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. 2020 Jul 10;15(7):e0234633. doi: 10.1371/journal.pone.0234633

Prevalence and risk factors for asthma, rhinitis, eczema, and atopy among preschool children in an Andean city

Cristina Ochoa-Avilés 1,2,*,#, Diana Morillo 1,2,#, Alejandro Rodriguez 2, Philip John Cooper 2,3, Susana Andrade 1, María Molina 1,2, Mayra Parra 1, Andrea Parra-Ullauri 4, Danilo Mejía 1, Alejandra Neira 1,5, Claudia Rodas-Espinoza 5,#, Angélica Ochoa-Avilés 1,#
Editor: Claudio Andaloro6
PMCID: PMC7351199  PMID: 32649729

Abstract

Background

Limited data are available on prevalence and associated risk factors for atopy and allergic diseases from high-altitude urban settings in Latin America.

Objective

To estimate the prevalence of atopy, asthma, rhinitis, and eczema, and associations with relevant risk factors in preschool children in the Andean city of Cuenca.

Methods

A cross-sectional study was undertaken using a representative sample of 535 children aged 3–5 years attending 30 nursery schools in the city of Cuenca, Ecuador. Data on allergic diseases and risk factors were collected by parental questionnaire. Atopy was measured by skin prick test (SPT) reactivity to a panel of relevant aeroallergens. Associations between risk factors and the prevalence of atopy and allergic diseases were estimated using multivariable logistic regression.

Results

Asthma symptoms were reported for 18% of children, rhinitis for 48%, and eczema for 28%, while SPT reactivity was present in 33%. Population fractions of asthma, rhinitis, and eczema attributable to SPT were 3.4%, 7.9%, and 2.9%, respectively. In multivariable models, an increased risk of asthma was observed among children with a maternal history of rhinitis (OR 1.85); rhinitis was significantly increased in children of high compared to low socioeconomic level (OR 2.09), among children with a maternal history of rhinitis (OR 2.29) or paternal history of eczema (OR 2.07), but reduced among children attending daycare (OR 0.64); eczema was associated with a paternal history of eczema (OR 3.73), and SPT was associated with having a dog inside the house (OR 1.67).

Conclusions

A high prevalence of asthma, rhinitis, and eczema symptoms were observed among preschool children in a high-altitude Andean setting. Despite a high prevalence of atopy, only a small fraction of symptoms was associated with atopy. Parental history of allergic diseases was the most consistent risk factor for symptoms in preschool children.

Introduction

The prevalence of asthma and other allergic diseases (e.g. rhinitis and eczema) has increased over the last twenty years worldwide [1–4]. Atopy is an important risk factor for asthma, rhinitis, and eczema, related to the allergic component of these diseases [5–7]. The International Study of Asthma and Allergies in Childhood (ISAAC) documented high prevalence rates of allergic diseases and atopy in Latin American (LA) countries such as Brazil, Paraguay, Uruguay, Ecuador, and Peru [2,3,8,9]. Allergic diseases are considered to arise through complex interactions between genetic susceptibility and environmental exposures [10], so that temporal trends in prevalence are most likely to be explained by changes in environmental exposure, lifestyle, and living conditions [1]. Among such changes considered to contribute to trends in allergic disease prevalence are climate [11], urbanization [12], air pollution [3], cigarette smoke exposure, breastfeeding, and other behavioral and lifestyles factors [1].

Few published studies have explored risk factors and prevalence of asthma and allergic diseases in preschool children living in urban areas of the high Andes (i.e. >2,500 m), and none have used representative samples in the region [13,14]. Previous cross-sectional studies of allergic disease risk factors were done in tropical and subtropical regions of coastal Ecuador at altitudes below 1,500 m [12,15–20].

The aim of the present study was to describe the prevalence of asthma, rhinitis, and eczema among a representative sample of pre-school children living in the high-altitude Andean city of Cuenca, Ecuador, and identify associated risk factors.

Materials and methods

Study design, setting, and sampling

A cross-sectional study was conducted in the city of Cuenca, located in the southern Andean highlands of Ecuador [21] at an altitude of 2,550 meters. The average annual daytime temperature in the city ranges between 15 to 20°C with an average humidity of 84% [22]. The urban area of the city has approximately 332,000 inhabitants of whom 28,603 are aged 3 to 5 years [23], and 90% are mestizos (mixed Spanish–Indigenous ethnicity). The population has on average 11.4 years of schooling [24].

The study involved a cluster random sample of pre-school children aged 3 to 5 years. A sample size of 535 children was required for an estimated atopy prevalence of 20% [16], ±5% precision, and non-participant rate of up to 10%. Thirty preschools or kindergartens were randomly selected with probability proportional to size, stratified by school type (public vs. private) and neighborhood based on a Quality of Life Index (QoL) (high vs. low QoL). QoL characterizes a neighborhood’s well-being based on satisfied basic needs (housing characteristics, basic services, educational level, and access to health services) with each neighborhood classified on a scale of 0 to 2 (where 0 represents complete lack of basic needs, 1 complete coverage, and >1 a quality of life above meeting basic needs [25]. High vs. low QoL scores were defined using the median as cut-off. Eligible preschools for inclusion were: (i) located in urban Cuenca, (ii) attended by children aged 3–5 years, and (iii) having at least 40 such children attending regularly. Within each selected preschool, 40 children were randomly selected from school lists, anticipating an acceptance rate of 50% (i.e. a total of 20 students for each of the 30 schools). The study protocol was approved by the Ethics Committee of the Universidad San Francisco de Quito, Quito, Ecuador (approval 2017-164E), and parents or legal guardians of selected children were asked to give informed written consent.

