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Keywords:

  • allergy prevalence;
  • children;
  • preventive factors;
  • risk factors;
  • skin prick test

Abstract

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Background:  We aimed to compare the prevalence of allergic diseases and sensitization in children living in urban and rural areas and to identify potential risk/protection factors associated with allergy.

Methods:  School children 12–16 years old, from urban community (n = 201) and rural area (n = 203) were recruited. The data obtained by questionnaire were referred to doctors’ diagnosis, skin prick tests (SPTs), and serum specific and total IgE assessment.

Results:  The prevalence of allergic diseases in urban children was significantly higher as compared with rural children [asthma 16.42%vs 1.97% (P < 0.001) allergic rhinitis 38.81%vs 10.84% (P < 0.001)]. Positive SPTs to at least one allergen was found in 63.7% of urban and 22.7% rural children (P < 0.001). Significantly higher percentage of allergic rural than urban children were monosensitized or sensitized to 2–4 allergens, but almost a fourfold higher percentage of allergic urban children was found to be sensitized to five or more allergens (P < 0.0001). The history of frequent upper respiratory factor (URT) infections, antibiotic therapy, tonsiltectomy/adenoidectomy were positively associated with development of atopy and sensitization.

Conclusion:  Our findings confirm that residence of rural area is associated with a significant lower prevalence of allergic sensitization and symptoms in school children. Several risk and protective factors related to environment and style of life could be identified in both environments.

The prevalence of allergic diseases and allergic sensitization has been increasing over last half century, and this trend has been well documented in highly developed countries and associated with so called ‘westernized’ style of life (1, 2). Several studies have shown that children grown up in rural farm environment have had a lower prevalence of allergic symptoms and atopic sensitization in childhood as compared with other rural or urban children (3–6). However, other studies failed to find significant differences between rural and urban children justifying further investigations of this phenomenon in new well defined populations (7–9).

Lower prevalence of allergy in rural environment was suggested to be caused by environmental exposures to farm animals and/or farm/unpasteurized milk consumption and these protective effects were attributed to mothers or children exposure to microbial compounds having potential immunosuppressive effects (10–12). On the other hand, potential risk factors in urban environment are far less well defined. The hygiene hypothesis suggests that with improving standards of living, decreased exposure to infective factors may facilitate development of sensitization. Several other factors present in urban environment, including children exposure to diesel exhaust particles, treatment with antibiotics or even maternal supplements of progesterone might contribute to increased allergization (13–16). Exposure to pets which is quite common in both urban and rural children has been shown to either have protective effect or to increase the risk of sensitization (6, 17–19). However, none of these factors offer definitive explanation for observed differences in the prevalence of allergy between rural and urban children.

Central and eastern European countries like Poland have been considered to have rather low prevalence of allergy, and the increase in the prevalence of allergy over last decades was less consistently documented in this region of Europe (20, 21).

In this study we assessed the prevalence of allergic symptoms and allergic sensitization in school children raised in urban and rural environment in central Poland, and, based on a detailed social and environmental survey, an attempt was made to identify potential risk/protective that could be associated with differences in the prevalence of allergy.

Patients and methods

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Sampling of the study population

School children aged 12–16 years were recruited into the study from two different living environments in central Poland. The first group included all 203 children attending two schools located in rural community of central Poland (99% of children aged 10–16 attending these schools were studied), and the second group consisted of 201 children randomly sampled from the population of 925 children attending two schools located in the centre of Lodz, an industrial city in central Poland (82% of sampled children were available for assessment). The parents of children filed in written questionnaire on general household characteristics, living conditions, various family and environmental exposures, farming characteristics (in rural children), dietary habits, maternal history of pregnancy and pet ownership. Following the initial review of the questionnaire the children were invited for assessment by a trained allergist which included history, physical examination, skin prick testing and blood withdrawal for IgE assessment. Based on history, clinical examination and results of skin prick test (SPT), the allergist proposed the final diagnosis with regard to allergic diseases. The study was approved by the Medical University ethics committee.

