Ilyas Muhammad, Agussalim Agussalim, Megawati Megawati, Massi Nasrum, Djaharuddin Irawaty, Bakri Syakib, As'ad Suryani, Arief Mansyur, Bahar Burhanuddin, Seweng Arifin, Prihantono Prihantono
Department of Pulmonology and Respiratory Medicine, Medicine Faculty, Hasanuddin University, Makassar, Indonesia.
Department of Internal Medicine, Medicine Faculty, Hasanuddin University, Makassar, Indonesia.
Open Access Maced J Med Sci. 2019 Jul 29;7(14):2298-2304. doi: 10.3889/oamjms.2019.663. eCollection 2019 Jul 30.
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 pro-inflammatory 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 mineralisation 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.
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.
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 spirometry measurement. Assessment of airway obstruction levels referred to the GOLD spirometry 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.
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. Given 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. Given 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.
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.
慢性阻塞性肺疾病(COPD)是一种慢性炎症性疾病,其细菌清除功能受到干扰。COPD患者有时会出现维生素D缺乏,维生素D缺乏在增加气道阻塞和全身阻塞的炎症反应、增加包括肿瘤坏死因子-α(TNF-α)在内的促炎细胞因子、降低细菌清除能力以及增加感染导致的病情加重风险等方面发挥着重要作用。此外,维生素D在钙代谢、骨骼矿化以及免疫系统调节中也起着重要作用。TNF-α在COPD的发病机制和炎症反应中也具有重要作用。在COPD患者中,研究维生素D水平与血清TNF-α浓度之间关系的研究相对较少,在印度尼西亚也是如此。
本研究旨在评估COPD患者中维生素D水平与TNF-α浓度之间的关系,以及它们与慢性阻塞性肺疾病严重程度的关系。
本研究是一项基于医院的描述性横断面研究。研究对象为2018年9月至2019年1月在马卡萨市瓦希丁·苏迪罗胡索多综合医院肺科和呼吸内科登记的50例COPD患者,平均年龄超过60岁。本研究的所有程序均经过哈桑uddin大学医学院研究伦理委员会的审查和批准。根据慢性阻塞性肺疾病全球倡议(GOLD)2015指南中COPD评估阶段的组合来评估COPD的严重程度,该组合包括COPD评估测试(CAT)评分、改良医学研究委员会(mMRC)问卷以及肺功能测定结果。气道阻塞水平的评估参照GOLD肺功能标准。通过胸部X光片来验证COPD诊断及严重程度。采用酶联免疫吸附测定(ELISA)法测定血清TNF-α浓度和维生素D3[1,25(OH)2D3]水平。
大多数COPD患者年龄超过60岁,共34例(68%),且大多数COPD患者为男性,共47例(94%)。大多数COPD患者属于D组(38%)。本研究中的所有受试者均为吸烟者,其中82%为重度吸烟者。21例研究对象血清TNF-α浓度较高(三分位数3 = 0.21 - 1.83 pg/dl),20例研究对象维生素D水平较低(三分位数I = 182.1 - 364.5 pg/dl)。根据GOLD综合评估,大多数研究对象(38%)属于重度COPD(COPD严重程度三分位数3中的D类)。考虑到维生素D水平与血清TNF-α浓度在气道阻塞方面的关系,维生素D水平升高与气道阻塞时血清TNF-α浓度升高之间存在显著正相关。考虑到维生素D水平与血清TNF-α浓度在COPD严重程度方面的关系,维生素D水平升高(三分位数1、2和3)与COPD严重程度时血清TNF-α浓度升高之间存在显著正相关,p值< 0.05。总体而言,在COPD严重程度方面,维生素D水平与血清TNF-α浓度之间存在非线性关系。
血清TNF-α浓度与气道阻塞水平及COPD严重程度呈正相关。低水平的维生素D与气道阻塞水平及COPD严重程度呈负相关。维生素D3水平(1,25(OH)2D)与血清TNF-α浓度、气道阻塞水平及COPD严重程度呈负相关。