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 efciency 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 (Prole Respiratory, UK) and a Pari LC+ [LC+] attached to a Pari Turbo BOYN (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 - ne particle dose MMAD (m) 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=205 mmHg; PP=105; best Peep =64 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 4.11.4 (mean SD) days of ventilation compared to 7.12.7 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.

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Thematic Poster Session

T UESDAY, S EPTEMBER 5 TH 2006
P3873 Leptin and apigenin: antagonists in the apoptotic pathway of lung adenocarcinoma cell line Andreina Bruno 1 , Maria Ferraro 1 , Elisabetta Pace 1 , Pascal Chanez 2 , Danila Di Majo 3 , Marco Giammanco 3 , Giovanni Bonsignore 1 , Vincenzo Bellia 3 , Mark Gjomarkaj 1 . 1 Istituto di Biomedicina e Immunologia Molecolare (IBIM), Consiglio Nazionale delle Ricerche, Palermo, Italy; 2 Clinique des Maladies Respiratoires, University Hospital and INSERM U454, Hpital Arnaud de Villeneuve, Montpellier, France; 3 Dipartimento di Medicina, Pneumologia, Fisiologia e Nutrizione Umana (DIMPEFINU), Universit degli Studi, Palermo, Italy Leptin, a hormone produced by adipose tissue, is a pleiotropic molecule that regulates metabolic and immune functions. It also exerts proliferative and anti-apoptotic activities in a variety of cell types. Apigenin, a common edible plant avonoid, is normally involved in antioxidant mechanisms. In cancer cells, apigenin may induce loss of mitochondrial transmembrane potential, increase of reactive oxygen species (ROS) production, induction of apoptotic pathway and antiproliferative effect. We studied the effect of leptin and apigenin in the apoptosis and in the proliferation of the A549 lung adenocarcinoma cell line. Flow cytometry was used to analyze the expression of leptin receptor in A549 cells and for Annexin V apoptotic test. Western blots and clonogenic test were performed to evaluate the caspase 3 expression/activity and to assess the long term proliferation respectively. First, we demonstrated that A549 express leptin receptor. Furthermore, we found that while apigenin increases the percentage of annexin V positive cells and the activation of caspase 3, leptin receptor activation decreases all these events. High concentrations of leptin are able to decrease but not to abolish the effects of apigenin in cancer cell proliferation and apoptosis. In conclusion, these results strongly suggest the utility of avonoids in the complementary therapeutic approach of cancer patients.

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

images were used to dene the passages. Then, a marching cube algorithm was employed to build a bounding 3D surface. Finally, the computational domain was meshed with tetrahedral elements using third party software, and airows during steady inspiration were simulated using FLUENT (Fluent Inc.). In Figure 1, the inuence of the realistic airway geometry on the ow eld during inspiration at resting conditions (0.5 l/s) is presented where streamlines are depicted. The scale indicates velocity magnitude. The highest velocity values are observed in the oropharynx and the presence of the epiglottis induces ow perturbations.

Fig. 1

We believe that CFD simulations using CT-derived realistic airways will benet inhalation therapy (particles and gases) protocols.

P3874 Airow simulations in CT-derived tracheobronchial airways Georges Caillibotte 1 , Ira M. Katz 1 , Gabriela Sbirlea-Apiou 1 , Ted B. Martonen 2 . 1 Medical Gases Group, Air Liquide R&D/CRCD, Les Loges en Josas, France; 2 President, CyberMedicine, Laguna Beach, CA, United States To target the delivery of inhaled drugs for the treatment of inammatory respiratory diseases it is necessary to understand the physics involved in the transport and behavior of pharmaceutical aerosols and medical gases. Computational uid dynamics (CFD) simulations can improve the protocols utilized in the administration of such airborne drugs. 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). An original reconstruction approach was used to describe the TB tree up to the 6th generation as shown in Figure 1. From this point, an accurate 3D surface mesh was obtained using a marching cube algorithm. Then, the CFD computational domain was meshed with tetrahedral elements using commercial software. Airows occurring during steady inspiration were simulated using FIDAP from Fluent Inc. The results in Figure 2 show the inuence of the realistic airway geometry on streamlines.

