Abstract
Rationale
Little is known about residence in a rural or farming environment and allergic diseases in Latin America.
Methods
Cross-sectional study of rural residence and current wheeze, current asthma and current symptoms of allergic rhino-conjunctivitis in 1,804 adolescents (ages 13–14 years) attending 31 schools in urban and rural areas of San Francisco (Córdoba, Argentina). Rural residence was classified as never, previous, and current. Duration of rural residence was categorized as 0, >0 but ≤ 5 years, and >5 years. Current wheeze, current asthma and current allergic rhino-conjunctivitis were defined on the basis of responses to an extensively validated questionnaire from the International Study of Asthma and Allergies in Childhood. Logistic regression was used for the multivariable analysis of rural residence and the outcomes of interest.
Results
After adjustment for current smoking and other covariates, current rural residence (odds ratio [OR]=0.15, 95% confidence interval [CI]=0.03 to 0.81) and rural residence for >5 years (OR=0.32, 95% CI=0.12 to 0.84) were significantly associated with reduced odds of current wheeze. In a multivariable analysis, current residence in a rural area (OR= 0.52, 95% CI= 0.32 to 0.86) and rural residence for >5 years (OR=0.44, 95% CI= 0.26 to 0.73) were significantly associated with reduced odds of allergic rhino-conjunctivitis. This association was no longer significant after additional adjustment for current residence in a dairy farm, which was significantly associated with reduced odds of allergic rhino-conjunctivitis. Similarly, current regular contact with farm animals was significantly associated with reduced odds of allergic rhino-conjunctivitis.
Conclusions
Among Argentinean adolescents, current rural residence and rural residence for >5 years were associated with reduced odds of current wheeze and allergic-rhino-conjunctivitis. These potential protective effects may be explained by a dairy farm environment, including regular contact with farm animals.
Keywords: rural residence, dairy farm, wheeze, hay fever, Argentinean adolescents
INTRODUCTION
Allergic diseases such as asthma and allergic rhino-conjunctivitis have become a global public health issue over the last few decades1, 2. A previously noted upward trend in the prevalence of asthma has reached a plateau in industrialized countries, but asthma prevalence continues to rise in developing countries2. Although a “western” urban lifestyle may partly explain these findings2, specific risk factors remain insufficiently characterized.
A relatively high prevalence of current wheeze and current symptoms of allergic rhino-conjunctivitis has been reported in Latin American adolescents with noticeable differences among cities and countries within the region3,4. Among children ages 13 to 14 years who participated in Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC), estimates of the prevalence of current wheeze were 13.6% in Córdoba (Argentina), 19.6% in Lima (Perú), and 24.6% in Salvador (Brazil); those for symptoms of allergic rhino-conjunctivitis were 16.9% in Córdoba (Argentina), 18.7% in Lima (Perú) and 21.1% in Salvador (Brazil) 4. Similarly, the prevalence of asthma among Latin American children ages 13 to 14 years ranges from 2.6% in Guatemala to 33.1% in Perú5. This variability can be partly explained by differences in socioeconomic status, environmental exposures (e.g., secondhand tobacco smoke, air pollution), psychosocial stress, obesity, healthcare access6, 7, urban growth, and migration8. In contrast to studies conducted in Central Europe showing that farming environment may protect against allergic diseases in childhood9,, studies from Latin America have yielded conflicting findings, with some reporting no urban-rural gradient in allergic diseases10 and others showing an inverse association between rural residence and asthma or allergies in children 11.
Argentina is one of the most urbanized countries in Latin America, with over 90% of the population living in cities12. Argentina experienced fast changes in lifestyle, thus providing a unique opportunity to study urban-rural differences in allergic diseases. In this report, we examine the relation between rural residence and asthma, wheeze, and allergic rhino-conjunctivitis among adolescents living in Córdoba, Argentina. Moreover, we examine which aspects of rural living may influence these conditions.
METHODS
Study population and design
From May to June 2007, all adolescents aged 13–14 years who were enrolled in school and resided in the city of San Francisco and the surrounding rural areas (Province of Córdoba, Argentina) were invited to participate in this study. Located in the center of Argentina, on a plain area with mild climate, San Francisco has 60,000 inhabitants and is an industrial center with low levels of air pollution. The surrounding rural areas have a similar climate, and dairy farm activities and grain harvests (soya, corn and wheat) are common.
The Education Ministry of the Province of Córdoba agreed to facilitate enrollment of all urban and rural students in public schools. A total of 31 public and private schools (13 urban and 18 rural) were contacted by the researchers and agreed to participate. A questionnaire was then distributed to all adolescents at their school. Of the 1,807 adolescents who were invited to participate, 1,804 (99.8%) completed the study questionnaire at her or his school, and were thus included in the current analysis.
Study questionnaire
All participants completed the Spanish version of the ISAAC Phase III core questionnaire1. This questionnaire, widely used in Argentina and other countries, has been shown to be a reliable tool to estimate the prevalence and risk factors of allergic diseases. The core questionnaire was supplemented with questions on socio-demographic and household characteristics, and the farming environment. Using a stadiometer, height and weight were measured by trained personnel after each participant completed the study questionnaire. Height and weight measures were approximated to the nearest centimeter and pound, respectively.
The study was approved by the Ethics Committee of the Regional Hospital and, informed assent was obtained from study participants.
Statistical analysis
Residence within the limits of San Francisco city was classified as urban, and that in the area outside any city or population within the San Justo Department was classified as rural (the Province of Córdoba is divided into departments, and San Francisco is the Head of the San Justo Department). Residence in a rural area was further considered as: 1) never, previous but not now, and current; and 2) (after examining the variable distribution and results from bivariate analyses) zero years, five years or less, and more than five years.
Variables included in the bivariate analyses included age, gender, maternal education (completion of high school vs. non-completion of high school), use of paracetamol in the previous year, physical exercise (none, 1–2 times per week, 3 or more times per week), current smoking (by the participants), maternal smoking, paternal smoking, number of smokers in the home (none, 1–2, 3 or more), number of older siblings (none, 1–2, 3 or more), use of wood for cooking, use of wood for heating, presence of a cat in the home in the previous year, presence of a dog in the home in the previous year, current residence in a dairy farm, residence in a dairy farm in the first year of life, current regular (at least once a week) contact with farm animals (poultry, cows, lambs, horses or pigs), regular contact with farm animals in the first year of life.
Current wheeze was defined as any wheeze in the previous year. Current asthma was defined as physician-diagnosed asthma and current wheeze. Current symptoms of allergic rhino-conjunctivitis (heretofore called allergic rhino-conjunctivitis, for ease of exposition) were defined as naso-ocular symptoms apart from colds in the previous year. Wald chi-square tests and t-tests were used for bivariate analyses of binary and continuous variables, respectively. Multivariable logistic regression was used for the analysis of rural residence and: current wheeze, current asthma, and allergic rhino-conjunctivitis. A stepwise approach was used to build the multivariable models. Variables associated with the outcome of interest at P <0.25 were included in the initial models. All final models included age, gender, and any variable that was associated with the outcome of interest at P <0.05 or that caused a change in the effect estimate (odds ratio) ≥ 10%. All statistical analyses were conducted using SAS 9.3 software (SAS Institute Inc., Cary, NC).
RESULTS
The main characteristics of study participants, according to the presence of current wheeze or current asthma, are shown in Table 1. Current wheeze and current asthma were reported by 12.5% and 4.3% of the 1,757 study participants, respectively. Compared with children without current wheeze, those with current wheeze were significantly more likely to have used paracetamol in the previous year. Moreover, children who were currently living in a rural area or who had lived in a rural area for over five years were less likely to report current wheeze, but this association was non-statistically significant (P ≥ 0.05 but <0.10 in both instances). Compared with children without current asthma, those with current asthma were significantly more likely to have used paracetamol in the previous year. There were no significant differences in other characteristics between participants with and without current wheeze or current asthma.
Table 1.