Skin prick testing

The sensitization status was determined by skin prick testing (n = 404) using the extracts of 15 allergens: Dermatophagoides pteronyssinus (Der P), D. farinae, cat, dog, rabbit, hamster, guinea-pig, rat, swine, birch, grass mix, mugwort, plantain, Alternaria tenius and Cladosporium herbarum and positive and negative controls (Allergopharma, Germany). The weal diameter of at least 3 mm was considered as positive test and, for the purpose of this study, allergic sensitization was defined as the presence of positive test to at least one allergen.

IgE assessment

Serum total IgE and specific IgE to Der p1 and timothy allergens were measured by the ImmunoCAP assay (Pharmacia Upjohn Diagnostics AB, Uppsala, Sweden).

Statistical analysis

Difference between rural and urban children (current allergy, sensitization and demografic data) were tested by chi-squared test. Relations between number of positive SPTs and prevalence of asthma and allergic rhinitis (AR) were analyzed by linear Pearson’s correlation after arcsin transformation. Odds ratios (OR) with 95% confidence intervals were calculated for all analyzed potential risk factors and separately for each of the outcomes (asthma, rhinitis food allergy and SPT positivity). The risk was assessed by means of univariate analysis to see how each potential explanatory variable affected the probability of having one of allergic diseases (asthma or AR) or sensitization to at least one allergen. Factors significantly associated with the above in the univariate analysis were examined in multivariate regression analysis. For all analyses a P-value of <0.05 was considered significant.

Results

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Respiratory symptoms

Rural children as compared with urban children were less likely to have had a history of rhinorhea: 10.8%vs 28.8% (P < 0.001), sneezing: 6.9 vs 15.4%, (P < 0.0001); exercise-induced dysponea: 15.2%vs 24.4% (P < 0.0001); or wheezing not related to infections: 2.5%vs 7.5%; (<0.001).

Current allergic diseases and allergic sensitization

At least one allergic disease was diagnosed by a doctor in 12.8% (n = 26) of rural children and in 43.3% (n = 87) of urban children (P < 0.0001). In rural children many-fold lower prevalence of doctors diagnosed bronchial asthma (eightfold), AR (fourfold) rhinoconjunctivitis, atopic eczema or food allergy were observed as compared with urban school children (Table 1).

Table Table1.   Current allergy and sensitization in rural and urban children
 Urban n (%)Rural n (%)P-valueOR
Doctors’ diagnosed current allergy
 Allergic rhinitis78 (39)22 (11)< 0.00015.21 (3.08–8.84)
 Conjunctivitis24 (12)0< 0.00010
 Asthma33 (16)4 (2)< 0.00019.77 (3.38–28.24)
 Food allergy5 (2.5)00.020
 Atopic eczema5 (2.5)1 (0.5)0.135.15 (0.59–44.80)
Allergic sensitization (SPT)
 HDM79 (39)31 (15)< 0.00013.59 (2.23–5.79)
 Cat42 (21)7 (3.5)< 0.00017.40 (3.23–16.95)
 Dog37 (18.5)3 (1.5)< 0.000115.04 (4.54–49.85)
 Pig16 (7.96%)0< 0.0001
 Rabbit 20 (9.95%)2 (0.99%)< 0.000111.1 (2.53–48.71)
 Birch42 (21)5 (2.5)< 0.000110.46 (4.03–27.14)
 Grasses63 (31)11 (5.5)< 0.00017.97 (4.04–15.71)
 Plantain33 (16.4)3 (1.5)< 0.00113.10 (3.93–43.62)
 Mugwort51 (25)7 (3)< 0.00019.52 (4.19–21.63)
 Hamster20 (10)1 (0.5)< 0.000122.32 (2.95–169.04)
 Alternaria31 (15)3 (1.5)< 0.000112.16 (3.64–40.62)
At least one positive SPT128 (63.7)46 (22.7)< 0.00015.98 (3.23–12.72)
Specific IgE Der p1 >1 class49 (24.4)22 (10.8)< 0.001 2.65 (1.53–4.59)
Specific IgE timothy >1 class54 (26.9)11 (5.4)< 0.00016.44 (3.23–12.72)
Total IgE (kU/ml) (mean)180.58 ± 347.82150.99 ± 324.280.377