Data collection and definitions

Data were collected between June and October 2018 by trained field workers. The ISAAC phase II [26] questionnaire, adapted to local conditions, was administered to the parents or guardian of each child. This questionnaire has been used widely in previous epidemiological studies of children in Ecuador [16–18,20] and collected data on sociodemographic (age, gender) and socio-economic (school type [public/private]) factors as well as on parental occupations, household income, material goods in the household, access to potable water, electricity, and sanitation), and environmental and other relevant risk factors (cat and/or dog inside the house since birth; contacts with animals outside the house; birth order; breastfeeding including duration; attendance at day-care facilities; parental history of allergic diseases; maternal smoking during and after pregnancy, and household exposures to tobacco smoke).

Data on allergic diseases were collected by maternal questionnaire. Here, the term “allergic diseases” is used to refer to symptoms of asthma, rhinitis, eczema, irrespective of the presence of atopy, as widely used in the literature. Asthma was defined as parental reported wheezing in the last 12 months, plus at least one of the following: i) asthma diagnosis ever, ii) wheezing during/after physical exercise in the last 12 months, and iii) sleep interruption due to wheezing in the last 12 months [27]. The presence of nasal congestion or sneezing not associated with a cold in the last 12 months was used to define rhinitis. Eczema was defined as the presence of an itchy rash at any point during the last 12 months involving the folds of the elbows, behind the knees, in front of the ankles, buttocks, or around the neck, ears or eyes [28].

Skin prick testing (SPT) was performed using the following: saline solution as negative control, histamine as positive control, grass mix (Dactylis glomerata, Festuca pratensis, Phoa pratensis, Phelum pratense, Lolium perenne), tree mix (ash and salix), weed mix (Plantago, Chenopodium, Artermisa, Ambrosia, Parietaria), fungi (Alternaria, Penicillum, Cladosporum), dust mites (Dermatophagoides pteronyssinus and D.farinae), tropical mite (Blomia tropicalis), dog dander, cat, feather mix (chicken, duck, and goose), cockroach, and latex (INMUNOTEK, Madrid, Spain). Allergens were stored at 4-8ºC and aliquots of antigens were transported to the field on ice packs. Allergens were pricked on the forearm and reaction sizes evaluated after 15 minutes. Reactions were considered positive if the mean wheal size was at least 3 mm greater than the negative saline control [29]. Atopy was defined as a positive reaction to any of the allergens tested.

Statistical analysis

Data were double entered into Epi Data (EpiData Association, Odense, Denmark). Socio-demographic attributes and risk factors for eczema, rhinitis, and eczema symptoms were reported as percentages. Prevalence of asthma, rhinitis, eczema, and atopy was reported as percentages with 95% confidence intervals (CI) adjusted for sampling using the svy command in Stata with schools as primary sampling units. Multiple correspondence analysis (MCA) was used to define socioeconomic status (SES) into 3 dimensions or groups (low, medium, and high) using father’s/mother's education, father’s/mother's occupation, and monthly household income (Fig 1) [18]. Cluster analysis was used to allocate subjects to SES groups identified by MCA. Asthma, rhinitis, and eczema were categorized as atopic vs. non-atopic based on having at least one positive SPT ([12]. Multivariable logistic regression was used to explore associations between allergic diseases and risk factors after controlling for potential confounders. Multivariable models included risk factors with P<0.1 in bivariate analyses after assessment of collinearity using Pearson correlation coefficients. The strength of associations was estimated using odds ratios (OR) with 95% confidence intervals (95% CI) with statistical significance inferred by P<0.05. Population attributable fractions (PAF) were calculated by PAF = PewX(OR-1)/OR, where Pew is the prevalence of allergen skin test reactivity among children with the specific symptom of interest as previously described [20]. All analyses were done using Stata V.12.0 (Stata Statistical Software: Release 12. College Station, TX: StataCorp LLC)

Fig 1. Multiple correspondence analysis.

Fig 1

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A) Spatial distributions of dimensions by socioeconomic groups (low, middle, and high) using the first two dimensions of MCA. B) Cluster analysis using object scores of MCA. Points represent individuals and colors represent socioeconomic groups (blue–low; green -medium; brown–high).

Results

We sampled a total of 535 children attending 30 preschools in the city of Cuenca. Mean age of participants was 4.1 ± 0.7 years (range 3–6 years) and 53.5% were male. Characteristics of the study population and distributions of risk factors are shown in Table 1. A greater proportion belonged to the medium SES (46.2%) than other groups. Most had access to basic services and facilities such as a bathroom (97.7%), electricity (98.7%), and potable water (96.6%). The majority of children were first or second in birth order (82.4%) and had been breastfed (93.8%). A minority had a dog (30.2%) or cat (10.9%) living indoors but did report the presence of animals including dogs and cats outside the home (72.5%). Relatively few parents reported a history of allergic diseases of which rhinitis was the most frequent (mothers 27.2% and fathers 23.5%).

