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Background: Pulmonary sarcoidosis has a variable course ranging from self-limiting disease to progressive fibrosis. Activation of fibroblasts, myofibroblast transformation, and matrix production may contribute to pulmonary damage in sarcoidosis. These processes are influenced by pulmonary cytokines which can be measured in bronchoalveolar lavage fluid (BALF). In order to clarify the incompletely understood fibrotic process in sarcoidosis, we classified activity of sarcoidosis according to WASOG criteria, measured TNF-α, IL-6, and HGF in BALF, and assessed the effect of HGF and BALF on proliferation and matrix production of human lung fibroblasts., Results: BALF was obtained from 34 consecutive patients with sarcoidosis. BALF of active sarcoidosis contained elevated levels of TNF-α, HGF, and IL-6 and stimulated fibroblast proliferation. BALF of inactive sarcoidosis, but not of active sarcoidosis, stimulated the production of matrix proteins. HGF levels in inactive sarcoidosis were below those of control patients. HGF suppressed TGF-β-induced matrix expression and transformation of fibroblasts into myofibroblasts., Conclusion: Prevention of TGF-β-induced myofibroblast transformation may account for the inhibitory effect of HGF on matrix production. The strong fibrogenic effect of BALF of inactive sarcoidosis corresponds to the worse clinical course of inactive sarcoidosis compared with active disease and may be related to a lack of protective HGF.

Cryoextraction is a procedure for recanalization of obstructed airways caused by exophytic growing tumors. Biopsy samples obtained with this method can be used for histological diagnosis. The objective of this study was to evaluate the parameters influencing the size of cryobiopsies in an in vitro animal model. New flexible cryoprobes with different diameters were used to extract biopsies from lung tissue. These biopsies were compared with forceps biopsy (gold standard) in terms of the biopsy size. Tissue dependency of the biopsy size was analyzed by comparing biopsies taken from the lung, the liver, and gastric mucosa. The effect of contact pressure exerted by the tip of the cryoprobe on the tissue was analyzed on liver tissue separately. Biopsy size was estimated by measuring the weight and the diameter. Weight and diameter of cryobiopsies correlated positively with longer activation times and larger diameters of the cryoprobe. The weight of the biopsies was tissue dependent: lung < liver < stomach. Only little tissue dependency was found for the biopsy diameter. The biopsy size increased when the probe was pressed on the tissue during cooling. Cryobiopsies can be taken from different tissue types with flexible cryoprobes. The size of the samples depends on tissue type, probe diameter, application time, and pressure exerted by the probe on the tissue. Even the cryoprobe with the smallest diameter can provide larger biopsies than a forceps biopsy in lung. It can be expected that the same parameters influence the sample size of biopsies in vivo.

Objectives and Methods: In idiopathic pulmonary fibrosis (IPF), proliferation of fibroblasts and increased matrix deposition result in pulmonary damage and respiratory insufficiency. We cultured human fibroblasts from lung biopsies of healthy adults and of three patients with IPF (histologically usual interstital pneumonitis, UIP) in order to compare proliferation ([(3)H]thymidine incorporation, cell count) and matrix protein expression (immune fluorescence, quantification of fibronectin synthesis using time-resolved immune fluorescence) of normal and UIP fibroblasts in response to various growth factors., Findings: The growth factors platelet-derived growth factor-BB (PDGF), epidermal growth factor (EGF), insulin growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), tumor necrosis factor alpha (TNFalpha), Transforming growth factor-beta (TGFbeta(1)), and fibroblast growth factor-2 (FGF-2) stimulate proliferation of normal lung fibroblasts significantly more than proliferation of UIP fibroblasts. Immunofluorescence reveals extensive expression of collagen I, collagen III, and fibronectin induced by serum, TGFbeta(1), and TNFalpha. This expression is more pronounced in UIP fibroblasts than in normal fibroblasts. Quantification of fibronectin synthesis reveals an enhanced fibronectin synthesis by UIP fibroblasts in response to PDGF, EGF, IGF-1, IGF-2, TNFalpha, TGFbeta(1), and FGF-2)., Conclusions: Fibroblasts from normal and UIP lungs differ in their response to growth factors: Whereas normal fibroblasts show a predominantly proliferative response, UIP fibroblasts show an enhanced synthetic activity. Different fibroblast responses may contribute to progressive pulmonary fibrosis in patients with UIP.

The association between nocturnal apneas and transient pulmonary hypertension (PHT) has been well documented. However, there is controversy over the frequency and pathophysiological mechanisms of daytime pulmonary hypertension in patients with obstructive sleep apnea (OSAS). The present study sought to evaluate frequency and mechanisms of pulmonary hypertension in patients with OSAS. It included 49 consecutive patients with polysomnographically proven OSAS without pathological lung function testing. All patients performed daytime measurements of pulmonary hemodynamics at rest and during exercise (50-75W). Six patients (12%) had resting PHT mean pulmonary of artery pressure (PAPM) of >20 mmHg), whereas 39 patients (80%) showed PHT during exercise (PAPM >30 mmHg). Multiple regression analysis revealed 3 independent contributing factors for mean pulmonary artery pressure during exercise (PAPMmax): body mass index, age and total lung capacity % of predicted. Twenty-five of the 39 patients with pathologically high PAPMmax (64%) showed elevated pulmonary capillary wedge pressures (PCWPmax > 20 mmHg), whereas no patient had elevated pulmonary vascular resistance (PVRmax > 120 dynes x s x cm(-5)). In conclusion, daytime PHT during exercise is frequently seen in patients with OSAS and normal lung function testing and is mainly caused by abnormally high PCWP, whereas PVR seems to play a minor role.