Obesity and the prevalence of asthma have increased over the past decade 1. Obesity causes serious health problems, particularly when present during childhood 2. Epidemiologic data indicate that obesity increases the prevalence and incidence of asthma and reduces asthma control 3,4. Recent studies have attempted to demonstrate an association between obesity and asthma 5–7. Asthma comprises diverse ‘phenotypes’ reflecting heterogeneity in a number of characteristics, including response to therapy. Recently published data suggest that obese adult patients with asthma may represent a distinct phenotype of asthma 1. The release of various cytokines and mediators such as IL-6, TNF-α, eotaxin, and leptin by adipocytes, as well as the reduction of anti-inflammatory adipokines in obese patients may possibly contribute to the development or increased clinical expression of asthma in promoting airway inflammation 8. The objectives of our study were to compare the characteristics and severity of asthma in obese and nonobese Egyptian children with asthma and to explore serum eotaxin level as a link between obesity and asthma.
Twenty-four nonobese asthmatic and 26 obese asthmatic children were included in the study. Informed consents were obtained from the parents of our study groups according to the guidelines of the ethical committee of the National Research Centre, Egypt. We recruited asthmatic obese and nonobese children from the Pediatrics outpatient clinic of the National Research Centre and Endocrine and Asthma outpatient clinics, El-Hussein Hospital – AL-Azhar University during the period between December 2007 and January 2009. Participants were eligible if they had physician-diagnosed asthma. Obese asthmatic children had BMI greater than or equal to 95th percentile whereas nonobese asthmatic children had BMI within the 85th percentile 9. Children who refused to provide informed consent, or had secondary obesity such as Cushing syndrome, children with obesity because of corticosteroid therapy or hypothyroidism or those with dysmorphic features suggestive of syndromes (e.g. Laurence–Moon–Biedl or Prader Willi), or received drug therapy that could interfere with the proposed tests were excluded.
All the children in the study were subjected to the following: a full history taking including the complete present history, with particular emphasis on episodes of wheezes, cough, dyspnea, nocturnal symptoms, allergic history, history of medication, and history of other systemic disease; social history including (housing condition, pets) family history and past history; and clinical examinations, both general and systemic, with particular emphasis on weight (Wt) and height (Ht) and BMI, which was calculated by dividing the person’s weight (kg) by the square of the height (m) kg/m2, with BMI plotted on Egyptian growth curves 10. Waist and hip circumferences were measured according to the WHO criteria: with participants wearing light clothing, waist circumference was measured at the level midway between the lowest rib margin and the iliac crest. Hip circumference was measured at the widest level over the greater trochanters in a standing position and then calculating the waist–hip ratio. Measurement of skin fold thickness, particularly around the triceps, subscapular, and abdominal skin fold thickness, was carried out.
For basal respiratory function test parameters, vital capacity (VC) forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow rate (PEFR) were determined using a Fleisch spirometer (Vitalograph Ltd., Buckingham, UK). We used % predicted values for comparison between groups.
Five milliliters of blood was withdrawn from the anticubital vein after a fast of 12–14 h under aseptic conditions.
Complete blood profile was determined. After centrifugation, serum was collected from each patient to evaluate the following:
- Lipid profiles (total cholesterol, HDL-cholesterol, LDL-cholesterol, TG) in the sera were determined using a chemistry analyzer Olympus AU 400.
- Thyroid hormone (in order to exclude cases of hypothyroidism from the study).
- Serum eotaxin level was assessed using the human serum eotaxin kit (LOT 7J12/1) manufactured by Invitrogen Corporation (http://www.invitrogen.com). The Invitrogen Hu Eotaxin kit is a solid-phase sandwich enzyme-linked immunosorbent assay 8.
Data were statistically presented in terms of range, mean±SD, median, frequencies (number of cases), and percentages when appropriate. Comparison of quantitative variables between the study groups was carried out using the Mann–Whitney U-test for independent samples. Spearman’s correlation coefficient ρ was used to determine the correlation between nonnormally distributed continuous variables. The χ2 test or Fisher’s exact test was used to compare between independent proportions. Linear regression analysis was carried out to determine the relationship between eotaxin as a dependent variable and independent variables (LDL, TG, cholesterol, waist circumference, triceps abdominal, subscapular skin fold, BMI). A probability value (P-value) less than 0.05 was considered statistically significant. All statistical calculations were carried out using computer programs SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA) version 15 for Microsoft Windows.
