ISRAEL SOCIETY OF PULMONOLOGY ANNUAL SCIENTIFIC

ISRAEL SOCIETY OF PULMONOLOGY
ANNUAL SCIENTIFIC MEETING
June 4-6, 2009
Inbal Jerusalem Hotel
Organizing Committee:
Neville Berkman, Amnon P. Ariel, Israel E. Priel
Editors – Abstract Book :
Israel E. Priel, Neville Berkman, Amnon P. Ariel
1
The Annual Scientific Meeting of the Israel Society of
Pulmonology 2009
Inbal Hotel , Jerusalem - June 4-6, 2009
Lebanese Cedars for Solomon’s Temple
Gustav Dore
2
The Annual Scientific Meeting of the Israel Society of
Pulmonology 2009
Inbal Hotel , Jerusalem - June 4-6, 2009
Program
June 4, 2009 Thursday:
1600 -1930
1700 - 1715
1720- 1735
1740- 1755
1800-1815
1820 - 1900
1905- 1925
2000 - 2100
2130 - 2300
3
EXHIBIT HALL OPENS
ZION C/D
Sleep Related Breathing Problems
Chair: Clement Cahan
Armanda Baharav, Yair Fuxman, Shuli Eyal,
Jonathan Halpern, Clement Cahan
Sleep Related Breathing Disorder Is
Prevalent in Elderly Complaining of Poor
Sleep
Armanda Baharav, Gabriella Dorfman
Furman, Clement Cahan
Evaluation of sleepiness: is standard MWT
the right tool?
Pulmonary Hypertension
Chairs: Yochai Adir, Issahar Ben Dov
Benjamin D Fox, Michael Kassirer, Israela
Weiss, Anat Amital, Yael Raviv, David Shitrit,
Mordechai R Kramer
Ambulatory rehabilitation improves
exercise capacity in pulmonary arterial
hypertension patients
ZION A
Respiratory Infections and Tuberculosis
Chairs: Zeev Weiler and Danielle Ben Dayan
Gabriel Izbicky, V.Furer, D Raveh, S. Goldberg,
E. Picard
Absence of leukocytosis in bacteremic
pneumococcal pneumonia
Avital Avriel, Lone S Avnon, Daniel King,
Leonora Kalasov, Yosef Ayzenberg, Hosni
Alkrinawy, Ivgeny Shnider, Dov Heimer, Amos
Douvdevani
Cell free DNA as a potential prognostic
marker in acute respiratory diseases
David Shitrit, Leonardo Fuks, Abdul Rachman
Nader, Victoria Rusanov
Isoniazid Mono-resistant Tuberculosis in
Central Israel: 2000-2008
Yochai Adir, Rafael Wolff, Daniel Weiler,
Michal Shteinberg, Shai Cohen and Daniel
Basil S. Lewis, and Offer Amir
Weiler- Ravell
Pulmonary Hypertension and Diastolic Left Empiric Initiation of anti- Tuberculosis
Ventricular Dysfunction- clinical and
Treatment in a Patient with Undiagnosed
hemodynamic characteristics
Chest Findings.
PLENARY PRESENTATIONS
Chairs: Gershon Fink, Neville Berkman
The A/H1N1 FLU – What the fuss is all about ?
Speaker: Ran Balicer, Director, Health Policy Research and Planning, Clalit Health Service
The NO AIR STUDY
Speaker : Gabriel Izbicky
GALA DINNER (Inbal Patio)
Show: THE THREE TENORS
Felix Lipschitz, Boris Erofeyev, Dimitry Semyonov
June 5, 2009 Friday:
0700 – 0830
BREAKFAST
0800
EXHIBIT HALL OPENS
ZION C/D
0830 -0845
0850- 0905
0910 – 0925
0930 – 0950
0955 -1010
1015-1030
1035 -1050
1055 – 1110
4
ZION A
Lung Transplantation
Chairs: Mordechai R. Kramer, Uri Laxer
COPD Smoking and exercise Physiology
Chairs: Amnon P. Ariel, Issahar Ben Dov
Philippe Biderman , Benjamin Medalion ,
Mordechai R Kramer, Yael Raviv, Pierre
Singer E. Porat
Interventional Lung assist (ILA,
Novalung) in severe acute respiratory
failure of the adult :a Bridge to lung
transplantation or to recovery , the
Belinson Experience .
S. Nusair, G. Gincberg, SB Wallach-Dayan,
O Almogi-Hazan, and R Breuer
Hematopoiteic mesenchymal cell role in
tracheal allograft acceptance by mixed
chimerism formation after reduced
intensity conditioning
Anat Amital, R. Taube, David Shitrit, Ben
Fox, Yael Raviv, Leonardo Fux, Ilana
Bakal, Benjamin Medallion, Milton Saute,
Yael Refaeli, Mordechai R. Kramer
Lung Transplantation for Pulmonary
Silicosis
COFFEE BREAK
David Stav and Meir Raz
The Effect of N-acetylcysteine on air trapping in
chronic obstructive pulmonary disease (COPD): a
randomized placebo controlled study
Thoracic Oncology
Chair : Amir Onn
Amir Onn
An Animal Model for the Study of the
Biology and Management of Malignant
Pleural Effusion.
A.Starr, Y.Shahar, E.Teniakov, Y.Greif and
Y.Schwarz
Role of ErbB-4 gene in tumorigenic and
metastatic behavior of human non-small
cell lung cancer orthotopically growing
in nude mice
Meir Krupsky
Reduced Repair of the DNA Damage,
Risk and Susceptibility of Airways Cancer
Amir Onn
Treatment Options for Advanced NonSmall Cell Lung Cancer
Dror. Ofir, Amnon Ariel, K.A. Webb, D.E. O’Donnell.
Gender Differences in Exertional Breathlessness in
Patients with Mild COPD.
Aviv Weinstein, Joel Greif, Zipi Yemini, Hedva Lerman,
Abraham Weizman , Einat Even-Sapir
Attenuation of cue-induced smoking urges and brain
reward activity in smokers treated successfully with
bupropion.
Barak Gershon
Training for a Marathon : my personal experience as
a non- professional athlete
Asthma
Chairs: Neville Berkman, Mordechai Ygla
Elizabeth Fireman
Occupational Asthma (OA) in Israel
Zeev Weiler, Yuri Zeldin, Nelly Poliakov, Eli Magen ,
Mona Kidon
Early diagnosis of airway hyperresponsiveness using
a biphasic exercise provocation test in patients with
suspected asthma
Ariel Rokach, Raphael Breuer, Gabriel S. Breuer.
Use of Complementary and Alternative Medicine
among Asthma Patients Attending Pulmonary Clinic
in Jerusalem
June 5, 2009 Friday (Continued):
ZION C/D
ZION A
1115 - 1130
The Lung in Systemic Disease
Chairs: Dov Heimer, Israel E. Priel
Amyloidosis
Luna Avnon , Dov Heimer ,
A middle aged man with secondary
pulmonary amyloidosis
Mordechai Ygla , Oren Fruchter,
The response to bronchodilator following negative
metacholine challenge test predicts development of
asthma.
1135 – 1150
Inflammatory Bowel Disease
Elizabeth Fireman, Farid Masarwy,
Yehuda Schwarz, Gabi Groisman, Moshe
Shtark, Yael Kopelman, Shmuel Kivity,
Zvi Fireman
Increased eosinophilia in induced sputum
of Ulcerative Colitis patients : The lung as
a mirror image of intestinal disease ?
COFFEE BREAK
Martin Kohan and Neville Berkman
EDA-fibronectin induces airway fibrosis via modulation
of lung fibroblast
phenotype in a murine model of chronic asthma
Pulmonary Fibrosis , Parenchymal and
Granulomatous Lung Diseases
Chair: Raphael Breuer and Elizabeth
Fireman
Amir Bar Shai , Joel Greif , Avi Man, Boaz
Tiran, Irina Fomin, Noa Hadayer, Yehuda
Schwarz
Primary vs. secondary COP, contradiction
in terms !?
Pazit Y. Cohen, Shulamit B/ Wallach-Dayan
and Raphael Breuer
Down regulation of Thy 1 expression
increases lung myofibroblast proliferation
Bronchology
Chairs: Yehuda Schwartz, Tiberiu Shulimzon
1155 – 1225
1230 – 1245
1250 – 1305
1310- 1325
1330 – 1345
1350- 1405
Shulamit B. Wallach-Dayan, Regina GolanGerstl and Raphael Breuer
Resolution of lung fibrosis in gld C5BL/6
+
mice by FasL immune cells
Mor Sabag Irina Fomin, Yehuda
Schwarz, Joel Greif, Elizabeth Fireman
TNF -α
α genotyping at position 308
secreted and TNF -α
α mRNA in Jewish
population
Victoria Rusanov, David Shitrit, Yael Raviv,
Anat Amital, Mordechai R Kramer
Serum Tumor Markers Correlated with
the Severity of IPF
1410 – 1425
1430 -1530
1930-2100
2100
5
LUNCH
DINNER
GUIDED TOUORS/WALKS
Boaz Tiran, Avi Man, Irina Fomin, Yehuda Schwarz
Pilot experience of Mitomycin C as an adjunct in
bronchoscopic laser management of benign tracheal
stenosis
Leonardo Fuks , David Shitrit , Yael Raviv , Anat Amital ,
Benjamin D. Fox , Mordechai R. Kramer
Post coital hemoptysis: Our experience and review of
the literature
Yehuda Schwarz , Galit Aviram, Avi Man, Boaz Tiran,
Irina Fomin, Ram Mor, Amir Bar Shai & Jacob Sosna
New optical navigation system for CT guided lung
biopsies: Initial animal and human experience
Leonardo Fuks, Anat Amital, Benjamin D Fox, Nadel
Abdel Rahman, Mordechai R . Kramer
Bronchoscopic treatment of intraluminal typical
carcinoid
Thoracic Surgery
Chair: Yael Refaely
Dov Weissberg
Surgery in China : The impressions of an Israeli
physician
Nachum Nesher, Yosef Paz,
Surgical controversies in Thoracic surgery:
Open versus VATS Lobectomy.
June 6, 2009 Shabbat:
0800 – 1000
BREAKFAST
1000 - 1400
GUIDED TOUORS/WALKS
1300 - 1500
LUNCH
Orientation Map – Meeting Halls
Inbal Hotel - Jerusalem
6
Thursday, June 4th – ZION C/D
SLEEP RELATED BREATHING DISORDERS
Sleeping Beauty
7
Sleep Related Breathing Disorder Is Prevalent in Elderly Complaining of Poor Sleep
Armanda Baharav, Yair Fuxman, Shuli Eyal, Jonathan Halpern, Clement Cahan
Background: Deterioration in sleep quality, efficiency and increased sleep related
breathing disorders (SBD) occur with ageing. Moreover respiratory events cause
arousals that have additional adverse effects on sleep quality and daytime function.
Objective: Evaluation of SBD in an elderly population complaining of poor
sleep/insomnia.
Methods: Active subjects over 60 years old complaining of poor night time sleep
were recruited for a yoga treatment study for insomnia. Prior to enrollment, they
were interviewed and examined by an experienced sleep physician. Subjects with
proved or suspected SBD were excluded. 77 subjects enrolled, age 74.2+7.0 years,
80.6% females, BMI 25.9+3.8. Sixty seven subjects had at least one home sleep
study, and 51 had two studies, performed with an Embletta x30 device with ECG,
oxygen saturation and pulse wave recordings. Automatic scoring based on HC1000P
software yielded sleep architecture information, arousals, sleep efficiency and AHI
(respiratory events per hour of sleep). Diagnosis was based on clinical information
obtained at enrollment and test results.
