Validity of Serum Surfactant Protein D as a Lung

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Administrative Information
‫المعلومات االدارية‬
03-06-10
:‫المرجع‬
Project Title - )‫عنوان المشروع (عربي وأجنبي‬
‫ في المصل كمؤشر مخبري في تشخيص مرض الربو و االنسداد‬surfactant D ‫مدى فعالية قياس مستوى البروتين‬
‫الرئوي المزمن‬
Validity of Serum Surfactant Protein D as a Lung-Specific Biomarker in the Diagnosis of
Asthma and Chronic Obstructive Pulmonary Disease
Principal Investigator - ‫الباحث الرئيسي‬
‫رقم الهاتف‬
Telephone
‫العنوان االلكتروني‬
e-mail
‫العنوان‬
Address
‫الوظيفية‬
Post
‫المؤسسة‬
Institution
‫االسم‬
Name
+961 3261 715
rjounblat@ul.edu.lb
Faculty of
Sciences II –
Department
of Biology
POB. 90656
Fanar Lebanon
AssociateProfessor
Lebanese
University
(LU)
Rania
Jounblat
Co-Workers - ‫الباحثون المشاركون‬
‫العنوان االلكتروني‬
e-mail
psalameh@ul.edu.lb LU- Faculty of Pharmacy
‫المؤسسة‬
Institution
‫االسم‬
Name
hcmacaa ecacsaP
mirnawaked@hotmail.com Balamand University- Faculty
of Medicine
Mirna Waked
schamat@ul.edu.lb LU- Faculty of Medicine
myrnahachem@ul.edu.lb LU- Faculty of Sciences II
hbtayoun@ul.edu.lb LU- Faculty of Public Health
Soulaima Chamat
Mirna Medlej Hachem
Hassna Bou Haroun
Tayoun
glsorensen@health.sdu.dk Southern Denmark University(SDU)Faculty of Medicine
3102 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2013
Programme de subvention à la recherche scientifique au Liban – 2013
Grith Sorensen
Page 1 of 4
fdcddP.PacaePamfkafd LU- SDU
zeinaakiki@hotmail.com LU- Université Paris Sud
Two Years : Start date: 01/08/2010
End date: 01/10/2012
Dalia Fakih
Zeina Akiki
: Duration -‫المدة التعاقدية للمشروع‬
Scientific Information
‫العلمية‬
‫المعلومات‬
ّ
Objectives - ‫الهدف‬
This project investigates the validity of serum surfactant protein D (SP-D) as a lung specific
biomarker for asthma and chronic obstructive pulmonary disease (COPD), which are both
considered as inflammatory lung diseases.
A case-control study encompassing three groups: asthma patients, COPD patients and controls
was conducted in the Lebanese population in order to correlate serum levels of SP-D with the
severity of asthma or COPD in patients, in comparison with the levels of non-specific
biomarkers of inflammation, namely the serum CRP and the plasma fibrinogen. In addition, we
studied genetic polymorphisms of the SP-D gene (SFTPD) in the population in order to
determine a potential genetic predisposition to asthma and COPD due to the abnormal levels of
SP-D associated with the presence of certain (SFTPD) alleles.
Achievements -‫أالنجازات المحققة‬
- Study subjects: Clinically defined asthmatic (n=202) and COPD Lebanese patients (n= 90)
and their matching controls (n=452) were recruited for the study at the Saint-Georges Hospital,
Beirut. Cases of asthma were selected among outpatient individuals with incident or prevalent
asthma. Inclusion criteria included a clinical and spirometric diagnosis of asthma, and age: 5 40 years, while exclusion criteria included any cancer diagnosis, and any other respiratory
disease such as COPD, lung cancer or fibrosis. Cases of COPD were selected among incident or
prevalent outpatient cases of mild, moderate or severe COPD, according to the ATS/ERS and
GOLD guidelines based on spirometry performance. Inclusion criterion encompassed being 40
years of age or above, while exclusion criterion were having any other diagnosed respiratory
disease such as asthma, lung cancer, fibrosis. Controls were healthy individuals or outpatient
individuals consulting for diseases other than respiratory problems.
- Data & Blood collection: Informed approval of selected patients and controls was obtained
before clinical data and blood collections. Clinical data were collected through a detailed
questionnaire that included the following sections: socio-demographic characteristics, disease
family history, clinical assessment of disease and symptoms, detailed smoking history, exposure
to allergens and pollution, evaluation of the chronic respiratory disease impact on the patients’
quality of life (Saint George Respiratory Questionnaire). For each patient or control: serum,
plasma and extracted leukocyte DNA was stored frozen until use.
