This section describes the damage to the respiratory system associated with e-cigarette use, as well as the risks of non-infectious respiratory diseases. Infections of the airways are discussed in Section 18.6.6 and the risk of cancer in the airways, such as lung cancer, in Section 18.6.4.
18.6.5.1 Exposure of the respiratory system to chemicals during e-cigarette use
Frequent exposure to fine and ultrafine particles, such as tobacco smoke, air pollution, and dusts, can contribute to pulmonary and systemic inflammatory processes and increase the risk of respiratory diseases.1 E-cigarette aerosols and the e-liquids used in these devices contain hundreds of potentially harmful chemicals, as described in Section 18.5.2 A 2022 review by the National Health and Medical Research Council identified 42 chemicals in e-liquids and aerosols that are harmful or potentially harmful by inhalation. These include formaldehyde, benzaldehyde and diacetyl, as well as toxic metals/metalloids such as arsenic, cadmium and mercury (see Section 18.5.5.2).3 Another eight chemicals were identified that are known or suspected respiratory sensitisers.3 Respiratory sensitisers have the potential to trigger long term inflammatory conditions in the respiratory system.
Most of the harmful chemicals in e-cigarette aerosols and e-liquids are present at relatively low levels.3 However, the use of e-cigarettes is associated with an increased risk of acute reductions in lung function, discussed below in 18.6.5.2.4 The specific chemicals causing these effects have not been identified, and may include some of the hundreds in e-cigarettes with unknown inhalation toxicity. Importantly, the health effects from multiple daily inhalation exposures to these chemicals at low levels, continuing for many years, are not yet known.
Some researchers caution that respiratory toxicants in e-cigarette aerosols may pose a threat to the respiratory health of users, particularly as the flavours have primarily been tested in regard to ingestion, rather than inhalation.38, 50-54 One study found that the concentrations of some flavour chemicals in e-cigarette fluids are sufficiently high for inhalation exposure by vaping to be of toxicological concern,5 and another found that flavours (along with product type and battery output voltage) significantly affected toxicity of e-cigarette aerosol, with a strawberry-flavoured product being the most cytotoxic.6
An analysis of e-cigarette refill liquids across nine European countries found that all of the samples analysed had additives that are classified to have some level of danger/risk of hazard based on the global classification system for respiratory irritants.7 In Australia, where nicotine e-cigarettes may only legally be sold to those with a prescription from a medical practitioner, the TGA has banned eight chemicals in these due to health risks. However, seven of these are also often found in non-nicotine e-cigarettes, which currently may legally be sold to adults in most Australian jurisdictions (see Section 18.5.5.3). Two of these, benzaldehyde and cinnamaldehyde, were detected in most of the e-liquid samples tested in a study conducted in Western Australia.8 Overseas researchers have suggested that regulatory limits should be considered for levels of some of the more worrisome chemicals as well as for total flavour chemical levels, and that ingredients should be labelled.5 Other public health experts advocate a ban on sale of all vaping products other than those that a prescribed by medical practitioners.9
18.6.5.2 Acute respiratory conditions associated with e-cigarette use
There is convincing evidence that the acute, and sometimes fatal, lung condition known as EVALI (E-cigarette or Vaping Associated Lung Injury) is caused by e-cigarette use, discussed in Section 18.6.5.4 below.
Aside from EVALI, there are no other acute respiratory conditions associated with e-cigarette use that are strongly supported by scientific evidence. However, there is evidence for damage to the lungs including inflammation, referred to as subclinical measures of respiratory function, as well as case reports of rare conditions that are potentially associated with e-cigarette use.10, 11
Subclinical measures of lung function, such as spirometry, are useful predictors of disease state. These measures are important for predicting the health effects of e-cigarette use, as clinical outcomes such as asthma and COPD may take many years to develop.11 Measures of exhaled carbon monoxide and nitric oxide are also used as markers of lung inflammation.11
Multiple reviews have found evidence for a decrease in lung function (based on spirometry and other tests) for non-smokers in the two hours after using an e-cigarette.4, 11, 12 However, the evidence comes from small trials and may be considered ‘limited’.11 There is also ‘limited’ evidence that e-cigarette use leads to decreased lung function and respiratory inflammation in healthy and asthmatic smokers up to 30 minutes after exposure.4, 11, 12
Use of nicotine-containing e-cigarettes may be associated with short-term increases in the urge to cough and cough sensitivity. However these data come mostly from studies described as ‘fair’ quality, so higher quality studies are needed for firmer conclusions.11, 12
Aside from the EVALI outbreak in 2019, described below, there are case reports and case series that indicate the potential for some acute respiratory diseases in e-cigarette users. These include diagnoses of eosinophilic pneumonia, hypersensitivity pneumonitis, organising pneumonia, diffuse alveolar haemorrhage and giant cell foreign body reaction.10 These pneumonia diagnoses appeared to involve lung damage in the absence of infection. Some of these conditions may have been early cases of EVALI. Common to EVALI and many of the earlier case reports are the presence in the lungs of immune cells called macrophages that had engulfed copious lipids (fats), consistent with a deposit of chemicals in the lungs. However, it’s not known whether the actions of these cells are part of a pathological mechanism leading to the disease, or if they are actually inhibiting lung pathology.10 One study found that dual users of cigarettes and e-cigarettes reported poorer general health and greater breathing difficulty in the past month compared to those who smoked only cigarettes.13 Since these studies come from case studies and case reports, larger studies are necessary before concluding that e-cigarette use is associated with an increased risk from these conditions (except for EVALI, for which the evidence is strong).