Results: 13% had no SBD; 22% had 5<AHI<10, 39% had 10<AHI< 20; 13% had
20<AHI<30 and 12% had AHI>30. Total sleep time 356.7 min+70.9; Sleep efficiency
84.8% +4.2; REM% 17.5+6; NREM% 69.3+14.2, arousals index 18.3+20.3. Similar
results were obtained during a second study (51 subjects).
Conclusions: We found that a majority (65%) of elderly active people complaining of
poor sleep quality have undiagnosed obstructive sleep apnea that cannot be
predicted by clinical findings or questionnaires. This high incidence occurs in a
woman predominant population with a multitude of medical problems
(hypertension, heart disease, diabetes) and use of various sleep promoting
medications. Efficient treatment of the SBD in these patients should have positive
impact on their general health and function and improve sleep quality. Since clinical
evaluation is unreliable at this age, elderly patients should have simple, cost
effective home diagnosis of their disorder, allowing for treatment, when needed.
8
Evaluation of sleepiness: is standard MWT the right tool?
Armanda Baharav, Gabriella Dorfman Furman, Clement Cahan
Background and Objective: Studies indicate that drowsiness is a contributing factor
in 22-24% of motor vehicle crashes or near crashes. Objective assessment of
sleepiness on task becomes an imperative. There is no consensus on how to
diagnose tendency to fall asleep, or if and how to monitor a driver while at the
wheel. Our aim was to characterize sleepiness and to develop a simple monitoring
tool of a drivers' tendency to fall asleep.
Methods: 10 healthy volunteers with no sleep disorder and no sleep deprivation
enrolled in the study that included a regular night sleep in the lab followed by 36
hours of sleep deprivation during which subjects performed 2 alternate tasks every 2
hours: (1) Maintenance of Wakefulness Test (MWT) standard conditions for 45
minutes; (2) Drivers simulation (90Km on a monotonous road using STISIM Drive
simulator). Two occipital, two central EEG, chin EMG, eye movement and ECG were
monitored and recorded continuously while audio-video was collected. MWT was
interrupted if 2 minutes of any sleep stage intervened. Micro sleeps (3-15 seconds
were manually detected) and crashes near crashes and driving errors were detected
from the simulator.
Results: Sleep latency during MWT and the frequency of micro sleeps increased
with increasing sleep deprivation. A circadian modulation of this tendency caused an
accentuation of the sleepiness during last hours of the night. A striking finding, in all
subjects, indicates large amounts of alpha activity with open eyes on MWT when
sleep debt accumulates. This is overwhelming after 24 hours. Drivers' simulation
tests around the same time indicate a large amount of crashes, accompanied by
theta EEG activity.
Conclusion: Standard MWT evaluation based on sleep latency is insufficient. The
presence of alpha activity with open eyes raises questions regarding scoring and
interpretation of MWT. The fact that the presence of alpha on MWT correlates very
well with performance on simulator indicates that alpha intrusion, even in the
absence of sleep onset/closed eyes may be an important factor when evaluating
drowsy drivers.
9
PULMONARY HYPERTENSION
Dr Ernst von Romberg
1865- 1933
reported 1n 1891 an authopsy as
Pulmonary Vascular Sclerosis
10
Ambulatory rehabilitation improves exercise capacity in pulmonary arterial
hypertension patients
Fox, Benjamin D BM MRCP(UK) ; Kassirer, Michael MD; Weiss, Israela MS, BPT ; Amit
al, Anat MD; Raviv, Yael MD; Shitrit, David MD; Kramer, Mordechai R, MD, FCCP
Pulmonary Institute, Rabin Medical Center, Petach Tikva ISRAEL
Objectives: To evaluate ambulatory pulmonary rehabilitation for patients with pulm
onary arterial hypertension (PAH).
Design: A prospective controlled non-randomized trial.
Setting: A tertiary referral center.
Participants: Twenty two patients with PAH, diagnosed by right heart catherization.
All patients were stable on PAH-specific medication.
Interventions: The partcipants were allocated to pulmonary rehabilitation (n=11) or
to the control group (n=11). The rehabilitation group underwent 24 one-hr sessions
of exercise training/rehabilitation over 12 weeks
Main Outcome Measures: Change in 6 minute walk (6MW), peak oxygen uptake (VO
2 peak).
Results: In the rehabilitation six minute walking distance (6MW) increased by 32
meters, in the control group 6MW decreased by 15 meters (p=0.002), figure 1. Peak
VO2 increased in the rehabilitation group by 1.1 ml/kg/min and decreased by 0.5mls
/kg/min in the control group (p<0.05). Peak work-rate during cardiopulmonary exerci
se test also increased in the rehabilitation group (p<0.05). Echocardiography and blo
od pro-NT brain natriuretic peptide levels were unchanged. No adverse events occur
red due to the rehabilitation.
Conclusions: Ambulatory pulmonary rehabilitation is a safe and efficacious
treatment for patients with PAH already on medical therapy.
Figure 1: Change in six minute walking distance
11
Pulmonary Hypertension and diastolic Left Ventricular Dysfunction- clinical and
hemodynamic characteristics
Yochai Adir, Rafael Wolff , Daniel Weiler, Basil S. Lewis and Offer Amir
Introduction: Over 50% of persons 65 years and older who suffer from heart failure
have a normal LV systolic function and they are diagnosed as having diastolic heart
failure. A subset of these patients will have a marked increase in pulmonary
pressures beyond the pressures which are needed to maintain the cardiac output.
Aim: To describe the clinical and hemodynamic data of a subgroup of patients with
left ventricular diastolic dysfunction and disproportionate pulmonary hypertension
Results: We retrospectively reviewed 13 cases with severe symptoms of effort
dyspnea and signs of right heart failure. Their average age was 76±7 year old and
85% (11/13) were females. On echocardiogram all had good left ventricular function
with EF>55% and systolic pulmonary artery pressure above 55 mmHg. Twelve of
these patients were with NYHA functional capacity (FC) of III and one patient with
FC of IV.
Ten patients (77%) had resting hypoxemia and five had an obstructive sleep apnea.
All were treated with CPAP. Eight patients (62%) had coronary artery disease and a
history of previous bypass surgery or interventional heart catheterizations. Atrial
fibrillation was present in 11(85%) of the patients and diabetes mellitus and
hypertension in 6 (46%) and 9 (69%) of the patients respectively.
On right heart catheterization (RHC) {mmHg}: Mean right atrial pressure was 14±6,
mean pulmonary artery pressure was 53±7, mean wedge pressure 24±5 and transpulmonary gradient of 26 ±5. The Pulmonary vascular and systemic vascular
resistances were 7.6±3 and 22±6 Wood units, respectively. Mean cardiac index was
2.3±0.6 L/Minute/M2. Only two patients (15%) had positive pulmonary vaso-reactive
response to NO inhalation.
Discussion: We describe a subset of patients with diastolic dysfunction and a marked
increase in pulmonary pressures. Interestingly, most of our patient were women and
had resting hypoxemia. On RHC all had a markedly elevated transpulmonary gradient
beyond the pressures which are needed to maintain the cardiac output. The optimal
treatment for this subgroup of patients with out of proportion pulmonary
hypertension is still unknown and a different therapeutic approach should be
considered.
12
The A/H1N1 FLU – What the fuss is all about
Spanish Influenza 1919
Edward Munch
1863- 1944
Self portrait -After the Spanish Influenza 1919
Edward Munch
1863- 1944
13
Plenary Session
The A/H1N1 FLU – What the fuss is all about ?
Ran Balicer
Director, Health Policy Research and Planning
Clalit Health Service
14
NO-AIR Asthma Study
15
National asthma observational survey to describe the disease, patients and
therapy characteristics of severe asthmatics in Israel.
G. Izbicki 1, A. Grossman 2, Weiller Z 3, G. Fink 4
1 Pulmonary Institute, ShaareZedek Medical Center, Jerusalem, Israel. Tel: 026666278, [email protected], ; 2 Pulmonary Institute, Maccabee Health Services, Tel
Aviv,; 3 Pulmonary Institute, Barzilai Medical Center, Ashkelon, ; 4 Pulmonary
Institute, Kaplan Medical Center, Rehovot, Israel.
The authors are from the 4 centers which recruited the most patients (according to the agreement
which was made with the Israel Pulmonary Society prior to the study).*
Objectives: To characterize adult patients with asthma, hospitalized for asthma
exacerbation during the last 12 months or asthma patients treated with
maintenance systemic steroids with regard to patient and disease characteristics and
treatment.
Methods: This survey is based on one patient visit conducted by pulmonologists,
members of the Israeli Pulmonary Society. Patients completed questionnaires
concerning asthma control, therapy compliance, and quality of life. Physicians also
completed questionnaires concerning the severity of the asthma, classification,
comorbidities, and treatment.
Results: Demographics and medical history: One hundred and twenty-three patients
contributed to the survey. One hundred and twelve (91.1%) were Jews. Median age
was 52 years (range 19-87 years), 65.3% were married, 62.0% had completed high
school or attended university, and 28.9% were working. Of those not working, 84.8%
were retired or could not work for health reasons. Seventy-nine percent lived in
urban areas and 39.7% in houses. Twenty-four percent had pets at home, of which
72.4% were dogs. Thirty-one percent had hypertension and 18.0% diabetes, as
concomitant diseases.
Asthma-related information: Asthma was diagnosed below the age of 40 years in
75.6% of patients. Median IgE was 200 U/mL (n=101). Fifty-five percent had a history
of allergic rhinitis, 19.5% had a food or drug allergy, and 13.0% had atopic dermatitis.
Eighty percent had never smoked, 17.9% were ex-smokers. Median FEV1 was 57%
(n=119) and PEF 53% (n=95). Reversibility was documented in 67.5%; skin test/RAST
was available in 57 (46.7%) patients, of which 40 (70.2%) were positive. The median
number of exacerbations was 4 (range 0-25) within the last 12 months and 5/year
(range 0-100 years) over the past 5 years. Seventeen percent had a history of
hospitalization in the intensive care unit and intubation. According to the Global
Initiative for Asthma (GINA) classification, asthma was partly controlled in 50.4% of
patients, uncontrolled in 43.9%, and well controlled in only 5.7%. Asthma severity
was assessed as severe persistent in 69.1%, moderate persistent in 27.6%, and mild
persistent in 3.3%.
Drug treatment: Concerning inhalation therapy, 90.2% of patients took short-acting
beta-2-agonists (salbutamol/albuterol preferred), 19.2% long-acting beta-2-agonists
(formoterol preferred), 15.0% corticosteroids (budesonide preferred), and 83.7%
16
combination therapy (salmeterol/fluticasone preferred). Other drugs included
montelukast (n=37), theophylline (n=29), and omalizumab (n=26). Fifty-two percent
received corticosteroids (prednisone preferred) systemically as maintenance
therapy; in these cases, the most common treatment-associated adverse events
included osteoporosis, obesity, and hypertension.
Quality of life and compliance: The median number of visits during the last year to
the emergency room was 2 (range 0-24), that of hospitalizations within the last 12
months 1 (range 0-20), hospitalizations in the last 5 years, 3 (range 0-60) with an
average duration of hospital stay of 4 days (range 0-25 days). The median number of
working days lost due to asthma per year was 15 (range 0-365 days). Forty-three
percent of patients used steroids daily and 51.2% were afraid or very afraid of side
effects. Eighty-three percent stated to be always compliant with the prescribed
treatments and 92.6% were aware to a great extent of the need for continuous
treatment. Ninety-five percent were of the opinion that a lack of compliance would
have a negative impact on their disease. Thirty-nine percent thought that treatment
with tablets was more efficient that inhalation, whereas only 17.4% of patients
denied that statement. Sixty-five percent of the patients stated that asthma
restricted their activities always or frequently. Fifty-six percent had asthma attacks
daily and 48.8% woke up 4 or more times a night per week due to asthma. Forty-nine
percent of patients stated that their asthma was not at all under control or under
little control, whereas only 8.3% thought is was under full control.
