Blog de Dr. José Antonio Sacre Hazouri

The burden of asthma in an inner-city area

Fri, 17 Jul 2026 14:46:56 GMT

The burden of asthma in an inner-city area: A historical review 10 years after Isaac

Blanca Estela Del-Rio-Navarroa, Elsy Maureen Navarrete-Rodrígueza*, Arturo Berberb, Nayely Reyes-Noriegaa and Luis García-Marcos Álvarezc, Grupo GAN México, Grupo ISAAC México

ABSTRACT

Background: According to the International Study of Asthma and Allergies in Childhood (ISAAC) methodology, in 2003, the prevalence of asthma symptoms in children 6–7 years old and adolescents 13–14 years old was 11.6% and 13.7%, respectively. Since then, the number of asthma cases has increased worldwide. The study was conducted in several districts in northern Mexico City to evaluate the prevalence of asthma in these age groups and examine possible risk factors. The data were compared to the 2003 results from the same area.

Methods: This was a comparative cross-sectional study following the official Global Asthma Network (GAN) methodology. The parents or guardians of participants completed a questionnaire that explored demographics, asthma symptoms, diagnoses, and possible risk factors. Central tendency measurements were determined for statistical analysis and chisquared distribution for possible risk factors.

Results: A total of 2515 children aged 6–7 years and 3375 adolescents aged 13–14 years participated in the study. Compared to the ISAAC results, we found a greater prevalence of wheezing in both children (at some time in life, 19.2% vs. 27.1%; over the last year, 6.8% vs. 10.6%) and adolescents (at some time in life, 16.9% vs. 19.7%), and for children with an asthma diagnosis (4.5% vs. 5.1%). For both groups, the most common risk factor associated with wheezing was the presence of rhinitis symptoms.

Conclusions: Asthma symptoms are highly prevalent in Mexico City, occurring in almost 20% of adolescents. Compared to a decade ago, there was a 7.9% increase in the prevalence of asthma symptoms in children. Almost half of the children and adolescents presenting with symptoms had experienced more than four episodes per year. However, less than 50% of children and adolescents with asthma symptoms had been diagnosed with this disorder, suggesting under-diagnosis.

Keywords: Asthma, Atopic allergic diseases, Wheezing, Rhinitis, Risk factors, ISAAC, GAN

aServicio de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

*Corresponding author. Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col. Doctores, Deleg. Cuauhtémoc, 06720, México, D.F., Mexico. E-mail: draenavarrete@gmail.com

Full list of author information is available at the end of the article http://doi.org/10.1016/j.waojou.2019.100092

Received 2 October 2018; Received in revised from 12 November 2019;

Accepted 14 November 2019

1939-4551/© 2019 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organization. This is an open access article under the CC BY- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND

Asthma is now considered one of the main chronic illnesses worldwide,1 affecting more than 300 million people.2 According to several studies, the prevalence of asthma has increased in many countries over the past decade.3,4 Asthma is associated with other atopic allergic diseases, including allergic rhinitis and atopic dermatitis, the prevalence of which has also increased, though to a lesser extent, over the past 10 years.4

Despite the many insights into asthma over the past few decades, the reasons behind the greater prevalence are still not clear. Genetics are known to play an important role, as well as environmental factors. Diet and exposure to microorganisms, pollutants, and allergens also contribute to the development of this condition in genetically pre- disposed individuals.5 Some hypotheses have been formulated with regard to asthma. One suggests immunological mechanisms that manifest as an imbalance in the Th1–Th2 immune response6 and related to changes in the epithelial microbiome. Another hypothesis proposes the involvement of obesity and other nutritional factors during in utero formation and after birth.

The International Study of Asthma and Allergies in Childhood (ISAAC), which began in 1991, was the first multinational effort to research the preva- lence of asthma and other allergic conditions in different countries around the world. It was carried out in three phases from 1992 to 2003. A vali- dated, standardized questionnaire was applied to two age groups at distinct places around the world (translated into the appropriate language): chil- dren aged 6–7 years and adolescents aged 3–14 years.7 The study described the prevalence and severity of asthma, rhinitis, and eczema in various regions, examined risk factors, and evaluated temporary trends in the prevalence of these conditions.

The last phase of ISAAC included a total of 1,059,053 children from 236 centres in 98 coun- tries.8 The prevalence of asthma symptoms was 13.7% in the older group and 11.6% in the younger group. Substantial variations were detected in the prevalence of the three illnesses, even among subjects with similar genetic backgrounds. Consideration was given to possible protective factors (vegetable consumption and immunization for DPT and measles) and aggravating factors (the presence of certain kinds of pollen, climactic factors, and outdoor pollution). The identified risk factors were the gross national income (GNI) of a country, climatic factors, the consumption of acidic trans fats, and the use of paracetamol and antibiotics. The prevalence of asthma symptoms increased at a similar or higher rate in developing and developed countries.

9Due to the success of the ISAAC program, the Global Asthma Network (GAN) was created in 2012 with the objective of approaching asthma as a significant, worldwide, non-contagious disease. Meanwhile, the existing multinational collabora- tion projects continued their research into the variations in asthma prevalence in children and adolescents, focusing on the same populations involved in the ISAAC study.

The current study was part of the GAN initiative and aimed to update the prevalence rates of asthma in Mexico City and examine the most relevant risk factors associated with this disease.

MATERIALS AND METHODS

A comparative cross-sectional study was carried out in school-aged populations of children 6–7 years old and adolescents 13–14 years old at the No. 515002 GAN Centre. This location corresponds to the northern region of Mexico City, including the districts of Azcapotzalco, Miguel Hidalgo, Gustavo A. Madero, and Venustiano Carranza. After providing informed consent, parents completed validated and standardized questionnaires given by GAN’s global coordination for the younger group, and the older group completed the questionnaires by themselves.10

Following the official GAN protocol,10 the sample unit was the whole population of children aged 6–7 years or adolescents aged 13–14 years in a given school. The schools were within a certain geographical radius of the study centre and were chosen randomly based on the school register (organized in alphabetical order). A minimum of 10 schools were necessary to obtain a representative sample, with a projected sample size of 3000 (a minimum of 1000) subjects per age group. This sample size gave the study enough statistical power to detect significant epidemiological differences in the prevalence and severity of asthma symptoms11 and complied with the guidelines of the ISAAC methodology.

The questionnaires focused on three areas (Supplemental Tables S1 and S2). Demographic factors were explored, including the age, date of birth, education level, and gender of the children. Specific questions were asked about asthma, including the existence of wheezing at some time in life and over the past year and the diagnosis of asthma by a doctor. The risk factors examined were the presence of rhinitis or eczema, the use of paracetamol and/or antibiotics, consumption of basic foodstuffs, education level of the mother, diagnosis of pneumonia, and exposure to cigarette smoke.

A period of 3 days was allowed for returning the questionnaire. After this period, the anthropo- metric parameters of the participants were established. Weight was measured on an 804 Seca digital scale and height with a portable Frankfort 213 Seca stadiometer. Waist measurements were taken at the mid-point between the last rib and the iliac crest with an inelastic measuring tape (without applying pressure). The subjects were in a standing position, feet together, arms at their sides, and abdomen relaxed. They were asked to inhale deeply and the measurement taken upon exhalation.

Data entry for the electronic GAN database was done by the medical personnel at the study center, with random selection of 10% of the questionnaires on two occasions to ensure that the margin of error was less than 1%. To limit possible mis- takes in the data entry process, the electronic data were cross-checked with the original physical questionnaires. The methodology for the ISAAC study in northern Mexico City, which was described previously12 was used. The present investigation was conducted by the same researchers involved in the previous study, allowing a comparison of both results to the original databases. The GAN and ISAAC databases were reviewed by the GAN and ISAAC committees, respectively, before performing statistical analyses.

Central tendency measurements (the average standard deviation [SD] and 95% confidence interval [CI]) were obtained for analysis of the accumulated and current prevalence of symptoms and diagnosis of asthma and asthma severity.

For qualitative variables, the chi-squared test was used.

The variables WHEZ12 (current wheeze) and ASTHMAEV (a previous asthma diagnosis) were chosen to examine the risk factors for asthma. Subsequently, factors that were likely to increase or decrease the prevalence of these two variables were identified (p ≤ 0.10) with the chi-squared test and Fisher correction on 2 × 2 tables. These factors were analysed by conditional logistic regression to create models that better explain WHEZ12 and ASTHMAEV risk.

Microsoft Excel 2016 v16.0.6568.2036 (Microsoft Corporation) was used to organize data and IBM SPSS Statistics v20.0 (SPSS Inc., IBM Company) for statistical analysis. The present study was approved by the Ethics, Research, and Biosafety committees of the Hospital Infantil de México Federico Gómez (HIMFG, protocol #HIM/2015/ 059) in accordance with the guidelines of the institution.

RESULTS

A total of 2900 children and 3600 adolescents from 67 schools were asked to participate in the study. The actual number of participants was 2515 children aged 6–7 years (44.9% male, 55.1% female) and 3375 adolescents aged 13–14 years (47.5% male, 52.5% female). The response rate to the questionnaire was 90%.

For the younger group, wheezing (ever or cur- rent wheeze) was more common in the present GAN data than in the ISAAC results for both male and female subjects (Fig. 1, Table 1). In the adolescent group, a similar significant increase was observed for the GAN versus the ISAAC study, but only in relation to the prevalence of wheezing at some point during life (WHEZEV). Females were affected more than males, especially with regard to asthma symptoms at some time in life (Fig. 2, Table 1). Interestingly, there was a much higher frequency of wheezing during both time periods than a previous asthma diagnosis with respect to both age groups and genders. Asthma symptoms assessed by WHEZEV were more frequent in male children than in female children. However, in adolescents, WHEZEV and WHEZ12 were more common in females (Table 1).

The variables linked to asthma severity were compared between the GAN (2017) and ISAAC (2003) data, utilizing the questions evaluating the intensity of NWHEZ12 (number of wheezing episodes in the last 12 months), AWAKE12 (number of times that the child/adolescent’s sleep has been disturbed due to wheezing), and SPEECH12 (difficulties with speech caused by wheezing) (Table 1). Almost double the number of children of both sexes reported 1–3 wheezing episodes over the past year in the GAN data than the ISAAC data. In addition, more participants in this study reported sleep interrupted by wheezing (especially for males; data not shown) and difficulties with speech caused by wheezing (both sexes) than in the previous study. For adolescents, the number of female subjects with 1–3 wheezing episodes over the past year was increased in GAN vs. ISAAC.

In both genders, there were significant increases in children in the frequency of WHEZEV, SPEECH12, NWHEZE12 (1–3 times a week), and AWAKE12 (≥1 times per week), but not ASTH- MAEV (Table 1), in GAN compared to ISAAC. In contrast, in the adolescents, the only significant increases between ISAAC and GAN were in WHEZEV and NWHEZE12 (1–3 times a week) (Table 1).

The presence of hay fever, eczema, early infections, tobacco use at home, and paracetamol use are possible risk factors for WHEZEV and WHEZ12 in both groups. In 2003, the analysis showed a higher risk of wheezing over the past year for participants diagnosed with allergic rhinitis (hay fever), those with symptoms of allergic rhinitis (e.g., sneezing, rhinorrhoea, or obstruction), and those diagnosed with atopic dermatitis (Table 2). Other risk factors include the use of antibiotics during the first year of life, having had a cat during the first year of life, and the administration of paracetamol for a fever over the past year.

The results from 2017 demonstrate the same trends for some of the risk factors, including the prevalence of rhinitis symptoms or wheezing over the past year. However, the results were different for the diagnosis of rhinitis or atopic dermatitis. Having been diagnosed with pneumonia at least once increased the risk of asthma symptoms over the past year (Table 2). Regarding an asthma diagnosis, the protective effect of changes made in the household to mitigate allergy or asthma symptoms was significant. This variable, which was not included in the 2003 ISAAC study, was added to the GAN questionnaire.

For adolescents in both the ISAAC and GAN studies, nasal symptoms (e.g., sneezing, rhinorrhoea, or nasal obstruction) increased the risk of wheezing episodes over the past year (Table 3). There was also a greater risk of a diagnosis of asthma in subjects previously diagnosed with rhinitis, which was not evaluated in the ISAAC study.

DISCUSSION

Epidemiological studies conducted in the 1980s–1990s found important increases in asthma and asthma symptoms in the Western world and Asia, but after the 1990s, the trends in these symptoms were contradictory; in some countries, the prevalence of asthma was still increasing, whereas in others it seemed to be stable or even decreasing slightly.13 In the ISAAC phase three study, centers previously reporting a low prevalence demonstrated an increase in current asthma symptoms, whereas the centers with a higher baseline prevalence had decreases, particularly in English-speaking countries and Western Europe.7,14

Other surveys conducted after ISAAC phase three have also found the prevalence to be stabilizing and a decrease in asthma prevalence in Western countries and Asia. For example, using 2001–2016 National Health Interview Survey data for children aged 0–17 years, current asthma prevalence in the United States increased from 8.7% in 2001 to 9.4% in 2010, followed by a plateau until 2013, and then decreased to 8.3% by 2016.15

Repeated surveys in the southeast Netherlands conducted in 1989, 1993, 1997, 2001, 2005, and 2010 demonstrated a decreased prevalence of current asthma symptoms in children from 1989 (13.4%) to 2001 (7.4%), with no significant change up to 2010 (6.2%).17,18 Similarly, in South Korea, a 6-year nationwide survey found a decrease in the prevalence of current asthma symptoms from 2009 (20%) to 2014 (13.2%) in children aged <10 years.19

In the present study, there was a frank increase in asthma symptoms and asthma severity in children. In the adolescent group, the only significant increases were in WHEZEV and NWHEZ12. There- fore, northern Mexico City has a mixed pattern of asthma prevalence increase in children and a possible stabilization in adolescents. This study is among the first reports to compare the prevalence of asthma symptoms between ISAAC and GAN.

