SUMMARY We previously demonstrated that infants with a history of bronchopulmonary dysplasia (BPD) exhibit airflow obstruction and air trapping. The purpose of this study was to assess longitudinal changes in pulmonary function in infants with a history of BPD over the first three years of life, and the relationship to somatic growth. Spirometry was measured using the raised volume rapid thoracoabdominal compression technique, and lung volumes measured by plethysmography. Eighteen infants (mean gestational age±SD 27.3±2.2 weeks, birthweight 971±259 g) underwent two lung function studies. Average age at first test was 58.8 wks. Spirometry demonstrated significant reductions in forced expiratory volume in 0.5 sec (FEV0.5, 76.0±15.9% predicted, Z score −2.13±1.69), forced expiratory flow at 75% of expired forced vital capacity (FEF75, 54.8±31.1%, −3.58±2.73) and FEF25–75 (67.8±33.3%, −1.79±1.76). Group mean total lung capacity (TLC) was in the low normal range (82.9±13.5% predicted) and residual volume (RV)/TLC was mildly elevated (122.4±38.2% predicted). Repeat testing was performed an average of 32.7 weeks after initial testing. At re-evaluation, group mean lung volumes and flows tracked at or near their previous values; thus, in general, there was a lack of catch-up growth. However, compared to infants with below average or average somatic growth (as represented by gm/day), infants with above average growth showed significantly greater improvements in percent predicted FVC, FEV0.5, TLC and RV/TLC (all p<0.05, ANOVA). We conclude that longitudinal measures of pulmonary function in infants and young children with BPD demonstrate significant airflow obstruction and modest restriction which tends to persists with time. On the other hand, infants with above average somatic growth showed greater lung growth than their peers. Additional studies examining the effects of various nutritional regimens on lung function are warranted.

Background We have isolated mesenchymal stromal cells (MSCs) from tracheal aspirates of premature infants with respiratory distress. Under the influence of transforming growth factor-β, MSCs differentiate into α-smooth muscle actin-expressing myofibroblasts. Myofibroblasts are increased in the lungs of patients with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely-born infants. Objective We tested whether isolation of MSCs from tracheal aspirates of premature infants with respiratory distress during the first week of life correlates with BPD. Patients and Methods Eighty-four infants born at gestational age <33 weeks and requiring mechanical ventilation were studied. Aspirates were collected during suctioning and centrifuged. Cell pellets were resuspended in culture medium and plated. Adherent cells were grown to confluence. Results MSCs were isolated from the tracheal aspirates of 56 infants; 28 infants showed no MSCs. There was no statistical difference in gestational age or birth weight between the ‘MSC’ and ‘no MSC’ groups. In the MSC group, 12 died and 25 developed BPD, as defined by a requirement for supplemental O2 at 36 wks post-menstrual age. In the ‘no MSC’ group, 6 infants died and 1 developed BPD. Accounting for the potential influences of gender, birth weight, gestational age, number of tracheal aspirate samples taken and the duration of endotracheal intubation (up to 7 days), isolation of MSCs increased the adjusted odds ratio of BPD over 21-fold (95% confidence intervals: 1.82, 265.85). Conclusions Isolation of tracheal aspirate MSCs predicts the development of BPD, which suggests that MSCs play an important role in the pathogenesis of this disease.

Objective To report the clinical safety and efficacy of 3D-printed, patient-specific, bioresorbable airway splints in a cohort of critically ill children with severe tracheobronchomalacia. Methods From 2012–2018, 15 subjects received 29 splints on their trachea, right and/or left mainstem bronchi. The median age at implantation was eight months (range, 3–25 months). Nine children were female. Five subjects had a history of ECMO (extra-corporeal membrane oxygenation), and eleven required continuous sedation, six of which required paralytics to maintain adequate ventilation. Thirteen were chronically hospitalized, unable to be discharged, and seven were hospitalized their entire lives. At the time of splint implantation, one subject required ECMO, one required positive airway pressure, and 13 subjects were tracheostomy and ventilator dependent, requiring a median positive end-expiratory pressure (PEEP) of 14 cmH2O (range, 6–20 cmH20). Outcomes collected included level of respiratory support, disposition, and splint-related complications. Results At the time of discharge from our institution, at a median of 28 days’ post-implantation (range, 10–56 days), the subject on ECMO was weaned from extracorporeal support, and the subjects who were ventilated via tracheostomy had a median change in PEEP (discharge – baseline) of −2.5 cmH2O (range, −15 to 2 cmH2O, p=0.022). At median follow-up of 8.5 months (range, 0.3–77 months), all but one of the 12 surviving subjects lives at home. Of the 11 survivors who were tracheostomy dependent pre-op, one is decannulated, one uses a speaking valve, six use a ventilator exclusively at night, and three remain ventilator dependent. Conclusion This case series demonstrates the initial clinical efficacy of the 3D-printed bioresorbable airway splint device in a cohort of critically ill children with severe tracheobronchomalacia.

Background There are limited data assessing bronchodilator responsiveness (BDR) in infants and toddlers with recurrent wheezing, and factors associated with a positive response. Objectives In a multicenter study of children ≤ 36 months old we assessed the prevalence of and factors associated with BDR among infants/toddlers with recurrent episodes of wheezing. Methods Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 76 infants/toddlers (mean (sd) age 16.8 (7.6) mos.) with recurrent wheezing before and after administration of albuterol. Prior history of hospitalization or emergency department treatment for wheezing, use of inhaled or systemic corticosteroids, physician treatment of eczema, environmental tobacco smoke exposure, and family history of asthma or allergic rhinitis were ascertained. Results Using the published upper limit of normal for post bronchodilator change (FEV0.5 ≥ 13% and/or FEF25–75 ≥ 24%) in healthy infants, 24% (n=18) of children in our study exhibited BDR. The BDR response was not associated with any clinical factor other than body size. Dichotomizing subjects into responders (defined by published limits of normal)or by quartile to identify children with the greatest change from baseline (4th quartile vs. other) did not identify any other factor associated with BDR. Conclusions Approximately one quarter of infants/toddlers with recurrent wheezing exhibited BDR at their clinical baseline. However, BDR in wheezy infants/toddlers was not associated with established clinical asthma risk factors.

Improving nutrition and BMI for patients with CF is achievable. There must be a motivated, multi-disciplinary team that includes patients and families. A patient-specific combination of interventions must be used. These interventions could be quite basic for patients with BMI percentile ≥ 25, yet more elaborate for patients with BMI percentile <25. Clinic-based algorithms such as ours can successfully improve the BMI percentile in patients with CF.