COPD acute exacerbations Oral Presentation Auditorium

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					                                                              TUESDAY, SEPTEMBER               20 TH 2005

Normal image: healthy lung images appear with an almost symmetrical, simulta-            a tumour in the mediastinum and 103 patients with enlarged lymph nodes in the
neous development of the VR, which correlates with airflow dynamics.                      mediastinum or the hillar regions. Bronchoscopy and TBNA have been performed
Disease states examples: Lung tumor image results in an asymmetrical appearance          in all patients without obtaining a diagnosis
and reduced VR and disturbed dynamics in the tumor area. Pleural fluid results in         Results: A total of 7 tumours and 204 lymph nodes were biosied. EBUS TBNA
reduced meniscus shape in the lower lobes and absence of VR in the area of the           was positive for cancer in 108 lymph nodes and 6 tumours. In 11 lesions the
pleural fluid.                                                                            specimen was without conclusive material.
Conclusion: The VRI provides dynamic lung image that differs significantly                In 85 patients a malignant diagnose was obtained. In 18 patients a specific
between healthy and diseased lungs. VRI may provide an innovative, noninvasive           non malignant diagnose was obtained). In 19 patients normal lymph cells were
method for evaluating lung condition.                                                    obtained. All the diagnosis was confirmed either by EUS, mediastinoscopy or
* www.deepbreeze.com                                                                     Thoracotomy/scopy. The diagnostic yield was 95% (193/204)
                                                                                         In 17 patients the malignant diagnose was obtained by puncture of N1 lymph
                                                                                         nodes
3034                                                                                     Conclusion: EBUS TBNA is an effective and non invasive method to obtain a
Magnetic resonance imaging (MRI) of the lung as a tool for the non-invasive              diagnose in patients with lesions of unknown origin in the mediastinum and hillar
evaluation of drugs in rat models of airways diseases                                    regions
Harry K. Quintana 1,3 , Catherine Cannet 1 , Bruno Tigani 1 , John R. Fozard 2 , Clive
P. Page 3 , Nicolau Beckmann 1 . 1 Discovery Technologies, Novartis Pharma,
Basel, Switzerland; 2 Respiratory Disease Area, Novartis Pharma, Basel,
Switzerland; 3 Sackler Institute of Pulmonary Pharmacology, King’s College,
London, United Kingdom

For many years, MRI has been applied to many disease areas in pharmaceutical
                                                                                                   299. COPD – acute exacerbations
research. Its main assets are non-invasiveness, high spatial resolution, and the
wealth of information the technique can provide.
MRI has only recently been applied in the area of pulmonary pharmacology.
Scans are performed in spontaneously breathing animals deriving anatomical and           3037
functional read outs in models of airways disease with the aim to profile drugs.          Early discharge for patients with exacerbations of COPD - a real life cohort
Two illustrative examples are allergen (ovalbumin, OVA) and lipopolysaccharide           study
(LPS) inducing distinct inflammatory responses in rats. For OVA, MRI signals              Gudrun E. Seebass, Paul K. Plant, Victoria Walker. Respiratory Medicine, St
correlate with eosinophilia and increased protein content in bronchoalveolar lavage      James University Hospital, Leeds, West Yorkshire, United Kingdom
fluid (BALF). Following LPS, MRI signals reflect secreted mucus as revealed in
BALF. Histology confirms these results.                                                   We reviewed all emergency admissions for COPD to a large teaching hospital over
The effects of airways remodeling and hyporesponsiveness induced by respectively         a 5 months period, comparing a cohort of 75 patients from East Leeds with access
OVA or LPS can also be monitored by detecting modulations of the parenchymal             to early supported discharge to 91 patients from other areas without this facility.
signal caused by changes in oxygenation levels.                                          41% of the patients from East Leeds took part in the early discharge scheme.
