|Year : 2019 | Volume
| Issue : 2 | Page : 132-138
Prevalence of Vitamin D deficiency in patients with acute exacerbations of bronchial asthma: A one-year hospital-based cross-sectional study
Srinija Kummaraganti, Gajanan S Gaude
Department of Respiratory Medicine, JN Medical College, Belagavi, Karnataka, India
|Date of Web Publication||4-Jun-2019|
Dr. Srinija Kummaraganti
9-223, Opp. Sarpavaram Police Station, Sarpavaram Junction, Ramanayyapeta, Kakinada - 533 005, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
BACKGROUND AND OBJECTIVES: Bronchial asthma is one of the most common chronic diseases. In India, bronchial asthma has 66% frequency of reported exacerbations. Vitamin D has action on pro-inflammatory mediators and smooth muscle function and proliferation, which has a direct relevance for lung function in asthma. This study was done to investigate the prevalence of Vitamin D deficiency in patients presenting with asthma exacerbations and to assess the correlation between decreased levels and various indicators of severity of exacerbations.
MATERIALS AND METHODS: A total of 118 participants of whom 93 patients had acute exacerbations of bronchial asthma were included in this study. Vitamin D levels were analyzed among different subgroups based on asthma control, severity, and severity of exacerbations. Vitamin D levels were correlated to forced expiratory volume in 1 s (FEV1)% predicted, body mass index (BMI), steroid use, and number of exacerbations in the previous 1 year.
RESULTS: Prevalence of Vitamin D deficiency was 88.2%. Mean Vitamin D (± standard deviation [SD]) level was 12.50 ± 6.41 ng/ml, which was lower than that of patients in remissions (30.61 ± 4.00 ng/ml). Mean FEV1% predicted (±SD) was 54.06% ±15.39%. Patients with severe asthma and uncontrolled asthma had the lowest Vitamin D levels compared to the other subgroups (P < 0.0001). Vitamin D levels were lower in patients with severe exacerbation (8.61 ± 4.16 ng/ml) as compared to mild-moderate exacerbation (17.44 ± 5.25 ng/ml). Vitamin D levels were positively correlated with FEV1% predicted (r = 0.66) and were negatively correlated with BMI (r = −0.89), steroid usage (r = −0.85), and the number of exacerbations in the previous 1 year (r = −0.83). All were statistically significant (P < 0.05).
CONCLUSION: Vitamin D deficiency is highly prevalent in patients during exacerbations of bronchial asthma. It is also associated with lower lung functions and increased number of exacerbations. Thus, improving Vitamin D status might be effective in the prevention and treatment of bronchial asthma and exacerbations.
Keywords: Bronchial asthma, exacerbations, FEV1% pred, severity, Vitamin D
|How to cite this article:|
Kummaraganti S, Gaude GS. Prevalence of Vitamin D deficiency in patients with acute exacerbations of bronchial asthma: A one-year hospital-based cross-sectional study. Indian J Health Sci Biomed Res 2019;12:132-8
|How to cite this URL:|
Kummaraganti S, Gaude GS. Prevalence of Vitamin D deficiency in patients with acute exacerbations of bronchial asthma: A one-year hospital-based cross-sectional study. Indian J Health Sci Biomed Res [serial online] 2019 [cited 2019 Jun 17];12:132-8. Available from: http://www.ijournalhs.org/text.asp?2019/12/2/132/259635
| Introduction|| |
Bronchial asthma is one of the most common chronic diseases worldwide with an estimated affected population of 300 million. The global prevalence of asthma in different countries ranges between 1% and 16% of the population with Indians reported to having 2.9%. Exacerbations of bronchial asthma are episodes characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing, or chest tightness and progressive decrease in lung function, i.e. they represent a change from the patient's usual status that is sufficient to require a change in treatment. About 66% of asthmatics in India report exacerbations every year. Exacerbations accelerate lung function decline and increase the direct costs of asthma, and preventing exacerbations should be an important consideration.