It has not been easy to identify the factors underlying the epidemiological changes. Some factors have been explored in ISAAC and GAN, such as changes in diet, time spent using screens (computers and video games), second-hand smoke, and the presence of pollutants.10,20

In the present study, possible risk factors identified for WHEZEV and WHEZ12 were the presence of other allergic diseases (hay fever and eczema), early infections, smoking at home, and paracetamol use. These patterns have been described previously; for example, the evolution of allergic sensitization followed by atopic dermatitis, allergic rhinitis, and asthma have been demonstrated in several epidemiological studies.21,22 A possible explanation for the association of atopic dermatitis, allergic rhinitis, and asthma could be the filaggrin loss-of-function mutations. Filaggrin is a skin epidermal protein that contributes to the natural skin barrier protecting against trans- cutaneous water loss, as well as preventing the entry of environmental allergens through the skin. Filaggrin loss-of-function mutations provoke epidermal barrier dysfunction, increasing the risk of eczema. These mutations are also associated with allergic sensitization and airway allergy, expressed as allergic rhinitis and asthma later in childhood.23

The relationship between passive tobacco smoke and asthma in children has been well- established by studying the levels of serum cotinine and the prevalence of asthma. High exposure to second-hand tobacco smoke is related to high risk of asthma, asthma exacerbations, and poorly controlled asthma in children.24,25

The use of paracetamol, perinatally and currently, has also been associated with allergic conditions, especially with asthma,26,27 but this association could be explained by confounding factors, such as fever and respiratory infections.27

How can we explain the differences in asthma symptom prevalence in different cities, regions, and countries? It is possible that all populations with Western life styles follow the same pattern of asthma evolution, but in different stages. In underdeveloped countries, the prevalence of asthma symptoms should increase, and then plateau and decrease over the subsequent years.

The ISAAC and GAN studies have tried to explore the possible causes of the heterogeneity in asthma prevalence. Yet, other factors should be considered in future studies, including exposure to pollutants of different kinds and sizes; changes in pollination patterns and type of flora; microbiome fluctuations; and the history, evolution, and aetiology of respiratory infections and parasitic diseases.

CONCLUSIONS

The prevalence of asthma in Mexico City is now higher than the prevalence in 2003. Almost 20% of adolescents present with symptoms of asthma at least once in their lifetime. Since the ISAAC study performed over a decade ago, there has been a 7.8% increase in the prevalence of asthma symp- toms in children. Almost half of the children and adolescents presenting with asthma symptoms had experienced more than four episodes per year. However, less than 50% of children and adolescents with asthma symptoms were diagnosed with asthma, suggesting under-diagnosis.

Abbreviations

Isaac: International Study of Asthma and Allergies in Childhood; Gan: Global Asthma Network; Himfg: Hospital Infantil de México Federico Gómez

Ethics approval and consent to participate

The authors declare that all procedures were carried out in accordance with the ethical standards of the institutional committee on human investigation, the World Medical Association, and the Helsinki Declaration.

The authors obtained informed consent from the parents or guardians of participants in the study. The corresponding author accepts responsibility for this manuscript.

The present study was approved by the Ethics, Research, and Biosafety committees of the Hospital Infantil de México Federico Gómez (HIMFG, protocol #HIM/2015/059) in accordance with the guidelines of the institution.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

Funding

The financing to carry out this project came from the resources of the researchers, as well as a donation from AstraZeneca laboratory to cover the costs of printing the questionnaires and data entry.

AUTHORS’ CONTRIBUTIONS

DRNBE - Made substantial contributions to conception, design, and acquisition of data.

NREM - Made substantial contributions to design, acquisition of data and drafting the manuscript.

BA - Made substantial contributions to the analysis and interpretation of data.

RNN - Made substantial contributions to design and acquisition of data.

GMAL - Involved in revising it critically for important intellectual content.

GAR - Made substantial contributions to conception and design.

MPJV - Made substantial contributions to conception and design.

SROJ - Involved in revising it critically for important intellectual content.

DRCJM - Involved in revising it critically for important intellectual content.

SMJJL - Involved in revising it critically for important intellectual content.

Declaration of competing interest

The authors declare that they have no conflict of interest in relation to the methods or materials employed in this study.

Acknowledgments

The authors thank AstraZeneca for their support in carrying out this project, specifically for the financial aid to cover the costs of printing the questionnaires and data entry. The authors thank The Global Asthma Network Steering Group especially Philippa Ellwod and Innes Asher for their constant help with our research.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.waojou.2019.100092.

Author details

aServicio de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. bAsesor Externo, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. cUnit of Clinical Research, Cartagena and Department of Paediatrics, University of Murcia, Murcia, Spain.

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Risk factors associated with allergic rhinitis in Mexican school children

Thu, 16 Jul 2026 23:19:31 GMT

Prevalence and risk factors associated with allergic rhinitis in Mexican school children: Global Asthma Network Phase I

Roberto García-Almaraza, Nayely Reyes-Noriegab, Blanca Estela Del-Río-Navarrob*, Arturo Berberc, Elsy Maureen Navarrete-Rodríguezb, Philippa Ellwoodd and Luis García Marcos Álvareze,

GAN Phase I group

ABSTRACT

Background: The International Study of Asthma and Allergies in Childhood (ISAAC) showed a wide variability in prevalence and severity of allergic rhinitis (AR) and rhinoconjunctivitis (ARC), in addition to other atopic diseases (Asher et al, 2006).1 The Global Asthma Network (GAN) has continued to study these conditions.

Objective: To estimate the prevalence of AR and ARC in children and adolescents in Mexico and to assess their association with different risk factors.

Methods: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016–2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by 35 780 parents of 6–7 year old primary school pupils (children) and by 41 399 adolescents, 13–14 years old.

Results: The current and cumulative prevalence of AR was higher in the adolescents (26.2–37.5%, respectively) in comparison to the children (17.9–24.9%, respectively), especially in female participants. This tendency was also observed in the current prevalence of ARC, where 15.1% of fe- male adolescents reported nasal symptoms accompanied with itchy-watery eyes in the past year. The most important risk factors for AR and ARC were the presence of wheezing in the past 12 months, wheezing in the first year of life, the previous diagnosis of asthma and eczema symptoms. Furthermore, allergic symptoms had a negative tendency concerning altitude.

Conclusion: This is the largest AR epidemiological study ever conducted in Mexico. It shows an increase in AR prevalence, as well as significant associations with modifiable risk factors, which could help to establish recommendations to reduce the burden of this condition.

Keywords: GAN, Allergic rhinitis, Rhinoconjunctivitis, Risk factors, Prevalence

aHospital Infantil de Tamaulipas, Ciudad Victoria, Tamaulipas, Mexico

*Corresponding author. Hospital Infantil de México Federico Gómez Dr. Márquez No. 162, Col. Doctores, Deleg. Cuauhtémoc, 06720 México, D.F., Mexico. E-mails: blancadelrionavarro@gmail.com; berio@himfg.edu.mx Full list of author information is available at the end of the article

http://doi.org/10.1016/j.waojou.2020.100492

Received 29 June 2020; Received in revised from 3 November 2020;

Accepted 10 November 2020 Online publication date xxx

1939-4551/© 2020 The Author(s). Published by Elsevier Inc. on behalf of World Allergy Organization. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ).

INTRODUCTION

Allergic Rhinitis (AR) is a global health problem, affecting 10–40% of the population around the world, with a prevalence of 8.38% in children and 14.93% in adolescents.1 It is the most common allergic disease of childhood, and its pervasiveness has increased particularly in countries with reported low prevalence values, as per the International Study of Asthma and Allergies in Childhood (ISAAC) Phase One.1 As a condition, AR’s severity is often underestimated as it is non-life-threatening. However, the dura- tion and severity of AR symptoms represent a substantial burden on quality of life and well-be- ing.2 Crucially, AR has a detrimental effect on quality of sleep and cognitive functioning, which can cause irritability and tiredness. AR is frequently associated with comorbidities such as asthma and atopic dermatitis (AD), among others3

ISAAC was the first study to survey the preva- lence of asthma and other allergic diseases in different countries around the world. It was carried out in 3 phases from 1992 to 2003.1

ISAAC Phase One was conducted from 1992 to 1995, where the prevalence of rhinoconjunctivitis (ARC) ranged between 0.8 and 14.9% (median 5.9%) in 6-7 year olds (children) and from 1.4% to 39.7% (median 13.6%) in 13-14 year olds (adoles- cents). In Mexico, the only centre that participated in this phase was Cuernavaca (Morelos) with an ARC prevalence of 8.6% and 9.4% in each age group, respectively. Overall, the highest preva- lence rates for ARC were observed in parts of Western Europe, North America, and Australia, whereas the lowest rates were found in parts of Eastern Europe and South and Central Asia.4

ISAAC Phase Three (2001–2003) was conducted in centres which had participated in ISAAC Phase One, as well as other centres. The aim of the study for ARC, was to observe variations in prevalence over time, and results showed that the prevalence rates had increased in Latin America. The highest prevalence was mainly observed in centres in middle and low-income countries, particularly in Panama, where the prevalence was 39.2% in chil- dren and Brazil, with a prevalence value of 42.1% in adolescents.5

Ten Mexican centres participated in ISAAC Phase Three. They reported an overall prevalence of current ARC in children of 11.6% (with a range between 6.7% in Ciudad Victoria and 17.8% in Mexico City), while the adolescents reported 15.4% (with a range between 7.1% in Cuernavaca and 28.1% in Mexicali).6

The development of AR in the children and adolescents entails a complex interaction between genetic predisposition and environmental expo- sure to different factors found according to life- style, socioeconomic status, diet, pollution, and early development of other allergic diseases.11 According to ISAAC Phase Three, in Mexico, the most important risk factors for AR were the history of asthma, the presence of atopic eczema, the use of paracetamol, and history of asthma in parents.12,13

The aims of this study are to investigate the current prevalence of AR and ARC in children and adolescents in Mexico and to assess their associ- ation with different risk factors.

METHODS

Study design

Global Asthma Network (GAN) Phase I is a cross-sectional, multi-centre, international, epidemiological study. Primary and secondary schools were randomly selected from a list of public and private institutions per centre to represent the target population. This phase included 15 centres in 14 cities of Mexico, including Puerto Vallarta (Vall, 7 metres above mean sea level [mamsl]), Matamoros (Mat, 8 mamsl), Mexicali (Mexi, 8 mamsl), Tijuana (Tij, 20 mamsl), Victoria City (CdVt, 316 mamsl), Cordoba (Cor, 860 mamsl), Juarez City (CdJz, 1120 mamsl), Chihuahua City (Chi, 1413 mamsl), Xalapa (Xal, 1417 mamsl), San Luis Potosi (SLP, 1864 mamsl), Aguascalientes (AgCa, 1888 mamsl), Morelia (Mor, 1920 mamsl), Mexico City (CdMx, 2250 mamsl), urban Toluca (ToUr, 2667 mamsl), and rural Toluca (ToRu, 2667 mamsl). The study was carried out in 6-7 year olds (children) where parents completed the question- naires and 13-14 year olds (adolescents) who self- completed questionnaires at school. In both age groups, parents granted written informed consent.

Global Asthma Network questionnaires

GAN used the same standardized written core questionnaires developed for ISAAC Phases One and Three, with the addition of doctor confirmed diagnosis of the asthma, hay fever, and eczema. In Mexico, the questionnaires were translated and back-translated from English to Spanish by 3 independent linguistic professionals, in accordance with the ISAAC English language questionnaire translation guidelines, in order to ensure that they had the same structure and logic as the original.14 Once the Spanish version of each questionnaire was finalized, a pilot test was carried out in schoolchildren and adolescents in Mexico City. It is worth mentioning that all the centres involved in this study applied the same version of the questionnaire by age group.

Questions were asked on demographic details such as age, sex, date of birth, school, and date of interview, as well as questions on prevalence and severity of rhinitis as well as rhinitis management and risk factors. Questionnaires were coded using a unique number for each centre, school, and participant to ensure confidentiality. In addition, height and weight measurements were taken by fieldworkers in schools.

Complete questionnaires for each age group can be consulted onhttp://www. globalasthmanetwork.org/surveillance/manual/study6.php and http://www.globalasthmanetwork. org/surveillance/manual/study13.php (accessed on March 23, 2020).

De ﬁ nitions

The standardized questions used in ISAAC Phase Three and GAN Phase 1 for rhinitis (hay fe- ver) AR, ARC, and severe ARC symptoms are:

1. Have you (has your child) ever had a problem with sneezing or a runny or blocked nose when you (he or she) DID NOT have a cold or “the flu”? (PNOSEEV).

