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Original Research (Original Article) 


Montasir Esam Moamena et al, 2019;3(8):654–658.

International Journal of Medicine in Developing Countries

Association between vitamin D deficiency and asthma control test in adults: a cross-sectional study in a college hospital in Jeddah, Saudi Arabia

Montasir Esam Moamena1, Hayfaa Mirghani Ahmed1, Motasim Esam Moamena2, Zahra Saeed Alduhilib1, Nameer Mohammed Alshinqeeti1, Hanaa Elsayed Abozeid3

Correspondence to: Hanaa Elsayed Abozeid

*College of Medicine, Ibn Sina National College, Jeddah, Saudi Arabia.

Email: hanaa1974.abuzeid [at] gmail.com

Full list of author information is available at the end of the article.

Received: 01 December 2018 | Accepted: 08 April 2019


ABSTRACT

Background:

The deficiency of vitamin D has been associated with an increased risk of asthma. However, its relation with asthma severity or prognosis is not yet established, especially among adults.


Methodology:

The cross-sectional study included 162 Saudi adults with bronchial asthma selected by a non-probability consecutive sampling from Ibn Sina National College Hospital in Jeddah, Saudi Arabia, from December 2017 to February 2018. Data were collected using a structured questionnaire and a baseline spirometry. Assessment of asthma control test (ACT) was done according to global initiative for asthma guidelines. The 25-hydroxyvitamin D [25(OH) D] was analyzed using enzyme-linked immunosorbent assay test.


Results:

The patients had a median ACT score of 19 (partially controlled asthma) with 48.1% controlled asthma and 22% increased the risk of future exacerbations. The median 25(OH) D was deficient (31.18 nmol/l) (34% insufficiency and 66% deficiency). There was a significant positive correlation between vitamin D and ACT (r = 0.91, p = 0.000). Asthmatics with future exacerbation had lower 25(OH) D level (p = 0.000) with more prevalence vitamin D deficiency (94.4%).


Conclusion:

Saudi adults with partially uncontrolled asthma had deficient vitamin D level, especially those at risk of future exacerbation. The association between ACT and vitamin D in the absence of any association with respiratory function could reflect the importance of low vitamin D as a marker of severity. Further clinical trials are needed to explore the possible cause and effect relationship.


Keywords:

Vitamin D, 25-hydroxy vitamin D, asthma, ACT.


Introduction

Vitamin D has been linked with several inflammatory diseases including asthma, probably due to its potent immunomodulation [1,2]. Still, vitamin D deficiency and insufficiency are prevalent worldwide even among sunny countries like Saudi Arabia [3]. The role of vitamin D in the pathophysiology of asthma has been studied in detail in many animals and human subjects but still remains a topic of debate among clinicians and scientists. In asthma subjects, low vitamin D levels in serum were found to be associated with increased inflammation, increase in exacerbations, decreased lung function, with the overall poor outcome [46]. Moreover, a link between vitamin D, asthma exacerbation and treatment resistance has also been reported by various study groups [710]. However, clinical trials using vitamin D supplementation have a disappointing effect on improvement of symptoms or onset of asthma [11,12]; few studies have reported some promising protective effects [810]. Obviously, there is a need to characterize the strength and the relation between clinical parameters of asthma and low vitamin D level in order to improve the construction of clinical trials of supplementation. Moreover, few studies suggested that there is no association between vitamin D level and asthma or its severity markers in adults in contrast to results seen in children [13]. The present study employed the asthma control test (ACT) as a tool to assess asthma control in the study subjects. The global initiative for asthma (GINA) [13,14], ACT is a commonly used tool to assess asthma control. The ACT uses a validated, self-administered, and short, questionnaire to assess the control of asthma. The questionnaire consists of five items: shortness of breath, use of rescue medication, limitation of activity, the frequency of night symptoms, and the overall control rate over the past 4 weeks. The score ranges from the worst (one point) to the best (five points) for each item with a maximum score of 25. The level of asthma control is classified into uncontrolled (<16), controlled (≥20), and partially controlled (16–19). The clinically significant changes in ACT score are considered to be ≥3 units. The current work was aimed at examining the serum levels of vitamin D among adults with asthma in relation to their disease severity and response to treatment.


