Joseph Michael Collaco

Diabetes is a highly prevalent complication of cystic fibrosis (CF), affecting 50% of adults with CF and over 80% of those with exocrine pancreatic insufficiency (PI) by age 50 years. Development of cystic fibrosis-related diabetes (CFRD) is associated with increased morbidity and mortality mostly due to advancement of chronic obstructive lung disease. Highly effective modulator therapy (HEMT), using precision medications targeting the cystic fibrosis transmembrane conductance regulator (CFTR), improves CFTR function and CF lung disease, but its impact on diabetes pathogenesis remains uncertain. We sought to determine whether two types of HEMT, ivacaftor and elexacaftor/tezacaftor/ivacaftor (ETI), alter diabetes prevalence in two large cohorts of individuals with CF and exocrine PI. For comparison, a non-highly-effective modulator, lumacaftor/ivacaftor (LUM/IVA), was also assessed. Data were provided by the CFTR2 project, a multinational CF registry (for ivacaftor and LUM-IVA), and by the CF Genome Project (CFGP), a predominantly US-based CF cohort (for ETI). Among 32,753 individuals with CF (2,803 treated), ivacaftor was associated with reduced diabetes prevalence (age-adjusted OR=0.55). In contrast, lumacaftor/ivacaftor (not highly effective) was not associated with diabetes prevalence (n=32,749). Among 2,854 individuals with CF (2,458 treated), ETI was associated with reduced diabetes prevalence (age-adjusted OR=0.47). Overall, HEMT (ivacaftor and ETI) was associated with a 25-39% reduction in diabetes prevalence in CF, while a non-highly-effective modulator (lumacaftor/ivacaftor) showed no difference. Precision targeted amelioration of CFTR dysfunction can delay onset of diabetes in a high-risk CF population.

Objective: To understand the prescribing patterns and clinical practices of providers for infants and children with bronchopulmonary dysplasia (BPD) in the outpatient clinic setting. Methods: We conducted a survey of BPD Collaborative programs from diverse geographic areas inside and outside the United States from January 2025 through March 2025. Results: Twenty‐nine of 45 centers in the BPD Collaborative completed the survey, including 27 from the U.S. and 2 from other countries. The majority of respondents identified as pediatric pulmonologists (72.4%). Most healthcare providers endorsed that patient symptomatology was a major driver of decision making (79.3%) and greater BPD severity correlated with a higher likelihood of medication use. Beta‐agonists and inhaled corticosteroids (ICS) were the most commonly prescribed medications across all levels of severity. While prescriptions for pulmonary hypertension (PH) medications and diuretics decreased with age, use of inhaled medications persisted or increased in frequency. Challenges obtaining medications included insurance authorization issues (69.0%) and medication costs (51.7%). Adherence to therapy was a concern for over half of BPD programs. Conclusions: Despite limited evidence for outpatient pharmacotherapy in children with BPD, we identified consistent cross‐center practice patterns. Providers reported that while the utilization of therapies was associated with higher BPD severity and greater respiratory support, medications were prescribed across the spectrum of disease severity. Treatment practices varied by age group and were often hindered by common barriers to accessing medications. These findings underscore the need to revise clinical guidelines to enhance long‐term outpatient pharmacotherapy for infants and children with BPD.

Introduction: Lung-function outcomes among preterm-born children referred for pulmonology care are highly heterogeneous, and early determinants remain incompletely defined. We aimed to identify early-life factors associated with school-age lung function after preterm birth and to examine whether school-age spirometry patterns relate to subsequent lung-function trajectories. Methods: Early-life analyses (n=511) examined predictors of forced expiratory volume in 1 s (FEV ₁ ) and forced vital capacity (FVC) z-scores at ages 6–8 years using multivariable regression. Spirometry-based phenotypes included prematurity-associated preserved-ratio impaired spirometry (pPRISm), prematurity-associated obstructive lung disease (POLD) and prematurity-associated dysanapsis. Longitudinal mixed-effects models assessed lung-function trajectories from ages 8 to 21 years. Parallel analyses were conducted in the National Health and Nutrition Examination Survey (NHANES). Results: Lower weight-for-height at 4 years was non-linearly associated with both FEV ₁ and FVC at school age. Invasive ventilation in the first year of life was associated with lower FEV ₁ (β −0.62, 95% CI −0.96 to −0.28) and FVC (β −0.54, 95% CI −0.92 to −0.18). In exploratory analyses, pPRISm was inversely associated with neighbourhood income (risk ratio (RR) 0.63 per SD increase, 95% CI 0.46 to 0.88), and POLD was associated with invasive ventilation (RR 8.07, 95% CI 3.33 to 19.5). Similar subtypes and associations were observed in NHANES. School-age pPRISm was associated with progressive FEV ₁ z-score decline (age x pPRISm β −0.08 SD/year, 95% CI −0.15 to −0.02), while POLD was associated with improving FVC z-score (age x POLD β 0.13 SD/year, 95% CI 0.07 to 0.20). Discussion: Early-childhood growth, neonatal respiratory exposures and school-age spirometry patterns help stratify long-term pulmonary risk among preterm-born children referred for pulmonary care.

