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Biologic Therapies and Biomarkers in Severe Childhood Asthma: A Systematic Review of Omalizumab and Mepolizumab.3 days agoSevere asthma in children is challenging to manage due to high exacerbation rates and significant impacts on quality of life. Despite corticosteroids and bronchodilators, many patients remain symptomatic, highlighting the need for alternative treatments. Biologic therapies, such as omalizumab and mepolizumab, offer potential to reduce exacerbations and oral corticosteroid use. This study aimed to evaluate the efficacy of novel biologic therapies in managing severe pediatric asthma.
A systematic review was conducted following the PRISMA protocol and registered on PROSPERO (CRD42025634956). Studies published between January 2019 and December 2024 were included. Eligible articles were randomized clinical trials, cohort, and case-control studies involving biologic therapies, excluding those with adults, animals, or unrelated topics. Data extraction was performed in Microsoft Excel, and bias was assessed using the Newcastle-Ottawa tool and the Jadad scale.
Most trials analyzed omalizumab, with only one evaluating mepolizumab. These therapies significantly reduced asthma exacerbations, with effects sustained up to 6 years. Reductions in hospitalizations, PICU admissions, and ED visits were noted. Most studies used manufacturer-recommended doses, while some adjusted doses based on weight and/or IgE levels. Pulmonary function improved in seven studies (increased FEV1), while three showed no significant changes. A reduction in inhaled and oral corticosteroid use, FeNO, and eosinophil levels was observed, suggesting reduced airway inflammation. Most patients tolerated therapies well, with mild adverse events reported.
Biologic therapies, particularly omalizumab, show promising clinical benefits for managing severe pediatric asthma. Further studies are needed to assess their long-term safety and effectiveness.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
The prevalence and unique clinical features of CPFE among patients with connective tissue disease-associated interstitial lung disease: a retrospective, real-world study.3 days agoCombined pulmonary fibrosis and emphysema (CPFE) is a distinct yet clinically underrecognised syndrome. Interstitial pneumonia is a common pulmonary manifestation of connective tissue diseases (CTDs), and some CTD-interstitial lung disease (CTD-ILD) patients have concurrent emphysema that is frequently overlooked clinically.
This study explored the clinical characteristics and factors associated with emphysema in CTD-ILD patients to guide clinical management.
This single-centre retrospective study included patients with CTD-related lung diseases from the ILD database of Xiangya Hospital. Patients were screened with standardised respiratory disease keywords and verified by chest HRCT. All eligible cases were stratified into CTD-ILD and CTD-CPFE groups based on emphysema presentation on re-assessed HRCT images.
Admission data, including demographics, comorbidities, inflammatory biomarkers, autoimmune antibodies, HRCT findings, pulmonary function test results and in-hospital treatment information, were collected for subsequent grouped analysis.
445 CTD-ILD patients were included, and 48 (10.8%) were CPFE. Patients with CPFE were predominantly male (68.8%), had a higher prevalence of a smoking history (68.8% vs 31.2%, p < 0.001), a lower body mass index (BMI) (20.4 vs 22.2 kg/m2, P = 0.004), and a higher prevalence of prior tuberculosis (TB) (14.6% vs 4.3%, p = 0.009). Multivariable regression analysis showed that sex, BMI, smoking status, and history of TB were independently associated with CPFE. Male sex was associated with a markedly increased likelihood of CPFE (p = 0.003). TB was associated with increased likelihood, whereas higher BMI was associated with reduced likelihood (odds ratio: 33 and 0.57, respectively).
CTD-CPFE may represent a distinct subgroup within CPFE, with several characteristic features, including a relatively lower prevalence of smoking history. A low BMI and a history of TB were associated with the presence of CPFE, highlighting the potential importance of nutritional and immune status in patients with CTD-ILD.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Comparing Multiple Breath Washout Parameters in a Matched Cohort of Children With Cystic Fibrosis and Primary Ciliary Dyskinesia.3 days agoCystic Fibrosis (CF) and primary ciliary dyskinesia (PCD) are congenital disorders characterized by impaired mucociliary clearance, resulting in chronic airway infection, inflammation, and progressive lung damage. CF lung disease involves defective CFTR function throughout the entire airway epithelium, whereas PCD originates from dysfunction of motile respiratory cilia located predominantly in proximal airways. Diagnostic tools such as FEV1 lack sensitivity to detect early peripheral lung damage. Lung clearance index (LCI), obtained via multiple breath washout (MBW), has emerged as a promising marker for early detection of lung abnormalities.
To compare LCI between age and FEV1-matched people with (pw) CF and PCD (without highly effective CFTR modulator treatment), hypothesizing more abnormal LCI in CF due to more peripheral airway involvement. Secondary objectives included comparing phase III slope parameters (Scond x VT, Sacin x VT) to explore ventilation inhomogeneity and localization of lung disease.
