Pediatric Pulmonology最新文献

Aim: To compare discrimination and calibration of prognostic models for pulmonary outcomes in very preterm (VPT) infants born < 32 weeks' gestation when including the mean airway pressure (MAP), the fraction of supplemental oxygen (FiO₂) and the respiratory severity score (RSS) reflecting parameters of ventilation and oxygenation during the first 24 and 72 h of life.

Methods: In this retrospective single center study of 168 VPT infants, the mean airway pressure (MAP), the fraction of supplemental oxygen (FiO₂) or RSS (considering MAP and FiO₂) were added to a baseline model of clinical risk factors to assess the improvements for prediction of bronchopulmonary dysplasia (BPD).

Results: The baseline model demonstrated good calibration (slope 1.02) and discrimination (AUC 0.85) for overall BPD (BPD28), and adding any of the parameters of ventilation resulted only in slight improvement in discrimination (AUC 0.86). For moderate/severe BPD (BPD36), overprediction in the lower extremes and underprediction in the upper extremes became evident for the baseline model. While adding MAP rendered optimal specificity (81%), sensitivity (91%) was highest for FiO₂. MAP was substantially better at improving calibration for BPD36 (slope 0.98) than FiO₂ (slope 0.87). Using RSS and expanding the models to the first 72 h of life did not result in any improvements.

Conclusion: Adding parameters of ventilation and oxygenation improves baseline models to predict the risk of BPD28 and BPD36 early after birth. Particularly, our data encourage considering MAP as potential predictor in the development of future risk models to improve the prediction accuracy and to solidify early treatment decisions intended to prevent BPD.

Introduction: Bronchopulmonary dysplasia (BPD) is a major complication of prematurity, marked by heterogeneous pulmonary phenotypes and variable clinical outcomes. The airway microbiome may influence disease severity and progression, yet quantitative associations between airway pathogens and clinically relevant outcomes remain poorly understood.

Methods: We conducted a retrospective analysis of 204 neonates who underwent flexible bronchoscopy with quantitative bronchoalveolar lavage (BAL) cultures in the NICU at the Children's Hospital of Philadelphia. Cultures yielding ≥ 10,000 colony-forming units per milliliter for a single bacterial species were classified as positive. Respiratory severity score (RSS), calculated as the product of mean airway pressure and fraction of inspired oxygen, served as the primary indicator of respiratory status. Linear, logistic, and negative binomial regression models were used to assess associations between bacterial species and clinical outcomes, adjusted for sex and race, with standard errors clustered at the patient level.

Results: No bacterial species were significantly associated with RSS after correction for multiple testing. Klebsiella pneumoniae was associated with a diagnosis of BPD (adjusted p = 0.026), but no organisms were significantly associated with prolonged time to extubation. In secondary analyses, the presence of several organisms was significantly associated with higher MAP, including K. pneumoniae (β = 2.66, FDR-adjusted p = 0.014).

Conclusions: Multiple bacterial species identified on quantitative BAL culture were associated with higher mean airway pressure, and K. pneumoniae was additionally associated with BPD diagnosis. These findings support the potential utility of quantitative microbiologic data in risk stratification and management of neonatal respiratory disease.

Objective: Thickened liquids are commonly used to treat oropharyngeal dysphagia in infants but the extent to which each viscosity improves swallow function is not well understood. Our objective was to determine improvements in swallow function with provision of thickened liquids as measured by penetration-aspiration scale (PAS) score changes on videofluoroscopic swallow study (VFSS).

Methods: We performed a retrospective cohort study of infants with aspiration or laryngeal penetration on VFSS. Records were reviewed for highest PAS reported, whether thickened liquids were tested, PAS for each viscosity, and PAS for viscosities recommended after VFSS. Safe swallow was defined as PAS ≤ 2. Proportions were compared with Fisher exact tests and means with t-tests.

Results: The cohort included 521 infants of whom 60% (310) had laryngeal penetration and 40% (211) aspiration with 93% (197/211) silent aspiration. Thickening was evaluated during VFSS in 71% (371) of patients and was more likely to be tested in infants that were older, had higher starting PAS score, deep and consistent laryngeal penetration, and aspiration (p < 0.001). The proportion of infants with safe swallowing was found to increase with increasing liquid viscosity with 73% (112/153) showing safe swallowing with mildly thick consistency. Of the 300 infants for whom thickening was recommended, 96% (287) were able to achieve PAS 1 or 2.