2. In the past 12 months, have you (has your child) had a problem with sneezing or a runny or blocked nose when you (he or she) DID NOT have a cold or “the flu”? (PNOSE12)

3. In the past 12 months, has this (has this child’s) nose problem been accompanied by an itchy nose? (ITCH12)

4. In the past 12 months, has this (has your child’s) nose problem been accompanied by itchy/ watery eyes? (IEYES12)

5. In the past 12 months, how much did this nose problem interfere with your (your child’s) daily activities? (Not at all, a little, a moderate amount, a lot) (IACTIV12)

6. Have you (has your child) ever had hay fever? (HFEVEREV)

7. Was your (your child’s) hay fever confirmed by a doctor? (HFEVDOC)

In this study, question 1 was used to estimate the cumulative prevalence of rhinitis. Question 2 estimated AR, questions 2 and 4 were used to estimate the current prevalence of ARC symptoms (ARC12). Questions 2, 4 and the answer “A LOT” to question 5 was used to estimate the prevalence of severe rhinoconjunctivitis symptoms. Question 6 was used to estimate the prevalence of hay fever ever (also known as rhinitis ever) and question 7 was used to estimate the prevalence of rhinitis diagnosed by a doctor.1,13

Sample size

A sample size of 3000 participants per age group per centre was used assuming no cluster sampling effect. The sample size provided greater than 99% (at the 1% level of significance) to detect differences in the prevalence. The average expected participation was of at least 80% for adolescents and 70% for children.15

Data collection and analysis

Data were entered on an electronic database collected by the medical personnel of each study centre from August 2016 to July 2019. For quality control, 10 percent of questionnaires were double entered to mitigate possible errors. GAN data- bases were checked and approved in 2019, by Murcia (Spain) data centre, which was responsible for the quality control of the Spanish-and Portu- guese-speaking centres. Each centre had to complete a detailed Centre Report verifying compliance with the methodological standards established by ISAAC and GAN. The report requested a description of the sampling frame, the school selection method, the number of schools excluded and rejected, the participant selection method and data entry, the record of changes made to the data, the number of children and adolescents who participated and refused, as well as a map of the sampling frame of the study area.16

Data analysis included central tendency measurements (mean, standard deviation [SD] and [95% CI]), as well as the cumulative and current prevalence of symptoms of rhinitis, AR, ARC, rhinitis diagnosed by a doctor, and severe ARC symptoms.

All possible factors which were likely to influ- ence the prevalence of current and cumulative prevalence of AR or ARC were identified (p < 0.05) by Fisher and chi-squared tests. These factors were analysed by backward conditional multivariate logistic regression to create models used to conduct exploratory analysis for ARC12 risk factors. It is important to consider that although a randomization process was carried out and the sample size obtained is large in this study, the statistical method used, backward conditional multivariate logistic regression, is a method that may present a selection bias, where the correlation coefficient may be overestimated and result in an optimistic model.48 However, before carrying out this analysis, the candidate explanatory variables were selected according to the theoretical evidence to avoid nuisance variables and variables with a p-value <0.05 were included in the discussion, as they were the variables less prone to a selection bias. However, current validation methods such as the area under the receiver operating characteristic curve (AUC) and calibration graphs or Hosmer-Lemeshow test were not explored.49

Microsoft Excel 2016 v16.0.6568.2036 (Micro- soft Corporation) was used to organize data and IBM SPSS Statistics v25.0 (SPSS Inc., IBM Company) was used for statistical analysis.

RESULTS

A total of 570 primary schools and 220 sec- ondary schools were included during the 2016 – 2019 period. A total of 77 179 questionnaires were considered in this analysis. Overall, 35 780 (88.3%) children and 41 399 adolescents (91.5%) participated in the study, and the global response rate was 90%.

The global current prevalence of AR and ARC in male and female participants are presented in Table 1 (children and adolescents). Prevalence values according to centre can be seen in Fig. 1 (children) and Fig. 2 (adolescents).

The current prevalence of AR was higher in ad- olescents than in children (26.2% vs 17.9%) especially in female participants, where 40% reported rhinitis symptoms ever and 29% experienced AR symptoms in the past 12 months. This tendency was also observed in the current prevalence of ARC, where 15% of female adolescents reported nasal symptoms accompanied by itchy-watery eyes.

Although the adolescent group had a higher prevalence of AR and ARC symptoms, the prevalence of rhinitis diagnosed by a doctor was higher in children in comparison to adolescents (8.2% vs 3.9%, respectively).

It is important to mention that the male adolescent group reported less severe symptoms of ARC in comparison with children (0.6% vs 0.9%) and less interference on their daily activities due to nasal and ocular symptoms, contrary to the interference frequency reported by children, where it ranged from moderate (6.9%) to severe (2.5%) with a significant difference between groups (p < 0.05).

Current prevalence of AR and ARC in each centre showed great variability. Figs. 1 and 2 shows the prevalence of AR and ARC rhinoconjunctivitis symptoms in different centres, according to their altitude (from the lowest to the highest). Fig. 1 corresponds to female children and Fig. 2 to the female adolescents. In female children, the cities of Mexicali and Matamoros have the highest prevalence of rhinitis symptoms (33–36%) while Morelia and Rural Toluca have the lowest ones (less than 25%). The prevalence of rhinitis confirmed by a doctor was also higher in the Mexicali and Matamoros centres.

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In females of both age groups, the altitude pattern had an impact; cities under 1500 m over mean sea level (Matamoros and Mexicali) had a higher prevalence of AR while centres above 1500 m (Toluca) had the lowest prevalence. Accordingly, the centres in the cities of Matamoros and Mexicali had the highest prevalence of rhinitis confirmed by a doctor (9.5–17.7%).

Tables 2 and 3 show the risk factors for current prevalence of ARC and AR in both groups, respectively. The most important risk factors were the presence of wheezing in the past 12 months (OR 2.84 [IC95% 2.54–3.18] - 3.35 [IC95% 3.05 – 3.67]), wheezing in the first year of life (OR 1.48 [IC95% 1.27–1.74] - 1.77 [IC95% 1.51–2.07]), the previous diagnosis of asthma (OR 1.70 [IC95% 1.50–1.93] - 2.72 [IC95% 2.23–3.32]) and eczema symptoms (OR 1.30 [IC95% 1.06–1.58] - 2.01 [IC95% 1.62–2.49]) p < 0.001.

The use of paracetamol during pregnancy and in the past 12 months was an important factor in the children, especially in females (p < 0.05). Additionally, in the children, breast feeding dura- tion showed a negative association with the presence of AR symptoms in both genders.

Meanwhile, in the adolescents, computer use of less than 1 h a day was a protective factor for AR (p < 0.05). Interestingly, in female adolescents, it was observed that the risk of manifesting symptoms of ARC decreased as the altitude increased. (p < 0.05).

DISCUSSION

This present cross-sectional study represents the most exhaustive effort to investigate the epidemiology and risk factors of AR and ARC in Mexico using a GAN methodology. Even though 32 states comprise Mexico, we consider that obtaining data from 10 states allows us to estimate the prevalence of symptoms of this disease, without the intention of assuming that it is representative of the entire country.

The cumulative prevalence of rhinitis decreased in the children (by 3.0% points) and increased in adolescents (by 4.2% points) taking ISAAC Phase Three as reference. Nevertheless, the current prevalence of nasal symptoms was lower than reported by ISAAC Phase three by 6.3% in children and 7.9% in adolescents. Similarly, the current prevalence of ARC, decreased by 0.4% in children and by 5.9% in adolescents compared to ISAAC Phase Three results.13

As in ISAAC Phase Three, we found wide variations among the participating centres. In children, the range of prevalence for AR was 6.6%–24.9%, and in adolescents from 12.7% —25.6% even in very close centres. Besides the worldwide ISAAC Phase Three study,6 many studies have been carried out during the last 20 years in children and adolescents in different Mexican cities and reported variations in the prevalence of AR and ARC in both age groups. Some of them used the ISAAC questionnaire, while others employed different validated questionnaires for AR in different age groups. For instance, Bäcker found a current prevalence of ARC of 10.5% in children in Mexicali, Baja California,8 and Bedolla-Barajas recorded a current prevalence of AR of 5.5% in children and adolescents aged 6 to 12 in Ciudad Guzmán, Jalisco.9 Furthermore, Ramirez-Soto has recently reported a global prevalence of AR of 5% and ARC of 19.2% in children in 5 cities in the central-western region of Mexico.10 Compared

with previous Mexican results, our study reported a current prevalence of AR greater than 5 percentage points in both age groups. However, the prevalence of ARC increased only in the adolescent group.

These regional variations are attributed to diversity and difference, population size, environ- mental factors such as humidity or pollution and socio-economic conditions, as reported by Arnedo et al in children of different regions of Spain.17

Our results are consistent with previous research on the differences in prevalence according to sex. Overall AR and ARC prevalence were higher in males in comparison to females in children. This trend changes during puberty and adolescence, with female adolescents showing higher prevalence rates in comparison to males. Differences in condition prevalence is explained by higher levels of endogenous sex steroids hormones with increased Th2 response in women, whereas in men, testosterone works by suppressing the Th2 response.18,19 However, it has been reported that this tendency decreases during middle-age, where males have a higher prevalence of rhinitis.20

Several studies have shown a lower prevalence of ARC in children raised in rural environments (mainly during the first 5 years of life) and contact from birth with domestic animals. It has been proposed that these factors increase the exposure to bacterial endotoxins and high microbial di- versity capable of inducing immune tolerance through Th1 stimulation and Th2 suppression, preventing the development of allergic dis- eases.21,22 Taking the aforementioned information into account, we can explain why rural centres in Toluca had the lowest prevalence of AR and ARC in children and adolescents.

This study showed an increase in the prevalence of severe symptoms of ARC in children and adolescents compared with ISAAC Phase Three (4.5% vs 0.8% and 2.7% vs 0.9%, respectively).6 Nevertheless, our results should not be taken as a real reflection of symptom severity, since our study only explored the level of affliction in daily life in parameters from null to severe, and did not include the criteria proposed by the Allergic Rhinitis and its Impact on Asthma (ARIA). This document proposed a system for assessing AR severity on the basis of the presence or absence of impairment in any of 4 health-related quality of life (HRQL) items: sleep, daily activities/sport, work/school, and troublesome symptoms, to classify severe rhinitis you must answer yes 3 or 4 items.23

For the diagnosis of rhinitis, the current prevalence of ARC and the prevalence of hay fever ever (also known as rhinitis ever) were similar in children. However, in the adolescents, less than half of the patients with symptoms of ARC and hay fever had a medical diagnosis. These data agree with the study carried out by Esteban et al where an insufficient diagnosis was reported in 24% of children with rhinitis symptoms and 53% of patients older than 7 years with AR symptoms.24 In Mexico, Villareal reported an AR prevalence diagnosed by a doctor of 6.7% in children of aged 6–8 and 5.4% in adolescents aged 11–14 in Ciudad Juarez, Chihuahua.7 One possible explanation could be that adolescents reported less deterioration in their quality of life compared to children, so they may not perceive it as a disease that requires medical attention. On the other hand, it is widely known that the diagnosis and treatment of allergic diseases depend largely on the education of the first-contact doctor and family members to detect symptoms in their mild to moderate manifestation and avoid a negative impact on patient’s quality of life.25

AR and asthma can be unified by the concept of a “united airway,” where allergic symptoms of the upper and lower airways can be thought of as manifestations of a common atopy, where over 80% of asthmatic patients have AR25 and a risk factor to develop asthma is AR.12,26 We found in our study that asthma and AR are comorbid diseases that coexisted in 25% of the patients. Asthma also increased at least twice the risk of having AR in children and adolescents. This confirms the close correlation between AR and asthma from an epidemiological perspective.

Other risk factors for ARC and AR with greater strength and importance of association were the presence of atopic dermatitis symptoms in the past and itchy rash in the past 12 months. Overall, these factors increase twice the risk of having nasal and ocular symptoms. The ISAAC Phase Three study in Mexico reported the same risk factors in all age groups.12 These conditions, far from being considered as isolated conditions, must be regarded as specific manifestations of systemic allergic disease in different organs, where they can coexist by having a common allergic basis.27

Another risk factor with a slight association for AR and other allergic diseases was the use of paracetamol during pregnancy and in the past 12 months, according to ISAAC Phase Three in chil- dren and adolescents.28,29 According to our results, there was an association between the frequency of paracetamol use and the presence of AR and ARC in both age groups. In a prospective pregnancy cohort and throughout the first 6 months of life, it was observed that the consumption of paracetamol during the first trimester was associated with an increased risk of AR until 10 years of age.30

The Epidemiology of Allergic Diseases in Poland (EACP), a large questionnaire-based survey in the East-Central part of Europe reported that the use of paracetamol in the past 12 months was associated with a significant dose-dependent in- crease in the risk for developing rhinitis symptoms, with a strong correlation, in terms of the odds ratio, with the use of paracetamol at least once a month in adolescents.31 In line with the above, our results reported that the low consumption of paracetamol in the past 12 months was a protective factor for ARC in both age groups. The mechanism involved implies oxidative stress in the airways related to a glutathione depletion that favours inadequate protection of the respiratory mucosa with antioxidants and detectable concentrations of metabolite NAPQI in the lungs, which stimulated the transient receptor potential ankyrin-1 (TRPA1) leading to neurogenic airway inflammation.32,33

Breastfeeding is strongly recommended for its numerous benefits to newborns. Some studies have shown a protective effect related to time and exclusivity, while others have not only found no benefit but an increased risk of allergic diseases.34 A systematic review evaluated the association between exclusive breastfeeding during the first 3 months after birth and AR. It found that although breastfeeding has a protective effect, its statistical significance was borderline (OR 0.74 [95%CI 0.54–1.01]).35 Likewise, the PROBIT study, a large clinical trial group that used the ISAAC questionnaire, did not observe a decrease in risk at 6.5 years of age, despite the duration and exclusivity of the maternal breastfeeding.36 In our study, we found that breastfeeding duration lower than 6 months was significantly associated with a higher risk of AR and ARC in children.

The western pattern diet is characterized by the high consumption of red and processed meats and low consumption of vegetables and cereals. This diet is rich in polyunsaturated fatty acids and contains high levels of omega-6 fatty acids compared to omega-3, which is considered an allergy risk factor. Research has documented a higher risk of ARC and AR in children that consume animal fats 3 or more times per week compared to children who consumed animal fats once or twice a week as well as a negative association between consumption of starchy foods, rice, nuts, shellfish, and all fresh/frozen fish with the presence of symptoms of ARC, atopic dermatitis, and severe asthma in adolescents.37,38 However, this factor did not behave as a risk factor in our study sample, despite the high consumption of red meat.

