Gianluigi Sergiacomi

Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients. 70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation. Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS >3, 6-min walking distance ≤72% predicted and composite physiologic index >41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients. In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression.

Solitary pulmonary nodules: morphological and metabolic characterisation by FDG-PET-MDCT

Purpose.This study was done to analyse the additional morphological and functional information provided by the integration of [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ([18F]-FDG-PET) with contrast-enhanced multidetector computed tomography (MDCT) in the characterisation of indeterminate solitary pulmonary nodules (SPNs).Materials and methods.Fifty-six SPNs, previously classified as indeterminate, were evaluated using a Discovery ST16 PET/CT system (GE Medical Systems) with nonionic iodinated contrast material and [18F]-FDG as a positron emitter. Images were evaluated on a dedicated workstation. Semiquantitative parameters of [18F]-FDG uptake and morphological, volumetric and densitometric parameters before and after contrast administration were analysed. Results were correlated with the histological and follow-up findings.Results.Twenty-six SPNs were malignant and 30 were benign. Malignant lesions at both PET/CT and histology had a mean diameter of 1.8±1.2 cm, a volume doubling time (DT) of 222 days, a mean standardized uptake value (SUV) of 4.7 versus 1.08 in benign lesions and a mean postcontrast enhancement of 44.8 HU as opposed to 4.8 HU in benign nodules. Malignant lesions had a significantly shorter doubling time and significantly greater postcontrast enhancement compared with benign nodules. Based on the SUV and using a cut-off value of >2.5, PET/CT had a sensitivity of 76.9%, specificity of 100%, diagnostic accuracy of 89.2%, positive predictive value (PPV) of 100% and negative predictive value (NPV) of 83.3%. Based on doubling time (cut off <400 days), it had a sensitivity of 76.9%, specificity of 93.3%, accuracy of 85.7%, PPV of 90.9% and NPV of 82.3%. Based on postcontrast enhancement (cut off >15 HU), it had a sensitivity of 92.3%, specificity of 100%, accuracy of 96.4%, PPV of 100% and NPV of 93.7%.Conclusion.PET/CT allows accurate analysis of anatomical/morphological and metabolic/functional correlations of SPN, providing useful data for identifying and locating the disease, for differentiating between malignant and benign nodules and for establishing the aggressiveness and degree of vascularity of pulmonary lesions. Therefore, partly in view of the considerable reduction in time and cost of the single examinations, we believe that PET/CT will gain an increasingly dominant role in the diagnostic and therapeutic approach to lung cancer, especially in the preclinical phase.

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.

Morphologic grading of emphysema is useful in the selection of candidates for unilateral or bilateral reduction pneumoplasty.

OBJECTIVE Radiologic morphology of emphysema proves useful in the selection of candidates for bilateral reduction pneumoplasty. We developed a simple morphologic grading system capable of identifying subsets of patients who had maximal functional improvement after unilateral or bilateral operation. METHODS Fifty-two patients who underwent unilateral (n=34) or bilateral (n=18) reduction pneumoplasty were evaluated. Emphysema morphology was visually scored by digital roentgenograms and high-resolution computed tomography. In each lung, severity of emphysema (ES), heterogeneity (DHT) and hyperinflation (DHF) degrees, were assessed. Asymmetric ratio of emphysema (ARE) between the lungs was expressed as: higher ES/lower ES scores. Morphometric data were correlated with absolute preoperative-postoperative FEV(1) change (DeltaFEV(1)). RESULTS No difference was found between the unilateral and the bilateral group for ES and DHT. DHF was greater in the bilateral group (3.1 vs. 2.7, P=0.02) whereas ARE was greater in the unilateral group (1.29 vs. 1. 05, P=0.0001). Stepwise logistic regression extracted as best predictors of maximal DeltaFEV(1), ARE (odds ratio=238, Wald test P=0.04) in the unilateral group, and DHT (odds ratio=24, P=0.03) in the bilateral group. Unilateral group DeltaFEV(1) was greater in patients with ARE>/=1.3 (0.44 vs. 0.24 l, P=0.02). Bilateral group DeltaFEV(1) was greater in patients with DHT>1 (0.50 vs. 0.31 l, P=0. 03). No difference was found when comparing DeltaFEV(1) resulting from unilateral RP and ARE>/=1.3, and bilateral RP (0.44 vs. 0.41 l, not significant). CONCLUSIONS This morphologic grading system identified subsets of patients who had maximal functional benefit from unilateral or bilateral reduction pneumoplasty and might be useful in the preoperative screening of candidates for either approach.

