title: Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study.
abstract: The safety of sputum induction and the reproducibility of measurements in induced sputum in multicenter studies is unknown. We examined the safety of sputum induction in a two-visit, six-center study in 79 subjects with moderate to severe asthma (mean +/- SD FEV(1) 71 +/- 12% predicted, 67% taking inhaled corticosteroids). In addition, we compared the reproducibility of markers of inflammation in induced sputum with the reproducibility of the FEV(1) and the methacholine PC(20). The FEV(1) decreased > or = 20% from the postbronchodilator baseline in 14% of all subjects and in 25% of subjects whose initial prebronchodilator baseline was 40 to 60% of predicted. All subjects responded promptly to additional albuterol treatment, and no subject developed refractory bronchoconstriction requiring treatment other than reversal of bronchospasm in the study laboratory. The reproducibility of measurements of the eosinophil percentage, eosinophil cationic protein, tryptase, and methacholine PC(20) were similar (concordance correlation coefficients of 0.74, 0.81, 0.79, and 0.74, respectively), without any significant among-center effect. We conclude that sputum induction can be performed safely in subjects with moderate to severe asthma in multicenter clinical trials when carried out under carefully monitored conditions. Importantly, we demonstrate that measurement of markers of inflammation in induced sputum is as reproducible as methacholine PC(20) and should prove useful in the assessment of airway inflammation in multicenter clinical trials.
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA. jfahy@itsa.ucsf.edu
authors.forename: J V
authors.initials: JV
authors.lastname: Fahy
authors.forename: H A
authors.initials: HA
authors.lastname: Boushey
authors.forename: S C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: E A
authors.initials: EA
authors.lastname: Mauger
authors.forename: R M
authors.initials: RM
authors.lastname: Cherniack
authors.forename: V M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: T J
authors.initials: TJ
authors.lastname: Craig
authors.forename: J M
authors.initials: JM
authors.lastname: Drazen
authors.forename: J G
authors.initials: JG
authors.lastname: Ford
authors.forename: J E
authors.initials: JE
authors.lastname: Fish
authors.forename: E
authors.initials: E
authors.lastname: Israel
authors.forename: M
authors.initials: M
authors.lastname: Kraft
authors.forename: R F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: R J
authors.initials: RJ
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: McLean
authors.forename: S P
authors.initials: SP
authors.lastname: Peters
authors.forename: C
authors.initials: C
authors.lastname: Sorkness
authors.forename: S J
authors.initials: SJ
authors.lastname: Szefler
mesh_terms: D000368:Aged; D001249:Asthma / Q000145:classification / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D001985:Bronchial Provocation Tests / Q000592:standards; D016085:Bronchoconstrictor Agents; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride; D011237:Predictive Value of Tests; D012260:Ribonucleases; D012697:Serine Endopeptidases / Q000032:analysis; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry* / Q000166:cytology* / Q000276:immunology; D053802:Tryptases
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D016085:Bronchoconstrictor Agents; D047091:Eosinophil Granule Proteins; D016210:Methacholine Chloride; D012260:Ribonucleases; D012697:Serine Endopeptidases; D053802:Tryptases