Table 1. Characteristics of the study population.

Frequency %
Sex
Male 286 53.5
Female 249 46.5
Age (years)
3 102 19.0
4 298 55.7
5 125 23.4
6 10 1.9
Socioeconomic status
Low 11 21.4
Medium 40 46.2
High 69 32.5
Home services
Bathroom 519 97.7
Electricity 527 98.7
Potable water (n = 533) 515 96.6
Household appliances
2 or less 84 15.7
3 153 28.6
4 298 55.7
Environmental Risk Factors
Breastfeeding 502 93.8
Breastfeeding (months) (n = 504)
< 6 88 17.5
6–12 189 37.5
13–24 167 33.1
Birth order (n = 534)
1st -2nd 440 82.4
> = 3rd 94 17.6
Day-care attendance (n = 532) 202 38.0
Mother smoking (n = 531) 20 3.8
Family smoking habits (n = 531) 92 17.3
Dog inside house (n = 534) 161 30.2
Cat inside house (n = 530) 58 10.9
Dog outside house 359 67.6
Cat outside house 144 27.2
Chicken outside house (n = 530) 97 18.3
Pig outside house (n = 530) 17 3.2
Any animal outside house 488 72.5
Contact with animals in farms (n = 530) 159 30.0
Parental history of allergic disorders
Maternal asthma (n = 528) 24 4.6
Maternal rhinitis (n = 515) 140 27.2
Maternal eczema (n = 499) 65 13.0
Paternal asthma (n = 484) 13 2.7
Paternal rhinitis (n = 472) 111 23.5
Paternal eczema (n = 463) 37 8.0
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Table 2 shows estimated prevalence of asthma, rhinitis, and eczema symptoms, and sensitization to aeroallergens. Prevalence of asthma, rhinitis, and eczema was 17.8% (95% CI 14.1–21.4), 48.0% (95% CI 43.0–53.2), and 28.0% (95% CI 23.4–32.7), respectively. Positive SPT was observed in 33.5% (95% CI: 29.0–38.0) of children, and domestic mites (D. pteronyssinus [21.0%] and D. farinae [19.6%]) were the dominant sensitizing allergens.

Table 2. Prevalence of atopy (measured by aeroallergen skin prick testing [SPT]) and symptoms of asthma, rhinitis, eczema and by atopic status.

Allergic diseases % (95% CI)
Atopy 33.5 (29.0–38.0)
Asthma 17.8(14.1–21.4)
Atopic asthma 7.8 (4.5–10.8)
Non atopic asthma 10.0 (7.8–12.0)
Rhinitis 48.0 (43.0–53.2)
Atopic rhinitis 19.0 (15.0–23.1)
Non atopic rhinitis 29.0 (24.4–33.6)
Eczema 28.0 (23.4–32.7)
Atopic eczema 10.8 (7.8–13.8)
Non atopic eczema 17.2 (13.0–21.4)
Sensitization to aeroallergens by SPT
Mites 24.3 (19.7–28.8)
D. farinae 21.0 (16.5–25.0)
D. pteronyssinus 19.6 (15.4–24.0)
B. tropicalis 4.3 (1.9–6.7)
Pollen* 3.7 (2.3–5.1)
Cockroach 2.6 (1.1–4.1)
Cat 2.1 (0.4–3.6)
Dog| 1.5 (0.4–2.5)
Salix 1.5 (0.04–2.6)
Feather mix*** 1.1 (0.1–2.1)
Ash tree 0.9 (0.009–1.9)
Fungi** 0.9 (0.003–2.0)
Latex 0.7 (0.02–1.4)
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* plantago, Chenopodium, mugwort, ragweed, Parietaria

** Alternaria, Cladosporium, Penicillium

*** chicken, goose, duck

Stratification of asthma, rhinitis, and eczema by the presence of atopy (measured by a positive allergen skin test) showed non-atopic symptoms to be more prevalent: asthma (atopic 7.8%, 95% CI 4.5–10.8% vs. non-atopic 10%, 95% CI 7.8–12.0%), rhinitis (atopic 19.0%, 95% CI 15–23% vs. non-atopic 29.0%, 95% CI 24.4–33.6%) and eczema (atopic 10.8%, 95% CI 7.8–10.8% vs. non-atopic 17.0%, 95% CI 13.0–21.4%). Only small fractions of symptoms were attributable to atopy (Table 3): asthma (PAF 3.4%), rhinitis (7.9%), and eczema (2.9%)

Table 3. Fractions of symptoms of asthma, rhinitis, eczema attributable to atopy.

Disease Prevalence of allergen skin prick test reactivity (%) Adjusted OR*  Population attributable fraction (%)
Asthma 7.9% 1.75 3.4
Rhinitis 19.1% 1.71 7.9
Eczema 10.8% 1.36 2.9
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*OR for association between symptoms and atopy

MCA identified three SES categories: a) low—associated with unemployed parents, basic occupations such as technical and crafts, low income (< = $460) and low parental educational level (<6 years); b) medium—associated with public or private employees, monthly income of $461-$921 and 7–12 years of parental education; and, c) high—represented by professionals, with higher parental educational level (>12 years) and income >$921. The results of multiple correspondence analysis are shown in Fig 1. The dimensions obtained by MCA for SES are shown in Fig 1A. Cluster analysis was used to allocate subjects to each socioeconomic group. Fig 1B shows the spatial distributions of individuals from the cluster analysis, in which dots represent subjects and different colors represent SES groups.

