Thematic Poster Session

T UESDAY, S EPTEMBER 5 TH 2006

Hall B2-11 - 12:50-14:40

351. Pathophysiology of lung disease
P3871 Relative lung deposition of tobramycin from a MicroAir nebuliser Marwan Mashat, Brian J. Clark, Khaled H. Assi, Henry Chrystyn. Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire, United Kingdom Jet nebulisers (JN) are widely used to nebulise tobramycin but their efficiency to deposit drug into the lungs is poor. New nebulisers based on vibrating mesh (VM) technology have recently been introduced. We have compared the relative lung deposition of nebulised tobramycin (TOBI, Chiron) from two JNs, a Sidestream [SIDE] attached to a Portaneb compressor (Profile Respiratory, UK) and a Pari LC+ [LC+] attached to a Pari Turbo BOY’N’ (Pari, Germany), to a VM, the MicroAir [MA] (Omron, Japan). Healthy volunteers inhaled 300mg TOBI from SIDE and LC+ and 150mg from MA with the co-administration of oral charcoal. Serial urine samples were collected upto 24 hours post dose. The in-vitro aerodynamic characteristics of the emitted TOBI dose were determined using the CEN methodology. 12 volunteers, mean(sd) age and weight of 32.5(6.2) years and 76.1(9.5) Kg, completed the study. The mean(sd) in-vitro characteristics and fate of the nebulised tobramycin doses were:
SIDE LC+ MA 11.3(1.7) 60.0(3.9) 14.4(1.3) 75.5(4.5)

Fate of nebulised dose (mg) Urinary Tobramycin 11.7(1.6) 14.7(1.4) Amount exhaled 41.4(3.3) 62.6(6.3) Amount left in NEB 139.0(4.9) 117.0(5.7) Amount inhaled 119.6(5.5) 120.4(7.0) Aerodynamic characteristics, MMAD - mass median aerodynamic diameter, FPD - fine particle dose MMAD (μm) 1.96(0.22) 2.01(0.16) FPD %(emitted dose) 60.7(4.05) 57.3(2.58)

1.18(0.03) 82.2(1.7)

From the urinary tobramycin the mean(sd) relative lung bioavailability from SIDE, LC+ and VM was 3.9(0.5), 4.9(0.5) and 7.5(1.1) % of the nominal dose, respectively. PARI LC+ and MicroAir provide better lung deposition than a Sidestream. 300mg TOBI nebulised using a PARI LC+ is equivalent to 200mg in the MicroAir.

P3872 Assessment of early combined super-imposed ventilation using high frequency, heliox and conventional pressure control in acute lung injury patients (ALIp) Francois Meurant. Intensive Care Unit, Kirchberg Hospital, Luxemburg-state, Luxemburg Introduction:We conducted a prospective study to investigate the impact of combined super-imposed ventilation (conventional pressure control plus high frequency jet ventilation (CPHFJV) plus Heliox) on intubated ALIp to prevent ARDS. Methods: 50 adult ALIp were randomly separated into 2 groups (G1:n=24;G2:n=22). G1 were ventilated using Open Lung Approach (PIC=20±5 mmHg; PP=10±5; best Peep =6±4 mmHg), this group served as our control group. G2 were ventilated by CPHFJV+ Heliox (60/40) (CV=1 ml/kg; rate=300/min; Driving pressure =1 atm; Inspiratory time=30% of cycle). Hypoxic state(HS), Lung compliance(LC) and ventilation/perfusion mismatching (V/Q) were compared every 4 hours during 48 hours (H0 to H48). For statistical analysis a Shapiro-Wilk test, Wilcox and a Student T-test were used. Results: 24% (n=6) of the patients in G2 developed ARDS, compared to a 58% incidence(n=14) in G1 (p<0.005). Extubation occurred in G2 after 4.1±1.4 (mean ± SD) days of ventilation compared to 7.1±2.7 days in G1 (p<0.005). LC increased by 30% in G2 at H8 with a maximum gain of 55% at H16 when compared to G1 achieving at most an improvement of 30% only at H16. In G2 V/Q mismatch dropped to 15% at H8 with a maximum reduction of 23% at H12 compared to 12% reduction in G1 at H16 and a maximum of 18% at H28. HS increased about 22% at H8 to a maximum of 36% at H16 in G2 when compared to 8% at H8 for a maximum of 34% at H32 in G1. Conclusion: In ALI, early aggressive ventilation using a combined approach leads to a more rapid improvement in gaz exchange, reduces ventilation time and raises lung compliance.