These approaches provide the basis for non-invasive testing of anti-inflammatory          Median length of hospital stay for all patients from East Leeds was 4 days less
compounds for respiratory diseases.                                                      than for the patients from other areas. Kaplan-Meier analysis shows no significant
* Grant from the 3R Foundation, Muensingen, Switzerland (Project 82/02 to NB)            differences in readmission and death rates for both groups. Most patients in the
                                                                                         early discharge scheme were very satisfied with their treatment.
                                                                                         Our selection criteria are similar to those used in randomized controlled trials,
3035                                                                                     who found 25% of their patients suitable for early discharge (Ram, F.S.F. et al.
Structural lung abnormalities in bronchopulmonary dysplasia: a new scoring               BMJ 2004; 329: 315-318). Our data suggests that early discharge with support of
system for standardised lung-CT scan evaluation                                          respiratory specialist nurses is a feasible and safe alternative to hospital treatment
Valeria Casotti 1 , Lorenzo Rubin 1 , Maarten H. Lequin 2 , Harm A. Tiddens 2 .          for over 40% of patients admitted with exacerbations of COPD.
1
  Paediatric and Radiology Department, Policlinico G.B. Rossi, Verona, Italy;
2
  Paediatric Pulmonology, Allergology and Radiology, Erasmus MC-Sophia,
Rotterdam, The Netherlands                                                               3038
                                                                                         The outcome of patients with COPD admitted to UK hospitals with an
Frequently in BPD patients lung function impairment and respiratory symptoms             exacerbation. Results from the RCP/BTS national COPD audit
persist in childhood. Little is known about the structural substrate responsible for     Harold S.R. Hosker, Katharine Anstey, Derek Lowe, Michael Pearson, Michael
these abnormalities.                                                                     C. Roberts. Clinical Effectivenss & Evaluation Unit, Royal College of Physicians,
Aims: To describe long term structural changes on CT scans of BPD patients,              London, United Kingdom
developing a scoring system to define these abnormalities in a systematic and
reproducible fashion.                                                                    Over 95% of UK acute hospitals took part in an audit of acute COPD care in
Methods: Retrospective analysis of patients with a diagnosis of BPD and who              september 2003. Hospitals supplied information on 1) resources and organisation
had a thorax CT scan. CT were evaluated to identify and record all structural            of care, and 2) clinical data on up to 40 consecutive COPD admissions detailing
abnormalities. Next, a scoring system was developed and 2 independent readers            both process of care and outcomes.
scored all scans to determine inter-observer reproducibility.                            There were 8013 admissions involving 7529 patients from 234 units in the UK.
Results: 19 BPD patients were identified. Age at CT was 1 to 15 years. A score            Mean age was 71 years, and median FEV1 (known for 43%) was 37% predicted.
was developed evaluating the 5 lobes, that includes the following lesions: decreased     64% had been admitted previously with an exacerbation. 36% lived alone and 21%
density of parenchyma, interstitial fibrosis, thickening of the interlobular septa,       had limited self-care or were bed/chair bound. 72% had other significant medical
triangular sub pleural opacities; emphysema, bulla, cysts; air trapping; atelectasis;    conditions. 39% were current smokers and 4% had never smoked.
consolidations; ground glass appearance; mucus plugging; bronchiectasis and air-         Median length of stay was 6 (IQR 3-11) days (6 days for units with an early dis-
way wall thickening. Mean CT score was 23 (8 to 45). Interobserver agreement             charge scheme and 7 days for those without a scheme). 15% of all COPD patients
(Spearman correlation) was excellent (R=0.976, p< 0,001). Bland and Altman               died within 90 days of admission. In-hospital death rate was 7.5%. Variation in
analysis showed no systematical errors between observers.                                90 day mortality between units was wide (IQR 9-21%). 81% of deaths were due
Conclusion: CT scans of a selection of BPD patients show considerable structural         to COPD. 31% (IQR 22-40) of all discharges had been readmitted to hospital
abnormalities. A CT-scoring system was developed that was highly reproducible.           within the 90 day period. Logistical regression showed that 25% of variation in
                                                                                         outcome (90 day mortality) was due to patient case-mix factors. The remainder is
                                                                                         unexplained.