Subjects and Methods

A cross-sectional study was carried out at the outpatient clinics in Ibn Sina National College for Medical Studies (ISNC), Jeddah, Saudi Arabia. Sample size calculation was done using open Epi [Version 3.04.04; 154 participants; power 80%, two-sided significance (1-alpha) 95, and pattern of exposed with the outcome: 20]. The sample size was further increased to 162 to compensate for any missing data. The study was approved by the local ethical committee at ISNC. Verbally informed consents were obtained from all the subjects prior to their participation in the study. Adult Saudis with bronchial asthma attending the medicine or chest clinics were selected by a non-probability convenient sampling with consecutive technique. Exclusion criteria included patients with current oral corticosteroids therapy, cigarette smoking, endocrine disorders, diabetes, or on drugs that could have an effect on bone (antiepileptic, antidepressants, vitamin D, and calcium). Selected participants were subjected to clinical history collection, pulmonary function test, chest X-ray, physical examination, and asthma control test. The risk of future exacerbation was also assessed. Using a structured questionnaire, demographic data (age, gender, and occupation) and bronchial asthma history were noted in detail (duration, provocations, frequency, and severity) with giving special emphasis to current medications of bronchial asthma. ACT was done according to GINA guidelines. The Global Strategy for Asthma Management and Prevention was used to assess for asthma exacerbation [13]. The risk was increased if one or more of the following were present: high use of relievers, inadequate corticosteroid inhalers, low forced expiratory volume in 1 second (FEV1), previous admission to intensive care unit, history of severe asthma exacerbation in the last 12 months, continuous exposure to allergens, reduced socioeconomic status or any major psychological disorders, eosinophilia or sputum eosinophils, pregnancy, and the presence of comorbidities. The pulmonary function test was performed according to the American thoracic society criteria [15] by using the electronic spirometer (Master Screen IOS; Jaeger, Höchberg, Germany). Patients were instructed to discontinue their short-acting bronchodilators 6 hours before the test. The test included forced vital capacity (FVC), FEV1, and their ratio FVC/FEV1. After overnight fasting, blood samples were drawn by venipuncture between 8:00 and 10:00 AM, in the winter season of December 2017 to February 2018 under complete aseptic condition. The samples were left in a plain tube at room temperature for 30–60 minutes for spontaneous clotting. Then, they were centrifuged at 3,000 rpm for 10 minutes for serum separation. The separated serum was kept at −70°C for freezing immediately until further future analysis of serum levels of 25 hydroxy vitamin D [25(OH)D] using the enzyme-linked immunosorbent assay technique with the available commercial kit. Vitamin D deficiency was defined if 25(OH)D level was of less than 50 nmol/l, insufficient if between 50 and 75 nmol/l, and normal if above 75–100 nmol/l [16].

The statistical package for the social sciences (SPSS) version 22 was used for statistical analysis. A descriptive analysis was performed on the demographics and clinical characteristics. Categorical and continuous data were reported as number (%), or median with the range. Chi-squared tests were used to examine the differences in categorical variables, and non-parametric tests Wilcoxon ranksum tests were applied to examine the differences in the non-normally distributed continuous variables. Pearson correlation and scatter plot graphs were used to test association. All statistical tests were two-sided, and a p-value less than 0.05 was considered significant.


Results

The study included 162 Saudi adults, 70.4% were females with a median age of 44 years (range 29). Their median body mass index (BMI) was high (30.11) in the range of obesity. The asthmatic patients had a median ACT score of 19, less than half was controlled 78 (48.1%) but 36 (22.2%) of them had a risk of future exacerbation. For vitamin D status, the prevalence of insufficiency was 55 (34%) and the deficiency was 107 (66%; Table 1).

Table 2 shows the significant correlations between ACT and other variables. ACT was found to be negatively correlated with age (r = −0.254, p = 0.001) and positively with BMI (r = 0.211, p = 0.007) and 25 (OH) D (r = 0.91, p = 0.000) (Figure 1). Comparison between asthma patients with and without risk of future exacerbations (Table 3) showed that asthmatic men and employed personnel were at higher risk for exacerbation than women (p = 0.028) and housewives (p = 0.001). Asthmatics with higher risk also showed to worsen the respiratory function with statistical significance (p = 0.000), higher BMI (p = 0.014), and lower 25(OH) D (p = 0.000). Vitamin D deficiency (94.4%) rather than insufficiency (5.6%) could explain the higher risk (5.6%) of future exacerbation (p = 0.000).

Table 1. The characteristics of the studied asthmatic patients.

