Summary
• Asthma is caused by reversible airway obstruction resulting in patient’s experiencing a wheeze, cough and dyspnoea1.
• In DEP a compound polycyclic aromatic hydrocarbon is thought to cause exacerbations of asthma2.
• A raised amount of IgE antibodies is associated with asthma and DEP are linked to stimulating its synthesis2, 3.
• The majority of research has found DEP is associated with exacerbations of asthma. However, contradictory research has also been found, concluding DEP is not always associated with an exacerbation of asthma.
• This review highlights the paramount importance of carefully examining the research available and considering confounding variables, which could influence results.
Methods
To collate information for this review a variety of databases were used. Databases include, Primo, PubMed, Google Scholar and Trip. Key terms such as “asthma and diesel exhaust particles”, “effect of diesel exhaust particles on asthma”, “’diesel exhaust particles’ and asthma” and “diesel exhaust particles exacerbation of asthma” were used. Studies conducted on non-human participants and those older than twenty-five years were rejected and not included in this review. In order to be included in this review, studies were required to have a minimum of 10 participants and conducted in a controlled setting with confounding variables to a minimum. All studies included in this review were critically appraised taking into consideration study design, sample size and location.
Table 1:
Database Search Terms Hits
TRIP Effect of diesel exhaust particles on asthma 52
“Diesel exhaust particles” and “asthma” 42
“Diesel exhaust particles exacerbation of asthma”, 24
Google Scholar “Diesel exhaust” and asthma 13,800
PubMed Effect of “diesel exhaust particles” on asthma 50
Primo Diesel exhaust particles and asthma 797
“Diesel exhaust particles” and asthma 129
“Pathogenesis” of asthma 4,130
Table 1 shows search terms used to generate appropriate results for this review. It also provides examples of how search terms were refined to generate more concise results.
Introduction
Asthma is defined as “recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person”4. It has been estimated up to 334 million people worldwide potentially have asthma5. Symptoms of asthma include a wheeze, cough, sputum production and intermittent dyspnoea1. Risk factors such as atopy and the development of IgE antibodies against allergens have been identified and are said to increase the likelihood of developing asthma6. There has been a strong association of DEP exacerbating asthma. DEP contain polycyclic aromatic hydrocarbons which are said to be the main toxic constituent as they are able to cause oxidative stress7. Carbon monoxide, nitrogen oxides and formaldehyde are compounds present in DEP which can cause irritation of the respiratory tract8.
This review aims to analyse and review studies that have aimed to investigate whether DEP cause an exacerbation of asthma. It is of paramount importance to research this as isolating and identifying known triggers for asthma can help reduce the number of exacerbations experienced by patients.
Studies that have found diesel exhaust particles cause an exacerbation of asthma
The effect DEP have on asthmatic patients is an area that has attracted increasing research over the past years.
27 severe asthmatics with a mean age of 57 years old were recruited to investigate the effect of DEP on their asthma against a control group2. Stringent criteria participants had to comply with were meeting GINA guidelines, having uncontrolled asthma for at least one year and two serious exacerbations of asthma requiring oral steroids2. In the presence of DEP, peripheral blood mononuclear cells were cultured and T- cell proliferation was monitored by flow cytometry, which were well-controlled methods2. The study concluded diesel exhaust particles cause an activation of T cells in asthmatic patients, particularly those with uncontrolled asthma which can lead to exacerbation of symptoms2. Furthermore, the study provided a table on participant’s profiles including age, gender, presence of atopy and FEV1 values allowing a more detailed understanding2. Similar studies in this field have failed to produce this.
Moreover, a London based study recruited 60 adults with mild or moderate asthma via advertisements and volunteer databases9. The study design was randomised crossover, which has very high reliability increasing the quality of the results9. Participants were exposed to DEP by walking between 10.30am – 12.30pm down Oxford Street (greater exposure to DEP) or around Hyde Park9. When compared to previous studies, this could affect the validity of the results as each participant may be exposed to different levels of DEP. However, it can be argued this method is less artificial than previous methods discussed in this review, leading to a higher external validity. Results were collated using a peak expiratory flow monitor before and after exposure, which is arguably less accurate than bronchoscopy and staining for example9. Results concluded in Oxford Street there was reduced FEV1 and FVC values and increased neutrophilic inflammation compared to Hyde Park9. The reduction in FEV1 and FVC was greater in participants with moderate asthma compared to mild asthma suggesting the severity of asthma can influence participant’s reaction to DEP9. However, the study acknowledges the FEV1 changes were small and as participants were not accompanied by symptoms, this should be taken into consideration when drawing definitive conclusions9.
Additional supporting evidence from a review analysing data from 2006-2007 found exacerbations of asthma is associated with living near a traffic source10. Ying-Ying et al, also found asthma is inadequately controlled in participants who live in highly polluted areas11.