3036                                                                                     This study confirms the high mortality and readmission rates associated with
EBUS-TBNA - endoscopic transbronchial real time ultrasound guided biopsy                 hospital admission due to COPD exacerbations. Further analyses of organisational
for diagnosis of mediastinal and hillar changes                                          and resource factors may explain further the wide variability in outcome between
Mark Krasnik, Felix Herth, Peter Vilmann, Ralf Eberhardt, Birgit Skov. Thoracic          units.
Surg, Gentofte University Hospital, Copenhagen, Denmark; Pulmonology,
Thoraxclinic Heidelberg, Heidelberg, Germany; Gastrosurgery, Gentofte
University Hospital, Copenhagen, Denmark; Pulmonology, Thoraxclinic                      3039
Heidelberg, Heidelberg, Germany; Pathology, Gentofte University Hospital,                The effect of unit organisation and resources on outcomes of hospital
Copenhagen, Denmark                                                                      admission for COPD exacerbations
                                                                                         Harold S.R. Hosker, Katharine Anstey, Derek Lowe, Michael Pearson, Michael
Aim: The aim of the present study was to test the use of EBUS-TBNA in the                C. Roberts. Clinical Effectiveness & Evaluation Unit, Royal College of
evaluation of mediastinal and hillar lesions in patients with an undiagnosed solid       Physicians, London, United Kingdom
lesion of unknown origin in the mediastinum and hillar regions or enlarged lymph
nodes in the mediastinum outlined by CT.                                                 An audit of 8013 admissions for exacerbation of COPD was conducted in the UK
Material: EBUS TBNA was prospective performed in 110 patients. 7 patients with           in September 2003. 95% of acute units took part. Units supplied information on


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         Oral Presentation                                                                                                Auditorium 10 - 08:30-10:30
                                                                     TUESDAY, SEPTEMBER                20 TH 2005

1) resources and organisation of care and 2) clinical data on up to 40 consecutive               3042
COPD admissions, detailing both process of care and outcomes.                                    Clinical value of C-reactive protein in severe acute exacerbations of COPD
Logistic regression showed that 25% of the variation in outcomes (death at 90 days,              Johannes M.A. Daniels 1 , Casper S. de Graaff 1 , Fer Vlaspolder 2 , Wim
readmisson, length of stay (LOS)) were explained by patient factors. The major                   G. Boersma 1 . 1 Pulmonology, Medical Center Alkmaar, Alkmaar, The
determinants were performance status; blood urea; SaO2 ; arterial pH; albumin and                Netherlands; 2 Medical Microbiology, Medical Center Alkmaar, Alkmaar, The
age.                                                                                             Netherlands
Random effects logistical regression modelling was used to investigate resource
and organisational factors in relation to outcomes. For mortality, number of respi-              Introduction: Acute exacerbations of COPD constitute a major health problem.
ratory consultants/1,000 beds showed an inverse relationship (OR = 0.75 for 90 day               It is important to improve treatment strategies to minimize the length and fre-
mortality, 0.67 for inpatient death). The % patients with LOS >7 days decreased                  quency of exacerbations. Not many tests are useful for monitoring exacerbations
with increasing number of respiratory consultants (OR = 0.81), availability of an                of COPD. C-reactive protein (CRP), an acute phase protein, is a good marker for
early discharge scheme (OR = 0.69) and presence of local guidelines (OR = 0.84).                 inflammation. We hypothesized that CRP might be useful in monitoring AECOPD.
