substantial socioeconomic burden. As an emerging concept in the field of precision medicine, treatable traits can help identify the characteristics most closely linked to clinical outcomes of the disease, thereby guiding precise treatment. In recent years, research on treatable traits in the context of COPD exacerbations has gradually deepened, covering pulmonary, extrapulmonary, and behavioral-risk aspects. This paper summarizes the research progress of treatable traits related to COPD exacerbations and outlines the identification and intervention approaches for these relevant traits, aiming to contribute to the clinical practice of precision diagnosis and treatment for COPD exacerbations.
Background Although hospitalization in idiopathic pulmonary fibrosis (IPF) is associated with poor outcomes, it occurs during the disease course and may lead to overestimation of its prognostic impact when analyzed as a fixed exposure. Objectives We aimed to evaluate the association between hospitalization and transplantation-free survival in patients with IPF by modeling hospitalization as a time-dependent exposure and applying a standardized definition of respiratory-related hospitalization. Design This was a retrospective cohort study conducted at Asan Medical Center, a tertiary referral center in Seoul, South Korea. Methods A total of 223 patients with IPF were included. Hospitalization was treated as a time-dependent exposure in Cox regression models. Changes in pulmonary function and exercise capacity before and after hospitalization were assessed using linear mixed-effects models. Results Seventy patients (31%) experienced hospitalization during follow-up, whereas 153 (69%) did not. Hospitalized patients had significantly worse lung function and exercise capacity at baseline compared with non-hospitalized patients. When modeled as a time-dependent exposure, hospitalization was strongly associated with increased risk of transplantation or death (adjusted hazard ratio: 8.87, 95% confidence interval [CI]: 5.57–14.11; P <0.001). After excluding patients who died within 10 days of hospitalization, long hospital stay (≥10 days) was associated with poorer transplantation-free survival than short stay (<10 days) ( P =0.022). Pulmonary function and exercise capacity declined significantly during hospitalization. Forced vital capacity decreased both before (−7.6%, 95% CI: −11.2 to −4.1; P <0.001) and after hospitalization (−4.8%, 95% CI: −9.4 to −0.2; P =0.04). Minimum oxygen saturation during the six-minute walk test decreased significantly both before (−2.5%, 95% CI: −3.8 to −1.3; P<0.001) and after hospitalization (−2.3%, 95% CI: −4.4 to −0.3; P=0.029). Conclusion Hospitalization in IPF was associated with poorer transplantation-free survival and subsequent physiological decline. It may serve as an important time-dependent marker of clinical deterioration and disease progression.
Background Antifibrotic therapy slows disease progression in idiopathic pulmonary fibrosis (IPF), but substantial prognostic heterogeneity persists among treated patients. Serum Krebs von den Lungen-6 (KL-6) is a biomarker of alveolar epithelial injury, but its prognostic value in IPF patients receiving antifibrotic therapy is not well established. Objectives This study aimed to investigate factors associated with all-cause mortality during follow-up in IPF patients receiving antifibrotic therapy and to evaluate the clinical value of baseline serum KL-6 levels in prognostic assessment. Design This was a single-center retrospective cohort study. Methods Patients diagnosed with IPF who received antifibrotic therapy between July 2022 and November 2024 were consecutively enrolled. Baseline clinical data and serum KL-6 levels were collected. Cox proportional hazards regression was used to identify factors associated with mortality risk, and receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of KL-6. Results A total of 126 patients with IPF receiving antifibrotic therapy were included. During a median follow-up of 21 months, 24 patients (19.0%) died. Non-survivors had significantly higher baseline KL-6 levels (P = 0.002), a higher prevalence of chronic obstructive pulmonary disease and cardiovascular disease, and lower baseline lymphocyte counts and percentage of predicted forced vital capacity (FVC% pred) compared with survivors. Multivariable Cox regression showed that cardiovascular disease (HR = 5.15, 95% CI: 1.86-14.24), lymphocyte count (HR = 0.50, 95% CI: 0.27-0.93), FVC% pred (HR = 0.98, 95% CI: 0.96-0.99), and baseline KL-6 level (per 100 U/mL increment, HR = 1.05, 95% CI: 1.02-1.07) were independently associated with all-cause mortality. ROC analysis identified an optimal KL-6 cut-off value of 746 U/mL. Patients with high KL-6 were associated with a markedly increased risk of death (HR = 7.57, 95% CI: 1.78-32.2). Conclusions In IPF patients receiving antifibrotic therapy, elevated baseline serum KL-6 level is independently associated with increased all-cause mortality. A cut-off value of 746 U/mL may help identify high-risk patients, and combining KL-6 with comorbidity burden, immune status, and lung function could facilitate individualized risk stratification.