Conclusions: Thickened liquids have a viscosity-dependent therapeutic effect in the treatment of infants with oropharyngeal dysphagia. Our results suggest it may be possible to facilitate safe swallowing in the majority of infants by using liquids at mildly thick consistency.

Background: Flexible bronchoscopy (FOB) is the current gold standard for diagnosing tracheobronchomalacia (TBM). While dynamic magnetic resonance imaging (cine-MRI) has emerged as a radiation-free alternative for TBM diagnosis, a direct comparison of its diagnostic performance with FOB has not yet been performed.

Objective: This study aimed to evaluate the diagnostic performance of cine-MRI versus FOB in detecting TBM and to assess the effect of bronchodilators on observed tracheobronchial collapse.

Methods: The study included 10 children (median age 11 years, range 8-17 years; five males) who were referred for suspected TBM. Cine-MRI was performed using a 3 Tesla GE 750 W scanner with specific sequences for static and dynamic imaging. Bronchodilator testing was conducted using 400 µg salbutamol. Children suspected of TBM underwent both FOB and cine-MRI. Cine-MRI protocol included spirometry-controlled static and dynamic sequences, pre- and post-bronchodilator administration. FOB diagnoses were made by pediatric pulmonologists, and cine-MRI assessments were independently evaluated by two trained observers, blinded to FOB results. Moreover, each child completed spirometry and a respiratory questionnaire. Descriptive statistics were used to summarize data. Diagnostic agreement and measurements repeatability were assessed using the intra-class correlation coefficient (ICC).

Results: FOB identified TBM in two children, whereas cine-MRI detected TBM in four. In three of these four children TBM was not diagnosed by FOB. Notably, no TBM was observed during static pre-bronchodilator cine-MRI assessment, but two of the four children diagnosed with cine-MRI met the diagnostic criteria of TBM only post-bronchodilation.

Conclusion: Cine-MRI, particularly post-bronchodilation shows a unique capability to detect TBM cases undetected by FOB. This may reflect its ability to perform dynamic functional measurements during active respiratory maneuvers, highlighting its potential as a valuable diagnostic tool for central airway disease in children.

Background: Asthma is an important global healthcare problem, and severe asthma affects 5%-7% of children with asthma. This small percentage results in a heavy burden of disease.

Objectives: To describe the characteristics of severe asthma patients in Argentina and their evolution over time, and to evaluate the effectiveness of a multidisciplinary team (MDT) approach in the clinical management of these children.

Methods: Prospective, observational, longitudinal study in an Argentinian Pulmonology Service.

Results: Fifty-three children aged 5-15 years old diagnosed with severe asthma were studied over a period of 6 months; 40/53 (76%) patients were unable to access therapy (WHO Group 1) and 27/40 were finally categorized as patients with difficult-to-treat asthma after completing the program. The remaining 13 patients in Group 1 who were non-responders were classified as severe therapy-resistant asthma (STRA). Of the 13 patients who were not initially in Group 1, 8/13 were responders who no longer had severe asthma and were thus classified as difficult-to-treat asthma and the remaining five had STRA; thus 35/53 (66%) of the treated patients were no longer classified as severe asthma after completing the program. We identified adverse psychosocial factors identified in 47%. 77% had allergic rhinitis. Most had normal spirometry. Blood eosinophil count was median of 320 cell/µL, and median total IgE was 313 UI/ml. During the program, asthma symptoms, quality of life and asthma exacerbations all improved significantly.

Conclusion: Our multidisciplinary approach was associated with better outcomes in most patients with severe asthma. This model could profitably be adopted in other low-resource settings.

Background: Cystic fibrosis (CF) is a life-threatening disease that requires extensive knowledge for effective management. This study aimed to assess the knowledge levels of parents of children diagnosed with CF through newborn screening (NBS), evaluate their experiences during the diagnostic process, and determine the impact of education on their CF knowledge.

Methods: This quasi-experimental study involved 47 parents of children aged 0-30 months diagnosed with CF through NBS at four CF centers in Istanbul, Turkey. Parents completed a questionnaire assessing their CF knowledge before and after receiving face-to-face education, informational brochures, and an online webinar. The questionnaire covered general CF features, lung health, sexual function and infertility, and gastrointestinal issues.

Results: The study revealed significant deficiencies in parental knowledge about CF and the NBS process. Only 25.5% of parents were informed about NBS prenatally, and 51.1% received information about CF when NBS results were positive. After educational intervention, correct response rates significantly increased for general characteristics (p = 0.003), sexual health (p < 0.001), lung health (p = 0.007), and overall knowledge (p < 0.001). Parents of children older than 12 months showed more pronounced improvement in knowledge across various sections compared to parents of younger children.

