Inhaled Budesonide in Neonatal Respiratory Distress Syndrome of Near-Term Neonates: A Randomized, Placebo-Controlled Trial

OBJECTIVE This study evaluates the value of inhaled budesonide (BUD) administration in neonatal respiratory distress syndrome (RDS) cases especially for near-term neonates. METHODS A randomized controlled trial involving 120 neonates with respiratory distress, which was diagnosed as RDS, was conducted from July 2016 to March 2018. The neonates studied were divided into 2 groups: group 1 (the inhaled BUD group), consisting of 60 neonates who received BUD (2 mL, 0.25-mg/mL suspension) inhalation, twice daily for 5 days; and group 2 (the placebo group), consisting of 60 neonates with RDS who received humidified distilled sterile water inhalation (2 mL). Downes score, RDS grades, and interleukin 8 (IL-8) levels were monitored and measured on the first and fifth days of incubation. RESULTS Statistically significant differences (SSDs) in RDS grades, Downes score, and IL-8 levels on the fifth day of admission were observed between groups 1 and 2 (p = 0.001) and between the first and fifth days of incubation in group 1 (p = 0.001). The SSDs in the duration of hospitalization (p = 0.001) and the number of neonates receiving mechanical ventilation (p = 0.032) were found between both groups. CONCLUSIONS Budesonide inhalation is associated with improvements in clinical and laboratory parameters in neonates with RDS

Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19

Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. Safe and effective treatments will need to be both affordable and widely available globally to be used alongside vaccination programmes. This analysis will estimate and compare potential generic minimum costs of a selection of approved COVID-19 drug candidates with available international list prices. Methods We searched for repurposed drugs that have been approved by at least one of the WHO, FDA or NICE, or at least given emergency use authorisation or recommended for off-label prescription. Drug prices were searched for, for dexamethasone, budesonide, baricitinib, tocilizumab, casirivimab and imdevimab, and sarilumab using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from a range of low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured for some treatments at very low per-course costs, ranging from $2.58 for IV dexamethasone (or $0.19 orally) and $4.34 for inhaled budesonide. No export price data was available for baricitinib, tocilizumab, casirivimab and imdevimab or sarilumab, but courses of these treatments are priced highly, ranging from $6.67 for baricitinib to $875.5 for sarilumab. When comparing international list prices, we found wide variations between countries. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Dexamethasone and budesonide are widely available and affordable, whilst monoclonal antibodies and IV treatment courses are more expensive.

CÓMO LEER Y GENERAR PUBLICACIONES CIENTÍFICAS. REVISIÓN CRÍTICA DEL ARTÍCULO “Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial”, de Sanjay Ramakrishnan y cols. PUBLICADO EN LANCET RESPIR MED

n

Efficacy of Budesonide, Epinephrine and Salbutamol Inhalation for Treatment of Transient Tachypnea of Newborn: Prospective Controlled Study

Background: Transient tachypnea of the newborn (TTN) is a neonatal lung disease which has a picture of lung edema due to delayed resorption of lung fluids. It is commonly seen in full-term or late-preterm in­fants with an occurrence rate of 5.7 in 1,000 infants. The aim of this work was to compare the efficacy of inhaled budesonide, epinephrine and salbutamol for treatment of TTN. Methods: This prospective controlled study was conducted on a100 full term neonates with presumed diagnosis of TTN. They were randomly assigned into four groups equally. Group I received nebulized budesonide, Group I received nebulized epinephrine, Group III received nebulized salbutamol and Group IV received nebulized normal saline. Results: Salbutamol significantly decreased respiratory rate and TTN clinical score, duration of respiratory support along with hospitalization time and helped with reaching full feeding earlier compared to other groups. Conclusions: Inhaled salbutamol significantly decreased TTN clinical score, shorter duration of respiratory support, hospitalization and earlier initiation of enteral feeding compared to placebo. Inhaled budesonide and epinephrine did not significantly reduce the duration of oxygen treatment, with no other significant effect on TTN.

Dampening of the respiratory cytokine storm is promoted by inhaled budesonide in patients with early COVID-19

SummaryVaccinations against SARS-CoV-2 are effective in COVID-19. However, with limited vaccine access, vaccine hesitancy and variant breakthroughs, there is still a need for effective and safe early treatments. Two community-based clinical trials of the inhaled corticosteroid, budesonide, have recently been published showing and improvement in patients with COVID-19 treated early with budesonide1,2. To understand mechanistically how budesonide was beneficial, inflammatory mediators were assessed in the nasal mucosa of patients recruited to the Steroids in COVID (STOIC1) trial and a cohort of SARS-CoV-2 negative individuals. Here we show that in early COVID-19, elevation in viral response proteins and Th1 and Th2 inflammation occurs. Longitudinal sampling in the natural course of COVID-19 showed persistently high interferon levels and elevated concentrations of the eosinophil chemokine, CCL11. In patients who deteriorate, the initial nasal mucosal signal is characterised by a marked suppression of the early inflammatory response, with reduced concentrations of interferon and inflammatory cytokines, but elevated eosinophil chemokines. Systemic inflammation remained altered in COVID-19 patients, implying that even after symptom resolution, changes in immunological mediators do not resolve. Budesonide treatment decreased IL-33 and IFN-γ, implying a reduction in epithelial damage and dampening of the interferon response. Budesonide treatment also increased CCL17 concentrations, suggesting an improved T-cell response; and significantly alters inflammatory pathways giving further insight into how this treatment can accelerate patient recovery.Abstract Figure

Budesonide nebulization in preterm neonates with evolving brochopulmonary dysplasia after 14 days of life: a case series

Bronchopulmonary dysplasia (BPD) with oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of premature newborns. BPD occurs due to pulmonary inflammation. Reducing pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD but is associated with an increased risk of long and short-term side effects. Local administration of corticosteroids via inhalation might be an effective and safe alternative. Currently, there is no recommendation for use of inhaled corticosteroids in neonatal respiratory care. However, it is being used in neonatal intensive care units (NICU) across the world in ventilator and oxygen-dependent babies. We shared our experience with the use of inhaled budesonide on nine ventilator-dependent very low birth weight (VLBW) preterm neonates in the form of case series and review the literature.