This study included 50 asthmatic children, among whom 26 were obese (13 males and 13 females) and 24 were of normal weight (14 males and 10 females). The obese asthmatic children ranged in age from 7 to 15 years, mean age 10.38±1.81 years, whereas asthmatic nonobese children ranged in age from 7 to 13 years, mean age 9.58±1.74 years, with no statistical variations in age or sex. Patients with asthma were classified according to the Global Initiative for Asthma guideline classification of asthma severity by clinical features 11. In the obese asthmatic group, no child had intermittent asthma, seven (27%) children had mild persistent asthma, 18 (69%) children had moderate persistent asthma, and one (4%) children had severe persistent asthma, whereas, in the nonobese asthmatic group, four (16.7%) children had intermittent asthma, 17 (70.8%) children had mild persistent asthma, three (12.5%) children had moderate persistent asthma, and none had severe persistent asthma. In terms of the severity of asthma, we found a significant difference among the groups (P-value<0.05), with mild, moderate, and severe persistent asthma mostly present in obese asthmatic children in contrast to intermittent asthma, which was mostly present in nonobese asthmatic children. Comparison of clinical and social data in obese asthmatic and nonobese asthmatic groups is shown in Table 1.
Regarding the patterns of asthma symptoms, we found that there was more seasonal exacerbation in the obese asthmatic group, showing a significant difference from the other group (P-value<0.05). For nocturnal and exercise-induced patterns, there were no significant differences between both the groups (P-value<0.05). In terms of the symptoms of asthma, both groups showed a nonsignificant difference (P-value>0.05), with a significant difference between both the groups (P-value<0.05). In the social data, we found a positive family history in 30.8% of obese asthmatic children and in 50% of nonobese asthmatic children, with no significant difference between the two groups (P-value=0.248). Also, in the obese asthmatic group, 19.2% had a history of exposure to smoking and 7.6% had pets, whereas in nonobese asthmatic children, 20.2% had a history of exposure to smoking and 4.2% had pets, with no significant difference between both the groups (P–value>0.05).
Other results of the comparative study are shown in (Tables 2–4). No significant variation was found in the total leukocyte count or the eosinophilic count between obese asthmatic and nonobese asthmatic children.
Our study showed a statistically significant elevation of both systolic blood pressure and diastolic blood pressure in the obese asthmatic group than in the nonobese asthmatic group (P<0.05 and <0.001, respectively).
The % predicted value of vital capacity was significantly lower in obese asthmatic children than in nonobese asthmatic children (P<0.01). In terms of the % predicted value of FEV1, FEV1/FVC, and PEFR, no statistical difference was found between the two groups. It was also found that there was a statistically significant elevation of both TG 131 mg/dl (133.54±14.07) and cholesterol 200 mg/dl (195.77±17) in the obese asthmatic group than in the asthmatic group 140 mg/dl (140.92±23.16). In terms of LDL, HDL, and the LDL/HDL ratio, the mean values were found to be higher in obese asthmatic children than in asthmatic nonobese children.
The mean serum eotaxin level in the obese asthmatic group was 340 (359.58±71.404 pg/ml), which was higher than that in the nonobese asthmatic group (P<0.001), in which the mean serum eotaxin level was (274.79±20.407), with a median value of 275 pg/ml.
Regarding correlation, serum eotaxin level was positively correlated with BMI (P<0.000, r=0.55), waist circumference (P<0.001, r=0.49), hip circumference (P=0.001, r=0.45), triceps skin fold thickness (P<0.001, r=0.60), subscapular skin fold (P<0.000, r=0.61), abdominal fat thickness (P<0.001, r=0.57), LDL (P<0.001, r=0.60), cholesterol (P<0.001, r=0.58), and TG (P<0.001, r=0.52), but there was no significant correlation with the waist-to-hip ratio.
