Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air

Authors


An-Soo Jang
Division of Allergy and Pulmonology
Department of Internal Medicine
Soonchunhyang University Hospital 1174. Jung-Dong, WonMi-Gu, Bucheon-Si Gyeonggido, 420-767,
Korea

Abstract

Background: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries.

Objective: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross-sectional study of a cohort of 670 children, aged 10–13 years.

Methods: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR.

Results: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 ± 0.48] compared to those in rural [31.9% (52/163), 9.84 ± 0.83] and coastal [33.3% (67/201), 7.17 ± 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P < 0.007]. Schoolchildren with atopy had lower PC20 than those without atopy (5.98 ± 0.60 vs 8.15 ± 0.45, P < 0.001). Positive allergy skin tests and living in a polluted area were risk factors in multivariate analyses adjusted for sex, parents’ smoking habits, age, body mass index, nose symptoms and lung symptoms (odds ratio for location = 2.4875, confidence interval 1.6542–3.7406, P < 0.000; odds ratio for allergy skin test = 1.5782, confidence interval 1.1130–2.2379, P < 0.0104).

Conclusion: Our findings demonstrate that more children living in polluted areas have airway hyperresponsiveness than do those living in less polluted areas.

It is well known that increased air pollution emanating from traffic and various industries has resulted in an increase in the incidence of allergic diseases. Acute exposure to air pollution is associated with increased respiratory symptoms and decreases in lung function in children. Chronic exposure to increased levels of respirable particles, SO2, and NO2 is associated with up to threefold increase in nonspecific respiratory symptoms, such as chronic cough, but not with asthma. Exposure to heavy traffic leads to significant increases in respiratory symptoms, while no clear effect on the inception of asthma has been documented. Outdoor air pollution levels have been associated with adverse effects in subjects with asthma (1), and exposure to traffic-related air pollution, in particular diesel-exhaust particles, may lead to reduced lung function in children living near major motorways (2). Relatively few studies have examined the health of subjects living near chemical factory pollution.

This study examined the prevalence of airway hyperresponsiveness in schoolchildren in Korea living in clear rural and coastal areas 10 km away from a chemical factory with those living near the chemical factory.

Methods

Study subjects

We examined children living in three cities in southeast Korea: Yeochon, the site of a chemical factory, has 100 000 inhabitants and covers an area of 200 km2; Yeosu, which is 10 km from the chemical factory, has 300 000 inhabitants and an area of 226 km2; and Namwon, a rural area at 650 m above sea level, has 80 000 inhabitants and an area of 100 km2. All the children were 10–13 years of age. The children were asked questions on respiratory and allergic disorders that are included in the survey developed for the International Study of Asthma and Allergies in Childhood (ISAAC). We asked about the presence of a wheeze in the last 12 months, the number of wheezing attacks in the last 12 months, and ‘sleep-disturbing’ and ‘speech-limiting’ wheezing in the last 12 months. Symptoms of allergic rhinoconjunctivitis (sneezing, runny or blocked nose without a cold, and itchy-watery eyes) were assessed (3). In addition, we asked about morning cough as a symptom of nonspecific airway irritation. (In the last 12 months, do you cough frequently after waking up in the morning?) The study was approved by the Research Committee of Seonam University and written informed consent was obtained from the parents of the subjects before the study.

Air pollution data

Air pollution and meteorological data were obtained from the Korea National Air Quality Monitoring Network, which is operated by the National Institute of Public Health and the Environment. Data were obtained for three cities (Yeochon, Yeosu, and Namwon). All the children lived within a circle with a radius of 20 km that included Yeochon, Yeosu, and Namwon. The air pollutants measured were ozone, NO2, SO2, and HF. In the analysis, the maximal 8-h moving average was used for ozone, and the 24-h mean was used for the other air pollutants.

Spirometry

Spirometry was performed according to the American Thoracic Society standards (4) using a SensorMedics 2200 spirometer (Cardiopulmonary Care CompanyTM, Yorba Linda, CA, USA). Representative values for FVC (forced vital capacity) and FEV1 (forced expiratory volume in 1 s) were selected according to International Thoracic Society criteria (5) and the reference values were taken from Choi et al. (6) and Kim et al. (7).

