BackgroundIt is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients.MethodsForty-five moderate asthmatics were administered sulforaphane (100 μmol daily for 14 days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption.ResultsSulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21 %; p = 0.01) in 60 % of these asthmatics. Interestingly, in 20 % of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly.ConclusionThese findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.

the SUPRA FVL pattern was frequent in BLT/HLT patients. High expiratory flows in SUPRA patients could result from increased lung elastic recoil or reduced airway resistance, both of which could be caused by the pTLC mismatch. Improved survival in the SUPRA cohort suggests potential therapeutic approaches to improve outcomes in BLT/HLT patients.

This report proposes a potentially sensitive and simple physiological method to detect early changes and to follow disease progression in obstructive pulmonary disease (COPD) based upon the usual pulmonary function test. Pulmonary function testing is a simple, although relatively insensitive, method to detect and follow COPD. As a proof-of-concept, we have examined the slope of the plateau for carbon dioxide during forced expiratory capnography in healthy (n=10) and COPD subjects (n=10). We compared the change in the rate of exhalation of carbon dioxide over time as a marker of heterogeneous ventilation of the lung. All subjects underwent pulmonary function testing, body-plethysmography, and forced exhalation capnography. The subjects with COPD also underwent high-resolution computed tomography of the chest. Regression lines were fitted to the slopes of the forced exhalation capnogram curves. There was no difference in the mean levels of exhaled carbon dioxide between the COPD and the healthy groups (p>0.48). We found a significant difference in the mean slope of the forced exhalation capnogram for the COPD subjects compared to the healthy subjects (p=0.01). Most important, for the COPD subjects, there was a significant positive correlation between the slope of the forced exhaled capnogram and a defined radiodensity measurement of the lung by high-resolution computed tomography (r2=0.49, p=0.02). The slope of the forced exhalation capnogram may be a simple way to determine physiological changes in the lungs in patients with COPD that are not obtainable with standard pulmonary function tests. Forced exhalation capnography would be of great clinical benefit if it can identify early disease changes and at-risk individuals.

Corresponding author's email: ecleris1@jhmi.edu: Obesity is associated with decreased lung volumes. It is hypothesized that the effects of weight on lung volume may lead to Background decreased lung volumes and decreased airway caliber leading to an increased risk of asthma.Examine the effects of obesity on airway size in adults based on asthma status. Purpose: Methods: Women ages 18-65 years old with and without asthma undergoing evaluation for bariatric surgery were compared to normal weight female controls. Asthma diagnosis confirmed using bronchoprovocation test. Data on pulmonary function was obtained using spirometry. Airway architecture was evaluated using multi-detector CT (MDCT) taken at end-inspiration (Seimens Definition 64; Siemens, Iselin, NJ). Airways were matched between groups. Lung volume and airway architecture (i.e. diameter, luminal area, wall thickness, wall-to-total fraction) area were measured using VIDA software (VIDA Diagnostics, Inc). Data were analyzed using one-way analysis of variance (ANOVA) with Bonferroni correction and multiple regression analysis. Significance was accepted at a two-tailed p≤0.05.: 9 normal weight and 22 obese women (16 non-asthma, 6 asthma) were recruited. The majority were white (54%) mean age of Results 43.4±9.2 (mean±SD) with an average BMI of 23.1 kg/m (controls) and 48.5 kg/m (obese). Obese subjects had significantly lower lung 2 2 volumes both by spirometry and MDCT measurements compared to controls, although only the FRC was reduced below normal to 61% predicted (Table 1). There was no difference in airway size noted by obesity status, except for significantly higher wall thickness in obese women compared to controls (2.0 mm± 0.2 vs. 1.7 mm±0.1, p<0.001). There was a significant interaction noted between obesity status and lung volumes (p=0.05), with TLC being correlated with airway diameter (r =0.52, p=0.01) and area (r =0.56, p=0.01) only in obese 2 2subjects. There was no difference in airway architecture in the obese group between those with and without asthma. : Obesity was found to be associated with decreased lung volume and increased airway wall thickness independent of asthma Conclusion diagnosis. Furthermore, among those who are obese, lung volume was found to be positively correlated with airway size. Further studies are needed to examine the effects of these obesity related changes in airway architecture on hyper-responsiveness. This abstract is funded by: NHLBI Am J Respir Crit Care Med 183;2011:A3638 Internet address: www.atsjournals.org Online Abstracts Issue