Pediatric Pulmonology最新文献

Background: For people with cystic fibrosis (pwCF) carrying susceptible mutations, elexacaftor/tezacaftor/ivacaftor (ETI) has changed the course of their lives. Organ manifestations critically affecting both respiratory and digestive tracts have been found to improve considerably. Consequently, ETI-associated reductions in sinonasal symptoms (SNS) deriving from the upper respiratory tract are consistently reported. However, although substantial ETI-related declines in the burden of abdominal symptoms (AS) have been reported using the CFAbd-Score, their correlation with SNS changes has not been studied.

Aims: Assessing correlations between ETI-related changes in pwCF SNS and AS.

Methods: The German adapted version of the Sinonasal-Outcome-Test 20 (SNOT-20-GAV) and the CFAbd-Score, the first CF-specific gastrointestinal (GI) patient-reported outcome measure developed and validated following FDA guidelines, were simultaneously administered. PwCF completing both paired questionnaires, at least once before and after ETI initiation, were included.

Results: In two German CF-centers, n = 31 pwCF (18 f, mean-age 13 years) were included, completing n = 106 paired questionnaires. During ETI therapy, significant decreases (p < 0.05) were observed for the mean total CFAbd-Score (10.9→5.8pts[-47%]) as well as all sub-scores ('pain': -61%, 'disorders of bowel movement': -56%, 'GERD': -54%, 'disorders of appetite': -50% and 'QoL-impairment':-67%). Analogously, SNS significantly improved (total SNOT: 10.1→3.4pts[-66%] and its 3 domains: primary and secondary nasal symptoms, and SNS-related QoL [-68%/-81%/-54%]). However, the correlation between changes in symptoms related to upper-respiratory and GI tracts was only modest.

Conclusion: The burden of symptoms captured with the CFAbd-Score and the SNOT-20-GAV significantly and markedly decreased after ETI initiation. The modest association between changes in both organ-specific symptom scores supports the previously reported individualized electrophysiological responses observed in nasal-potential and intestinal-current measurements.

Introduction: Infants with severe bronchopulmonary dysplasia (BPD) are at increased risk of hypoxemia and often fail hypoxic challenge testing (HCT). The predictive value of clinical characteristics and structural lung abnormalities on HCT outcomes is unclear.

Methods: This prospective cohort study included preterm-born infants (≤ 32 weeks of gestation) with severe BPD enrolled in a standardized follow-up program. Perinatal and neonatal data were extracted from medical records. At 6 months corrected gestational age, structural lung abnormalities were quantified on chest CT using PRAGMA-BPD scoring. HCT was performed using a sealed body plethysmograph and failure was defined as inability to maintain oxygen saturation ≥ 85% for 20 min. Univariate and multivariable logistic regression analyses identified predictors of HCT failure.

Results: Among 156 infants, 28.8% failed HCT. Of the perinatal and neonatal factors, patent ductus arteriosus (odds ratio 2.73, 95% confidence interval 1.29-6.14), pulmonary hypertension (2.57, 0.99-6.62), and longer duration of supplemental oxygen therapy (odds ratio per interquartile range increase [OR_IQR] 2.40, 1.55-3.71) were associated with failure. For structural lung abnormalities, higher composite PRAGMA-BPD scores (OR_IQR 2.18, 1.36-3.48), higher hyper-attenuation (OR_IQR 1.75, 1.17-2.63), and hypo-attenuation (OR_IQR 1.45, 1.08-1.98) scores predicted failure. In multivariable analysis, only longer duration of supplemental oxygen therapy (OR_IQR 2.04, 1.22-3.42) and higher composite PRAGMA-BPD scores (OR_IQR 1.95, 1.15-3.31) remained independent predictors.

Conclusion: Duration of supplemental oxygen therapy and structural lung abnormalities independently predict HCT failure, highlighting the clinical relevance of both structural and functional impairments in severe BPD.

Background: Pediatric asthma remains a leading global health concern and disproportionately affects children in low-income and environmentally burdened communities. Chemical and non-chemical stressors, including air pollution, allergens, climate-related events, and psychosocial stress, contribute to asthma exacerbations and hinder effective disease management.

Objectives: This paper explores the intersection of childhood asthma and community resilience, emphasizing the influence of environmental exposures, public health infrastructure, and targeted interventions on pediatric respiratory outcomes.

Methods: A series of case studies is used to examine how environmental and social stressors shape asthma risk and management. These case studies highlight patterns of exposure, community-level challenges, and the role of public health systems and community-engaged strategies.

Results: Findings illustrate that combined environmental burdens and insufficient public health infrastructure contribute to persistent asthma disparities. Case studies also show that communities with stronger resilience-through resources, engagement, or adaptive systems-experience improved support for children with asthma.

Conclusions: Longitudinal research, policy reform, and community-engaged interventions are essential to mitigate asthma disparities and support children's health in the face of environmental adversity.