Background Antifibrotic agents slow disease progression and improve survival in IPF, yet real-life data on their use in Turkey are limited. Objectives This study aimed to compare the side effects of antifibrotics in IPF patients. Design A cross-sectional survey was conducted in 8 centers across 6 provinces in the Aegean Region. Methods There were 470 IPF patients who completed a 30-item face-to-face questionnaire. Adverse events and their management were compared between pirfenidone and nintedanib users. Results Among 470 patients, 50.6% used pirfenidone and 49.4% nintedanib. Overall, 70.6% reported at least one side effect (75.5% nintedanib vs. 66% pirfenidone, p=0.023). Medical treatment was required in 30.9% and dose reduction in 18.9%. The most common side effects were diarrhea (30.6%), appetite loss (24.9%), and nausea (22.3%). Diarrhea (p<0.001) and weight loss (p=0.010) were more frequent with nintedanib, while rash, photosensitivity, and fatigue were more common with pirfenidone (all p<0.001). Nausea, vomiting, appetite loss, and fatigue were more frequently reported in women, and vomiting, anorexia, and rash were more frequently observed in patients with comorbidities. Conclusion Adverse events are frequent in IPF patients receiving antifibrotics. Nintedanib mainly causes gastrointestinal symptoms, whereas pirfenidone leads to skin reactions and fatigue. Female sex and the presence of comorbidities were associated with a higher frequency of certain adverse events. Supportive treatment and dose adjustments are crucial for maintaining adherence.
Achromobacter species (spp) is an emerging opportunistic organism more frequently isolated from immunocompromised patients’ and hospital settings. This bacterium was once considered an environmental bacterium, but now it is recognized as a serious cause of respiratory infections, bloodstream infections, and urinary tract infections, particularly among patients with cystic fibrosis (CF), chronic illnesses, and medical devices. The purpose of this review is to highlight Achromobacte ’s clinical significance, pathogenic mechanism, and recent approaches for diagnosis and treatment. By utilizing specific keywords relevant to Achromobacter spp., a comprehensive literature search was performed in PubMed and Google Scholar. To summarize existing knowledge and highlight gaps in the literature, peer-reviewed studies on clinical relevance, pathogenicity, antimicrobial resistance, and therapeutic approaches were gathered, screened, and narratively assembled. Among the 19 identified species, Achromobacter xylosoxidans ( A. xylosoxidans) is the most prevalent and clinically relevant, especially in CF settings. This review explores the organism’s microbiological characteristics, virulence strategies—including robust biofilm formation, motility, and secretion systems—and its alarming intrinsic and acquired resistance to antibiotics. Misidentification due to phenotypic overlap with other non-fermenting Gram-negative bacilli complicates diagnosis, while limited MALDI-TOF MS and database representation hinders species-level identification. Genotyping methods, including multi-locus sequence analysis and housekeeping gene sequencing, offer superior resolution but remain underutilized in clinical diagnostics. With rising resistance mediated by β-lactamases, efflux pumps, and adaptive genomic traits, Achromobacter spp presents a growing challenge for treatment and infection control. This review highlights the urgent need for improved diagnostic strategies, species-level clinical and microbiological data, and tailored therapeutic approaches to manage Achromobacter spp. infections effectively.