A modern urban lifestyle implies that children and adolescents spend most of their time indoors, watching TV or playing on a computer resulting in reduced physical activity, with a potential of junk food consumption. These unhealthy lifestyle behaviours are strongly associated with the presence of allergic diseases. Computer use is a risk factor for developing AR, especially when it is used more than 3 h per day and is not frequently cleaned. This is due to computer hardware being a source of dust, hair, and mites, all of which increases the risk of contact with allergens and allergic sensitization.39 According to our results, this was also reported in the adolescent group where the use of computer or television for less than an hour, behaved as a protective factor for AR.

Finally, a negative tendency was found between a higher altitude (>1500 m above sea level) and a lower prevalence of ARC and AR in female ado- lescents. Elevated altitude (>1500 m) is thought to be an important factor in determining the incidence of asthma. As altitude increases, lower rates of asthma have been recorded.40 The hypothesis regarding altitude is that it significantly reduces the level of exhaled nitric oxide (NO), a determinant of inflammation of the local airways in patients with moderate or severe intrinsic asthma; increases blood levels of interleukin 10 (a cytokine with powerful anti-inflammatory properties) and decreases the concentration of interferon-g (IFN-g), responsible for inflammation of the local airways. Also, at higher altitudes, there is a lower concentration of allergens (pollens and mites) and air pollution.41,42 These observations have been reported in asthma, however, given the results per centre of AR, we consider that these observations can be extrapolated to these comorbidities.

In addition to the relationship between asthma and altitude, other studies have reported hormonal changes in females living at high altitude. For example, González and Ortiz et al reported a delay in puberty as altitude increased.43 Similarly to the above, it has been reported that oxidative stress due to hypoxia caused by altitude, results in late menarche, a prolonged ovarian cycle due to high levels of the hormone FSH and, therefore, a delay reproductive age in adolescents. As described above, female sex hormones promote a Th2-type inflammatory response during adolescence.44-46 However, based on the aforementioned results, altitude appears to have an important effect on the hypothalamic-pituitary- gonadal axis by increasing the corticotropin- releasing hormone and negatively affecting the hypothalamic secretion of gonadotropin-releasing hormone, thus reducing the release of gonadotropins.47

In accordance with our results, it was observed that the prevalence of AR and ARC was higher in females belonging to the centres with lower altitude above sea level compared to males. It is possible that the females who participated in the height centres (more than 1500 mamsl) such as Toluca could present low levels of sex hormones and therefore, a lower inflammatory response of the Th2 type during adolescence. However, there is no record of gynecological history or any biochemical marker that allows us to assert this argument since the questionnaire used did not address these biological aspects of the patients, therefore, no conclusions can be drawn regarding this effect in the female sex yet.

Limitations

This multicentre cross-sectional study has limitations typical of an observational study. Apart from questionnaire responses, we didn’t apply any objective measure or clinical evaluation to confirm rhinitis symptoms or diagnosis in these populations. On the other hand, self-reporting of symptoms in the adolescent group could lead to higher estimates on the presence of AR and ARC symptoms and the self-selection of centres included in this study might not be representative of the country. However, GAN has shown that this type of study is an adequate and high quality method to explore the prevalence of symptoms related to allergic diseases, which have been increasing in the last decade internationally. The information was obtained with a common methodology with a previously validated instrument and with a high response rate from all the centres involved. This study allows us to identify important associations and potential risk factors by sex and age. Additionally, environmental factors such as altitude can be established as a possible modulating factor for current wheezing in the Mexican population. This opens up the opportunity to carry out prospective studies to analyse modifiable environmental factors related to the increased prevalence of AR and ARC in different areas of the world. It represents an area of opportunity to develop detection strategies for the population at risk with symptoms of rhinitis with allergic comorbidities.

CONCLUSION

This is the first report of the largest epidemiological study that has been carried out in Mexico related to AR and ARC in children and adolescents. It gives us a global idea of the magnitude of this health problem in the country, showing an increasing trend throughout the last 18 years, especially in cities un- der 1500 m over mean sea level.

This study allows us to confirm the association between allergic diseases and other risk factors previously reported and describe modifiable factors such as consumption of paracetamol in pregnancy, the duration of the breastfeeding and television and computer use for long periods of time. Although we are far from establishing causal relationships, we can give preventive recommendations to avoid the impact of this disease.

Abbreviations

ISAAC: International study of asthma and allergies in childhood; GAN: Global asthma network; AR: Allergic rhinitis; ARC: Allergic rhino conjunctivitis

GAN Phase I group

Mérida Palacio Valente Juan- Baja California, Mexico. MD, drvalente@clinicadeasma.com, Ramos García Beatriz Del Carmen- San Luis Potosí, Mexico. MD, b.aty@live.com.mx, Escalante Domínguez Alberto José- Hospital General Tijuana, Baja California, Mexico. MD, drajed@yahoo.com.mx, Linares Zapién Francisco Javier- Toluca, Mexico. MD, fjlinaresz@prodigy.net.mx, Gardea Moreno Leonardo- Chihuahua, Mexico. MD, hmorenogardea49@gmail.com, Ochoa López Georgina - Ciudad Juárez, Chihuahua. Mexico. MD, gina8a_77@hotmail.com, Hernández Mondragón Luis Octavio- Morelia, Michoacán, Mexico. MD, dr.hdezmondragon@gmail.com, Lozano Sáenz José Santos- Xalapa, Veracruz, Mexico. MD, Lozanosaenz57@gmail.com, Sacre Hazouri José Antonio- Córdoba, Veracruz, Mexico. MD, sacre_1@hotmail.com, Juan Pineda Ángeles- Puerto Vallarta, Jalisco, Mexico.

MD, angjuan@hotmail.com, Sánchez Coronel Ma. Guadalupe- Aguascalientes, Mexico. MD, mgsc4@hotmail.com, Rodríguez Pérez Noel- Matamoros, Tamaulipas, Mexico. MD, drnoelrodriguez@me.com, Ambriz Moreno María de Jesús, Tamaulipas, Mexico. MD, draambriz@latinmail.com, Del Río Chivardi Jaime Mariano- Mexico City, Mexico. MD, delriojaime@yahoo.com, Saucedo Ramírez Omar Josué- Mexico City, Mexico. MD, dr.omar.saucedo@gmail.com.

Authors’ contributions

GAR- Made substantial contributions to conception and drafting the manuscript.

RNN.- Made substantial contributions to design, acquisition of data and drafting the manuscript.

DRNBE.- Made substantial contributions to conception, design, acquisition of data and drafting the manuscript.

BA.- Made substantial contributions to the analysis, interpretation of data and drafting the manuscript.

NREM.- Made substantial contributions to design and acquisition of data.

EP.- Made substantial contributions to the analysis and drafting the manuscript.

GMAL.- Made substantial contributions to the analysis and drafting the manuscript.

MPV.- As centre coordinator, made substantial contributions on the acquisition of data.

RGBDC.- As centre coordinator, made substantial contributions on the acquisition of data.

EDAJ.- As centre coordinator, made substantial contributions on the acquisition of data.

LZF.- As centre coordinator, made substantial contributions on the acquisition of data.

GML.- As centre coordinator, made substantial contributions on the acquisition of data.

OLGG.- As centre coordinator, made substantial contributions on the acquisition of data.

HMLO.- As centre coordinator, made substantial contributions on the acquisition of data.

LSJS.- As centre coordinator, made substantial contributions on the acquisition of data.

SHJA.- As centre coordinator, made substantial contributions on the acquisition of data.

JPMA.- As centre coordinator, made substantial contributions on the acquisition of data.

SCMG.- As centre coordinator, made substantial contributions on the acquisition of data.

RPN.- As centre coordinator, made substantial contributions on the acquisition of data.

AMMDJ.- As centre coordinator, made sub- stantial contributions on the acquisition of data.

DRNBE.- Involved in revising it critically for important intellectual content.

SROJ.- Involved in revising it critically for important intellectual content.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The authors obtained informed consent from the parents or guardians of participants in the present study. The corresponding author accepts responsibility for this manuscript.

The present study was approved by the Ethics, Research, and Biosafety committees of the Hospi- tal Infantil de México Federico Gómez (HIMFG, protocol HIM/2016/065) in accordance with the guidelines of the institution.

Authors’ consent for publication. If any of this information is not applicable, we ask that you please provide a statement to this effect.

Funding

No financial support for this work that could have influenced its outcome.

Agreement to publish the work

All authors consent to the publication of this work.

Declaration of competing interest

The authors declare that they have no conflict of interest in relation to the methods or materials employed in this study.

Acknowledgments

We thank all the school children, adolescents and parents, who collaborated in the GAN study, for obtaining information and updating the prevalence of asthma. All the authors involved in this article who contributed to the design, elaboration, writing and analysis of this work. We appreciate the financial support of the Mexican College of Pediatricians Specializing in Allergy and Clinical Immunology (COMPEDIA) to print the questionnaires used for this important project. Likewise, we would like to thank the support of Dr Innes Asher and her team of collaborators, for their direction in preparing this study, as well as for their support for the inclusion of Mexico in this important international study. Finally, we thank the support of Dr Virginia Pérez Hernández, Axel Arturo Berber-Del-Río, Dr Yolanda Rodríguez Galván, Dra Laura Alicia Sacre, Dr Ricardo Regules García, Dr Juan José Luis Sienra Monge and Dr Jaime Mariano Del Río Chivardi for their contribution to the revision and editing of this article.

Appendix A. Supplementary data

Supplementary data related to this article can be found at https://doi.org/10.1016/j.waojou.2020.100492.

Author details

aHospital Infantil de Tamaulipas, Ciudad Victoria, Tamaulipas, Mexico. bServicio de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. cAsesor Externo del Servicio de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. dDepartment of Paediatrics: Child and Youth Health, University of Auckland, Auckland 1023, New Zealand. ePediatric Allergy and Pulmonology Units, ‘Virgen de la Arrixaca’ University Children’s Hospital, University of Murcia, ARADyAL network and Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain

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Prevalence of asthma symptoms, risk factors and altitude associations

Thu, 16 Jul 2026 23:08:12 GMT

Global Asthma Network Phase I study in Mexico: prevalence of asthma symptoms, risk factors and altitude associations—a cross-sectional study

BMJ Open Respiratory Research

Blanca Estela Del-Río-Navarro,1 Arturo Berber,1 Nayely Reyes-Noriega ,1

Elsy Maureen Navarrete-Rodríguez,1 Roberto García-Almaraz,2 Philippa Ellwood,3 Luis Garcia-Marcos,4 Omar Josué Saucedo-Ramírez,1

Valente Juan Mérida-Palacio,5 Beatriz Del Carmen Ramos-García,6 Alberto José Escalante-Domínguez,7 Francisco Javier Linares-Zapién,8 Héctor Leonardo Moreno-Gardea,9 Georgina Ochoa-López,10

Luis Octavio Hernández-Mondragón,11 José Santos Lozano-Sáenz,12 José Antonio Sacre-Hazouri,13 Ángeles Juan-Pineda,14

Ma Guadalupe Sánchez-Coronel,15 Noel Rodríguez-Pérez,15 María de Jesús Ambriz-Moreno,16 The GAN Phase I group

To cite: Del-Río-Navarro BE, Berber A, Reyes-Noriega N,

et al. Global Asthma Network Phase I study in Mexico: prevalence of asthma symptoms, risk factors and altitude associations—a cross-sectional study.

BMJ Open Resp Res

2020;7:e000658. doi:10.1136/

bmjresp-2020-000658

Received 2 June 2020

Revised 12 November 2020

Accepted 17 November 2020

ABSTRACT

Background Global Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally.

Objective To survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico.

Methods GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016– 2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6–7-year-old primary school pupils (school children) and by 13–14-year-old adolescents.

Results A total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres’ sea level altitude higher than 1500 m above mean sea level (p<0.005).

Conclusions The most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.

