Discussion
The present study represents the most exhaustive effort to investigate the epidemiology of asthma in Mexico. Yet, it is not representative of all the Mexican regions, as only 14 cities participated in the study. Preliminary results had shown an increase in the prevalence of asthma in some centres in comparison to ISAAC Phase Three. In the school children group, there was an increase in the prevalence of ‘wheeze ever’ in North Mexico City, Toluca and Victoria City. The prevalence of asthma symptoms in North Mexico City, Victoria City and Mexicali was also higher, with a general increase of 1.8%. In the adolescent group, there was an increased prevalence of ‘wheeze ever’ in North Mexico City and Mexicali; however, the prevalence was the same as reported in ISAAC Phase Three.1 10 Another study reported the results obtained from the GAN study in Mexico City and compared them with the ISAAC Phase Three study. Del-Rio-Navarro and collaborators observed that the prevalence of asthma symptoms increased by 3.8% in the group of school children and decreased one percent in the adolescents’ group.11
ISAAC Phase Three also reported several parental and child characteristics associated with asthma symptoms in school children. Such factors included parental smoking12; use of paracetamol in the first year of life as well as dose-dependent current use of paracetamol13; use of antibiotics in the first year of life14; dietary habits15 16; overweight and obesity17 and sedentarism.18
Some studies analysed the complete databases from ISAAC Phase Three, searching for risk factors for asthma symptoms at an individual and school level. The most critical associations at individual and school levels in the school children group were current use of paracetamol (OR 2.06; 95% CI 1.97 to 2.16), early life use of antibiotics (OR 1.65; 95% CI 1.58 to 1.73) and open fire cooking (OR 1.44; 95% CI 1.26 to 1.65). Meanwhile, in the adolescent’s group, the most significant associations were the current use of paracetamol (OR 1.80; 95% CI 1.75 to 1.86), open fire cooking (OR 1.32; 95% CI 1.22 to 1.43) and maternal tobacco use (OR 1.23; 95% CI 1.18 to 1.27).19
In the present study, the main risk factors for asthma symptoms in school children and adolescents were the presence of symptoms and diagnosis of rhinitis and eczema, the use of paracetamol, and the presence of smoking in the female adolescent’s group. Interestingly, our study reported a negative association between altitude and asthma symptoms in both age groups.
These results agree with what has been published in a recent study carried out in children in Angola, where the ISAAC study was used as a reference and reported that asthma symptoms were significantly associated with paracetamol use (OR 3.94; 95% CI 2.29 to 6.81 p<0.001), antibiotic uptake in the first year of life (OR 2.54; 95% CI 1.97 to 3.29 p<0.001), allergic rhinitis symptoms (OR 8.74; 95% CI 7.06 to 10.82 p<0.001) and itchy rash in the past 12 months (OR 4.40; 95% CI 3.56 to 5.44 p<0.001).20 The association between paracetamol intake and those conditions may be due to the depletion of glutathione, a key antioxidant of the airways, as proposed by Cheelo et al.21
On the other hand, associations between asthma outcomes in children and secondhand smoking have been described in the literature with exposures associated with an increased risk of asthma, asthma exacerbations, wheezing and reduced lung function, as reported in ISAAC Phase Three.22 23 Tobacco smoke is a mixture of compounds, including carbon and nitrogen oxides, particulate matter, nitrosamines and other chemicals, many of which are toxicants that can induce inflammation and altered immune responses.24
According to our results, having the habit of smoking increased the risk of asthma symptoms in female adolescents. This has been reported previously in other countries. For example, the Canadian National Population Health Survey reported that female smokers had a 70% higher prevalence rate of asthma compared with non-smokers, and the interaction between smoking and gender was particularly evident among women aged less than 25 years (OR 2.18)25
Mexico, like other Latin American countries, has suffered at least 25 years of economic stagnation, increasing inequalities and decreasing wages. This economic context has marked the course of the tobacco epidemic, which has been reflected with the consumption of tobacco in adolescents and young people under 25 years of age.26
Similarly, the tendency of adolescents to present with exacerbations of asthma symptoms during adolescence should be considered. It has been argued that the increment of sex hormones and/or to differences in gender-specific responses to environmental or occupational exposures make them susceptible to presenting with bronchial symptoms.27 Tantisira and collaborators reported in a large cohort of children that after the age of 11 years, the provocative concentration of methacholine necessary to cause a 20% decrease in forced expiratory volume in 1 s (PC20) increased in men, suggesting an improvement in airway responsiveness during puberty in men but not in women.28 Sex hormones have a wide variety of effects beyond the β2 adrenoreceptor. For example, they alter the function of epithelial cells. The progesterone receptor is expressed in the epithelium of the airways, and progesterone inhibits the beat frequency of the cilia, which can affect mucociliary clearance during the menstrual cycle among women.29 At the same time, experimental studies suggest that testosterone has a relaxing effect on precontracted tracheal smooth muscle and androgens may modulate the density of choline receptors.30 Interestingly, worldwide studies had reported that women with premenstrual asthma are at higher risk for severe asthma, required more corticosteroids therapy, and have a higher risk for emergency room visits and admission to the intensive care unit.31
In recent years, the increase in the prevalence of multimorbidity of allergic diseases in paediatric patients has been evident. As an example of the above, Dogru reported that 50% of patients under the age of 10 with mild to severe allergic rhinitis also had a asthma diagnosis.32 Similarly, the ARIA guidelines had reported a 10%–14% prevalence of asthma in adult patients with allergic rhinitis.33 In line with this, our results showed that patients with symptoms of rhinitis had twice the risk of developing asthma symptoms. Additionally, other studies have reported that the presence of eczema during the first year of life and preschool, increases the risk of wheezing at school age by three times.34 Following this, it could be possible to infer that patients, who show eczema or rhinitis symptoms from the first year of life, have a higher risk of asthma symptoms at school age which persist during adolescence.
