A study of inflammatory biomarkers in crystalline silica exposed rock drillers.

BACKGROUND: Crystalline silica (CS) exposure can cause serious lung disease in humans, but mechanisms of pulmonary toxicity have not been completely elucidated. AIMS: To assess pro-inflammatory and anti-inflammatory biomarkers and biomarkers related to the development of chronic obstructive pulmonary disease and fibrosis in serum of rock drillers exposed to CS. METHODS: Rock drillers (N = 123) exposed to CS and non-specified particulate matter (PM) were compared to 48 referents without current or past exposure to PM in a cross-sectional study. RESULTS: The rock drillers had been exposed to CS for 10.7 years on average. Geometric mean (GM) current exposure was estimated to 36 µg/m3. Their GM concentration of matrix metalloproteinase 12 (MMP-12) was significantly higher (16 vs. 13 ng/L; p = 0.04), while interleukin (IL) 6 and IL-8 were significantly lower compared to the referents. Also pentraxin 3 was significantly lower (3558 vs. 4592 ng/L; p = 0.01) in the rock drillers. A dose-response relationship was observed between cumulative exposure to CS and MMP-12, the highest exposed subgroup having significantly higher MMP-12 concentrations than the referents. CONCLUSION: Exposure to CS may increase circulating MMP-12 concentrations in a dose-response related fashion. The results may also suggest a down-regulation of pro-inflammatory pathways.

A study of pneumoproteins in crystalline silica exposed rock drillers.

Objective: The objective was to assess serum concentrations of club cell protein 16 (CC-16) and the surfactant proteins A (SPs-A) and D (SP-D) in male rock drillers (N = 123) exposed to crystalline silica and in 48 occupationally non-exposed. Methods: The arithmetic mean (AM) duration of exposure was 10.7 years. The geometric mean (GM) crystalline silica exposure was 36 µg/m3 at the time of the study. The GM cumulative exposure was 239 µg/m3. Results: The concentrations of SP-D (GM 12.7 vs. 8.8 µg/L, p < 0.001) and SP-A (AM 1847 vs. 1378 ng/L, p = 0.051) were higher among rock drillers than among occupationally non-exposed. A positive significant association was observed between cumulative crystalline silica exposure and the SP-D concentrations (ß = 0.07; p < 0.05). Rock drillers with small airway obstruction with maximal mid-expiratory flow % (MMEF%) <70% (N = 29) had higher SP-D concentrations than rock drillers with MMEF% ≥ 70% (N = 91) (GM 17.3 vs. 11.4 µg/L, p = 0.001). Rock drillers with MMEF% ≥70% (N = 91) had higher concentrations of SP-A (1957 vs. 1287 ng/L, p = 0.01) and SP-D (11.4 vs. 9.0 µg/L, p = 0.007) than non-exposed with MMEF% ≥70% (N = 39). Rock drillers with airway obstruction (FEV1/FVC < 0.70, N = 11) had significantly lower CC-16 concentrations than rock drillers with FEV1/FVC ≥0.70 (N = 109) after adjusting for relevant potential confounders (p = 0.02). Conclusion: The results indicate that pulmonary surfactant is a target for crystalline silica toxicity. The alterations appear to be driven by pulmonary alterations in the small airways and by exposure itself. Further studies on pneumoproteins and pulmonary function in other groups of workers exposed to crystalline silica are needed.

Novel associations between cytokines and pulmonary involvement in juvenile dermatomyositis - a cross-sectional study of long-term disease.

OBJECTIVES: To examine associations between cytokines and pulmonary involvement in patients with medium- to long-term JDM. METHODS: In a cross-sectional study, 58 patients examined median (range) 16.8 (6.6-27.0) years after symptom onset were stratified in inactive (JDM-inactive) and active (JDM-active) disease (updated PRINTO criteria); 56 age/sex matched controls were included. Twenty-nine cytokines (in serum) were analysed (Luminex technology/ELISA). Pulmonary function test included forced vital capacity, total lung capacity (TLC) and diffusing capacity for carbon monoxide reported as % of predicted and low forced vital capacity/TLC/diffusing capacity for carbon monoxide. In patients, the presence of clinical pulmonary damage was assessed and high resolution computed tomography scans were scored for interstitial lung disease, chest wall calcinosis and airways disease. RESULTS: Median age of patients was 21 (7-55) years, 59% were female and 36% inactive. In JDM-active and all patients, higher MCP-1, IP-10 and eotaxin correlated with high-resolution computed tomography findings (rs 0.34-0.61; P < 0.05). MCP-1 and eotaxin correlated with pulmonary damage in JDM-active and all patients (rs 0.41-0.49; P < 0.01). Higher TGF-ß1 and PDGF (growth factors) were associated with lower lung volumes (forced vital capacity/TLC measures) in all patients; PDGF in JDM-active and TGF-ß1 in JDM-inactive patients. IP-10 correlated with TLC% in JDM-active patients. No associations between cytokines and pulmonary function test were found in controls. CONCLUSIONS: In JDM, we found a novel association (not previously described in myositis) between eotaxin and pulmonary involvement; we have previously shown an association between eotaxin and cardiac dysfunction. The associations between IP-10/growth factors/MCP-1 and pulmonary involvement are novel in JDM and were mostly seen in JDM-active patients.

High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis.

OBJECTIVE: Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis. METHODS: Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff. RESULTS: High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001). CONCLUSIONS: The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc.