Pediatric Pulmonology最新文献

Background: Cystic fibrosis (CF) is a genetic disease that affects individuals across the globe, yet people with CF (pwCF) in low- and middle-income countries (LMICs) have historically been under-represented in research due to diagnostic barriers, limited resources, and lack of registry infrastructure.

Aims: The COVID-19 pandemic created an urgent need for real-time, standardized data on SARS-CoV-2 infection in pwCF. The aim of this work was to determine the impact of infection on the CF community.

Methods: Leveraging existing international relationships and national registries, CF leaders rapidly mobilized a global collaboration spanning 47 countries, integrating both high-income countries (HICs) and LMICs. The global CF community developed standardized data definitions and offered multiple collection platforms, including registry extractions, REDCap databases, and Excel-based forms, minimizing technical requirements and allowing centers without registries to contribute. Data were collated and analyzed to quantify the impact of SARS-CoV-2 infection on lung function as well as to identify those at risk for hospitalization and death.

Results: Through this international effort, data were collected on over 7000 pwCF diagnosed with COVID-19 across 47 countries, and 6500 were included in the analysis, of which 515 cases were from an LMIC. Most pwCF who contracted COVID-19 experienced mild or moderate illness. Severe outcomes, including hospitalization and mortality, did occur but were generally confined to individuals with advanced lung disease, those who had received lung transplants, or those with other high-risk factors.

Conclusion: The global CF COVID-19 initiative demonstrated that flexible, low-cost tools, capacity building, and intentional engagement of LMIC partners can reduce barriers to participation. Lessons learned, particularly around equity, sustainability, and harmonization, are directly applicable to future global CF research. Building on this model, the newly formalized Global CF Collaboration: Data & Research aims to strengthen LMIC partnerships, expand registry capacity, and ensure no region is left behind in advancing CF care and outcomes.

Objectives: To evaluate the prevalence of ineligibility for Elexacaftor/Tezacaftor/Ivacaftor (ETI) and Ivacaftor (IVA) and to compare data from four centers in Brazil, considering the racial/ethnic background of each population.

Methods: This cross-sectional study used data from the Brazilian Cystic Fibrosis (CF) Registry. Individuals with a confirmed diagnosis of CF by the identification of two variants in the CFTR gene and/or elevated sweat chloride levels were included. Variables studied were treatment center, age at diagnosis, current age, sex, race/ethnicity, genotype, and ineligibility for ETI and IVA. The chi-square test compared the distribution of race/ethnicity across centers and associations between ineligibility, treatment center, and the presence of the 3120 + 1 G > A variant. Binary logistic regression was applied to assess the strength of association between the main variables.

Results: Six hundred forty-nine individuals were included, with a median age at diagnosis and current age of 0.25 and 11.6 years, respectively. One hundred thirty-eight participants (21.26%) were ineligible for ETI or IVA. Racial/ethnic distribution varied across centers, in the total sample, and among ineligible individuals. Non-White individuals were 20% more likely to be ineligible than White individuals. The ineligibility for ETI did not vary significantly among the centers.

Conclusions: The ineligibility for ETI was high across all analyzed regions, but was not different among the centers. In Brazil, characterized by widespread admixture, the public health policies must consider the genotypic heterogeneity and wide variation in ancestry of the Brazilian population.

Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare and diffuse lung disease in children that presents significant diagnostic challenges worldwide, especially in Colombia, where comprehensive studies are limited. This retrospective review examines 10 clinical cases of NEHI diagnosed at Fundación Santa Fe de Bogotá between 2013 and 2023. The study reviewed 10 cases, comprising 6 males and 4 females. Patients presented with a median age of 9 months (range: 5-20 months) and commonly exhibited symptoms such as low oxygen saturation, tachypnea (100%), retractions in half of the cases. Chest CT scans revealed ground-glass opacities and bronchial thickening, while polysomnography demonstrated baseline desaturation (median minimum oxygen saturation: 74%), with central apneas observed in a subset of patients. Treatment strategies included supplemental oxygen, inhaled steroids, leukotriene inhibitors, and azithromycin. This study emphasizes the urgent need for a better understanding and management of NEHI, particularly in high-altitude regions such as Bogotá, highlighting the diagnostic challenges and clinical implications for affected children.