Variable Results
Gender Female 114 (70.4%)
Male 48 (29.6%)
Occupation House wife 100 (61.7%)
Employed 62 (38.3%)
Age: Median years (Range) 44 (29)
BMI: kg/m2: Median (Range) 30.11 (22.22)
Respiratory function, Median (Range) FVC 2.66 (1.67)
FEV1 1.6400 (2.38)
FVC/FEV1 ratio. 1.67 (1.30)
Exacerbation Risk No exacerbation 126 (77.8%)
Future exacerbation 36 (22.2%)
Asthma Control Uncontrolled 48 (29.6%)
Partially controlled 36 (22.2%)
Controlled 78 (48.1%)
Asthma control test (ACT): Median (Range) 19 (16)
Vitamin D level: 25(OH)D: nmol/l. 31.18 (59.20)
Vitamin D status Deficiency (<50 nmol/l) 107 (66%)
Insufficiency (50–75 nmol/l) 55 (34.0%)
Sufficiency >75 nmol/l 0 nmol/l

Table 2. Correlations between the ACT and other parameters.

Pearson correlation p
Age −0.254* 0.001*
FVC −0.141 0.073
FEV1 −0.129 0.101
FVC/FEV1 ratio 0.098 0.216
BMI 0.211 0.007*
Vitamin D 0.921** 0.000*

*Significant.


Discussion

In this study, Saudi adults with partially uncontrolled asthma had deficient vitamin D level [66%] especially those at risk of future exacerbation (94.4%). Interestingly, although we did not find a direct association between ACT and respiratory function, vitamin D showed a strong association with respiratory function. In agreement of the present study results, few other studies showed low 25(OH) D levels in adults with asthma [17,18] especially those with the severe and/or uncontrolled state [17]. Furthermore, few other studies reported contrasting findings with low vitamin D levels in adults with asthma [19,20].

Figure 1. Correlation between vitamin D levels and ACT.

Our findings are in agreement with study groups who found that low vitamin D levels were associated with an increased asthma exacerbation [21,22], low asthma outcome [23], and steroid-resistant asthma [24] independent of other risk factors for asthma severity [24]. Moreover, one study demonstrated that sufficient vitamin D was associated with decreased number and severity of asthma exacerbations and the number of emergency room visits [25]. On the other hand, most of the studies did not find an association between vitamin D and asthma severity [13] or markers of asthma control [26]. The difference between our study and others may be partly explained by high BMI among selected patients. In this study, results showed a strong association between ACT and age, and BMI which may confound the association between ACT and vitamin D. The median BMI was high among selected patients which may by itself represent a risk factor for low vitamin D [27]. Similarly, in a study involving adults with inhaled corticosteroid-treated asthma, lower vitamin D level was associated with higher BMI [26]. Despite these confounding factors, we still believe in the strong association between low vitamin D and ACT partly because of the absence of such an association with respiratory function test (Table 2). The association between low vitamin D and asthma exacerbation and poor control may be explained by its influence on the innate immunity and increased incidence of respiratory viral infection [28]. Vitamin D increases the production of antimicrobial [29] and anti-inflammatory peptides including anti-viral factors [30]. The active vitamin D is known to exert an inhibitory effect on airway hyperreactivity and increase glucocorticoid bioavailability [31].

The strength of our study lies in the investigation of the relation between 25(OH) D with both the clinical and functional asthma parameters among adults. On the other hand, the limitations of the current study is that presence of other confounding factors were not addressed in the analysis including sun exposure, physical activity, dietary habits, dose, and the form of corticosteroid medications.

Table 3. Comparison between patients with and without future exacerbation.

No exacerbation Future exacerbation p
Age: median years (range) 44 (29) 43.5 (9) 0.883
Gender Female 94 (74.6%) 20 (55.64%) 0.028*
Male 32 (25.4%) 16 (44.4%)
Occupation Housewife 86 (68.3%) 14 (38.9%) 0.001*
Employed 40 (31.7%) 22 (61.1%)
BMI 30.30 (22.22) 28 (14.72) 0.014*
Respiratory function test FVC 2.43 (1.53) 2.92 (1.26) 0.000*
FEV1 1.58 (1.72) 1.97 (1.88) 0.000*
FVC/FEV1 ratio 1.69 (1.33) 1.60 (0.65) 0.001*
25 (OH) D Levels. 46.47 (59.2) 6.62 (53.19) 0.000*
Vitamin D status Vitamin D deficiency 73 (57.9%) 34 (94.4%) 0.000*
Vitamin D insufficiency 53 (42.1%) 2 (5.6%)

*Significant.


Conclusion

Saudi adults with partially uncontrolled asthma had deficient vitamin D level, especially those at risk of future exacerbation. The association between ACT and vitamin D in the absence of any association with respiratory function could reflect the importance of low vitamin D as a marker for severity. Therefore, we can recommend screening for low vitamin D in patients with uncontrolled asthma or poor response to therapy. Although the role of vitamin D replacement in asthma control still remains unclear, we could still recommend treating asthmatics with documented hypovitaminosis D.