Conclusions: In this survey, FEV1 and PEF indicate a persistent and severe disease in
the patients assessed. Asthma impaired quality of life and was a major cause of
hospitalizations, emergency room visits, and absence from work. The majority of
patients were compliant with drug treatment; however, this did not translate into a
sufficient disease control, as in only 5.7% of the patients, asthma was well
controlled. Other treatment options for severe asthmatic patients should be
considered.
•
The following centers participated in this study: (Names of the principal Investigator)
Shaarei Zedek Medical Center , jerusalem – Gabriel Izbicki – MD; Hillel Jaffe Medical Center ,
Hedera– Marinella Beckerman, MD; Barzilay Medical Center , Ashkelon – Zeev Weiler, MD;
Kaplan Medical Center , Rehovot – Gershon Fink, MD; Poriah Medical Center, Tiberias, Claudia
Simsolo, MD; Asaf Harofe Medical Center – David Stav, MD; Clalit Health Sevices , Ahmad
Atamnah , MD; The Edith Wolfson Medical Center, Holon – Israel E. Priel, MD
Central hospital for the Emek, Afula - Mahmud Younnes , MD; Hadassah Ein Karem Hospital ,
Jerusalem – Raphael Breuer, MD; The Chaim Sheba Medical Center, Tel Hashomer – Issahar Ben
Dov, MD; Maccabi Sick Fund – Ania Grossman , MD; Meuchedet Sick Fund – Ania Grossman < MD
Novartis supported this study with an unrestricted grant to the Israel Pulmonary Society
17
Thursday, June 4th – ZION A
PULMONARY INFECTIONS and TUBERCULOSIS
Pasteur – The chemist who transformed medicine
Robert A Thom
1915- 1979
18
Absence of leukocytosis in bacteremic pneumococcal pneumonia
Izbicki G1,2, Furer V1, Raveh D3, Goldberg S2, Picard E2.
1
Department of Internal Medicine, 2Pulmonary Institute and3Infectious Diseases Unit
and, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah
Medical School, P.O.Box 3235, Jerusalem 91031, Israel
Background: Evaluation of patients with respiratory symptoms in primary medicine
is often based on peripheral white blood count that dictates the extent of diagnostic
work-up. Normal white count may lead to a limited work up often avoiding chest
radiograph performance.
Method: We performed a retrospective analysis on bacteremic community-acquired
pneumococcal pneumonia patients, diagnosed from 2000 to 2007 in a community
care academic medical center. Eighty one cases (42 children and 39 adults) were
eligible for analysis. The records were reviewed for symptoms, signs, and laboratory
data including pneumococcal serotypes, chest radiographs on admission and
outcome.
Results : Twenty one percent of all the patients with bacteremic pneumococcal
pneumonia presented with normal white blood count: 16.6% of children and 25.6%
of adults had neither leukocytosis nor left shift on admission. Ninety percent of
adults and seventy percent of children presenting with normal white blood count
developed leukocytosis later during their hospitalization
Table: White blood cell count at presentation according to age groups, hospital
stay length, and outcome.
P value
>15,000
10,000-15,000
<10,000
WBC Count
NS (0.26)
30(71.43)
5(11.9)
7 (16.6)
Children №(%), n=42
NS (0.26)
21(53.8)
8(20.51)
10 (25.6)
Adults №(%), n=39
NS (0.21)
5.2±4.6
8.0±5.1
8.0±4.6
Hospital Stay, Children (days)
NS (0.46)
10.6±12.7
9.25±12.7
11.6±13.9
NS (0.69)
17
6
9
4 (19%)
2 (25%)
1 (10%)
Hospital Stay, Adults (days)
Adult outcome alive
dead
NS=non significant
Conclusion: In as much as one fifth of all the patients with bacteremic pneumococcal
pneumonia, there was no leukocytosis at presentation. The absence of leukocytosis
at presentation is not a predictor factor for pneumococcal pneumonia outcome.
Moreover, there is no predictive tool to define a group of patients who would not
develop leukocytosis at presentation. We therefore suggest that every patient with
suspected (pneumococcal) pneumonia should undergo a chest X-ray even if the
white blood count is normal.
19
Cell Free DNA As a Potential Prognostic Marker In Acute Respiratory Diseases
Avital Avriel1, LoneS Avnon1, Daniel King1, Leonora Kalasov2, Yosef Ayzenberg2, Hosni
Alkrinawy2, Ivgeny Shnider2, Dov Heimer1, Amos Douvdevani3
1
Lung Unit, 2Emergency Department, 3Nephrology research laboratory, Soroka
University Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel
Background: High levels of circulating cell free DNA (CFD), originating from apoptotic
and necrotic cells, have been associated with poor prognosis in various malignant
and inflammatory states. Currently there is slight data in the literature about the use
and the clinical significance of elevated CFD levels in the setting of acute respiratory
illness. Moreover, the available data have been obtained by either slow
electrophoresis or PCR, methods which are not practical for routine use.
Objective:The primary aim was to evaluate quick novel methods for the detection of
circulating CFD in patients with acute respiratory diseases in comparison with other
acute illness. To correlate CFD levels with clinical and prognostic signs such as:
saturation, blood pH, PCO2, WBC, intensive care unit (ICU) admission, need for
respiratory support and death.
Methods:The study population included patients with acute respiratory illness, and
randomly selected patients with non respiratory acute disease. All were included
upon arrival to the Emergency Room (ER). A serum concentration of CFD was
quantified by a novel rapid fluorometric assay, while WBC, pH and PCO2 were
measured simultaneously. Other clinical information was taken from patients files.
Results:82 patients, mean aged 68.4 with respiratory illness were included. Their
primary diagnosis was: 33 (40.2%) patients with COPD exacerbation, 26 (31.8%) with
pneumonia and 23 (28%) with dyspnea. They were compared to 639 patients with
non-respiratory acute illness (mean CFD 1008±53 ng/ml). Levels of CFD were higher
in the group of patient with acute respiratory illness (mean CFD1312±110, P<0.01).
In patients who had acute respiratory illness, significant correlation was found
between higher levels of CFD and lower levels of SAT (R=-0.42, 95% CI -0.65 to 0.121, P=0.0076). We also found that higher levels of CFD correlated significantly
with the days spent in hospital (R=0.25, 95% CI 0.0307 to 0.446, P=0.026). Higher
levels of CFD correlated also with the following parameters: WBC>10,000cells/mm;
PH<7.35; PCO2>40mmHg; however it was not statistically significant.
Conclusions: With this rapid novel method, peak CFD levels were higher significantly
in patients with acute respiratory illness, comparing to other patients who arrived to
the ER. The levels were correlated significantly with lower levels of saturation and
days in hospitalization. The use of CFD as a prognostic sign in acute respiratory
illness requires further investigation
20
Isoniazid Mono-resistant Tuberculosis in Central Israel: 2000-2008
David Shitrit, Leonardo Fuks, Abdul Rachman Nader, Victoria Rusanov
Rehovot Tuberculosis Center, Maccabi Medical Service,Israel. Pulmonary Institute,
Rabin Medical Center, Petach Tiqwa 49100, Israel
Objective: Only limited data exists about demographic characteristics of tuberculosis
(TB) isolates with resistant to isoniazid.
Design: A retrospective analysis of demographic characteristics of all TB cases in
2000 to 2008.
Setting: Rehovot Tuberculosis Center, Maccabi Medical Service, Israel.
Participants: All TB cases in our center during 2000-2008.
Main outcome measures: Demographic and treatment outcome for persons with
isoniazid-monoresistant TB compared with persons with TB susceptible to all first
line anti TB medications and persons with multidrug resistant (MDR) TB.
Results: 590 cases of TB were diagnosed during 2000-2008. 44 patients (7.5%)
developed MDR-TB while 38 patients (6.4%) had isoniazid mono resistant TB. Among
the isoniazid-monoresistant TB patients, 71% (27) born in USSR, 16% in Israel and
13% were Etiopean. In the patients with MDR-TB, 66% were from USSR, 30% were
Etiopean and only 4% were native Israeli. Mean length of treatment was 24± 4
months for MDR-TB, 10±3 months for isoniazid-monoresistant TB cases and 8±2
months for all other TB cases.
Conclusions: Physicians should maintain heightened vigilance for Isoniazid resistance
when evaluating certain at risk populations for TB in Israel.
21
Empiric Initiation of anti- Tuberculosis Treatment in a Patient with Undiagnosed
Chest Findings.
Michal Shteinberg1, Shai Cohen2 and Daniel Weiler- Ravell1.
Unit of Pulmonology1, Dept. Internal Medicine B2, Carmel Medical Center
Setting : A Patient hospitalized in a department of Internal Medicine.
Case Description: A 70 year old woman Russian immigrant was hospitalized for
weight loss and fever of several months' duration. She recalled fever and accelerated
weight loss in the two months preceding her hospitalization. Imaging demonstrated
bilateral lung infiltrates, presumed to be pneumonia but she did not improve after
three courses of antibiotics.
She was cachectic, with low grade fever. There were coarse rales over right
hemithorax. Liver, spleen or lymph nodes were not enlarged. Liver enzymes were
elevated and the CBC showed mild pancytopenia. CT scan showed bilateral chest
infiltrates and pleural effusions. Bronchoscopy was normal and washings negative
for acid fast bacilli. Blood cultures were sterile. A bone marrow aspiration was lipoid
with normal cellularity, and a bone marrow biopsy was normal.
The patient became progressively hypoxemic and serial chest x-rays showed
worsening of lung infiltrates. Based on the patient's country of origin, the
progressive lung infiltrates and a lipoid bone marrow aspirate, we diagnosed an
overwhelming infection with tuberculosis and initiated anti- tuberculosis treatment
with five drugs and systemic glucocorticoids. There was an almost immediate
dramatic improvement. Two weeks after initiation of therapy, Mycobacterium
tuberculosis was detected in cultures from bronchoscopic washings.
Discussion: Miliary tuberculosis is a disseminated infection that involves several
organs. Typically, the bacillary load is low, leading to insidious, low grade clinical
symptoms. In many cases the sputum smear is negative due to low bacillary load,
complicating the diagnosis. Mortality from miliary tuberculosis has been reported to
be 20-30 % in adults, necessitating prompt initiation of therapy.
Conclusions: Miliary tuberculosis is a potentially fatal disease, and its diagnosis is
challenging. It is important to initiate empiric treatment when there is a strong
suspicion for this condition, even in the absence of microbiological proof. We report
a case of miliary tuberculosis in which initiation of empiric therapy led to recovery of
a critically ill patient.
22
Friday June 4th – ZION C/D
LUNG TRANSPLANTATION
Joel Cooper, MD
Performed the word’s first lung transplantation in Canada
23
Interventional Lung assist (ILA ,Novalung ) in severe acute respiratory failure of
the adult : a Bridge to lung transplantation or to recovery , the Belinson Experience
Biderman P MD ¹ ,Medalion B MD¹, Kramer MR MD², Raviv Y MD², Singer P MD
³,Porat E MD¹.
¹ Cardiac and Thoracic surgery department,² Pulmonary institute,³ General intensive
care department, Belinson Medical Center.
Objective : To evaluate the efficacy of the ILA in patient with acute or acute on
chronic respiratory severe respiratory acidosis despite mechanical ventilation .
