Study of vitamins, antioxidant and trace elements on various spirometric parameters and quality of life in patients of bronchial asthma

Introduction: Imbalance between reactive oxygen species and antioxidant defence mechanism produce oxidative stress which further augments and aggravates airway inflammation in asthma. The objective of this study is to find out the effect of antioxidants, trace elements supplementation on pulmonary functions and quality of life in asthmatics. Material and Methods: A prospective, interventional study was conducted in the department of Respiratory Medicine, K.G.M.U., Lucknow. 84 newly diagnosed patients of asthma were recruited. Patients were randomly allocated into two groups using lottery system. One group (A) were given only anti-asthmatic treatment while other group (B) received vitamin, antioxidant, trace element supplementation along with anti-asthmatic treatment. Spirometric parameters (FEV1%) and quality of life were assessed at baseline and at regular intervals and the results were compared between the groups. Results: In our study, males (58.33%) outnumbered females (41.67%). Maximum number of cases were in the age group 1830 (39.29%) followed by 31-40 (25.00%). Mean age of patients was 35.9 ± 13.64 years. Mean ± SD of FEV1% in group A was 72.3 ± 2.7 while in group B it was 72.7 ± 2.9, which showed that there was no statistically significant difference in spirometric parameters post treatment between the two groups (p= 0.3734). Similarly, quality of life also showed insignificant results (total score, p=0.1141). Conclusion: From the results of our study, it was concluded that there was no additional benefit of vitamins, antioxidant, trace elements supplementation on pulmonary functions and quality of life in asthmatic patients.


Introduction
Bronchial asthma is a chronic inflammatory disease of the airways, characterized by hyper-responsiveness and airflow limitation leading to recurrent attacks of breathlessness, wheezing and disease exacerbation which varies in severity and frequency. 1 Its burden on society is enormous and imposes negative impact on the clinical outcome and quality of life of patient.
According to Global Asthma Report (2018) asthma affects approximately 339.4 million people worldwide and the prevalence increases by 50% every decade. 2 The occurrence of asthma deaths are over 80% in low and lower -middle income countries. WHO estimate of asthmatic patients in India is 15-20 million. 3 Globally prevalence of asthma increases by 50% every decade and estimated to range 3-38% in children and 2-12% in adults. 4 Since it is disease with multiple etiologies, currently there is no definite cure for asthma, the disease can only be controlled and improved symptomatically with the help of medications. Inflammation of the bronchus is the hallmark of asthma and studies have shown that oxidative stress augment and aggravates airway inflammation. Imbalance between production of reactive oxygen species and antioxidant defence mechanism produce oxidative stress in the body. 5 Environmental triggering factors make the respiratory tract susceptible to oxidative stress. Reactive oxygen species production as a result of oxidative stress causes inflammation which in turn initiate sequence of events leading to oxidant mediated cellular injury. Studies have shown that patients with asthma are deficient in antioxidants leading to oxidative stress burden and pulmonary dysfunction. 4 Oxidative stress initiated in the airway of bronchial asthma patient because of exogenous and endogenous reactive species leads to epithelial cell injury, induction of transforming growth factor β1 secretion from epithelial cells resulting in remodeling of airway. 5 Antioxidants keep the airway healthy by neutralizing the damaging effects of oxidative radicals. Enzymatic antioxidants such as superoxide dismutases, catalase, glutathione peroxidases require trace elements like Cu, Zn, Se to catalyze free radicals. Non-enzymatic antioxidants such as Vitamin A, E, C and a large group of flavenoids directly react with free radicals and reduce their potency. 4 It has been hypothesized that essential elements may play an important roles in asthma genesis since they take part in oxidative stress reactions as cofactors of antioxidant enzymes.
Intracellular and extracellular fluid in lungs has vitamin C a free radical scavenger that protect against exogenous and endogenous free radicals. 6 It is the most abundant antioxidant substance which contributes to regeneration of membrane bound oxidized vit E to function again and has an antihistaminic effect too. Vit E has a structural role in stablizing membrane. By reducing external attacks in the lung and neutralizing oxidants effects, antioxidants vitamins modulate the development of asthma and the impairment of pulmonary function. 6 Trace elements such as Cu, Zn, Se have an important role in inflammation, oxidant /antioxidant imbalance and may further affect the disease status. Zn has beneficial roles in respiratory epithelium: as an antioxidant, anti-inflammatory agent, antiapoptotic agent, cofactor for DNA synthesis .Se has a crucial role in the inflammatory asthmatic process with the ability to affect the adhesion molecules expression. 7 Severity of airflow limitation, its reversibility, variability and confirmation of asthma can be assessed by measurement of lung function. Spirometry (FEV 1 %) is the most commonly and widespread acceptance methods to assess airflow limitation. 6 Antioxidant and trace element deficiencies seems to be important factors in this regard. There are no clinical trials producing concrete results suggestive of vitamins, antioxidants, trace elements role in clinical outlook of asthma.

