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