P3876 Asthmatics with persistent airway hyperresponsiveness showed deteriorations in AQLQ a three year follow-up study Vibeke Backer, Linda M. Rasmussen, Celeste Porsbjerg. Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen NV, Denmark Background: The presence of airway hyperresponsiveness (AHR) among asthmatics has been shown to worsen AQLQ independently of the severity of asthma. The purpose was to study the changes in AQLQ in asthmatics with persistent AHR. Materials and Methods: Data on 205 asthmatics with AHR to methacholine (PD20 < 8 ymol), were analysed with regard to the impact of persistent AHR on the AQLQ score, after three years of follow-up. Results: Of 205 patients, 168 (82%) had persistent AHR and in 37 (18%) AHR had resolved at follow-up. At entry, LogRDR was slightly increased among those with persistent AHR (1.110.4 vs 880.3, p<0.01), whereas AQLQS and FEV1 was comparable. An association between persistent AHR and mean changes in AQLQS (p<0.01) and environment domain (p<0.05) was found, whereas compliance, use of ICS, atopy, asthma severity and lung function were of no importance. However, when analyzing clinical signicant changes in AQLQS, including all domains, 27% experienced improvement in AQLQS (>0.5), whereas improval in activity domain showed negative association with persistent AHR (19%) versus those without AHR (36%)(p=0.02). Furthermore, univariate analysis supported the deterioration in mean activity score during the observation period ( 0.200.8 vs 0.151.3, respectively p<0.05). Conclusion: Asthmatics in whom AHR resolves during anti-asthmatics treatment experience an improvement in mean AQLQS and a clinical relevant improvement in activity score, whereas asthmatics with persistent AHR have deterioration in AQLQ independent of lung function, severity of asthma and use of ICS, of which activity score showed clinical signicant declines.

Fig. 1

Fig. 2

At 0.5 l/s, a swirling ow pattern appears that will strongly modify motion. Our data suggest that CFD simulation may be a useful tool in the medical arena.

P3877 Nitric oxide (NO) inhibits ion transport in human non-CF and CF proximal and distal airways Luc Dannhoffer 1 , Sabine Blouquit 1 , Emmanuel Naline 1 , Pierre Bonnette 2 , Thierry Chinet 1 . 1 UPRES EA220, UFR Paris Ile de France Ouest, Boulogne-Billancourt, France; 2 Service de Chirurgie Thoracique, Hpital Foch, Suresnes, France NO is produced by airway epithelium and is involved in several airway functions, such as ciliary beat frequency and anti-microbial properties. Previous studies have shown that exhaled NO is reduced in cystic brosis (CF). Since NO may affect epithelial ion transport, we studied the effects of NO on Na and Cl transports in human non-CF and CF proximal and distal airways. 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. Na and Cl transports were assessed by measuring the effects of amiloride and forskolin on Isc. Addition of SNP, a NO donor, decreased the baseline Isc in all non-CF and CF bronchial and bronchiolar preparations (p< 0.05 for all). The effect of amiloride was signicantly reduced in non-CF and in CF cultures (p< 0.05 for both) and the effect of forskolin was signicantly reduced in non-CF preparations (p< 0.05).

P3875 Airow simulations in CT-derived extrathoracic airways Georges Caillibotte 1 , Ira M. Katz 1 , Gabriela Sbirlea-Apiou 1 , Ted B. Martonen 2 . 1 Medical Gases Group, Air Liquide R&D/CRCD, Les Loges en Josas, France; 2 President, CyberMedicine, Laguna Beach, CA, United States Knowledge of air ow patterns within the human head and throat is necessary to quantify particle deposition processes (e.g., aerosol therapy for asthma) and/or to optimize the delivery of medical gases (e.g., oxygen). 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 uid dynamics (CFD) simulations. CT images were used to produce an accurate 3D geometrical model in a series of steps. To begin, the grey level CT scanned

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Thematic Poster Session

T UESDAY, S EPTEMBER 5 TH 2006
We then explored the mechanism of this inhibitory effect of NO in non-CF bronchial cultures. Br-cGMP combined with zaprinast, a phosphodiesterase inhibitor, signicantly reduced Isc and the effects of amiloride and forskolin (p< 0.05 for all). The presence of ODQ, an inhibitor of soluble guanylate cyclase, inhibited the SNP-induced reduction in baseline Isc. 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.