Short telomere syndromes (STS) are rare telomere biology disorders caused by germline variants affecting telomere maintenance and may present with organ-limited disease (e.g., pulmonary fibrosis) or multisystem involvement. We report a Vietnamese family carrying a heterozygous TERT p. Ala880Thr variant. The proband was a 42-year-old man with cryptogenic cirrhosis who was incidentally found to have a probable usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) and later developed progressive interstitial lung disease (ILD). He also had marked premature graying, platypnea, digital clubbing, and hepatopulmonary syndrome. Cascade evaluation identified two monozygotic twin sisters (41 years) who also had ILD with discrepant severity: one symptomatic with probable UIP and FVC 47% predicted, while the other was asymptomatic with mild probable UIP changes and FVC 84% predicted. Further pedigree assessment identified maternal cryptogenic cirrhosis and two siblings who died in early childhood with transfusion-dependent anemia, suggesting additional hepatic and hematologic manifestations within the family. Panel-based targeted NGS identified the heterozygous TERT p. Ala880Thr variant in the proband and one affected twin sister, and targeted Sanger sequencing confirmed the familial variant in additional relatives. This case series provides detailed clinical and segregation data from a Vietnamese kindred carrying the previously reported TERT p. Ala880Thr variant. It also highlights the need to suspect telomere-related disease when ILD presents at a young age or is accompanied by extrapulmonary features such as cryptogenic liver disease, premature graying, or a suggestive family history. Early genetic testing and cascade counseling may improve recognition and longitudinal surveillance of at-risk relatives.
Background In non-cystic fibrosis bronchiectasis, small airway airflow limitation is primarily driven by mucus plugging, chronic neutrophilic inflammation, and epithelial injury. These primary mechanisms lead to subsequent airway remodelling and luminal narrowing. Such functional impairment is clinically significant, as a reduced distance–saturation product (DSP) of <280 m% during the 6-minute walk test (6MWT) is associated with increased mortality. Objective To evaluate the association between small airway dysfunction (SAD), exercise-induced desaturation (EID), and impaired exercise capacity in patients with bronchiectasis. Design A retrospective, cross-sectional study. Methods This retrospective study included 114 patients with bronchiectasis (non-desaturators, n = 57; desaturators, n = 57) and 53 non-bronchiectasis controls. Impulse oscillometry (IOS), spirometry, and 6MWT data were analysed. Desaturators were defined as a maximal decline in peripheral oxygen saturation (ΔSpO 2 ) ≤ −4% during the 6MWT. Results Compared with bronchiectasis non-desaturators (n = 57), desaturators (n = 57) exhibited more pronounced IOS-defined SAD, characterised by higher R 5 –R 20 , F res , and A X , and lower X 5 , as well as spirometry-defined SAD with lower MMEF%pred and FEF50%pred. Desaturators also demonstrated a shorter 6-minute walk distance (6MWD). Greater R 5 –R 20 , F res , and A X , and lower X 5 , MMEF%pred, and FEF50%pred were associated with a larger reduction in ΔSpO 2 , shorter 6MWD, and lower DSP. The multiple linear regression showed age, BRICS, and R 5 -R 20 are independent predictors for DSP. Among them, R 5 -R 20 (β=-0.345) is a stronger predictor than BRICS (β=-0.285) for DSP. Conclusion SAD is independently associated with EID and reduced exercise capacity in bronchiectasis, highlighting its potential role as a functional marker beyond structural disease severity.