Characteristics of study participants, according to the presence of current wheeze or current asthma
| Variable | Current wheeze | Current asthma | ||||
|---|---|---|---|---|---|---|
|
| ||||||
| No (n=1,537) | Yes (n=220) | p-value | No (n=1,656) | Yes (n=74) | p-value | |
| Age, years | 13.5 ± 0.5 | 13.5 ± 0.5 | 0.54 | 13.5 ± 0.5 | 13.4 ± 0.5 | 0.26 |
| Male gender | 792 (51.8) | 99 (45.00) | 0.06 | 828 (50.2) | 44 (59.5) | 0.12 |
| Body mass index(kg/m2) | 19.6 ± 3.5 | 19.7 ± 3.0 | 0.76 | 19.6 ± 3.5 | 19.4 ± 2.8 | 0.53 |
| Mother completed high school | 683 (44.5) | 101 (46.1) | 0.66 | 742 (44.9) | 33 (44.6) | 0.96 |
| Use of paracetamol in the previous year | 945 (62.6) | 159 (74.0) | 0.001 | 1032 (63.4) | 54 (75.0) | 0.045 |
| Physical exercise | ||||||
| None | 110 (7.2) | 13 (6.0) | 0.80 | 114 (6.9) | 6 (8.1) | 0.76 |
| 1–2 times/week | 802 (52.6) | 116 (53.2) | 871 (52.9) | 36 (48.7) | ||
| ≥ 3 times/week | 614 (40.2) | 89 (40.8) | 661 (40.2) | 32 (43.2) | ||
| Current smoking | 163 (11.0) | 31 (14.6)§ | 0.12 | 185 (11.5) | 7 (9.7) | 0.64 |
| Maternal smoking | 336 (22.0) | 56 (25.6) | 0.24 | 368 (22.3) | 19 (25.7) | 0.50 |
| Paternal smoking | 463 (30.4) | 71 (32.6) | 0.51 | 503 (30.6) | 21 (28.4) | 0.69 |
| Number of smokers at home | ||||||
| None | 823 (53.7) | 114 (52.1) | 0.58 | 881 (53.3) | 43 (58.1) | 0.63 |
| 1–2 smokers | 601 (39.2) | 85 (38.8) | 650 (39.3) | 25 (33.8) | ||
| ≥ 3 smokers | 110 (7.2) | 20 (9.1) | 122 (7.4) | 6 (8.1) | ||
| Number of older siblings | ||||||
| None | 534 (34.7) | 73 (33.3) | 0.74 | 572 (34.5) | 26 (35.1) | 0.85 |
| 1–2 | 758 (49.3) | 114 (52.1) | 860 (49.5) | 38 (51.4) | ||
| ≥ 3 | 245 (15.9) | 32 (14.6) | 264 (15.9) | 10 (13.5) | ||
| Use of wood for cooking | 90 (5.9) | 17 (7.8) | 0.27 | 98 (5.9) | 7 (9.5) | 0.21 |
| Use of wood for heating | 287 (18.7) | 43 (19.6) | 0.74 | 315 (19.0) | 12 (16.2) | 0.55 |
| Cat in the house in the previous year | 624 (41.1) | 79 (36.1) | 0.16 | 668 (40.8) | 24 (32.4) | 0.15 |
| Dog in the house in the previous year | 1318 (86.5) | 193 (88.9) | 0.33 | 1427 (86.9) | 64 (87.7) | 0.85 |
| Currently living in a dairy farm | 96 (6.6) | 8 (3.9) | 0.13 | 99 (6.3) | 5 (7.3) | 0.76 |
| Lived in a dairy farm, first year of life | 229 (15.4) | 24 (11.1) | 0.10 | 243 (15.1) | 9 (12.2) | 0.49 |
| Current contact with farm animals1 | 198 (12.9) | 29 (13.2) | 0.90 | 213 (12.9) | 13 (17.6) | 0.25 |
| Contact with farm animals1, first year of life | 175 (11.4) | 25 (11.4) | 0.99 | 189 (11.5) | 9 (12.2) | 0.85 |
| Rural residence | ||||||
| Never | 1162 (78.4) | 173 (82.4) | 0.09 | 1257 (78.8) | 55 (76.4) | 0.89 |
| Previously, but not now | 165 (11.1) | 25 (11.9) | 180 (11.3) | 9 (12.5) | ||
| Currently | 156 (10.5) | 12 (5.7) | 159 (10.0) | 8 (11.1) | ||
| Duration of rural residence (years) | ||||||
| 0 | 1159 (79.6) | 173 (83.6) | 0.08 | 1254 (80.0) | 55 (77.5) | 0.79 |
| >0 but ≤ 5 years | 122 (8.4) | 20 (9.7) | 135 (8.6) | 6 (8.5) | ||
| > 5 years | 175 (12.0) | 14 (6.8) | 179 (11.4) | 10 (14.1) | ||
Data are presented as No. (%) for binary variables or mean (standard deviation) for continuous variables.