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

P3878 Protective effect of leukotriene receptor antagonist montelukast in bleomycin induced pulmonary brosis Nurhayat Topaloglu 1 , Goksel Sener 2 , Emine Bas 3 , Cigdem Ataizi Celikel 3 , Berrin Ceyhan 1 , Tunc Lacin 4 , Ozer Sehirli 2 . 1 Pulmonary Disease, Marmara University Faculty of Medicine, Istanbul, Turkey; 2 Pharmacology, Marmara University Faculty of Pharmacy, Istanbul, Turkey; 3 Pathology, Marmara University Faculty of Medicine, Istanbul, Turkey; 4 Thoracic Surgery, Marmara University Faculty of Medicine, Istanbul, Turkey Idiopathic pulmonary brosis(IPF),with unknown aetiology,is a interstitial lung disease.Inammatory cells release oxygen species and cytokines that result in parenchymal injury.Oxygen metabolites cause the release of arachidonic acid(AA). Leukotrienes(LT) are generated by AA,increase permeability and are chemoattractant.Montelukast(M) is a cisLT-1 receptr antagonist,decreases inammation and permeability in the lung.We investigated the early and late term effects of M on bleomycin(BLM) induced pulmonary brosis.Totally 48 rats;16 controls,32 rats with a single dose of 5 mg/kg BLM intratracheally,16 of these M was given with a dose of 10 mg/kg/day intraperitoneally ve days before BLM.Bronchoalveolar lavage uid was collected and pneumonectomy was applied 4 days and 15 days after BLM administration in order to evaluate early and late term inammatory and oxidative stress effects.TNF and TGF1 levels in lavage uid,Malondialdehit(MDA),gluthation(GSH), Myeloperoxidase(MPO) and collagen levels in the lung tissue were measured.Results;TNF,TGF1,MDA and MPO levels were higher in BLM group,compared with control and BLM+M group in the early and late term.TGF1 level in late term was 60.12.9pg/ml and 34.7 3.7pg/ml for BLM and BLM+M groups, respectively(P<0.001).Collagen contents in the late term were higher in BLM group when compared with control and BLM+M groups (29.69.1 prot/g and 17.22.8prot/g, respectively (p < 0.01).GSH levels were lower in BLM group,when compared with other.In conclusion; BLM associated inammatory response and oxidative injury in lungs could be prevented by Montelukast.So; antileukotriene antagonists may be used to treat IPF.

