Louise Jeanette Pauline Persson

Chronic Obstructive Pulmonary Disease Is Associated with Low Levels of Vitamin D

Introduction COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported. Methods Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40–76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models. Results COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22). Conclusion COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels.

Predictors of exacerbations in chronic obstructive pulmonary disease - results from the Bergen COPD Cohort Study

Background COPD exacerbations accelerate disease progression. Aims To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration. Methods 403 COPD patients, GOLD stage II-IV, aged 44–76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years. Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO2<8 kPa), cough, use of inhaled steroids, and the inflammatory markers leucocytes, C-reactive protein (CRP), neutrophil gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor 1 (sTNF-R1), and osteoprotegrin (OPG). Negative binomial models with random effects were fitted to estimate the annual incidence rate ratios (IRR). For analysis of AECOPD duration, a generalized estimation equation logistic regression model was fitted, also adjusting for season, time since inclusion and AECOPD severity. Results After multivariate adjustment, significant predictors of AECOPD were: female sex [IRR 1.45 (1.14–1.84)], age per 10 year increase [1.23 (1.03–1.47)], >1 AECOPD last year before baseline [1.65 (1.24–2.21)], GOLD III [1.36 (1.07–1.74)], GOLD IV [2.90 (1.98–4.25)], chronic cough [1.64 (1.30–2.06)] and use of inhaled steroids [1.57 (1.21–2.05)]. For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39–0.92)], years since inclusion [1.19 (1.03–1.37)], AECOPD severity; moderate [OR 1.58 (1.14–2.18)] and severe [2.34 (1.58–3.49)], season; winter [1.51 (1.08–2.12)], spring [1.45 (1.02–2.05)] and sTNF-R1 per SD increase [1.16 (1.00–1.35)]. Conclusion Several COPD characteristics were independent predictors of both AECOPD frequency and duration.

Comparison of inflammatory markers in induced and spontaneous sputum in a cohort of COPD patients

BackgroundSputum induction is a non-invasive method for obtaining measurements of inflammation in the airways. Whether spontaneously sampled sputum can be a valid surrogate is unknown. The aim of this study was to compare levels of six inflammatory markers in sputum pairs consisting of induced and spontaneous sputum sampled on the same consultation either in a stable state or during exacerbations of chronic obstructive pulmonary disease (COPD).Methods433 COPD patients aged 40-76, Global initiative for chronic Obstructive Lung Disease (GOLD) stage II-IV were enrolled in 2006/07 and followed every six months for three years. 356 patients were followed for potential exacerbations. Interleukin-6, interleukin-8, interleukin-18, interferon gamma-inducible protein-10, monokine induced by gamma interferon and tumor necrosis factor-alpha (IL-6, IL-8, IL-18, IP-10, MIG and TNF-α) were measured by bead based multiplex immunoassay in 60 paired sputum samples from 45 patients. Albumin was measured by enzyme immunoassay, for concentration correction. Culturing for bacterial growth was performed on 24 samples. Bland-Altman plots were used to assess agreement. The paired non-parametric Wilcoxon signed-rank test, the non-parametric Spearman’s rank correlation test and Kruskal-Wallis test were used for statistical analyses. For all analyses, a p-value < 0.05 was considered significant.ResultsAgreement between the two measurements was generally low for all six markers. TNF-α was significantly higher in spontaneous sputum at exacerbations (p = 0.002) and trending higher at the steady state (p = 0.06). Correlation coefficients between the levels of markers in induced and spontaneous sputum varied between 0.58 (IL-18) to 0.83 (IP-10). In spontaneous sputum IL-18 and MIG were higher in ex-smokers (p < 0.05). The levels of all markers were higher in GOLD stage III & IV except for IL-6 in spontaneous sputum and IL-18 in induced sputum, compared with GOLD stage II, although not statistically significant. In spontaneous sputum the levels of IL-6 were significantly higher if Haemophilus influenzae (HI) was not cultured.ConclusionWe observed a low agreement and significant differences in inflammatory markers between induced and spontaneous sputum, both at steady state and exacerbations. We recommend considering sampling method when reporting on inflammatory markers in sputum.

Vitamin D, vitamin D binding protein, and longitudinal outcomes in COPD.

Background Associations between Vitamin D3 [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported. We aimed to further investigate these associations on longitudinal outcomes. Methods 426 COPD patients from western Norway, GOLD stage II-IV, aged 40–76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency. Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively. Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression. Results 1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01). Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death. Conclusion Severe vitamin D deficiency may affect decline in lung function parameters in COPD. Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression.

Antimicrobial peptide levels are linked to airway inflammation, bacterial colonisation and exacerbations in chronic obstructive pulmonary disease

Antimicrobial peptides (AMPs) are effectors of host defence against infection, inflammation and wound repair. We aimed to study AMP levels in stable chronic obstructive pulmonary disease (COPD) and during acute exacerbations of COPD (AECOPD), and to examine their relation to clinical parameters and inflammatory markers. The 3-year Bergen COPD Cohort Study included 433 COPD patients and 325 controls. Induced sputum was obtained and analysed for levels of the AMPs human cathelicidin (hCAP18/LL-37) and secretory leukocyte protease inhibitor (SLPI), and for the inflammatory markers interleukin (IL)-8, IL-6 and tumour necrosis factor-α (TNF-α) using immunoassays. Systemic hCAP18/LL-37 and vitamin D levels were also studied. Treating AMPs as response variables, non-parametric tests were applied for univariate comparison, and linear regression to obtain adjusted estimates. The risk of AECOPD was assessed by Cox proportional-hazard regression. Sputum AMP levels were higher in patients with stable COPD (n=215) compared to controls (n=45), and further changed during AECOPD (n=56), with increased hCAP18/LL-37 and decreased SLPI levels. Plasma hCAP18/LL-37 levels showed a similar pattern. In stable COPD, high sputum hCAP18/LL-37 levels were associated with increased risk of AECOPD, non-typeable Haemophilus influenzae colonisation, higher age, ex-smoking and higher levels of inflammatory markers. Altered levels of selected AMPs are linked to airway inflammation, infection and AECOPD, suggesting a role for these peptides in airway defence mechanisms in COPD. Sputum AMP patterns are associated with airway microbial presence, inflammatory markers and clinical outcomes in COPD http://ow.ly/qVFi306wBNW