25-hydroxyvitamin D (25[OH]D) has an immunomodulatory action, and its deficiency has been associated with asthma epidemics. Evidence suggests that there might be a cause-and-effect relationship between them. 25(OH)D deficiency has been associated with increased airway hyperreactivity, lower lung functions, poor asthma control, and resistance to steroids., Many studies have reported 80%–90% prevalence of Vitamin D deficiency in bronchial asthma., Very few studies have reported the clinical significance of Vitamin D in exacerbations of asthma. Therefore, the present study was done to prospectively investigate the prevalence of Vitamin D insufficiency and its deficiency in patients with bronchial asthma presenting with exacerbations and to assess the correlation between decreased Vitamin D levels and various indicators of severity of exacerbations of bronchial asthma.
| Materials and Methods|| |
A total of 93 consecutive patients with a diagnosis of exacerbation of bronchial asthma and 15 patients in asthma remission according to the GINA 2016 guidelines presenting to the Department of Respiratory Medicine at KLES Dr. Prabhakar Kore Hospital and Medical Research Centre (Belagavi, India) were included in the study. Ten healthy individuals were taken as controls. Patients were divided into groups based on the severity of asthma as mild, moderate, and severe and into well controlled, partly controlled, and uncontrolled, depending on the control of the disease according to the GINA 2016. Asthmatics in exacerbations were divided into mild-moderate, severe, and life threatening based on symptoms at the time of presentation according to the GINA 2016 guidelines. Patients admitted with repeated exacerbations of bronchial asthma during the study period were enrolled only once, and the number of exacerbations was recorded. Patients on barbiturates, bisphosphonates, sulfasalazine, omega-3, and Vitamin D supplements; patients with asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome; diabetics; smokers; and patients who have a comorbid disease in addition to bronchial asthma that could affect Vitamin D levels such as rheumatoid arthritis, cystic fibrosis, multiple sclerosis, ulcerative colitis, Crohn's disease, celiac disease, osteomalacia, sarcoidosis, and thyroid dysfunction were excluded.
25(OH)D levels: Two milliliters of venous blood was obtained from each patient and centrifuged; serum was separated and stored at −20°C until assayed for Vitamin D levels. Serum level of 25(OH) D was measured using the immunodiagnostic enzyme immunoassay. Vitamin D levels were categorized as sufficient (>30 ng/ml), insufficient (20–30 ng/ml), and deficient (<20 ng/ml).
Spirometry was performed according to the standard guidelines and forced expiratory volume in 1 s (FEV1)% was recorded.
Serum 25(OH)D levels were analyzed among different subgroups based on asthma control, severity, and severity of exacerbations. The Vitamin D levels were correlated to FEV1% predicted, patient's body mass index (BMI), steroid use, and number of exacerbations in the previous 1 year.
Approval of this study was received from the Institutional Ethical and Research Committee, and written informed consent was obtained from all the participants.
The data obtained were entered into the Microsoft Excel spreadsheet. The results of the study were analyzed and presented as numbers, percentages, or mean ± standard deviation. The categorical data were analyzed using unpaired t-test for 2 groups and ANOVA for >2 groups. Karl Pearson's correlation was used for continuous quantitative variables. MedCalc for Windows, version 17.0, (MedCalc Software, Acacialaan 22, 8400 Ostend, Belgium) was used for the analyses. P < 0.05 was taken as statistically significant.
| Results|| |
A total of 108 patients with bronchial asthma were included in the study out of which 93 were having exacerbations and 15 were in remission. 10 were healthy volunteers. According to the severity of asthma there were 15 patients with mild asthma, 33 with moderate asthma and 45 with severe asthma. Seven patients had well-controlled asthma, 45 had partly controlled asthma, and 41 had uncontrolled asthma. Forty-one patients had mild-moderate exacerbation and 52 had severe exacerbation. Forty-two patients required an increase in inhaled steroids for control of the exacerbation, but 51 required systemic steroids [Table 1].