cotization as a normal procedure for the abdominal operation and twitch treacheal pressure(TwPtrnar ), twitch esophagus pressure(TwPesnar )and twitch transdiaphragmatic pressure(TwPdinar )were dynamically monitored during that. Results (1)The r values between Pdimax and MIP, TwPdi and TwPmo, TwPdinar and TwPtrnar , Pesmax and MIP, TwPes and TwPmo, TwPesnar and TwPtrnar were (0.9760.030), (0.8160.155), (0.9230.446), (0.9810.185), (0.8290.168) and (0.9550.292) respectively. (2)The CV of MIP, Pesmax , Pdimax , TwPmo, TwPes and TwPdi were (14.24.7)%, (15.24.3)%, (15.54.1)%, (30.415.9)%, (10.85.1)% and (9.94.0)%, respectively. The CV of TwPmo was the highest(compare with others, all P<0.05= and that of TwPes and TwPdi was the lowest(compare with others, all P<0.05=.There was not differentiation among the MIP, Pesmax and Pdimax (P>0.05). (3)The r between the changing values of TwPtrnar and TwPdinar or TwPesnar during narcotization were 0.839(P=0.000)&#21644;0.894(P=0.000), respectively. 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, which could be dynamically monitored by TwPtrnar . P3881 Prolonged stimulation of dry inhalation with CO2 -enriched air through a jet-nebulizer: safety and efcacy Bart P.H. Wittgen, Pieter E. Postmus, Anco Boonstra, Herman Groepenhoff, Sebastiaan Holverda, Atie van Wijk, Peter W.A. Kunst. Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands Rationale: CO2 -enriched air increases tidal volume (Vt) during short inhalation sessions without unpleasant side effects. Aim: to determine safety and efcacy 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. They were randomly assigned to different levels of [CO2 ]. A metabolic monitor documented Vt and respiratory rate (RR). Vital functions were documented at determined intervals. Subjects completed a questionnaire of possible adverse events after every session. Results: subjects inhaled ambient air mixed with 2.83 0.37% (n = 7) or 3.66 0.31% CO2 (n= 5) in 2 sessions and ambient air only in 1 session. No signicant changes in pulse, O2 -saturation, and blood pressure were observed during the study. Increase in Vt was signicant for both concentrations (p < 0.05 and p < 0.001 respectively). Mean increase in Vt during stimulation with 2.83 and 3.66% CO2 were 22 15% and 30 2.5% respectively compared to baseline. The increase in Vt persisted during the time of stimulation. No signicant changes in RR were documented. Adverse events that were reported are xerostomy 83%, headache 33%, drowsiness 25%, dizziness 8%, and palpitations 8%. All existed in common toxicity criteria grade 1, and disappeared after the end of the study. 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. Whether this translates into better deposition has to be investigated.

P3879 Evaluation of clinical efciency of thiotriazolin in complex treatment of patients with community acquired pneumonia Iryna A. Ilyuk 1 , Vasily P. Malenky 2 . 1 Department of Hospital Therapy #1, Vinnitsa National Medical University, Vinnitsa, Ukraine; 2 Department of Hospital Therapy #1, Vinnitsa National Medical University, Vinnitsa, Ukraine Our aim was to study clinical efciency of Thiotriazolin in the complex treatment of patients with community acquired pneumonia. 89 patients with community acquired pneumonia of the 3rd group were examined. 40 of them, treated by standard therapy (antibiotics, anti inammatory drags, bronholitics) were a control group. The rest 49 pathients formed a basic group and were treated by standard therapy in addition with Thiotriazolin which has antioxidant, antiinammation and detoxication effects, stabilize the membranes of mast cells. 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<0,05). The temperature became normal, breathlessness decreased, appetite became better, indices of intoxication (leukocytes index of intoxication, level of middle molecular substance, sorption function of red blood cells) decreased considerably. At the 3rd day of treatment 59% of the patients in the basic group had grater reduction of neutrol count in phlegm cytogram than in the control group (p<0, 05). The use of Thiotriazolin in patients with community acquired pneumonia of the 3rd group inuences positively the course of the disease, prevents the complications and decreases the term of hospitalization up to 3 days. This study allows including Thiotriazolin to the basic treatment of patients with community acquired pneumonia of the 3rd group.

P3880 The relationship between mouth pressure or tracheal pressure and esophagus pressure and diaphragmatic pressure Zeguang Zheng. ICU, Guangzhou Institute of Respiratory Diseases, Guangzhou, Guangdong, China Objective To investigate the relationship between mouth pressure(Pmo) or tracheal pressure(Ptr) and esophagus pressure(Pes) or transdiaphragmatic pressure. Methods Seventeen patients were involved in the study. Maximal inspiratory pressure(MIP), maximal trandiaphragmatic pressure(Pdimax ), maximal esophagus pressure(Pesmax ), twitch mouth pressure(TwPmo), twitch transdiaphragmatic pressure(TwPdi)and twitch esophagus pressure(TwPes) were measured before nar-

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