INTRODUCTION

Asthma is a significant public health problem. It is estimated that 339 million people suffer from this chronic disease in the world ¹ and that the daily number of deaths due to asthma is around 1150. ² Worldwide, there were 10.5 million years of life lost (due to premature death) attributed to asthma- related premature deaths in 2016. ¹ Globally, it was estimated that the costs associated with asthma exceeded those of tuberculosis and HIV/AIDS combined and the burden of asthma is relevant for the health system in terms of both direct (hospitalisation and treatment) and indirect costs (absenteeism in school and work for the parents). ³

Therefore, significant efforts have been made to assess and compare the prevalence of asthma in different countries around the world, including the factors associated with asthma symptoms. For instance, the Global Asthma Network (GAN) was established in 2012 as an evolution of the International Study of Asthma and Allergies in Childhood (ISAAC) to improve asthma care globally, with a focus on low-income and middle-income countries (http://www.globalasthmanetwork. org/). ISAAC was carried out in three phases. ISAAC Phase One (1994– 1995) used a written questionnaire for school children and adolescents in 56 countries and demonstrated a large variation in the prevalence of asthma symptoms in children in different geographical locales, including unstudied populations. ⁴ ISAAC Phase Three (2001–2003) described asthma prevalence and severity of 237 study centres. Ninety-eight countries not previously considered for ISAAC Phase One were included. According to the global ISAAC Phase Three results, the highest prevalence of asthma in adolescents (³20%) was generally observed in English speaking countries of Australasia, Europe and North America, and in parts of Latin America (http:// isaac.auckland.ac.nz/phases/phases. html). ¹ ⁵ GAN used the same methodology used in ISAAC Phases One and Three. However, questions regarding risk factors and management of asthma were added. ⁶

According to ISAAC Phase Three in Mexico, where ten centres from eight cities participated, the prevalence of current wheezing (wheezing in the past 12 months) in adolescents ranged from 3.9% in Mexico City to 14.4% in Victoria City, Tamaulipas. ⁶ Additionally, the asthma risk factors in Mexico City were identified using data from ISAAC Phase Three. The most important risk factors for current wheeze were rhinitis and eczema symptoms, as well as early and current use of paracetamol and anti- biotics in school children and adolescents. Maternal contact with farm animals in men aged 6–7 and smoking in men and women aged 13–14 were also risk factors for current wheeze. ⁷

The aims of GAN Phase I are to survey asthma, allergic rhinitis and atopic dermatitis in school children and adolescents from different countries, to investigate and evaluate the prevalence, severity, management and risk factors in reference to ISAAC Phase Three. Furthermore, the correct management of asthma, and access to essen- tial asthma treatments are assessed. ⁵

PATIENTS AND METHODS

GAN Phase I is a cross-sectional, multicentre, interna- tional, epidemiological research study. Primary and secondary schools were randomly selected from a list of public and private institutions per centre to represent the target population. This phase included 15 centres in 14 cities of Mexico, including Puerto Vallarta (Vall, 7m above mean sea level (mamsl)), Matamoros (Mat, 7 mamsl), Mexicali (Mexi, 8 mamsl), Tijuana (Tij, 20 mamsl), Victoria City (CdVt, 316 mamsl), Cordoba (Cor, 860 mamsl), Juarez City (CdJz, 1120 mamsl), Chihuahua City (Chi, 1413 mamsl), Xalapa (Xal, 1417 mamsl), San Luis Potosi (SLP, 1864 mamsl), Aguascalientes (AgCa, 1888 mamsl), Morelia (Mor, 1920 mamsl), Mexico City (CdMx, 2250 mamsl), urban Toluca (ToUr, 2667 mamsl) and rural Toluca (ToRu, 2667 mamsl). The study was carried out in 6–7 years old (school children) where parents completed the questionnaires and 13–14 years old (adolescents) who self-completed questionnaires at school. In both age groups, parents granted written informed consent.

Details on the GAN methodology can be found in its corresponding manual (http://www.globalasthmanet- work.org/surveillance/manual/manual.php; accessed on 23 March 2020).

GAN used the same standardised written core question- naires developed for ISAAC Phases One and Three, with the addition of doctor confirmed diagnosis of asthma, hay fever and eczema. In Mexico, the questionnaires were translated and back-translated from English to Spanish by three independent linguistic professionals, following the ISAAC English language questionnaire translation guidelines, to ensure that they had the same structure and logic as the original. ⁸ Once the Spanish version of each questionnaire was finalised, a pilot test was carried out in school children and adolescents in Mexico City. It is worth mentioning that all the centres involved in this study applied the same version of the questionnaire by age group.

The written questionnaires focus on demographics and anthropometric characteristics such as age, date of birth, sex, school and date of interview, as well as questions on prevalence and severity of asthma, asthma management and risk factors like the use of paracetamol, antibiotics, physical activity, food consumption and air pollution. Questionnaires were coded using a unique number for each centre, school, and participant to ensure confidentiality. Also, height and weight measurements were taken by fieldworkers in schools.

Complete questionnaires for each group could be consulted in online (http://www.globalasthmanetwork. org/surveillance/manual/study6.php and http:// www.globalasthmanetwork.org/surveillance/manual/ study13.php (accessed on 23 March 2020)).

DEFINITIONS

The standardised questions used in ISAAC Phase Three and GAN Phase I for asthma and asthma symptoms are:

1. Have you (has your child) ever had wheezing or whis- tling in the chest at any time in the past? (WHEZEEV).

2. Have you (has your child) had wheezing or whistling in the chest in the past 12 months? (WHEZ12).

3. In the past 12 months, has wheezing ever been severe enough to limit your (your child’s) speech to only one or two words at a time between breaths? (SPEECH12).

4. In the past 12 months, how often, on average, has your (has this child’s) sleep been disturbed due to wheez- ing? (AWAKE12).

5. How many attacks of wheezing have you (has this child) had in the past 12 months? (NWHEZ12).

6. Have you (has your child) ever had asthma? (ASTH- MAEV).

7. Was your (this child’s) asthma confirmed by a doctor? (ASTHDOC).

8. Do you (Does this child) have a written plan which tells you how to look after your asthma? (ASTHPLAN). In this study, question 1 was used to estimate the cumulative prevalence of wheeze. Question 2 estimated the prevalence of current asthma symptoms, positive answers to question 2 and questions 3, 4 and 5 were used to esti- mate the prevalence of severe asthma symptoms. Ques- tion 6 was used to estimate the prevalence of asthma ever; question 7 was used to estimate the prevalence of asthma diagnosed by a doctor and question 8 was used to estimate the prevalence of a medical plan for asthma symptoms.

SAMPLE SIZE

A sample size of 3000 participants per age group per centre was used, assuming no cluster sampling effect. The sample size provided significance greater than 99% (at the 1% level of significance) to detect differences in prevalence. The average expected participation was at least 80% for adolescents and 70% for children.5

DATA COLLECTION AND ANALYSIS

Data were entered on an electronic database by the medical personnel of study centres from October 2015 to December 2019. Ten per cent of questionnaires were double entered to mitigate possible errors. GAN data- bases were checked and approved in 2019, by Murcia’s (Spain) data centre, which was responsible for the quality control of the Spanish-speaking and Portuguese- speaking centres. Each centre had to complete a detailed Centre Report verifying compliance with the methodo- logical standards established by ISAAC and GAN. The report requested a description of the sampling frame, the school selection method, the number of schools included, excluded and rejected, the participant selec- tion method and data entry, the record of changes made to the data, the number of children and adolescents who participated and refused, as well as a map of the sampling frame of the study area.9

Data analysis included central tendency measurements (mean, SD and 95% CI), as well as the prevalence of asthma symptoms, severity and asthma diagnosed by a doctor.

Current asthma symptoms (WHEZ12) was the depen- dent variable in the analyses examining the risk factors for asthma. All possible factors which were likely to influ- ence the prevalence of current wheeze were identified (p<0.05) by the Fisher and 2 tests. These factors were further analysed by backward conditional logistic regres- sion to create models to predict current wheeze.

Microsoft Excel 2016 V.16.0.6568.2036 was used to organise data and IBM SPSS Statistics V.25.0 for statistical analysis.

PATIENT AND PUBLIC INVOLVEMENT

Since this study strictly relied on existing data via an approved written consent, we did not engage with patient stakeholders in the design or conduct of the analyses nor interpretation of the findings.

RESULTS

The response rate of the delivered questionnaires was 88.34% for school children and 91.53% for adolescents.

In both age groups, 15 centres participated. A total of 570 schools were included in the 6–7 group, with a total of 35 780 school children. In the 13–14 group, 220 schools were included with a total of 41 399 adolescents.

The prevalence of wheezing ever, current asthma symp- toms and severity of symptoms related to asthma are presented in table 1. Cumulative prevalence of wheeze and the prevalence of current asthma symptoms were higher in men in the school children group. Nonetheless, in the adolescent group, these prevalences were higher in women. One-third of school children with a history of ‘wheezing ever’ started in the first year of life and just over 25% after 5 years of age. Among school children, 50% had wheezed 1–3 times (more men than women) and 10% had 4–12 episodes of wheezing in the past year. In the female adolescent group and among those current wheezers, almost 50% had 1–3 episodes of wheezing and, 9% reported 4–12 episodes of current wheezing.

Severe asthma symptoms (defined as waking up at night due to wheezing at least one or more times per week and any episode of wheeze severe enough to limit the ability to speak in the past year) were present in more than 30% of both men and women in the school chil- dren group and 25% of women in the adolescent group, among those with current wheezing.

Despite the somewhat high prevalence of asthma symp- toms (9%–13.6%), only 6%–9% of school children and adolescents had received a medical diagnosis of asthma and, less than 5% had a written plan of action in case of asthma symptoms.

Tables 2 and 3 show the risk factors for asthma symptoms in the school children and adolescent groups, respectively. The most significant associations were the presence of rhinitis and rash symptoms in the past 12 months, the previous diagnosis of allergic rhinitis or atopic dermatitis, as well as the use of paracetamol in the past 12 months in both groups. Early pneumonia history and wheeze in the first year of life were important factors in the school children group.

Asthma symptoms in the female school children group were significantly associated with a maternal history of smoking during pregnancy and contact with farm animals in the first year of life. Additionally, in the female adoles- cent group, the presence of asthma symptoms was significantly associated with occasional smoking. On the other hand, there was a negative association between the altitude of the centres and the presence of current wheeze in both the school children and adolescent groups.

Figure 1A,B shows the prevalence of asthma symp- toms by city ordered from the lowest to the highest alti- tude in school children males and female adolescents as they were more representative of the effect. The corresponding values of the Pearson correlations for WHEZEV, WHEZ12, SPEECH12 and ASTHMAEV with altitude were −0.583 (p=0.023); −0.794 (p<0.001); −0.707 (p=0.003); −0.427 (p=0.112) in school boys, and −0.652 (p=0.008); −0.747 (p=0.001); −0.646 (p=0.009); −0.341 (p=0.231) in female adolescents.

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 preva- lence 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 collabo- rators 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 symp- toms 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 parac- etamol (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 alti- tude 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 inflamma- tion and altered immune responses.24

According to our results, having the habit of smoking increased the risk of asthma symptoms in female adoles- cents. This has been reported previously in other coun- tries. 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 consump- tion 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 occupa- tional 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 methacho- line necessary to cause a 20% decrease in forced expira- tory 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 2 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 diag- nosis.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 life- style 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 alti- tude 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 hospital- isations in comparison to the previous year. These find- ings 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 proper- ties) and decreases the concentration of interferon-, 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 derma- titis 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 chil- dren. Studies are beginning to demonstrate rural paedi- atric 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

CONCLUSIONS

In the present study, we show overall, increases in the prevalence of asthma symptoms and severity in 14 cities across Mexico in the last 15 years, compared with the ISAAC Phase Three Study. The most important risk factors for asthma symptoms were the presence of allergic symptoms and diagnosis of rhinitis and eczema, as well as the current or past use of paracetamol. On the other hand, sea level altitude higher than 1500 m was seen as a protective factor. The urban and rural centres of Toluca had a lower prevalence of asthma symptoms compared with the cities under 1000 mamsl. The identification of risk factors and their pattern could help implement strategies to mitigate the incidence of asthma such as a reduction of paracetamol exposure in atopic families, as well as residence change, when possible, in selected patients.

Further studies are necessary to explore the impact of urban and rural environments in the prevalence of asthma and other allergic diseases.

LIMITATIONS

This multicentre cross-sectional study has limitations typical of an observational study. However, the GAN meth- odology, following the ISAAC methodology is an internationally recognised method that can successfully identify the prevalence of symptoms related to allergic diseases, which have increased in the last decade worldwide. The information was obtained with a standard methodology with a previously validated instrument and with a high response rate from all the centres involved. This study allows us to identify important associations and potential risk factors by sex and age along with access to environmental factors like altitude as a possible modulating factor for current wheezing in the Mexican population. This opens the opportunity to carry out studies that allow analysing the intrinsic and environmental factors related to the increase in the prevalence of asthma in different areas of the world. It represents an opportunity area to develop national strategies necessary to detect and care for the population at risk with asthma symptoms and other allergic diseases.

Author affiliations

1Allergy and Immunology, Hospital Infantil de México Federico Gomez, Mexico City, Mexico

2Allergy and Immunology, Hospital Infantil de Tamaulipas, Ciudad Victoria, Mexico

3Paediatrics: Child and Youth Health, The University of Auckland, Auckland, New Zealand

4Paediatric Allergy and Pulmonology Units ‘Virgen de la Arrixaca’ University Children’s Hospital, University of Murcia, Universidad de Murcia, Murcia, Spain

5Allergy and Immunology, Clínica de Asma-Alergia, Mexicali, Mexico 6Allergy and Immunology, Instituto Mexicano del Seguro Social, San Luis Potosí, San Luis Potosí, Mexico

7Allergy and Immunology, Hospital General de Tijuana, Tijuana, Mexico 8Allergy and Immunology, Centro de Investigación, Diagnóstico y Tratamiento de Asma y Alergias, Toluca, Estado de México, Mexico

9Allergy and Immunology, Hospital Ángeles Chihuahua, Chihuahua, Mexico 10Allergy and Immunology, Hospital Ángeles Ciudad Juárez, Chihuahua, Mexico

11Allergy and Immunology, CRIT Michoacán, Morelia, Michoacán, Mexico 12Allergy and Immunology, Hospital Ángeles Xalapa, Xalapa, Veracruz, Mexico 13Allergy and Immunology, Universidad Veracruzana, Córdoba, Veracruz, Mexico

14Allergy and Immunology, Private practice, Puerto Vallarta, Jalisco, Mexico 15Allergy and Immunology, Benemérita Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico

16Allergy and Immunology, Hospital General de Matamoros, Matamoros, Mexico

Acknowledgements We thank all the school children, adolescents and parents, who collaborated in the GAN study, for obtaining information and updating the prevalence of asthma. All the authors involved in this article who contributed to the design, elaboration, writing and analysis of this work. We appreciate the financial support of the Mexican College of Pediatricians Specializing in Allergy and Clinical Immunology (COMPEDIA) to print the questionnaires used for this important project. Likewise, we would like to thank the support of Dr Innes Asher and her team of collaborators, for their direction in preparing this study, as well as for their support for the inclusion of Mexico in this important international study. Finally, we thank the support of Dr Virginia Pérez Hernández, Axel Arturo Berber-Del-Río, Dr Joaquín Alberto Alejandro Pimentel Hayashi, Dr Yolanda Rodríguez Galván, Dra Laura Alicia Sacre, Dr Ricardo Regules García, Dr Juan José Luis Sienra Monge and Dr Jaime Mariano Del Río Chivardi for their contribution to the revision and editing of this article.

