Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings

Michel, Olivier; Murdoch, Robert; Bernard, Anne‐Marie

doi:10.1016/j.jaci.2005.01.067

Cited by 47 publications

(47 citation statements)

References 35 publications

(34 reference statements)

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“…Interestingly, although we found plasma CC16 concentration to be lower in patients with ALI/ ARDS than those with CPE, other studies in animal models 41,42 and humans 33 have shown acute increases in plasma CC16 concentration following inspired or intratracheal LPS administration. Additionally, a study of critically ill mechanically ventilated patients found higher plasma CC16 levels in patients with ALI/ARDS compared to those at risk, and patients with ALI/ARDS who died had higher CC16 levels than survivors.…”

Section: Discussioncontrasting

confidence: 79%

Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

Kropski

Fremont

Calfee

et al. 2009

Chest

124

111

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Background: Acute lung injury (ALI) and ARDS are common clinical syndromes that are underdiagnosed. Clara cell secretory protein (CC16) is an antiinflammatory protein secreted by the Clara cells of the distal respiratory epithelium that has been proposed as a biomarker of lung epithelial injury. We tested the diagnostic and prognostic utility of CC16 in patients with non-trauma-related ALI/ARDS compared to a control group of patients with acute cardiogenic pulmonary edema (CPE). Methods: Plasma and pulmonary edema fluid samples were obtained from medical and surgical patients with ALI/ARDS or CPE requiring intubation for mechanical ventilation. The etiology of pulmonary edema was determined using consensus clinical criteria for ALI/ARDS and CPE and the edema fluid-to-plasma protein ratio. Plasma and edema fluid CC16 levels were measured by sandwich enzyme-linked immunosorbent assay. CC16 levels were log transformed for analysis, and comparisons were made by the Student t test or 2 as appropriate. Results: Compared to patients with CPE (n ‫؍‬ 9), patients with ALI/ARDS (n ‫؍‬

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Section: Discussioncontrasting

confidence: 79%

Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

Kropski

Fremont

Calfee

et al. 2009

Chest

124

111

View full text Add to dashboard Cite

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“…24 However, subclinical chorioamnionitis may also have affected serum levels of CC16. In animals 21 and humans, 25 lipopolysaccharide-induced, acute lung inflammation increases leakage of CC16 from lung into the blood, whereas neonates with postnatal infections have elevated CC16 in the bronchoalveolar lavage. 26 Interestingly, in a recent study, Thomas et al 27 reported lower CC16 in the tracheobronchial aspirates of extremely premature neonates with histological evidence of systemic inflammation compared with the control group, although no difference could be documented in the umbilical cord levels of the protein.…”

Section: Discussionmentioning

confidence: 99%

Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates

et al. 2010

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Objective: Clara cell 16 kD protein (CC16) and interleukin (IL)-6 have been used as peripheral blood biomarkers of alveolar leakage and inflammation, respectively. Thus, their measurement in the bloodstream could be used to assess ventilator-induced lung injury. The objective of this study was to evaluate the effect of optimized synchronized intermittent mandatory ventilation (SIMV) and high-frequency oscillatory ventilation (HFOV) on circulating CC16 and IL-6 levels when used as the initial ventilation modes in preterm neonates.Study Design: Single center, prospective, randomized clinical study in preterm neonates (gestational age p30 weeks) requiring mechanical ventilation within the first 2 h of life. Serum CC16 and IL-6 were measured on establishment of the assigned ventilation mode after admission, at days 3 and 14 of life as well as at 36 weeks postmenstrual age. Demographicperinatal data and clinical parameters were also recorded.Result: Of the 30 neonates studied, 24 (gestational age 27.1 ± 1.7 weeks, birth weight 942±214 g) were finally analyzed, equally assigned into the SIMV and HFOV groups. Both groups had comparable demographicperinatal characteristics and clinical parameters. Serum CC16 and IL-6 altered significantly over time (repeated-measures analysis of variance, both P<0.001). However, changes were not affected by the ventilation mode. Post hoc analysis showed a significant decrease in CC16 and IL-6 from birth up to 36 weeks postmenstrual age in both groups. Conclusion:In preterm neonates, SIMV and HFOV are associated with comparable circulating CC16 and IL-6 levels. These findings suggest a similar alveolar leakage and systemic inflammation with any of the ventilation modes evaluated when their usage is optimized.

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“…CC-16 is produced by Clara cells and functions as a protective immunosuppressant during lung injury. Serum CC-16 concentrations show an acute increase after the inhalation of LPS (and ozone) in healthy subjects [19,20]. Interestingly, serum and induced sputum CC-16 concentrations are reduced in COPD patients compared with controls [21,22].…”

Section: Introductionmentioning

confidence: 99%

Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects

Aul

Armstrong

Duvoix

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Neutrophilic airway inflammation is a feature of chronic obstructive pulmonary disease (COPD). Inhaled lipopolysaccharide (LPS) challenge in healthy non‐smokers has been used to assess the anti‐inflammatory effects of novel drugs on neutrophilic airway inflammation.WHAT THIS STUDY ADDS• We performed inhaled LPS challenge in smokers to study an inflammatory response in subjects who more closely resemble COPD patients. Inhaled LPS caused reproducible pulmonary inflammation in smokers, associated with changes in systemic biomarkers. Inhaled LPS appears to be a suitable model for studying exacerbations of COPD.AIMS Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFκB dependent cytokine production. We investigated LPS inhalation in healthy smokers as a model of COPD bacterial exacerbations. We studied safety, reproducibility, the translocation of the NFκB subunit p65 in sputum cells and changes in systemic biomarkers of inflammation.METHODS Twelve smokers inhaled 5 and 30 µg LPS and safety was monitored over 24 h. IL‐6, CRP, CCl‐18, SP‐D, CC‐16 and β‐defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24 h. Sputum was induced at baseline, 6 and 24 h for cell counts and p65 expression. Repeated challenges were performed after a 2 week interval in 10 smokers.RESULTS LPS inhalation was well tolerated. Significant increases occurred in sputum neutrophil counts with both doses, with a maximum increase of 21.5% at 6 h after 30 µg which was reproducible, ri (intraclass correlation coefficient) = 0.88. LPS increased sputum cell nuclear p65 translocation and phospho‐p65 expression. All of the serum biomarkers increased following challenge but with different temporal patterns.DISCUSSION Inhaled LPS challenge in smokers causes pulmonary and systemic inflammation that involves NFκB activation. This appears to be a suitable model for studying bacterial exacerbations of COPD.

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Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings

Cited by 47 publications

References 35 publications

Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates

Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects

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