Airway inflammation and mannitol challenge test in COPD.
BACKGROUND
Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD.


METHODS
Twenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV1 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection). AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum.


RESULTS
There was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum. Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge. ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum.


CONCLUSIONS
In mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation. The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD.


BACKGROUND
Netherlands Trial Register (NTR): NTR1283.
Department of Respiratory Medicine, Academic Medical Centre and University of Amsterdam, Amsterdam, The Netherlands. S.B.deNijs@amc.uva.nl
Selma B
SB
de Nijs
Niki
N
Fens
Rene
R
Lutter
Erica
E
Dijkers
Frans H
FH
Krouwels
Barbara S
BS
Smids-Dierdorp
Reindert P
RP
van Steenwijk
Peter J
PJ
Sterk
D000280:Administration, Inhalation; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D016084:Bronchoconstriction; D003430:Cross-Sectional Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D008875:Middle Aged; D009426:Netherlands; D009195:Peroxidase / Q000032:analysis; D011014:Pneumonia / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D011657:Pulmonary Eosinophilia / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D012372:ROC Curve; D012720:Severity of Illness Index; D013183:Sputum / Q000276:immunology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D008353:Mannitol; D009195:Peroxidase
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