Pulmonary aspergillosis refers to a spectrum of lung diseases caused by Aspergillus species, ranging from allergic manifestations such as allergic bronchopulmonary aspergillosis (ABPA) to chronic and invasive forms, including chronic cavitary pulmonary aspergillosis (CCPA) and aspergilloma. The coexistence of ABPA and aspergilloma is uncommon and poses unique therapeutic challenges, particularly in those unsuitable for surgical intervention. We present the case of a 26-year-old female with CCPA and concomitant ABPA. Despite prolonged antifungal therapy, imaging revealed a persistent left upper lobe aspergilloma accompanied by elevated total and Aspergillus -specific IgE levels. She subsequently underwent bronchoscopic debridement with peri-procedural itraconazole. Following the procedure, she demonstrated significant clinical and immunologic improvement, with more than a 20% reduction in IgE levels and normalization of pulmonary function, which had previously shown a restrictive pattern. This case highlights that a multimodal, minimally invasive approach integrating bronchoscopic debridement with peri-procedural antifungal therapy, offers a viable and effective alternative for non-surgical candidates, promoting both functional and immunologic recovery.
Background Endobronchial hamartoma and leiomyoma are rare benign airway tumors that may cause significant airway obstruction and require bronchoscopic intervention. However, comparative data on their clinical characteristics and interventional outcomes, particularly according to anatomic location, remain limited. Objectives The objective of this study was to compare the clinical characteristics and bronchoscopic resection outcomes of endobronchial hamartoma and leiomyoma, with a focus on the impact of airway location. Design This study was a retrospective observational cohort study conducted over a 21-year period at a single tertiary referral center. Methods In this retrospective cohort study, we analyzed 107 patients with benign airway tumors, specifically comparing 56 hamartomas and 51 leiomyomas. Data on clinical presentation, radiologic findings, and bronchoscopic intervention outcomes were collected. A stratified analysis by airway level (trachea to segmental bronchi) was performed. Results Endobronchial leiomyomas were predominantly located in the central airways (trachea, 29.4%), while endobronchial hamartomas were more frequent in peripheral bronchi (segmental, 35.7%; P for trend = 0.011). Peripheral tumors showed significantly higher degrees of stenosis ( P for trend < 0.001) and more frequent secondary CT findings, such as obstructive pneumonia. The complete resection rate was significantly higher for leiomyomas than for hamartomas (94.1% vs . 80.4%; P = 0.035). However, this difference was driven by anatomic location rather than histology; complete resection rates declined from 100% in the trachea to 64.5% in the segmental bronchi ( P for trend < 0.001). Major complications included three pneumothoraxes and one massive hemorrhage during distal airway dissection. No recurrences occurred during a median follow-up of 10 months. Conclusion Bronchoscopic resection is highly effective for benign airway tumors. Anatomic location, rather than histological subtype, is the primary determinant of procedural success and technical difficulty. Meticulous preoperative anatomical mapping is essential to identify danger zones near major vessels and optimize therapeutic strategies.
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by persistent airflow limitation and driven by interconnected pathways of oxidative stress, inflammation, and cell death. While nuclear factor E2-related factor 2 (Nrf2) is well-established as a central regulator of antioxidant defense, its role in COPD is now understood to be far more extensive. Beyond redox balance, Nrf2 modulates inflammatory responses and critical processes like autophagy, apoptosis, and ferroptosis, highlighting its pleiotropic nature and therapeutic potential. This review delineates the multifaceted functions of Nrf2 in COPD and explores its promise as a target for precision therapy, providing a foundation for future research and drug development.