Associations between symptoms of asthma, rhinitis, eczema, and the presence of atopy with potential risk factors are shown in Table 4. In multivariable analysis, maternal history of rhinitis was positively associated with asthma and rhinitis symptoms in children. Participants whose mothers had a history of rhinitis were twice as likely to have asthma (OR 1.85, 95% CI 1.0–3.4, P = 0.04) and rhinitis (OR 2.3, 95% CI 1.31–3.98, P = 0.005) symptoms, while those with a paternal history of eczema were four times as likely to have eczema (OR 3.73, 95% CI 1.51–9.20, P = 0.07) and twice as likely to have rhinitis (OR 2.07, 95% CI 1.11–3.86, P = 0.02) symptoms. Daycare attendance was associated with a lower prevalence of rhinitis (OR 0.64, CI 95% 0.46–0.88, P = 0.009). The presence of a dog living inside the house was associated with a greater risk of atopy (OR 1.67, 95% CI 1.05–2.66, P = 0.03). Prevalence of rhinitis symptoms was greater in children of high or medium compared to low SES (high, OR 2.09 [95% CI 1.10–3.96, P = 0.03]; medium, OR 1.75 [95% CI 0.97–3.13, P = 0.06])

Table 4. Risk factors associated with atopy and symptoms of asthma, rhinitis, and eczema.

