Methodological aspects on measurement of Clara cell protein in urine as a biomarker for airway toxicity, compared with serum levels

Abstract

The Clara cell protein CC16, secreted from Clara cells in the lung, is discussed as a potential biomarker for toxic effects on the airways. An increased concentration of CC16 in serum may be caused by increased permeability of the lungs, caused by high levels of air pollution. Since CC16 is eliminated by renal excretion, it may be possible to use urine instead of serum samples. Few studies have been conducted on urinary CC16 (U-CC16), however. The aim was to investigate the optimal way of sampling and quantifying CC16 in urine samples and compare CC16 in human serum and urinary samples. Repeated sampling was performed in two groups of healthy subjects. First morning urine, 24 h urine, and matched blood and urine samples were collected. The excretion of U-CC16 increased over the day, e.g. from 0.08 microg h(-1) in the morning to 0.28 microg h(-1) in daytime and 0.16 microg h(-1) in the evening (medians in males). Morning samples (microg h(-1)) from males properly reflected the 24 h excretion (r = 0.91). The best correlation with 24 h excretion was obtained with creatinine-corrected first morning urine samples (r > 0.9). Generally, females had lower excretion of CC16 than males (medians 2.5 microg 24 h(-1) in females and 16 microg 24 h(-1) in males). There was significant intraindividual variation, but the interindividual variation was larger in both groups. There was an association between serum CC16 (S-CC16) and U-CC16 in morning samples. With optimal methods for sampling U-CC16, urine samples may be used in experimental studies of air pollution.

Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy

“…9 Urine biomarkers offer several advantages compared with serum samples, as they simplify collection, reduce costs, and may decrease participant attrition. 30 In addition, biomarkers can shed light on the mechanisms of disease pathogenesis. In the present study, an inverse association was found between urine levels of CC16 at the time of an infant LRTI and the odds of subsequent childhood wheeze.…”

“…Urine levels of CC16 could be also affected by several other factors (e.g., post-renal excretion of CC16, diurnal variation, and physical activity). 13,30,53 However, it is unknown if these factors are truly important in children, as the limited data available are in adults. 13,14 Furthermore, urine levels of CC16 have been highly correlated to serum levels (which are less likely to be affected by some of these factors) in other studies using a similar instrument.…”

“…This same kit has been previously validated for urine in another study. 30 Next, urine levels of CC16 (ng/mL) were measured according to the manufacturer's recommendations. All samples were tested in duplicate.…”

“…30 As a result, there has been a recent interest in the utility of urine CC16 as a potentially useful, cost-effective, and noninvasive biomarker for respiratory disorders. 30,31 The authors have previously demonstrated a severitydependent relationship between infant LRTIs and the risk of developing asthma.…”

“…30 As a result, there has been a recent interest in the utility of urine CC16 as a potentially useful, cost-effective, and noninvasive biomarker for respiratory disorders. 30,31 The authors have previously demonstrated a severitydependent relationship between infant LRTIs and the risk of developing asthma. 8 As CC16 may be a marker of both lung injury and immune response, the authors hypothesized that urine levels of CC16 at the time of an infant LRTI are associated with the development of childhood wheezing illnesses.…”