Virtual International Pediatric Pulmonary Network (VIPPN)

Editor's Choice

February 2019

José Castro-Rodríguez MD

Yoshihara S, Tsubaki T, Ikeda M, Lenney W, Tomiak R, Hattori T, Hashimoto K, Soutome T, Kato S. The efficacy and safety of fluticasone/salmeterol compared to  fluticasone in children younger than four years of age. Pediatr Allergy Immunol. 2018 Dec 17. doi: 10.1111/pai.13010.

This is the first randomized, double-blind study designed to evaluate the use of combination therapy (ICS/LABA) in preschoolers with asthma. 

The authors randomized 300 asthmatic preschoolers (8 months to 4 years of age) comming from 70 pediatric centers in Japan. One group received fluticasone/salmeterol (50/25 ug) or fluticasone (50ug) 1 or 2 puff​ BID, according with age, for 8 weeks. They reported that preschoolers from the fluticasone/salmeterol group were not superior to those from the ICS group in improving total daily asthma score (main outcome), nor in secundary outcomes such as AM or PM asthma score, exacerbations, or rescue medication. The only secundary outcome were fluticasone/salmeterol was superior than ICS was in the Japanese Pediatric Asthma Control parameter, which is a local asthma score but without minimal clinically important difference (MCI) stablish, therefore this particular results is questionable. The adverse events were similar betwee groups.

No data on adherence was reported, and it was not clear if preschoolers less than 2 years of age received the therapeutic doses of salmeterol (50 ug BID).

In contrast to randomized studies done in schoolers or adolescents with moderate to severe asthma were ICS/LABA has advantage over ICS in asthma control and some lung function parameters, it appears that at this moment in asthmatic preschoolers there is no clear space for adding LABA. 

More randomized studies need to be done before we incorporate LABA in preschoolers with moderate-severe asthma.

January 2019

Tom Ferkol, MD

Ghosh A, Coakley RC, Mascenik T, et al. Chronic e-cigarette exposure alters the human bronchial epithelial proteome. Am J Respir Crit Care Med. 2018;198:67-76.

Lured by deceptive marketing tactics and popular flavorings, electronic cigarettes have emerged as a threat to the health of children and adolescents. During the past decade, electronic cigarettes have rapidly risen in popularity among young people in many countries. In the United States (US), use of electronic cigarettes rose nearly 80% last year, with one-in-five high school students using these products regularly.

Even though the US National Academies of Sciences, Engineering, and Medicine found substantial evidence that exposure of potentially harmful ingredients from electronic cigarettes is lower than combustible cigarettes, it does not mean that electronic cigarette aerosols are “harmless”, contrary to industry claims. Several lines of evidence from in vitro and animal studies have revealed the deleterious effects of electronic cigarette vapors, showing that e-cigarette exposure causes inflammation, oxidative stress, and is toxic to pulmonary, endothelial, and stem cells in culture. However, remarkably few clinical studies have examined their effects on the human lung.

In this study, published last year in the American Journal of Respiratory Critical Care Medicine, Arunava Ghosh and colleagues from the University of North Carolina at Chapel Hill performed proteomic analyses of lavage samples collected from healthy non-smokers (n = 8), smokers (n = 9) and vapers (n = 9) who used the product for more than 6-months clearly showed that electronic cigarette vapors exert marked and extensive biological effects on human airways. Specifically, the authors found that 191 proteins were significantly up- or down-regulated in airway secretions from electronic cigarette users, in contrast to 292 altered proteins in smokers. A total of 113 proteins were uniquely changed in vapers, affecting fourteen pathways involved in mucin production, innate immunity, early endosomes and trafficking, macromolecular complexes, and mitochondria. Moreover, these effects were primarily mediated by the propylene glycol/vegetable glycerin base.

While long-term consequences are still unknown, vaping indisputably exerted extensive biological effects on human airways, leading the authors to conclude that “inhalation of e-cigarette vapor is not without consequences and by no means innocuous, and they should not be prescribed as a safe or harmless tobacco alternative.”