Conclusion: The study highlights the need for a more robust educational framework to equip parents with comprehensive knowledge about CF. Improved communication strategies about NBS processes and repeated educational interventions are necessary to address knowledge gaps and enhance the quality of life for CF patients and their families.

Objective: To assess the clinical utility and predictive ability of three commonly used definitions of bronchopulmonary dysplasia (BPD) (2001 NHLBI, 2018 NICHD, 2019 NRN) in forecasting lung function outcomes in children with a history of prematurity and BPD.

Study design: A retrospective chart review of 138 children with a history of prematurity and BPD who were recruited from two outpatient clinics at large tertiary medical centers was performed. Each subject's lung disease was classified based on the three definitions of BPD. Regression analyses were performed to assess the association between lung function (FEV1%predicted, FVC %predicted) and BPD status, defined dichotomously and by severity. Additional analyses compared lung function outcomes by need for supplemental oxygen at hospital discharge and history of pulmonary hypertension.

Results: None of the three definitions evaluated met the criteria for an ideal definition that can both identify individuals at risk for long-term pulmonary impairment and stratify disease severity in a clinically meaningful way. In dichotomized analysis (BPD vs. no BPD), both the 2018 NICHD and 2019 NRN definitions identified preterm-born individuals with significantly lower lung function parameters compared to preterm-born individuals without BPD whereas the 2001 NHLBI definition failed to distinguish between affected and unaffected individuals. A clear gradient of worsening lung function with increasing BPD severity was appreciated using the 2001 NHLBI criteria, highlighting an aspect of the definition's relative strength in stratifying long-term risk.

Conclusions: Newer definitions of BPD (2018 NICHD, 2019 NRN) more effectively identify children at risk for impaired pulmonary function than the older NHLBI definition. The association of supplemental oxygen requirement and diagnosis of pulmonary hypertension with lung function parameters suggests that there may be clinical indicators that are more predictive of long-term respiratory outcomes than the currently available definitions. There continues to be a need for significant refinement in the definition of BPD to improve its predictive value and guide long-term management strategies.

Background: Dupilumab is a human monoclonal antibody targeting the IL-4 receptor. There is a paucity of evidence regarding its efficacy and safety in pediatrics. Pediatric-specific data are limited, and most evidence comes from recent phase 3 trials and post hoc analyses.

Objective: To summarize the current evidence of the efficacy, safety, and biomarker effects of dupilumab in children with moderate-to-severe asthma, while identifying key gaps in the pediatric evidence base.

Methods: This study is a systematic review following PRISMA guidelines, and aims to assess the efficacy, safety, and biomarker response of dupilumab in pediatric patients with moderate to severe asthma. We evaluated the studies using the Cochrane Risk of Bias Tool 2.0.

Results: Six studies from 2021 to 2024 met the inclusion criteria: three of them are phase 3 randomized controlled trials and the other three post hoc analyses, mostly including children aged 6-11 years with type 2 inflammation, defined by elevated blood eosinophils and/or FeNO. Both allergic and nonallergic asthma phenotypes were represented across studies, with post hoc analyses indicating consistent benefit in each group. Dupilumab decreased the rate of severe exacerbations annually by 59.3% in children with type 2 inflammation. The study populations are mainly children between 6 and 11 years of age with moderate-to-severe asthma, characterized by eosinophilic or allergic phenotypes (type 2 asthma), including those with elevated blood eosinophils and/or FeNO levels. Dupilumab reduced the annual rate of severe exacerbation by ~59%, with greater reductions in children with FeNO ≥50 ppb (69%) or eosinophils ≥300 cells/µL (65%). The lung function showed improvement by 0.15-0.30 L in pre-bronchodilator FEV₁, accompanied by gains in asthma control and quality of life. Biomarker reductions (FeNO, eosinophils, IgE, TARC) were consistent across phenotypes. Adverse event rates were like placebo; eosinophilia and injection site reactions were more common but usually mild.

Conclusion: This systematic review provides an early synthesis of emerging pediatric phase 3 evidence on dupilumab. While results suggest substantial benefits in reducing exacerbations, improving lung function, and modulating type 2 biomarkers, the evidence remains limited to short-term studies in a narrow age range. Longer-term follow-up, broader age representation, and real-world data are needed to define the long-term role of dupilumab in pediatric asthma. Prospero Code: CRD42024557750.