Abstract:
Background: Transient Tachypnoea of the Newborn (TTN) is the most common cause of neonatal respiratory distress and results primarily from delayed clearance of fetal lung fluid. Although usually self-limiting, TTN may progress to severe complications such as persistent Pulmonary Hypertension of the Newborn (PPHN). Lung Ultrasound (LUS) has emerged as a reliable, radiation-free bedside modality that improves diagnostic accuracy and monitoring of neonatal respiratory disorders compared with conventional chest radiography.
Objective: To evaluate the efficacy and safety of inhaled salbutamol as an adjunct to non-invasive nasal Continuous Positive Airway Pressure (nCPAP) in neonates with TTN, with particular emphasis on dynamic assessment using lung ultrasound.
Methods: This is a multicentre, double-blind, randomized, placebo-controlled phase III trial including 608 neonates (gestational age 32-42 weeks) presenting with early respiratory distress consistent with TTN. Participants are randomized (1:1) to receive nebulized salbutamol or placebo (0.9% NaCl), both combined with nCPAP.
Lung ultrasound is a key component of the study protocol and is performed at two predefined time points: Within 6 hours of enrolment and 6-10 hours after the last dose of the intervention. A modified LUS scoring system is applied, incorporating four lung regions (including posterior fields) and a 5-point grading scale (0-4), where higher scores reflect increasing severity of aeration loss and presence of consolidations. The total LUS score ranges from 0 to 16.
LUS is used to:
- Support early diagnosis of TTN and differentiate it from other neonatal respiratory conditions.
- Quantify the severity of pulmonary involvement.
- Monitor response to treatment and fluid clearance dynamics.
Primary outcome is the incidence of PPHN. Secondary outcomes include respiratory distress severity (modified TTN Silverman score), need for intubation, duration of nCPAP and hospitalization, and biochemical parameters. Correlation between LUS scores and clinical outcomes will be analyzed.
Results (expected): It is anticipated that neonates receiving salbutamol will demonstrate faster improvement in LUS scores, reflecting enhanced alveolar fluid clearance. A reduction in LUS score is expected to correlate with clinical improvement, shorter respiratory support duration, and lower risk of progression to PPHN. LUS may provide earlier detection of treatment response compared with clinical or laboratory parameters alone. Statistical analysis is currently ongoing, and final results will be available for presentation at the upcoming conference.
Conclusions: Lung ultrasound represents a central, non-invasive tool in this trial, enabling real-time, repeatable assessment of pulmonary status without radiation exposure. Integration of LUS into the management of TTN may enhance diagnostic precision, guide therapeutic decisions, and serve as a sensitive marker of treatment efficacy. If successful, this study will support the combined use of salbutamol and LUS-guided monitoring as an optimized strategy for managing TTN and preventing its complications.