Collaborators The GAN Phase I group: OJ Saucedo-Ramírez (Mexico City, Mexico), V Merida-Palacio (Mexicali, Mexico), BC Ramos-García (San Luis Potosí, Mexico), AJ Escalante-Dominguez (Tijuana, Mexico), F Linares-Zapien (Toluca, Mexico), HL Moreno-Gardea (Chihuahua, Mexico), G Ochoa-Lopez (Ciudad Juárez, Mexico), LO Hernández-Mondragón (Morelia, Mexico), JS Lozano-Saenz (Xalapa, Mexico), JA Sacre-Hazouri (Córdoba, México), A Juan-Pineda (Puerto Vallarta, Mexico), MG Sánchez Coronel (Aguascalientes, Mexico), N Rodríguez-Pérez (Tamaulipas, Mexico), MJ Ambriz-Moreno (Tamaulipas, Mexico).

Contributors BED-R-N, NRN, EMNR, RG-A, PE and LG-M: study conception, design, acquisition of data and drafting the manuscript. AB: statistical analysis. OJSR, VJMP, BDCRG, AJED, FJLZ, LGM, GGOL, LOHM, JSLS, JASH, AJP, MGSC, NRP,

MdJAM: data acquisition and drafted the initial version of the article. All authors contributed to data interpretation and read, commented on and approved the final version.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Patient consent for publication Not required.

Ethics approval The present study was approved by the Ethics, Research, and Biosafety committees of the Hospital Infantil de México Federico Gómez (HIMFG, protocol HIM/2016/065) by the guidelines of the institution and according to the Mexican law, was valid to all participant centres.

Provenance and peer review Not commissioned; externally peer reviewed.

Data availability statement Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information. Information regarding this article can be requested from Dra Blanca Estela Del Río Navarro at blancadelrionavarro@gmail.com.

Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

ORCID iD

Nayely Reyes-Noriega http://orcid.org/0000-0002-1701-7517

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Eczema symptoms in the Mexican pediatric population

Thu, 16 Jul 2026 22:51:17 GMT

Have the prevalence of eczema symptoms increased in the Mexican pediatric population?

Prevalence and associated factors according to Global Asthma Network Phase

Elsy Maureen Navarrete-Rodríguez, MD, PhD ^a , Blanca Estela Del-Río-Navarro, MD ^a *, Nayely Reyes Noriega, MD ^a , Arturo Berber, MD, PhD ^b , Valente Mérida Palacio, MD ^c , Roberto García-Almaráz, MD ^d and Philippa Ellwood, MPH ^e , GAN Phase I Study group

ABSTRACT

Background: In children, atopic dermatitis or eczema is the most common inflammatory disease of the skin. According to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase IIIB in Mexico, 5.8% of children and 4.9% of adolescents had eczema symptoms. In 2012, Global Asthma Network (GAN) was established to update the prevalence of eczema and estimate potential factors contributing to its development.

Objective: To estimate the prevalence and associated factors for atopic eczema symptoms and diagnosis in children and adolescents according to GAN Phase I and compare the results with ISAAC Phase IIIB in Mexico.

Methods: A cross-sectional, multicenter survey was conducted in 15 Mexican centers during the period of 2015–2017 using the GAN Phase I questionnaires in children (6–7-year-olds) and ado- lescents (13–14-year-olds). The prevalences obtained from the GAN Phase I study, were compared with ISAAC Phase IIIB results; a Spearman’s correlation analysis was conducted between tem- perature, relative humidity, and altitude and eczema symptoms, and a logistic regression was performed to predict current eczema symptoms by age group.

Results: A total of 35 777 children and 41 399 adolescents were included. Since ISAAC Phase IIIB, the prevalence of itchy rash in the past 12 months significantly increased in the children’s group [6.6% (95% CI 5.7–7.4) vs 7.8 (95% CI 7.5–8.1), p ¼ 0.000] and adolescents’ group [5.8% (95% CI 5.0–6.7) vs 6.7% (95% CI 6.5–7.0), p ¼ 0.000].

In the adolescents’ group, the prevalence of nocturnal awakenings caused by rash symptoms on more than one night per week had a negative correlation between altitude (Spearman’s Rho ¼ —0.558, p value ¼ 0.031), and a positive correlation with the average annual temperature (Spearman’s Rho ¼ 0.604, p value ¼ 0.017) and annual relative humidity (Spearman’s Rho ¼ 0.742, p value ¼ 0.002). The most significant associations in children were the presence of sneezing or runny or blocked nose in the past 12 months [(OR 3.13, 95% CI 2.60–3.77), p ¼ 0.000], the use of paracetamol in the first year of life ([OR 1.52, 95% CI 1.15–2.01), p ¼ 0.003] and the use of an- tibiotics in the first year of life [(OR 1.30, 95% CI 1.08–1.55) p ¼ 0.004]. Moreover, altitude at 100– 1000 m above sea level was associated with current eczema symptoms in adolescents (p ¼ 0.001).

Conclusions: There has been a significant increase in eczema symptoms in both age groups since ISAAC Phase IIIB study. Additionally, eczema symptoms were associated with temperature, relative humidity, asthma, hay fever symptoms, the use of paracetamol and antibiotics.

Keywords: Eczema, Prevalence, Associated factors, GAN, Pediatric

Atopic dermatitis (AD), or atopic eczema, is the most common inflammatory disease of the skin.1 As a skin inflammatory disorder, “atopic eczema” or “atopic dermatitis” is commonly described by intense itching, erythematous patches, blisters, scabs, and in late stages, lichenification or thickening of the skin associated with a personal or family history of another allergic disorder.2,3 According to estimates, this condition affects 20% of the worldwide pediatric population, although the prevalence varies widely among countries.2 In the first 2 years of life, over 41% of children develop this disease with periods of exacerbation;4,5 and is considered an early manifestation of the atopic march, which describes IgE-mediated symptoms of allergic rhinitis and asthma during childhood.6 According to the IgE blood level, AD patients can be classified into 2 categories: intrinsic (normal and non-allergic IgE) and extrinsic (high levels of IgE associated with greater disease severity).7

Furthermore, atopic eczema symptoms can be influenced by genetic,8immunological, and environmental factors,9 suggesting that there are several subgroups of atopic eczema and other allergic diseases that vary in their symptoms and course of development.10,11

Children and adults who suffer from eczema have significant challenges that affect their quality of life, regardless of the severity and location of their lesions.12 It is estimated that over 40% of children with AD suffer from sleep disturbances for constant scratching, sore skin, or skin infections,13,14 25% suffer from depression or anxiety, and 31.6% from social problems,15 representing an impactful global health care economic burden.16.

There have been numerous efforts to determine the prevalence of atopic eczema around the world with the objective of monitoring changes in prev- alence and severity of symptoms and under- standing the possible causes of variability across countries. The International Study of Asthma and Allergies in Childhood (ISAAC) is one of the largest and most useful of these efforts.17 The study began in 1991 and was a multinational study to determine the prevalence of atopic eczema and other allergic diseases. The study described the prevalence and severity of atopic eczema, asthma, and rhinitis in various regions, examined risk factors, and evaluated temporary trends in the prevalence of these conditions in three phases from 1992 to 2003.18

The ISAAC Phase I study with 256 410 children aged 6 to 7 and 458 623 adolescents aged 13 to 14 found a prevalence of atopic eczema symptoms of just over 7%.2,17–19 At both ages, the highest prevalence was found in urban Africa, the Baltics, Australia, as well as Northern and Western Europe.19 As part of ISAAC Phase I, Mexico participated with a center (Cuernavaca). The prevalence of eczema symptoms in children and adolescents was 4.9% and 4.4%, respectively.17

According to ISAAC Phase IIIB, there has been a significant change in the prevalence of atopic eczema, with an increase in low-income countries such as Africa and East Asia. There has also been a large variation in the prevalence of current symp- toms of eczema among groups aged 6–7 years (from 0.9% to 22.5%) and 13–14 years (from 0.2% to 24.6%). ² ^, ²⁰ Solé et al reported a prevalence of 10% of eczema symptoms among Latin American children (n ¼ 93,851) and 8.3% among adolescents (n ¼ 165,917). Mexico participated in this phase with 8 centers from 7 cities in the group for children (n ¼ 23 391) and 10 centers from 8 cities in the group for adolescents (n ¼ 29 723). There was a 5.8% (95% CI 5.0–6.7) prevalence of eczema symptoms among children and a 4.9% (95% CI 4.1–5.7) prevalence among adolescents and no associations observed between mean temperatures, altitudes, or air pollution levels in 35 Latin American countries and the current prevalence of eczema symptoms. ²⁰

Based on the valuable data regarding the vari- ability of eczema symptoms among pediatric pop- ulations around the world and the contrast of factors associated with this disease, the Global Asthma Network (GAN) was established in 2012 in order to update the prevalence and associated factors of various allergic diseases, including atopic eczema. ²¹

In accordance with the results of GAN Phase I, this study aimed to estimate the prevalence and associated factors of eczema symptoms and di- agnoses in children and adolescents, as well as compare the results with the findings of ISAAC Phase IIIB in Mexico.

METHODS

Study design

A comparative cross-sectional study was carried out in school-age populations of 6–7-year-olds (children) and 13–14-year-olds (adolescents) in 15 centers of 14 cities in Mexico including Puerto Vallarta, Matamoros, Mexicali, Tijuana, Ciudad Victoria, Córdoba, Ciudad Juárez, Chihuahua City, Xalapa, San Luis Potosí, Aguascalientes, Michoa- cán, Mexico City north area, Toluca urban area, and Toluca rural area.

According to the methodology established by GAN, the sample unit was the entire population of children or adolescents within each school. Each center’s public and private schools were randomly selected. ²¹ Children’s questionnaires were completed by their parents, and adolescents’ questionnaires were completed at school by themselves. Legal guardians of children and adolescents signed informed consent forms. In addition to the standardized written core questionnaires developed for ISAAC Phases I and III, GAN questionnaires also included a question regarding a doctor-confirmed diagnosis of eczema. In Mexico, the questionnaires were trans- lated and back-translated into Spanish by 3 inde- pendent linguistic professionals according to the ISAAC English language questionnaire translation guidelines. ²² After the Spanish version of each questionnaire was completed, a pilot test was conducted in Mexico City with children and adolescents. Each of the centers involved in this study used the same version of the questionnaire according to the age group. Written questionnaires collected information regarding demographics such as age, date of birth, gender, school, and date of interview, as well as questions regarding eczema prevalence and severity, and associated factors such as paracetamol use and antibiotic use in the first year of life, physical activity, place of residence, food consumption, and daycare attendance. To ensure confidentiality, the questionnaires were coded using a unique number for each center, school, and participant. Additionally, fieldworkers took height and weight measurements in schools using a standardized approach. Details on the GAN methodology can be found at the Global Asthma Network Manual. ²¹

Deﬁnitions

Regarding the symptoms and diagnosis of eczema, we considered the following 8 questions (Supplementary material 1). According to the ISAAC Phase IIIB study and GAN study, “current eczema symptoms” prevalence was estimated based on affirmative responses to the questions: “Have you (has this child) had this itchy rash at any time in the past 12 months?” and, “Has this itchy rash at any time affected any of the following places: the folds of the elbows; behind the knees; in front of the ankles; under the buttocks; or around the neck, ears, or eyes”. “Severe eczema symptoms” prevalence was defined as current symptoms being the cause of awakening 1 or more times per week, with a positive answer to: “In the past 12 months, how often, on average, have you (has this child) been kept awake at night by this itchy rash? (one or more nights per week). ²⁰ ^, ²³

Sample size

A sample size of 3000 was sought in each age group (with a minimum of 1000 deemed accept- able), which would have sufficient power (>90%) to detect 5% differences in eczema prevalence (at a significance level of 0.01) and allow for testing multiple hypotheses. ²¹ All Mexican centers reached the average level of participation (at least 80% for adolescents and 70% for children). ²⁴

Data collection and analysis

Data entry was carried out by the medical personnel at the study center for the electronic GAN database. To minimize the possibility of er- rors, 10% of questionnaires were double entered. ²¹ As part of the quality control process for Spanish and Portuguese-speaking centers in Spain, the GAN databases were checked and approved in 2019 by the Murcia data center.

In accordance with the years in which the field work was conducted at each center, climatic data such as precipitation, temperature, relative hu- midity, the percentage of urban populations, and the type of climate according to Köppen-Geiger climate classification was obtained from the na- tional databases of the Instituto Nacional de Esta- dística y Geografía ( https://www.inegi.org.mx/ ) and Comisión Nacional del Agua ( https://smn. conagua.gob.mx/es/ ).

A descriptive data analysis was conducted using central tendency measurements (mean, standard deviation [SD], and 95% confidence intervals [95% CI ]), in addition to percentages and frequencies corresponding to each of the questions described in the Supplementary Material 1 on eczema prevalence. The prevalences obtained from the GAN Phase I study (including 15 centers) were compared with the prevalences obtained from the ISAAC Phase IIIB study (including 8 centers for children and 10 centers for adolescents) by chi- square test with a statistically significant p-value <0.05 for both age groups. We performed a Spearman’s correlation analysis between climatic variables and the prevalences of eczema symptoms by center, (previously described in Supplementary Material 2), with a statistically significant p-value <0.05. Furthermore, an association analysis was performed between the current and cumulative eczema prevalence by sex and variables related to asthma symptoms, hay fever symptoms, history of breastfeeding, contact with domestic animals (dog, cat), frequency of consumption of antibiotics and paracetamol, frequency of hours of television, hours of exercise, food consumption by category and body mass index. Chi-square tests was used to identify all variables that might be influencing the prevalence of current symptoms (p < 0.05). These factors were further analyzed using backward conditional logistic regression to develop models to predict current eczema symptoms by age group.