P<0.10;
P<0.05;
P<0.01 for the comparison between cases and controls
Farm animals include poultry, cows, lambs, pigs, and horses
Table 2 shows the results of the multivariable analysis of rural residence and current wheeze. After adjusting for age, gender, paracetamol use, and current smoking, current residence in a rural area was significantly associated with 85% reduced odds of current wheeze (Model 1), while residence in a rural area for more than five years was significantly associated with 68% reduced the odds of current wheeze (Model 2). In this analysis, both paracetamol use and current smoking were significantly associated with increased odds of current wheeze. Rural residence was not significantly associated with current asthma after adjusting for the same covariates as in the analysis of current wheeze (data not shown).
Table 2.
Multivariable analysis of rural residence and current wheeze
| Model 1 | Model 2 | |||
|---|---|---|---|---|
|
| ||||
| OR (95% CI) | p-value | OR (95% CI) | p-value | |
| Paracetamol use in the previous year | 1.73 (1.23, 2.43) | 0.02 | 1.71 (1.21, 2.40) | 0.002 |
| Current smoking | 1.52 (0.99, 2.34) | 0.06 | 1.61 (1.05, 2.49) | 0.03 |
| Currently living in a dairy farm | 3.51 (0.68, 18.2) | 0.13 | 1.60 (0.56, 4.55) | 0.38 |
| Rural residence | ||||
| Never | 1.0 | |||
| Previously, but not now | 0.88 (0.54, 1.42) | 0.07 | ||
| Now | 0.15 (0.03, 0.81) | 0.03 | ||
| Duration of rural residence | ||||
| 0 | 1.0 | |||
| >0 but ≤ 5 years | 0.97 (0.56, 1.67) | 0.10 | ||
| > 5 years | 0.32 (0.12, 0.84) | 0.02 | ||
Data presented as odds ratio, 95% confidence interval (OR, 95% CI). All models additionally adjusted for age and gender.
Table 3 shows the characteristics of study participants, according to the presence of allergic rhino-conjunctivitis, which was reported in 19% of study participants. Compared with subjects with allergic rhino-conjunctivitis, those without allergic rhino-conjunctivitis were significantly more likely to be male, to not have used paracetamol in the last year, to live in a farm and be in contact with farm animals, and to have lived in a rural area for more than five years.
Table 3.
Characteristics of participants, according to the presence of allergic rhino-conjunctivitis
| Characteristic | Allergic rhino-conjunctivitis
|
||
|---|---|---|---|
| No (n=1430) | Yes (n=338) | p-value | |
| Age (years) | 13.5 ± 0.5 | 13.5 ± 0.5 | 0.14 |
| Male gender | 760 (53.4) | 123 (36.6) | <0.001 |
| Body mass index (kg/m2) | 19.6 ± 3.5 | 19.9 ± 3.1 | 0.13 |
| Mother completed high school | 639 (44.8) | 147 (43.6) | 0.71 |
| Use of paracetamol in the previous year | 861 (61.2) | 252 (76.4) | <0.001 |
| Physical exercise | |||
| None | 97 (6.8) | 24 (7.1) | 0.78 |
| 1–2 times/week | 744 (52.5) | 183 (54.3) | |
| ≥ 3 times/week | 577 (40.7) | 130 (38.6) | |
| Current smoking | 154 (11.1) | 43 (13.2) | 0.30 |
| Maternal smoking | 313 (22.0) | 90 (27.0) | 0.05 |
| Paternal smoking | 425 (30.0) | 115 (34.4) | 0.11 |
| Number of smokers at home | |||
| None | 781 (54.7) | 163 (48.4) | 0.08 |
| 1–2 smokers | 547 (35.3) | 143 (42.4) | |
| ≥ 3 smokers | 100 (7.0) | 31 (9.2) | |
| Number of older siblings | |||
| None | 506 (35.4) | 106 (31.4) | 0.37 |
| 1–2 | 700 (49.0) | 175 (51.8) | |
| ≥ 3 | 224 (15.7) | 57 (16.9) | |
| Use of wood for cooking | 81 (5.7) | 25 (7.4) | 0.22 |
| Use of wood for heating | 271 (19.0) | 62 (18.3) | 0.79 |
| Cat in the house in the previous year | 555 (39.2) | 149 (44.6) | 0.07 |
| Dog in the house in the previous year | 1232 (86.9) | 286 (85.2) | 0.54 |
