Angiogenic activity of sera from interstitial lung disease patients in relation to clinical and radiological changes

Abstract

ObjectiveClinical symptoms and radiological changes are useful in monitoring patients with interstitial lung diseases (ILD). Neovascularization participates in the pathogenesis of idiopathic pulmonary fibrosis and other ILD. The objective of the study was to examine the relationships between angiogenic activity of sera from ILD patients and clinical or radiological status.Material and methodsSerum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with collagen diseases with pulmonary manifestation (CD), 13 with scleroderma (SCL), 14 with Wegener's granulomatosis (WG), 12 with pulmonary Langerhans cell histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy volunteers. As an angiogenic test we used a cutaneous angiogenesis assay according to Sidky and Auerbach. Clinical status was evaluated using a special questionnaire. In all patients chest radiographs were performed.ResultsThe angiogenic properties of sera from ILD differed depending on the clinical diagnosis. The strongest proangiogenic effect was induced by sera from patients with HP (mean number of new vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF (16.2), and PNC (15.7). In the case of DLD (13.2), the effect was comparable to healthy controls (13.5). In contrast, sera from SCL (mean number of the vessels 10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with controls. The angiogenic activity of sera from patients with hilar or mediastinal lymph nodes involvement was higher than that of sera from patients with lung fibrosis. There were also differences in the serum angiogenic activity in relation to the severity of dyspnea.ConclusionsThe data showed that sera from ILD patients constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. Sera from HP, sarcoidosis, IPF, and CD patients demonstrated the strongest proangiogenic activity. However, sera from SCL and HIS inhibit angiogenesis. Angiogenic activity of examined sera was related to the clinical and radiological changes.

Physiology of the lung in idiopathic pulmonary fibrosis

“…In one series, static lung compliance was reduced in all but one out of 25 patients with IPF [32]. Among 31 IPF patients with a mean vital capacity (VC) of 79±17% predicted values, static lung compliance was constantly and strikingly reduced (44±6% pred) [33]. In another series of 14 IPF patients, none had normal static lung compliance [34].…”

Angiogenic activity of sera from interstitial lung disease patients in relation to pulmonary function

“…Blood samples were taken from patients before treatment with steroids or immunosuppressants. The diagnosis of ILD was based on clinical, radiological, functional, serological, BAL, and pathological findings according to the previously described criteria [ 10 ]. The group of collagen or vascular diseases with pulmonary manifestations, confirmed by high resolution computed tomography, consisted of 14 patients with WG, 13 with SCL, 7 with rheumatoid arthritis, 4 with systemic lupus erythematosus, 2 with dermatomyositis, 2 with a mixed connective tissue disease, and 1 patient with psoriatic arthritis.…”

“…The group of collagen or vascular diseases with pulmonary manifestations, confirmed by high resolution computed tomography, consisted of 14 patients with WG, 13 with SCL, 7 with rheumatoid arthritis, 4 with systemic lupus erythematosus, 2 with dermatomyositis, 2 with a mixed connective tissue disease, and 1 patient with psoriatic arthritis. For the control purpose, we used sera from 36 healthy volunteers recruited from our medical staff previously characterized [ 10 ].…”

“…Angiogenesis was evaluated by a leukocyte-induced angiogenesis assay in an animal model described by Sidky and Auerbach [ 12 ], with some modification [ 10 ]. The Balb/c mice served as recipients of mononuclear cells (MNC) preincubated in PBS supplemented with 25% of serum from ILD patients or from healthy volunteers for one hour at 37°C.…”

“…Thalidomide, a strong antiangiogenic drug has been used successfully in some cases of ILD [ 9 ]. Previously, we described a modulation of angiogenesis by sera from patients with ILD and its relation to clinical symptoms and radiological changes [ 10 ]. Little is known about the extent of neovascularisation in ILD in relation to pulmonary function.…”