Chest

Chest

Volume 123, Issue 3, March 2003, Pages 778-783
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Clinical Investigations
Bronchitis
Long-term Repeatability of Induced Sputum Cells and Inflammatory Markers in Stable, Moderately Severe COPDa

https://doi.org/10.1378/chest.123.3.778Get rights and content

Study objectives

Neutrophilic inflammation is a major feature of COPD. Induced sputum is increasingly used to monitor inflammatory airway diseases. Although short-term repeatability of selected sputum markers has been extensively studied in several populations, data on the long-term repeatability of induced sputum markers in stable COPD are scant.

Design

Sputum supernatant of 12 patients with stable COPD was analyzed on three separate occasions with 4-weekly intervals. Sputum cells and inflammatory markers interleukin (IL)-8 and soluble intercellular adhesion molecule (sICAM)-1 were measured in supernatant using enzyme-linked immunosorbent assay. Repeatability of sputum markers was expressed by intraclass correlation coefficients (Ri).

Measurements and results

Sputum induction was safe in all patients. None of the sputum parameters analyzed changed significantly throughout the study. The repeatability for cell differential counts in stable COPD was as follows: total cells, Ri = 0.07; neutrophils, Ri = 0.66; macrophages, Ri = 0.47; eosinophils, Ri = 0.49; and lymphocytes, Ri = 0.58. The repeatability of soluble markers was as follows: IL-8, Ri = 0.50; and sICAM, Ri = 0.58. Sputum neutrophils were negatively correlated with lung function on each separate occasion, whereas soluble markers were not correlated with sputum cells (p > 0.16, all correlations) or lung function (p > 0.24, all correlations).

Conclusions

Clinically stable, moderate COPD is associated with equally stable sputum inflammatory markers. Repeatability of induced-sputum markers of neutrophilic inflammation in stable COPD is satisfactory, even over extended periods of time. These data support the usefulness of serial monitoring of induced-sputum inflammatory markers in COPD.

Section snippets

Patients

Twelve patients with diagnosed COPD were included into the analysis. All patients fulfilled diagnostic criteria of the Global Initiative for Obstructive Lung Disease for stage 2 (moderate) COPD.19 All patients had negative skin-prick test results to standard aeroallergens, a smoking history of at least 10 pack-years, FEV1 values between 40% and 70% of predicted, a FEV1/FVC ratio (FEV1%FVC) of < 70%, and a postbronchodilator reversibility of FEV1 < 12%, measured at baseline 15 min after

Sputum Cells

All patients were able to produce adequate sputum samples on each occasion. During the whole study period, there was no significant change in total sputum cells, cell differentials (percentage), or absolute cell counts per milliliter of sputum. The reproducibility of sputum cell differentials was generally acceptable with Ri values > 0.47. However, total sputum cells were poorly reproducible (Ri = 0.07), as well as the total neutrophil and eosinophil count per milliliter of sputum (Ri = 0.33

Discussion

Neutrophilic inflammation is an important feature of COPD, and targeting the neutrophil is regarded as a potential future treatment for COPD. The present study was designed to assess the repeatability of sputum cells and markers of neutrophilic inflammation by repeated measurements over a time period of 8 weeks. First, our observations clearly demonstrate that clinical stability in moderate COPD is also reflected by the “stability” of surrogate markers in induced sputum. None of the parameters

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    Copyright © 2003 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.