Design : Consecutive patients with severe respiratory failure resistant to
conventional mechanical ventilation , use of the extra corporeal pumpless
oxygenator . Patients admitted in the general ICU or the cardio thoracic ICU of the
Belinson medical center ,Campus Rabin Petach Tikva Israel
Population : 12 patients, 4 patients waiting for lung transplantation and 8 patients
with ARDS (from January 2007 to December 2008) .
Intervention : Connection to the ILA device through a femoral canulation in a
ventilated patient for a period from 8 to 28 days until recovery or transplantation.
Main outcome: Changes in PCO2 ,PO2, survival and disconnection from mechanical
ventilation .
Results : Overall survival: 6 patients, one patient was successfully transplanted after
8 days of ILA connection ,one patient waiting for lung transplantation was weaned
from the device but not from the ventilator, 2 patients waiting for transplantation
died .
In the ARDS group 4 patients survived and were disconnected from the ventilator .
Conclusions: ILA (Novalung system) is a new and efficient therapeutic approach in
the treatment of severe respiratory failure resistant to conventional mechanical
ventilation .This system can be use as a bridge to lung transplantation.
Our results are comparable to the German results despite the higher gravity of the
respiratory failure in our group (lower Ph and higher Pco2).
Philippe Biderman MD
Director ICU unit, Cardiothoracic surgery department
Belinson Medical Center ,Campus Rabin, [email protected]
[email protected]
24
Hematopoiteic mesenchymal cell role in tracheal allograft acceptance by mixed
chimerism formation after reduced intensity conditioning
1
S Nusair, 1,2G Gincberg, 1SB Wallach-Dayan, 2O Almogi-Hazan, 2R Or and 1R Breuer
1. Lung Cellular and Molecular Biology Laboratory, Hadassah-Hebrew University
Medical Center, Institute of Pulmonary medicine, Jerusalem, Israel , 91120.
2. The Cancer Immunobiology, Research Laboratory, Hadassah-Hebrew University
Medical Center, Department of Bone Marrow Transplantation, Jerusalem, Israel ,
91120.
Objective: Chronic pulmonary allograft rejection, as characterized by the obliterative
bronchiolitis (OB) lesion in small airways, decreases five-year survival to 45% posttransplant. In the animal model of heterotopic allogeneic tracheal graft, tolerance
induction by the formation of recipient-donor mixed chimerism can allow allograft
acceptance. We performed this study to evaluate a possible role of donor
hematopoietic stem cells in the regeneration of the tracheal allograft lining epithelial
cells, using bone marrow cells (BMC) from C57BL/6 mice transgenic for green
fluorescence protein (GFP) to facilitate tracking the fate of these cells in the recipient
animals.
Design & Interventions: Tracheal allografts were obtained from C57BL/6 mice and
were implanted in BALB/c mice subcutaneously on d=0. Mixed chimerism was
induced by giving 30X106 BMC from C57BL/6 GFP+ mice simultaneously with the
tracheal allografts (d=0), with a repeated aliquot on d+2 after implantation.
Conditioning consisted of giving intravenous busulfan (10mg/kg) on d-1 and
intraperitoneal cyclophosphamide (200mg/kg) on d+1. The control group underwent
similar conditioning without giving BMC. Tracheal allografts were harvested on d+30
and d+110 and evaluated by histopathology and immunohistochemistry.
Results: While allograft rejection was evident at d+30 in the control group, tracheal
allografts were preserved in the group given donor BMC up to d+110, with normal
intact epithelial cells and patent allograft lumen on histological examination, with no
inflammation within the airway wall. GFP was not detected within epithelial cells of
accepted allografts. However, we observed accumulation of donor GFP+
mesenchymal cells within the sub-epithelial layer of the tracheal allograft tissue.
Conclusions: Our findings suggest that donor mesenchymal cells play an important
role in the preservation of tracheal allografts, in agreement with their wellrecognized immunosuppressive properties. Further studies will elucidate
mechanisms involved in the action of these mesenchymal cells in tolerance induction
after mixed chimerism formation.
25
Lung transplantation for pulmonary silicosis
Amital A, Taube R, Shitrit D, Fox B, Raviv Y, Fux L, Bakal I, Medallion B, Saute M,
Refaeli Y, Kramer MR
Setting: Silicosis is a rare indication for lung transplantion. Out of 280 lung
transplantations in RMC between 1997-2008 we observed 3 patients, that
underwent lung transplantation for silicosis-progressive massive fibrosis.
Case Description
Three men, mean age of 50,underwent single lung transplantation for progressive
massive fibrosis, end stage lung disease. Two patients had worked in a granite
polishing and one in jewelry factory with unprotected exposure to silica for 16-32
years. All had CT scan demonstrating mediastinal lymph node enlargement with
typical calcifications, interstitial lung disease and confluent fibrosis in the lungs
involving the pleura.
Assessment/results
In all the patients the native lung extraction was very difficult because of severe
pleural adhesions.
All the patients had intra-operative bleeding; two patients were hemodynamically
unstable, one patient died because of massive bleeding. The others had prolonged
ischemic time. One patient had postoperative severe primary graft dysfunction. Five
weeks later he was doing well his FEV1 being 50%. He eventually died of recurrent
pneumothoraxes in the native lung. The third patient underwent intrapericardial
pneumonectomy because of adhesive calcified lymph nodes also his phrenic nerve
was injured. The patient was intubated for 7 months and hospitalized for 10
months. His present FEV1 is 28% and he still needs oxygen during activity.
Discussion
Data concerning lung transplantation for progressive massive fibrosis is sparse
This is the first work concerning these patients.
In all of the cases operative difficulties related to silicosis led to operative and perioperative complications including massive bleeding, paralysis of the diaphragm, and
late pneumothorax in the native lung.
Conclusions
Lung transplantation in patients with silicosis -progressive massive fibrosis is difficult.
An expert surgeon should join the team that takes out the native lung.
Anesthesiologists should be prepared for severe bleeding.
The coordinator should consider timing of prolonged lung extraction in order to
avoid prolonged ischemic time.
26
THORACIC ONCOLOGY
27
CLAUDE MONET
1840 – 1926
Monet died of lung cancer at the age of 86
28
An Animal Model for the Study of the Biology and Management of Malignant
Pleural Effusion.
Amir Onn, MD
Pulmonary Oncology, Sheba Medical Center
Objective: Recurrent malignant pleural effusion is a debilitating clinical problem with
no effective therapy. It is associated with high levels of vascular endothelial growth
factor (VEGF), also known as vascular permeability factor (VPF).
Methods: We used our recently developed orthotopic model of human lung cancer
in nude mice (Onn, Clin Cancer Res 2003) to study malignant pleural effusion, and
examined the effect of ZD6474 (ZACTIMA™), a novel tyrosine kinase inhibitor, on
H441 human pleural effusion producing adenocarcinoma tumor cells, injected
orthotopically into the lungs of nude mice.
Results: Microscopic nodules were identified 5 days (median), and bloody malignant
pleural effusion was detected 15 days (median) after tumor implantation (0.5 x 106
cells in matrigel). Pleural metastasis was necessary for effusion production.
Immonohistochemical staining revealed that the developed tumors expressed VEGF,
VEGF receptor (VEGFR) and activated VEGFR, and ELISA revealed high VEGF level in
the effusion. Groups of mice (n=10) injected with H441 cells were randomized on
day 15 to receive daily vehicle (control) or oral ZD6474 (50 mg/kg). The mice were
sacrificed 3-4 weeks later. Therapy with ZD6474 diminished pleural seeding from
80% to 10% and amount of pleural effusion from 220 micro litter to 50 (control vs.
treatment, median), caused no change in VEGFR level and decreased expression of
phosphorylated VEGFR on primary tumor cells. Using the same therapeutic regimen
we determined in another study that ZD6474 improved mouse survival from 30 to 80
days (control vs. treatment, median).
Conclusions: These data suggest that VEGF/VPF has an important role in malignant
pleural effusion production, and its inhibition with molecular targeted therapy may
be used for the management of this condition. A human clinical trial is underway.
29
Role of ErbB-4 gene in tumorigenic and metastatic behavior of human
non-small cell lung cancer orthotopically growing in nude mice
A.Starr, Y.Shahar, E.Teniakov, Y.Greif and Y.Schwarz
Department of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv
Our previous clinical and experimental studies demonstrated that high expression of ErbB4 receptor (Epidermal Growth Factor Receptor family) is accompanied by increased
malignant potential and correlates with poor clinical outcome of human NSCLC.
The goal of this study was to evaluate the role of the ErbB-4 gene in tumorigenicity and
metastasis of NSCLC innude mouse model following orthotopic inoculation. In our
previous work we obtained cell clones with different ErbB-4 expression by transfection of
ErbB-4 gene into human NSCLC H1299 cell line (Starr et al, 2006). These clones
demonstrated different proliferation in vitro that correlated with ErbB-4 expression as
determined by Western blot analysis and immunostaining..
To study the role of ErbB-4 in NSCLC malignant behavior, we injected transfected clones
of H1299 as well as parental and mock-transfected cells into the lungs of nude mice. The
tumors grown in the lungs as well as their metastatic lesions were studied by gross and
microscopic examination and correlated with ErbB-4 protein expression. Regional
(mediastinal and tracheal), remote (axillary) lymph nodes and metastases in the
contralateral lung were studied by gross and microscopic examination as well as tumor
invasiveness into chest wall and diaphragm.
The cellular properties of H1299 clones such as proliferation, adhesion to different
substrates and spreading, aggregation, motility and in vitro invasiveness were
investigated. These properties showed correlation with the clone's tumorigenicity and
metastasis. Availability of these properties produces so called "metastatic cellular
phenotype" that is responsible for malignant tumor behavior. The results of this study
will contribute to further understanding of the role of ErbB-4 gene in tumor progression
of NSCLC as well as treatment of the disease.
30
Reduced Repair of the DNA Damage, Risk and Susceptibility of Airways Cancer
Meir Krupsky MD
The Pulmonary Institute, Tel – Aviv Sourasky Medical CTR
Reduced DNA-repair capacity plays an important role in hereditary as well as in a
variety of sporadic epithelial cancers. We have adopted a functional assay approach
to studying the role of DNA repair in the etiology of human cancer and shown that
reduced repair of the oxidative DNA lesion 8-oxoguanine is a risk factor for Non–
Small Cell Lung Cancer (NSCLC). This was accomplished by using an enzymatic assay
for 8-oxoguanine DNA glycosylase (OGG) - the enzyme which removes 8-oxoguanine
from DNA. The interest in 8-oxoguanine stems from the fact that it is a common
mutagenic DNA lesion which is formed by intracellular oxidation as a byproduct of
both cellular metabolism and exposure to external carcinogens, such as radiation
and tobacco smoke. Importantly, the combination of reduced OGG activity and
smoking was associated with a high estimated relative risk of f-120, illustrating the
cumulative effect of genes and the environment and making the OGG test a
potential screening tool for lung cancer prevention among smokers. DNA repair is a
housekeeping process that operates in all cell types. This raises the question of
tissue specificity in cancer risk caused by reduced OGG and its interrelationship with
tobacco smoke.
In this presentation, we report that reduced OGG activity is associated with risk of
Squamous cell Carcinoma of the ENT / head and neck (SCCHN), and that the
combination of smoking and low OGG activity is associated with an even higher risk
for the disease.
Our study shows that OGG activity in peripheral blood mononuclear cells from 37
cases with Squamous cell carcinoma of the ENT / head and neck (SCCHN) was
significantly lower than in 93 control subjects, frequency matched for age and
gender. Retesting of OGG activity up to 4 years after diagnosis and successful
treatment of 18 individuals who recovered from the disease, showed that OGG
activity values were similar to those determined at diagnosis, suggesting that
reduced OGG activity in case patients was not caused by the disease. Individuals in
the lowest tertile of OGG activity exhibited an increased risk of SCCHN with an OR of
7. The combination of smoking and low OGG was associated with a highly increased
estimated relative risk for SCCHN.