Units with better composite organisational scores had less patients with LOS > 7                 Methods: Ninety patients with severe AECOPD were admitted to our clinic and
days (OR = 0.80). There was no association with size of hospital or ’star ratings’.              treated for seven days with intravenous steroids followed by oral steroids. Sponta-
No organisational or resource factors influenced readmission rates.                               neously expectorated sputum samples, spirometry and CRP were obtained at day
We conclude that organisational factors affect LOS, number of respiratory consul-                1, 8 and 21. Clinical outcome was assessed on day 8 and 21. We investigated
tants affects LOS, inpatient death rates and death rates at 90 days, but no hospital             bacterial presence and CRP as markers for clinical succes.
organisational or resource factors affect readmission rates.                                     Results: Mean age was 73 years and 61% were men. Mean FEV1 was 43% of
                                                                                                 predicted and 73% of sputum spamles were purulent. Clinical succes was 78% at
                                                                                                 day 8 and 71% at day 21. Clinical succes at day 8 and 21 was associated with
3040                                                                                             improvement of FEV1 (p=0.003 and p=0.058). CRP level at day 8 and 21 was
The hospital management of COPD exacerbations in the UK: does it conform                         associated with clinical outcome (p=0.003 and p=0.044). CRP had a sensitivity of
to national guidance?                                                                            87% as a marker for clinical succes. Bacterial presence was not associated with
Harold S.R. Hosker, Katharine Anstey, Derek Lowe, Michael Pearson, Michael                       treatment outcome or FEV1 .
C. Roberts. Clinical Effectiveness & Evaluation Unit, Royal College of                           Conclusion: CRP is a useful as a marker for outcome in patients with AECOPD.
Physicians, London, United Kingdom                                                               Bacterial presence is not associated with clinical outcome or CRP.

95% of UK acute hospitals took part in an audit of acute COPD care in 2003. Units
supplied data on 1) resources and organisation of care, and 2) clinical data on                  3043
40 COPD admissions detailing both process of care and outcomes. We compared                      Time course of sputum and serum interleukin-6 during COPD exacerbations
process of care with national guidance.                                                          R. Perera, R. Hurst, A. Wilkinson, C. Donaldson, A. Wedzicha. Academic Unit of
There were 8013 admissions involving 7529 patients. 14% of admissions entered                    Respiratory Medicine, St Bartholomew’s Hospital, London, United Kingdom
an early discharge scheme.
Performance against indicators of quality care are shown in the table. 21% of cases              Patients with COPD have higher levels of sputum interleukin(IL)-6 at onset of
received high flow oxygen in the ambulance, 85% had arterial blood gases checked                  an exacerbation.We compared the time course of serum and sputum IL-6 in 72
and 76% received controlled oxygen after admission. 1805 (23%) patients had a                    patients with COPD.
pH < 7.35 during admission but only 33% of these received ventilatory support                    72 exacerbations were studied in 72 COPD patients [mean(SD) age 69(8) years,
(IQR = 16-55).                                                                                   FEV1 1.07(0.47) l, % predicted FEV1 44(18.2) %, median(IQR) pack years 41(25-
                                                                                                 58)] who completed daily diary cards. They were sampled in the stable state, at
Hospital variation statistics                                                                    onset of an exacerbation and after 7,14, 35 days.
Factor                                                Median   IQR (25-75th centiles)   Range
                                                                                                 Sputum IL-6 increased significantly between baseline and onset of the exacerba-
                                                                                                 tion [mean(SD) sputum IL-6 increased from 1.93(0.58) to 2.16(0.46) log10 ng/ml,
% predicted FEV1 was known                              40             21-62             0-100   p=0.02], then returned progressively towards baseline by day 35, p=0.322. Serum
Uncontrolled high flow oxygen prior to admission         21             11-31             0-97    IL-6 increased significantly at onset of the exacerbation, [mean(SD) serum IL-6
Respiratory rate recorded                               84             71-93             9-100   increased from 0.77(0.37) to 1.07(0.51) log10 ng/ml; p=0.001], and decreased
Blood gases checked                                     85             76-92            19-100   significantly below baseline at day 7 to 0.52(0.39) log10 ng/ml, p=0.001. There
Received systemic steroids                              83             75-90            10-100   was no significant correlation between the serum and sputum markers at the
Did not see respiratory specialist during admission     27             13-44             0-100
                                                                                                 different sampling points. Patients with a higher number of symptoms at onset of
Under respiratory specialist at discharge               45             30-63             0-100
                                                                                                 the exacerbation had higher levels of sputum IL-6 in the stable state (rho=0.303,
Received ventilatory support if pH<7.35                 33             16-55             0-100
                                                                                                 p=0.04) and at day 7(rho=0.452,p=0.001).
