Serum levels of inflammatory mediators as prognostic biomarker in silica exposed workers.

Silicosis is a diffuse interstitial lung disease caused by sustained inhalation of silica and silicates. Several cytokines are activated by their inhalation and can mediate the process of pulmonary fibrosis. The identification of biomarkers could allow an early diagnosis before the development of radiological alterations and help monitor the evolution of patients. The objetive of this study was to determine the clinical significance of specific biomarkers, to estimate their association with the development, severity and/or progression of silicosis, and identify determinants of this evolution. We conducted a prospective observational study in patients attending the pulmonology clinic from 2009 to 2018. Serum levels of the following inflammatory mediators were assessed: interleukin-6 (IL-6), interleukin 2 receptor subunit alpha (IL2R) interleukin 1 beta (IL1B), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-ß1), alpha-1 antitrypsin (AAT), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin in subjects exposed to silica, with and without silicosis. Association between those inflammatory mediators with lung function measurements and radiological severity of disease and their impact on prognosis were analysed. 337 exposed to silica (278 with silicosis) and 30 subjects in the control group were included. IL-8, α1AT, ferritin, CRP and LDH levels were higher in silicosis than in those exposed to silica without silicosis. IL-8, LDH and AAT levels were associated with progression of silicosis and IL-6, IL-8, LDH, AAT, ferritin, and CRP with vital status. The results of the ROC analysis indicated the potential of IL-8 as a biomarker in the presence of silicosis and for the prediction of mortality.

Prevalence and clinical impact of systemic autoimmune rheumatic disease in patients with silicosis.

BACKGROUND: Silicosis is associated with an increased risk of developing systemic autoimmune rheumatic disease (SARD). The prognostic implications of this association are poorly characterized. The aim of this study was to determine the prevalence of SARD and autoimmune markers in a cohort of patients with exposure to silica and assess their impact on prognosis. METHOD: We performed a prospective observational study of all patients attending the dedicated silicosis clinic of our pulmonology unit between 2009 and December 2017. Diagnosis was confirmed by a rheumatologist according to Spanish Rheumatology Society criteria. Autoimmune markers, pulmonary function tests, radiological progression, visits to the emergency department and primary care center, and hospital admissions for respiratory causes, and mortality were analyzed. RESULTS: Overall, 489 cases of silicosis and 95 cases of exposure were studied. In total, 54 (11.0%) patients with silicosis had SARD: 12 (2.4%) rheumatoid arthritis, 10 (2.0%) systemic lupus erythematosus, 10 (2.0%) systemic sclerosis, 3 (0.6%) Sjögren syndrome, 2 (0.4%) vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA +), 6 (1.2%) psoriatic arthritis, 3 (0.6%) ankylosing spondylitis, and 8 (1.6%) other autoimmune diseases with no special features. The patients with SARD visited the emergency room more often (63.0% vs. 42.5%; p = 0.004), and progressed more rapidly (22.2 vs. 11.7%; p = 0.030). CONCLUSIONS: The presence of systemic rheumatic autoimmune diseases involves radiological progression and a higher clinical impact.

Prevalence and Clinical Impact of Systemic Autoimmune Rheumatic Disease in Patients with Silicosis. / Prevalencia e impacto clínico de las enfermedades reumatológicas autoinmunitarias sistémicas en pacientes con silicosis.

BACKGROUND: Silicosis is associated with an increased risk of developing systemic autoimmune rheumatic disease (SARD). The prognostic implications of this association are poorly characterized. The aim of this study was to determine the prevalence of SARD and autoimmune markers in a cohort of patients with exposure to silica and assess their impact on prognosis. METHOD: We performed a prospective observational study of all patients attending the dedicated silicosis clinic of our pulmonology unit between 2009 and December 2017. Diagnosis was confirmed by a rheumatologist according to Spanish Rheumatology Society criteria. Autoimmune markers, pulmonary function tests, radiological progression, visits to the emergency department and primary care center, and hospital admissions for respiratory causes, and mortality were analyzed. RESULTS: Overall, 489 cases of silicosis and 95 cases of exposure were studied. In total, 54 (11.0%) patients with silicosis had SARD: 12 (2.4%) rheumatoid arthritis, 10 (2.0%) systemic lupus erythematosus, 10 (2.0%) systemic sclerosis, 3 (0.6%) Sjögren syndrome, 2 (0.4%) vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA +), 6 (1.2%) psoriatic arthritis, 3 (0.6%) ankylosing spondylitis, and 8 (1.6%) other autoimmune diseases with no special features. The patients with SARD visited the emergency room more often (63.0 vs. 42.5%; p = 0.004), and progressed more rapidly (22.2 vs. 11.7%; p = 0.030). CONCLUSIONS: The presence of systemic rheumatic autoimmune diseases involves radiological progression and a higher clinical impact.

