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Purpose:To correlate conventional invasive pressure indexes of pulmonary circulation with pulmonary fi rst-order arterial mean transit time (MTT) and time to peak enhancement (TTP) measured by means of three-dimensional timeresolved magnetic resonance (MR) angiography in patients with combined pulmonary fi brosis and emphysema (CPFE). Materials and Methods:The study was institutional review board approved. All subjects involved in the study provided written informed consent. Eighteen patients with CPFE were enrolled in this study. Thirteen healthy individuals matched for age and sex served as control subjects. Three-dimensional timeresolved MR angiography was performed by using a 3.0-T MR imager. Regions of interest (ROIs) were drawn manually on fi rst-order pulmonary arteries. Within the ROIs, signal intensity-versus-time curves refl ecting the fi rst pass of the contrast agent bolus in the pulmonary vessels were obtained. MTT and TTP were calculated. Pulmonary arterial pressure and pulmonary capillary wedge pressure were measured with a double-lumen, balloon-tipped catheter that was positioned in the pulmonary artery. The mean pulmonary arterial pressure (mPAP) and the pulmonary vascular resistance (PVR) were determined. Results:MTT and TTP values were prolonged signifi cantly in patients with CPFE compared with those in the control subjects ( P , .001). Mean TTP and mean MTT correlated directly with mPAP and PVR index ( P , .005). At multiple linear regression analysis, MTT was the only factor independently associated with PVR index and mPAP. Conclusion:Three-dimensional time-resolved MR angiography enables determination of pulmonary hemodynamic parameters that correlate signifi cantly with the pulmonary hemodynamic parameters obtained with invasive methods and may represent a complementary tool for evaluating pulmonary hypertension in patients with CPFE.

Idiopathic pulmonary fibrosis has been associated with emphysema in cigarette smokers as a new clinical entity: combined pulmonary fibrosis and emphysema (CPFE). In order to compare histomorphometrical, roentgenological and immunohistochemical aspects of usual interstitial pneumonia (UIP) with and without associated pulmonary emphysema, 17 patients with biopsy-proven UIP were evaluated. Morphometrical evaluation of lung parenchyma destruction was used to divide patients in two subgroups: emphysema/UIP (n=9) and UIP alone (n=8); four patients with biopsy-proven emphysema without fibrosis were also evaluated. At HRTC scan, emphysematous lesions were prevalent in the upper fields of both emphysema/UIP and emphysema groups and the distribution of fibrotic lesions was similar in emphysema/UIP compared to UIP alone. The semiquantitative histopathological fibrotic score was also similar in emphysema/UIP and UIP alone. In addition, the expression of tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-2, MMP-9, MMP-7 and membrane type 1-metalloproteinase (MT1-MMP) by fibroblasts of myofibroblastic foci was similar in emphysema/UIP and UIP alone patients. In contrast, fibroblasts in areas of parenchymal destruction of emphysema/UIP expressed MMP-2, MMP-9, MMP-7 and MT1-MMP at variable but significantly higher levels when compared to emphysema subjects, in the presence of similar levels of TIMP-1, TIMP-2 and TNF-alpha. Fibrotic and emphysematous lesions in emphysema/UIP patients appear to follow the roentgenological and histopathological patterns expected for either UIP or emphysema. Interstitial fibroblast activation is more pronounced in the areas of lung destruction in emphysema/UIP compared to those with emphysema alone, as for exaggerated tissue remodeling.

Inflammation is a hallmark of pneumonia. Therefore, managing inflammation is an attractive adjunct to targeted antibiotic therapy, mainly in severe pneumonia. Recent investigations indicate that glucocorticoids given in physiological doses (from 10-fold to 100-fold less than doses administered in the past) could be of benefit. We could also manage inflammation by administering or influencing cytokines. A major concern is that drugs designed to target a single cytokine or receptor could prove ineffective due to the redundancy of signaling pathways involved. This may require selection of drugs with broad activity or the targeting of molecules common to inflammatory signaling pathways. Drugs affecting multiple molecules or key inflammatory pathway intermediates could be more effective, but their use will need to be weighed against the risk of impairing innate immunity. Indirect approaches to manage inflammation, such as neutralizing cytotoxic substances in the lung (e.g., inhibiting, neutralizing and eliminating endotoxin), could be used in combination with other approaches. Ideally, potential treatment of life-threatening bacterial pneumonia will combine immunoadjuvant and conventional antibiotic therapy, although intense clinical research with immunotherapy has not yet yielded a successful treatment adjunct. We believe that compounds capable of stimulating early host defense and microbial clearance, but not the later phases of inflammatory tissue injury associated with sepsis, may be advantageous.

In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage.The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL). Haemosiderin was assessed by Perls' stain, BAL fluid malondialdehyde (MDA) by high-performance liquid chromatography, BAL cell iron-dependent oxygen radical generation by fluorimetry and the frequency of hereditary haemochromatosis HFE gene variants by reverse dot blot hybridisation.Macrophage haemosiderin, BAL fluid MDA and BAL cell unstimulated iron-dependent oxygen radical generation were all significantly increased above controls ( p<0.05). The frequency of C282Y, S65C and H63D HFE allelic variants was markedly higher in IPF compared with controls (40.4% versus 22.4%, OR 2.35, p=0.008) and was associated with higher iron-dependent oxygen radical generation (HFE variant 107.4±56.0, HFE wild type (wt) 59.4±36.4 and controls 16.7±11.8 fluorescence units per 10 5 BAL cells; p=0.028 HFE variant versus HFE wt, p=0.006 HFE wt versus controls).The data suggest iron dysregulation associated with HFE allelic variants may play an important role in increasing susceptibility to environmental exposures, leading to recurring injury and fibrosis in IPF. @ERSpublications HFE gene variants that cause iron-related fibrosing diseases implicate lung iron dysregulation in IPF pathogenesis

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3D time-resolved contrast-enhanced MRI allows quantitative evaluation of pulmonary regional perfusion in patients affected by COPD, identifying patients in which perfusion defects are resolved in the clinical-stabilization phase. This technique might allow the identification of patients in whom vasospasm may be the main responsible of pulmonary hypoperfusion during acute COPD exacerbation, with potential advantages on the clinical management of these patients.