Urban school children had very high rate of sensitization to common allergens: 63.7% (128/201) of urban children had positive SPT to at least one allergen tested as compared with 24% (46/203) of rural children [OR = 6.0 (3.9–9.3); P < 0001)] and SPTs to each of 15 allergens tested were also more prevalent in urban school children.

Significantly higher percentage of allergic rural, rather than urban children was monosensitized or sensitized to two to four allergens. In contrast almost fourfold higher percentage of allergic urban children was found to be sensitized to five or more allergens (Fig. 1).

image

Figure 1.  Percentage of children with one, two to four, and five or more positive skin prick tests to inhalant allergens. *(P < 0.05); **(P < 0.01); ***(P < 0.0001) in urban compared to rural children – chi square test.

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Specific serum IgE (sIgE) to Der p1 and timothy allergen were found more frequently in urban than rural children (Fig. 1). The sIgE class distribution was shifted towards higher classes in urban children: none of rural children but 12% of urban children had sIgE to Der p1 allergen in either class 5 or 6. Similarly, 16% of allergic urban children had sIgE to timothy in classes 5 or 6 as compared with 9% of rural children (Fig. 2a,b).

image

Figure 2.  A and B. Distribution of specific IgE classes to (A) Dermatophagoides pteronyssinus (Der P) and (B) timothy allergen in urban and rural children. The difference between urban and rural children were significant at class 2 (P = 0.004), class 5 (P = 0.04) and class 6 (P = 0.04) for Der P and at class 1 (P = 0.026), class 2 (P = 0.007), class 4 (P < 0.001), and class 5 (P = 0.008) for timothy allergen; (chi-squared test).

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A similar percentage of rural and urban children (30% and 34%, respectively) had serum total IgE levels above normal value (107 kU/l) and no significant difference in mean total sIgE levels were found between both groups (Table 1).

Risk factors associated with allergic diseases and sensitization

Potential risk factors associated in previous studies with development of allergy were significantly different in urban and rural environment (Table 2) thus further analysis was performed separately for each group of children.

Table 2.   Demographic profile and environmental differences between urban and rural children
 Urban (no of cases 201) n (%)Rural (no of cases 203) n (%)P-value OR (−95 CL, +95 CL)
Mothers’ history
Number of pregnancies    
Mean (range)1.73(0–7)2.36(1–12)< 0.0001 
Premature labor (miscarriage)40 (20)21 (10)0.0062.19 (1.24–3.89)
Treatment with progesterone27 (13)0< 0.0001
Treatment with antibiotics10 (5)00.001
Contact with animals during pregnancy
 Cat or dog63 (31)190 (94)< 0.00010.24 (0.19–0.32)
 Livestock17(8)175(86)< 0.00010.10 (0.07–0.15)
 Caesarian labor41 (20)10 (5)< 0.00011.94 (1.44–2.62)
Children’s history
Breast feeding for at least 3 month28 (14)54 (27)< 0.00010.40 (0.24–0.67)
Daily contact with livestock30 (15)177 (87)< 0.00010.02 (0.01–0.04)
Daily contact with dog/cat115 (57)197 (97)< 0.00010.04 (0.02–0.11)
Frequent URT infections90 (45)8 (4)< 0.000119.88 (9.27–42.66)
Kindergarten attendance156 (78)55 (27)< 0.00019.33 (5.92–14.7)
History of bronchitis89 (44)45 (22)< 0.00012.89 (1.87–4.46)
Frequent course of antibiotic therapy31 (15)12 (6)< 0.00013.86 (1.88–7.92)
Tonsillectomy/adenoidectomy31 (15)8 (4)< 0.00014.42 (1.97–9.91)
Food consumption
Home-made food49 (24)168 (83)< 0.00010.06 (0.04–0.10)
Nonpasteurized milk46 (23)116 (57)< 0.00010.22 (0.14–0.34)
Nonboiled water64 (32)132 (65)< 0.00010.25 (0.16–0.38)
Sauer milk50 (25)146 (72)< 0.00010.12 (0.08–0.19)
Living conditions
Individual house 20 (10)7 (3)< 0.00013.09 (91.27–7.51)
Apartment house173 (86)0< 0.0001
Farm0196 (97)< 0.0001
Central heating109 (54)0< 0.0001
Parental smoking
 Mother67 (33)28 (14)< 0.00013.25 (1.97–5.35)
 Father68 (34)77 (38)0.51.15 (0.76–1.73)