In patients with exacerbations, Vitamin D deficiency was observed in 88.17% of the patients and insufficiency in 9.68% [Table 2].
|Table 2: Prevalence of Vitamin D deficiency in asthmatics in exacerbations|
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Mean Vitamin D levels in patients with asthma exacerbations were 12.50 ± 6.41 ng/ml, 30.61 ± 4.00 ng/ml in asthmatics in remissions, and 34.91 ± 5.82 ng/ml in healthy population (P < 0.0001). The mean FEV1% predicted in asthmatics in exacerbations was 54.06% ±15.39%, in patients with remissions was 66.27% ±11.40%, whereas healthy individuals had FEV1% predicted of 89.80% ±5.82%, (P < 0.0001). The mean BMI in patients with exacerbations was 33.58 ± 4.19 kg/m2, whereas patients in remissions had BMI of 22.15 ± 1.94 (P < 0.0001) [Table 3].
Mean Vitamin D level in patients with mild asthma was 20.38 ± 6.06 ng/ml, moderate asthma was 14.49 ± 3.38 ng/ml, and severe asthma was 8.42 ± 4.96 ng/ml, which was statistically significant between all the groups (P < 0.0001). Mean Vitamin D level in patients with well-controlled asthma was 25.02 ± 5.24 ng/ml, partly controlled asthma was 15.19 ± 3.69 ng/ml, and uncontrolled asthma was 7.42 ± 3.65 ng/ml, which was statistically significant between all the groups (P < 0.0001). The mean Vitamin D level in mild-moderate exacerbation was 17.44 ± 5.25 ng/ml, whereas in severe exacerbation, it was 8.61 ± 4.16 ng/ml, which was highly significant (P < 0.0001) [Table 4].
There was a significant association between higher Vitamin D levels and better lung function as measured by FEV1% predicted, where P < 0.0001 [Table 5]. Vitamin D levels are positively correlated with FEV1% predicted, with a Karl Pearson's correlation coefficient r = 0.656 [Figure 1].
|Figure 1: Vitamin D levels are positively correlated with forced expiratory volume predicted in 1 s, with a Karl Pearson's correlation coefficient r = 0.656|
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Patients who required only an increase in the dose of inhaled steroids had a mean Vitamin D levels of 17.42 ± 5.27 ng/ml, whereas patients requiring systemic steroids to treat the exacerbation had a mean Vitamin D level of 8.45 ± 3.97 ng/ml (P < 0.0001) [Table 4]. Patients who required a medium-dose inhaled steroid to treat their exacerbation had a mean Vitamin D level of 20.55 ± 4.84 ng/ml, whereas those who required high dose had a mean level of 13.25 ± 1.76 ng/ml.
There was a strong negative correlation between Vitamin D levels and BMI (Karl Pearson's correlation coefficient r = −0.892), inhaled steroids or cumulative dose of systemic steroids required for the treatment of exacerbations (r = −0.693, r = −0.848), and the number of exacerbations in the previous year (r = −0.832) [Figure 2], [Figure 3] and [Table 6].
|Figure 2: Vitamin D levels and body mass index were negatively correlated with Karl Pearson's correlation coefficient r = −0.892|
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|Figure 3: Vitamin D levels and cumulative dose of systemic steroids required to treat the exacerbation were negatively correlated with r = −0.848|
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| Discussion|| |
Vitamin D has a significant impact on respiratory system as it can influence immunity and cell functions. The ability of lung epithelial cells to synthesize active Vitamin D by 1-α hydroxylase and the presence of Vitamin D receptor polymorphisms support this hypothesis. Studies have demonstrated an association between lower Vitamin D levels and many lung diseases including respiratory tract infections, rhinosinusitis, COPD, tuberculosis, and bronchial asthma. Many studies have linked Vitamin D deficiency with asthma exacerbations.,
Sun exposure is the major source of Vitamin D. Vitamin D metabolism is affected by various factors such as age, skin pigmentation, obesity, and chronic illnesses. Sedentary lifestyle and dietary changes have caused an increased prevalence of Vitamin D insufficiency and deficiency in the general population. In our study, Vitamin D deficiency was found in 75.92% of the patients with bronchial asthma and in 88.17% of the patients in exacerbations. It is in agreement with studies by Li et al. and Montero-Arias et al. who reported around 80%–90% prevalence of Vitamin D deficiency in patients with bronchial asthma. The low levels can be attributed to limited sunlight exposure due to outdoor activity limitation in patients with bronchial asthma.