Background Asthma is a common respiratory disease with a high disease burden in China. The patient population with severe asthma remains largely unexplored. Objectives To describe the disease burden, treatment pattern and eosinophilic phenotype of Chinese patients with moderate-to-severe asthma. Design This is a retrospective baseline analysis of the real-world, observational, multicenter PRESENT study (NCT06422663). Methods Patients receiving Global Initiative for Asthma Step 3–5 treatment were categorized into protocol-specified severe asthma (uncontrolled asthma with medium-dose inhaled corticosteroids [ICS], or asthma with high-dose ICS) and moderate asthma subgroups. This baseline analysis reported patient characteristics, disease burden, treatment patterns, eosinophilic phenotype and testing rates of biomarkers at enrolment. Disease burden was assessed by historical asthma exacerbation rate within the past year, Asthma Control Test (ACT) score and lung function. Results Of the 498 patients included, 203 (40.8%) were identified as having protocol-specified severe asthma. Notable disease burden was observed, as reflected by the high proportion of patients experiencing asthma exacerbation (severe asthma: 35.0%; moderate asthma: 14.6%), low ACT score (mean [SD]: severe asthma: 17.4 [3.8]; moderate asthma: 20.6 [3.7]) and declined pre-bronchodilator forced expiratory volume in one second (pre-BD FEV 1 ; median [interquartile range]: severe asthma: 2.0 [1.5, 2.5]; moderate asthma: 2.2 [1.7, 2.8]). Overall, testing rates of blood eosinophil (EOS) were 25.3% (in the past seven days), 49.0% (in the past three months) and 68.9% (in the past one year). Among patients who tested EOS once and twice in the past one year, 62.5% (180/288) and 76.4% (42/55) had blood EOS counts ≥150 cells/μL, respectively. Testing rates of different biomarkers varied but were generally low. Conclusion Notable disease burden and sub-optimal management were observed in Chinese patients with moderate-to-severe asthma. Biomarker-based phenotyping of severe asthma was unsatisfactory. Treatment escalation and routine monitoring of blood EOS level might be considered. Registration ClinicalTrials.gov , NCT06422663, registered on March 19, 2024, https://clinicaltrials.gov/study/NCT06422663 .
Background Malnutrition is common in patients with idiopathic pulmonary fibrosis (IPF), and potentially affects the tolerability of antifibrotic therapy and survival. The prognostic nutritional index (PNI) is a validated prognostic marker in various diseases; however, its role in antifibrotic therapy remains unclear. Objectives To investigate associations between the PNI and adverse effects associated with nintedanib, treatment discontinuation, and survival in patients with IPF. Design Multicenter retrospective study. Methods Data from 167 Japanese patients with IPF who received nintedanib therapy were retrospectively analyzed. Information on clinical characteristics, laboratory data, and adverse events was collected, and the PNI was calculated. The optimal PNI cut-off value was determined using receiver operating characteristic (ROC) curves. Risk factors for treatment discontinuation and survival were identified using Cox proportional hazards models. Results The median treatment duration and survival time were 18 and 55 months, respectively. The PNI was significantly higher in patients who experienced nintedanib-associated adverse effects than in those who did not. ROC curve analysis identified an optimal PNI cut-off value of 47.3. Patients with a high PNI had significantly longer treatment durations and survival than those with a low PNI. Multivariate analyses identified the PNI as the only factor independently associated with both time to nintedanib discontinuation and survival. Conclusion The PNI predicted treatment feasibility and survival in patients with IPF. These findings highlight the clinical utility of the PNI as a dual biomarker of nutritional status and demonstrate its potential to guide individualized treatment strategies based on nutritional status.
BACKGROUND:Patient-reported outcome measures are essential tools for assessing disease burden in bronchiectasis. The Quality of Life-Bronchiectasis questionnaire (QoL-B) is widely used in clinical research, but a validated Italian version has not been available. OBJECTIVES:To perform a cross-cultural validation of the Italian QoL-B in a real-world cohort of patients with bronchiectasis. DESIGN:Prospective observational cross-cultural validation study. METHODS:Adult patients with bronchiectasis attending a tertiary referral clinic were prospectively enrolled. The Italian QoL-B was administered at baseline (T0) and after 15 days (T1) in clinically stable patients to assess internal consistency and test-retest reliability. Construct validity was evaluated through predefined hypotheses by comparing QoL-B domain scores across clinically relevant subgroups, including exacerbation frequency, dyspnea severity, lung function impairment, and Bronchiectasis Severity Index (BSI) class. Exploratory analyses assessed score variation during exacerbations. RESULTS:A total of 108 patients were included (median age 64.5 years; 75.9% female). Internal consistency was good across domains (Cronbach's α 0.78-0.89), and test-retest reliability showed stable scores between T0 and T1 with high intraclass correlation coefficients. Construct validity was supported by significant discrimination across disease-burden groups: patients with frequent exacerbations, severe BSI class, or greater dyspnea reported consistently lower scores, particularly in physical functioning and respiratory symptoms domains. The Emotional Functioning domain showed weaker associations with disease severity indicators and was primarily related to mood disorders. QoL-B scores were substantially lower during exacerbations. CONCLUSION:The Italian QoL-B demonstrates good reliability and construct validity and provides a robust instrument for assessing quality of life in Italian-speaking patients with bronchiectasis.
