Novel immunologic and physiologic predictors of pediatric lung disease in premature children. A prospective cohort study
BACKGROUND: BPD is the most frequent cause of severe lung morbidity in premature and very low birth weight (VLBW) infants, with serious long-term consequences. However, today we are unable to precisely identify those children destined to experience severe pulmonary problems until they can perform a spirometry. The forced oscillation technique (FOT) is a modern non-invasive tool to estimate respiratory mechanics. FOT has been shown to be a sensitive tool to detect early disease changes in other etiologies such as asthma and COPD. Despite this, its clinical utility in preschool preterm born children has not yet been established. GAP: The need for sedation during evaluations of pulmonary function at a young age and the absence of good biomarkers for asthma greatly contribute to this diagnostic limitation. Forced oscillatory test (FOT) uses the children’s spontaneous respiration without sedation to indicate the condition of the small and large airways. HYPOTHESIS: We hypothesize that FOT in children 2.5-4 years of age will be a feasible technique and able to discriminate preterm young children from healthy controls. METHODS: This study was a prospective, observational multi-center study part of the Discovery-BPD Program. Preterm children with birth weight < 1250 gr were studied at 3-6 years of age. This study was then supplemented with additional participants living in Porto Alegre, Brazil. The FOT measurements were made with purpose‐built equipment in accordance with the guidelines and recommendations of the ATS/ERS. Mechanical impedance of the respiratory system (Zrs) resistance (Rrs) and reactance (Xrs) were recorded. The oscillatory signal was applied to the respiratory system via a mouthpiece during tidal breathing (Picture 1). Zrs spectra was measured using in the frequency range 6–32 Hz as well as with a 10-Hz signal as a novel FOT modality, to establish the changes in Zrs between end expiration and end inspiration (within-breath). RESULTS: Mechanical resistance of the respiratory system was significantly increased in VLBW born children in all spectra as well as total respiratory resistance. Reactance was also significantly different at X6, X8 and X10 Hz in VLBW subjects compared to term born children (. Lastly, intra-breath oscillometry showed changes on both impedance and resistance at the end of inspiration (XeI, ReI) and at the end of expiration (XeE, ReE). We showed that it is a feasible technique that detects changes in small airway disease of prematurity with the hopes of identifying individuals and designing interventions to prevent the developing of this life-long pulmonary disease. IMPACT: Early life, accurate and simple prediction of lung disease in premature babies should allow -after validation in similar populations- early, personalized evaluation of novel interventions to prevent a serious and growing lifelong public health problem that affects quality of life and life expectancy.