Relationship between Vitamin D Level and Serum TNF-α Concentration on the Severity of Chronic Obstructive Pulmonary Disease
Authors: Ilyas Muhammad , Agussalim Agussalim , Megawati Megawati , Massi Nasrum , Djaharuddin Irawaty , Bakri Syakib , As’ad Suryani , Arief Mansyur , Bahar Burhanuddin , Seweng Arifin , Prihantono Prihantono 
Published: September 2019

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease and disturbed bacterial clearance. Vitamin D deficiency is sometimes observed in COPD patients and as significant roles in increasing inflammation of airway obstruction and systemic obstruction, increasing proinflammatory cytokine including TNF-α, reduction of bacterial clearance and increase exacerbation risk due to infection. Also, vitamin D plays significant roles in the metabolism of calcium and mineralization of bones and regulation system of immune. TNF-α also has essential roles in pathogenesis and inflammation of COPD.  Several studies that investigate the relationship between vitamin D level and serum TNF-α concentration in COPD patients are relatively uncommon, including in Indonesia. For that reason, this study aimed to assess the relationship between vitamin D level and TNF-α concentration in patients on the severity of the chronic obstructive pulmonary disease.
Methods This study was a hospital-based descriptive cross-sectional study. Total samples were 50 COPD patients with the average age of older than 60 years during their enrollments at the Department of Pulmonology and Respiratory Medicine of the Dr.Wahidin Sudirohusodo General hospital  Makassar in September 2018-January 2019. All procedures of the present study were reviewed and approved by the Research Ethics Committee of Medicine Faculty of Hasanuddin University. The severity of COPD was assessed according to the combination of COPD assessment stages that referred to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline 2015 that consisted of the combination of scoring COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) questionnaire and results of the spirometric measurement. Assessment of airway obstruction levels referred to the GOLD spirometric criteria. Determination of thoracic photographs was conducted to verify the COPD diagnosis of the severity of COPD. Determination of serum TNF-α concentration and vitamin D3 [1,25(OH)2D3] level used the ELISA method.
Results  The majority of COPD patients were observed in the category of older than 60 years old accounted for 34 COPD patients (68%), and the majority of COPD patients were males accounted for 47 males with COPD (94%). The majority of COPD patients were observed in the group of D (38%). All the study subjects observed in this study were smokers, and 82% of them were in the category of heavy smokers. 21 study subjects had higher concentration of serum TNF-α  (tertile 3 = 0.21-1.83 pg/dl), 20 study subjects  and lower level of vitamin D (tertile 1 = 182.1-364.5 pg/dl). The majority of the study subjects (38%) were in the category of severe COPD (category D of the severity of COPD at the tertile 3) according to the GOLD Combine Assessment. In view of the relationship between vitamin D level and serum TNF-α concentration on the airway obstruction, there were significant positive correlations between the increase of vitamin D levels and the increase of serum TNF-α concentrations on airway obstruction. In view of the relationship between vitamin D level and serum TNF-α concentration on the severity of COPD, there were significant positive correlations between the increase of vitamin D levels (tertiles 1, 2 and 3) and the increase of serum TNF-α concentrations on the severity of COPD at p-value<0.05. Overall, there were non-linear relationships between vitamin D level and serum TNF-α concentration on the severity of COPD.
Conclusions: Serum TNF-α concentration was positively associated with airway obstruction level and severity of COPD. Low level of vitamin D was negatively associated with airway obstruction level and severity of COPD. Vitamin D3 level (1,25(OH)2D) was negatively associated with serum TNF-α concentration and airway obstruction level and severity of COPD.