Serum Clara Cell Protein as an Indicator of Pulmonary Impairment in Occupational Exposure at Aluminum Foundry

Abstract

Objectives: Although some of the exposures in aluminum (Al) smelting have been well characterized, and respiratory disorders in aluminum production workers are well known, the relationship between internal aluminum loads and appropriate lung biomarkers have not been elucidated. The aim of our work was to carry out a comprehensive investigation in workers employed in the Aluminum Foundry Casting Department with special reference to currently existing hygiene standards, known as threshold limit values (TLV) based on aluminum effects on the respiratory system. The measurement of serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral marker of the lung epithelium function. Materials and Methods: A group of 50 casting smelters, 5 locksmiths, 11 sawyers and auxiliary workers exposed to dust containing 14% of aluminum, and a group of 42 controls were examined. Respiratory function tests were performed and forced volume capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), forced expiratory volume in the first percent (FEV 1 %), forced expiratory flows in 50% VC (FEV 50 ), and markers of foundry workers' exposure and body burden, Al concentration in the breathing zone, blood and urine, biomarkers of the effects of exposure, concentration of CC16 and hyaluronic acid (HA) in serum were determined in all examined workers. Additional measurements comprised determinations of serum iron (Fe) levels, myeloperoxidase (MPO), eosinophil cationic protein (ECP), immunoglobulin E (IgE), glutathione S-transferase (GST), and superoxide dismutase (SOD) activity in erythrocytes. Results: The group of casting smelters was characterized by the highest levels of aluminum in urine (Al-U) (43.7 mg L -1 ), high levels of MPO, ECP and IgE, high SOD activity, low CC16 levels, and low activity of GST. Lower Al-U excretion was observed in locksmiths (35.2 mg L -1 ) and sawyers (21.7 mg L -1 ). Serum CC16 proved to be the most sensitive biomarker, showing high inverse relationship with serum Al (Al-S) concentrations in casting smelters (p = 0.006). Conclusions: The study showed that in conditions of occupational exposure, dusts containing Al 2 O 3 < 1 mg m -3 cause changes in the respiratory system and biomarkers in serum, especially in CC16, connected with altered functioning of this system. Changes in concentrations of the examined biomarkers and also in respiratory parameters of the study subjects were observed when Al-U concentration was > 40 mg L -1 .

Prognostic significance of low serum levels of Clara cell phospholipid-binding protein in occupational aluminium neurotoxicity

“…Lowering CC16 serum level was one of the most sensitive, however not-specific biomarker in occupational exposure [8,9,13]. The relationship between low CC16 level in serum and abnormal results of the VEP brain function tests and concomitant high Al serum level may also indicate possibility of the interaction between Al in serum and transfer of protein originated from epithelial respiratory cells.…”

“…As a cell-specific marker for nonciliated bronchiolar epithelial Clara cells, which play a part in immunomodulatory and/or antiinflammatory processes, assessment of Clara cell protein in serum (CC16) was proposed by various authors [6,7]. Recent studies have shown that CC16 is a sensitive biomarker of respiratory epithelial injury in exposures of humans and animals to welder fumes [8], nitric oxides [9], glutaraldehyde [10], or low CC16 levels in serum were noted in active smokers [11,12] and in silicaexposed workers [13].…”

Aluminio en el Tracto Respiratorio Bajo de Residentes de la Ciudad de México

“…Las investigaciones muestran que el nivel de toxicidad del Al puede ser muy bajo (21) y puede provocar enfermedades respiratorias (4,16,21,22), neurológicas (15,17,23) y recientemente se ha reportado su efecto cancerígeno (24,25).…”

“…Los efectos respiratorios se han observado principalmente en trabajadores expuestos (4,5,26,27) y estudios experimentales indican que la presencia de Al se correlaciona con proceso inflamatorio pulmonar (22,28).…”

Extrinsic interstitial lung disease activity markers

“…При этом у курящих больных асбестозом синтез СС16 был достоверно выше по сравнению со здоровыми курильщиками, но ниже, чем у некурящих больных, что дало возможность предложить СС16 в качестве биомаркера при проф заболеваниях как у курящих, так и некурящих [17,18]. Установлена обратная зависимость между кон центрациями СС16 и ионов алюминия в сыворотке крови у рабочих алюминиевой промышленнос ти [19]. Хроническое воздействие аллергенов вызы вает метаплазию булавчатых клеток, что приводит к снижению их защитных свойств и уровня СС16 в жидкости бронхоальвеолярного лаважа, при этом противовоспалительная терапия способствует вос становлению нормального фенотипа булавчатых клеток и их функций [20].…”