Univariate model

In urban children, the risk of asthma increased if a child had a history of frequent URT infections [OR = 5.20 (2.56–10.56); P < 0.0001] or if it was delivered by Cesarean labor [OR = 2.36 (1.03–5.41); P = 0.049]. Children contact with livestock during first 3 years of life protected against development of asthma [OR =0.22 (0.09–0.59), P < 0.001)]. Diagnosis of AR was positively associated with attendance to kindergarten [OR = 2.50 (1.55–4.02); P < 0.0001], history of frequent URT infections [OR = 3.80 (2.32–6.22); P < 0.0001], antibiotic therapy in early childhood [OR = 2.90 (1.03–4.24); P = 0.045] and tonsiltectomy/adenoidectomy [(OR = 3.33 (1.5–7.4), P = 0.003], but negatively related to contact with livestock [OR = 0.23 (0.13–0.40), P < 0.0001] or with cat [OR = 0.58 (0.23–1.6); P = 0.03].

Allergic sensitization was increased in children attending kindergarten (OR = 2.29 (1.53–3.40); P < 0.0001] or having history of frequent URT infections [OR = 2.86 (1.80–4.59); P < 0.0001], antibiotic therapy [OR = 2.12 (1.16–3.85); P = 0.015] and tonsilectomy/adenoidectomy [OR = 2.92 (1.45–5.87); P = 0.002].

In rural children because of low prevalence of allergic sensitization and allergic symptoms only a few associations were found. Asthma in rural children was positively associated with history of frequent antibiotic treatment [OR = 18.7(2.4–146); P = 0.018] and the risk of AR was increased in children with history of tonsillectomy or adenoidectomy [OR = 5.53 (1.2–24.9); P = 0.04] and frequent antibiotic treatment [OR = 4.75(1.3–17.3); P = 0.03].

For both groups of children the risk of allergic sensitization was decreased if children were born of third or later pregnancy as compared with children born from first two pregnancies [OR = 0.31 (0.14–0.72); P = 0.003].

Multivariate model

In urban children multivariate logistic regression analysis confirmed the positive association of asthma development with frequent URT infections during their first 3 years of life [OR = 14.3(2–105.5) P = 0.009], child’s birth from first or second pregnancy [OR = 3.6 (1.46–8.79); P = 0.005], and presence of sIgE for Der p1 (class 1–6) [OR = 3.5 (1.8–6.70); P < 0.0001].

Negatively associated with asthma in urban children were; attendance to kindergarten [OR = 0.05, (0.004–0.48); P = 0.001], daily contact with dog/cat during their first 3 years of life [OR = (1.46–8.79); P < 0.005] and sleeping on feather pillows [OR = 0.09 (0.01–0.6); P = 0.017]. History of past miscarriages in mothers living in urban areas increased the risk of AR in children [OR = 2.84 (0.98–8.25); P = 0.054]. Daily contact with livestock during the first 3 years of life and current passive smoking decreased the risk of allergic sensitization [OR = 0.179 (0.054–0.57); P = 0.005] and [OR = 0.18 (0.054–0.597); P < 0.005] respectively.

