[2008] [FRI0258] A VEGF DEFICIENCY CHARACTERIZES SCLERODERMA INTERSTITIAL LUNG DISEASE

M. De Santis¹, G. Peluso¹, R. Inzitari², E. Capoluongo², B. Tolusso¹, S. Bosello¹, S. Alivernini¹, M. Pinnelli¹, C. Zuppi², M. Castagnola², G. Ferraccioli^{1 1}Department of Rheumatology; ²Institute of Biochemistry, Catholic University, Rome, Italy

Background: Vascular endothelial growth factor (VEGF) is abundantly expressed in adult lung tissue, it is secreted by almost all the cell types found in airspace or lining. Although excess of VEGF leads to pathological consequences, underexpression also seems to have deleterious effects on the pulmonary vasculature and alveolar structure. Moreover, animal studies and clinical data support a protective role for VEGF in lung injury and decreased VEGF expression was found to be associated with impaired recovery from lung injury. So it has been suggested that VEGF within the lung may play a dual role, not only in contributing to the regulation of the alveolar-capillary permeability but also by promoting lung repair. VEGF resulted measurable in bronchoalveolar lavage fluid (BALF) of all normal subjects and was found to be reduced in patients with pulmonary fibrosis (1). Poor and discordant data have been reported about systemic sclerosis (SSc) lung involvement and serum or BALF VEGF concentration.
Objectives: The aim of the study was to evaluate VEGF concentration in BALF of SSc patients lung involvement and to correlate BALF VEGF levels with functional, radiological and cellular parameters of lung involvement and with the progression of lung disease.
Methods: Plasma and BALF VEGF levels were analysed trough ELISA (Biosource) in 47 SSc patients with evidence of lung involvement on high resolution computed tomography (HRCT) undergoing bronchoalveolar lavage (BAL). Pulmonary function tests (PFTs) and HRCT were repeated in all the patients after 14.8±5.9 months of follow up.
Results: BALF VEGF levels resulted significantly lower in the patients with alveolitis than patients without (median 274.14 vs 1682.14 pg/mL; p=0.02). BALF VEGF was detectable only in 4 (4,2%) of the patients with alveolitis and in 11 (47.8%) of the patients without (OR=4.58(CI95%1.07-22.3)). The significant association between lower BALF VEGF levels and alveolitis was further confirmed by the inverse correlation between BALF VEGF levels and the alveolar score on HRCT (p=0.037, r=-0.31), BALF total cell count (p=0.004, r=-0.41), macrophage count (p=0.028, r –0.32) and lymphocyte count (p=0.035, r=-0.31). In addition the patients with undetectable BALF VEGF had an higher BALF neutrophil count (17.7±11.2 vs 4.8±9.3, p=0.022). The possible protective role of constitutive lung VEGF expression was confirmed by the association between lower BALF VEGF level and worsening of lung involvement at follow up. The patients with undetectable BALF VEGF levels presented a significant worsening in the interstitial score at follow up (T0 7.3±1.8 T1 8.5±3.0, p=0.045 vs T0 7.1±1.6 T1 7.6±2.5, p=ns). There was no significant association either between BALF VEGF levels and PFTs worsening at follow up or with age, disease duration and smoke habit. No correlation was found between BALF and plasma VEGF levels.
Conclusion: Scleroderma lung disease is characterized by a VEGF deficiency. Lower BALF VEGF levels were found in the patients with a worse lung involvement and with the progression of pulmonary disease.
References: 1. Koyama S. Am J Respir Crit Care 2002;166:382-5.

Ann Rheum Dis 2008;67(Suppl II):366

Scleroderma, Myositis and related syndromes