INTRODUCTION

Asthma, which is one of the most common chronic diseases, has increased in recent decades. According to the World Health Organization, asthma affects more than 330 million people worldwide.¹ The global prevalence of self-reported asthma in adults is 4.2%, with this figure being higher in industrialized countries. However, the prevalence in developing countries is believed to be underreported because of the difficulty of patient access to health services.²

Asthma represents a significant burden for society with a greater impact in developing countries due to the limited access to adequate treatments.³ Despite the reduction in mortality due to asthma in the last two decades achieved by the development and use of inhaled therapies, especially inhaled corticosteroids (ICS), a large global disparity persists in the years of life lost to the disease.^2,4 This forces us to propose modern and novel treatment strategies to reduce the global mortality and economic and social burden that asthma imposes on the population.

Thus, in recent years, international organizations have made efforts to know the worldwide prevalence of asthma. The International Study of Asthma and Allergies in Childhood (ISAAC) was carried out in three phases (1991-2012) to describe the prevalence and severity of asthma, rhinitis, and eczema in children.⁵ According to the results of phase 3 carried out in 237 centers in 98 countries, 17 of which were in Latin America, asthma prevalence varies widely depending on the geographic region. A higher prevalence of asthma symptoms was found above all in low- and middle-income countries. In the Mexican Republic, the prevalence of asthma in 6 cities ranged between 5 and 14%. The self-reported prevalence of current wheezing in children was 3.9% in Mexico City and 3% in Monterrey, Nuevo Leon, increasing to 30.8% in San Salvador, El Salvador. In contrast, in children aged 6 to 7 years, the prevalence in Mexico was 3.6%, increasing in Costa Rica to 37.6%. Furthermore, the prevalence of asthma ranged from 1.2% in Monterrey, Mexico, to 33.1% in Lima, Peru.⁶

Later in 2012, the Global Asthma Network (GAN) was established by scientists from ISAAC and the Interna tional Union against Tuberculosis and Lung Diseasesto understand the impact of asthma on the population and thus prevent and improve disease care around the world with a special focus on low- and middle-income countries (http://www.globalasthmanetwork. org/). The GAN used the same methodology as ISAAC phases one and three focusing on the three base diseases to evaluate their prevalence, diagnosis, severity, visits to the emergency room for asthma, hospital admissions, management, and drugs used.⁷

Our study's objectives are to report the results of our population that is part of the GAN phase I, with a particular focus on the prevalence and severity of asthma, rhinoconjunctivitis, and eczema in children and adolescents living in the city of Monterrey, Mexico.

METHODS

This was a comparative cross-sectional study following the official Global Asthma Network (GAN) methodology.

RESULTS

The prevalence and severity of asthma symptoms in children and adolescents are presented in Table 1. It is important to mention that 29.4% (n = 143/486) of children in the 6 to 7-year-old range presented wheezing at any time in their life; the majority were boys. The age at which most of the children presented wheezing for the first time was before their first year of life; however, in girls, it occurred mostly between the first and second year of age. Of these patients, 8% (n = 39/486) had some wheezing episodes in the last 12 months; the majority were boys . Most of these patients had had 1 to 3 attacks of wheezing in the past year, and only 2 girls had more than 12 attacks. Regarding the number of nocturnal awakenings due to asthma symptoms in the last 12 months, 3.3% (n = 16/486) of the children woke up only once at night while 1.2% (n = 6/486) woke more than once. It is important to mention that among the patients who ever had asthma symptoms, only 50% (n = 35/70) had a diagnosis of asthma confirmed by a physician. Of these, only 32.9% (n = 23/70) had a plan for managing their illness.

We describe the prevalence and severity of rhinitis symptoms in children and adolescents in Table 2. In this same group of children, 29.5% (n = 143/485) presented allergic rhinitis symptoms such as sneezing, rhinorrhea, or nasal congestion without presenting an upper airway infection. When stratifying by age group, we found that most of the children started with these problems between 5 and 6 years of age, while >50% of the children started with these symptoms between 3 and 6 years of age. Allergic hinitis symptoms were present in 23.7% (n = 115/485) at some point in the last 12 months. The symptom that most frequently affected this group was nasal itching in 15.2% (n = 74/485) in the last 12 months, followed by ocular itching and epiphora in 11.1% (n=54/485). In 8.4% (n = 41/115) of the children, these symptoms only mildly interfered with their daily activities, and only 0.6% were frequently affected.

The prevalence and severity of atopic dermatitis in presented in Table 3. In this same age group, 9.2% (n = 44/479) had an intermittent itchy skin rash for at least 6 months at some point in their life. Of these, 6.7% (n = 32/479) presented this symptom in the last 12 months. The risk factors associated with suffering from an atopic disease (asthma, rhinitis and/or atopic dermatitis) that were found in this group of children was having had wheezing in the last 12 months (OR: 1.21; CI: 1.12-1.31; p = <0.001) and presenting a rash in the last 12 months (OR: 1.22; CI: 1.11-1.35; p = >0.001).