Table 5 shows the results of linear regression. Regression analysis shows that LDL is the strongest predictor of serum eotaxin level.
Mild, moderate, and persistent asthma were statistically significantly present in obese asthmatic children, whereas an intermittent pattern of asthma was presented in nonobese asthmatic children. This result agrees with that of Litonjua and Gold 6, who reported that being overweight, especially obese (BMI≥30), was a risk factor for developing asthma and obese children were likely to have more severe asthma than nonobese children. Also, Dolan et al. 12 and Mosen et al. 13 showed that obesity was associated with more severe asthma phenotypes and may also be associated with worse asthma symptoms and outcomes, with an increased risk of asthma-related hospitalization.
Our study showed a significant increase in blood pressure (systolic and diastolic) in obese asthmatic children than in nonobese asthmatic children. Our result was in agreement with that of Ribeiro et al. 14, who found that obesity causes elevation in the systolic blood pressure and a minimal change in diastolic blood pressure, wwhereas there were no significant differences in blood profiles between obese and nonobese asthmatic children.
Body size affect the pulmonary function test (PET), this may explain the decrease in PET detected in our obese asthmatic children. Body size has a huge effect on PFT values. If patients are too obese, the abdominal mass prevents the diaphragm from descending as far as it can and the PFT results will show a smaller measured PFT outcome than expected. Our result was in agreement with that of other studies 15,16.
We found a higher TG level, cholesterol level, LDL, and LDL/HDL ratio in obese asthmatic children than in nonobese asthmatic children. This result agrees with that of Lai et al. 17, who showed that obesity was associated with hypertriglyceridemia, a high level of LDL cholesterol, but not HDL, which was low. Our result also agrees with that of Miller et al. 18, who found that obesity during childhood and adolescence is associated with a number of cardiovascular risk factors, including hypercholesterolemia, hypertriglyceridemia, hypertension, and reduced levels of HDL.
Eotaxin level was significantly higher in the obese asthmatic group than in the nonobese asthmatic group. Eotaxin, a chemokine, is important in extrinsic asthma, as it causes an inflammatory disorder and is a key chemotactic agent responsible for eosinophil-mediated bronchial inflammation 19. Serum eotaxin levels in humans have been shown to be associated with the presence and severity of asthma. Increased eotaxin levels with obesity are one of the factors that lead to the increased frequency and severity of asthma in obese individuals 20. Also, some authors showed that circulating levels of eotaxin in serum/plasma are increased by diet-induced obesity in humans 8,21. Dulkys et al. 22 reported that serum eotaxin levels were higher in obese patients and adipose tissue levels correlated positively with serum eotaxin levels. Adipose tissue biopsy from obese patients showed increased secretion of eotaxin compared with biopsy from lean patients. In obese patients, plasma eotaxin levels were higher than that in lean controls and reduced significantly after weight loss, and eotaxin levels were four-fold to seven-fold higher in visceral than in subcutaneous adipose tissue.
No correlation was found between the serum eotaxin level and general adiposity. This was in contrast to the result of Vasudevan et al. 8, who confirmed the correlation between obesity and an increasing level of serum eotaxin. No correlation was found between serum eotaxin level and PFT. In contrast, we found that eotaxin level was statistically significantly correlated with BMI, skin fold thicknesses, and waist and hip circumference. Shore 23 suggests that elevated systemic levels of eotaxin derived from adipose tissue could contribute to the signs and symptoms of asthma by promoting allergic inflammation in the lung and possibly by directly altering the airway to become more hyperresponsive.
Regression analysis was carried out to determine the relationship between eotaxin as a dependent variable and independent variables LDL, TG, cholesterol, waist circumference, triceps abdominal, subscapular skin fold, and BMI. Interestingly, it was found that LDL alone represents the strongest causal relationship with eotaxin. To our knowledge, this is the first study evaluating the causal relationship of LDL with eotaxin in obese and nonobese asthmatic children. This could explain the results obtained by Cottrell et al. 24, who found a statistically significant association between asthma and an abnormal lipid profile.
Conflicts of interest
There are no conflicts of interest.
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