Predictors Asthma (N = 95/535) Rhinitis (N = 257/535) Eczema (N = 150/535) Atopy (N = 179/535)
Frequency Bivariate Multivariable Frequency Bivariate Multivariable Frequency Bivariate Multivariable Frequency Bivariate Multivariable
N (%) OR (95% CI) P Value OR (95% CI) P Value N (%) OR (95% CI) P Value OR (95% CI) P Value N (%) OR (95% CI) P Value OR (95% CI) P Value N (%) OR (95%CI) P Value OR (95% CI) P Value
Socioeconomic status
Low 13 (13.7) 1 35 (13.6) 1 33 (22.0) 1 29 (16.2) 1
Medium 47 (49.5) 1.83 (1.08–3.12) 0.03 1.42 (0.71–2.83) 0.31 114 (44.4) 1.96 (1.22–3.15) 0.07 1.75 (0.97–3.13) 0.06 80 (53.3) 1.18 (0.69–2.00) 0.52 88 (49.2) 1.63 (1.09–2.45) 0.02 1.17 (0.92–1.48) 0.20
High 32 (33.7) 1.76 (0.91–3.37) 0.08 0.90 (0.38–2.10) 0.80 99 (38.5) 3.07 (1.79–5.25) <0.001 2.09 (1.10–3.96) 0.03 33 (22.0) 0.57 (0.28–1.14) 0.10 58 (32.4) 1.47 (0.88–2.47) 0.13 1.47 (0.88–2.47) 0.13
Type of school
Public 43 (45.3) 130 (50.6) 92 (61.3) 88 (49.2)
Private 52 (54.7) 1.56 (1.00–2.45) 0.05 127 (49.4) 1.34 (0.91–1.98) 0.13 58 (38.6) 0.67 (0.43–1.07) 0.09 0.80 (0.43–1.48) 0.47 91 (50.8) 1.37 (0.96–1.97) 0.08 1.43 (0.96–2.13) 0.07
Bathroom
Hygienic service 94 (99.0) 251 (97.7) 148 (98.6) 171 (95.5)
Latrine or field) 1.0 (1.1) 0.41 (0.07–2.58) 0.33 4 (1.6) 0.53 (0.24–1.21) 0.13 1 (0.6) 0.23 (0.04–1.34) 0.10 0.49 (0.11–2.11) 0.34 6 (3.3) 2.04 (0.54–7.61) 0.29
Household appliances
2 or less 18 (19.0) 47 (14.4) 28 (18.6) 32 (17.9)
3 or more 77 (81.1) 0.93 (0.67–1.29) 0.67 220 (85.7) 1.30 (0.97–1.74) 0.078 1.04 (0.75–1.44) 0.79 122 (81.2) 0.78 (0.6–1.00) 0.05 0.97 (0.67–1.41) 0.89 147 (82.1) 0.92 (0.74–1.15) 0.46
Birth order
1–2 18 (19.0) 45 (17.5) 31 (20.6) 33 (18.4)
3 or more 77 (81.1) 0.90 (0.47–1.69) 0.73 212 (82.5) 1.01 (0.67–1.53) 0.95 118 (78.6) 0.74 (0.52–1.06) 0.10 0.74 (0.43–1.29) 0.28 145 (81.0) 0.91 (0.57–1.45) 0.69
Breastfeeding (months)
< 6 14 (14.7) 47 (18.3) 22 (14.6) 30 (16.8)
6–12 30 (31.6) 92 (35.8) 48 (32.0) 63 (35.2)
12–24 33(34.7) 71 (27.6) 47 (31.3) 60 (33.5)
>24 14 (14.7) 1.19 (0.94–1.51) 0.14 30 (11.7) 0.90 (0.76–1.07) 0.22 24 (16.0) 1.22 (1.01–1.49) 0.04 1.05 (0.79–1.39) 0.72 17 (9.5) 0.96 (0.78–1.20) 0.74
Daycare
Yes 35 (36.8) 119 (46.3) 49 (32.6) 63 (35.2)
No 60 (63.2) 1.06 (0.68–1.65) 0.78 136 (52.9) 0.49 (0.37–0.64) 0.001 0.64 (0.46–0.88) 0.009 101 (67.3) 1.38 (0.88–2.16) 0.16 114 (63.7) 1.16 (0.77–1.77) 0.48
Mother smoking
Yes 2 (2.1) 11 (4.3) 6 (4.0) 3 (1.7)
No 93 (97.9) 0.50 (0.14–1.78) 0.27 244 (94.9) 1.34 (0.61–2.92) 0.47 142 (94.6) 1.11 (0.39–3.22) 0.84 133 (96.6) 0.34 (0.12–0.96) 0.04 0.39 (0.11–1.34) 0.13
Family smoking
Yes 19 (21.0) 47 (18.3) 34 (22.6) 22 (12.3)
No 75 (79.0) 1.26 (0.65–2.45) 0.47 207 (80.5) 1.17 (0.69–2.00) 0.56 115 (76.6) 1.65 (1.12–2.44) 0.01 1.30 (0.75–2.24) 0.32 156 (87.2) 0.57 (0.36–0.90) 0.01 0.67 (0.38–1.16) 0.15
Dog (inside house)
No 63 (66.3) 185 (71.9) 103 (68.6) 137 (76.5)
Yes 32 (33.7) 0.82 (0.49–1.37) 0.43 72 (28.0) 1.22 (0.82–1.80) 0.33 47 (31.3) 0.93 (0.62–1.38) 0.70 42 (23.5) 1.64 (1.11–2.44) 0.01 1.67 (1.05–2.66) 0.03
Maternal rhinitis
No 38 (56.8) 154 (60.0) 43 (28.6) 125 (69.8)
Yes 54 (40.0) 2.21 (1.38–3.55) 0.002 1.85 (1.01–3.41) 0.04 92 (35.8) 2.75 (1.79–4.22) 0.001 2,29 (1.31–3.98) 0,005 98 (28.6) 1.25 (0.78–2.01) 0.35 46 (25.8) 0.98 (0.67–1.42) 0.91
Maternal eczema
No 18 (18.9) 201 (78.2) 108 (72.0) 145 (81.0)
Yes 69 (72.3) 2.03 (0.96–4.28) 0.064 1.58 (0.68–3.79) 0.27 38 (14.8) 1.63 (0.84–3.17) 0.15 28 (18.6) 2.28 (1.42–3.68) 0.001 1.73 (0.91–3.28) 0.08 25 (13.9) 1.25 (0.72–2.15) 0.43
Paternal rhinitis
No 21 (22.1) 158 (61.5) 90 (60.0) 114 (63.7)
Yes 58 (61.1) 1.22 (0.68–2.17) 0.49 68 (26.5) 2.03 (1.34–3.07) 0.001 1.16 (0.67–2.00) 0.58 35 (23.3) 1.39 (0.88–2.19) 0.16 39 (21.8) 1.17 (0.75–1.84) 0.48
Paternal eczema
No 68 (71.6) 200 (77.8) 101 (67.3) 143 (80.0)
Yes 9 (9.5) 1.69 (0.76–3.75) 0.186 25 (9.7) 2.35 (1.30–4.26) 0.005 2.07 (1.11–3.86) 0.02 21 (14.0) 4.22 (2.30–7.75) <0.001 3.73 (1.51–9.20) 0.07 11 (6.1) 0.84 (0.38–1.84) 0.65
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Discussion

To our knowledge, this is the first study to provide an unbiased estimate of the prevalence of atopy and symptoms of asthma, rhinitis, and eczema among preschool children (aged 3–5 years) from a high-altitude setting in Latin America. Our data indicate that despite a high prevalence of symptoms of asthma (17.8%), rhinitis (48.0%), and eczema (28.0%), only a small fraction of these symptoms (i.e. <8%) were attributed to atopy, consistent with findings of previous studies in non-affluent settings in Latin America, including low-attitude tropical regions of Ecuador [3,20,30,31].

Different patterns of risk factors have been identified for atopic and non-atopic asthma. Atopic asthma [12,31–33] has been associated with male sex, previous geohelminth infections, familial history of allergic disease, and respiratory viral infections, while non-atopic asthma has been associated with birth order and sedentary behavior [12,32]. Such observations suggest that atopic and non-atopic asthma may have distinct causal mechanisms and underline the need for more research in Latin American settings [34]. The strength of the association between atopy and asthma tends to increase with age: atopic asthma tends to be associated with a more persistent disease likely to continue into adulthood [12,35–37]. Longitudinal studies have provided evidence of three different phenotypes of asthma in childhood: 1) transient asthma associated with viral respiratory tract infections that often resolves by 6 years of age, 2) non-atopic asthma associated with viral respiratory tract infections that may persist beyond 6 years but which resolves by adulthood, and, 3) atopic asthma that persists into adulthood accompanied by a more severe clinical course [12].