                                                                                                 Sputum and serum IL-6 both show a significant rise at onset of an exacebation
Although compliance with national guidance is generally good, this study high-                   followed by a return towards baseline by day 35. However serum IL-6 differs from
lights some deficiencies, shows considerable variation in care provided to COPD                   sputum IL-6 by dropping below baseline at day 7. A higher baseline sputum IL-6
patients in the UK (table), and provides a benchmark for future audits.                          was associated with a higher number of symptoms at onset and persistently higher
                                                                                                 airway inflammation at day 7.

3041
Elevation of cardiac enzymes in COPD patients with respiratory failures                          3044
Ekrem Cengiz Seyhan, Sedat Altin, Erdogan Cetinkaya, Kursat Epozturk,                            Procalcitonin-guided antibiotic therapy in acute exacerbations of COPD
Sinem Timur. Chest Disease, Yedikule Chest Diseases and Chest Surgery                            (AECOPD): a randomised trial - the ProCOLD study
Education and Research Hospital, Istanbul, Turkey                                                Daiana Stolz, Mirjam Christ-Crain, Roland Bingisser, Mikael Gencay,
                                                                                                 Joerg Leuppi, David Miedinger, Christian Müller, Peter Huber, Beat Müller,
Objectives: This study aimed to compare the levels of cardiac myoglobin, CK-MB                   Michael Tamm. Pneumology, Endocrinology and Internal Medicine, University
and troponin I (cTnI), and their associations with myocardial injury during COPD                 Hospital, Basel, Switzerland
exacerbations and stable periods of the patients.
Methods: For this study, 45 patients (36 males, 9 females; mean age: 63.9±9.1,                   Background: Despite limited evidence supporting the use of antibiotics in AE-
range: 43-80) with respiratory failure due to COPD were enrolled. The patients                   COPD, antibiotic therapy is still widely prescribed. Procalcitonin (ProCT) has
were evaluated according to their clinical complaints, arterial blood gases, blood               been shown to identify patients with relevant bacterial infection. We performed
levels of CRP and cardiac enzymes, and electrocardiograpic findings both during                   a trial to evaluate the outcome of AECOPD comparing a standard with a ProCT
exacerbations and stable periods                                                                 guided antibiotic approach.
Results: In none of the patients, ECG revealed any finding of myocardial injury.                  Methods: 180 patients with AECOPD were included in this prospective, ran-
Twelve of the patients (26%) had chest pain. There was no significant difference                  domised, single centre trial. In the ProCT-group, antibiotic therapy was discouraged
between levels of cardiac enzymes, CRP, and arterial blood gases of patients with                (ProCT<0.1ng/ml) or encouraged (ProCT > 0.25ng/ml) based on ProCT levels.