Cystic fibrosis has been transformed by the development of CFTR modulator therapies, with substantial improvements in survival and quality of life. However, access to these therapies remains profoundly unequal worldwide. The greatest benefits have been realized in high-income countries, while people with cystic fibrosis in low- and middle-income countries and underserved populations within high-income settings continue to face limited access and poorer outcomes. Underdiagnosis is a major contributor to these disparities, as limited newborn screening, restricted access to sweat testing, and incomplete genetic characterization directly limit treatment eligibility and registry inclusion. Beyond diagnosis, disparities are driven by differences in genetic variant distribution, pricing and reimbursement policies, regulatory processes, and health system capacity. This review examines how these interrelated factors shape global access to therapies, with particular emphasis on CFTR modulators. Emerging strategies-including differential pricing, licensing mechanisms, regulatory adaptation, international collaboration, and health system strengthening-are discussed. Achieving equitable access will require coordinated action across diagnostic, economic, and policy domains to ensure that advances in cystic fibrosis care benefit patients regardless of geographic or socioeconomic context.

Introduction: Antenatal exposure to maternal smoking negatively impacts on fetal lung development resulting in infant lung function abnormalities. Lung clearance indices (LCI) were worse in term born infants exposed to antenatal maternal smoking compared to not. Our aim was to assess the effect of antenatal maternal smoking on lung function, in particular LCI, in very prematurely born children.

Methods: Lung function testing was undertaken at 11-14 years, when household members smoking and active smoking were assessed. Antenatal maternal smoking had been recorded. Lung function was assessed by LCI, spirometry, plethysmography, gas transfer and fraction of exhaled nitric oxide.

Results: Two hundred and thirty children with a median gestation age of 27 weeks were assessed. Fifty-five had antenatal exposure to maternal smoking. Those with exposure to antenatal maternal smoking were more likely to live with a household member that smoked (67% vs. 18%, p < 0.001). Children of mothers who smoked in pregnancy were also more likely to be active smokers at follow up (indicated by urinary cotinine levels greater than 15 ng/mL) (49% vs. 7%; p < 0.001). Lung clearance index was higher in children exposed to maternal smoking in pregnancy (mean (SD): 7.8 (1.1) vs. 7.4 (1.2); mean difference (95% CI): -0.44 (-0.91, 0.02); p = 0.031). There were no significant differences in other measures of lung function.

Conclusion: Very prematurely born children exposed to antenatal maternal smoking had greater ventilation inhomogeneity and were more likely to be active smokers and live with a household member that smoked. These findings were not explained by active smoking or household smoking contact at follow up, but those who had BPD had greater ventilation inhomogeneity.

Introduction: Pulmonary hemorrhage (PHem) is a severe and often fatal condition in neonates, particularly affecting preterm and very low birth weight infants. It is associated with significant morbidity and mortality, yet distinctions between early- and late-onset PHem and their respective risk factors remain unclear. This study aimed to evaluate clinical characteristics, risk factors, management strategies, and outcomes of neonates with PHem, with a focus on early versus late onset.

Materials and methods: In this retrospective cross-sectional study, medical records of neonates diagnosed with PHem in a tertiary NICU between January 2014 and December 2020 were analyzed. Early PHem was defined as onset within the first 7 days of life, and late PHem as onset thereafter. Collected data included antenatal, perinatal, and postnatal variables, surfactant and PDA management, and clinical outcomes. Statistical analyses included univariate and multivariate logistic regression to identify risk factors for early PHem and mortality.

Results: A total of 80 neonates with PHem were included (mean gestational age 27.7 ± 3.6 weeks; mean birth weight 1092 ± 587 g). Early PHem accounted for 83.7% (n = 67) and late PHem for 16.3% (n = 13) of cases. Infants with early PHem had significantly higher mean airway pressure (MAP) at 12 h (p = 0.044) and a greater need for post-PHem surfactant therapy (p = 0.044). Conversely, late PHem was associated with higher rates of sepsis (p = 0.009), coagulopathy (p = 0.019), and hemodynamically significant PDA (92.3% vs. 47.8%, p = 0.008). Duration of mechanical ventilation (p < 0.001) and oxygen therapy (p = 0.002) were longer in the late PHem group. Overall mortality was 82.5%, with no statistically significant difference between early and late PHem (80.6% vs. 92.3%, p = 0.446).

Conclusion: PHem remains a significant cause of neonatal morbidity and mortality. Early and late PHem represent distinct clinical entities with different risk profiles, their management and long-term outcomes are similar. Despite these differences, mortality remains high in both groups. Identification of key risk factors, especially delivery room resuscitation, may guide preventive strategies and optimize neonatal care.

Background: Bronchiectasis (BE) is a chronic obstructive pulmonary disease characterized by bronchial dilatation and structural damage due to persistent inflammation and infections. While pulmonary impairments in BE are extensively documented, cognitive-motor functions and motor imagery in children with BE remain understudied. This study aimed to evaluate cognitive functions, reaction time, and motor imagery in children with BE compared to healthy controls.