Background: Biologic therapy uptake for poorly controlled severe asthma is suboptimal despite guideline recommendations. Objectives: To evaluate real-world biologic initiation trends and predictors among patients with severe uncontrolled asthma (SUA) and SUA with eosinophilic phenotype (SUA-EP). Design: A retrospective real-world cohort study that used Komodo Health administrative claims to identify US patients with SUA (controller/rescue medication use and ⩾2 asthma exacerbations in a year) and a subgroup of patients with SUA-EP (blood eosinophil count ⩾150 cells/µL in the year pre- or post-exacerbation). Methods: Biologic initiation trends following first asthma exacerbation were assessed, and factors associated with lack of biologic initiation following second exacerbation (SUA-EP only) were identified using LASSO regression models; odds ratios (OR), 95% confidence intervals (CIs), and p -values were calculated using logistic regression. Results: Biologic initiation rates following the first exacerbation were low at 12.7% (4360/34,246) and 12.2% (309/2526) of patients with SUA and SUA-EP, respectively; mean time between second exacerbation and initiation was 13.4 and 11.9 months. Predictors of lack of biologic initiation included young age (12–17 years; OR (95% CI) 3.65 (1.69–7.89)), primary care physician specialty at index relative to respiratory specialist (2.89 (2.04–4.10)), and antibiotic use (2.29 (1.44–3.66); all p < 0.05), indicating that younger patients, those managed by primary care and those treated with antibiotics for exacerbations, were less likely to receive biologics. Biologic initiation was more likely among patients with a cumulative systemic corticosteroid dose ⩾500 mg (prednisone equivalent; 0.38 (0.25–0.57)), those using leukotriene modifiers (0.42 (0.28–0.62)) or single-inhaler triple therapy (0.06 (0.01–0.40)), and those with eosinophilic disorders (0.19 (0.07–0.52); all p < 0.05). Conclusion: Despite eligibility, most patients with SUA and SUA-EP did not receive any biologic; younger age and primary care management were predictors of lack of biologic initiation. This highlights the need for improved specialist referral and biologic uptake.
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with progressive, irreversible scarring and a median survival of approximately 3–5 years after diagnosis. Current therapies (nintedanib, pirfenidone) modestly slow progression but do not halt or reverse fibrosis, creating a critical therapeutic plateau and unmet need. Improved human-centric models are essential to dissect how genetic susceptibility and chronic epithelial exhaustion drive aberrant repair in IPF. Lung organoids, as three-dimensional (3D) constructs that recapitulate human lung architecture and cellular responses to pathological cues have increasingly been used as important human-relevant platforms for IPF research. In this review, we summarize recent advances in the application of lung organoids to IPF research, including disease modeling, mechanistic studies, and preclinical drug testing, and we discuss the potential and current limitations of patient-derived organoids (PDOs) in personalized medicine. We also outline ongoing efforts to improve these models through the incorporation of vascular, immune, and mechanical components, such as assembloids and lung-on-a-chip systems. Although important challenges remain, including maturation, standardization, and scalability, lung organoids may provide a valuable complementary platform for future IPF research and translational studies.