and without chest pain. Nine of the paitents with exacerbation (20%) had cTnI                    The standardised work-up included CRP, WBC, sputum bacteriology, viral serol-
levels higher than normal. The levels of cTnI, myoglobin and CRP measured
during exacerbations showed significant decrease during stable periods (p<0.001).                                                 Standard group       ProCT guided-group      p-value
It has been observed that the patients with high levels of cTnI had lower PaO2
(45.1±3.4 vs 55±3.4 mmHg, p<0.001) and pH (7.23 vs 7.39, p<0.001) levels.                        Age, male gender (%)             71 y, 48 (53%)         70 y, 48 (53%)          ns
The level of cTnI had negative correlations with PaO2 (r= -0.74, p<0.001) and                    Antibiotics at admission (%)        19 (21%)               20 (22%)             ns
pH levels(r= -0.61, p<0.001), and a positive correlation with CRP level (r= 0.36,                Anthonisen Typ I (%)                43 (48%)               49 (54%)             ns
p<0.05).                                                                                         Positive bacteriology sputum         31/45                   28/57              ns
                                                                                                 GOLD III + IV %                       68%                    83%              0.039
Conclusion: In patients with respiratory failure due to COPD exacerbation, my-
                                                                                                 FEV1 mean (L) (%)              0.99±0.48 (44.9%)      0.85±0.32 (38.4%)         ns
ocardial injury has been observed on biochemical basis.
                                                                                                 Antibiotic use (%)                 62 (68.8%)             35 (38.8%)         0.0001
                                                                                                 Antibiotic use in days ± SD            7±5                    4±5            0.0001



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           Oral Presentation                                                                                                     Auditorium 10 - 08:30-10:30
                                                             TUESDAY, SEPTEMBER               20 TH 2005

ogy, spirometry, chest-X-ray. At 6 months, patients were re-evaluated in regard to      p<0.01). Intravenous theophylline, administered 30 min after mIL-5 treatment
clinical and laboratory parameters, spirometry and number of AECOPD.                    decreased blood eosinophil dose dependently (3 mg/kg; 8.83, 10 mg/kg; 7.13,
Results: see table.                                                                     30 mg/kg; 5.46, ×104 cells/mL). Interestingly, a component ratio of eosinophil in
Conclusion: A procalcitonin guided-approach allowed a 56% reduction of antibi-          the femoral bone marrow significantly decreased after mIL-5 treatment (Vehicle;
otic use in AECOPD requiring hospitalisation.                                           3.62%, mIL-5; 3.00%, p<0.01), and intravenous injection of theophylline inhibited
                                                                                        this decrease of component ratio (3 mg/kg; 3.32%, 10 mg/kg; 3.40%, 30 mg/kg;
                                                                                        3.45%). Similar effects of theophylline were also observed in the rat.
                                                                                        These results strongly suggest that intravenous injection of theophylline inhibits
                                                                                        mobilization of eosinophil from their internal pool such as bone marrow into the
                                                                                        blood. Our results also suggest the clinical efficacy of theophylline when used via
          300. Improving asthma control in                                              intravenous route.

           the harder-to-reach population
                                                                                        3048
                                                                                        Inhibitors of PDE4 delay eosinophil apoptosis
                                                                                        Jouni Parkkonen, Eeva Moilanen, Hannu Kankaanranta. The
                                                                                        Immunopharmacological Research Group, University of Tampere and Tampere
3045                                                                                    University Hospital, Tampere, Finland
Salmeterol treatment improves corticosteroid responsivness in patients with
corticosteroid-insensitive severe asthma                                                Eosinophils play a major role in asthma. One described mechanism leading to
Yasuo To, Ian M. Adcock, Peter J. Barnes, Kazuhiro Ito. Airway Disease Section,         impaired clearance of eosinophils from the lungs is the delay in their programmed
NHLI, Imperial College, London, United Kingdom                                          cell death (apoptosis). Phosphodiesterase 4 (PDE4) hydrolyses cyclic adenosine
                                                                                        monophosphates (cAMP) and inhibition of its activity leads to an increase in the
Corticosteroids are usually highly effective in the control of asthma. However, a       concentration of cAMP. Specific inhibitors of PDE4 are under development for the
small proportion of patients are corticosteroid-insensitive (CI) and may present        treatment of lung diseases because of their anti-inflammatory and bronchodilatory
considerable management problems. Long-acting β2 -adrenergic agonists (LABA)            actions. The aim of the present study was to find out whether inhibitors of PDE4
affect corticosteroid action by enhancing glucocorticoid receptor activation. In this   modulate human eosinophil apoptosis.