Previous studies have identified genetic, environmental, behavioral, and socioeconomic factors associated with the development of allergic diseases in childhood, likely to reflect complex interactions between genes and environmental exposures [38], [39,40]. Genetic studies have identified polymorphisms associated with both atopic and non-atopic asthma [27,41,42], highlighting the importance of family history as a risk factor. Bjerg. et al. [43] reported parental asthma as a risk factor for childhood asthma, and data from Europe showed that family history of rhinitis was associated with a four-fold increased risk of developing asthma and two to six-fold increased risk of developing rhinitis [44,45]. In our study, family history of allergic disorders was the most consistent factor associated with symptoms of asthma, rhinitis, and eczema. The potential role of epigenetic changes representing the role of gene-environment interactions in the development of asthma has been explored also. Yang and colleagues [40] identified 81 regions on the genome that were differentially methylated in asthmatic children aged between 6 and 12 years. Further studies to identify polymorphisms and epigenetic alterations associated with allergic diseases, as well as variants in genes associated with reduced pharmacologic response, are required for a better understanding of asthma and its treatment among Andean children with asthma [41,46–49].

Among environmental factors, helminth infections in early life [50,51], exposure to dust mites, cockroach, cigarette smoke [38], and the presence of pets and/or farm animals during childhood have all strong effects on allergic diseases [3,11,50,52]. Most previous studies from Ecuador have identified factors related to poverty and dirt (lack of access to potable water, migration, home infrastructure, household pets, contact with farm animals, and socioeconomic level) as risk factors for asthma in poor tropical populations [16–18,20]. In the present study, environmental and socioeconomic factors were most likely to affect the prevalence of rhinitis symptoms: daycare attendance was associated with a lower prevalence of rhinitis. Attendance at daycare facilities is associated with a greater contact among young children and much greater exposure to infections during childhood in comparison with children who stay at home [51,53–55]. There is some evidence that exposure to infections may affect allergic rhinitis [53]; helminth infections have been associated with a lower incidence of allergic rhinitis [53,54,56,57]. Higher socioeconomic status was associated with increased prevalence of rhinitis as indicated by previous studies [50,58–60]. The only factor associated with atopy in the present study was having a dog living in the house at any time since the child’s birth. Although previous studies have reported dog ownership during pregnancy and first year of life as protective against allergic diseases [61], associations with atopy have been less clear. Studies in Europe have reported low levels of mite allergens in high altitude settings (>1500 m) related to low humidity [62,63]. Previous studies in Quito, another high altitude city (2,800 m altitude) in the Ecuadorian Andes, showed significant levels of indoor dust mites (D. pteronyssinus and D. farinae) [64] and mite allergens associated with respiratory allergy [65]. Data from this study indicate that mites are important sensitizing allergens in pre-school children in another Andean urban setting of Ecuador with a relatively high humidity (average 83.7%, range 77.5–89.4%) [66].

Research in pre-school children (3–5 years) in China using the ISAAC questionnaire reported similar prevalence to that observed in the present study: asthma (14%), rhinitis (40%), and eczema (21%) [67]. Although we were unable to identify studies of representative samples of young children elsewhere in Latin America, our estimate of rhinitis was higher than that reported previously among children aged 1 to 4 years in 6 Colombian cities (32%) [68] while eczema prevalence (28%) was similar to that reported among schoolchildren in Bogotá, Colombia (25%) [69] and 6 to 7 year-olds in ISAAC (22%) [70]. Cuenca and Bogotá are Andean cities with high altitude near the Equator with low mean annual temperatures (range 9 to 21ºC): it has been suggested that eczema prevalence may be inversely associated with temperature through differences in sun exposure [11]. The estimated prevalence of eczema in children in ISAAC was higher in Latin America than that reported from temperate countries [71]. Recent analyses comparing ISAAC with other definitions of eczema showed a tendency for the ISAAC definition to overestimate eczema prevalence in tropical compared to sub-tropical settings [72], largely because of conditions (e.g. miliaria and arthropod bites) whose clinical presentations may inflate ISAAC-based estimates. It should be emphasized, however, that in the subtropical climate of Cuenca, such conditions are less common. Previous studies in Ecuador showed a lower prevalence of asthma and rhinitis compared to our results [15,18]. Differences in asthma and rhinitis prevalence could be related to the fact that previous studies in Ecuador have been conducted in older children living in humid rural tropical communities at sea level [15,19,73]. Aside from the population characteristics, urbanization, altitude [74], temperature, humidity, [11,75–77], and regional differences could also be linked to variations in prevalence [26].

A limitation of the present study was the cross-sectional design that does not allow us to determine the direction of causality between potential risk factors and disease outcomes. However, the representative sample used in the study allowed us to minimize potential biases in estimating prevalence and our findings are likely to be relevant to young children living in Andean cities. Because allergen extracts of pollen from representative plants are not commercially available for the Andean region, we used pollen extracts from European plants in the present study; this could have underestimated allergic sensitization to plant pollens in our study population.

