Gabriella Pezzuto

HRCT and histopathological evaluation of fibrosis and tissue destruction in IPF associated with pulmonary emphysema

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.

Combined pulmonary fibrosis and emphysema: 3D time-resolved MR angiographic evaluation of pulmonary arterial mean transit time and time to peak enhancement

PURPOSE To correlate conventional invasive pressure indexes of pulmonary circulation with pulmonary first-order arterial mean transit time (MTT) and time to peak enhancement (TTP) measured by means of three-dimensional time-resolved magnetic resonance (MR) angiography in patients with combined pulmonary fibrosis 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 time-resolved MR angiography was performed by using a 3.0-T MR imager. Regions of interest (ROIs) were drawn manually on first-order pulmonary arteries. Within the ROIs, signal intensity-versus-time curves reflecting the first 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 significantly 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 significantly with the pulmonary hemodynamic parameters obtained with invasive methods and may represent a complementary tool for evaluating pulmonary hypertension in patients with CPFE.

A pilot comparison of helium dilution and plethysmographic lung volumes to assess the impact of a long-acting bronchodilator on lung hyperinflation in COPD

BACKGROUND Currently, two methods for measuring TLC, RV, and FRC are used in clinical pulmonary function laboratories: body plethysmography and helium dilution. However, these methods are not interchangeable. In moderate-to-severe airflow obstruction, dilution method tends to underestimate and body plethysmography tends to overestimate RV. PURPOSE In 21 patients suffering from COPD (basal FEV(1): 56.69+/-13.64), we investigated whether the two methods of measuring FRC and RV could respond differently to a 2-week treatment with tiotropium 18 microg/day. MAIN RESULTS Tiotropium induced a significant increase in FEV(1) and FVC but not in IC. At baseline, FRC(pleth), RV(pleth) and TLC(pleth) were higher than FRC(He), RV(He) and TLC(He). At the end of the study FRC(pleth), RV(pleth) and TLC(pleth) decreased and FRC(He), RV(He) and TLC(He) increased but only changes in FRC(pleth) and RV(pleth) were statistically significant. CONCLUSION The use of body plethysmography seems to be more appropriate in clinical trials aimed at assessing the impact of a therapeutic procedure in patients with COPD and lung hyperinflation.

Acute COPD exacerbation: 3 T MRI evaluation of pulmonary regional perfusion – Preliminary experience

OBJECTIVES To compare pulmonary perfusion parameters by means of dynamic perfusion magnetic resonance in patients affected by chronic obstructive pulmonary disease (COPD), during and after acute exacerbation. METHODS Fifteen patients were successfully evaluated with perfusional MRI during an acute exacerbation of COPD and upon clinical stabilization. Inclusion criteria were a PaCO2 > 45 mmHg and respiratory acidosis (arterial blood pH < 7.35) at admittance. RESULTS In the acute phase a reduction of pulmonary blood flow (PBF) and pulmonary blood volume (PBV), and a significant prolonging of the mean transit time (MTT) and time to peak (TTP) were observed in all patients. In the stabilization phase a significant increase of PBF and PBV and a significant reduction of MTT and TTP were observed in 6 patients; no significant variations were observed in the other 9 patients. CONCLUSION 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.

A 6MWT index to predict O2 flow correcting exercise induced SpO2 desaturation in ILD

INTRODUCTION Ambulatory oxygen (O2) is prescribed to interstitial lung disease (ILD) patients with mild hypoxemia, breathlessness and dyspnea on exertion. Oxygen titration is generally done with the 6 minute walk test (6MWT) to determine the O2 flow preventing oxygen saturation by pulse oximetry (SpO2) from falling below 88%. His study was designed to generate a 6MWT index predicting the O2 flow allowing completion of the 6MWT without oxygen desaturation. METHODS Oxygen titration data from a group of 66 ILD patients and 30 controls, were used to generate the algorithm determining an index (O2-GAP) predicting oxygen flow required to complete a 6MWT without desaturation below 88%. This index was validated in a group of 93 ILD patients. RESULTS The O2-GAP index, as obtained from the derivation population, (r(2) = 0.97, p < 0.001) was shown to correctly predict the oxygen flow required to complete the 6MWT without SpO2 falling below 88% validated in the validation population (r(2) = 0.842; p < 0.001). CONCLUSIONS The O2-GAP index appears to be a useful tool to titrate ambulatory O2 with a single 6MWT on room air in ILD patients with breathlessness and dyspnea on exertion.

The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils

Only very few studies have investigated the influence of eosinophils on the functional progression of COPD. We aimed at retrospectively analyzing the trend of pulmonary function tests over time in patients with COPD according to two baseline blood eosinophil cell count strata (<2% [EOS−] and ≥2% [EOS+]). We used the last 9-year data present in the database of our outpatient clinic and selected only those who had two blood counts that would guarantee the stability of the value of eosinophils and serial spirometry for 4 consecutive years. The analysis of the time course of the spirometric variables analysed showed differences in FEV1 and FVC decline between the subjects of the EOS− group and those of the EOS+ group. The integrated evaluation of our results suggests that the different level of blood eosinophils in the two groups may have influenced independently the time course of the pulmonary function tests and identify two subgroups of subjects with specific disease characteristics: the hyperinflator and the rapid decliner, respectively.

Impact of pulmonary vascular volume on mortality in IPF: is it time to reconsider the role of vasculature in disease pathogenesis and progression?

The article by Jacob et al. [1], reporting a computer-based computed tomography (CT) approach able to provide a precise quantification of disease extension in idiopathic publmonary fibrosis (IPF) patients by means of specific computer algorithm, CALIPER, is very interesting. Vascular disarrangement as a possible central event in disease progression in idiopathic pulmonary fibrosis (IPF) http://ow.ly/hln3307TyBk