In the group of adolescents between 12 and 14 years of age (n = 2557), 26.5% reported having experienced wheezing at some point in their life, with a slight pre dominance of the female gender (28%). In the previous 12 months, 9.6% had 1 to 3 episodes of wheezing, and only 0.5% suffered more than 12 attacks. Regarding nocturnal awakenings due to asthma symptoms in the previous 12 months, 14.6% of adolescents woke up once, while only 1% woke up more than once. Even though 679 of the adolescents have ever presented asthma symptoms, only 239 (35.2%) were confirmed by a specialist, and 149 (22%) claim to have a written action plan in case of presenting asthma symptoms.

About half of the adolescent group (48.2%) had allergic rhinitis symptoms such as sneezing, rhinorrhea, or nasal congestion without a cold or influenza. The most reported symptom in the last 12 months was nasal itching (38.5%), followed by ocular itching and epiphora in 21.9% of adolescents.

In this same group of adolescents, 20.% had an itchy skin rash intermittently for at least 6 months at some point in their life, and 14.9% of these had been present in the last 12 months. The risk factors associated with suffering from an atopic disease in adolescents 12-14 years of age were having wheezing during the last 12 months (OR: 1.13; CI: 1.09-1.16; p = <0.001) or the presence of wheezing during exercise or immediately after (OR: 1.21; CI: 1.05-1.40; p = 0.007). Similarly, an association was found, although less clearly, if the child had nasal problems with nasal pruritus in the last 12 months (OR: 1.08; CI: 1.00-1.16; p = 0.039) or if the rash that occurred in the last 12 months completely disappeared in the same period (OR: 1.07; CI: 1.031.11; p = <0.001)

DISCUSIÓN

As the most common chronic respiratory disease, asthma affects approximately 300 million people worldwide.⁸ Although its prevalence fluctuates in different regions of the world, in Latin America, an average of 17% is estimated.⁹ In Mexico, according to the World Health Organization, 7% of the population has asthma, which represents about 8.5 million Mexicans with this condition⁸