study, we investigated the effect of salmeterol on corticosteroid sensitivity in 6      Inhibitors of PDE3 and PDE4 (cilostazol and rolipram) inhibited spontaneous
CI severe asthma patients and compared with those of 12 normal subjects(NR).            apoptosis of isolated peripheral eosinophils during in vitro culture maximally
Peripheral blood mononuclear cells (PBMCs) were stimulated with TNF-α for               by 15 - 25%. Cell-permeable analogues of cAMP (dibutyryl-cAMP and 8-Br-
16 h in the presence or absence of dexamethasone (10-11 –10-6 M) with or with-          cAMP) also inhibited eosinophil apoptosis in a concentration dependent manner.
out salmeterol (10-8 M). Interleukin(IL)-8 levels in supernatant were measured by       A beta2 -agonist salbutamol delayed eosinophil apoptosis. Rolipram and cilostazol
ELISA. The IC50 value of dexamethasone on IL-8 production in patients with CI           potentiated the antiapoptotic effect of salbutamol. However, PDE-inhibitors did
asthma was significantly higher than those in normal healthy volunteers (IC50 : NR:      not affect GM-CSF-induced survival of eosinophils.
23.3±40 nM, CI asthma: 196.9±92nM, p=0.0017), suggesting CI patients were               The present results show that selective inhibitors of PDE3 and PDE4 delay
approximately 9 times more corticosteroid insensitive than NR. Add-on treatment         eosinophil apoptosis and thus increase their survival in vitro. The results suggest
of salmeterol completely restored dexamethasone sensitivity in CI asthma (IC50 :        that their effects may be mediated via an increase in intracellular cAMP con-
CI asthma with salmeterol; 37.6±30 nM, p=0.0043) though salmeterol did not              centration. Furthermore, inhibition of PDE3/4 during beta2 -selective adrenergic
enhance corticosteroid sensitivity in NR. These results suggest that salmeterol         activation may amplify beta2 -agonist-induced delay in eosinophil apoptosis and
is preferentially effective in corticosteroid sensitivity in CI asthma and may be       this combination of drugs may worsen the eosinophilic inflammation in asthma.
beneficial for the treatment of CI asthma patients.

                                                                                        3049
3046                                                                                    Esomeprazole 80 mg single-dose improves the bronchial response to MCh in
The new approaches to the oral corticosteroid dosage decrease in patients               non atopic ger-related asthma
with severe steroid-resistant bronchial asthma                                          Roberto W. Dal Negro, Silvia Tognella, Claudio Micheletto, Fiorenza Trevisan.
Natalia L. Shaporova, Vasiliy I. Trofimov, Olga V. Dudina, Irina A. Fedoseeva,           Lung Dept, Orlandi Hospital, Bussolengo, Verona, Italy
Dolores P. Lebedeva. Hospital Therapy Department, Pavlov’s State Medical
University, Saint-Petersburg, Russia                                                    The role of acidic gastro-oesophageal reflux (GER) in priming non-specific
                                                                                        bronchial hyper-responsiveness (BHR) still represents a quite challenging topic of
We examined 27 patients with severe steroid-resistant bronchial asthma (BASR)           investigation [1,2].
with the average age 53,1±1,9 years old and duration of disease 13,8±1,5 years.         Aim of the study: to investigate the role of a PPI single-dose, namely esomeprazole
All patients received more then 20 mg of oral prednisolone daily, the dosage was        80mg, in affecting BHR.