In order to organize the data, Microsoft Excel 2016 v16.0.6568.2036 (Microsoft Corporation) was used, along with IBM SPSS Statistics v25.0 (SPSS Inc., IBM) and Stata Statistical Software (Stata Corporation, LLC, College Station, TX, 2017) for statistical analysis.

RESULTS

A total of 35 777 children and 41 399 adolescents were included from 790 schools; 51.7% of the population were female. The mean weight and height of children were 24.60 5.48 kg and 1.21 0.06 m, respectively. Among adolescents, the mean weight and height were 54.28 11.53 kg and 1.59 0.81 m, respectively.

The national response rate of the delivered questionnaires was 88.55% for children and 91.19% for adolescents. A description of the cli- matic characteristics and percentage response by center can be found in Supplementary Material 2.

Comparison of the results of the ISAAC Phase IIIB and GAN Phase I study

Since ISAAC Phase IIIB, the national prevalence of itchy rash in the past 12 months significantly increased in the children’s group [6.6% (95% CI 5.7–7.4) vs 7.8 (95% CI 7.5–8.1), p ¼ 0.000] and adolescents’ group [5.8% (95% CI 5.0–6.7) vs 6.7%

(95% CI 6.5–7.0), p ¼ 0.000]. The prevalence of eczema ever in the children’s group also increased by 2.4% points [3.3% (95% CI 2.6–3.9) vs 5.7% (95% CI 5.5–6.0), p ¼ 0.000] (see Table 1 ).

In both age groups, the prevalence of flexure rash decreased by 1.1–1.2 percentual points, and the prevalence of clearance of rash in the past 12 months decreased significantly [7.1% (95% CI 6.2– 8.0) vs 5.9% (95% CI 5.6–6.1), p ¼ 0.000] in the children’s group and in the adolescents’ group [12.2% (95% CI 11.5–12.9) vs 5.9% (95% CI 5.7– 6.1), p ¼ 0.000]. The prevalence of current symp- toms of eczema decreased in the adolescents’ group [4.9% [95% CI 4.1–5.7) vs 4.6% (95% CI 4.4– 4.8), p ¼ 0.000], and the current prevalence of severe eczema symptoms ranged from 0.6 to 0.8 in both age groups, without a significant difference ( Table 1 ).

In the 4 centers that participated in ISAAC Phase IIIB and GAN Phase I (Mexico City north area, Mexicali, Toluca urban area, and Ciudad Victoria), the prevalence of itchy rash in the past 12 months increased significantly, as did the prevalence of eczema symptoms in the first 2 years of life and eczema ever in at least 3 of the 4 centers in both age groups (p < 0.05). Please refer to Table 2 .

Children in the north area of Mexico City re- ported a decrease in current eczema symptoms by 1.6% points and adolescents by 4.6% points. In adolescents, a significant decrease of over 3% points was also observed in the prevalence of itchy rash ever [11.3% (95% CI 10.3–12.3) vs 8.0% (95% CI 7.1–8.9), p ¼ 0.000] and rash in flexures [10.1% (95% CI 9.1–11.0) vs 4.0% (95% CI 3.4–4.7), p ¼ 0.000].

On the other hand, Ciudad Victoria reported the highest increase in current eczema symptoms in children and adolescents (3.8% points, p ¼ 0.000 and 1.4% points, p ¼ 0.030, respec- tively) and in symptoms of severe eczema in chil- dren (0.8% points, p ¼ 0.001). However, both groups reported the lowest prevalence of eczema medical diagnoses (3.4% in children and 1.3% in adolescents).

According to Mexicali, in adolescents, nighttime awakenings due to rash in the past 12 months increased by 0.4% points (p ¼ 0.026), as did cur- rent symptoms of severe eczema by 0.5% points (p ¼ 0.002). In the children group, the prevalence of eczema ever increased significantly by 7.8% points (p ¼ 0.000) and reported the highest prev- alence of eczema medical diagnoses [11.1% (95% CI 9.7–12.5)].

The Toluca urban area reported a significant increase of at least 2% points in the prevalence of itchy rash ever [7.8% (95% CI 6.9–8.7) vs 9.9% (95% CI 8.8–11.0), p ¼ 0.004]), itchy rash in the last 12 months [5.9% (95% CI 5.1–6.7) vs 8.9% (95% CI 7.8– 10.0), p ¼ 0.000]), and eczema ever among chil- dren [3.4% (95% CI 2.8–4.0) vs 7.7% (95% CI 7.8– 10.0), p ¼ 0.000]).

GAN Phase I study results

There was a wide variety of the current preva- lence of eczema between centers. According to the children group, Córdoba, Ciudad Victoria, and Ciudad Juárez had the highest prevalence (more than 6%). Among adolescents, Mexico City, Mex- icali, Chihuahua, and Puerto Vallarta had the highest current prevalence of eczema (>7%), while Michoacán had the lowest prevalence in both age groups (<3.5%). (Supplementary materials 3a and 3b) The prevalence of eczema confirmed by a doctor ranged from 2.1% (95% CI 2.0–2.2) to 5.4% (95% CI 5.2–5.7) in adolescents and children, respectively (see Table 1 ). Additionally, over fifty percent of the children and adolescents with current eczema symptoms were also diagnosed as having asthma or hay fever by a doctor.

Tables 3 and 4 present factors associated with current symptoms of eczema in children and adolescents by sex, respectively. The most significant associations in children were the presence of sneezing or runny or blocked nose in the past 12 months [males (OR 3.13, 95% CI 2.60–3.77), p ¼ 0.000] vs [females (OR 2.92, 95% CI 2.42–3.52), p ¼ 0.000], the use of paracetamol during the pregnancy of the child more than once a month [males (OR 2.02, 95% CI 1.38–2.93), p ¼ 0.000] vs [females (OR 1.50, 95% CI 1.01–2.21), p ¼ 0.040], the use of paracetamol in the first year of life [males (OR 1.10, 95% CI 0.84–1.45), p ¼ 0.471] vs [females (OR 1.52, 95% CI 1.15–2.01), p ¼ 0.003] and the use of antibiotics in the first year of life [males (OR 1.19, 95% CI 0.98–1.45), p ¼ 0.066] vs [females (OR 1.30, 95% CI 1.08–1.55) p ¼ 0.004].

For the adolescents’ group, the most significant associated factors were wheezing or whistling in the past 12 months [males (OR 2.45, 95% CI 1.97–3.03), p ¼ 0.000] vs [females (OR 2.03, 95% CI 1.77–2.35) p ¼ 0.000], sneezing or a runny or blocked nose without a cold or a flu in the past 12 months [males (OR 2.93, 95% CI 2.44–3.52), p ¼ 0.000] vs [females (OR 3.01, 95% CI 2.64– 3.42), p ¼ 0.000], hay fever ever [males (OR 2.14, 95% CI 1.67–2.75), p ¼ 0.000] vs [females (OR 1.84, 95% CI 1.55–2.18), p ¼ 0.000] and the use of paracetamol at least once a month [males (OR 1.68, 95% CI 1.29–2.20), p ¼ 0.000] vs (females [OR 1.71, 95% CI 1.39–2.10), p ¼ 0.000].

Among the children, living in centers located between 1500 and 2000 m above sea level was reported by both sexes as a protective factor for current eczema symptoms (males ¼ OR 0.74, 95% CI 0.56–0.96, p < 0.028 ; females ¼ OR 0.65, 95% CI 0.50–0.84, p < 0.001). In the adolescent group, living in centers with an altitude of 100–1000 m above sea level was reported as an associated factor for current eczema symptoms in both sexes (males ¼ OR 1.50, 95% CI 1.14–1.96, p < 0.003 ; females ¼ OR 1.34, 95% CI 1.12–1.61, p < 0.001).

Fig. 1 Spearman’s correlation between the prevalence of nighttime awakening due to itchy rash in the past 12 months and the altitude of the fifteen GAN Phase I centers in 13–14-year-old.

Fig. 2 Spearman’s correlation between the prevalence of nighttime awakening due to itchy rash in the past 12 months and the average annual temperature of the fifteen GAN Phase I centers in 13–14-year-old.

DISCUSSION

According to the GAN Phase I methodology, this study represents one of the most compre- hensive attempts to estimate the prevalence of atopic dermatitis symptoms in children and ado- lescents in Mexico. ISAAC Phase IIIB and GAN prevalence data were examined over time to determine patterns of change over more than a decade (2002–2017) and found that prevalence and severity of eczema vary by age group, center, and can be correlated with climatic characteristics. Additionally, in both age groups, GAN Phase I results indicated a national increase in eczema ever prevalence (from 0.4 to 2.4% points) and itchy rash in the past 12 months prevalence (from 0.9 to 1.2% points) compared to the ISAAC Study Phase IIIB. Nevertheless, it was determined that among the 4 centers involved in both phases, eczema prevalence increased by at least 1.5% points among children in the 4 centers and 1 percentage point among adolescents in Mexico City and Ciudad Victoria centers.

We found a substantial burden of current eczema symptoms in Ciudad Victoria and Mex- icali: 6 to 7 out of 100 children and 4 to 6 ado- lescents had eczema symptoms in their flexures areas or on their face within the last 12 months, and 1 out of 100 had nocturnal awakenings as a result. An estimated 46%–80% of children with AD suffer from sleep disturbances, manifesting as difficulty falling asleep, frequent awakenings during the night, and excessive sleepiness during the day. ²⁵ ^, ²⁶ Sleep disturbance is the second most common cause of impairment of quality of life among children with AD, after itch. ²⁷ An interesting finding in adolescents was the moderate positive correlation between nocturnal awakenings caused by eczema symptoms and the annual temperature of the centers at the time of recruitment, along with a high positive correlation with relative humidity. Even though relative humidity is influenced by temperature and air condition, it has been observed that high humidity could encourage the growth and reproduction of allergens such as mold, ²⁸ and high temperatures are associated with poorly controlled eczema. ²⁹ Sargen et al found that for every 5 ^◦ F increase in temperature, the odds (OR ¼ 0.85, 95% CI 0.82–0.89, p < 0.001) for patients who describe their disease as poorly controlled increased by 15%. In addition, the association between temperature and disease control (OR ¼ 0.90, 95% CI: 0.87–0.93, p ¼ 0.001) was statistically significant after adjusting for potential confounders such as race, ethnicity, sex, annual household income, and use of topical medications (topical steroids, topical tacrolimus, topical pimecrolimus). With respect to humidity, this study initially reported a 10% increase in the odds of poorly controlled diseases (OR ¼ 0.90, 95% CI 0.81–1.00, p ¼ 0.04) for every 10% increase in humidity.

Nevertheless, the statistical significance of this association was lost in the multivariate analysis (OR ¼ 0.93, 95% CI 0.84–1.02, p ¼ 0.14). ²⁹ In contrast, in the centers of Spain, Suárez-Varela et al reported a positive correlation between the prevalence of eczema symptoms and humidity and a negative correlation between annual temperature and eczema symptoms in children between 6 and 7 years of age. ³⁰ Numerous studies have shown that eczema incidence increases in low temperatures and low humidity as a consequence of dehydration, ³¹ increased production of IL-a1 ³² and mast cell granulation. ³³ However, one explanation for our findings may be that high relative humidity and elevated temperatures may reduce evaporative heat loss during sweating and irritate the skin when central heating is increased, which may result in increased itching due to neuropeptide- induced vasodilation. ^34–37 The external humidity was taken into account in this study and not the indoor humidity or the possibility of heating or air conditioning.

For altitude, it was found that higher altitudes were associated with a lower prevalence of nocturnal awakenings at least once a week in ad- olescents, while lower altitudes were associated with an increased risk of eczema symptoms in centers below 1000 m. Furthermore, altitudes of 1500 to 2000 m were observed to protect against eczema symptoms in a group of schoolchildren. This is consistent with a systematic review that included 15 observational studies involving 40,148 patients with atopic dermatitis on therapy at high altitude centers (>1000 m). In this study, 96% of patients (n ¼ 39,006) reported decreased disease activity during treatment, 64% reported improved symptoms in the last 12 months following treat- ment (n ¼ 2670), ³⁸ and 82% (n ¼ 1178) reduced or stopped the use of local corticosteroid during treatment and at the 12-month follow-up (72% of the n ¼ 3008). ³⁹ Also, urinary eosinophilic protein X (EPX) ⁴⁰ decreased and was significantly correlated with SCORAD. ⁴¹ However, the authors reported a very low quality of the information due to heterogeneity between the studies and the lack of description in some outcomes. ⁴²

There have been high rates of eczema reported in pediatric populations near the equator, but alti- tude has not been associated with eczema in ISAAC studies. ⁴³ ^, ⁴⁴ However, other studies that have used questionnaires other than the ISAAC methodology, including the Prevalence and Risk Factors of Allergies in Turkey (PARFAIT), have assessed the prevalence and risk factors of asthma, hay fever, and eczema among children, as well as the geographical variables and weather conditions associated with them. Several factors were associated with atopic dermatitis prevalence in this study, including altitude <1000 m, annual temperature >15 ^◦ C, relative humidity >70%, and atmospheric pressure >1000 mbars. ⁴⁵ Considering the heterogeneity of the associations between altitude, temperature, and relative humidity, it is necessary to conduct multicenter studies in order to determine how these factors relate to eczema symptoms.