These results suggest that low OGG is associated with the risk of SCCHN, and if
confirmed by additional epidemiologic studies, screening of smokers for low OGG
activity should be used as a strategy for the prevention of the entire respiratory
cancers in the " tobacco smoke pathway" i.e. Bronchogenic Cancer as well as
Squamous cell Carcinoma of the ENT / head and neck.
31
Treatment Options for Advanced Non-Small Cell Lung Cancer
Amir Onn, MD
Pulmonary Oncology, Sheba Medical Center
Lung cancer, the number one cause of cancer-related death worldwide, is diagnosed
after the onset of metastases in most cases. Recent research has translated into a
small yet significant improvement in patient outcome. Chemotherapy is now
considered based on tumor biology, aiming to improve survival and symptom
control.
Treatment options for first line of therapy: Patient with adenocarcinoma are
considered for the combination of cisplatin/pemetrexed, which improved survival
from 10.9 months (cisplatin/gemcitabine) to 12.6 months.
Younger patients with adenocarcinoma but without significant cardiovascular comorbidities are considered for platinum based therapy with bevacizumab (avastin).
The major toxicities are pulmonary bleeding or thromboembolic events.
Patients with EGFR expressing tumors may be suitable for combination therapy with
cetuximab (erbitux) based on the FLEX (First Line ErbituX in lung cancer) study, a
multinational phase III trial of cisplatin and vinorelbine plus cetuximab versus
chemotherapy alone in 1125 chemotherapy-naive patients. Median overall survival
was significantly longer for patients in the cetuximab group than in the controls (11·3
vs 10·1 months; hazard ratio for death 0·87, 95% CI 0·76—1·0, p=0·044). The main
serious adverse events related to cetuximab were rash, infusion reactions, febrile
neutropenia, and sepsis. (Lancet, May 2009).
Another emerging concept is management of patients with EGFR-mutation
expressing tumors with EGFR tyrosine kinase inhibitors (gefitinib or erlotinib).
Treatment options for second line of therapy: Monotherapy with pemetrexed,
docetaxel or erlotinib are considered. Patients with adenocarcinoma fare better with
pemetrexed compared with patients with squamous cell histology.
Discussion: More therapeutic options are available for patients with advanced lung
cancer. In many cases, the routine NSCLC histology is not sufficient to direct patients
for a specific therapy, and a more precise diagnosis is needed. These novel
approaches are associated with agent-specific safety profiles.
32
THE LUNG IN SYSTEMIC DISEASE
The Physician - 1653
Gerritt Dou 1613- 1675
33
A middle aged man with secondary pulmonary amyloidosis
Avnon L & Heimer D
Pulmonary Clinic. Soroka University Medical Center, Beer Sheva.
Faculty of Health Sciences Ben Gurion University of the Negev.
Setting: The pulmonary clinic at Soroka University Medical Center
Case description: A 47 years old Bedouin man was admitted with fever, cough and
shortness of breath for two to three weeks. The patient is known since childhood to
suffer from juvenile rheumatoid arthritis. In 1994 he was admitted with nephrotic
syndrome and found to suffer from amyloidosis on a kidney biopsy. He was treated
with systemic steroids and chlorambucil with considerable improvement and was
lost to follow-up. He has a 25 pack years smoking history. Laboratory results are
normal except 24 hours urine sample for protein: 7646 mg. CRP: 7.84 mg%, Sputum
for acid fast bacilli was negative, culture is pending. Blood and urine cultures were
sterile. Pulmonary function tests: show moderate restriction: FVC: 59%, VC: 64%
FEV1: 66%, FEV1/FVC: 91%. Pulse-oximeter saturation: 95%.
Assessment: Chest X- ray is near normal without consolidation or pleural fluid; the
size of the heart is normal. CT of chest high resolution shows a diffuse reticulonodular pattern almost military without enlarged lymph nodes. Gallium scan shows
diffuse increased uptake in parotids and lacrimal glands. The uptake in the lung
parenchyma is not homogenous; the hilar uptake is in the form of Lambda sign.
Management: The patient was treated with IV Zinacef and Tavanic without
response. On bronchoscopy, his airways were normal. BAL for acid fast was negative.
In the transbronchial biopsy no tumor tissue or granulomatous inflammation was
identified. The alveolar space is filled with macrophages without an inflammatory
component. The alveolar walls have a mild inflammation mostly monocytic. On
further staining foci of amyloid depositions for Congo red TFT and amyloid AA were
identified.
Discussion: Pulmonary amyloidosis may be primary or secondary, both conditions
are rarely encountered. We review the literature and discuss the diagnostic means,
and that gallium scan supports a diagnosis of amyloidosis.
Conclusion:We report a 47 years old man with juvenile rheumatoid arthritis with
known secondary amyloidosis of the kidney with massive proteinuria and now
developed the very rare form of nodular amyloidosis of the lungs.
34
Increased Eosinophilia In Induced Sputum Of Ulcerative Colitis Patients: The Lung
as A Mirror Image Of Intestinal Disease ?
Elizabeth Firemana, FaridMasarwyb,YehudaSchwarza, Gabi Groisman,cMoshe
Shtarka, YaelKopelmanb, ShmuelKivitya, ZviFiremanb
a
Department of Pulmonary and Allergic Diseases, Tel Aviv Sourasky Medical Center,
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; bDepartment of
Gastroenterology, cDepartment of Pathology, Hillel Yaffe Medical Center, Hadera,
Bruce Rappaport Faculty of Medicine, The Technion, Haifa.
Background:Ulcerative colitis (UC) is a systemic disease of unknown etiology with
extra-intestinal manifestation. Induced sputum (IS) non-invasively assesses
extrapulmonary involvement in Crohn's disease. We sought to determine whether
there is a cellular marker of lung injury in UC patients detectable by IS.
Methods: Nineteen UC patients (mean age 46.4±11.3 years, disease duration
8.6±7.5 years [range 1-25 years] 68.4% males) were studied, six with active disease
and 13 in remission. Eleven received 5-ASA, 5 received steroids and/or azathioprine
and 3 patients were untreated. UC patients were compared to 27 healthy nonsmoker controls. IS was recovered after 20'inhalation of 3% saline with an ultrasonic
nebulizer by the selecting plugs method, and 300 cells were differentially cell
counted in cytospinGiemsa-stained slides. CD4/CD8 subsets were identified by FACS.
Pulmonary function tests were performed by the Jaeger Masterlabspirometer.
Results: UC patients’ IS contained higher % eosinophils than controls (p=0.05) and
lower FEV1/FVC ratios (p=0.001). Steroids- and/or azathioprine-treated patients had
significantly lower FEV1/FVC ratios than only 5-ASA-treated patients (p=0.019).
Eosinophil infiltration in airways was high in 5-ASA-treated patients compared to
those receiving steroids and/or azathioprine (p = 0.046) and those with less
extensive disease (p=0.05). Using a cutoff of 3% eosinophils, IS had a sensitivity of
67% and specificity of 73% to differentiate patients with a cutoff 70 eosinophils/mm2
in biopsy
Conclusions: The percentage in sputum eosinophils is significantly different between
UC patients with proctitis and pancolitis. These immune abnormalities may be a
common pattern present throughout the mucosae.
35
PULMONARY FIBROSIS and INTERSTITIAL LUNG DISEASES
Bernardino Ramazzini da Capri
The father of Occupational Medicine
1633 - 1714
The first description of interstitial lung disease appears to come from Ramazzini
The author, in the chapter on the Diseases of Sifters, Measurers, and Handlers of Grain, of his
famous book De morbis artificium diatriba, described the occurrence of dry cough, weight loss,
breathing difficulty, and dropsy in these workers.
36
PRIMARY VS. SECONDARY COP, CONTRADICTION IN TERM !?
Amir Bar Shai M.D., Joel Greif M.D, Avi Man, Boaz Tiran, Irina Fomin, Noa Hadayer,
Yehuda Schwarz
Pulmonary Medicine Department, Sourasky Medical Center, Tel Aviv, Israel.
Objects: OP (Organizing Pneumonia) is a clinicopathological entity, which may be
idiopathic or secondary to many types of lung injury. The goals of this study are to
describe the clinical course and outcomes in patients who were diagnosed and
treated for OP in our medical center over a decade. Primary (cryptogenic) and
secondary OP were compared.
Methods and Materials: A retrospective study of patients with OP seen at the Tel
Aviv Sourasky Medical Center, Israel, from January 1, 1995, through December 31,
2005,was conducted. Initial features were obtained from medical records. Imaging
studies and pathology specimens were reviewed for this study. Resolution and
relapse were obtained from medical records.
Results: Ninety-two patients had a clinical diagnosis of OP. Sixty three patients
(68%) had pathologically confirmed OP. Forty one patients (45%) had cryptogenic
OP and 51 patients (55%) had secondary OP. No difference was found between
cryptogenic and secondary OP in type or severity of symptoms, signs, laboratory
and pulmonary function tests. Ground glass pattern in CT was more frequent
inpatients with secondary disease than in primary OP (19.9% vs. 2.6%, respectively;
p=0.02). The inflammation seen in tissue biopsies was of a Parenchymal or
bronchiolitic pattern. In the primary OP a parenchymal pattern was predominant
(80% vs. 48%, respectively; p=0.049) compared to a more bronchiolitic one in the
secondary disease. Relapses were seen in 18.5% of all patients. No significant
therapeutic or relapses differences were found amongst the study groups.
Conclusions: We present our experience of more than 10 years in the diagnosis and
treatment of primary or secondary OP. Patients with secondary OP have delayed
diagnosis, more parenchymal pattern involvement and prolonged disease
compared to the idiopathic type, which responded better to corticosteroid
treatment. We did not find any significant clinical differences between primary and
secondary OP.
37
Down regulation of Thy1 expression increases lung myofibroblast proliferation
Pazit Y. Cohen MSc; Shulamit B. Wallach-Dayan, PhD and Raphael Breuer, MD
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah- Hebrew
University Medical Center, Jerusalem, Israel
Background: Two subpopulations of fibroblasts have been shown in lungs of mice and humans
distinguished by their expression of Thy1 molecule. The Thy1- subset has been shown to be
predominant in lungs of humans with IPF and in bleomycin-treated mice.
Hypothesis: We hypothesize that Thy1- accumulation in lung fibrosis is a result of down
regulation of Thy1 expression, which leads to an increase in proliferation and reduced
apoptosis.
Methods: Thy1 expression was assessed in lung myofibroblasts that were isolated from control
and bleomycin treated mice at different time points following bleomycin instillation (IT), by
flow cytometry. Cell proliferation and apoptosis were studied in Thy1 positive or Thy1 negative
myofibroblasts from bleomycin treated mice, from Thy1 deficient and wild type untreated
mice, and in fibroblasts following Thy1 gene expression manipulation, using Thy1-siRNA or Thy1
cDNA expression vector. Apoptosis and proliferation were assessed by detecting cleavage of
pro-caspase 3 and by BrdU uptake or cell mass measurement, respectively. The identification of
cell cycle target genes that may be affected by Thy1, was performed by gene chip expression
analyses using RNA extracted from lung with/without Thy1 stimulation
Results: Thy1 expression in lung myofibroblasts isolated from lungs of bleomycin treated mice
is decreased at day 14 following IT. Thy1- are more proliferative than Thy1+ myofibroblasts.
Moreover, Thy1 down regulation causes an increase in myofibroblast proliferation rate.
Upregulation of Thy in transformed fibroblasts that lack Thy1 expression causes decrease in the
proliferation rate. In contrast to proliferation, the apoptosis rate didn’t change. In addition,
Thy1 activation down regulated cell cycle gene expression in lung myofibroblasts.