equal 38,9±1,69 mg in average, and the average duration of oral corticosteroids CS      Methods: after written consent, the BHR to MCh was checked in baseline and
treatment was 6,6±1,0 years. We observed different complications of CS therapy in       24h following Esomeprazole (ESO) 80mg single-dose in 18 non-smokers (9 m.;
all the cases. 9 patients with the Roncoleukin (IL-2) to be introduced intravenously    18-60y; basal FEV1>80%pred; PD20 MCh <400mcg) with mild atopic (n=8)
in the complex BA therapy, and 18 patients of the control group with traditional        and non-atopic GER-related (n=10) asthma. GER was assessed by a 24h gastro-
anti-inflammatory and bronchodilative treatment have been examined to investigate        oesophageal pH monitoring), Statistics: Wilcoxon test, and p<0.05 assumed.
the oral CS dosage diminution possibility. The oral CS dosage has been decreased        Results in Table 1 (means ± sd; PD20 MCh in mcg).
under the intravenous Roncoleukin therapy (on 4,00±2,60 mg of prednisolone in
average) in the main group. And we observed the oral CS dosage increase in the          Table 1
control group (on 0,91±0,61 mg in average). We also revealed the considerable                                          PD20 bsln               PD20 ESO                  P
diminution of the TNFa (t=3,02, p=0,012), the increase of CD16+ lymphocytes
                                                                                        ger-induced asthma            138.6±99.8              375.5±398.0              0.001
content and significant decrease of IgE blood level (td=4,20; p=0,001) in the main
                                                                                        atopic asthma                 106.4±91.5               98.7±71.7                 ns
group after the Roncoleukin therapy. So the intravenous Roncoleukin therapy can
be used in the complex treatment of patients with the severe steroid-resistant BA
in order to decrease the oral CS dosage.                                                Results: subjects were well matched for age, weight, height, basal FEV1, and
                                                                                        basal PD20 MCh. ESO 80mg single-dose induced a significant increase in PD20
                                                                                        FEV1 MCh (p< 0.01) only in non-atopic GER-related asthmatics.
3047                                                                                    Conclusions: 1) in the presence of acidic GER, the non specific BHR is affected
Theophylline inhibits mobilization of eosinophil induced by interleukin-5               by the PPI’s gastric acidity blockade; 2) a single-dose of Esomeprazole 80mg
(IL-5) from femoral bone marrow into the blood                                          assumed 24h before the bronchial challenge is effective in improving BHR; 3) the
Takeshi Otani 1 , Kenjiro Yamana 1 , Motokazu Kato 2 . 1 Depts of Pharmaceutical        role of acidic GER in priming BHR is further emphasized in non-atopic asthma.
Development Group 2, Nikken Chemicals Co., Ltd., Saitama, Saitama, Japan;               References: [1] Ayres JG et al. Eur Respir J 1996; 9: 1073-78.
2
  Depts of Respiratory and Allergic Medicine, Kishiwada City Hospital,                  [2] Dal Negro et al. Eur Respir Mon, 2003; 23: 260-277
Kishiwada, Osaka, Japan

Theophylline, a non-specific phosphodiesterase inhibitor, has been used for the          3050
treatment of asthma for a long time, however, its inhibitory actions on inflammatory     Efficacy of specific allergy vaccination in house dust mite asthma
cells have not been studied sufficiently. Especially, there are few evidence which       Guna Blumberga 1 , Lisbet Groes 2 , Lars Haugaard 1 , Ronald Dahl 1 . 1 Respiratory
indicate anti-inflammatory actions of theophylline when it is administered intra-        Diseases, Aarhus University Hospital, Aarhus, Denmark; 2 ALK-Abello’,
venously. In the present study, we examined the effect of intravenous theophylline      Horsholm, Denmark
on eosinophilia induced by IL-5 in the mouse and rat.
In the mouse, blood eosinophil number was significantly increased 2 hr after in-         Aim: The purpose of this 3-year randomised, double-blind, placebo-controlled
travenous injection of 1 µg/kg mIL-5 (Vehicle; 5.56, mIL-5; 9.01, ×104 cells/mL,        study was to evaluate an inhaled corticosteroid (ICS)-sparing effect of specific


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         Oral Presentation                                                                                              Auditorium 10 - 08:30-10:30

				
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