Translational Study on the Relationships Between Body Mass Index, Levels of Serum Inflammatory Factors and Bronchial Asthma in Children
FANG Ding-zhu1, LI Xiao-bin2,*
1. Department of Pediatric Respiration, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200093, China
2. Department of Thoracic Surgery, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China
*Corresponding Author:LI Xiao-bin, E-mail: 18916121438@163.com
Abstract

Objective: To explore the relationships between body mass index (BMI), levels of serum inflammatory factors and bronchial asthma in children.Methods: According to BMI, the enrolled 128 children with asthma in acute-outbreak period were assigned into obese group (n=29), skinny group (n=34) and control group (n=65). The children in three groups were all given routine treatment, including steroid aerosol, bronchodilators, fluid infusion and correction of acidosis, and returned visit after 4 weeks. The asthma control condition, levels of serum inflammatory factors, BMI and childhood asthma control test (C-ACT) scores were compared among three groups, and the relationships between C-ACT scores, BMI and levels of serum inflammatory factors were analyzed.Results: Both completely and partially controlled rates were obviously lower in obese group and skinny group than in control group (P<0.05), but there was no statistical significance between obese group and skinny group (P>0.05). The levels of serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were all higher in obese group than in skinny group and control group, and these indicators above in skinny group were higher than those in control group. The differences were statistically significant (P<0.05 or P<0.01). C-ACT scores increased in sequence among obese group, skinny group and control group, and the differences were statistically significant between two any groups (P<0.01). Correlation analysis revealed that C-ACT scores had a significantly negative correlation with levels of hs-CRP, IL-6 and TNF-α (r=-0.856, P=0.000; r=-0.616, P=0.000; r=-0.296, P=0.001). BMI was not correlated with C-ACT scores and levels of hs-CRP, IL-6 and TNF-α (P>0.05).Conclusion:Both obesity and emaciation can lead to increased levels of serum inflammatory factors in children with asthma, which is adverse to asthma control. Maintenance of normal body weight can effectively decrease the levels of serum inflammatory factors and improve asthma control rate.

Key words: Body mass index; Inflammatory factorsL; Bronchial asthma; Children; Obesity
Introduction

Bronchial asthma, also called asthma, is a common chronic respiratory disease that causes reversible narrowing of the airways because of bronchoconstriction, inflammation and mucus production. It affects 3.4%-12.6% of children and the number of new patients is still growing [1]. Asthma is under the influence of heredity and environment, and its pathogenesis is complicated. An imbalance between pro-inflammatory and anti-inflammatory mechanisms as well as autonomic dysfunction plays an important role in asthma attacks [2]. In recent years, there is increasing evidence that obesity is related to asthma development and severity, and can be considered as an independent risk factor for asthma. Chen et al.[3] found that a high body mass index (BMI) may increase the risk of developing asthma, and could precede asthma symptoms. Furthermore, a dose-response effect of BMI on asthma symptoms has been detected[4]. It is largely unknown whether weight reduction in overweight/obese children can improve clinical symptoms, lung function and amount of medication, or can prevent the development of asthma. Most weight-reduction studies[5, 6, 7] on asthma have been conducted in adults. Ulrik et al. [7]believed that weight reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Nowadays, a handful of studies [8, 9, 10]performed in children provided some interesting evidence that weight reduction can induce beneficial changes in childhood asthma outcomes, including asthma control, asthma-related quality of life (QOL), and improvements in lung function. But until now, there are few studies on the relationships between BMI, inflammatory factors and asthma control. This study mainly investigated the relationships between BMI, levels of serum inflammatory factors and asthma control in children with asthma so as to provide more theoretical evidence for asthma control in clinic.

Materials and Methods
General data

A total of 128 children with asthma in acute-outbreak period were selected in Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October, 2014 to October, 2014. All of them met the relevant standards in Guidelines for the Diagnosis and Management of Asthma in Adults and Children [11], and the disease state was mild at attacks. The children with severe malnutrition, severe complications and psychological problems were excluded. Among 128 children, there were 69 males and 59 females. They were 2-8 years old, with the mean age of (5.6± 1.2) years. According to different BMIs, the children were assigned into obese group (n=29), skinny group (n=34) and control group (n=65). The judging criteria for BMI: < 15 kg/m2 was defined as emaciation, 15-18 kg/m2 as normal, and > 18 kg/m2as obesity. There was no statistical significance by comparison to the general data among three groups (P> 0.05) (Table 1). This study was approved by Ethics Committee of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. All parents signed the informed consent.