Conclusion: Down regulation of Thy1 expression increases lung myofibroblast proliferation.
This may serve as a mechanism for myofibroblast accumulation in lung fibrosis.
38
Resolution of Lung Fibrosis in gld C57BL/6 Mice By FasL+ Immune Cells
Shulamit B. Wallach Dayan PhD, Regina Golan-Gerstl MSc, and Raphael Breuer MD
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine
Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Background FasL is expressed predominantly on activated T lymphocytes and is the major effector
molecule for CD4+ CTL-mediated apoptosis of unwanted cells. We have previously reported that
normal-lung myofibroblasts are sensitive to Fas- and immune cell-induced apoptosis, but acquire a
FasL – dependent resistance to apoptosis, and evasion from allogeneic-in vivo-immune rejection,
during the development of bleomycin-induced fibrosis.
We hypothesized that FasL positive- rather than FasL negative-CD4+T cells have the potential to
induce apoptosis in normal- and FasL-deficient-lung myofibroblasts and thus to regulate their
accumulation following injury to avoid the development of the fibrotic process.
Methods
A. In vitro: Apoptosis of fibroblasts, at different time-points of lung injury, was assessed upon
coculture with wild-type (FasL+), or gld (FasL-), activated CD4+T cells, using Annexin- V and PI staining.
B. In vivo: Accumulation of myofibroblasts and collagen was assessed in gld mice, with FasL
deficient fibroblasts and immune cells, compared to gld mice reconstituted with wild-type (FasL+)
immune cells, by αSMA-positive staining of lung tissue sections and by Sircoll Red assay,
respectively.
Results FasL+, but not FasL- T cells induce apoptosis of normal, but not fibrotic lung myofibroblasts.
FasL-deficiency in myofibroblasts decreases their resistance to immune T cell-induced apoptosis.
Dissipation of myofibroblasts and decreased collagen deposition were noted in lungs of bleomycintreated gld mice, following their reconstitution with FasL+ immune cells.
Conclusion FasL expression, on T cells, is critical for their ability to induce apoptosis in normaland FasL deficient lung myofibroblasts. Lung myofibroblast accumulation is controlled, at least in
part, by FasL-positive immune cells.
39
TNF-α
α Genotyping At Position 308, Secreted and TNF-α
αmRNA In a Jewish
Population.
Mor Sabag1,2, 3, Irina Fomin1,3,Yehuda Schwarz1,3, Joel Greif,1,3 Elizabeth Fireman.1,2, 3,
1
Pulmonary and Allergic Dis Tel-Aviv Medical Center,2Nat Lab Service for ILD, 3Sackler
School of Medicine, Tel Aviv University, Tel-Aviv, Israel
Background
Sarcoidosis (SA) is a granulomatotic multisystem disease of unknown etiology. TNF-α
plays an important role in its pathogenesis and its inhibitors may be useful in
treatment.
Objectives
To determine the relationship between TNF-α -308A single nucleotide polymorphism
(SNP), soluble and TNF-α mRNA to clinical parameters in a Jewish SA population.
Methods
51 SA patients mean age 56±11 (years) 23M/28F, stages 0-II 67.4% and stages III-IV
32.6% compared to 55 anonymous healthy donors DNA for SNP's (controls CO1) and
27 healthy controls(CO2) age 40±17 (years) 12M/15F for RNA studies.
Induced Sputum (IS) was done after 20' inhalation of 3% saline. 300 IS-cells were
counted in Giemsa stained cytopreps. CD4/CD8 T IS-subsets were done by FACS,
TNF-α level in IS and serum by ELISA (R&D Inc.) TNF-α mRNA IS levels by Real-Time
PCR and DNA-SNP's by NCO I -restriction enzyme.
Results
The incidence of TNF -308A SNP's in SA DNA-samples vs CO1 was similar with no
association to any clinical parameter in SA patients (n=51) or staging subgroups.
Genotype GA/AA showed elevated serum TNF levels and higher IS neutrophils count
compared to homozygote 8.94±2 vs. 2.8±1.7 (p=0.02) and 62.3±11% vs. 47.3±21.8%
(p=0.036) respectively. High lymphocytes levels and CD4/CD8 ratio was found in ISSA vs IS-CO2 14.7±9% vs. 9.7±5.4% (p=0.014); 5.3±4.1 vs. 2.9±1.6 (p=0.001)
respectively. Macrophages correlated with IS-TNF levels (r=0.452, p=0.003).
Conclusions
GA/AA genotype incidence is similar in both populations but well correlated with
soluble TNF in serum and neutrophilia in IS. Further studies with larger population or
other SNP's are needed.
40
Serum Tumor Markers Correlated with the Severity of IPF
Victoria Rusanov, David Shitrit, Yael Raviv, AnatAmital, Mordechai R Kramer
Pulmonary Institute, Rabin Medical Center, Petach Tiqwa 49100, Israel
Objective: Recent studies suggest correlation between tumors markers and
idiopathic pulmonary fibrosis (IPF).
Design: A prospective study of patients with IPF.
Setting: Pulmonary Institute, Rabin Medical Center, Petach Tiqwa, Israel
Participants: 30 consecutive patients with IPF.
Main outcome measures: All tumor markers including CA 125, CA 15-5, CEA, CA 199. The data were correlated to the disease severity parameters including pulmonary
lung functions, 6 minute walk distance test, cardiopulmonary exercise test and
pulmonary arterial pressure as measured by Echo. Mean follow up was 1 years. The
patients were divided to two groups: survival patients (19 patients) versus died or
lung transplant patients (11 patients).
Results: Mean CA 125, CA 15-3, CA 19-9 were in the lung transplant /died group
compared to the survival patients (37.6±23 vs 25.8±21, 102±86 vs 71±37, 266±365 vs
77±141, respectively). Significant correlation was noted between PAP, DLCO and the
tumor markers.
Conclusions: Serum tumor markers can serve as surrogate markers for disease
severity in IPF. Further studies are needed to assess their reproducibility.
41
Granulomatous Lung Diseases/ Sarcoidosis
Morten Ansgar Kveim
Norwegian pathologist, born December 27, 1892, Gjerstad;
died March 24, 1966
Kveim' test
Intra-cutaneous reaction for Boeck’s sarcoid using Kveim antigen.
Kveim's antigen
An extract of sarcoid tissue, usually spleen, liver or lymph node from patients with
sarcoidosis (Boeck’s sarkoid). Used for Kveim’s test.
Kveim-Siltzbach granulomas
Granuloma sometimes formed in sarcoidosis about four weeks after injection of
Kveim's antigen.
Kveim-Siltzbach test
Louis Siltzbach developed a revised test using splenic suspension, and affirmed its
specificity.
Kveim made the observation that sarcoid lymph-node tissue inoculated intradermally
gave rise to papules of sarcoid tissue in 12 of 13 of his sarcoidosis patients.
Simultaneous control injections with Frei antigen and tuberculin did not produce this
response. Since this reaction did not occur in normal subjects, nor in patients with lupus
vulgaris, he concluded that the papules were specific lesions due to an unknown agent
and that the test served to differentiate sarcoidosis from tuberculosis.
The Kveim test is no longer used
42
Friday June 4th – ZION A
COPD , Smoking and Exercise Physiology
Giovanni Batista Morgagni
1682 – 1771
Morgagni (1769 )described 19 cases in which the lungs were turgid , particularly
from air
43
The Effect of N-acetylcysteine on air trapping in chronic obstructive pulmonary
disease (COPD): a randomized placebo controlled study
David Stav M.D. & Meir Raz M.D.
Background: FEV1 is used for classification of disease severity and is a good predictor
of COPD mortality, it is a poor predictor of clinical symptoms, exercise tolerance, and
response to bronchodilators in COPD. Progressive reduction in IC during exercise
reflects dynamic hyperinflation (DH) and is a good predictor of decreased exercise
ability as well as increased exertional dyspnea. N-acetyl cysteine (NAC) an
antioxidant/mucous modifier showed to modify in animal models of COPD changes
at small airways, which mainly caused lung hyperinflation.
Objective: To examine the effect of 1200 mg NAC per day on lung hyperinflation at
rest and after exercise in patients with moderate and severe COPD.
Methods: Randomized, double-blind, cross-over study. Included 24 eligible patients
over 40 years old with a diagnosis of COPD, and FEV1 < 70% of predicted, FEV1/FVC
ratio < 0.70, and functional residual capacity (FRC) > 120% of predicted normal.
Patients were randomized to placebo or NAC twice daily for six weeks. This was
followed by 2 weeks of washout, and then patients were crossed over to alternate
therapy for another 6 weeks. Evaluation was performed after each 6 weeks of each
treatment.
Result: The inspiratory capacity (IC), and vital capacity (FVC) were higher especially
after exercise compared to placebo treatment. In addition, the relationship of
residual volume to total lung capacity (RV/TLC) was reduced in a similar pattern.
Furthermore, the endurance time was longer after NAC treatment compared to
placebo.
Conclusion: NAC treatment of stable moderate and severe COPD patients have
beneficial effect on their physical performance, probably due to reduction in air
trapping.
44
Gender Differences in Exertional Breathlessness in Patients with Mild COPD.
D. Ofir1,2, A, Ariel 3, K.A. Webb 2, D.E. O’Donnell 2.
1. Zinman College of Physical Education and Sport Sciences, Wingate Institute ,
Israel.; 2. Queen’s University, Kingston, Ontario, Canada.; 3. Emek Medical Center,
Afula, Israel.
We postulated that females with mild COPD (GOLD 2006 criteria: postbronchodilator (BD) FEV1/FVC ratio<0.7 and FEV1>80% predicted) would perceive
greater respiratory difficulty due to greater ventilatory constraints during exercise
compared with their male counterparts.
Methods: We compared ventilation (V’E), breathing pattern, operating lung volumes
and intensity of breathing discomfort (dyspnea) during symptom-limited incremental
cycle exercise in 8 females (61±5 years) and 13 males (67±8 years) with mild COPD:
post-BD FEV1/FVC 62±4 and 59±7 %, FEV1 90±6 and 93±7 % predicted, respectively
(mean±SD).
Results: Dyspnea intensity (Borg scale) was greater in females than males for a given
work rate (WR), absolute V’E and oxygen uptake (V’O2): Borg ratings at 60 W were
3.2±1.4 and 1.6±1.7, respectively (p<0.05). However, gender differences in dyspnea
were not significant when corrected for predicted values of WR, V’E and V’O2. In
females, the inspiratory reserve volume (IRV) was significantly lower, 13.5±6.8 vs
21.4±8.8 % predicted TLC at a standardized WR of 60 W (p<0.05); and a tidal volume
(VT) plateau combined with a higher breathing frequency was seen at a lower V’E
than males.
Conclusion: Females with mild COPD perceived greater breathing discomfort during
physical exertion. This reflected (1) a relatively reduced maximal ventilatory capacity
and (2) greater mechanical constraints on VT expansion during exercise in females.
Dr. Dror Ofir was supported by: The Center for Absorption in Science, Israel. And the
Ontario Thoracic Society, Canada.
45
Attenuation of cue-induced smoking urges and brain reward activity in smokers
treated successfully with bupropion.
Aviv Weinstein Ph.D1,2, Joel Greif M.D 3, Zipi Yemini3, HedvaLerman M.D2, Abraham
Weizman MD4 , Einat Even-Sapir MD Ph.D2
1
Dept. of Nuclear Medicine Hadassah Hospital, Jerusalem, Israel.
2
Dept. of Nuclear Medicine Sourasky Medical Center, Tel Aviv, Israel.
3
Lung Institute Sourasky Medical Center, Tel Aviv, Israel.