This retrospective cross-sectional study included pwCF and pwPCD aged 6-20 years with available MBW and spirometry data (2011-2024).
PwCF (n23, median age 14.4 y) had similar FEV1 z-scores compared to 23 pwPCD (median age 14.4 y) (-0.1 vs. -1.1, p: 0.33). LCI values were more abnormal in the CF group compared to the PCD group (7.8 vs. 7.1; p: 0.04). FEF25-75%pred and phase III slope parameters were not significantly different, though a trend toward higher Scond x VT in CF was noted (0.08 vs. 0.06; p: 0.11).
Despite similar FEV1 abnormalities, reflecting proximal airway impairment, pwCF exhibit greater peripheral airway involvement than pwPCD, as indicated by higher LCI values.Chronic respiratory diseaseCardiovascular diseasesAccessAdvocacy -
Clinical Feasibility and Safety of Nasal Allergen Provocation Testing in Pediatric Allergic Rhinitis.3 days agoNasal allergen provocation testing (NAPT) has been shown to be a safe and reproducible test in adults; however, pediatric data are limited. This study aims to investigate the clinical applications, feasibility, reproducibility and safety of NAPT in the pediatric population.
In this prospective study, 294 patients (4.16-14.25 years old, mean of 7.33 years), with symptoms and medical history of allergic rhinitis (AR) and IgE-mediated sensitization to Dermatophagoides pteronyssinus and Dermatophagoides farinae were recruited. Participants underwent NAPT with negative control and with increasing concentrations of crude Dermatophagoides farinae (50 µg/ml, 500 µg/ml, and 5000 µg/ml) at 15 min intervals. Pre- and post-test subjective symptom scores and objective active anterior rhinometry measurements were analyzed.
Among the 245 participants (83.3%) with a positive NAPT, the majority (n = 193, 78.8%) tested positive at 500 µg/ml or less. They (n = 226, 92.2%) were diagnosed based on an increase in total nasal symptoms score (TNSS) ≥ 5 points. The remaining 7.8% (n = 19) required objective measurements to fulfill the criteria for a positive result. Five participants were unable to fully comply with the instructions provided. There were no adverse events recorded during the study. The group which tested positive on NAPT recorded higher sIgE levels than that which tested negative. Furthermore, those with higher serum sIgE levels tested positive on NAPT at lower allergen concentrations. The baseline visual analog scale (VAS) was significantly higher in the group testing positive on NAPT at the lowest allergen concentration, compared with the other groups.
Our study demonstrates that NAPT is safe and feasible to be conducted on the pediatric population.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
A Case-Control Study of Factor V Leiden G1691A and MTHFR A1298C Polymorphisms and Clinical Outcomes in Patients With COVID-19.3 days agoThe clinical relevance of inherited thrombophilia-related polymorphisms in COVID-19 remains uncertain. This study investigated the distribution of Factor V Leiden (FVL) G1691A and MTHFR A1298C polymorphisms in patients with COVID-19 and associations with laboratory findings and short-term mortality.
This case-control study included 150 patients with PCR-confirmed COVID-19 and 300 controls. Genomic DNA was isolated from peripheral blood, and FVL G1691A and MTHFR A1298C polymorphisms were analyzed. Associations with d-dimer levels, hospitalization duration, and 30- and 90-day mortality were evaluated using multivariable linear and Cox regression analyses.
The FVL GG genotype was less frequent in patients than controls (77.3% vs. 87.0%, p = 0.009), whereas the MTHFR AA genotype was more frequent (76.7% vs. 61.3%, p = 0.001). Heterozygosity in both genes did not differ between groups (8.0% vs. 6.3%, p = 0.552). Patients with heterozygosity in both genes had higher d-dimer levels (median 435.0 vs. 201.0 ng/mL, p = 0.024) and longer hospitalization (median 7.5 vs. 5.0 days, p = 0.037). After adjustment, heterozygosity in both genes remained associated with higher log-transformed d-dimer levels (β = 0.758, 95% CI: 0.239-1.277; p = 0.005), as did MTHFR A1298C (β = 0.432, 95% CI: 0.007-0.856; p = 0.046). None of the polymorphisms was associated with 30- or 90-day mortality, while age independently predicted both outcomes.
Thrombophilia-related polymorphisms may influence d-dimer levels and hospitalization duration in COVID-19 but do not appear to affect short-term mortality.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Functional Exercise Capacity and Exploratory ICF-Aligned Interpretation of the Incremental Shuttle Walk Test in Children With Asthma.3 days agoChildren with asthma may experience functional exercise limitations that are not fully reflected by resting lung function or conventional clinical assessments. Field-based exercise tests provide complementary information regarding functional capacity, and the International Classification of Functioning, Disability and Health (ICF) offers a biopsychosocial framework to contextualize activity limitations. However, the integration of objective exercise performance with ICF-aligned interpretation in pediatric asthma remains limited.