In contrast, other ISAAC based studies focused on the effect of a healthy lifestyle index in the prevalence of asthma, rhinoconjunctivitis and eczema. The healthy lifestyle index was the combination of five factors: the absence of parental smoking, following a Mediterranean diet, average healthy body mass index, high physical activity and consequent non-sedentary behaviour. The combination of 4–5 of these factors may diminish the risk of current wheezing by 13% (OR 0.87; 95% CI 0.84 to 0.89). The management of these factors as a healthy lifestyle index could reduce the burden of asthma by 16%.35
Similarly, our results in school children showed that vigorous physical activity at least once or twice a week is a protective factor to prevent wheezing. At the same time, a history of maternal smoking during pregnancy and obesity (reported in the male adolescent’s group) increases the risk of asthma symptoms.
On the other hand, previous studies using the database of Mexican National Social Security found that altitude higher than 1500 m is a major factor on the incidence of asthma, with the new-onset asthma risk decreasing as altitude increases.36 37 Vargas et al demonstrated that asthma incidence rates tended to be higher in centres located on or near the coast. However, some centres in the northern region of Mexico also had high asthma rates. According to their study, asthma incidence was maintained relatively constant up to an altitude of ∼1500 m, with a progressive decline after that, with a statistically significant change at an altitude of 1539 m.36 The above agrees with our results, mainly in the adolescent group, where it is observed that the risk of presenting with asthma symptoms decreases as the altitude increases from 1500 m above sea level. Additionally, a clinical trial on high altitude climate treatment for severe asthma for 12 months found a decrease of 34% in the number of exacerbations and 36% in the hospitalisations in comparison to the previous year. These findings support the possible protective effect of high altitude in the incidence of asthma as well as in the control of the symptoms.38 The hypothesis regarding altitude, besides less pollution, is that it significantly reduces the level of exhaled nitric oxide, increases blood levels of interleukin 10 (a cytokine with powerful anti-inflammatory properties) and decreases the concentration of interferon-γ, responsible for inflammation of the local airways.39
An ISAAC Phase Three analysis of all available centres in Latin America (56 centres in 17 countries) studied the relationship between asthma symptoms and geographic characteristics in adolescents. Regarding altitude, there was a small but significant inverse correlation between altitude and asthma symptoms (r=−0.27, p=0.04). However, no significant correlation was found when the centres with higher altitude (>2000 m) were excluded for the analysis.7 This suggests that there are other factors, in addition to altitude, such as female predisposition and environmental factors that could increase the prevalence of asthma symptoms in the last decade.
In this sense, a Mexican study in children explored the prevalence of asthma, allergic rhinitis and atopic dermatitis and the possible related factors identified with a rural environment following the ISAAC methods. Nonetheless, it could not demonstrate that a rural environment protects against asthma or other allergic diseases.40 In the present study, contact with farm animals in the first year of life was only a marginal risk factor for developing asthma symptoms in school girls. Additionally, comparing urban and rural Toluca centres, the prevalences of asthma symptoms were similar in both locations in school children. Studies are beginning to demonstrate rural paediatric asthma prevalence to be similar to urban.41 Yet, in the adolescent group, women from the rural centre had a lower prevalence of wheeze ever in comparison to participants in the urban centre. This could be explained as the outside air quality in rural areas is, in general, better than in urban areas, and children and adolescents may experience less exposure to pollutants associated with worse asthma outcomes (such as diesel exhaust).42 Urban children are more likely to live in multi-unit housing, which is associated with cockroach, rodent, and dust mite allergen exposure, which are often known to cause allergic sensitisation and asthma exacerbations.43
Finally, another aspect to consider is asthma underdiagnosis of 50% as reported in this study. Asthma underdiagnosis is a public health problem in multiple countries. For example, van Gent et al reported that of a sample of 1614 Dutch children, 130 (8%) had undiagnosed asthma and 81 (5%) had diagnosed asthma, suggesting that in Dutch school children 62% of subjects with current asthma were undiagnosed.43 Generally, population-based studies indicate that 7%–10% of the adult and paediatric population have current asthma, and in those with current asthma, between 20% and 73% remain undiagnosed.44 Is widely known that the diagnosis and treatment of allergic diseases depend to a great extent on the education of the first contact doctor and the family members to detect symptoms in their mild to moderate manifestation and avoid a negative impact on the patient’s quality of life. Therefore, it is essential to invest in this type of study at an international level, so that we can analyse multiple factors that may contribute to developing asthma symptoms, and sustain national health strategies for diagnosis and management of allergic diseases to improve the quality of life of patients at any age.8