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved lung function and growth in people with cystic fibrosis (pwCF). However, its impact on cystic fibrosis hepatobiliary involvement (CFHBI) remains unclear. This study aims to investigate the impact of ETI on biochemical surrogates of CFHBI using a large population database.

Methods: This 1:1 retrospective cohort study utilized TriNetX, a de-identified multicenter database, and included people aged 6-21 years with ICD-10 diagnostic codes for cystic fibrosis who were prescribed pancreatic enzyme replacement therapy. ETI group (pwCF on ETI seen from 1/1/2020 to 1/1/2024) and non-ETI group (pwCF not on ETI seen from 1/1/2014 to 1/1/2018) were analyzed. Groups were matched using propensity scores, and statistical analyses were performed on TriNetX (significance set at p = 0.05).

Results: There were 533 children with CF (CwCF) aged 6-12 years and 1177 adolescents and young adults with CF aged 13-21 years in each cohort. In CwCF, the ETI group had significantly lower ALT (33 ± 44 U/L vs. 45 ± 57 U/L, p = 0.003) and GGT levels (18 ± 20 U/L vs. 28 ± 51 U/L, p = 0.004), as well as improved albumin and PT/INR compared to non-ETI group. In pwCF (13-21), the ETI group had significantly lower GGT (21 ± 26 U/L vs. 32 ± 63 U/L, p = 0.002), and improved albumin and PT compared to non-ETI group; however, indirect bilirubin was higher (0.7 ± 0.5 mg/dL vs. 0.3 ± 0.4 mg/dL, p < 0.001).

Conclusion: Our findings suggest that earlier ETI use in children with CF is associated with improved liver enzymes, offering reassurance against widespread drug-induced liver injury. Long-term follow-up including imaging and biopsy when available, pre- and post-ETI, is needed to better assess the impact of ETI on CFHBI and advanced CF liver disease.

Objectives: Short stature has been associated with reduced life expectancy in people with Cystic Fibrosis (pwCF). We aimed to evaluate linear growth and final height in a Dutch cohort of children with CF, diagnosed in early childhood and now aged ≥ 18 years and identify risk factors for impaired linear growth.

Methods: A multicenter longitudinal retrospective cohort study was performed in pwCF born between 1997 and 2004, before implementation of newborn screening (NBS). Anthropometric measurements and CF-related risk factors for poor growth (pulmonary infections, malnutrition, CF-Related Diabetes [CFRD], CF-related liver disease [CFLD]) were obtained annually from ages 0.5 to 10 years and biannually from ages 10 to 18. Measurements were converted to Height-For-Age-For-Target-Height (HFA-TH) Z-scores. Differences in HFA-TH Z-scores between pwCF and healthy standards, and risk factors associated with linear growth were analyzed.

Results: A total of 128 pwCF (60 males) were included. Most patients did not receive modulator-therapy during pubertal growth. In boys, mean HFA-TH Z-scores at age 18 years (HFA-TH₁₈) were lower in comparison to healthy standards (-0.66 [0.96], p < 0.001). In girls at age 18, a normal mean HFA-TH z-score was found (-0.18 [0.78]). Development of CFRD and a greater change in BMI Z-scores between 0.5 and 6 years of age (ΔBMI_0.5-6) were associated with lower HFA-TH₁₈ Z-scores in boys. In both sexes, pulmonary function and BMI Z-scores were positively associated with linear growth.

Conclusion: Boys with CF may have impaired final height, especially those with CFRD or a ΔBMI_0.5-6. Glucose metabolism and nutritional status should be monitored closely in pwCF, as these factors may contribute to impaired linear growth.

Background: People with cystic fibrosis (pwCF) and primary ciliary dyskinesia (pwPCD) are particularly vulnerable to the harmful effects of air pollution due to the impairment of mucociliary clearance (MCC). Despite growing evidence supporting the use of indoor air purification in common lung conditions, its role in CF and PCD remains unexplored.

Methods: The Clean Air for Rare MCC dIsorders (CARMUCI) study is a randomized, double-blind, cross-over, sham-controlled trial aiming to evaluate the impact of indoor air purification on the respiratory health of pwCF and pwPCD (children and adults) in Cyprus. Sixty-two participants will receive two 3-month intervention periods using identical-looking air purifiers: one 3-month period with active filtration via high-efficiency filters and one 3-month period with a sham unit. Primary outcome will be a mean difference of at least 10% change in lung clearance index, and secondary outcomes will include spirometry, pulmonary exacerbations, inflammatory biomarkers, and health-related quality of life. Exposure to indoor particulate matter (PM) will be continuously monitored using device operation logs and wearable activity trackers.

Results: By August 2025, 24 pwCF and 26 pwPCD (20 females, age: 31 [16.1] years) have been enrolled. CARMUCI continues enrollment and will start data collection in September 2025. Results are expected to provide novel evidence on the efficacy of air purification in reducing indoor PM exposure and improving respiratory outcomes in people with chronic MCC disorders.

Conclusion: CARMUCI trial first results are expected in late-2027 and may inform future clinical guidelines and environmental health strategies for managing rare MCC disorders.