Vitamin D plays an important role in bronchial asthma through its role in innate and adaptive immunity. Vitamin D protects against aeroallergen-stimulated asthma by promotion of tolerogenic dendritic cells, enhanced regulatory T (Treg) cell action to suppress inappropriate Th2 responses, reduced immunoglobulin E synthesis by B-cells, increased interleukin-10 (IL-10) secretion, and decreased mast cell activation. Vitamin D also decreases the synthesis of cytokines such as IL-17, which has distinct features in steroid-resistant asthma. Vitamin D could also be involved in asthma pathogenesis through effects on bronchial and vascular smooth muscle, which lead to airway remodeling., In this study, serum Vitamin D was less in asthmatics (16.70 ± 10.20 ng/ml) compared to healthy individuals (34.91 ± 5.82 ng/ml) with P < 0.0001, which was statistically significant. This finding was similar to that by Shebl et al., Samrah et al., and El Aaty et al. who found a significant difference (P < 0.05) in Vitamin D levels between asthmatics and healthy individuals.
Vitamin D has antimicrobial actions by activating antimicrobial peptides such as cathelicidins and defensins. Cathelicidin is known to be active against a wide range of bacteria, viruses, mycobacteria, and fungi, and its deficiency is related to a higher susceptibility to infection and asthma exacerbations. Viral infections trigger IL-33 release. Vitamin D inhibits IL-33 actions and decreases innate lymphoid cell-2 stimulation and production of IL-5, thereby decreasing eosinophilic inflammation and exacerbations. Observational studies also have shown that Vitamin D deficiency contributes to increased respiratory tract infections and causes asthma exacerbations. In our study, patients in asthma exacerbations had much lower levels (12.50 ± 6.41 ng/ml) compared to asthmatics in remission (30.61 ± 4.00 ng/ml) with P < 0.0001. El Aaty et al. showed that Vitamin D levels were lower in asthmatics with severe exacerbations (mean: 17.28 ng/ml) as compared to asthma in between attack groups (mean: 29.66 ng/ml). The present data showed that Vitamin D levels were negatively correlated (r = −0.83) with the number of exacerbations in the past 1 year. The lesser the Vitamin D levels, more were the number of exacerbations. Brehm et al. reported that Vitamin D was the strongest predictor of the number of hospitalizations in bronchial asthma. Studies by Samaha et al., Gupta et al., and Solidoro et al. also confirmed the same.
The Vitamin D levels differed significantly according to control and severity of the disease, with the least levels observed in severe (8.42 ± 4.96 ng/ml) and uncontrolled (7.42 ± 3.65 ng/ml) asthma. This is similar to studies by Samrah et al. and Krishnan et al. who found a statistically significant relation between asthma severity, control, and Vitamin D status. The strong correlation between Vitamin D levels and asthma severity and control suggests an impact of its hormonal effects on the pathogenesis of bronchial asthma. Reduced Vitamin D levels are associated with increased expression of pro-inflammatory cytokines and thus have pro-inflammatory effects in asthma. It also complements the action of glucocorticoids and reduces steroid resistance. We hypothesize that there might be a dose-response relationship between Vitamin D levels and asthma severity and control. Severe asthma might be due to greater Vitamin D deficiency causing increased steroid resistance and thus requirement of higher dose of steroids for control of asthma. Lower Vitamin D levels might cause more inflammation and remodeling, leading to poorer asthma control.