ISAAC phase three included a total of 1,059,053 children in 236 centers in 98 countries around the world. In this study, a prevalence of asthma symptoms of 13.7% in the 13 to 14-year-old group and 11.6% in the 6 to 7-year-old group was reported.¹⁰ According to the data obtained from the ISAAC phase three in our regional center for allergy and clinical immunology in the city of Monterrey, Nuevo Leon, a general prevalence of 26.5% of asthma (wheezing at some time) was reported in the 13 to 14-years group, and 29.4% in the 6 to 7 years group. In recent years, the prevalence of allergic diseases has increased due to multiple environmental factors such as urbanization and rapid population growth, which has favored lifestyle changes and greater exposure to environmental pollutants.¹¹ This increase is evidenced in a recent study where 15 centers that participated in GAN phase I in the Mexican Republic were analyzed. In this study, a prevalence of asthma of 23.9% was reported in adolescents, while in children aged 6 to 7 years, it was 26.2%.¹² These data differ to those obtained in our study population, where the prevalence of asthma was 7.6% and 11.6% in the children and adolescent groups, respectively.When we compared our results with those obtained by Chinratanapisit et al. as part of the GAN phase I in Thailand, an important similarity was observed in the frequency of asthma symptoms, 26% in the group aged 6 to 7 years and 22.9% in the group of adolescents 13 to 14 years.¹³ Similar to the findings in Mexico, a significant increase occurred in the frequency of asthma symptoms when comparing the previous results with the ISAAC phase III in the population of Bangkok, a prevalence of asthma of 14.6% vs. 15.0% was reported in the groups of children and adolescents, respectively.¹⁴ In recent years, multiple studies have been carried out to determine the prevalence of allergic diseases worldwide. A significant increase has been seen due to the increasing urbanization of developing countries, such as Mexico or Thailand, in addition to multiple factors, such as the increase in population density, the increase in environmental pollution, and epigenetic alterations that affect this vulnerable population.¹⁵ In the information obtained from our population, we noticed that the wheezing attacks in the last year (before the survey applica tion) were similar in both boys and girls (12.8 vs. 7.4%). Still, when making a global comparison for asthma diagnosis, we found that in the 6 to 7-year group, the male gender predominated (54.5% vs. 42.3%); in the adolescent group, there was a female gender predominance (43.5 vs. 40.3%). This predominance of female gender over male gender at puberty could be due to the predisposition that adolescent girls have to present symptoms and exacerbations of asthma during puberty and close to the menstrual cycle.¹⁶ When stratifying by age, we found that most children begin with wheezing episodes before the first year of life (34.3%), and about 80% present them before 6 years of age. Our results are similar to those reported by Del-Río-Navarro et al,¹² with an onset before 6 years of age in 87% of cases. These data show and corroborate the greater presentation of asthma symptoms in early childhood, a period when a diagnosis can be difficult due to the greater frequency of cases of wheezing due to viral infections.¹⁷ It is vitally important to sensitize primary health service providers and the general population about clinical data suggestive of asthma to provide timely detection and treatment. Children and adolescents in our city had a lowe number of nocturnal awakenings due to asthma symptoms (3.3 vs. 3.4%) compared to children in Thailand (5.4 vs. 4.2%) and a different prevalence of nocturnal awakenings compared to the rest of the Mexican population (12.2 vs. 8.2%). Nighttime awakenings are an important variable to consider as part of the control of a disease as heterogeneous as asthma since this variable not only affects the lung function of patients but also sleep quality and school performance, which have a direct impact on their quality of life. Despite the efforts made by international organizations to raise awareness of asthma around the world, only slightly more than half of the patients diagnosed with asthma by a doctor have an effective treatment plan and adequate adherence. Similar data have been reported in other Latin American countries, where only 40% of patients comply with their long-term treatment.¹⁸ This leads us to conclude that specialist physicians must generate strategies in our population to educate patients and improve their adherence to long-term treatment. As is well known, viral and bacterial infections play a very important role in the pathogenesis of asthma. The viruses most commonly involved in lower respiratory tract infections and the development of wheezing and asthma have been rhinovirus (RV) and respiratory syncytial virus (RSV), with rhinovirus being the main trigger for asthma attacks.¹⁹ There is strong evidence that shows that children having wheezing episodes at 3 years of age, wheezing due to RSV (OR 2.6), RV (OR 9.8), or both RSV and RV (OR 10.0), have a higher risk of developing asthma at 6 years of age.²⁰ On the other hand, in a study by García-Marcos et al. of more than 28,000 subjects in Latin America, it was reported that the main risk factors for developing asthma were attending daycare and having an upper respiratory infection in the first 3 months of life, as well as maternal smoking during pregnancy. The same authors identified maternal breast milk ingestion for more than 3 months and maternal education higher than high school as protective factors.²¹ Ojwang et al., in a prospective study conducted in Finland, studied the relationship of early exposure to dogs, cats, and farm animals and its relationship with the development of asthma. They found that having a dog at home was associated with a 40%, 28%, and 23% reduction in the risk of developing asthma, allergic rhinitis, and atopic sensitization by the age of 5, respectively. Contrary to what was found in our population, exposure to farm animals during the first year of life was not associated with these results. However, in a recent study by Levin et al. conducted in South Africa where environmental factors associated with allergic diseases were analyzed, it was found that exposure to farm animals in childhood and maternal exposure during pregnancy were a protective effect for developing allergic diseases in rural areas.^22,23,24 The results of this variable in multiple studies have been heterogeneous. Other factors specific to the farm environment must be taken into account to establish an adequate recommendation depending on our population.²⁴ The GAN phase I has been a very important project since it offers a global perspective of the frequency of the main allergic diseases that affect the population. Regarding the symptoms of allergic rhinitis in our population of children between 6 to 7 years of age, the prevalence was lower than that reported in the Bangkok population of the same age (29.5 vs. 47.3%). However, when comparing this finding with data from ISAAC phase III, we found that the prevalence of these symptoms has not significantly changed in recent years in our population (29.5 vs. 31.8%).10 In the same way, allergic rhinitis symptoms were lower in our population when compared with the GAN phase I results from Bangkok (11.3 vs. 24.5%), and they were significantly higher when compared to those reported in the ISAAC phase III (4.6%). In the last 12 months, school children from Monterrey presented a lower prevalence of nasal pruritus (15.2 vs. 38.2) and ocular pruritus (11.1 vs. 15%) than children from Bangkok. Likewise, in the adolescent population, in the last 12 months, nasal pruritus appeared less frequently in the Mexican population than in the Thai population (24.1 vs. 48.8%), in contrast eye symptoms were more prevalent (21.9 vs. 18.0%). When comparing GAN phase I atopic dermatitis data with ISAAC phase III in our center, we noticed a very significant increase in both age groups. In children aged 6 to 7 years, the presence of eczema at some point in life was higher in GAN phase I children compared to those of ISAAC phase III (9.3 vs. 2.9%); also in the adolescent group (20.1 vs. 1.5%). Regarding the presence of eczema in the last 12 months, the GAN phase I showed a frequency of 6.7% and 14.9% in children and adolescents, respectively. Similarly, this shows significantly higher figures than those obtained in ISAAC phase I in both groups (4.1 and 4%).

CONCLUSION

In this study, the results obtained using the GAN phase I material showed the increasing appearance of allergic diseases throughout the world over time, without forgetting the Mexican population. Although allergic diseases have a very important genetic component, environmental and social factors play a significant role in their development. Therefore, the results of studies like this will give us a complete perspective of the current burden of allergic diseases in our population to generate strategies that allow us to provide our patients with better comprehensive, and timely care.