Further studies conducted in this area found DEP cause an exacerbation of asthma in patients using inhaled corticosteroids regularly12. A total of 14 non-smoking participants with an average age of 26 years old were exposed to DEP to see the effect this had on their asthma12. Compared to previous studies, the sample size is small and can affect the ability to generalise results. Participants all had stable, controlled asthma and were hyperesponsive to methacholine12. The study design was single-blind which introduces experimental bias12. Participants were exposed to DEP via a chamber for 1 hour on 2 separate occasions12. Results were collated via lung function tests, sputum induction and a methacholine inhalation test12. The study concluded a brief exposure to DEP causes airway hyper-responsiveness in asthmatic patients and an increase in IL-6 and is therefore associated with an exacerbation of asthma12. The lack of control group in this study reduces the validity of results as healthy participants may have reacted the same as asthmatics. This point is supported by a study conducted by Nightingale et al, who found 2 hours exposure of diesel exhaust particles in healthy volunteers provoked a neutrophilic response and lead to inflammation of airways13.
From the studies analysed, it can be concluded DEP exposure is associated with an exacerbation of asthma in mild, moderate, uncontrolled and severe asthmatics. However, Brandt et al, acknowledges whilst a wealth of research has shown a link between asthma exacerbation and exposure to DEP, the mechanism of it causes this is not fully understood14. This highlights an area that may warrant further research in order to isolate any other confounding variables that could affect research findings.
Studies that have found diesel exhaust particles do not cause an exacerbation of asthma
Whilst a vast amount of research has shown DEP is linked to exacerbation of asthma, contradictory evidence has been found from studies detailed below.
A randomised double-blind study with 55 participants (aged 18-45 years) investigated whether DEP elicited an airway inflammatory response in asthmatics15. Participants were recruited via advertisement; a method which is subject to bias15. The use of a control group eliminated any confounding variables, thus increasing the validity of the results. To participate, asthmatic participants were required to meet criteria in the GINA guidelines, have mild-moderate asthma controlled with a maximum of short-acting B2 agonists and/or inhaled corticosteroids15. GINA guidelines have previously been criticized as arguably the definition asthma and how it should be diagnosed is unclear16. This could pose potential problems when using it as criteria for recruitment. Participants with co-morbidities were excluded, eliminating confounding variables15. Participants were exposed to DEP from a Volvo engine in a controlled chamber on two occasions for two hours, three weeks apart15. This method of exposure is highly artificial and not representative of environmental daily exposure of DEP. This can be viewed as a limitation of the study. A further limitation of the study is highlighted by Hesterberg et al, who notes older diesel engines expose patients to more DEP compared to newer diesel engines used currently17. This means participants in the study could be exposed to an amount DEP that is not found in the environment. Biopsies were taken via bronchoscopy 18 hours post-exposure, which is justified by the study based on previous research findings15. The study concluded healthy participants produced neutrophilic inflammation of their airways whilst the asthmatic group did not15. Such findings were further replicated by Behndig et al’s study further increasing the validity of results18.
The European Respiratory Journal also found similar findings. 15 subjects with an average age of 30 years were recruited. Subjects had asthma which was controlled by inhaled B2 agonists when required 19. A control group was present19. Comparable to previous studies in this field, a sample size of 15 participants is relatively small, making it difficult to generalise results. Results were collated by bronchoscopy and biopsies were from the proximal cristae19. Taking all biopsies from the same site allows fair and accurate comparison between participants. Results found the healthy control group had neutrophilic airway inflammation post DEP exposure which was not seen in mild asthmatic participants19. However, the mild asthmatic group showed an increase in IL-10 post DEP exposure whilst the control group showed a decrease in IL-1019.
Whilst asthmatic participants in this study failed to elicit a neutrophilic response, the role and effect IL-10 has on asthma should be taken into consideration. IL-10 has been found to have immunosuppressive and anti-inflammatory properties which could explain the increased level in asthmatic participants20. However, research has also shown IL-10 to increase IgE production, which would lead to airway inflammation21. Additionally, the study recognises bronchoscopy may have been taken too early, providing a possible explanation for why a neutrophilic response was not seen in asthmatic participants19. However, a follow up study conducted by Behndig et al found even 18 hours post-exposure there was still lack of neutrophilic response in asthmatic participants18. The two studies discussed, use neutrophil levels to assess the effect DEP has on asthma. Not all studies included in this review use neutrophilic response as a measure of airway inflammation. The lack of consistency of measuring airway hyper-responsiveness proves it is difficult to make accurate and valid comparisons.
From the studies analysed, it is evident that not all participants with asthma elicit an inflammatory response when exposed to DEP. Whilst participants did not elicit a neutrophilic response, other molecules were noted highlighting further research is required to see the effect they have on the exacerbation of asthma.
Furthermore, an important variable to consider is a participant’s genetic predisposition to asthma. Dijkstra et al, concluded a gene SERPINE1 is associated with the severity of asthma22. This could be an important variable, which could account for how participants react differently to DEP exposure, as their genetic predisposition will affect their severity of asthma.