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(Chest. 2006;130:1157-1164.)
© 2006 American College of Chest Physicians

Repeated Sputum Inductions Induce a Transient Neutrophilic and Eosinophilic Response*

Hester van der Vaart, MD; Dirkje S. Postma, MD, PhD; Wim Timens, MD, PhD; Henk F. Kauffman, MD, PhD; Machteld N. Hylkema, PhD and Nick H.T. ten Hacken, MD, PhD

* From the Departments of Pulmonology (Drs. van der Vaart, Postma, and ten Hacken), Pathology (Drs. Timens and Hylkema), and Allergology (Dr. Kauffman), University of Groningen, Groningen, the Netherlands.

Correspondence to: Nick H.T. ten Hacken, MD, PhD, University Medical Centre Groningen, Pulmonology, hanzeplein 1 Groningen 9713 RB, the Netherlands; e-mail: n.h.t.ten.hacken{at}int.umcg.nl

Abstract

Introduction: Sputum induction is a tool to monitor airway inflammation, yet it may induce by itself a neutrophilic response when repeated within 24 to 48 h. This limits its repeated use in clinical trials.

Objective: We aimed to investigate the induction and resolution of inflammation generated by repeated sputum inductions.

Subjects and design: Sixteen healthy intermittent smokers participated in a study on the short-term effects of smoking. The nonsmoking arm consisted of seven successive sputum inductions with increasing time intervals (3, 6, 12, 24, 48, and 96 h). Inflammatory cellular characteristics and different soluble mediators were investigated.

Measurements and results: The median percentage of sputum neutrophils increased significantly from baseline to 6 h (58.9% [range, 31.8 to 94.2%] to 83.2% [range, 26.7 to 98.3%], respectively). Surprisingly, the percentage of eosinophils also increased significantly from baseline to 6, 12, 24, and 48 h, as follows: 0.3% (range, 0.0 to 1.2%) to 1.7% (range, 0.0 to 15.5%), 2.2% (range, 0.5 to 12.5%), 1.2% (range, 0.0 to 4.8%), and 0.8% (range, 0.0 to 2.8%), respectively. Interleukin-8 increased significantly from baseline to 24 h (1,553 pg/mL [range, 462 to 8,192 pg/mL] to 2,178 pg/mL [range, 666 to 128,544 pg/mL]).

Conclusions: Repeated sputum inductions should preferably be avoided within 48 h. It induces not only a short-lived neutrophilic response but also a prolonged eosinophilic inflammatory response in healthy subjects, possibly by local changes in osmolarity, and subsequent epithelial and/or mast cell activation.

Key Words: eosinophils • inflammation • neutrophils • sputum induction






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