Bronchial and alveolar exhaled nitric oxide as a marker of systemic involvement in patients with Crohn’s disease

printing supported by . Visit Chiesi at Stand D.30 WEDNESDAY, SEPTEMBER 28TH 2011 Figure 1 (continued) Methods: Thirty CD patients (age 43.10±14.6 yrs) without clinical evidence of pulmonary diseases and 21 non smokers, not atopic healthy controls (age 35.1±13.2 yrs) were enrolled. Results: Bronchial (14.9±10.2 ppb vs 10.1±6.3 ppb, p=0.049) and alveolar FENO (4.4±2.2 ppb vs 2.6±1.9; p=0.006) were significantly higher in CD patients than in healthy controls, respectively. Both bronchial (p=0.0016) and alveolar FENO (p=0.017) were positively correlated with Crohn’s Disease Activity Index. Conclusions: Our results for bronchial and alveolar FENO confirm subclinical pulmonary involvement in Crohn’s disease. FENO may be of clinical value during follow-up of these patients as a surrogate marker of systemic inflammation. P4780 Are the flow independent NO parameters flow dependent? Marieann Högman1,2, Pekka Meriläinen2. 1Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden; 2Department of Medical Sciences, Uppsala University, Uppsala, Sweden Background: The interest in alveolar NO, one of the flow independent parameters, is increasing since it is elevated in severe and nocturnal asthma and in COPD. The nonlinear approach (Högman-Meriläinen Algorithm) with low, medium and high flow rates has been used to calculate CANO, DawNO and CawNO. The aim was to set how low and how high these flow rates should be. Methods: Subjects (n=32), without classifications of disease, volunteered to exhale with eight flow rates between 10 and 350 mL/s. NO was measured by CLD 88sp NO analyzer (ECO Medics AG, Switzerland). The subjects were grouped according to low, normal and high FENO0.05. The correction for axial diffusion was applied (Condorelli et al. 2004). Results: There was a significant difference (p=0.001) in CawNO and DawNO (p=0.001) with the use of 30 instead of 10 mL/s. The CANO values were significantly different with the use of 250 instead of 350 mL/s (p=0.001). The three groups had CANO of 0.9±0.2, 0.9±0.1 and 0.9±0.3 ppb respectively. With correction of axial diffusion the CANO became 0.3±0.2, -0.5±0.2 and -2.7±0.6 ppb with majority of values being negative. Conclusion: The flow independent NO parameters are flow dependent. With the use of the nonlinear model with the HMA approach to calculate CANO, DawNO and CawNO the flow rates to be used use are 10, 100 and 350 for adults. Further studies have to be done in children that cannot perform these low and high flow rates. Most importantly, the axial diffusion correction is of limited value with the HMA method. Abbreviation: HMA=Högman-Meriläinen algorithm, CANO= alveolar NO, CawNO=airway wall NO, DawNO=airway transfer factor of NO P4781 There is no need for complicated equations and mathematical models. Exhaled nitric oxide can be partitioned with two simple exhalations Paolo Paredi, Omar Usmani, Katharine Hurt, Neil Pride, Peter Barnes. Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom Background: By measuring eNO at multiple flows and applying mathematical models of eNO exchange dynamics, the signal can be partitioned into its proximal airway [Jno (nl/sec)] and distal airway/alveolar contributions [CA(NO) (ppb)]. This method is time consuming, requires at least 3 exhalations and is affected by a number of limitations such as axial diffusion and turbulent flow. We eveloped a more practical method based on the production of NO (Vno) at two exhalation flow rates. Methods: In a group of 27 normal subjects (38±2 yr; 20 male), 13 steroid naive asthmatic patients (34±3 yr; 6 male, FEV1 70±4% predicted), 14 patients with chronic obstructive pulmonary disease (COPD) (65±2 yr; 10 male, FEV1 58±3%), and 12 patients with cystic fibrosis (21±4 yr; 8 male, FEV1 60±3%) we compared CA(NO) and Jno with the variation of total NO production at 50 and 200 ml/s [Vno50-200 (nl/s)]. Vno was measured by calculating the average area under the curve (NO concentration/time) of two successive exhalations at each flow rate. Results: Vno50-200 was strongly correlated with Jnoin normal subjects (r=0.94, p<0.001), asthma (r=0.98, p<0.001), COPD r=0.93, p<0.001), and CF patients (r=0.74, p<0.05). This agreement was confirmed by the Bland and Altman test. Vno50-200 did not correlate significantly with CA(NO) in any of the study groups. Conclusions: The flow dependent component of exhaled NO, which is affected by its bronchial production, can be estimated by measuring Vno50-200. This method is simple, does not require sophisticated equipment or equations and is in agreement with Jno calculated mathematically. P4782 Can nasal-NO be used to differentiate between primary and secondary ciliary dyskinesia? Christina Krantz1, Andrei Malinovischi2, Annika Hollsing1, Kjell Alving1. 