Material and Methods
The present study was an interventional study conducted in the Department of Pharmacology At each visit spirometric parameters will be done along with the questionnaire related to any new symptom and improvement in quality of life

Statistical evaluation
Continuous variables are expressed as mean + SD and pre post data gas been compared by student's t test. P values less than 0.05 will be considered as statistically significant.

Results
Demographic and health characteristics 84 patients were studied during the 12 months study period. The age group ranged from 18 years and above (Table 1). Maximum number of cases were in the age group 18-30 (39.29%) followed by 31-40 (25.00%). Majority (64.29%) of the patients were in the age group of 18-40 years. The total number of males in the study was 49 (58.33%) and females were 35 (41.67%) ( Table 2).Mean age of patients was 35.9 ± 13.64 years

Post treatment Spirometric parameters between groups
Post treatment mean ± SD of FEV 1 % in group A was 72.3 ± 2.7 and in group B it was 72.7 ± 2.9 which showed that there was no significant difference in spirometric parameters between the two groups (p= 0.3734).

Relation between vitamins, antioxidant, trace elements supplementation and pulmonary functions:
There was no significant improvement in FEV 1% between two groups (p = 0.3734) which denotes that there was no additional benefit of giving vitamins, antioxidant and trace element supplementation on pulmonary functions and quality of life in asthmatic patients.

Quality of Life Mini asthma quality of life questionnaire (mini AQLQ) for Asthma
Domains of health related to quality of life were expressed as four domains of the mini asthma quality of life questionnaire (mini AQLQ) containing 15 questions grouped under four domains -Symptoms, Activity limitation, Emotional function, Environmental stimuli. Mean score for each domain was calculated pre and post treatment. Total score was recorded as the average of the scores in 15 questions. For both the groups post treatment mean ± SD value of MQLQ domains were compared shown in Table 4.

Discussion
Asthma is a chronic disease associated with inflammation of airways and immuno-allergic abnormality. Studies from past has provided, substantial evidence regarding the role of oxidative stress in the pathogenesis of chronic diseases such as asthma. But its confirmatory role is yet to be established. Studies also suggest that concurrent administration of antioxidants along with the current pharmacological treatment can be beneficial in the long term symptomatic improvement of the disease process. In our study, the age group for asthma ranged from 18 years and above. Maximum number of cases were in the age group 18-30 (39.47%) followed by 31-40 (25.44%). Majority (64.91%) of the patients were in the age group of 18-40 years. According to our study, mean age of 35.9 ±13.64 years favors the fact that disease was common in economically productive age group compared to other ages. Similar finding was shown in study done by Nitant T et al, 8 in Gujarat which showed age group of 13 -64 years were more commonly affected with mean age of 39.8 years. However, finding in a study done by Micheal B et al, 9 in Bengaluru, Karnataka showed 41-60 years as affected age group with mean age of 51.1 years.
Total number of males in the study was 49 (58.33%) which out-numbered female 35(41.27%). The results were comparable with other studies as in by More SR et al, 10 in Maharashtra, showed that 54.5% were male and 45.5% were female. In a study by Arumugam V et al, 11 in Dehradun, 64% were males and 36% were females and in other studies by Puranik A et al, 12 MM Rafeeqet al, 13 Basavaraju et al, 14 Micheal B et al 9 showed similar trend of gender distribution. However, Rajathilagam T et al 15 and Nitant T et al 8 study showed female preponderance of the disease as compared to males. The reason for more males in our study may be attributed to more male to female ratio in Uttar Pradesh. 16 Also, may be female patients are reluctant to utilize health care facilities unless they are critically ill.
In our study post treatment FEV 1 % in group A was 72.3 ± 2.7 and in group B was 72.7±2.9 which showed that there was no significant difference in spirometric parameters between the two groups (p= 0.3734). In a similar case-controlled study conducted by picado C et al, 17 no association was found between bronchial asthma and the intake or the circulating levels of micronutrients or antioxidants. In contrast, cross sectional study by Ochs Balcom 18 showed the association of antioxidant nutrients and markers of oxidative stress with forced expiratory volume in the first second (FEV1%). The study data included 218 persons with chronic airflow limitation showed that serum beta-cryptoxanthin, lutein/zeaxanthin, and retinol, and dietary beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, Vitamin C and lycopene were positively associated with FEV 1 % (P<0.05).
The quality of life was analyzed using Mini asthma quality of life questionnaire (mini AQLQ) in asthma patients and it was found that total mean score post treatment in group A and B were 4.67 ± 0.70 and 4.77± 0.72 respectively. In our study statistically insignificant difference was found in the average total score post treatment (p=0.1141). This signifies that addition of vitamin, antioxidant and trace element supplementation does not improve the quality of life of asthma patient. When compared between the various domains of mini AQLQ, mean score for individual domains also showed insignificant improvement post treatment.

Conclusion
In conclusion, we have not found any significant improvement by vitamin, antioxidant, trace element supplementation on pulmonary functions and quality of life in asthma patients.