Infant Pulmonary Function Testing (iPFT)
All measurements were performed according to the ATS-ERS guidelines10–12. Infants were clinically stable for at least 4 weeks prior to testing. Prior to testing, parental written consent was obtained. Infants were sedated using 100–150mg/kg triclofos sodium syrup or the equivalent 50-75mg/kg chloral hydrate syrup.
Prior to 2019, flows and volumes were measured via a custom made iPFT device using a heated pneumotachograph (series 3700A, Hans Rudolph Inc., USA) connected via a low-dead-space Rendell Baker face mask to a differential pressure transducer and signal conditioner set to 100 Hz (SCIREQ TD-05 & SC-24), as previously described13–16. Subsequent to 2019, flows and volumes were measured using a commercial device MasterScreen BabyBody (JAEGER/Vyaire). Differences in flow and volume measurements between the two testing devices were normalized for all infants tested, regardless of inclusion in current study.
iPFT measurements were uniform and included: Tidal breathing analysis with measurements of respiratory rate (RR), tidal volume (Vt), and Minute ventilation (MV); Baby-body plethysmograph for the measurement of functional residual capacity (FRCpleth) and airway resistance (Raw); Measurement of respiratory system compliance (Crs) with the multiple breaths occlusion technique prior to 2019 (for the control group) and with the single breath occlusion technique after 2019 (for the SARS-CoV-2 group); and Tidal and raised rapid thoraco-abdominal compression techniques for the measurements of forced expiratory airway flows. Forced expiratory flow at FRC (V̇maxFRC) was obtained from the tidal forced expiratory flow-volume curve, and the forced vital capacity (FVC), forced expiratory volume after 0.5 sec (FEV0.5) and forced expiratory flows at 50%, 75% and 85% of vital capacity (FEF50%, FEF75% and FEF85%) from the raised-volume expiratory flow-volume curve. Residual volume (RV) and total lung capacity (TLC) were calculated from the results of the plethysmography measurements and of maximal expiratory flow-volume curves.
Bronchodilator responsiveness (BDR) was defined positive if an improvement of 20% in the V̇maxFRC was documented twenty minutes after an inhalation of nebulized salbutamol as previously described17 or 4-5 puffs of Salbutamol inhaler (100mccg/puff) via valve holding chamber.
Pulmonary function results of all infants included in the study were categorized according to the physiological pattern diagnosed18: normal lung function pattern - V̇maxFRC (%pred)> 80%, and FRC(%pred) 80% -110%, and FVC(% pred)>80%; Obstructive pattern - VmaxFRC(% pred) <80% and FRC(% pred)> 80%; Restrictive pattern - VmaxFRC(%pred)<80% and FRC(% pred)<80%; Mixed pattern (obstructive and restrictive) - infants who do not meet any of the previous criteria.