| Currently living in a dairy farm | 96 (7.1) | 8 (2.5) | 0.002 |
| Lived in a dairy farm, first year of life | 207 (14.9) | 40 (12.1) | 0.20 |
| Regular contact with farm animals1, now | 200 (14.0) | 29 (8.6) | 0.008 |
| Regular contact with farm animals1, first year of life | 172 (12.1) | 31 (9.2) | 0.14 |
| Rural residence | |||
| Never | 1073 (78.3) | 274 (82.8)§ | 0.06 |
| Previously, but not now | 151 (11.0) | 36 (10.9) | |
| Now | 146 (10.7) | 21 (6.3) | |
| Duration of rural residence (years) | |||
| 0 | 1069 (79.5) | 274 (83.4) | 0.006 |
| >0 but ≤ 5 years | 108 (8.0) | 32 (9.8) | |
| > 5 years | 168 (12.5) | 21 (6.4) | |
Results are shown as No. (%) for binary variables or mean (standard deviation) for continuous variables.
P-value for the comparison between cases and controls
Farm animals include poultry, cows, lambs, pigs, and horses
Table 4 shows the results of the multivariable analysis of rural residence and allergic rhino-conjunctivitis. After adjustment for age, gender and other covariates, current (but not prior) residence in a rural area was significantly associated with 48% reduced odds of allergic rhino-conjunctivitis (Model 1). In this model, there was no significant association between previous residence in a rural area and allergic rhino-conjunctivitis. After additional adjustment for either current residence in a dairy farm (Model 2) or current regular contact with farm animals (Model 3), there was no longer a significant association between current residence in a rural area and allergic rhino-conjunctivitis. In these models, current residence in a dairy farm and current regular contact with farm animals were significantly associated with 73% and 40% reduced odds of allergic rhino-conjunctivitis, respectively.
Table 4.
Multivariable analysis of rural residence and allergic rhino-conjunctivitis
| Model 1 | Model 2 | Model 3 | ||||
|---|---|---|---|---|---|---|
|
| ||||||
| OR (95% CI) | p-value | OR (95% CI) | p-value | OR (95% CI) | p-value | |
| Rural residence | ||||||
| Paracetamol use in the previous year | 1.99 (1.50, 2.64) | <.001 | 1.92 (1.45, 2.56) | <.001 | 1.98 (1.49, 2.63) | <.001 |
| Cat in the house in the previous year | 1.40 (1.08, 1.80) | 0.011 | 1.47 (1.14, 1.91) | 0.003 | 1.43 (1.11, 1.85) | 0.006 |
| Currently living in a dairy farm | 0.27 (0.08, 0.88) | 0.03 | ||||
| Current regular contact with farm animals1 | 0.60 (0.37, 0.94) | 0.04 | ||||
| Rural residence | ||||||
| Previously, but not now2 | 0.87 (0.58, 1.31) | 0.44 | 0.88 (0.59, 1.33) | 0.71 | 0.92 (0.61, 1.39) | 0.64 |
| Now2 | 0.52 (0.32, 0.86) | 0.03 | 0.98 (0.38, 2.56) | 0.93 | 0.68 (0.39, 1.18) | 0.23 |
|
|
||||||
| Model 4 | Model 5 | Model 6 | ||||
| OR (95% CI) | p-value | OR (95% CI) | p-value | OR (95% CI) | p-value | |
|
| ||||||
| Duration of rural residence | ||||||
| Paracetamol use in the previous year | 1.99 (1.50, 2.64) | <.001 | 1.93 (1.45 2.58) | <.001 | 1.98 (1.49, 2.64) | <.001 |
| Cat in the house in the previous year | 1.40 (1.08, 1.81) | 0.01 | 1.46 (1.13, 1.90) | 0.004 | 1.44 (1.11, 1.86) | 0.006 |
| Currently living in a dairy farm | 0.32 (0.12, 0.86) | 0.02 | ||||
| Current regular contact with farm animals1 | 0.61 (0.38, 0.98) | 0.04 | ||||
| Duration of rural residence | ||||||
| ≤ 5 years2 | 1.08 (0.69, 1.67) | 0.05 | 1.11 (0.70, 1.74) | 0.25 | 1.16 (0.75, 1.82) | 0.06 |
| > 5 years2 | 0.44 (0.26, 0.73) | 0.001 | 0.66 (0.34, 1.28) | 0.17 | 0.54 (0.32, 0.93) | 0.01 |
All models were additionally adjusted for age and gender.