667s
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France. induction of apoptotic pathway and antiproliferative effect. 2 At 0. 1 Fig. Sabine Blouquit 1 . whereas AQLQS and FEV1 was comparable. Primary cultures of human non-CF and CF bronchial and bronchiolar epithelia were placed in Ussing chambers and the baseline short-circuit current (Isc) was measured. such as ciliary beat frequency and anti-microbial properties. P3875 Airflow simulations in CT-derived extrathoracic airways Georges Caillibotte 1 . is normally involved in antioxidant mechanisms. Fig. Les Loges en Josas. the computational domain was meshed with tetrahedral elements using third party software.12:50-14:40 images were used to define the passages. Then.g. CA. these results strongly suggest the utility of flavonoids in the complementary therapeutic approach of cancer patients. the CFD computational domain was meshed with tetrahedral elements using commercial software. Hôpital Foch.). France NO is produced by airway epithelium and is involved in several airway functions. P3877 Nitric oxide (NO) inhibits ion transport in human non-CF and CF proximal and distal airways Luc Dannhoffer 1 . whereas asthmatics with persistent AHR have deterioration in AQLQ independent of lung function. 1 UPRES EA220. Airflows occurring during steady inspiration were simulated using FIDAP from Fluent Inc. UFR Paris Ile de France Ouest. whereas compliance. CyberMedicine. Emmanuel Naline 1 . Apigenin. Ira M. Inc. the influence of the realistic airway geometry on the flow field during inspiration at resting conditions (0. Previous studies have shown that exhaled NO is reduced in cystic fibrosis (CF). Rasmussen. when analyzing clinical significant changes in AQLQS.Thematic Poster Session T UESDAY. Furthermore. Ted B. use of ICS. Thierry Chinet 1 . However. Denmark Background: The presence of airway hyperresponsiveness (AHR) among asthmatics has been shown to worsen AQLQ independently of the severity of asthma.05 for both) and the effect of forskolin was significantly reduced in non-CF preparations (p< 0. leptin receptor activation decreases all these events. 1 Istituto di Biomedicina e Immunologia Molecolare (IBIM). whereas improval in activity domain showed negative association with persistent AHR (19%) versus those without AHR (36%)(p=0. CyberMedicine.01) and environment domain (p<0. we demonstrated that A549 express leptin receptor. 2 President. The results in Figure 2 show the influence of the realistic airway geometry on streamlines. 2 Clinique des Maladies Respiratoires. asthma severity and lung function were of no importance. Department of Respiratory Medicine. decreased the baseline Isc in all non-CF and CF bronchial and bronchiolar preparations (p< 0.01). Hall B2-11 . The scale indicates velocity magnitude. Flow cytometry was used to analyze the expression of leptin receptor in A549 cells and for Annexin V apoptotic test. Furthermore. 1 We believe that CFD simulations using CT-derived realistic airways will benefit inhalation therapy (particles and gases) protocols. 168 (82%) had persistent AHR and in 37 (18%) AHR had resolved at follow-up. In conclusion. Hôpital Arnaud de Villeneuve. Elisabetta Pace 1 .5 l/s) is presented where streamlines are depicted. At entry. p<0. we found that while apigenin increases the percentage of annexin V positive cells and the activation of caspase 3. Laguna Beach. Bispebjerg University Hospital. Consiglio Nazionale delle Ricerche. a NO donor.8 vs 0. We studied the effect of leptin and apigenin in the apoptosis and in the proliferation of the A549 lung adenocarcinoma cell line. Italy. An association between persistent AHR and mean changes in AQLQS (p<0.02). Palermo. Italy Leptin.. The highest velocity values are observed in the oropharynx and the presence of the epiglottis induces flow perturbations. France. atopy. France. including all domains. Celeste Porsbjerg. Copenhagen NV. oxygen). a common edible plant flavonoid. we studied the effects of NO on Na and Cl transports in human non-CF and CF proximal and distal airways. Linda M. CT images were used to produce an accurate 3D geometrical model in a series of steps. Marco Giammanco 3 . Computational fluid dynamics (CFD) simulations can improve the protocols utilized in the