Table 1 Comparison of the General Data Among Three Groups (ヌ± S)
Methods

BMI calculation: (1) The children must wear light clothes and go to the toilet. The children’ s body weight was measured by lever-type health meter; (2) The body height was measured using vertical height measure, but the children must be barefoot; (3) Both body weight and height were measured twice in the morning and evening, and the average value was calculated.. BMI=body weight (kg)/body height (m2).

Detection of serum inflammatory factors: Before treatment, the peripheral venous blood 2 mL was drawn from children with empty stomach in three groups, and then the serum was separated after centrifuging 10 min at 2 000 r/min, finally it was preserved in a refrigerator at -20℃. The level of serum high sensitive C-reactive protein (hs-CRP) was detected using immunoturbidimetry, and those of interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α ) using enzyme linked immunosorbent assay (ELISA). All the operations were conducted strictly based on the kit instructions.

Asthma control: The children in three groups were all treated with steroid aerosols and bronchodilators for relieving asthma, stopping cough and resolving phlegm, and meanwhile, routine treatment was also given. For children complicated with infections, corresponding antibiotics were applied timely. All the children insisted on taking drugs. Asthma control was evaluated 4 weeks after treatment.

Observational indexes

The asthma control condition, levels of serum inflammatory factors, such as hs-CRP, IL-6 and TNF-α , BMI and childhood asthma control test (C-ACT) scores were all compared in three groups, and the relationships between C-ACT scores, BMI and levels of serum inflammatory factors were also analyzed.

Judging criteria

C-ACT questionnaire used to assess the asthma control included 7 questions, totally 27 points, in which questions 1-4 were finished by children themselves. Children could ask medical staff for help and then answer the question if they couldn’ t understand. Questions 5-7 were finished by parents. < 19 points, 19-22 points and ≥ 23 points were uncontrolled, partially controlled and completely uncontrolled, respectively.

Statistical analysis

SPSS 17.0 statistical software was applied. The quantitative data were compared by t test and expressed by the mean ± standard deviation (ヌ± S). The enumeration data were compared by Chi-square test and expressed by percentages. The correlation was analyzed using Person correlation test. P< 0.05 was considered to be statistically significant.

Results
The asthma control condition among three groups

Among 128 children, 22 cases (17.2%) were completely controlled, 69 (53.9%) partially controlled, and 37 (28.9%) uncontrolled. Both completely and partially controlled rates were obviously lower in obese group and skinny group than in control group (P< 0.05), but there was no statistical significance between obese group and skinny group (P> 0.05) (Table 2).

Table 2 Comparison of Asthma Control Among Three Groups [n(%)]
Levels of serum inflammatory factors among three groups

The levels of hs-CRP, IL-6 and TNF-α were all higher in obese group than in skinny group and control group, and these indicators above in skinny group were higher than those in control group. The differences were statistically significant (P< 0.05 or P< 0.01) (Table 3).

Table 3 Comparison of Levels of Serum Inflammatory Factors Among Three Groups(ヌ± S)
Comparison of BMI and C-ACT scores among three groups

C-ACT scores increased in sequence among obese group, skinny group and control group, and the differences were statistically significant between two any groups (P< 0.01) (Table 3).

Relationships between C-ACT scores, BMI and levels of serum inflammatory factors

Pearson correlation analysis revealed that C-ACT scores had a significantly negative correlation with levels of hs-CRP, IL-6 and TNF-α (r=-0.856, P=0.000; r=-0.616, P=0.000; r=-0.296, P=0.001) (Figures 1-3). BMI was not correlated with C-ACT scores and levels of hs-CRP, IL-6 and TNF-α (P> 0.05).

Figure 1 Correlation Between C-ACT Scores and hs-CRP Level in Children with Asthma

Figure 2 Correlation Between C-ACT Scores and IL-6 Level in Children with Asthma

Figure 3 Correlation Between C-ACT Scores and TNF-α Level in Children with Asthma

Discussion

Asthma, one of the common chronic respiratory diseases in children, has conspicuous heterogeneity, and its pathogenesis is relatively complicated. Nowadays, it is believed that the occurrence of asthma may be associated with immunity, endocrine levels, neurological function, mental state, heredity and environmental factors [12]. Obesity is one of the health problems related to wrong eating habits in children. It is usually seen when energy intake exceeds energy consumption and it is a clinical condition characterized by increased adipose tissue. During the past 20-30 years, changes of environment and life styles in developed countries have resulted in an increase in the prevalence of obesity and asthma [13]. In obese individuals, proinflammatory adipokines may contribute to asthma and airway hypersensitivity via stimulating airway inflammation or increasing pre-existing inflammation. On the other hand, the pressure on abdominal and chest wall produced by increased adipose tissue in obese individuals may affect asthma symptoms and airway hypersensitivity by some mechanical effects, including airway narrowing and gastroesophageal reflux [14, 15].

In recent years, more and more studies [16, 17, 18] have shown that obesity is a risk factor which increases the prevalence of asthmatic and asthma-related symptoms. By analyzing the relationship between weight status and asthma characteristics in children, Lang et al. [19]found that obesity was more common than underweight status among children with asthma. Both underweight and obese children with asthma have worse lung function and asthma-related outcomes when compared to children with similar normal weight, though the phenotypic characteristics of underweight and obese asthmatics differed considerably. Through examining the differences in quality of life and health outcomes in obese and overweight children with asthma, Manion et al. [20]demonstrated that obese children were at a higher risk of experiencing severe asthma symptoms and supported obesity as a potentially modifiable risk factor for asthma mitigation and prevention. The emerging data have also shown that nonatopic mechanisms may be relevant in obese asthmatics, and that these mechanisms may directly influence the response of obese asthmatics to asthma therapies, especially inhaled glucocorticoids [21]. Ye et al. [22] found that regular inhalation of glucocorticoids could improve the ventilation function of major airways, and have a little impact on the ventilation function of small airways in asthmatics with normal body weight, whereas the obesity could inhibit the improvement effect of glucocorticoids on lung function. C-ACT is a sort of asthma control test questionnaire, suitable for 4-11-year-old children with asthma. It is used to monitor the disease state for a long term, simple in operation and high in feasibly. In this study, both completely and partially controlled rates were obviously lower in obese group and skinny group than in control group, but there was no statistical significance between obese group and skinny group. These results demonstrate that for asthma control, it is very important to strictly control the body weight of children with asthma, and emaciation or obesity is unfavorable to asthma control.

There is a complicated interactional relationship between obesity and asthma. Proinflammatory factors mainly come from adipose tissue, but obesity is a chronic systemic inflammatory disease, characterized by accumulation of adipose tissues in many parts of body and increase of circulating cytokines. Obesity can result in adipocyte hypertrophy, and promote the release of macrophages in adipose tissue. However, expression of macrophages is conductive to gene products in proinflammatory environment, and adipose tissue can produce lots of inflammatory factors, such as interferon, CRP and TNF, which are out of balance in obese children and usually cause chronic inflammatory reactions in the pathogenic process of obesity [23]. Kim et al. [24]found that the increased levels of cytokines, including IL-6, TNF-α and leptin, may be the major pathological basis of obesity-aggravated asthmatic airway inflammation. The effect of obesity on asthma in the study made by Beuther et al.[4] was statistically significant and there was a clear dose-response relationship, and obesity-asthma phenotype is primarily characterized by neutrophil inflammation [25]. Through detection of serum inflammatory factors in children with asthma, this study showed that all the levels of hs-CRP, IL-6 and TNF-α decreased successively among obese group, skinny group and control group, suggesting that the levels of inflammatory factors in obese children were significantly higher than those in normal children, consistent with the research results of Gong et al. [26]. The possible reasons are as follows: (1) Inflammatory environment is present before secretion of adipokines; (2) Obesity-induced insulin resistance results in metabolic disturbance; (3) Obesity-asthma is a new type of asthma, mainly manifesting non-eosinophilic inflammation. C-ACT scores increased in sequence among obese group, skinny group and control group, indicating that the asthma control of children with normal body weight was the best, and that of obese children was the worst. Pearson correlation analysis revealed that C-ACT scores had a significantly negative correlation with levels of hs-CRP, IL-6 and TNF-α ; BMI was not correlated with C-ACT scores and levels of hs-CRP, IL-6 and TNF-α . These results displayed that asthma control had a linearly dependent tendency with levels of inflammatory factors instead of BMI, which might be associated with excessively increased or decreased BMI that impacted asthma control and levels of inflammatory factors [27].

To sum up, both obesity and emaciation can lead to increased levels of serum inflammatory factors in children with asthma, which is adverse to asthma control. Maintenance of normal body weight can effectively decrease the levels of serum inflammatory factors and improve asthma control rate.

Declaration

The authors of this manuscript declare that they have no conflict of interest.

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