1Women and Childrens Health, Uppsala University Hospital, Uppsala, Sweden; 2Medical Sciences, Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden Bakground: Nasal nitric oxide (n-NO) has been suggested as a screening test for primary ciliary dyskinesia (PCD) as patients with PCD have lower n-NO levels than healthy controls. Recent studies on n-NO in PCD and secondary ciliary dyskinesia (SCD) show an overlap between these two groups. Aim: To investigate in a pilot study if n-NO can differentiate between patients with diagnosed PCD and SCD treated at our centre. Methods: n-NO was measured in duplicate by aspiration at 5 ml/s with NIOX Mino in 21 patients with clinically diagnosed PCD (n=12) or SCD (n=9). The electron microscopy (EM) results on brush samples from the nose were available in all subjects. Results: Reproducibility of n-NO was good in each patient. A group of patients (n=6) had clearly low n-NO (5-69ppb) compared with the rest (216-857ppb). In the group with low n-NO there were only patients with PCD while in the group with high n-NO there were both patients with SCD and PCD, including 2 with Kartagener’s syndrome. Regarding EM findings, the only 3 subjects with no dyneinarms were in the low n-NO while 8 subjects without structural abnormalities had high n-NO values. The relatively large group with more atypical or inconclusive results was also heterogenous with regard to n-NO levels. Conclusion: A low n-NO value had a good positive predictive value for PCD in our material, but some PCD patients had normal n-NO levels. As structural findings on EM and n-NO appear to dissociate in some subjects, we continue to investigate all PCD and SCD patients at our centre including even functional tests of ciliary clearance, to see if n-NO correlates more to the cilia function than structural abnormalities. P4783 Comparison of alveolar nitric oxide concentrations using two different methods for the assessment of small airways inflammation in asthma Daiki Kobayashi, Yoshihiro Tochino, Hiroshi Kanazawa, Yukikazu Ichimaru, Kyoh Shigenori, Kazuhisa Asai, Kazuto Hirata. Graduate School of Respiratory Medicine, Osaka City University, Osaka City, Osaka Prefecture, Japan Background and objectives: Fractional exhaled nitric oxide (FENO) is considered a potentially useful biomarker to detect airway inflammation. Two-compartment model (2CM) of pulmonary NO dynamics has been used for the evaluation of bronchial NO flux (J’awNO) and peripheral airway/alveolar NO concentration (CANO) in asthmatic patients. Recently, the trumpet shape of airway tree and axial diffusion model (TMAD) has been reported as the correction of 2CM. This study was designed to determine the validity of measurement of CANO using the TMAD model for the assessment of small airways obstruction in asthma Methods: A total of 52 asthmatic patients and 12 normal controls were included in this study. Methacholine inhalation challenge testing, pulmonary function tests, sputum induction, and exhaled NO measurements at several flow rates were performed. And then J’awNO and CANO were calculated using both the 2CM (CANO 2CM, J’awNO 2CM) and the TMAD model (CANO TMAD, J’awNO TMAD) respectively. Results: Both J’awNO and CANO were significantly higher in asthmatic patients than normal controls. CANO 2CM was significantly correlated with FEV1/FVC (r=-0.35, p=0.01), FEF25-75 (r=-0.45, p<0.001), and sputum eosinophils (r=0.32, p=0.02). In contrast, CANO TMAD was significantly correlated with FEF25-75 alone (r=-0.42, p=0.002), and not with FEV1/FVC or sputum eosinophils. Conclusions: CANO TMAD is more selective as an indicator of small airways obstruction than CANO 2CM. Assessment of small airways obstruction using the TMAD model may reveal the role of the small airways in the pathogenesis of