To interpret functional exercise capacity in children with asthma using Incremental Shuttle Walk Test (ISWT) performance through an exploratory operational framework conceptually aligned with ICF activity qualifiers and to examine its association with lung function, asthma control, quality of life, and demographic characteristics.
In this cross-sectional study, 39 children with asthma (mean age 8.6 ± 2.3 years) underwent spirometry, completed the Asthma Control Questionnaire (ACQ-6) and the Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and performed the ISWT. Functional exercise capacity was expressed as a percentage of predicted ISWT distance and interpreted using an exploratory operational framework conceptually aligned with generic ICF activity qualifiers, generating two categories of activity limitation (mild/moderate and severe).
Resting lung function was relatively preserved (mean FEV1 82.0 ± 16.4% predicted), whereas functional exercise capacity was markedly reduced (mean ISWT 41.4 ± 18.7% predicted). Based on the exploratory ICF-aligned framework, 72% of participants were categorized as having severe activity limitation. Children with severe limitations walked significantly shorter distances than those with mild/moderate limitations (32.0 ± 11.5% vs. 65.3 ± 10.1% predicted; p < 0.001), with a very large effect size. Spirometric indices, asthma control, and quality of life scores did not differ between functional categories. ISWT performance was not correlated with lung function, asthma control, or quality of life and demonstrated a negative association with age.
Children with asthma may present substantial functional exercise limitations despite relatively preserved lung function and similar levels of asthma control and quality of life. The exploratory operational alignment of ISWT performance with generic ICF activity qualifiers may provide a clinically useful framework to support interpretation of activity limitations not captured by conventional assessments. However, this approach should be interpreted cautiously and requires future validation before broader clinical application.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Endoscopic Trichloroacetic Acid Chemocauterization for Recurrent Tracheoesophageal Fistula: A Single-Center Retrospective Cohort Study.3 days agoTracheoesophageal fistula (TEF) is a rare congenital anomaly commonly associated with esophageal atresia (EA-TEF). Management involves early surgical repair. TEF recurrence is not rare and repeat surgery carries significant complication risks. Endoscopic treatment is an alternative to iterative surgery. This retrospective case series describes the diagnosis, management, and outcomes of children treated with endoscopic chemocauterization for RTEF after EA-TEF surgical repair (RTEF) or isolated congenital TEF in our center.
We reviewed the charts of all patients who underwent endoscopic treatment for TEF at a single pediatric tertiary center from 2016 to 2023. Patients were divided into three groups: isolated congenital TEF, medium-sized or large recurrent RTEF. Chemocauterization was performed via rigid bronchoscopy by applying a trichloroacetic acid (TCA)-soaked cotton swab to the fistula. Postoperative follow-up included clinical assessment and bronchoscopy as indicated by clinical evolution.
Chemocauterization was performed on 13 patients following diagnosis of RTEF. A single chemocauterization procedure was sufficient for 12 patients, while three procedures were required for one patient. This patient developed aspiration pneumonia 1 month after his initial chemocauterization. No complications were observed in other patients. One patient was diagnosed with an isolated congenital TEF and benefited from endoscopic treatment as the primary approach, with a successful single procedure.
Endoscopic chemocauterization using TCA appears to be a safe and effective technique for managing RTEF. This study also presents a successful first-line endoscopic treatment of an isolated congenital TEF using chemocauterization. Further studies are needed to compare its effectiveness with surgery.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
A Narrative Review of the Correlation Between Comorbidity and Acute Exacerbation of COPD Patients.3 days agoChronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Most COPD patients have one or more additional chronic diseases (comorbidities), which significantly increase the risk of acute exacerbations-sudden worsening of symptoms that often lead to hospitalization and death.
A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, CBM, Web of Science, and Scopus databases until January 2026. Cohort studies, randomized controlled trials, real-world studies, and high-quality reviews were included for narrative synthesis and descriptive comprehensive analysis. No PROSPERO registration was performed as this is a narrative review, not a systematic review.
Over 70% of COPD patients worldwide have two or more comorbidities, with heart disease, diabetes, and high blood pressure being most common. These comorbidities increase acute exacerbation risk through multiple pathways: direct organ stress (heart failure increases risk 2.3-fold), immune dysfunction (diabetes raises hospitalization 1.8-fold), behavioral changes (depression/anxiety increase risk 1.5-2.1-fold), and self-management breakdown (cognitive impairment affects 32% of patients and drives medication non-adherence). Body-wide inflammation serves as a central biological mechanism linking lung disease to multi-organ damage. New prediction tools using artificial intelligence and dynamic risk scores improve forecasting of exacerbations. Additional about 30 papers were identified through the Snowball Method (citation tracking of included articles and reference list screening), ensuring comprehensive coverage of relevant evidence.
