Repeatability of Inflammatory Parameters in Induced Sputum of COPD Patients

Abstract

Rationale: Limited information is available on repeatability of inflammatory parameters in whole induced sputum samples from patients with COPD. Objectives: To study short-term and long-term repeatability in induced sputum samples in 22 patients with moderate to severe, stable COPD (mean age 64 yr, mean FEV1 1.91 L = 65% of predicted). Samples were collected on 71 occasions twice within 1 to 7 days (mean 3.8 days) and on 12 occasions twice with an interval of 3 months while clinically stable. Cell differentials, markers of neutrophilic and eosinophilic inflammation, respiratory membrane permeability and size-selective permeation were assessed. Findings: Parameters of permeability and of size-selective permeation, % eosinophils and % neutrophils showed the best short-term repeatability with intra-class correlation coefficients (Ri) of 0.61 to 0.90, followed by total cell count (TCC) with Ri of 0.52. Repeatability of soluble cell activation markers was less satisfactory (Ri 0.34 to 0.52). Mean short-term within-patient variability for TCC and permeability was approximately 2-fold and for cell activation markers 3-fold; mean between-patients variability was twice as high. Inducing sputum slightly enhanced eosinophil numbers and % neutrophils and decreased % macrophages in successive IS samples. Long-term repeatability was comparable to short-term repeatability but variability increased. Conclusions: Repeatability of parameters assessed in whole sputum is similar as reported previously for sputum plugs. In COPD an induced sputum procedure has a minor pro-inflammatory effect. The current data facilitates power calculations but also indicates that studies using inflammatory markers in sputum may easily be underpowered.