Conclusion

In the present study, we observed a high prevalence of asthma, rhinitis, eczema symptoms among a representative sample of preschool children living in a high-altitude Andean city in Ecuador. Despite a high prevalence of atopy, predominantly to domestic mites, only a small proportion of ‘allergic’ disease symptoms (<8%) were attributable to atopy. Parental history of allergic diseases was the most consistent risk factor for symptoms in these young children, indicating the importance of genetic susceptibility, while few of the standard environmental exposures measured by questionnaire were associated with symptoms. Future studies should examine a wider range of environmental exposures relating to urbanization such as the role of indoor and outdoor pollution.

Supporting information

S1 Data

(XLS)

Click here for additional data file. (169KB, xls)

Acknowledgments

We are grateful for the participation and support of students, parents, school directors, and teachers in the study. Additionally, we acknowledge the contribution of staff of CEDIA, University of Azuay, the Bioscience Department of the University of Cuenca and to Elizabeth Rodas for language editing. This work was developed within a joint postgraduate program of Vlir Network Ecuador.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

Funding was provided by CEDIA (Corporación Ecuatoriana para el desarrollo de la Investigación y la Academia), Universidad del Azuay (UDA), Dirección de Investigación, Universidad de Cuenca (DIUC) and Universidad Tecnológica Indoamérica The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Claudio Andaloro

20 Feb 2020

PONE-D-20-02044

Prevalence and risk factors for asthma, rhinitis, eczema and atopy among preschool children in an Andean city.

PLOS ONE

Dear Mrs Ochoa,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Although this is an interesting epidemiological study adding also new points of view on risk factors for asthma, rhinitis, eczema and atopy, there are several points which need further elaboration in the paper: definitions of "eczema" or "atopy" are not clearly defined throughout the paper, skin prickt test issue raised by a reviewer, a deeper discussion regarding the association of high-altitude and atopy should be provided (if any), as well as some issues regarding the logistic regression analysis should be addressed

We would appreciate receiving your revised manuscript by Apr 05 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

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Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Claudio Andaloro

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is an interesting epidemiological study concerning prevalence of Eczema, Asthma and Rhinitis in a Highland pediatric Population of the Andes which seems to be a new Patient collective. Also, it adds some Information, whether higher social income is also a Risk factor in developping countries in the same way as in the industrialized world.

Although the study is well written with a highly sophisticated Level of statistical work-up, I fave some very Basic Major remarks mainly concerning the definitions used in this paper.

The high prevalence of eczema patients is astounding and makes me suspicious that the term "eczema" is too vaguely defined in a pediatric Population especially prone to viral infections with a high Risk of developping infection-connected eczema rather than true atopic eczema.

Also the term "atopy" is not clearly defined throughout the paper: how do the authors use this term? An atopic parent?, A positive Skin prick test?

Minor remark: Is the Skin prickt test series truely representative for the plants abundant in the Highland Andes? They rather seem to be fit for a central European Population completely ignoring endemic plant species in the Highland Ecuador and more General Altiplano Region. Also Information regarding the manufacturer of the test substances is missing.

This was a field study. How did the authors guarantee that allergenicity was not lost by using Skin prick test Solutions that were not stored properly betwenn 4 and 8 Degree Celsius. Especially house dust mite extracts will soon loose their activity through the proteolitic activity of the Major house dust mite allergen components when stored at room temperature for longer time.

Methods: The authors describe "Scratch test". Hopefully this is only a wrong description and the authors used "Skin prick Tests"?

Reviewer #2: 1) Please elaborate more about the rationale about high attitude level (higher than 2,500m) and the atopy.

2) Regarding the logistic regression analysis, the value of each variable should be display also. By showing only the percentage and Odds ratio are not enough for determining the degree of association of risk factors.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Stefan Wöhrl, Floridsdorf Allergy Center (FAZ), Austria, Europe

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 10;15(7):e0234633. doi: 10.1371/journal.pone.0234633.r002

Author response to Decision Letter 0

25 Mar 2020

-The high prevalence of eczema patients is astounding and makes me suspicious that the term "eczema" is too vaguely defined in a pediatric Population especially prone to viral infections with a high Risk of developing infection-connected eczema rather than true atopic eczema.

R: We thank the reviewer for this insightful comment. We did observe a high prevalence of eczema in our pediatric population of children aged 3 to 5 years (28%). We used the ISAAC definition for eczema, that has been used widely in epidemiological studies in children and estimated a prevalence similar to that described in other epidemiological studies in Latin America using the same definition. For example, a similar prevalence (22.5%) was estimated among Ecuadorian children aged 6-7 years in the ISAAC Phase III study (Odhiambo et al. 2009). The differential diagnosis of eczema in 3-5-year olds in this setting include seborrheic dermatitis, scabies and other arthropod bites, miliaria, fungal infections, etc. Recent analyses comparing ISAAC with other definitions of eczema have shown a tendency of the ISAAC definition to overestimate eczema prevalence in tropical compared to sub-tropical settings (Sánchez, Sánchez, and Cardona 2018). It should be emphasized that the City of Cuenca is sub-tropical where conditions that might inflate ISAAC-based prevalence estimates, such as miliaria and scabies, are less common. We have added now text explaining this to the Discussion (page 14).

