Sputum club cell protein concentration is associated with pulmonary exacerbation in cystic fibrosis

Laguna, Theresa A.; Williams, Cynthia; Brandy, Kyle R.; Welchlin-Bradford, Cole; Moen, Catherine E.; Reilly, Cavan; Wendt, Christine

doi:10.1016/j.jcf.2014.10.002

Cited by 20 publications

(26 citation statements)

References 26 publications

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“…These proteins produced by Clara cells possess anti-inflammatory qualities. Previously it was observed that CCSP expression and production are decreased in chronic asthmatic patients [178] and decreased levels of CCSP in broncho-alvelolar lavage fluid were also found in CF patients [179]. Patients with mucoid P. aeruginosa variants also had a significantly lower CCSP concentration in sputum.…”

Section: Discussionmentioning

confidence: 95%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

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BackgroundThe airways of patients with cystic fibrosis (CF) are highly complex, subject to various environmental conditions as well as a distinct microbiota. Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and the predominant cause of morbidity and mortality in CF. A multifarious interplay between the host, pathogens, microbiota, and the environment shapes the course of the disease. There have been several excellent reviews detailing CF pathology, Pseudomonas and the role of environment in CF but only a few reviews connect these entities with regards to influence on the overall course of the disease. A holistic understanding of contributing factors is pertinent to inform new research and therapeutics.DiscussionIn this article, we discuss the deterministic alterations in lung physiology as a result of CF. We also revisit the impact of those changes on the microbiota, with special emphasis on P. aeruginosa and the influence of other non-genetic factors on CF. Substantial past and current research on various genetic and non-genetic aspects of cystic fibrosis has been reviewed to assess the effect of different factors on CF pulmonary infection. A thorough review of contributing factors in CF and the alterations in lung physiology indicate that CF lung infection is multi-factorial with no isolated cause that should be solely targeted to control disease progression. A combinatorial approach may be required to ensure better disease outcomes.ConclusionCF lung infection is a complex disease and requires a broad multidisciplinary approach to improve CF disease outcomes. A holistic understanding of the underlying mechanisms and non-genetic contributing factors in CF is central to development of new and targeted therapeutic strategies.

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Section: Discussionmentioning

confidence: 95%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

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“…However, the levels did not return to normal despite intensive antibiotic treatment, hence negating their potential use as a marker of response to treatment [110]. Biomarkers that correlate to PA colonisation also include club cell secretory protein (CCSP), which is inversely related to the NE concentration in CF sputum and patients with pseudomonas aeruginosa have significantly lower CCSP than non-colonised individuals [112]. Furthermore, levels of leukotriene B4 (LTB4) correlate with PA colonisation in CF compared to other organisms [104].…”

Section: Sputum and Bronchoalveolar Lavage Fluid Biomarkersmentioning

confidence: 99%

Factors Affecting Prognosis and Prediction of Outcome in Cystic Fibrosis Lung Disease

McCarthy¹,

O’Carroll²,

Franciosi³

et al. 2015

Cystic Fibrosis in the Light of New Research

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Cystic fibrosis CF is a multisystem disorder with a significantly shortened life expectancy with the major cause of mortality related to lung disease. Inflammation is seen in the CF airways from a very early age and contributes significantly to symptoms and disease progression. "s the condition worsens over time, lung function declines, usually measured by Forced Expiratory Volume in second FEV % predicted, and extra-pulmonary complications often manifest. While the life expectancy in CF is still short, the median age of death and predicted survival age are continually increasing. Therapeutic interventions for CF have improved significantly in the last years and now there are targeted therapies towards specific elements in CF that may impact upon exacerbation frequency, symptoms, and eventually mortality due to lung disease.

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“…Three biomarkers – desmosine, club cell secretory protein (CCSP) and cathepsin B have previously been associated with CF lung disease; however, their applicability to CF infants has not been investigated [ 10 – 18 ]. We have shown that sputum CCSP concentration was both higher in adults with CF in the outpatient setting compared to during a CF pulmonary exacerbation and negatively associated with sputum NE concentration [ 17 ]. CCSP is produced by bronchial epithelial cells and known to have anti-inflammatory properties and may reflect CF lung disease activity [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have shown that sputum CCSP concentration was both higher in adults with CF in the outpatient setting compared to during a CF pulmonary exacerbation and negatively associated with sputum NE concentration [ 17 ]. CCSP is produced by bronchial epithelial cells and known to have anti-inflammatory properties and may reflect CF lung disease activity [ 17 ]. We have also shown that both sputum and urinary desmosine concentration decrease significantly during a CF pulmonary exacerbation [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of inflammation in infants with cystic fibrosis

et al. 2018

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BackgroundThere are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants.MethodsUrine, blood and lung function data were collected for 2 years from clinically stable infants diagnosed with CF by newborn screening. A subset of CF infants had bronchoscopy with lavage performed at 6 months and 1 year. Urine was collected quarterly from healthy control infants. Expectorated sputum and urine were collected quarterly for 2 years from clinically stable CF adults. Desmosine, club cell secretory protein (CCSP) and cathepsin B concentrations were measured and compared. Mixed effects models were used to identify associations between biomarker concentrations and clinical characteristics. Receiver operator characteristic curves were generated to investigate the sensitivity and specificity of the biomarkers.ResultsUrinary cathepsin B was significantly higher in CF infants compared to healthy infants (p = 0.005). CF infant airway and urinary cathepsin B concentrations were significantly lower compared to adult CF subjects (p = 0.002 & p = 0.022, respectively). CF infant airway CCSP was significantly higher than adult CF subjects (p < 0.001). There was a significant correlation between CF infant plasma CCSP and BALF CCSP (p = 0.046). BALF CCSP was negatively associated with IL-8 (p = 0.017). There was no correlation between biomarker concentration and FEV0.5.ConclusionsCathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0713-8) contains supplementary material, which is available to authorized users.

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Sputum club cell protein concentration is associated with pulmonary exacerbation in cystic fibrosis

Cited by 20 publications

References 26 publications

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

Factors Affecting Prognosis and Prediction of Outcome in Cystic Fibrosis Lung Disease

Biomarkers of inflammation in infants with cystic fibrosis

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