Fig 1.
Study design, participant and procedure flow.
Reasons for screen failures were: Elevated alanine aminotransferase level (N = 5); % predicted forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) < 90% (N = 6); minimal airway obstruction on pulmonary function testing (N = 1); abnormal chest x-ray (N = 1); abnormal electrocardiogram (N = 1); history of childhood asthma (N = 1); smoking within 1 year of enrollment (N = 1); body mass index outside range (N = 1). Withdrawals were volunteers who signed the consent after completing the screening procedures and were given the blinded study drugs but withdrew from the study prior to initiating the imaging and bronchoscopy procedures and were lost to follow up. FDG-PET = positron emission tomography imaging with 18F-fluorodeoxyglucose. i.b. = intrabronchial. qD = once per day. Q6hr = once every six hours.
Table 1.
Baseline clinical characteristics.
Table 2.
Effect of endotoxin on clinical characteristics.
Fig 2.
Positron emission tomography (PET) and computed tomography (CT) images from a representative volunteer in each treatment cohort.
White outlines show the volumes of interest (VOIs) used to determine the time-activity curves for the Patlak graphical analysis and standard uptake values. VOIs were sometimes smaller in volume on the left due to the heart.
Fig 3.
Patlak graphical analysis results from18F-fluorodeoxyglucose (18F-FDG) PET images in the right and left lungs before and after endotoxin instillation.
Arrows indicate presence of both Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs), arrowheads only the Asp299Gly SNP. The arrowhead for the left lung data of the zileuton treatment cohort points to the post-endotoxin data point that decreased slightly after endotoxin. Ki = influx constant describing rate of 18F-FDG uptake into the lung region of interest, determined by Patlak graphical analysis. * = p < 0.05 when comparing post-endotoxin (After) to pre-endotoxin (Before) value.
Fig 4.
Mean standard uptake value (SUV) results from18F-fluorodeoxyglucose PET images in the right and left lungs for each treatment cohort.
Arrows indicate presence of both Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs), arrowheads only the Asp299Gly SNP. The arrow and arrowhead for the left lung of the placebo cohort point to the top two post-endotoxin data points. * = p < 0.05 when comparing post-endotoxin (After) to pre-endotoxin (Before) value.
Table 3.
BAL cell counts and differentials.
Fig 5.
Serum adiponectin and urinary leukotriene E4 (LTE4) levels by treatment cohort.
* = p < 0.05 when comparing post-endotoxin (After) to pre-endotoxin (Before) values. Serum adiponectin levels are expressed as mg/mL serum. Urinary LTE4 levels are expressed as pg LTE4/mg creatinine (pg/mg).