Chronic inflammation negatively influences lung function by increased hyperresponsiveness. Vitamin D inhibits airway inflammation, fibroblast proliferation, and smooth muscle hypertrophy, thus reducing airway remodeling. We found a positive correlation (r = 0.66) between serum Vitamin D levels and FEV1% predicted, measured on spirometry. Similar results have also been found by Korn et al., El Aaty et al., Brumpton et al., and many others.,
Literature states that adipocytes accumulate cytokines and chemokines, which can lead to inflammation. Vitamin D can also get sequestrated in the adipose tissue. Our study also revealed a significant negative correlation (r = −0.89) between higher BMI levels and lower Vitamin D levels, indicating that obesity and bronchial asthma are related via Vitamin D. This finding is consistent with results from studies by Shebl et al., Korn et al., and Sutherland et al. Thus, weight reduction measures might improve asthma control and severity of exacerbations.
Airway colonization with bacteria such as Haemophilus influenzae, oxidative stress, and Vitamin D deficiency itself are major causes for acquired steroid resistance in asthma. Vitamin D enhances antimicrobial pathways and also promotes antioxidant responses. Steroid-insensitive patients have impaired production of IL-10, and Vitamin D increases IL-10 secretion through its actions on Treg cells. Obesity itself is also associated with an impaired response to glucocorticoids and reduced Vitamin D levels in overweight and obese patients which might contribute to reduced steroid response in them. When the relationship between Vitamin D levels and response to steroids was studied, it was found that asthmatics with lower Vitamin D levels required higher dose of steroids to treat exacerbations, and there was a negative correlation between the dose of systemic steroids and levels of Vitamin D (r = −0.85). This finding is in agreement with Gupta et al. who reported that steroid-resistant asthma has lower levels of Vitamin D than others. Brehm et al. also reported similar results.
With this background, trials have started to see if supplementation of Vitamin D reduces the number of exacerbations of asthma. Vitamin D supplementation improved control and severity of asthma in randomized control trials done by Menon et al. and Tachimoto et al. Higher FEV1, forced vital capacity (FVC), and FEV1/FVC and lower cytokine indices were observed when Vitamin D was supplemented. There was decreased asthma recurrence and re-hospitalization rate, suggesting that Vitamin D supplementation increases asthma control rate and improves lung functions., As Vitamin D deficiency in pregnancy is associated with increased incidence of respiratory infections and asthma in the newborn, supplementation during pregnancy might have beneficial effects on infant respiratory outcomes by modifying the immune system.
Strengths of the study
Many of the studies available are related to Vitamin D influencing the severity and control of asthma, and most of them are in children. Studies in patients presenting with exacerbations are very few, and this study can contribute to further literature on this topic.
Limitations of the study
The patients included are from a large tertiary care referral center and therefore might not be a representative of the overall asthma population. Serum Vitamin D was measured only once and was not compared to that in the period of remission in the same patient. Vitamin D can have seasonal fluctuations, with lower concentrations in the winter, which was not taken into consideration. The ability to convert pre-Vitamin D3 to active Vitamin D diminishes with age. Adjustment for age was not done, which might have affected the Vitamin D levels. Unequal sex distribution is a limiting factor. Furthermore, asthmatics spend more time indoors and thus have less physical activity and less exposure to sunlight, which are confounding factors. Obesity affects Vitamin D levels independently, which is also a confounding factor. Dietary habits of patients over the past 3–4 weeks were not considered, which might have affected Vitamin D levels.
| Conclusion|| |
Vitamin D deficiency was highly prevalent in patients with exacerbations of bronchial asthma in North Karnataka. It was associated with increased number and severity of exacerbations, poorer asthma control, lower lung functions, and higher BMI. Future randomized control trials should determine if supplementation of Vitamin D has a significant positive effect in decreasing the severity and number of exacerbations of bronchial asthma.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]