Comorbidities are not merely accompaniments to COPD but active drivers of acute exacerbations through interconnected biological and behavioral pathways. Effective COPD management requires integrated care that addresses heart disease, metabolic disorders, mental health conditions, and cognitive function alongside lung disease, using team-based approaches and locally adapted strategies.Chronic respiratory diseaseMental HealthAccessAdvocacyEducation -
Prevalence, Associate Factors, and Disease Awareness of Chronic Obstructive Pulmonary Disease: A Large-Scale Cross-Sectional Epidemiological Survey.3 days agoChronic obstructive pulmonary disease (COPD) represents a significant global health burden with substantial morbidity and mortality worldwide. While smoking remains the predominant associate factor, emerging evidence suggests biomass fuel exposure and other environmental factors contribute significantly to disease development. Large-scale epidemiological studies are essential to identify modifiable associate factors and inform evidence-based prevention strategies.
We conducted a cluster-sampling cross-sectional survey of 65,680 participants aged 35-75 years during Jan 2023 to Dec 2024, to investigate COPD prevalence and associated associate factors in Tianjin, China. COPD diagnosis was established using post-bronchodilator spirometry with FEV1/FVC<70% as the diagnostic criterion. Comprehensive associate factor assessment included demographic variables (age, gender), anthropometric measures (BMI), smoking status (never, current, former), biomass fuel use for cooking or heating, and chronic cough symptoms. Statistical analysis employed univariate comparisons and multivariate logistic regression modeling to identify independent associate factors, calculating odds ratios (OR) with 95% confidence intervals (CI).
The overall COPD prevalence was 7.9% (5,160/65,680 participants) with significant demographic variations. Mean participant age was 54.5±10.9 years, with 41.6% male representation. Multivariate logistic regression identified several independent associate factors: advancing age (OR=1.049, 95% CI: 1.046-1.052, P<0.001), male gender (OR=1.402, 95% CI: 1.312-1.499, P<0.001), current smoking (OR=1.560, 95% CI: 1.445-1.684, P<0.001), former smoking (OR=1.460, 95% CI: 1.306-1.631, P<0.001), and biomass fuel use (OR=1.470, 95% CI: 1.317-1.641, P<0.001). BMI and chronic cough showed no significant associations in the multivariate model.
This large-scale epidemiological study confirms a substantial COPD burden with multiple modifiable associate factors. Beyond traditional smoking risks, biomass fuel exposure emerges as a significant independent predictor, highlighting the importance of environmental interventions. These findings support comprehensive prevention strategies targeting smoking cessation and clean energy initiatives, particularly for high-risk populations including older males and those with environmental exposures.Chronic respiratory diseaseAccessAdvocacyEducation -
Construction and Validation of a Machine Learning Model Based on Clinical and Microbiomic Features for Predicting High Mucus Secretion in COPD.3 days agoTo evaluate clinical and airway microbiome features of excessive mucus secretion (CMH) in COPD progression and apply machine learning for CMH status identification.
A total of 319 COPD patients from Changzhi People's Hospital (May 2020-March 2024) were consecutively enrolled and divided by sputum volume and characteristics into a high mucus secretion group (n=173) and a non-high mucus secretion group (n=146). Patients were randomly assigned to training (80%) and testing (20%) sets. Airway microbiome structure was analyzed via 16S rRNA sequencing. From clinical and microbiome data, 70 features were extracted. Six machine learning algorithms (SVM, KNN, RF, BN, GBDT, NN) were used to build classification models. Feature selection employed filtering methods, and hyperparameters were optimized by 10-fold cross-validation. Model performance was assessed using sensitivity, specificity, accuracy, and AUC.
The CMH group and the non-CMH group differed significantly in a number of factors, including age, the length of the disease, and pulmonary function indices, according to a comparison of baseline patient data. Analysis of airway microbiome characteristics revealed that the CMH group had significantly lower observed ASVs and Shannon indices (p<0.001), along with significant enrichment of potentially pathogenic bacterial genera such as Haemophilus and Pseudomonas. Following feature selection, disease duration, Haemophilus abundance, history of AECOPD, Pseudomonas abundance, and predicted FEV1% were identified as significant predictive factors. With a sensitivity of 0.867, specificity of 0.789, PPV of 0.805, NPV of 0.855, and AUC of 0.911, the Bayesian Network (BN) model outperformed the other six machine learning models on the testing sets; its generalization ability was significantly superior to other algorithms such as SVM and RF.
CMH in COPD is linked to airway dysbiosis and pathogen enrichment. The BN model effectively identifies this phenotype with strong generalization ability.Chronic respiratory diseaseAccessCare/ManagementAdvocacy