Patient and clinical characteristics.

<p>*Values shown are medians (inter-quartile range) with superscript numbers indicating days in addition to gestation in weeks; ^∧ values shown are numbers of infants (percentage of total in group).</p><p>Patient and clinical characteristics.</p

Neutrophil chemotaxis to preterm BALF.

<p>Chemotaxis of adult human neutrophils to pooled BALF from BPD infants after incubation for 60 min. Conditions are detailed on the x-axis while concentration of neutrophils (cells/ml) are expressed on the y-axis. Bars are at means (± SEM) of three independent experiments, each done in triplicate. Conditions were compared by one-way ANOVA with Dunnet's correction, comparing against a control column (BALF only). (*** = p<0.001).</p

Modulation by proteinase-3.

<p>Summary of processing of rhIL-8₇₇ by purified proteinase-3 showing recovery of total IL-8 (squares) and IL-8₇₇ (circles) and release of MMP-9 from neutrophils in response to the products of conversion (triangles). Time (hours) is represented on the x-axis while IL-8/MMP-9 (fold change from 0-hour values) is represented on the y-axis. Points plotted are means (± SEM) of three independent experiments, each measured by ELISA in duplicate. Statistical differences in concentration compared to buffer-control at each time-point was tested by 2-way ANOVA with Bonferroni's correction. (* = p<0.05, ** = p<0.01, *** = p<0.001).</p

Expression of IL-8 and IL-8₇₇ in preterm BALF.

<p>(a) Peak concentration of total IL-8, (b) corresponding IL-8₇₇ and (c) proportion of IL-8₇₇, expressed as a percentage of total IL-8, in preterm BALF from infants in the No-BPD group (circles, n = 11) and BPD group (squares, n = 11). Groups are represented on the x-axis while concentration of each antigen (pg/ml, log scale) or proportion (as a percentage) is represented on the y-axis. Each point represents a single infant and bars are at medians. (* = p<0.05)</p

Expression of IL-8₇₇ from cultured cells.

<p>Proportion of IL-8₇₇, expressed as a percentage of total IL-8, from un-stimulated (open bars) and stimulated (shaded bars) (a) airway epithelial cells and (b) term cord-blood neutrophils and monocytes. Cells-types are represented on the x-axis while percentage of IL-8₇₇ is represented on the y-axis. Bars are means (± SEM) of three independent cell-culture experiments, each conducted in duplicate. All supernatants were separately measured by ELISA in duplicate.</p

Convertase activity of preterm BALF.

<p>(a) Concentration of IL-8₇₇ detected by ELISA at 0 hours and after incubation in different conditions for 18 hours. Conditions are detailed on the x-axis and fold change of IL-8₇₇ (compared to concentration at “0-hour”) on the y-axis. All bars are at means (± SEM). Conditions were compared by repeated measures ANOVA with Dunnets correction, comparing against a control column (BALF at 18 hour, n = 18). (b) Concentration of IL-8₇₇ detected by ELISA at 18 hours in No-BPD (open bar, n = 9) and BPD (shaded bar, n = 9) infants. Infant groups are detailed on the x-axis and concentration of IL-8₇₇ (fold change from “0-hour”) on the y-axis. All bars are at means (± SEM). (* = p<0.05, ** = p<0.01, *** = p<0.001)</p

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial

Importance  The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective  To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years’ corrected age. Design, Setting, and Participants  Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years’ corrected age was completed on December 9, 2022. Interventions  Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures  The key secondary outcome of death or moderate to severe NDD was assessed at 2 years’ corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results  Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, −7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance  In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration  anzctr.org.au Identifier: ACTRN12611000916943</p