4
Research Unit, Geha Mental Health Center and Felsenstein Medical Research
Center, Tel Aviv University, Tel Aviv, Israel.
Location of work and address for reprints: Department of Nuclear Medicine,
Sourasky Medical Center, TelAviv, 64239, Israel.
Corresponding author: Dr. Aviv Weinstein, Department of Nuclear Medicine,
Sourasky Medical Center, TelAviv, 64239, Israel.
[email protected] 972-3-6973536 Fax- 972-3-6973895
Abstract
Twenty two regular smokers (15+ cigarettes per day) were treated with bupropion
and group therapy for two months. Subjects underwent Positron Emission
Tomography (PET) studies using measures of brain global and regional glucose
metabolism (rCMRglc) with [18 F] -Fluorodeoxyglucose (FDG) twice, after a smoking
movie and after watching a control movie in counter-balanced order. Questionnaire
of smoking urges (QSU) was filled in before and after watching both movies. Changes
in brain metabolic rates of FDG were analyzed using Statistical Parametric Maps
(SPM 2) in 11 smokers who abstained from smoking in comparison with 11 smokers
who continued to smoke during the second month of treatment. Still-smokers had
higher craving scores after watching the smoking videotape compared with nonsmokers. Secondly, watching the smoking videotape compared with the control
videotape in still smokers resulted in increased metabolic rates in the striatum,
thalamus and mid-brain. Thirdly, the ratings of the urge to smoke cigarettes while
watching the smoking videotape in still smokers was associated with brain metabolic
activity in the ventral striatum, anterior cingulate, orbito-frontal cortex, middle
temporal lobe,hippocampus, insula, midbrain, and thalamus. In conclusion,
successfully treated smokers showed attenuated craving and reduced activity in the
meso-limbic reward circuit.
46
Training for a Marathon, my personal experience as a non professional athlete
Barak Gershon, The Pulmonary Institute, Rehabilitation Program, Sheba Medical
Center, Tel Aviv University, Sackler Medical School
Running a Marathon is a physiological and a mental challenge.
Training for a marathon involves preparation that must be based, among other
factors on principles of pulmonary and exercise physiology.
I shall describe my experience as a non professional runner (n=1) with 3 attempts to
complete the run. My specific goal was to achieve it in less than 3 hours (world
record = 2.03:59 hours).
I shall describe the physical, dietary and mental preparations and the difficulties and
barriers during the preparation phase and during the Marathon itself.
My conclusion is that with appropriate motivation and preparations, almost anyone
can achieve the goal that was first achieved by the ancients Greeks.
47
ASTHMA
Girolamo Cardano (Cardan)
1501 – 1576
Italian Physician, Philosopher, Astrologist, Mathematician, Inventor, Gambler
Summoned to treat the Archbishop of Scotland in 1552, Cardano correctly diagnosed
feather pillows as the cause of the Archbishop's asthma. Though Cardano was
already an established professor of medicine at the University of Padua, the event
solidified his reputation as a renowned physician, and helped him secure a list of
wealthy patrons and valuable political connections.
48
OCCUPATIONAL ASTHMA (OA) IN ISRAEL
Elizabeth Fireman, PhD
Pulmonary and Allergic Dis., Nat. Lab Service for ILD, Tel-Aviv Medical Center, Sackler
Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
OA is defined as "a disease characterized by variable airflow limitation and/or
airway hyperresponsiveness due to conditions attributable to a particular
occupational environment". Current clinical investigation of OA is based on the
demonstration of functional changes after exposure to occupational agents, but it
does not include any means of monitoring airway inflammation, one of the
hallmarks of this disease.
Non-invasive techniques have been recently implemented for assessing airway
inflammation in OA, among them induced sputum (IS) and exhaled nitric oxide (NO).
As in asthma, the eosinophils are the cells that most often increase in the sputum of
individuals with OA. Several studies have shown that individuals with OA had higher
eosinophil counts when at work compared with periods away from work. NO is a
central mediator in the body that is more strongly expressed in the bronchial
epithelium of asthmatic patients. The elevated exhaled NO levels in asthma and the
fall following therapy with inhaled corticosteroids support the contention that
exhaled NO may represent a convenient, safe, non-invasive surrogate marker of
airway inflammation. Given the simplicity of measuring NO, it has been proposed as
a potential epidemiological tool for the early detection of OA. Individuals with
positive specific inhalation challenges to occupational agents seem to show a greater
increase in exhaled NO than those with negative specific inhalation challenges. In
Israel, these new techniques together with peak expiratory flow monitoring are now
available and are expected to be implemented in the assessment and diagnosis of
OA in the near future.
49
Early Diagnosis Of Airway Hyperresponsiveness Using a Biphasic Exercise
Provocation Test In Patients With Suspected Asthma
Zeev Weiler, Yuri Zeldin, Nelly Poliakov, Eli Magen , Mona Kidon
Objective:
To assess the clinical validity of a biphasic exercise challenge test
Design :
Prospective randomized with a morphologically matched control group
Setting and population:
Study group was recruited from the 1500 patients referred for respiratory symptoms
to the pulmonary institute at the Barzilai medical center (BMC), aged 17-28.
Outcome measures:
All patients underwent a systematic disease staging including pulmonary function
tests (PFT's) as well as a biphasic exercise challenge test (BECT) and a methacholine
challenge test (MCT).
55 patients whose initial PFT's were within normal limits as well as their BECT and
MCT were followed for a median of 5 years, at the end of which a repeat assessment
was done that included the afore mentioned tests, as well as methacholine
challenge test (MCT) as well as a clinical asthma questionnaire regarding disease
severity as well as treatment.
Results:
Of the qualified group of 36 patients demonstrating a post exercise airway hyperreactivity (PEAR) followed and reevaluated subsequently, 23 (64%) filled both the
PEAR test positivity as well as the positive clinical score test for asthma ranging from
mild to moderate.
Only 1 patient (5%) of 19 patients with a negative PEAR test developed asthma by
both challenge and clinical evaluation methods making for a sensitivity of 96%,
specificity of 56%, a NPV of 95% and a PPV of in this population
Conclusion:
The PEAR test could serve as an adjunct more sensitive measure for evaluation of
suspected asthma patients thus preventing from the symptomatic PEAR positive
patients, the need for further challenge testing and earlier initiation of antiinflammatory therapy.
50
Use of Complementary and Alternative Medicine among Asthma Patients
Attending Pulmonary Clinic in Jerusalem
Ariel Rokach MD MHA1, Raphael Breuer MD2, Gabriel S. Breuer MD3.;
1- The Institute of Pulmonology Shaare Zedek Medical Center, Jerusalem;
Pulmonary Medicine Hadassah-Hebrew University Medical Center,
Jerusalem;
2- Rheumatology Unit, Department of Internal Medicine, Shaare Zedek Medical
Center
E-mail- [email protected]
Background- In this study we aimed to evaluate the prevalence of complementary
and alternative medicine (CAM) use among asthma patients. We analyzed the
demographic features of CAM users, the satisfaction from CAM and the correlation
between the severity of asthma and the use of CAM.
Methods- We conducted a survey among asthma patients attending outpatient
pulmonary clinic in Jerusalem between January and June 2005. One hundred and
six concomitant asthma patients were approached and passed a face-to-face
structured interview. In addition to demographic data, the survey included,
questions regarding education level and occupation status. Severity of asthma was
evaluated according to the GINA criteria. CAM usage was evaluated by specific
questions regarding past or present use, the specific method of CAM and satisfactory
with the treatment. Statistical analysis evaluated correlation between demographic
factors and CAM usage. Analysis aimed to find correlation between the severity of
asthma and CAM usage.
Results- One hundred and six patients were interviewed, sixty females (57%) and
forty-six males (43%). Mean age 44.7+17. Forty five percent of the patients used
CAM. Patients with advanced education tended to use CAM more commonly than
patients with lower education (53.5% vs. 35.4% P=0.06). No correlations were found
between age, gender, origin, family status or occupation and use of CAM. We did not
find correlation between asthma severity and the use of CAM. Homeopathy and
acupuncture were the most commonly used types.
Patients filled in a questionnaire regarding self-perceived efficacy scale of 1-10. The
mean score of the whole group was 5.
Conclusions- The use of CAM among asthma patients is very common (45%). There is
correlation between advanced education and the use of CAM. No other correlations
were found between age, gender, origin, family status, occupation or asthma
severity and use of CAM.
51
.
The response to bronchodilator following negative metacholine challenge test
predicts development of asthma.
Mordechai Yigla., Oren Fruchter
Division of Pulmonary Medicine, Rambam Health Care Campus. The B. Rappaport
Faculty of Medicine, Technion, Institute of Technology, Haifa, Israel.
Background: Metacholine challenge test (MCT) is a reliable tool for excluding
asthma, although a false negative rate of up to 10% still raises concern. We looked
into the long-term predictive value for asthma of the magnitude of the response to
bronchodilator (BD) administered following a negative MCT.
Methods: Over 5 –year period, starting from January 1st 2004, the change in the
forced expiratory volume in the first second (FEV1) after inhaling BD (Salbutamol)
was recorded among subjects with negative MCT. Subjects with a significant
response to BD (defined as improvement in FEV1 of more than 200 ml and 12%) were
questioned for the presence of asthma on January 2009. A receiver-operatorcharacteristic curve was used to calculate the optimal cutoff level of the response to
BD as a predictor for future diagnosis of asthma.
Results: Overall 645 subjects (mean age 21.4 ± 2.3 yr) underwent MCT of whom
negative MCT (defined as PC20> 16 mg/ml) was noted in 482 (74.7%) patients.
Significant response to BD was identified in 90 of them, of whom 35 responded to
questionnaire. Over a median observation time of 2.1 years, 11 patients (31.4%)
were diagnosed with asthma. Improvement of FEV1 by 20% predicted asthma with
sensitivity, specificity, and positive predictive values of 86.9%, 66.6 %, 83.3%,
respectively, P = 0.0022.
Conclusions: Our findings suggest that administration of BD following a negative
MCT enhances its diagnostic accuracy as it identifies subjects who are likely to
develop clinical asthma in the future.
52
EDA-fibronectin induces airway fibrosis via modulation of lung fibroblast
phenotype in a murine model of chronic asthma
Martin Kohan and Neville Berkman
Institute of Pulmonology, Hadassah-Hebrew University Medical Center
Rationale: Airway remodeling is defined as qualitative and quantitative changes
occurring in structural components of the airways. Asthma severity and
refractoriness are likely to be attributable to airway remodeling. Myofibroblast
differentiation and subepithelial fibrosis are key features of airway remodeling. EDAfibronectin (FN), an alternatively-spliced form of the extra-cellular matrix protein FN,
plays a critical role in myofibroblast differentiation during wound healing.
Aim: To determine the role of EDA-FN in airway remodeling using a murine model of
chronic allergen-induced asthma.
Methods: EDA -/- and wild type mice were sensitized and exposed to inhaled
ovalbumin (OVA) or saline for 5 weeks and sacrificed 24 hours after the last
inhalation. Bronchoalveolar cell counts, peribronchial collagen production
(Trichrome staining and Sircoll assay), smooth muscle (SM) area (IHC) and mucus
expression (PAS staining) were assessed. EDA-FN expression was determined by PCR
and IHC. Cytokine and growth factor expression was determined by ELISA.
Functional behavior of lung fibroblasts from OVA-treated wild type and EDA-FN null
mice were studied using ex vivo cultures.
Results: Increased EDA-FN expression was observed in lungs OVA-treated wt mice
and in lung fibroblasts isolated from wt OVA-treated mice. OVA-treated EDA-/- mice
showed a reduction of collagen deposition and active TGF-β1 expression as
compared with wt mice, whereas no changes were observed in other aspects of
remodeling or inflammation. Lung fibroblasts from OVA-treated EDA -/- mice
showed reduced migration, proliferation, collagen deposition, α-SMA expression and
contractility.