administration of such airborne drugs. Visit Nonin Medical.11±0. Air Liquide R&D/CRCD. Finally. It also exerts proliferative and anti-apoptotic activities in a variety of cell types. Università degli Studi. Pierre Bonnette 2 . an accurate 3D surface mesh was obtained using a “marching cube” algorithm. a hormone produced by adipose tissue.05). Na and Cl transports were assessed by measuring the effects of amiloride and forskolin on Isc. severity of asthma and use of ICS. of which activity score showed clinical significant declines. P3876 Asthmatics with persistent airway hyperresponsiveness showed deteriorations in AQLQ – a three year follow-up study Vibeke Backer. The purpose was to study the changes in AQLQ in asthmatics with persistent AHR.5). 27% experienced improvement in AQLQS (>0. Pneumologia. France. and airflows during steady inspiration were simulated using FLUENT (Fluent Inc. Katz 1 . An original reconstruction approach was used to describe the TB tree up to the 6th generation as shown in Figure 1. 1 Medical Gases Group. Fig. is a pleiotropic molecule that regulates metabolic and immune functions. Materials and Methods: Data on 205 asthmatics with AHR to methacholine (PD20 < 8 ymol).3. United States Knowledge of air flow patterns within the human head and throat is necessary to quantify particle deposition processes (e. University Hospital and INSERM U454. aerosol therapy for asthma) and/or to optimize the delivery of medical gases (e. Martonen 2 . after three years of follow-up. Maria Ferraro 1 . the grey level CT scanned 668s Abstract printing supported by Nonin Medical. Danila Di Majo 3 . United States To target the delivery of inhaled drugs for the treatment of inflammatory respiratory diseases it is necessary to understand the physics involved in the transport and behavior of pharmaceutical aerosols and medical gases. 3 Dipartimento di Medicina. 2 Service de Chirurgie Thoracique. The aim of this study is to propose a method to build realistic morphological models of human extrathoracic airways based on computed tomography (CT) for use in computational fluid dynamics (CFD) simulations. Addition of SNP. respectively p<0. Fisiologia e Nutrizione Umana (DIMPEFINU). Les Loges en Josas. Then. apigenin may induce loss of mitochondrial transmembrane potential. High concentrations of leptin are able to decrease but not to abolish the effects of apigenin in cancer cell proliferation and apoptosis. The effect of amiloride was significantly reduced in non-CF and in CF cultures (p< 0. a “marching cube” algorithm was employed to build a bounding 3D surface. P3874 Airflow simulations in CT-derived tracheobronchial airways Georges Caillibotte 1 .g. Air Liquide R&D/CRCD. Mark Gjomarkaj 1 . S EPTEMBER 5 TH 2006 P3873 Leptin and apigenin: antagonists in the apoptotic pathway of lung adenocarcinoma cell line Andreina Bruno 1 . Western blots and clonogenic test were performed to evaluate the caspase 3 expression/activity and to assess the long term proliferation respectively.05). Gabriela Sbirlea-Apiou 1 . Laguna Beach. Vincenzo Bellia 3 . Inc. In Figure 1.05 for all). To begin. Giovanni Bonsignore 1 . increase of reactive oxygen species (ROS) production. Pascal Chanez 2 .4 vs 88±0. From this point.15±1. Boulogne-Billancourt. The aim of this study is to propose a methodology to build realistic morphological models of the human tracheobronchial (TB) tree based on computed tomography (CT). Our data suggest that CFD simulation may be a useful tool in the medical arena. Since NO may affect epithelial ion transport. a swirling flow pattern appears that will strongly modify motion. Katz 1 . Montpellier. Martonen 2 . Suresnes. 2 President. Conclusion: Asthmatics in whom AHR resolves during anti-asthmatics treatment experience an improvement in mean AQLQS and a clinical relevant improvement in activity score.. at stand C09 .5 l/s. CA. univariate analysis supported the deterioration in mean activity score during the observation period (– 0. were analysed with regard to the impact of persistent AHR on the AQLQ score. Gabriela Sbirlea-Apiou 1 . Ted B.3. In cancer cells.05) was found.20±0. First. Results: Of 205 patients. Ira M. LogRDR was slightly increased among those with persistent AHR (1. Palermo. 1 Medical Gases Group.