Airway hyperresponsiveness

The methacholine challenge tests followed the modified method described by Chai et al. (8). Concentrations of 0.075, 0.31, 1.25, 2.5, 5, 10, and 25 mg/ml methacholine were prepared by dilution with buffered saline. A Micro-dosimeter (S & M Instrument Co., Doylestown, PA, USA) was used to deliver the aerosol generated by a DeVilbiss 646 nebulizer. The subjects inhaled five breaths of increasing concentrations of methacholine, until the FEV1 fell by more than 20% of its basal value or the highest concentration was reached. The largest value of triplicate FEV1 at 30, 90, or 180 s after each inhalation was adopted for analysis. If PC20 was less than 16 mg/ml, that subject was considered to have AHR to methacholine.

Allergy skin prick tests

Allergy skin prick tests were performed using commercially available inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Aspergillus spp., alder, birch, hazel, rye, timothy, mugwort, ragweed, and cockroach; Allergopharma, Germany) and histamine (1 mg/ml, Allergopharma, Germany). None of the subjects had received antihistamines orally in the 3 days preceding the study. All tests included positive (1 mg/ml histamine) and negative (diluent) controls. After 15 min, the mean diameter of any wheal formed by the allergen was compared with that formed by histamine. If the former was the same or larger than the latter (A/H ratio ≥1.0), the reaction was deemed positive. One or more positive tests were considered atopy.

Body mass index

The body mass index for an individual was defined as weight (in kg) divided by the square of height (cm).

Statistical analysis

All data were analyzed using the SPSS version 7.5 for Windows. Data are expressed as mean ± SEM. Comparison of variables was performed using Student's t-test, Mann–Whitney U-test. Pearson's correlations and Spearman's correlations were used to assess relationships between variables. A P-value of <0.05 was considered significant.

Results

Air pollution exposure

The characteristics of the 670 schoolchildren enrolled in the study are given in Table 1. Three hundred and three children living within 2000 m of the chemical factory were considered to live in the polluted area. The outdoor ozone levels in Korea during the 30-day study period in the polluted and coastal areas averaged 23 and 10.5 ppb, respectively (Table 2). SO2 and NO2 levels were also much higher in the polluted area than in the coastal area.

Table 1.  Characteristics of subjects
 Polluted area with chemical factoryCoastal area near chemical factoryRural area
Age10.96 ± 0.0410.95 ± 0.0511.02 ± 0.06
Sex (M/F)147/15694/10281/90
Height (cm)136.9 ± 0.40136.7 ± 0.51137.1 ± 0.53
Weight (kg)31.08 ± 0.4031.15 ± 0.4633.23 ± 0.49
FEV1 (%pred)103.4 ± 0.48103.6 ± 0.61104.1 ± 00.64
FVC (%pred)102.3 ± 0.13102.5 ± 0.59101.9 ± 0.32
FEV1/FVC98.4 ± 0.2499.02 ± 0.7698.6 ± 0.18
Table 2.  Mean values of air pollutants
VariablesMean values
Polluted area with chemical factoryCoastal area near chemical factory
  1. * Eight-hour moving average.

  2. SO2, sulfur dioxide; NO2, nitric dioxide; HF, hydrogen fluoride, irritant.

Ozone* (ppm)0.0230.0105
SO2 (ppm)0.02480.014
NO2 (ppm)0.02440.0085
HF (ppm)0.76640.2145

Symptom prevalence

Of the schoolchildren, 375 (55.9%) had lung symptoms and 434 (64.7%) had nose symptoms. There was significantly more AHR in children with lung symptoms than in those without (6.12 ± 0.45 vs 7.57 ± 0.54, P < 0.04). There was no significant difference in AHR between children with and without nose symptoms.

Atopy

The sensitization rates (skin prick test A/H ≥ 1+) to common inhalant allergens were D. pteronyssinus (DP) 17.9%, D. farinae (DF) 17.4%, cockroach 8.2%, alder 7.1%, birch 5.2%, hazel 3.3%, mugwort 3.3%, timothy 2.8%, rye 2.3%, ragweed 2.2%, and Aspergillus 2.2%. Atopy was significantly more prevalent in the polluted area than in the rural area [35.6% (109/306) vs 23.3% (38/163), P < 0.007]. Atopy prevalence was similar in the rural and coastal areas [23.3% (38/163) vs 27.3% (55/201), P < 0.228].

Airway hyperresponsiveness

All of the children had normal pulmonary function, while 257 (38.3%) had AHR. A significantly greater proportion of children had AHR in the polluted area [45.0% (138/306), 6.50 ± 0.48] than in the rural [31.9% (52/163), 9.84 ± 0.83] or coastal [33.3% (67/201), 7.17 ± 0.68] areas. Schoolchildren with atopy had a lower PC20 than those without atopy (5.98 ± 0.60 vs 8.15 ± 0.45, P < 0.001). In the multiple logistic regression model, positive allergy skin test and living in the polluted area near the chemical factory were independently associated with AHR (odds ratio for location = 2.4875, CI 1.6542–3.7406, P < 0.01; odds ratio for allergy skin test = 1.5782, CI 1.1130–2.2379, P < 0.05), when adjusted for sex, parents’ smoking habits, age, body mass index, nose symptoms, and lung symptoms (Table 3).

