Clinical Application Of Clinical Evaluation Of Clinical Evaluation Of Lymphatic Fibroids (LAM) And Birt-Hogg-Dubé (BHD) Syndrome

Part One:Serum bio markers in lymphangioleio myomatosis (LAM).Objective:To assess the usefulness of serum vascular endothelial growth factor D (VEGF-D) as a marker of LAM severity, progression and response to rapamycin therapy and to study the diagnostic efficacy of serum platelet-derived growth factor-BB(PDGF-BB) and basic fibroblast growth factor-2(bFGF-2) in LAM patients.Method:We analyzed the correlation between VEGF-D and clinical data of 231 patients who were diagnosed as definite or probable sporadic LAM in Peking Union Medical College Hospital during Jan 2010 to Jun 2014. The clinical data included pulmonary function testing, arterial blood gas analysis at rest,6-minute walking distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ) and the use of rapamycin. We also measured the serum PDGF-BB and bFGF-2 level in LAM patients, other diffuse lung cystic diseases patients and healthy women by ELIS A.Results:The serum VEGF-D level in LAM patients without rapamycin therapy correlated with the percentage of diffusing capacity of the lung for carbon monoxide to the predicted value (%DLCO (n=131, r=-0.250,P=0.004), arterial partial pressure of oxygen(PaO2)(n=155, r=-0.232, P=0.003), difference of alveoli-arterial oxygen pressure(P(A-a)O2)(n=155, r=0.285, P＜0.001) and 6-minute walking distance(6MWD) (n=252, r=-0.184,.P=0.014) but not correlated with forced expiratory volume in one second(FEVi), the percentage of FEV1 to the predicted value (%FEV1), the percentage of forced vital capacity to the predicted value (%FVC), FEV1/FVC, the percentage of residual volume to the predicted value (%RV), the percentage of total lung capacity to the predicted value (%TLC), RV/TLC and SGRQ scores (P>0.05). The change velocity of VEGF-D in LAM Patients with rapamycin therapy was 9-folds faster than that without rapamycin therapy (P＜0.001). There was no difference in the serum PDGF-BB and bFGF-2 level in LAM patients, other diffuse lung cystic diseases patients and healthy women.Conclusion:Serum VEGF-D level can be a marker of LAM severity, progression and response to rapamycin therapy. Serum PDGF-BB and bFGF-2 may not be specific biomarkers for LAM diagnosis.Part Two:Efficacy of rapamycin in patients with lymphangioleiomyomatosis (LAM).Objective:To assess the changes of clinical measures before and after rapamycin therapy in LAM patients.Method:We analyzed clinical measures of 98 patients who were diagnosed as definite or probable sporadic LAM in Peking Union Medical College Hospital and had received rapamycin treatment during Jan 2010 to Jun 2014. The changes of clinical measures of pre and post rapamycin therapy included pulmonary function testing, arterial blood gas analysis at rest,6MWD, SGRQ and VEGF-D were elevated.Results:The LAM patients who received rapamycin treatment in our study are mostly those whose pulmonary function decreased rapidly or damaged severely. Among LAM patients who had the clinical measures both pre and post rapamycin therapy, the mea±SE change range of FEV1 before and after rapamycin therapy were-31.12±30.78ml/month and 16.11±36.00ml/month(n=18, P=0.002), of PaO2 were-0.55±0.60 mmHg/month and 0.30±1.19 mmHg/month(n=l 8, P=0.018), of 6MWD were 358.8±114.4m and 415.6±118.6m(n=46, P=0.004), of SGRQ total scores were 57.2±21.0 and 47.5±22.8(n=50, P＜0.001). The median VEGF-D concentration pre-therapy was 3075.6pg/ml, and decreased to 1609.4pg/ml after rapamycin treatment(n=39, P＜0.001). Conclusion:Rapamycin therapy can stabilize the pulmonary function and arterial partial pressure of oxygen, improve the 6-minute walking distance, and decrease SGRQ scores and serum VEGF-D level in LAM patients whose pulmonary function decreased rapidly or damaged severely.Part Three:Clinical features of 17 cases Birt-Hogg-Dube (BHD) syndrome in Peking Union Medical College Hospital.Objective:To assess clinical features, especially pulmonary cysts feature in Chinese Birt-Hogg-Dube syndrome patients.Method:We analyzed clinical measures of 17 patients from 11 unrelated Chinese families who were diagnosed as BHD syndrome in Peking Union Medical College Hospital during 2012 to 2015.Results:Ten of eleven (91%) unrelated Chinese families had family history of spontaneous pneumothorax or pulmonary cysts. Among the 17 cases BHD syndrome (male 4 cases and female 13 cases), one (6%) patient had skin lesion, all patients had pulmonary cysts and eleven (65%) patients had have pneumothorax. Fifteen patients had done abdominal CT scan or ultrasound. Three (20%) cases had found renal cysts but not renal cancers. Nine of thirteen (69%) patients whose Chest CT films available showed numerous cysts (>20), and the cysts were mainly distributed in bilateral, lower lobes and para-mediastina.Conclusion:Most of Chinese BHD patients have family history of spontaneous pneumothorax or pulmonary cysts. The main clinical manifestations are pulmonary cysts and pneumothorax. Skin lesions and renal tumors are uncommonly seen. The pulmonary cysts are mainly distributed in bilateral, lower lobes and para-mediastina.