Pdimax . P3879 Evaluation of clinical efficiency of thiotriazolin in complex treatment of patients with community acquired pneumonia Iryna A. Tunc Lacin 4 . maximal esophagus pressure(Pesmax ). Malenky 2 . antiinflammation and detoxication effects. Mean increase in Vt during stimulation with 2. twitch mouth pressure(TwPmo). Maximal inspiratory pressure(MIP). Istanbul.decreases inflammation and permeability in the lung. Marmara University Faculty of Medicine. inhibited the SNP-induced reduction in baseline Isc.1)% and (9.6±9.829±0.with unknown aetiology. drowsiness 25%. O2 -saturation. (0.001).0. Aim: to determine safety and efficacy of prolonged CO2 -stimulated dry inhalation by a jet-nebulizer Methods: 12 healthy subjects received 3 20-minute dry inhalation sessions by a jet-nebulizer.000).816±0.9)%.So. Guangzhou. all P<0.Montelukast(M) is a cisLT-1 receptör antagonist. Guangzhou Institute of Respiratory Diseases.In conclusion. Inc.1±2. 89 patients with community acquired pneumonia of the 3rd group were examined. (10. Subjects completed a questionnaire of possible adverse events after every session.83 and 3.is a interstitial lung disease. headache 33%.37% (n = 7) or 3.05 for all). anti – inflammatory drags.Thematic Poster Session T UESDAY. Results (1)The r values between Pdimax and MIP. Pesmax and MIP.4±15.increase permeability and are chemoattractant. Vinnitsa.32 rats with a single dose of 5 mg/kg BLM intratracheally. The use of Thiotriazolin in patients with community acquired pneumonia of the 3rd group influences positively the course of the disease. Berrin Ceyhan 1 .446). and palpitations 8%.TGFβ1 level in late term was 60.H.05). Myeloperoxidase(MPO) and collagen levels in the lung tissue were measured.923±0. The level of endogenous intoxication of patients who took Thiotriazolin improved reliably quicker comparing with patients of the control group already at the 3rd day of treatment (p<0. A metabolic monitor documented Vt and respiratory rate (RR). Guangdong. 2 Pharmacology. This study allows including Thiotriazolin to the basic treatment of patients with community acquired pneumonia of the 3rd group. Sebastiaan Holverda.3)%. No significant changes in pulse. Vinnitsa National Medical University.TGFβ1. Inc. Anco Boonstra. 4 Thoracic Surgery.2±4. twitch transdiaphragmatic pressure(TwPdi)and twitch esophagus pressure(TwPes) were measured before nar- ± 669s Abstract printing supported by Nonin Medical. Marmara University Faculty of Medicine.12:50-14:40 P3878 Protective effect of leukotriene receptor antagonist montelukast in bleomycin induced pulmonary fibrosis Nurhayat Topaloglu 1 . S EPTEMBER 5 TH 2006 We then explored the mechanism of this inhibitory effect of NO in non-CF bronchial cultures.TNFα and TGFβ1 levels in lavage fluid. (0. (15.05 and p < 0.Results.976±0. significantly reduced Isc and the effects of amiloride and forskolin (p< 0.292) respectively.Oxygen metabolites cause the release of arachidonic acid(AA). respectively(P<0. Vital functions were documented at determined intervals. treated by standard therapy (antibiotics. 40 of them. Marmara University Faculty of Pharmacy.16 of these M was given with a dose of 10 mg/kg/day intraperitoneally five days before BLM. respectively.MDA and MPO levels were higher in BLM group.0)%. Vinnitsa National Medical University. stabilize the membranes of mast cells.05=.A. Kunst. Turkey.030). prevents the complications and decreases the term of hospitalization up to 3 days. appetite became better.Bronchoalveolar lavage fluid was collected and pneumonectomy was applied 4 days and 15 days after BLM administration in order to evaluate early and late term inflammatory and oxidative stress effects.8±5. Atie van Wijk. (0. (3)The r between the changing values of TwPtrnar and TwPdinar or TwPesnar during narcotization were 0. 