Rationale: Bronchopulmonary dysplasia (BPD) is the most common respiratory complication of preterm birth, and various environmental exposures have been associated with long‐term outcomes. Rural patients face unique challenges with regard to their environmental exposures and distance to care. Objective: To assess differences in acute and chronic respiratory outcomes between infants and children with BPD residing in rural areas, as defined by distance to tertiary care and population density, and those residing in urban and suburban areas. Methods: A retrospective cohort study of 1116 subjects who were recruited from an outpatient BPD Clinic between January 2008 and January 2025 was performed. Data were collected through chart review and caregiver questionnaires obtained at routine clinic visits. Rurality was defined by both distance to Johns Hopkins Children's Center (JHCC) in miles as well as population density in persons per square mile (ppsm) of an individual's home zip code. Data were analyzed using chi‐square, t‐tests, and logistic regression. Results: 22.5% of the study population lived in rural zip codes with < 500 ppsm. Rural patients were more likely to be white and have private health insurance. When comparing clinical outcomes, patients living in rural areas were less likely to be prescribed oral steroids compared to those living in suburban or urban settings. Conclusions: Although there are demographic differences between those living in rural versus urban or suburban settings, outpatient respiratory outcomes are similar. Further work should explore specific environmental exposures and health care access issues that affect the rural population with BPD.

Objectives: An estimated 23% of children with grade 3 bronchopulmonary dysplasia (BPD) require tracheostomy for long term positive pressure ventilation. Transition from an intensive care unit (ICU) ventilator to a portable home ventilator (PHV) is one of the key steps in the process of discharging a patient home. The objective of this study was to identify clinical factors and ventilator settings associated with successful transition to a PHV in infants with grade 3 BPD. Study Design: We performed a retrospective record review of 74 ventilator‐dependent infants with grade 3 BPD hospitalized at 15 centers within the BPD Collaborative who transitioned to PHV between March 2021 and March 2023. Hierarchical cluster analysis of patient demographics and ICU ventilator settings at the time of transition was identify similar groups and compare factors associated with successful transitions. Results: Patients with higher mean airway pressure (MAP) on the PHV compared with the MAP on their ICU ventilator were more likely to successfully transition on the first attempt, had fewer days from their first attempt until successful transition, and transitioned at an earlier postmenstrual age than patients with a lower MAP on their PHV. Cluster analysis of baseline ICU ventilator settings did not predict successful transition to PHV. Conclusions: We conclude that higher PHV pressures may enable patients with severe BPD to transition to a PHV. Premature weaning of ventilator pressures may be associated with prolonged need for an ICU ventilator.

Objectives: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, which can have life‐long effects. Commonly used definitions of BPD severity are based on respiratory support at 36 weeks post‐menstrual age. The utility of these definitions for tertiary referral centers outside the initial birth hospitalization is unclear. Study Design: Retrospective cohort study of infants born < 34 weeks gestation in the BPD Collaborative registry using three common definitions of BPD severity at 36 weeks post menstrual age and associated their severity with outpatient respiratory outcomes during the first 3 years of life. Results: BPD severity by all three definitions was applied to 608 patients. Although the definitions had different distributions of BPD severity for the cohort, a majority of participants (75.7%) had moderate/Grade 2 or severe/Grade 3 BPD irrespective of the definition. Using clustered logistic regression models, we found no association between any of the definitions of BPD and outpatient acute care use or the BPD control score. Conclusions: In this multi‐center cohort study, we did not observe a significant association between BPD definitions and respiratory morbidity following the initial birth hospitalization. Alternative risk‐based BPD definitions that can be integrated into the care of preterm infants following discharge need to be developed.

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.