Methods: This cross-sectional controlled study involved 20 children with BE (aged 7-18 years) and 20 age-matched healthy controls. Pulmonary functions were assessed by spirometry. Cognitive functions were evaluated using the Stroop Test and Trail Making Test (TMT). Reaction times were measured using the Nelson Hand and Foot Reaction Test. Motor imagery abilities were assessed with the Movement Imagery Questionnaire-3 (MIQ-3), Vividness of Visual Imagery Questionnaire (VVIQ), and mental chronometry test.

Results: Children with BE exhibited significantly reduced pulmonary function compared to controls (FEV1 64.2% vs. 85.75%, p = 0.003; FEV1/FVC 64.1% vs. 93.2%, p < 0.001). The BE group showed significantly worse error scores than the control group across all subtests of the Stroop Test (p < 0.05), showed impaired cognitive performance particularly in the TMT Part B short form (9.7 s vs. 5.3 s, p = 0.027), and exhibited increased reaction time for foot responses (0.22 s vs. 0.19 s, p < 0.001). Children with BE also showed poorer motor imagery performance than controls, with lower MIQ-3 internal, external, and kinesthetic imagery scores, VVIQ total score, and a higher mental chronometry ratio (p < 0.05).

Conclusions: Children with BE demonstrate impairments in cognitive functions, reaction time, and motor imagery abilities. These deficits suggest the necessity for cognitive assessments and targeted physiotherapy interventions in managing children with BE.

Background: Hypochloremic hypokalemic metabolic alkalosis (HHMA) may occur in unscreened, undiagnosed, and unsupplemented children with cystic fibrosis (cwCF) or in diagnosed people with CF (pwCF) who are inadequately supplemented with salt. It may also present as a clinical manifestation in children with cystic fibrosis transmembrane conductance regulator-related disorder (cwCFTR-RD) who have borderline or normal sweat chloride test (SCT) levels.

Methods: In this single-center retrospective study, we included cwCF and cwCFTR-RD who experienced at least one HHMA episode between January 2002 and August 2024. We compared the demographic, genetic, clinical, and laboratory characteristics of both groups within the context of the CFTR variant diversity observed in Türkiye.

Results: A total of 103 children (91 cwCF, 12 cwCFTR-RD) were evaluated, comprising 150 HHMA episodes. Median SCT levels were significantly lower in cwCFTR-RD than in cwCF (43 [IQR, 34-53] vs. 90 [IQR, 75-99] mmol/L, p < 0.001). Variants such as F1052V, D1152H, and F200I were observed in 6 of 24 variants (25%) in cwCFTR-RD. CF-related complications including diabetes (15.3%), chronic Pseudomonas aeruginosa infection (18%), and pancreatic insufficiency (83%) occurred only in cwCF.

Conclusion: HHMA represents an early and clinically significant manifestation in both cwCF and cwCFTR-RD. Clearer acknowledgment of HHMA as a manifestation of CFTR-RD within guidelines is crucial for improving diagnostic clarity and guiding appropriate management decisions. Salt supplementation, family education, and long-term follow-up are essential components of care for both groups. Furthermore, limited access to CFTR functional assays and the ineligibility of one-third of cwCF for current modulators together show the ongoing diagnostic and therapeutic gaps.

In recent years, it has become evident that there may be a gross underestimation of the true disease burden of cystic fibrosis (CF) in low-and-middle-income countries. Data on incidence of CF in India are sparse, and optimal CF care is impeded by lack of standardized epidemiological data, limited awareness on the disease impact of CF, and inadequate diagnostic and clinical infrastructure to manage CF. Lack of universal neonatal screening, insufficient sweat testing equipment, and expensive genetic testing preclude timely diagnosis and treatment. Restricted access and costs prohibit consistent use of many CF-specific treatments, leading to high morbidity and early mortality. Early diagnosis is crucial and may be achieved by providing CF-specific education to physicians, ancillary staff, medical trainees, and the community, and by initiating neonatal screening. CF clinical diagnostic scores and indigenously developed sweat collection and analysis are inexpensive diagnostic options when c resources are limited. Targeted mutation panels based on regional heterogeneity of CFTR variants need further investigation. Increasing the number of specialized CF centers will improve access to timely care and reduce travel time significantly. Cost-effective clinical protocols following standardized guidelines (with resource-based modifications) for nutritional health, preventive care, and airway clearance through shared care models are invaluable. Ongoing support for the CF registry initiated by the Indian Council of Medical Research is important for epidemiological assessments and policy change, and patient advocacy through organizations such as CF Trust is vital to increase referrals and diagnostic access, subsidize medications, and procure modulator therapies.