- Measurement of serum Sp-D, CRP and fibrinogen: Different ELISA tests to measure
serum Sp-D, CRP and plasma fibrinogen were performed.
- SFTPD polymorphism: Genotyping of exon 2, 5 and 8 of the SP-D gene (SFTPD) was
3102 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2013
Programme de subvention à la recherche scientifique au Liban – 2013
Page 2 of 4
performed for a group of patients and controls by PCR followed by automated sequencing.
- Data statistical analysis: Data entry and analysis were done by SPSS software, version 18.
Perspectives - ‫آفاق البحث‬
Surfactant protein D seems to be a promissing lung-specific biomarker mainly for COPD
patients. It would be highly interesting to validate its potential use as a diagnostic tool
replacing the routine spirometry test by a prospective study conducted on COPD patients in the
Lebanese population.
Publications & Communications - ‫المنشورات والمساهمات في المؤتمرات‬
PhD thesis
Dalia Fakih. PhD project entitled : SP-D multimerization in pulmonary diseases. Cotutelle
thesis between the Univeristy of Southern Denmark and the Lebanese University. Start date :
March 2012.
International Publications
Two manuscripts from the thesis of Dalia Fakih are currently in preparation, the work was cofunded by the L-CNRS.
International Conferences
R. Jounblat, D. Fakih, M Waked, Z. Akiki, P. Salameh, H. Bouharoun-Tayoun, I. Tornøe, G.L.
Sørensen, S. Chamat.
Validity of Serum Surfactant Protein D as a Lung-Specific Biomarker in Monitoring Asthma,
Chronic Obstructive Pulmonary Disease and Chronic Bronchitis in Lebanese Patients:
Preliminary results. Abstract/Poster presentation at the 22nd Annual Congress- European
Respiratory Society (ERS), 1-5/09/2012, Vienna, Austria.
National Conferences
R. Jounblat, D. Fakih, M Waked, Z. Akiki, P. Salameh, H. Bouharoun-Tayoun, I. Tornøe, G.L.
Sørensen, S. Chamat. Poster presentation at the 19th LAAS conference- 5/05/2013 at LAU,
Beirut, Lebanon.
3102 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2013
Programme de subvention à la recherche scientifique au Liban – 2013
Page 3 of 4
Abstract - ‫موجز عن نتائج البحث‬
Surfactant protein D (SP-D) is an oligomeric lung-derived lectin with important roles in innate
host defence against infectious microorganisms. Since several studies have shown that patients
with inflammatory lung disease such as COPD have elevated levels of circulating SP-D, serum
SP-D has been suggested to be used as a reliable biomarker.
Our objective was to validate for the first time in the Lebanese population, SP-D as a clinical
biomarker for asthma and chronic obstructive pulmonary disease (COPD). In addition, we
studied the correlation between SP-D level and the disease severity in COPD and asthmatic
Lebanese patients. A case-control study was conducted in the Lebanese population. 202 cases
of asthma, 90 cases of COPD and 452 controls have been analysed. Lung function
measurements were performed by spirometry, a standardized questionnaire was filled and
serum levels of SP-D, CRP and plasma fibrinogen levels were measured using ELISA
techniques.
For COPD patients, no association was found for SP-D with age (p= 0.7), gender (p= 0.08) or
smoking (p= 0.23). However, SP-D levels in controls increased with age, with a significant
difference between the age group < 40 and the age group > 60 (p= 0.021). The mean level of
SP-D was significantly elevated in COPD patients (1661.33 ng.ml-1; p<0.001), in asthmatic
patients (1373.92 ng.ml-1; p=0.004) when compared to controls (1221.64 ng.ml-1). Furthermore,
serum SP-D levels correlated with the disease severity in COPD but not significantly (p = 0.7).
Levels of CRP and fibrinogen did not correlate with disease severity. In addition, a study of the
genetic polymorphisms of the SP-D gene (SFTPD) in the sample population was done and data
analysis is ongoing in order to determine a potential genetic predisposition to asthma and
COPD.
We conclude that SP-D could be used as a biomarker for asthma and COPD and seems to be
more specific than general systemic markers of inflammation, CRP and fibrinogen. A
prospective study should provide further information on the clinical utility of using SP-D as a
biomarker to monitor disease evolution of COPD and asthmatic patients.
‫توقيع الباحث‬
3102 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2013
Programme de subvention à la recherche scientifique au Liban – 2013
Page 4 of 4
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