Farm animals include poultry, cows, lambs, pigs, and horses
Compared to those who never lived in rural areas
Table 4 also shows the results of the multivariable analysis of duration of rural residence and allergic rhino-conjunctivitis. In a multivariable model, residence in a rural area for over five years was significantly associated with 56% reduced odds of allergic rhino-conjunctivitis (Model 4). In this model, rural residence for five years or less was not significantly associated with allergic rhino-conjunctivitis. After additional adjustment for current residence in a dairy farm (Model 5), duration of rural residence was no longer significantly associated with allergic rhino-conjunctivitis. In this model, however, current residence in a dairy farm was significantly associated with 68% reduced odds of allergic rhino-conjunctivitis. In a multivariable model adjusting for current regular contact with farm animals instead of current residence in a dairy farm, residence in a rural area for at least five years was significantly associated with 56% reduced odds of allergic rhino-conjunctivitis. In this model, current regular contact with farm animals was also significantly inversely associated with allergic rhino-conjunctivitis. In all multivariable models shown in Table 4, having had a cat in the house in the previous year and paracetamol use in the previous year were both significantly associated with increased odds of allergic rhino-conjunctivitis.
DISCUSSION
To our knowledge, this is the first study to show that current residence in a rural area or duration of rural residence greater than five years is significantly associated with reduced odds of current wheeze and current symptoms of allergic rhino-conjunctivitis among Argentinean adolescents. We further demonstrate that our findings for allergic rhino-conjunctivitis are partly explained by current residence in a dairy farm, including regular contact with farm animals.
A protective effect of a farming environment on allergic diseases has been reported in alpine regions of Central Europe. In rural regions of Austria, Germany, and Switzerland, children living in farms have been shown to have 20% to 57% lower risk of asthma, hay fever, and atopic dermatitis than those not living in farms13. Moreover, farm living has been associated with 55% decreased odds of current wheeze among non-atopic children in the same areas14. Similar results were shown in a study in Poland, where farming activities are slightly different from those in the Alpine area15. In a Swedish study, farm living during the first 5 years of life was associated with reduced risk of allergic rhinitis. In that study, degree of urbanization was associated with increased risk of allergic rhinitis, independently of farm living in early life16. Similar results for a farming environment or a rural lifestyle and allergic diseases have been reported in China17, Korea18, Australia19, and Canada20.
In contrast to studies in other geographic areas, residence in rural areas of Latin America has not been consistently associated with reduced risk of allergic diseases. In a recent study of 6,821 school-aged children living in a tropical area of Ecuador, estimates of the prevalence of current wheeze were very similar and not significantly different between urban (9.4%) and rural (10.1%) areas. In that study, there were no significant urban-rural differences in atopy or eczema, but urban residence was significantly associated with increased odds of current rhinitis10. In contrast, a study of 2,854 school-aged children living in high-altitude urban and rural areas of Oropeza Province (located in Bolivia, the second poorest country in Latin America) showed that rural residence was significantly associated with 50% decreased odds of current wheeze (95% confidence interval [CI] for the odds ratio [OR]= 0.4 to 1.0) and 60% decreased odds of severe rhino-conjunctivitis (95% CI for the OR=0.2 to 0.8)11. Similar results were shown in a study conducted in Valdivia (southern Chile), in which rural residence was significantly associated with reduced odds of current symptoms of asthma (OR=0.4, 95% CI=0.2 to 0.9) and rhino-conjunctivitis (OR=0.3, 95% CI=0.2 to 0.7)21.