In rural children, no risk factor was associated in multivariate analysis with asthma but risk of AR significantly decreased if mothers reported daily contact with pigs during pregnancy [OR = 0.142 (0.027–0.75); P < 0.02] and the risk was increased when child fed with nonfarm milk [OR = 10.33 (1.4–78.6) P = 0.024]. The risk of allergic sensitization also increased in children fed with nonfarm milk [OR = 3.37 (1.4–8.2) P = 0.007].

Association of sensitization with respiratory symptoms

For the whole group with an increasing number of positive SPTs, there was a linear increase in the prevalence of asthma and AR: r2 = 0.75 and 0.74 for asthma and AR, respectively,(P < 0.001) (Fig. 3). In urban children the presence of sIgE to Der p1 was positively correlated to diagnosis of both asthma (OR = 3.46 (1.78–6.75); P < 0.0001] and AR (OR = 2.32 (1.36–3.98); P = 0.002]. Serum IgE specific to timothy was associated with diagnosis of AR in both urban (OR = 1.61 (1.05–2.47); P = 0.03] and rural children (OR = 3.9 (1.42–10.63); P = 0.008].

image

Figure 3.  Association between number of positive skin prick tests (SPTs) and prevalence of children allergic diseases: asthma (r2 = 0.738, P = 0.0002) and allergic rhinitis (AR): (r2 =0.745, P = 0.0001). Proportion of children with asthma and AR is presented as arcsin transformation; lines of regression have 95% confidence limit.

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Discussion

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Our study demonstrated striking differences in the prevalence of allergic diseases and sensitization to atopic allergens between school children from rural and urban communities in central Poland. Although comparing with other studies our population of children is relatively small, we could avoid a selection bias, as we managed to include almost all (99%) children form two selected rural schools, and 82% of randomly selected urban school children. These results are generally in line with previous reports from European and other countries (22, 23) documenting significantly lower prevalence of allergic sensitization and symptoms in farming as compared with nonfarming children. However, the magnitude of differences observed in our study is even higher than previously reported: prevalence of asthma was eightfold and AR 3.5-fold lower, and sensitization to all allergens tested was 2–20 times lower in rural children. It is important to stress that all children recruited to the study were seen by trained allergists, and clinical allergy diagnosis was based not only on history, as in most epidemiological studies, but also on physical examination and allergic testing.

As opposed to most previous studies, children living in farming environment were contrasted with urban children and not with nonfarm rural children. It was because of the fact that almost all children recruited from schools in rural area were exposed to farm environment. For example, up to 89% of rural children were constantly exposed to livestock and 97% to either cat or dog during the first 3 years of live and similarly high rates of exposure to livestock and pets were reported by mothers during pregnancy. It has been proposed that exposure early in life to microorganisms associated with farm animals, might prevent development of allergic sensitization and symptoms of allergy probably by stimulation of innate immunity (24–26). With much lower exposure to livestock (but not to pets) in urban children, frequent contacts with farm animals could be related to lower prevalence of allergy in our rural children. Moreover, rural children differed in dietary habits – large majority of them was exposed to home-made foods, farm milk or sour milk which are known sources of probiotics and bacteria. Previous studies suggested that consumption of such foods may have a significant immunomodualtory effect leading to decreased rate chance to allergic sensitization (11, 12).