Bronchiolitis obliterans (‘popcorn lung’) is a rare inflammatory disease of the small airways of the lungs (bronchioles) that results in obstruction and permanent scar tissue in the lungs. This irreversible lung damage leads to shortness of breath and a dry cough. The name “popcorn lung” came about due to the disease sometime being caused by inhalation of the artificial butter flavouring chemical diacetyl, which is used to flavour popcorn. Diacetyl, added to some e-liquids, and another chemical called methylglyoxal that also causes bronchiolitis obliterans, have been detected in the emissions from e-cigarettes.14-16 Although these chemicals are present in very low amounts in e-cigarette emissions, one study has estimated that diacetyl levels in the emissions of some e-cigarettes exceed the proposed safe levels of exposure.15 However, aside from one case study,17 they is currently no evidence of widespread bronchiolitis obliterans in people who use e-cigarettes.
18.6.5.3 Chronic respiratory conditions associated with e-cigarette use
Due to the limited time in which e-cigarette use has been popular, there is currently no definitive evidence whether or not e-cigarettes cause long-term respiratory diseases in humans.11, 12 Based on long-term exposure to the chemicals that damage the respiratory system and the emerging evidence for a risk of short-term inflammation and decreased lung function, e-cigarette have the potential to cause chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema and asthma. There are also carcinogens (cancer-causing chemicals) at low levels in e-cigarette aerosols, which have the potential to cause cancer in the respiratory tract, discussed in Section 18.5.5.2
Numerous studies indicate an association between e-cigarette use and asthma in adolescents, as described in Section 18.6.2.18-20 Much of the supporting data, however come from cross-sectional studies,18 whereas prospective studies would provide stronger evidence for this association. A 2022 Australian review concluded that there was insufficient evidence to support an association of e-cigarette use and asthma.11
18.6.5.4 EVALI (E-cigarette or Vaping Associated Lung Injury)
An outbreak of serious acute lung injury associated with e-cigarette use began in the US in July 2019, peaking in August and gradually declining from September 2019. The Centers for Disease Control and prevention (CDC) report 2,807 instances of hospitalisation and 68 deaths from EVALI in the US from August 2019 until February 2020, when data collection stopped due to the COVID pandemic.21 EVALI is also referred to as Vaping-Associated Pulmonary Injury (VAPI), and has also been referred to as acute lipoid pneumonia in case reports.11
Symptoms of EVALI include shortness of breath, fever, cough, vomiting and diarrhoea, occurring in the absence of infection or other lung injury. EVALI is difficult to diagnose as there is no confirmatory diagnostic test and the symptoms are similar to other respiratory diseases such as influenza. The lungs of people with EVALI are inflamed and contain abnormally high numbers of inflammatory cells.22
Case reports have indicated that EVALI more often occurred in healthy white men who were adolescent or young adults, usually using e-cigarettes containing tetrahydrocannabinol (THC; the major psychoactive ingredient of cannabis) and the additive vitamin E acetate (VEA). E-cigarettes used by these people were more likely to come from illicit sources.22
A recent, comprehensive review from Australia found conclusive evidence that e-cigarette use causes EVALI in smokers and non-smokers.11 The exact mechanisms by which e-cigarettes are causing EVALI are unknown. The strong association of EVALI with recent use of e-cigarettes containing THC and VEA indicates that either VEA, or another chemical often present in THC/VEA e-cigarettes, may be triggering this disease.21 VEA is found in the lung fluid of 94% of people with EVALI, but not people without EVALI.23 Increased awareness of the potential dangers of VEA as an ingredient in illicit THC cigarettes and the removal of VEA from some products may have contributed to the steady decline in the number of people diagnosed with EVALI.24
Whilst VEA (or a contaminate or breakdown product of VEA) is a strong candidate for a cause of EVALI, it may not be the only cause. Not all people with EVALI were recent users of THC/VEA e-cigarettes. In one study, 51% of people with EVALI reported recent use of both THC and nicotine e-cigarettes and 17% reported sole use of nicotine e-cigarettes.22 A study that measured chemicals in the lung fluid from EVALI patients reported that 94% contained THC and 64% contained nicotine or its breakdown products (metabolites).23 Taken together, these studies indicate that between 6% and 17% of people with EVALI were not recent users of THC-containing e-cigarettes. However, the apparent absence of THC/VEA in some EVALI patients could also reflect a misdiagnosis of this condition, for which diagnosis remains challenging.
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References
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