Chest
Volume 128, Issue 4, October 2005, Pages 2316-2326
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Clinical Investigations
Sputum Cathelicidin, Urokinase Plasminogen Activation System Components, and Cytokines Discriminate Cystic Fibrosis, COPD, and Asthma Inflammation

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Background

Interest in airways inflammatory disease has increasingly focused on innate immunity. We investigated several components of innate immunity in induced sputum of patients with cystic fibrosis (CF), COPD, and asthma, and healthy control subjects.

Methods

Twenty eight patients with mild CF lung disease (age ≥ 12 years; FEV1, 74 ± 3% predicted [mean ± SE]), 74 adults with COPD (FEV1, 55 ± 2% of predicted), 34 adults with persistent asthma (FEV1, 66 ± 2% of predicted), and 44 adult control subjects (FEV1, 85 ± 1% of predicted) were studied while in stable clinical condition. Levels of sputum interleukin (IL)-8, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, human cationic antimicrobial protein 18 (CAP18), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 were determined. Cell sources were investigated by flow cytometry and immunohistochemistry. Spirometry was performed prior to sputum induction.

Results

CF patient sputum showed greatest increase in IL-8 compared to that of patients with COPD and asthma (which were also greater than control subjects), and elevated levels of TNF-α and IL-10 compared to other groups. There were no differences in IFN-γ. CAP18 levels were elevated in CF and COPD patients compared to control subjects, while asthma patients had reduced CAP18 levels. uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients, while PAI-1 levels were elevated in all three disease groups. CAP18 localized to neutrophil secondary granules; neutrophils were also sources of IL-8 and PAI-1. CAP18 and PAI-1 negatively correlated with pulmonary function.

Conclusion

Induced-sputum innate immune factor levels discriminate inflammatory changes in CF, COPD, and asthma, suggesting potential roles in pathophysiology and as well as providing disease-specific biomarker patterns.

Section snippets

Subjects

We recruited 28 patients with CF (age, 12 to 50 years) followed up at the CF Center clinic at Stanford University Medical Center. CF diagnoses in all patients were made by positive (> 60 mEq/L) pilocarpine iontophoresis sweat test results, with homozygous or compound heterozygous for ΔF508 CF transmembrane conductance regulator mutations. All patients had chronic infection with Pseudomonas aeruginosa by serial sputum culture and were in stable clinical condition (no pulmonary exacerbation

Subject Groups

The CF patients (17 women and 11 men) were generally young adults (mean ± SD age, 23.7 ± 11.1 years) with well-preserved pulmonary function (mean ± SD FEV1, 74.0 ± 17.4% predicted). The patients with COPD (24 women and 50 men) were, as expected, older (59.2 ± 9.9 years) with generally greater airflow obstruction (FEV1, 54.6 ± 13.7% predicted). The patients with asthma (19 women and 15 men) were intermediate between these other groups in age (47.4 ± 13.9 years) and airflow obstruction (FEV1,

Discussion

Research123031 has focused on the role of deranged aspects of innate immunity in the pathobiology of chronic inflammatory airways diseases such as CF, asthma, and COPD. In the present study, we were interested in aspects of the innate immune response in CF, in particular the following: (1) the role of the uPA system and the antimicrobial cathelicidin CAP18 that have not received much attention, and (2) how any abnormalities in CF compared to COPD and asthma as well as healthy persons. In order

Acknowledgment

We thank Theresa Chen for helping with Chinese-English translation.

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    This study was funded by the Ross Mosier and Berger Raynolds Funds.

    Drs. Moss, Ishizaka, and Kirikae have assigned entire right, title, and interest in the CAP18 immunoassay described here to Seikagaku Corporation, Tokyo, Japan.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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