Acknowledgment

This work was supported by the research Center at IbnSina National College for medical studies in Jeddah. The authors would like to thank all health care workers at the college hospital and all participants for their cooperation.


List of Abbreviations

25(OH) D 25-hydroxyvitamin D
ACT Asthma control test
FEV1 Forced expiratory volume in 1 second
FVC Forced vital capacity
GINA Global initiative for asthma
ISNC Ibn Sina National College for medical studies

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.


Funding

None.


Consent for publication

Informed consent was obtained from all the participants.


Ethical approval

The study was approved by the local ethical committee at ISNC under number 015MP05092018 dated on 19/9/2018.


Author details

Montasir Esam Moamena1, Hayfaa Mirghani Ahmed1, Motasim Esam Moamena2, Zahra Saeed Alduhilib1, Nameer Mohammed Alshinqeeti1, Hanaa Elsayed Abozeid3

  1. Intern, College of Medicine, Ibn Sina National College, Saudi Arabia
  2. Medical student, College of Medicine, Ibn Sina National College, Saudi Arabia
  3. Assistant Professor, Department of Medicine, College of Medicine, Ibn Sina National College, Saudi Arabia

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How to Cite this Article
Pubmed Style

Moamena ME, Ahmed HM, Moamena ME, Alduhilib ZS, Alshinqeeti NM, Abozeid. HE. Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. IJMDC. 2019; 3(8): 654-658. doi:10.24911/IJMDC.51-1543646262


Web Style

Moamena ME, Ahmed HM, Moamena ME, Alduhilib ZS, Alshinqeeti NM, Abozeid. HE. Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. http://www.ijmdc.com/?mno=19700 [Access: July 23, 2019]. doi:10.24911/IJMDC.51-1543646262


AMA (American Medical Association) Style

Moamena ME, Ahmed HM, Moamena ME, Alduhilib ZS, Alshinqeeti NM, Abozeid. HE. Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. IJMDC. 2019; 3(8): 654-658. doi:10.24911/IJMDC.51-1543646262



Vancouver/ICMJE Style

Moamena ME, Ahmed HM, Moamena ME, Alduhilib ZS, Alshinqeeti NM, Abozeid. HE. Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. IJMDC. (2019), [cited July 23, 2019]; 3(8): 654-658. doi:10.24911/IJMDC.51-1543646262



Harvard Style

Moamena, M. E., Ahmed, . H. M., Moamena, . M. E., Alduhilib, . Z. S., Alshinqeeti, . N. M. & Abozeid., . H. E. (2019) Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. IJMDC, 3 (8), 654-658. doi:10.24911/IJMDC.51-1543646262



Turabian Style

Moamena, Montasir Esam, Hayfaa Mirghani Ahmed, Motasim Esam Moamena, Zahra Saeed Alduhilib, Nameer Mohammed Alshinqeeti, and Hanaa Elsayed Abozeid.. 2019. Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. International Journal of Medicine in Developing Countries, 3 (8), 654-658. doi:10.24911/IJMDC.51-1543646262



Chicago Style

Moamena, Montasir Esam, Hayfaa Mirghani Ahmed, Motasim Esam Moamena, Zahra Saeed Alduhilib, Nameer Mohammed Alshinqeeti, and Hanaa Elsayed Abozeid.. "Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia." International Journal of Medicine in Developing Countries 3 (2019), 654-658. doi:10.24911/IJMDC.51-1543646262



MLA (The Modern Language Association) Style

Moamena, Montasir Esam, Hayfaa Mirghani Ahmed, Motasim Esam Moamena, Zahra Saeed Alduhilib, Nameer Mohammed Alshinqeeti, and Hanaa Elsayed Abozeid.. "Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia." International Journal of Medicine in Developing Countries 3.8 (2019), 654-658. Print. doi:10.24911/IJMDC.51-1543646262



APA (American Psychological Association) Style

Moamena, M. E., Ahmed, . H. M., Moamena, . M. E., Alduhilib, . Z. S., Alshinqeeti, . N. M. & Abozeid., . H. E. (2019) Association between Vitamin D deficiency and Asthma control test in adults: A cross-sectional study in a college hospital in Jeddah, Saudi Arabia. International Journal of Medicine in Developing Countries, 3 (8), 654-658. doi:10.24911/IJMDC.51-1543646262