The 6-Minute Walk Test as a Tool for Determining Exercise Capacity and Prognosis in Patients with Silicosis. / La prueba de la marcha de 6 minutos como factor pronóstico y de capacidad de ejercicio en pacientes con silicosis.

OBJECTIVE: To evaluate exercise capacity using the 6-minute walk test (6MWT) in patients with complicated silicosis, and to determine how results shape the prognostic value of 6MWT for hospitalization and mortality. METHOD: Prospective observational study in 143 patients with complicated silicosis who performed the 6MWT in our outpatient pulmonology clinic between 2009 and the end of 2016. Lung function tests, computed tomography findings and 6MWT parameters (distance walked and oxygen desaturation) were evaluated. RESULTS: Patients with complicated silicosis walked 387±92m. Results deteriorated as silicosis severity increased; category A: 407±97m, B: 370±88m, and C: 357±68m (P=.022). The 6MWT correlated positively with lung function and inversely with dyspnea determined by mMRC (P<.001). Patients with moderate/severe emphysema and greater CT90 presented a worse result on 6MWT. Patients who walked<350m had more hospitalizations (3.7±4.0) than those who walked>350m (1.1±2.9). There was an impact on survival: non-survivors walked 327.9±73.0m, while survivors walked 404.5±89.7m (P<.001). CONCLUSIONS: Spirometry values and category of complicated silicosis correlated with 6MWT and distance walked was a prognostic factor for hospitalization and mortality. The 6MWT is a useful tool in occupational health for monitoring patients with silicosis.

Clinical Significance of Environmental Mycobacteria Isolated From Respiratory Specimens of Patients With and Without Silicosis.

OBJECTIVE: To describe the clinical, functional and radiographic differences of respiratory disease caused by environmental mycobacteria (EM) in patients with and without silicosis. METHOD: Retrospective, observational study in patients with nontuberculous mycobacteria isolated in the Hospital Meixoeiro (University Hospital of Vigo) microbiology laboratory between January 2007 and December 2013. Patients were grouped according to the presence or absence of silicosis and mycobacterial lung disease, using American Thoracic Society criteria. RESULTS: In 156 cases, at least one species of EM had been isolated from the respiratory culture. A total of 71% were identified in men, 40 (25.6%) of whom had silicosis. Sixty patients (38.5%) met American Thoracic Society microbiological criteria: 62.5% of the silicosis group and 30.2% of the non-silicosis group. The most common species were Mycobacterium avium complex, Mycobacterium genavense and Mycobacterium chelonae. American Thoracic Society criteria for environmental mycobacterial disease were met in 34 (22.7%) patients: 14 in the silicosis group and 20 in the non-silicosis group. Treatment was administered in 24 cases, with better bacteriological eradication levels in the non-silicosis group. CONCLUSIONS: In our series, a history of silicosis was related with a higher incidence of environmental mycobacterial disease. The causative species in the majority of cases in our setting was Mycobacterium avium complex, followed by Mycobacterium genavense. Patients with silicosis showed lower cure rates after treatment.

Guidelines for the diagnosis and monitoring of silicosis.

Silicosis is one of the occupational respiratory diseases most commonly encountered in our setting. It is caused by inhalation of crystalline silica that triggers a fibrotic response in the lung parenchyma. It presents as diffuse interstitial disease and clinical expression ranges from asymptomatic forms to chronic respiratory failure. Diagnosis is based on clinical history and radiological findings. There is no effective treatment, and once diagnosed, the patient must avoid all sources of occupational exposure. In these guidelines, the clinical, radiological and functional aspects of silicosis are reviewed, and strategies for diagnosis, monitoring and classification of patients are proposed, along with recommendations regarding the occupational implications of this disease.