Weight reduction improves immune system and inflammatory cytokines in obese asthmatic patients

Abstract Background: Activation of immunological and systemic inflammation markers are common in obesity and asthma. Objective: The target of this study was to assess impact of weight reduction on immunological and systemic inflammation markers in obese asthma patients. Material and methods: Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflammatory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B). Results: The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count . However, findings of group (B) showed no significant changes. Moreover, Comparison between both groups at the end of the study revealed significant differences. Conclusion: Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.


Introduction
Recently, bronchial asthma affects about 300 million subjects and this number will reach 400 million of worldwide subjects by 2025 1 . Asthma characterized with attacks of obstruction, chronic inflammation and airway hyper-responsiveness of airways 2 . However, obesity is a the most common medical problem worldwide 3,4 . Several studies confirm association between the degree of adiposity and asthma [5][6][7] .
Both obesity and asthma prevalence is increasing concomitantly 8 . Obesity elevates the severity of asthmatic symptoms 9 and reduce their response to medications 10,11 , due to many mechanisms include mechanical, anatomical [12][13][14] or inflammatory causes 15,16 . Obesity is considered as a pro-inflammatory state as it is usually associated with persistent low-grade systemic inflammation 17 .
Several studies reported impaired immune system response and high susceptibility for infections and many disorders related to the degree of obesity [18][19][20][21] . In addition, there is close relation between asthma and obesity 22 . Obese adipose tissue is the site of marked accumulation of immune cells [23][24][25] .
Weight reduction intervention is the most recent management policy for control of obesity via exercise, diet regimen and life style modification 26 . The purpose of this research was to measure response of systemic inflammation and immunological parameters to weight loss in obese asthmatic patients.

Subjects and methods Subjects
Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m 2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflam-matory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B) according to the CONSORT diagram that outline the details of the screening and randomization (figure 1). All participants signed the consent before joining the study. In addition, ethical clearance was obtained from the concerned committee of King Abdulaziz University.

Statistical analysis
The statistical analysis was conducted using SPSS version 21 , where comparison between mean values of parameters in both groups was assessed with unpaired t-test .However, paired t-test used to compare the differences between mean values in the same group ( level of significance P<0.05).

Results
The descriptive statistics proved that weight reduction group (group A) or control group (group B) were homogenous as there were no significant differences between both groups regarding the baseline criteria (table  1).
The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count (Tables 2). However, findings of group (B) showed no significant changes (table 3). Moreover, Comparison between both groups at the end of the study revealed significant differences (table 4).

Discussion
Recently, millions of subjects are affected with asthma and obesity, therefore life style intervention is essential for clinical management of these population 28, 29 . The present study aimed to detect to response of systemic inflammation and immunological parameters to weight loss in obese asthmatic patients. The main findings of this study indicated that weight reducing program resulted in modulation of immune system and inflammatory cytokines in asthma patients, our results agrred with manprevious researches [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] .
A study conducted by Dandona et al. approved that TNF-α significantly reduced in obese subjects as result of weight reduction 30 . In addition, Sandoval and Davis found that approved that IL-6 reduced and insulin sensitivity improved following bariatric surgery 31  Another main finding of our study, weight reduction was associated improved immunological parameters, these results agreed with Wasinski et al. reported that weight loss associated with low macrophage and greater number of CD8+ T and CD4+ T cells after exercise and diet control in mice 40 . In addition, Lamas et al. confirmed that one month of diet control significantly reduced body weight improved immunological parameters in overweight rats 41 . Reduction of serum level of pro-inflammatory cytokines as TNF-α , IL-6 and CRP [42][43][44] , in addition to increased anti-inflammatory cytokines as IL-10 may be the mechanism for improved immunological parameters with weight reduction 43 .
The main points of strength in current study were that all exercise sessions were supervised and the randomization of this study . In the other hand, the small sample size in both groups which limit the ability to generalize the findings of this study. Finally, it is recommended to have further studies to detect the impact of life style intervention in another biochemical parameters and quality of life in asthma patients.

Acknowledgment
This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant no. (G-219-142-40). The authors, therefore, acknowledge with thanks DSR technical and financial support.

Conclusion
Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.