Clara cell 16 protein in COPD sputum: a marker of small airways damage?
ABSTRACT The development of chronic obstructive pulmonary disease (COPD) in smokers and their susceptibility to infections is not fully understood. Recent evidences suggest that Clara cells play a part in host defense, immunomodulatory response and airways remodelling through the production of specific factors such as Clara cell 16 (CC-16). This protein has never been related to patients' lung function tests, blood gases parameters and diseases severity.
To evaluate a possible correlation between CC-16 expression in sputum, measured by a new methodological approach, and the degree of severity in patients with moderate and severe COPD. We also analyzed possible correlations between CC-16 and cytological sputum population, arterial blood gases and lung function.
We analyzed 20 patients, mean age 72.95, classified on the basis of the global initiative for chronic obstructive lung disease guidelines (GOLD 2006). The samples were processed for cytological analysis and CC-16 levels were assessed by Western blot. We found lower levels of CC-16 in severe COPD compared to moderate ones (p<0.027). No statistically significant differences were found between CC-16 expression and sputum cellularity (except for macrophages), arterial blood gases, and spirometric parameters. Multiple linear regression analysis of CC-16 versus functional and cytological parameters showed no significance.
We found a significantly different expression of CC-16 in COPD patients, according to their stage of severity, as defined by the GOLD 2006 guidelines. Considering CC-16 properties in innate immunity, a possible link between protein expression, innate immune system, and COPD infectious exacerbations may be hypothesized but further investigation are needed.
- SourceAvailable from: Francesco Blasi[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy. METHODS: We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0--2 and lag 3--5 in both single and multi-pollutant models, adjusted for daily weather variables. RESULTS: An increase in ozone (O3) levels at lag 3--5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0--2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO2), CO, nitrate dioxide (NO2), and particulate matter (PM10 and PM2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0--2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association. CONCLUSIONS: Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.Respiratory research 10/2012; 13(1):95. · 3.64 Impact Factor
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ABSTRACT: RATIONALE: A genome-wide association study (GWAS) for circulating COPD biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. OBJECTIVES: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. METHODS: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, interleukin-6, interleukin-8, and tumor necrosis factor-α) in 1951 COPD subjects. For genome-wide significant SNPs (p < 1 x10-8), association with COPD susceptibility was tested in 2939 COPD cases and 1380 smoking controls. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. MAIN RESULTS: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus ~25 Mb away from SCGB1A1 were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (p values 0.009-0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (p values 0.001-0.049), although these COPD associations were not replicated in two additional cohorts. CONCLUSION: Distant genetic loci as well as biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility.American Journal of Respiratory and Critical Care Medicine 11/2012; · 11.04 Impact Factor
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ABSTRACT: The authors discuss the role of inflammatory biomarkers to predict mortality in chronic obstructive pulmonary disease (COPD) in this narrative literature review with expert opinion. The severity of COPD has traditionally been graded using the degree of obstruction as measured by the forced expiratory volume in 1 s because this variable has been predictive of outcomes. However, it is now accepted that COPD is a complex disease with important systemic consequences and that a multidimensional index such as the BMI, obstruction, dyspnea and exercise capacity index is a better predictor of outcome than lung function alone. Because inflammation is thought to play a pivotal role in the genesis of COPD, several serum inflammatory biomarkers have been investigated. Of the ones studied, C-reactive protein, IL-6, pulmonary and activation-regulated chemokine and fibronectin:C-reactive protein ratio have been observed to be independently associated with increased risk of death. When added to known clinical variables such as the BMI, obstruction, dyspnea and exercise capacity index, only IL-6 has been shown to further contribute to mortality prediction. It is likely that the use of an integrative approach combining biomarkers investigated through high-output technology with clinical parameters, combined with new information from the fields of genomics, transcriptomics, proteomics and metabolomics, will improve the authors capacity to predict mortality in COPD.Expert Review of Respiratory Medicine 02/2013; 7(1):57-64.