The prevalence of asthma, AR/conjunctivitis, eczema or food allergy in rural children was substantially lower than reported in other studies ; for example asthma was diagnosed only in 2% of rural children, while in the Parsifal study, the respective figure was 6.2% (27). Atopy was diagnosed in 22% of rural children in central Poland and even lower prevalence of allergic sensitization (7%) was reported recently among young rural population in southern Poland (28). Such low prevalence of allergy in Polish rural children may be related to particular farm characteristics quite different from farms in western Europe. In the area where the study was carried out typical farm is rather small, based on self-employment of the family members, and grows a variety of crops and raises a different species such as, cattle, horse, pigs and poultry. In such environment, most children are likely to have contact with all types of animals outside the house and the exposure to potential protective factors allegedly associated with farm animals, and crops seem to be far more constant and intensive than in western-type more specialized farms in western Europe. In contrast children from urban schools had a high prevalence of allergic symptoms and at least, one atopic disease was diagnosed in 43.3% of them. In the urban environment, the known protective factors like exposure to farm animals or consumption of nonprocessed foods were less prevalent. On the other hand, in the urban environment the potential risk factors (e.g premature or cesarean labor, treatment with antibiotics or frequent URT infections) were more prevalent and might have contributed to the higher rate of allergy.

Increased rate of sensitization in urban children was documented for all 15 allergens tested and surprisingly even to allergens, which seemed to be typical for rural environment e.g. pig and rabbit. Interesting phenomenon not reported previously refers to the proportion of polysensitized children in both environments. The rural children were sensitized to a significantly small number of allergens: almost 40% of rural allergic children were sensitized to one allergen, but only 11% were sensitized to five or more allergens. In contrast, although only 22.7% of urban allergic children were mono sensitized, 41.4% of them were sensitized to five or more allergens. At the same time serum specific IgE levels to mite and timothy were significantly shifted towards higher classes in urban as compared with rural children. These observations suggest operation of environment specific regulatory mechanisms affecting not only risk of sensitization but also the magnitude of specific IgE production (29, 30).

Exposure to most risk factors previously associated with development of allergic diseases and allergic sensitization (e.g. related to history of mother’s pregnancy, type of housing or food/milk consumption) were significantly different in urban and rural environments. Such dramatic differences between rural and urban environments in the presence of potential risk/protective factors prompted us to separate analyses of children living in both environments. Significantly, more of both risk and protective factors could be identified in urban rather than rural children, which may reflect a very small number of cases of allergy among rural children and uniform environmental exposures. In contrast to most previous studies (31–35) in both children populations history of frequent URT infections and other factors traditionally related to infections (attandence to kindergarten, antibiotic therapy in early childhood, tonsiltectomy/adenoidectomy) carried a significant risk for development of allergic sensitization and allergic symptoms. Although kindergarten attendance was also associated with increased risk of allergy in other studies (36), we cannot exclude that our children had early symptoms of allergy, which were misdiagnosed, and the children were treated as having respiratory infections.

On the other hand, exposure to animals both at home and at farm had a significant protective effect against sensitization and allergic symptoms. These data are in agreement with many previous studies pointing at protective role of contact with farm and home animals. The potential protective role of microbial exposure by the digestive tract was suggested by observation that children fed with pasteurized milk during first 3 years of life as opposed to children fed with unpasteurized milk had increased risk of allergic sensitization. The history of miscarriages in mothers increased the risk of AR in children raised in urban but not rural areas pointing to the important, but still not well defined role of maternal risk factors. Paucity of protective factors identified in rural children in our study suggests that other as-yet-unidentified confounding factors in the rural environment could be responsible for the observed differences.

In conclusion this study demonstrated dramatic differences in the prevalence of allergic diseases and sensitization between school children living in rural and urban environments A range of social and environmental factors may both increase and decrease the risk of allergy development in children raised in rural and urban environments

Acknowledgments

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

This study was supported by National Research Committee grant No 3PO5D 050 22. The authors would like to thank the principals and teachers of participating schools: 1st and 28th Middle School’s in Lodz, Middle School’s in Mierzyce and Slupia for their assistance. We also thank allergologists Dr M. Czarnecka, Dr B. Kubicka – Kozik for their support and Dr W. Szymczak for statistical analysis of data.

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  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
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