Vitamin D Levels, Lung Function, and Steroid Response in Adult Asthma

被引:289
作者
Sutherland, E. Rand [1 ,3 ]
Goleva, Elena [2 ,4 ]
Jackson, Leisa P. [2 ]
Stevens, Allen D. [1 ]
Leung, Donald Y. M. [2 ,4 ]
机构
[1] Natl Jewish Hlth, Dept Med, Denver, CO USA
[2] Natl Jewish Hlth, Dept Pediat, Denver, CO USA
[3] Univ Colorado, Dept Med, Denver, CO USA
[4] Univ Colorado, Dept Pediat, Denver, CO 80202 USA
基金
美国国家卫生研究院;
关键词
asthma; vitamin D; glucocorticoids; treatment; NECROSIS-FACTOR-ALPHA; BODY-MASS INDEX; RESISTANT ASTHMA; 25-HYDROXYVITAMIN-D LEVELS; CORTICOSTEROID RESISTANCE; KINASE PHOSPHATASE-1; PERSISTENT ASTHMA; HEALTHY-ADULTS; MAP KINASE; T-CELLS;
D O I
10.1164/rccm.200911-1710OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale. Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma. Objectives: To determine the effect of vitamin D levels on phenotype and GC response in asthma. Methods: Nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function, airway hyperresponsiveness (AHR), and GC response, as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells. Measurements and Main Results: A total of 54 adults with asthma (FEV(1), 82.9 +/- 15.7% predicted [mean +/- SD], serum vitamin D levels of 28.1 +/- 10.2 ng/ml) were enrolled. Higher vitamin D levels were associated with greater lung function, with a 22.7 (+/- 9.3) ml (mean +/- SE) increase in FEV(1) for each nanogram per milliliter increase in vitamin D (P = 0.02). Participants with vitamin D insufficiency (<30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine inducing a 20% fall in FEV(1) of 1.03 (+/- 0.2) mg/ml versus 1.92 (+/- 0.2) mg/ml in those with vitamin D of 30 ng/ml or higher (P = 0.01). In ICS-untreated participants, dexamethasone-induced MKP-1 expression increased with higher vitamin D levels, with a 0.05 (+/- 0.02)-fold increase (P = 0.02) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D, a finding that occurred in the absence of a significant increase in IL-10 expression. Conclusions: In asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response, suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response. Clinical trials registered with www.clinicaltrials.gov (NCT00495157, NCT00565266, and NCT00557180).
引用
收藏
页码:699 / 704
页数:6
相关论文
共 36 条
[1]   Molecular mechanisms of corticosteroid resistance [J].
Adcock, Ian M. ;
Barnes, Peter J. .
CHEST, 2008, 134 (02) :394-401
[2]  
American Thoracic Society, 2000, AM J RESP CRIT CARE, V162, P2341
[3]  
[Anonymous], NIH PUBL
[4]   Body fat content and 25-hydroxyvitamin D levels in healthy women [J].
Arunabh, S ;
Pollack, S ;
Yeh, J ;
Aloia, JF .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (01) :157-161
[5]   Can guideline-defined asthma control be achieved? The gaining optimal asthma control study [J].
Bateman, ED ;
Boushey, HA ;
Bousquet, J ;
Busse, WW ;
Clark, TJH ;
Pauwels, RA ;
Pedersen, SE .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 170 (08) :836-844
[6]   EVIDENCE FOR ALTERATION OF THE VITAMIN-D-ENDOCRINE SYSTEM IN OBESE SUBJECTS [J].
BELL, NH ;
EPSTEIN, S ;
GREENE, A ;
SHARY, J ;
OEXMANN, MJ ;
SHAW, S .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (01) :370-373
[7]   Evidence of a role of tumor necrosis factor α in refractory asthma [J].
Berry, MA ;
Hargadon, B ;
Shelley, M ;
Parker, D ;
Shaw, DE ;
Green, RH ;
Bradding, P ;
Brightling, CE ;
Wardlaw, AJ ;
Pavord, ID .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (07) :697-708
[8]   Overweight, obesity, and incident asthma - A meta-analysis of prospective epidemiologic studies [J].
Beuther, David A. ;
Sutherland, E. Rand .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 175 (07) :661-666
[9]   Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma [J].
Boulet, Louis-Philippe ;
Franssen, Edmee .
RESPIRATORY MEDICINE, 2007, 101 (11) :2240-2247
[10]   Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica [J].
Brehm, John M. ;
Celedon, Juan C. ;
Soto-Quiros, Manuel E. ;
Avila, Lydiana ;
Hunninghake, Gary M. ;
Forno, Erick ;
Laskey, Daniel ;
Sylvia, Jody S. ;
Hollis, Bruce W. ;
Weiss, Scott T. ;
Litonjua, Augusto A. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2009, 179 (09) :765-771