Table 3.  Multivariate logistic regression on AHR
VariablesOdds ratio95% confidence intervalP-value
  1. * Stepwise logistic regression was used to select factor significantly associated AHR risk (P < 0.05). All variables in the table were included simultaneously in the logistic regression model.

Allergy skin test*1.61921.1444–2.29080.0065
Parent smoking1.00080.7085–1.4136 
Sex1.02380.7431–1.4105 
Body mass index0.98770.9225–1.0576 
Age0.87550.7134–1.0744 
Polluted area*2.41831.6138–3.62380.0000

Discussion

In this study, we found a statistically significant increase in AHR in children living in a polluted area, implying that controlling air pollution is important for respiratory health in schoolchildren.

The prevalence of AHR has increased over the last few decades and it is generally believed that this is because of environmental factors. Air pollution is convincingly associated with many signs of asthma aggravation, including pulmonary function decrements, increased AHR, visits to emergency departments, hospital admissions, increased medication use, and reported symptoms; it is also associated with inflammatory changes, interactions between air pollution and allergen challenges, and immune symptom changes (9). A significant association between traffic-related air pollution and wheeze has also been reported in children (10, 11), and exposure to diesel-exhaust particles may reduce lung function in children living near motorways. Long-term exposure to ambient ozone has been associated with the development of asthma in adult males (12). Peter et al. (13) observed significant, physiologically important losses in FVC, FEV1, peak expiratory flow rate, and maximal mid-expiratory flow associated with pollution levels in females in 3293 Southern California public schoolchildren and adolescents. Kreit et al. (14) found an enhanced response to a methacholine provocative challenge only in the subjects with asthma after a 2-h exposure to 0.4 ppm ozone. In a meta-analysis, Folinsbee (15) found a small, but significant, trend to increased AHR after controlling for NO2 exposure in subjects with asthma. A significant relationship was found between the mean annual SO2 level and the prevalence of asthma in adults aged 25–29 years (16). In asthmatic children attending school in urban Amsterdam, black smoke was the most important air pollution indicator associated with acute changes in lung function, respiratory symptoms, and medication use (17).

To our knowledge, this is the first epidemiological study to investigate the effects on AHR of air pollution near a chemical factory. In this study, we found that relatively more schoolchildren living near a chemical factory had AHR compared with schoolchildren living further away, suggesting that exposure to air pollution from the chemical factory had led to the development of AHR. However, this study was cross-sectional, and selection effects may have occurred.

In a 6-year follow-up study of children, Sherrill et al. (18) reported that atopy because of house dust mites or cats was related to a lower FEV1/FVC. Low ozone concentrations, similar to those commonly occurring in urban areas, can increase bronchial responsiveness to allergens in atopic subjects with asthma (19). We found that atopy was prevalent in the children from the polluted area compared with the rural area, and schoolchildren with atopy were more likely to have AHR than those without atopy, suggesting that air pollution contributes to increase the prevalence of atopy and that atopy is a risk factor for AHR.

Subjects with asymptomatic AHR had a greater increase in AHR and developed asthma symptoms more frequently than normoresponsive subjects in a 3-year follow-up study (20). Our results must be followed up to further evaluate the risk factors for the development of asthma.

As our study populations consisted entirely of schoolchildren, the results cannot be extrapolated to other populations, such as adults. Nevertheless, our results suggest that air pollution was a potent effect-modifier of AHR in the children living near the chemical factory.

In this study, although the mean ambient air concentrations of ozone, SO2, and NO2 were below recommended levels, the levels of these pollutants were higher in the area near the chemical factory than in the less-polluted areas. This raised the question of whether our observations of AHR could be explained by confounding factors, such as demographics. We, therefore, examined the roles of sex, parents’ smoking habits, age, body mass index, AHR, polluted area, and atopy as risk factors, and the results suggested that air pollution and atopy contributed to AHR in the schoolchildren living near the chemical factory.

Conclusion

Our results suggest that air pollution in the area near the chemical factory affects the development of AHR, and that controlling air pollution is important for preventing the development of asthma. Prospective investigations are needed to further delineate the effects of air pollution on respiratory health.

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