1 Pulmonary Disease.168) and (0.9pg/ml and 34. P3881 Prolonged stimulation of dry inhalation with CO2 -enriched air through a jet-nebulizer: safety and efficacy Bart P.gluthation(GSH). (2)The CV of MIP. a phosphodiesterase inhibitor. Herman Groepenhoff. The increase in Vt persisted during the time of stimulation.155). Ukraine Our aim was to study clinical efficiency of Thiotriazolin in the complex treatment of patients with community acquired pneumonia. We conclude that NO non-selectively inhibits ion transport in non-CF and CF human bronchial and bronchiolar epithelia and that this effect is mediated by the cGMP pathway.839(P=0. and disappeared after the end of the study. Cigdem Ataizi Celikel 3 . Pesmax . (15.16 controls. No significant changes in RR were documented.Inflammatory cells release oxygen species and cytokines that result in parenchymal injury. Istanbul. BLM associated inflammatory response and oxidative injury in lungs could be prevented by Montelukast. Whether this translates into better deposition has to be investigated. The temperature became normal.GSH levels were lower in BLM group. at stand C09 . Emine Bas 3 .000)&#21644. P3880 The relationship between mouth pressure or tracheal pressure and esophagus pressure and diaphragmatic pressure Zeguang Zheng. an inhibitor of soluble guanylate cyclase. The Netherlands Rationale: CO2 -enriched air increases tidal volume (Vt) during short inhalation sessions without unpleasant side effects.5% respectively compared to baseline. Ukraine.Totally 48 rats. Leukotrienes(LT) are generated by AA. twitch esophagus pressure(TwPesnar )and twitch transdiaphragmatic pressure(TwPdinar )were dynamically monitored during that. China Objective To investigate the relationship between mouth pressure(Pmo) or tracheal pressure(Ptr) and esophagus pressure(Pes) or transdiaphragmatic pressure. Postmus.31% CO2 (n= 5) in 2 sessions and ambient air only in 1 session.7)%. Ozer Sehirli 2 . TwPdinar and TwPtrnar . (0. Istanbul.7± 3.185). Visit Nonin Medical. antileukotriene antagonists may be used to treat IPF.001 respectively). Conclusion: Stimulation of ventilation with CO2 -enriched ambient air during dry inhalation via a jet nebulizer is safe and sustains during a 20-minute inhalation period. 1 Department of Hospital Therapy #1.Malondialdehit(MDA).955±0. Turkey. Results: subjects inhaled ambient air mixed with 2. Pesmax and Pdimax (P>0. Pieter E. Ilyuk 1 .compared with control and BLM+M group in the early and late term. Br-cGMP combined with zaprinast. 2 Department of Hospital Therapy #1. 05). which could be dynamically monitored by TwPtrnar . breathlessness decreased. level of middle molecular substance.8μprot/g. Turkey Idiopathic pulmonary fibrosis(IPF). 3 Pathology. Vasily P.05). Amsterdam.We investigated the early and late term effects of M on bleomycin(BLM) induced pulmonary fibrosis. and blood pressure were observed during the study. Pulmonary Diseases. sorption function of red blood cells) decreased considerably.Collagen contents in the late term were higher in BLM group when compared with control and BLM+M groups (29. Istanbul.01). indices of intoxication (leukocytes index of intoxication. The CV of TwPmo was the highest(compare with others.2±2. VU University Medical Center. All existed in common toxicity criteria grade 1. maximal trandiaphragmatic pressure(Pdimax ). TwPmo. TwPdi and TwPmo.83 ± 0.5±4. Conclusion The test of MIP and TwPmo should be repeated and the highest value was the choice in order to reduce the possibility of underestimating the function of diaphragm. At the 3rd day of treatment 59% of the patients in the basic group had grater reduction of neutrofil count in phlegm cytogram than in the control group (p<0. Hall B2-11 . respectively (p < 0.1 μprot/g and 17. TwPes and TwPmo. respectively.TNFα. Goksel Sener 2 . Adverse events that were reported are xerostomy 83%. The rest 49 pathients formed a basic group and were treated by standard therapy in addition with Thiotriazolin which has antioxidant.05= and that of TwPes and TwPdi was the lowest(compare with others. bronholitics) were a control group. TwPesnar and TwPtrnar were (0. ICU.981±0. They were randomly assigned to different levels of [CO2 ]. (30. dizziness 8%. Turkey. Methods Seventeen patients were involved in the study.2±4. Wittgen. The presence of ODQ.when compared with other.There was not differentiation among the MIP. all P<0. Marmara University Faculty of Medicine.66% CO2 were 22 ± 15% and 30 ± 2.9±4. Increase in Vt was significant for both concentrations (p < 0.66 ± 0.7pg/ml for BLM and BLM+M groups. Peter W. TwPes and TwPdi were (14.1)%. Vinnitsa.894(P=0. cotization as a normal procedure for the abdominal operation and twitch treacheal pressure(TwPtrnar ).

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