The current study differs from those described above with regard to geographic area, climate, altitude, prevalence of helminthic infections, and/or economic development of the study sites10, 11, 21. Whereas Ecuador and Bolivia are less urbanized and developed than Argentina, the per capita domestic gross product (GDP) of Chile is similar to that of Argentina ($18,200 vs. $17,900, in 2012 U.S. dollars)6. In contrast to previous reports from Latin America, we present results from multivariable analyses, adjusting for potential confounders. Unlike prior studies, we also examined variables that could mediate potential effects of rural residence (e.g., residence in a dairy farm, contact with farm animals) or have independent effects on allergic conditions (e.g., current smoking, paracetamol use). Moreover, we assessed duration of residence in a rural area (categorized as yes/no in prior reports from Latin America).
Contact with livestock and animal feed/shed, consumption of unprocessed cow’s milk, and microbial (bacterial or fungal) exposures may explain the beneficial effects of a farming environment against allergic diseases9. In a mouse model, chronic exposure to low-dose endotoxin [lipopolysaccharide (LPS)] or farm dust prevented house dust mite (HDM)–induced allergic airway inflammation (AAI), reduced levels of interleukin (IL)-5 and IL-13, and activated dendritic cells (DCs). Compared to controls, LPS-treated mice had lower serum IgE to HDM, decreased airway responsiveness, and fewer eosinophils in bronchoalveolar lavage. Induction of an ubiquitin-modifying enzyme, A20, in lung epithelium was suggested to play a role in reducing AAI22. Findings from the Finnish PASTURE (Protection Against Allergy: Study in Rural Environments) cohort study23, 24 suggest that farming environments affect the function of dendritic cells and induce a T-regulatory and Th1-skewed phenotype, promoting immune tolerance23, 24.
Consistent with a prior report from Argentina25, current smoking was common among adolescents in the current study. A report from ISAAC estimated that active tobacco consumption contributed to more than 27% of asthma symptoms among adolescents from Chile26. Among our participants with current wheeze, 14.6% were current smokers. Moreover, current smoking was significantly associated with 61% increased odds of current wheeze, emphasizing the need for more stringent tobacco control measures directed to Argentinean children. The observed association between paracetamol use in the previous year and current wheeze or allergic rhino-conjunctivitis may be due to “reverse causation” (e.g., if children with wheeze due to a viral illness or upper respiratory tract infections are prescribed paracetamol), yet worthy of further exploration in longitudinal studies, given recent findings implicating paracetamol or acetaminophen use in early life on childhood asthma27.
We recognize several study limitations. First, we cannot adequately assess early-life exposures or temporal relationships in a cross-sectional study. Thus, negative findings for early-life exposures previously shown to influence allergic diseases28,29,30 (e.g., residence in a dairy farm or regular contact with farm animals in the first year of life) may be due to recall bias. However, our results are consistent with an inverse dose-response relationship between a rural Argentinean environment and current wheeze or allergic rhino-conjunctivitis. Second, we lack data on consumption of unpasteurized milk, exposure to animal fed and grains (hay, corn, and wheat), family history of allergic diseases, puberty and detailed dietary intake, and exposure to air pollution, all of which could mediate or confound our findings. However, frequency of weekly consumption of fruit or vegetables and rice was not different between subjects with current wheeze or allergic rhino-conjunctivitis and control subjects in our study (data not shown). Third, we lack objective measures of atopy (e.g., allergy skin testing or allergen-specific IgEs) and had insufficient statistical power for the analysis of current asthma (given a relatively small number of cases and potential under-diagnosis). However, we had adequate statistical power for the analyses of current wheeze and allergic rhino-conjunctivitis, which were defined using an extensively validated questionnaire.
In summary, our findings suggest that residence in a rural area –particularly when current or longer than five years- has a potential protective effect against current wheeze or allergic rhino-conjunctivitis in Argentinean adolescents. Moreover, our results suggest that this is partly explained by current residence in a dairy farm (including regular contact with farm animals). Longitudinal studies are needed to further examine the mechanisms underlying any protective effects of a rural environment in Argentina, and in other Latin American countries with diverse climates and degrees of economic development.
Acknowledgments
Funding
Dr. Celedón’s contribution was supported by grants HL117191 and HL119952 from the US National Institutes of Health (NIH), and by The Heinz Endowments. Dr. Forno’s contribution was supported by grant HD052892 from the NIH.
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