-Also, the term "atopy" is not clearly defined throughout the paper: how do the authors use this term? An atopic parent? A positive Skin prick test?

R: We thank the reviewers comment, the term atopy was defined as “a positive [skin test] reaction to any of the allergens tested” on page 6 of the manuscript following the definition of the European Academy of allergen and clinical immunology (EAACI)(Johansson et al. 2004). The definition of atopy is provided also in the abstract: “Atopy was measured by skin prick test (SPT) reactivity to a panel of relevant aeroallergens”. We have clarified the definition of atopy used in this study in the relevant section of the Results on page 9. We acknowledge that the words ‘allergic’ and ‘atopic’ are often used interchangeably so have clarified that ‘allergic diseases’ refers to ‘symptoms of the commonly called ‘allergic diseases”, asthma, rhinitis, eczema, without determination of the actual presence of atopy’ (page 6).

-Minor remark: Is the Skin prick test series truly representative for the plants abundant in the Highland Andes? They rather seem to be fit for a central European Population completely ignoring endemic plant species in the Highland Ecuador and more General Altiplano Region. Also Information regarding the manufacturer of the test substances is missing.

R: The plant species used for skin prick testing in this study were based on clinical experience and availability of purified extracts. Commercially available extracts representative of the plant species in highland Ecuador or the Andean region are not available. We have added a statement to the limitation paragraph on page 15 discussing this limitation. Information on commercial source of allergens manufacturer has been added to methods (page 6).

-This was a field study. How did the authors guarantee that allergenicity was not lost by using Skin prick test Solutions that were not stored properly between 4 and 8 Degree Celsius. Especially house dust mite extracts will soon lose their activity through the proteolytic activity of the Major house dust mite allergen components when stored at room temperature for longer time.

R: Allergens were stored at 4-8ºC and aliquots of antigens were transported to the field on ice packs. This sentence has been added to the text on page:

-Methods: The authors describe "Scratch test". Hopefully this is only a wrong description and the authors used "Skin prick Tests"?

R: We thank the reviewer for highlighting this error in the text - we did skin prick tests. The word ‘scratch’ has been replaced by ‘prick’. Text now reads: “Allergens were pricked on the forearm and reaction sizes evaluated after 15 minutes” (page 6).

-Please elaborate more about the rationale about high attitude level (higher than 2,500m) and the atopy.

Text about atopy and high alttitude level has been added to the manuscript.

-Regarding the logistic regression analysis, the value of each variable should be display also. By showing only the percentage and Odds ratio are not enough for determining the degree of association of risk factors.

The value of each value has been added to the fig. 4

Attachment

Submitted filename: Response to reviewers.docx

Click here for additional data file. (31KB, docx)

Decision Letter 1

Claudio Andaloro

20 Apr 2020

PONE-D-20-02044R1

Prevalence and risk factors for asthma, rhinitis, eczema and atopy among preschool children in an Andean city.

PLOS ONE

Dear Mrs Ochoa,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

You have provided sufficient efforts to address previous peer review report, but the manuscript needs some minor

adjustments. You need to check for grammatical and typographical errors in the text.

We would appreciate receiving your revised manuscript by Jun 04 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Claudio Andaloro

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: (No Response)

Reviewer #3: There is an error in the fourth sentence in the discussion section. After "and eczema (28.0%)" you should have a comma. Please check carefully for other errors.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Stefan Wöhrl

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 10;15(7):e0234633. doi: 10.1371/journal.pone.0234633.r004

Author response to Decision Letter 1

26 May 2020

Rebuttal Letter Article: [PONE-D-20-02044]-[EMID:81850e4da8ff6666]

Title: Prevalence and risk factors for asthma, rhinitis, eczema, and atopy among preschool children in an Andean city.

We appreciate the valuable comments. This document is written as follows: reviewer’s

comments are in italic and bold, responses to the comments are preceded by the letter R; extracts of the manuscript are in blue.

Reviewer's Report:

There is an error in the fourth sentence in the discussion section. After "and eczema (28.0%)" you should have a comma. Please check carefully for other errors.

R: we appreciate the careful revision that has been made to the manuscript. We corrected the error in the fourth sentence of the discussion.

“… symptoms of asthma (17.8%), rhinitis (48.0%), and eczema (28.0%), only a small fraction of…”

You need to check for grammatical and typographical errors in the text.

R: grammatical and typographical errors were carefully checked trough the manuscript. All the modifications made were highlighted in the text in blue.

Attachment

Submitted filename: Response to reviewers.docx

Click here for additional data file. (13.7KB, docx)

Decision Letter 2

Claudio Andaloro

1 Jun 2020

Prevalence and risk factors for asthma, rhinitis, eczema, and atopy among preschool children in an Andean city.

PONE-D-20-02044R2

Dear Dr. Ochoa,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Claudio Andaloro

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Claudio Andaloro

10 Jun 2020

PONE-D-20-02044R2

Prevalence and risk factors for asthma, rhinitis, eczema, and atopy among preschool children in an Andean city.

Dear Dr. Ochoa-Avilés:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Claudio Andaloro

Academic Editor

PLOS ONE

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