The toxicity of E-cigarettes and children’s respiratory health

Summary

Electronic cigarettes (E-cig), also referred to as Electronic Nicotine Delivery System (ENDS), were initially developed in 2003 to reduce the harmful effects of tobacco smoking. Since then, E-cig have become widely available in many countries and are used by many young people who would be unlikely to take up cigarette smoking. However, the adverse effects on child health remain largely unknown. E-cigs are available through regulated sale in many countries, but easily accessible by the internet in others.

Adverse effects may be ascribed to the nicotine itself, to the accompanying substances in the aerosol (often referred to as vapour) or to temperature modifications of the content. There is a lack of human studies to assess respiratory effects of nicotine exposure to the unborn or young child. Also assessing the effects of the vaping content apart from nicotine is challenging, with the huge variety of exposure by frequency, duration and content, but experimental studies are on the way that may indicate the level of harm by such products.

This article will summarize what is currently known about the use of E-cigs in children and in pregnancy, and discuss adverse effects of direct or in utero exposure to E-cig on the respiratory health of children. We thereby hope to provide a background for discussing potential harms to the respiratory system of children by E-cig exposure in pregnancy and early post-natal life, in a setting where an increasing proportion of adolescent and young adults use E-cigs, marketed to be 95% less harmful than conventional cigarettes.

Introduction

An E-cig is produced to deliver nicotine-containing aerosol by heating a solution often containing glycerol and a battery, a vaporizer and a cartridge with fluid aerosolized through a mouthpiece. With the large variation in content, doses and concentrations of nicotine, flavouring and other substances, often with poor labelling, it will be challenging to determine the effects on children’s respiratory wellbeing. Indeed, acute and life-threatening nicotine poisoning due to ingestion of the cartridge contents has been reported [1].

The invention of the electronic cigarette (E-cig) in 2003, or Electronic Nicotine Delivery System (ENDS) (hereafter referred to as E-cig), has been attributed to a Chinese pharmacist (Hon Lik) [2] to reduce the harmful effects of cigarette smoking. Electronic cigarettes became available in the United States of America in 2007 selling for $20 million in 2008, with sales increasing to $1.7 billion in 2014 and expected to grow about 25 percent a year through 2018 [3]. Rapidly increasing use of E-cigs has been observed also in other countries with increased availability [2] followed by heated public and medical debates [4], [5] on potential benefits versus harmful effects of E-cigs. To combat potential harmful effects, regulating the sale of E-cig is currently implemented in 68 countries, often by regulations that have not been developed to embrace ENDS [2]. However, most include a minimum age for purchase and restrictions of indoor use, production, import and marketing [2] of E-cigs, often challenged by how to classify and regulate E-cigs related to content of nicotine and flavoured additions to the aerosols. Arguments against regulations include claims [6], [7] or beliefs [3], [8] that E-cigs are substantially less harmful than conventional cigarettes or even safe [8]. However, the increasing use of E-cigs among the young and potential future parents and the hitherto unclear harmful effects on the offspring, challenges the overall societal harm-reduction benefits of E-cigs. In line with many countries around the world [2], the European Commission recently concluded that the use of refillable electronic e-cigarettes, and the potential exposure to e-liquids containing nicotine in high concentrations, may pose risks to public health [9].

Potential benefits of E-cigs would be related to cessation or reduced smoking in established smokers, and E-cigs have been claimed to be 95% less harmful than smoking conventional cigarettes. In fact, in the Royal College of Physicians report. “Nicotine without smoke: Harm reduction” from 2016, E-cigs are classified as a Nicotine Replacement Therapy (NRT) [7], with the clear intention of preventing unnecessary deaths in smokers. However, documentation of E-cigs being effective in smoking cessation is controversial [10], and the claimed 95% harm reduction compared to conventional cigarettes [6], [7] has not been documented [4], [7]. Worryingly, E-cigs have become widely used by young people who were unlikely to take up smoking [11], [12], [13], and cigarette smoking appears to be more common among adolescents who tried E-cigs than among those who had not [13]. The overall harm-reducing effects of E-cigs to society and to individuals are therefore questionable, as there is no safe or risk free level of nicotine exposure [14]. Also, there are limited human studies to outline potential harmful effects of E-cigs with and without nicotine [15]. The public acceptance of E-cig –use [16] to reduce harm from cigarette smoking, challenges the efforts to prevent tobacco or nicotine use in young people, in a setting where harmful effects of E-cigs are largely unknown. Based upon the known harmful respiratory effects in the offspring by maternal (or grandmother) cigarette smoking, snuff use and nicotine exposure in animal models [17], we need rapid action to prevent avoidable respiratory disease in the child.

The prevalence of E-cig use among women and men of child-bearing age is not available in many countries. However, from the United States, current (last 30 days) use of tobacco was reported by 20% of high-school students and 7.2% of middle-school students in 2016. This was most often reported as use of E-cigs in 11.3% of the high-school and 4.3% of the middle-school students [18]. In Finland, reported ever-use of E-cigs increased among 12- to 18-year-old children from 17.4% in 2013 to 25% in 2015, half of them having tried nicotine e-liquids [12]. Weekly use was, however low, at 1.5% [12]. Although males more commonly reported any type of tobacco use as well as E-cigs, 9.5% of American high-school females reported current use of E-cigs, carrying a significant risk of using E-cigs in future pregnancies [19]. Data on the beliefs and use of E-cigs before or during pregnancy is emerging [19], [20], [21]. In an online survey of 455 pregnant women in the United States, 6.52% reported sole use of E-cigs, 5.6% sole use of conventional cigarettes and 8.45% both E-cigs and conventional cigarettes during pregnancy [19], whereas another anonymous survey of 316 pregnant women showed ever-use in 13%, but current daily use in 0.6% only [21].

Adverse effects on child respiratory health by exposure to tobacco smoking before, during and after pregnancy has been firmly established [17], whereas the effects of exposure to nicotine by other routes are less well documented. Registry studies from Sweden, where snuff has been on sale for many years, have shown that snuff use increases the risk of stillbirths [22], preterm delivery, pre-eclampsia, infant apnoea [23], neonatal mortality [24] with a modest reduction in birth weight [24]. Snuff was subsequently not seen as a safe alternative to smoking in pregnancy [24]. There is however a lack of follow-up studies in children to determine the possible role of pre-natal snuff exposure on respiratory development and consequences for health of the child. Spindel and McEvoy [17] recently concluded that the effects on off-spring pulmonary development by prenatal nicotine exposure in animal models were strikingly similar to those of maternal cigarette smoking in pregnancy. With the current rapid increase in use of E-cigs, there is an urgent need to determine both short-term and long-term potential adverse effects on the growing child, including foetal and post-natal development of the respiratory system.