It was found that the use of paracetamol and antibiotics was also associated with the presence of eczema symptoms in children and the frequency of paracetamol use among adolescents. It has been reported that in Latin American children, paracetamol use in the first year of life was asso- ciated with the presence of eczema with an OR of 1.49 (1.26–1.76) ⁴⁶ and in Polish adolescents, paracetamol use at least once per month was associated with eczema with an OR of 1.5 (1.11– 2.01), p < 0.05. ⁴⁷ Even though the use of paracetamol and antibiotics in children are usually associated with respiratory infections, there are also other reasons for its use, such as otitis media, vaccination fever, infections in other organs, etc. Paracetamol, at recommended therapeutic doses, may deplete glutathione and glutathione-dependent enzymes, and reduce the body’s ability to withstand oxidative stress. ⁴⁸ As a result, reactive oxygen species in response to allergic, viral, or other non-allergic stimuli, may lead to enhanced inflammation and the develop- ment or worsening of pre-existing asthma, rhino- conjunctivitis, or eczema, depending on the organ system affected. ^49–51 In addition, long-term use of broad-spectrum antibiotics has been shown to cause dysbiosis of the intestinal tract, which negatively impacts extraintestinal organs such as the lungs, the brain, and the skin, leading to chronic AD progression and asthma. ⁵² ^, ⁵³ However, it is important to take into account the potential confounding effects of familial and genetic factors in this association. ⁵⁴

Studies have found that having parents with a history of allergic disease and/or having a diag- nosis of allergic disease are risk factors for devel- oping another disease involving an allergic component in the future. ⁵⁵ In the ISAAC Phase III study, 0.8–1.2% of children and adolescents had asthma, rhinitis, and eczema symptoms, with significant associations between the three conditions. ¹⁷ ^, ⁵⁵ As a result of our study, wheezing, nasal symptoms in the past 12 months, and hay fever are the most significant risk factors for eczema. Despite a similar association between asthma symptoms and hay fever with eczema among children of both sexes, wheezing in the past year and hay fever were more prevalent among adolescent males. According to research, asthma, allergic rhinitis, and atopic eczema are more common among children of both sexes during their school years; ⁵⁶ ^, ⁵⁷ however, males are more sensitive to grass pollen, mites, and tree pollens ⁵⁸ resulting in a greater likelihood of developing allergic disorders by the age of 14. Women, however, are more likely to develop eczema symptoms during their reproductive years (between 15 and 49 years old), when they are most likely to become sensitized to environmental allergens. ⁵⁹

Finally, according to our study, more than 50% of children and adolescents with current eczema symptoms were also diagnosed as having asthma or hay fever by a doctor. Although eczema symp- toms have increased since the ISAAC study in Mexico, less than 5.5% of patients in both groups received a diagnosis from a doctor. There are similar results in the literature, as only 6% of 17.1% of American patients with eczematous symptoms were diagnosed with atopic dermatitis ⁶⁰ and 93% of Puerto Rican children with symptoms of atopic dermatitis and sensitization to at least one allergen were not diagnosed with this disease. ⁶¹ This suggests significant underdiagnosis and undertreatment of the condition in low-income settings, possibly related to limited access to healthcare specialists.

Limitations

As an observational study, this multicenter cross-sectional study has certain limitations, such as memory bias. Furthermore, this study did not include representative centers from southern Mexico due to a lack of information, preventing analysis by region (Pacific, Northeast, Bajío, Cen- tral, and Southeast).

While the GAN study has demonstrated an adequate method for estimating the prevalence of allergic disease symptoms, we did not obtain biological samples to determine genetic differences or levels of IgE or confirm the presence of atopic eczema lesions.

CONCLUSION

This is Mexico’s most extensive epidemiological study to estimate eczema symptoms in children and adolescents. There has been an increase in eczema symptoms in both age groups since the ISAAC Phase IIIB study and a low prevalence of diagnosis of eczema. Several interesting and potentially associated factors were also described, including temperature, relative humidity, asthma and hay fever symptoms, paracetamol use, and antibiotic use, so further investigation is required.

Abbreviations

GAN, Global Asthma Network; ISAAC, International Study of Asthma and Allergies in Childhood; OR, Odds ratio; 95% CI, 95% Confidence interval

Funding

No financial support for this work could have influenced its outcome.

Authors’ contributions

NREM: Made substantial contributions to conception and drafting the manuscript.

DRNBE: Made substantial contributions to conception, design, acquisition of data and drafting the manuscript. RNN: Made substantial contributions to design, acquisition of data and drafting the manuscript.

BA: Made substantial contributions to the analysis, interpretation of data and drafting the manuscript. MPV: Made substantial contributions to design and acquisition of data.

GAR: Made substantial contributions to design and acquisition of data.

EP: Made substantial contributions to the analysis and drafting the manuscript.

RGBDC: As centre coordinator, made substantial contributions on the acquisition of data.

EDAJ: As centre coordinator, made substantial contributions on the acquisition of data.

LZF: As centre coordinator, made substantial contributions on the acquisition of data.

GML: As centre coordinator, made substantial contributions on the acquisition of data.

OLGG: As centre coordinator, made substantial

contributions on the acquisition of data.

HMLO: As centre coordinator, made substantial contributions on the acquisition of data.

LSJS: As centre coordinator, made substantial contributions on the acquisition of data.

SHJA: As centre coordinator, made substantial

contributions on the acquisition of data.

JPMA: As centre coordinator, made substantial contributions on the acquisition of data.

SCMG: As centre coordinator, made substantial

contributions on the acquisition of data.

RPN: As centre coordinator, made substantial contributions on the acquisition of data.

AMMDJ: As centre coordinator, made substantial contributions on the acquisition of data.

DRNBE: Involved in revising it critically for important

intellectual content.

SROJ: Involved in revising it critically for important intellectual content.

Ethics approval and consent to participate

The authors obtained informed consent from the parents or guardians of participants in the present study. The corresponding author accepts responsibility for this manuscript.

The present study was approved by the Ethics, Research, and Biosafety committees of the Hospital Infantil de México Federico Gómez (HIMFG, protocol HIM/2016/065) in accordance with the guidelines of the institution.

Consent for publication

All authors consent this article for publication.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of competing interest

The authors declare that they have no conflict of interest in relation to the methods or materials employed in this study.

Acknowledgments

In the GAN study, we would like to thank all the children, adolescents, and parents who participated in obtaining information and updating the prevalence of eczema. This work was designed, elaborated, written, and analyzed by all of the authors involved. In order to complete this important project, we would like to acknowledge the financial support provided by the Mexican College of Pediatricians Specializing in Allergy and Clinical Immunology (COMPEDIA). In addition, we would like to thank Dr. Luis Garca-Marcos Álvarez and Dr. Virginia Pérez for their support.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.waojou.2022.100710.

Author details

aServicio de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. bAsesor Externo del Servicio de Alergia e Inmunología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. cClínica de Asma-alergia Mexicali, Baja California, Mexico. Hospital Infantil de Tamaulipas, Ciudad Victoria, Tamaulipas, Mexico. eDepartment of Paediatrics: Child and Youth Health, University of Auckland, Auckland, 1023, New Zealand.

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Alergias respiratorias

Mon, 03 Oct 2022 18:23:01 GMT

Padecer una alergia respiratoria es más común de lo que crees y es por ello que hoy quiero que conozcas un poco más sobre este tipo de alergias y sus reacciones más frecuentes para que estés atento a ellas.

¿Qué es una alergia respiratoria?

Una alergia respiratoria es una reacción o manifestación que presenta el sistema respiratorio ante sustancias nocivas como polvo, polen o pelo de algunos animales.

¿Cuáles son los síntomas?

Algunos de los síntomas que se presentan cuándo existe una alergia respiratoria son:

Picor o ardor en la nariz
Congestión nasal
Mucosidad
Tos y estornudos frecuentes
Lagrimeo y enrojecimiento de ojos

Sin embargo, uno de los síntomas más fuertes es la dificultad para respirar , misma que debe tratarse de manera inmediata para evitar complicaciones.

¿Qué tratamientos existen?

Para el tratamiento de las alergias se pueden tratar con medicamentos o la inmunoterapia, que consiste en vacunas que buscan reducir las reacciones de cualquier tipo de alergia.

Para conocer más sobre el tipo de alergia respiratoria que estás presentando o el tratamiento que necesitas, agenda tu consulta con nuestro especialista, el Dr. José Antonio Sacre Hazouri.

¿Qué es el EPOC?

Fri, 20 May 2022 18:18:30 GMT

Uno de los sistemas de defensa más importantes del cuerpo tiene que ver con los pulmones y los bronquios . Estos en realidad cuentan con mecanismos naturales para eliminar partículas que llegan a entrar en la respiración. Los bronquios se encargan de producir el moco , que sirve para expulsar los elementos extraños que están en los pulmones.

Si bien, en el tabaquismo la entrada de partículas es particularmente mayor y sobrepasa la capacidad de los mecanismos de los bronquios, se produce un incremento del moco, el cual es posteriormente eliminado con la tos . Es común en los fumadores la expectoración y la tos, hasta llegar a ser una bronquitis crónica. Al reducir el calibre de los bronquios, es esfuerzo que se realiza para movilizar el aire es mayor, por lo que se produce una dificultad respiratoria o EPOC (Enfermedad Pulmonar Obstructiva Crónica).

En estos casos, los bronquios se van obstruyendo progresivamente y el pulmón forma un enfisema , por aspirar humo de tabaco y otras substancias. Por lo general, es una enfermedad tratable y hay medicamentos o terapias que dan resultados favorables, pero en casos avanzados, es una enfermedad irreversible y mortal.

Fibromialgia

Thu, 27 Jan 2022 18:14:57 GMT

La Fibromialgia hace referencia al dolor de músculos y el tejido fibroso (ligamentos y tendones). Esta enfermedad se caracteriza por un dolor musculoesquelético generalizado y sensación de dolor ante la presión en unos puntos específicos.

La fibromialgia es frecuente, sobre todo en mujeres. Puede presentarse como única alteración o asociada a otras enfermedades.

Podemos decir que consiste en una anomalía en la percepción del dolor, de manera que se perciben como dolorosos, estímulos que habitualmente no lo son. Sin embargo, además de dolor, la fibromialgia puede ocasionar rigidez generalizada, sobre todo al levantarse por las mañanas, y sensación de inflamación mal delimitada en manos y pies. En algunas ocasiones el dolor puede presentarse como quemazón, molestia o desazón, es muy común que el dolor varía en relación con la hora del día, el nivel de actividad, los cambios climáticos, la falta de sueño o el estrés.

No se conoce la causa de esta alteración, pero se piensa que hay muchos factores implicados como, por ejemplo, una infección bacteriana o viral, un accidente de automóvil o en otros casos aparece después de que otra enfermedad que limite la calidad de vida.

La fibromialgia se reconoce como un síndrome, es muy importante establecer un diagnóstico firme porque ahorra mucho tiempo al buscar diagnósticos o tratamientos.

La enfermedad no tiene cura definitiva, pero existen tratamientos que ayudan a mejorar el dolor y tratar los síntomas acompañantes, para conseguir una gran mejoría en la calidad de vida de estos pacientes. Es importante conocer la naturaleza de la enfermedad y cuáles son los factores desencadenantes que la provocan.

Gastritis

Thu, 13 Jan 2022 18:12:32 GMT

La gastritis es una enfermedad que afecta al sistema digestivo, el estómago se inflama y se pierde la capa que recubre la superficie, al no tener este recubrimiento es mucho más fácil que los alimentos ácidos irriten el estómago.

Existen tres tipos de gastritis:

gastritis aguda

gastritis crónica

ulcera péptica

Una de las causas por las que no mejora las gastritis es por una bacteria llamada Helicobacter Pylori, esta es la causa más común de la úlcera gastroduodenal y ciertos tipos de cáncer de estómago.

Esta bacteria puede ser transmitida o contraída por:

De persona a persona en la niñez

Contacto de boca a boca

Comida y agua contaminada

Enfermedades gastrointestinales con vómito

Contacto con materia fecal

Otras de las razones por las que se puede tener gastritis son:

Abuso de analgésicos

Consumo excesivo de alcohol

Trastornos autoinmunitarios

Estrés extremo

Algunos de los síntomas que se pueden presentar cuando existe la gastritis son malestar, dolor punzante en la parte superior del abdomen, náuseas, vómitos y sensación de saciedad.

Apnea del sueño

Mon, 27 Dec 2021 18:09:48 GMT

La apnea del sueño es un trastorno un tanto grave, ya que se provoca cuando la respiración se detiene y recomienza repetidas veces. Si al dormir roncas sonoramente y sientes cansancio incluso después de una noche completa de sueño, es posible que tengas apnea del sueño.

Existen diferentes tipos de apnea del sueño, los principales son los siguientes:

Apnea obstructiva del sueño , este es el tipo de apnea más común y ocurre cuando los músculos de la garganta se relajan.

Apnea central del sueño , ocurre cuando el cerebro no envía señales correctas a los músculos que controlan la respiración.

Síndrome de apnea del sueño compleja , ocurre cuando alguien tiene apnea obstructiva del sueño y apnea central del sueño

Si crees que tienes apnea del sueño pon atención en los síntomas que enlistamos a continuación:

Ronquidos fuertes
Episodios en los que dejas de respirar durante el sueño (lo cual señala otra persona)
Despertarse con la boca seca
Dolor de cabeza por la mañana
Problemas para mantenerse dormido (insomnio)
Jadeos al respirar durante el sueño
Dificultad para prestar atención mientras estás despierto
Irritabilidad
Sensación de sueño excesiva durante el día (hipersomnia)

Si presentan alguno de los síntomas anteriores no dudes en consultar al médico y realizarte las pruebas pertinentes para definir que tipo de apnea tienes.