Conclusions: We conclude that OVA-treated EDA -/-mice are protected from the
development of airway fibrosis due to a critical role for EDA-FN in lung fibroblast
activation and differentiation. Taken together, our data suggest that EDA-FN plays an
essential role in airway remodeling in asthma.
53
BRONCHOLOGY
Chevalier Jackson , MD in Philadelphia, PA, USA
1865- 1958
Rigid bronchoscopy was introduced in 1895 by Gustav Killian ( 1860 – 1921) in
Germany. He used a rigid esophagoscope and a forceps to remove a piece of bone
from the right bronchus of a farmer.
Chevalier Jackson in Philadelphia invented modern esophagoscopes and
bronchoscopes and endoscopic instruments.
He was the author of 12 textbooks and over 400 articles . in 1907 he published
“Tracheobronchoscopy , Esophagoscopy and Gastroscopy”
54
Pilot experience of Mitomycin C as an adjunct in bronchoscopic laser management
of benign tracheal stenosis
Boaz Tiran, Avi Man, Irina Fomin, Yehuda Schwarz
Pulmonary Medicine Department, Sourasky Medical Center, Tel Aviv, Israel.
Complications of endotracheal intubation and tracheostomy include the formation
of obstructing tracheal granuloma and tracheal stenosis. While the traditional
standard management of symptomatic lesions has been surgical, many patients have
considerable co-morbidities precluding such major surgery, or prefer to defer
surgery for less-invasive options. In addition, post-surgical anastomosis-site
granulation tissue formation and scarring may cause recurrent tracheal obstruction.
Indeed, emerging bronchoscopic techniques have facilitated less-invasive
management in such patients, although most cases require multiple procedures.
Bronchoscopic measures generally incorporate techniques for expanding the
tracheal lumen (e.g. bougienage, stenting) or removal of obstructing tissue (e.g. laser
photoresection, argon plasma coagulation, electrocautery, etc.). A common
occurrence is the reformation of granulation tissue and scarring resulting in
recurrence of symptoms and the necessity of multiple procedures.
Mitomycin-C (MyC) , derived from the Streptomycescaespitosus bacterium, is an
alkylating agent which cross-links DNA, and therefore can inhibit cell division, protein
synthesis, and fibroblast proliferation. It has been applied topically in various surgical
and endoscopic procedures as an adjunctive measure to reduce restenosis and scar
tissue formation, although the evidence of its efficacy and safety is scant and based
on retrospective reports on small series.
In this presentation we describe our experience in the use of MyC as an adjunct in
bronchoscopic laser management of tracheal stenosis in six patients that needed
repeated laser/bougienage bronchoscopic treatments.
These patients needed repeated laser treatments in an interval of 2-3 weeks. By
adding submucosal injections of MyC we were able to increase the bronchoscopic
intervals from doubling the time interval up to preventing another treatment.
55
Post coital Hemoptysis: Our experience and review of the literature
Leonardo Fuks MD, David Shitrit MD, Yael Raviv MD, AnatAmital MD, Benjamin D.
Fox BM, Mordechai R. Kramer MD
Pulmonary Institute, Rabin Medical Center,Beilinson Campus, Petah Tiqwa; affiliated
with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
SETTING: Hemoptysis after physical activity is a well known phenomenon.
Hemoptysis following sexual intercourse seems however to be rare.
We describe a case series of three patients with post coital hemoptysis occurring
only after sexual activity and not following other types of physical effort. The
underlying causes were congestive heart failure, uncontrolled hypertension and
Takayasu arteritis.
Design: We summarized all case reports, reviewed the medical literature and
described our case series. The study was retrospective.
Results: The patients described in previous case communications were diagnosed
with Hypertension, mitral stenosis, left ventricular failure, pulmonary embolism,
coronary artery disease, mitral regurgitation, amyloidosis, and
lymphangyoleiomyomatosis and combined mitral regurgitation and pulmonary
hypertension .We describe three women who presented with hemoptysis following
sexual intercourse
Conclusion: We conclude that hemoptysis can present rarely following sexual
activity and usually associated with cardiovascular decompensation but it is always
necessary to search for other underlying diseases.
56
New optical navigation system for CT guided lung biopsies: Initial animal and
human experience
Yehuda Schwarz ,Galit Aviram, Avi Man, Boaz Tiran, Irina Fomin, Ram Mor, Amir
Bar Shai & Jacob Sosna
Purpose: To evaluate the spatial accuracy and performance of a stereotactic
computer guidance optical needle tracking system in CT guided lung biopsies. Free
hand technique for instrument insertion is usually employed but is greatly
dependent on operator experience and on the complexity of the path. This
technique often requires multiple re-positioning or re-insertion to correct for wrong
initial insertion angles. Multiple insertions increase the likelihood of complications
such as pneumothorax. The purpose of this presentation is to report on the
evaluation of a recently developed, optical stereotactic tracking and guiding system.
The new ActiSight Needle Guidance System (ActiViews Ltd. Haifa Israel) is a
stereotactic accessory for Computed Tomography (CT) systems meant to assist
trained physicians in guiding intervention tools to pre-identified target locations. The
system displays a real-time image on a computer monitor of a CT-based model of the
target location and the projected tool path intersection with the plane of the target.
These aid the interventionist in aligning the direction of the tool for accurate
placement into the target area.
Methods: The guidance system tracks the needle by means of the small optical
sensor attached to the proximal end of the needle and a label sticker attached to the
surface of the body at the desired point of entry. ActiSight employs a skin pad with
eight x-ray absorbing fiducial points that are easily identified and segmented on the
CT images and provide a frame of reference in which the coordinates of the lesion,
which is the target of the intervention, can be located. In addition, the system can
recognize with high sensitivity any bending of the tool outside the body. An
algorithm that takes into account the measured curvature of the tool outside the
body and the elastic properties of typical intervention tools, enables compensating
for the bending and predicting the actual location of the tip of the tool. The system
provides the operator a real time positional data including six degrees of freedom
(3D location and angles for complete guidance during the procedure. After
performing 675 measurements with a testing chamber an animal study was
performed on four domestic swine using implanted, 2 mm seeds in 5 lung targets.
Then, after obtaining informed consent with IRB approval, 20 patients, with lung
lesions suspicious for malignancy underwent CT guided interventions using the novel
guidance system. Accuracy of reaching the pre-selected points within the target
lesions, number of needle passes and rate of complications were recorded.
Results: In the animal experiments the mean (SD) distance between the needle tip
and the targets was 0.5 mm (0.1 mm). In the human subject, all lesions (mean
diameter 4.3 cm) have been successfully reached with one needle pass. Mean
distance between the needle's tip and the pre-selected points within the lesions was
2 mm (1.4). One patient developed a small post procedural pneumothorax.
Conclusions: Our preliminary experience suggests that the use of a stereotactic
computer guidance system is accurate. Additional clinical trials are underway
57
Bronchoscopic Treatment Of Intraluminal Typical Carcinoid
Leonardo Fuks MD, AnatAmital MD, Benjamin D Fox MD, Nader Abdel Rahman
MD,Mordechai R Kramer MD
Pulmonary Institute, Rabin Medical Center, Petach Tikwa, Israel
Setting: Typical pulmonary carcinoid represent less then 2% of lung tumors. The
tumor is commonly found endobronchially. Although the common practice to treat
these tumors is lung resection endobronchial resection is another option. We report
here the long term outcome of patients with endobronchial resection of carcinoid
tumors.
Patients and Methods: 10 patients with endobronchial carcinoid were treated
endobronchialy. There were 3 female and 7 males ages 24 to 70 years old. The
tumor was located at various sites (2 Lt Main bronchus, 1 LT upper lobe bronchus,
2 RT main bronchus, 2 RT mid lobe bronchus and 3 RT lower lobe bronchus.
Symptoms included cough, hemoptysis and recurrent pneumonia. If the tumor
persisted after 4 bronchoscopic treatment surgery was recommended. The
endobronchial treatment included YAG-laser under local sedation in an outpatient
setting. We followed the patients for 29months (Range from 12 to 156 months).
Results: Complete eradication of the tumors was observed in all patients. Number
of procedures was 2-5 follow up included repeat bronchoscopy and chest CT every 6
months.
Conclusions: Endobronchial complete resection of carcinoid tumor is a feasible
option in a subgroup of patients. Follow up of these patients is mandatory.
58
THORACIC SURGERY
The surgeon’s consultation room
Balthasar van den Bossche
1681- 1715
59
Surgery in China – Impressions of an Israeli Physician
Dov Weissberg, MD
Several years ago I was invited to the Medical Center of the Shandong University in
China, to teach thoracic surgery. I was stationed at the QuFu People’s Hospital. Two
interpreters fluent in English accompanied me at all times. The physicians whom I
met did not know English; all teaching of medicine in China is in Chinese (Mandarin)
only. I participated in clinical conferences, bedside rounds, work in the outpatient
clinics, and operations.
My impressions were mixed. The technical skills of the surgeons whom I met were
excellent, but I have serious objections and criticism regarding preoperative
evaluation, postoperative care, and the general approach to surgical care.
Practical clinical examples will be discussed.
60
Surgical controversies in Thoracic surgery: Open versus VATS Lobectomy.
Nachum Nesher, M.D., Yosef Paz, M.D.
Dept. of Cardiothoracic Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv.
The momentum for minimally invasive thoracic surgery has been growing. Since the
first video-assisted thoracoscopic surgery (VATS) lobectomy was performed in 1992,
thousands of such procedures have been performed. However, currently, most
lobectomies are still performed via a thoracotomy. Although most lobectomies could
be performed with video-assisted thoracoscopic surgery, less than 5% are currently
performed this way (less than 30% of all partial lung resections).
Compared with a thoracotomy, video-assisted thoracoscopic surgery offers patients
less pain, a quicker recovery and a shorter length of stay without compromising the
adequacy of the operation. The purpose of this review is to discuss the current uses
for minimally invasive procedures in thoracic surgery and to present our surgical
techniques and current data regarding these procedures.
RECENT FINDINGS: 411 thoracic operations were performed at the Tel-Aviv Sourasky
Medical Center between January 2008 and May 2009. 57% of the patients
underwent anatomic or non-anatomic lobectomies, segmentectomies and other
wedge resections together with node dissections, routinely performed
thoracoscopically without any rib spreading and >5 cm incision. 42% were operated
for other than partial lung resections (mediastiniscopy, pleurodesis, decortication
and pleurectomy, etc.). Less then one percent were classified as others.
All surgical procedures, apart from the aforementioned one percent, were
performed thoracoscopically with only eight patients converted to thoracotomy for
bleeding, extension of the resection and chest wall removal. There were six
pneumonectomies which started as VATS and were converted for better airway
resection control. Two pneumonectomies were completed thoracoscopically. The
median length of stay after video-assisted thoracoscopic surgery lobectomy was
three days.
Two patients died due to broncho-pleural fistula after pneumonectomies; however,
the complication rate was less than 15%, mainly due to air-leak and pneumonia.
Discussion: Studies comparing video-assisted thoracoscopic surgery and
thoracotomy suggest that minimally invasive surgery causes less pain, has a smaller
impact on postoperative pulmonary function, and provides a quicker return to
regular activity, with at least comparable survival for cancer patients – if not better.
SUMMARY: Current data suggest that video-assisted thoracoscopic surgery has
advantages for lung cancer anatomic pulmonary resections.
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The Doctor
Sir Samuel Luke Fildes
1891
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The Queen of Sheba bringing gifts and gold to King Solomon in Jerusalem
Rubens 1620
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