Integrated multislice CT and Tc–99m Sestamibi SPECT–CT evaluation of solitary pulmonary nodules

Purpose.The purpose of this study was to evaluate efficacy of multislice computed tomography (MSCT) and single photon emission computed tomography (SPECT)–CT with Tc–99m Sestamibi in the assessment of solitary pulmonary nodules of uncertain significance. Scintigraphy was performed using a ‘hybrid’ g–camera that allows simultaneous acquisition of SPECT and CT images, with interesting results in diagnostic oncology.Materials and methods.Between September 2003 and August 2004, 23 patients with a solitary pulmonary nodule detected on CT underwent SPECT–CT using Tc–99m Sestamibi as a radiotracer. Nodules with positive scintigraphy were immediately subjected to biopsy or surgical resection. Nodules with negative scintigraphy were followed up after 3–4 months by MSCT with automatic segmentation software (Advanced Lung Analysis, ALA) and histological characterisation.Results.Of the 23 nodules (size range 0.8–2 cm) discovered with MSCT, 11 showed intense uptake of Tc–99m Sestamibi. Ten lesions were true positive: seven adenocarcinomas, one squamous cell carcinoma, one large cell carcinoma and one metastasis. The only false positive was histologically classified as a large cell granuloma. Twelve lesions had negative scintigraphy: five fibrous lesions, three hamartomas, three granulomas and one adenocarcinoma (false negative). Benign nodules without tracer uptake underwent another CT scan 3–4 months later, which confirmed stability of the nodule size. Correlation of Sestamibi SPECT with histology showed sensitivity (Se) of 90.9 %, specificity (Sp) of 91.6 %, diagnostic accuracy of 91.3 %, positive predictive value (PPV) of 90.9% and negative predictive value (NPV) of 91.6 %.Conclusions.The integrated use of MSCT and Tc–99m Sestamibi SPECT–CT could be very useful in the management of solitary pulmonary nodules (SPNs). In particular, in our preliminary study, scintigraphy provided significant diagnostic information to differentiate benign from suspicious pulmonary nodules. The use of scintigraphy could be helpful to anticipate histological assessment and surgical treatment of SPNs identified at CT.

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.

Ground-glass opacity: high-resolution computed tomography and 64-multi-slice computed tomography findings comparison.

OBJECTIVE Comparative evaluation of ground-glass opacity using conventional high-resolution computed tomography technique and volumetric computed tomography by 64-row multi-slice scanner, verifying advantage of volumetric acquisition and post-processing technique allowed by 64-row CT scanner. METHODS Thirty-four patients, in which was assessed ground-glass opacity pattern by previous high-resolution computed tomography during a clinical-radiological follow-up for their lung disease, were studied by means of 64-row multi-slice computed tomography. Comparative evaluation of image quality was done by both CT modalities. RESULTS It was reported good inter-observer agreement (k value 0.78-0.90) in detection of ground-glass opacity with high-resolution computed tomography technique and volumetric Computed Tomography acquisition with moderate increasing of intra-observer agreement (k value 0.46) using volumetric computed tomography than high-resolution computed tomography. CONCLUSIONS In our experience, volumetric computed tomography with 64-row scanner shows good accuracy in detection of ground-glass opacity, providing a better spatial and temporal resolution and advanced post-processing technique than high-resolution computed tomography.

Associated Pulmonary Hypertension Is an Independent Contributor to Exercise Intolerance in Chronic Fibrosing Interstitial Pneumonias

Background: Associated pulmonary hypertension (APH) is frequently observed in fibrosing interstitial pneumonias (FIP), such as idiopathic pulmonary fibrosis (IPF). APH is associated with worse prognosis, but it remains unclear whether it is associated with greater functional impairment. Six-minute walk distance (6MWD) is widely used to assess functional capacity in pulmonary hypertension and FIP. Objectives: To investigate if APH independently contributes to exercise intolerance in FIP, irrespective of the extent of underlying fibrosis. Methods: Patients diagnosed with FIP (September 2009 to June 2017) were included in the study if they underwent right heart catheterization, high-resolution chest computed tomography (HRCT), and 6MWD within 3 months. Recruitment was not limited only to patients undergoing lung transplant assessment. APH was defined as mean pulmonary artery pressure (mPAP) ≥25 mm Hg. The extent of fibrosis was quantified on HRCT using a visual fibrosis score by 2 separate observers. Results: Seventy-two patients (60 with IPF) were identified. Fifty-five patients had APH. mPAP was not significantly different in subgroups stratified according to the extent of fibrosis on HRCT. Pulmonary vascular resistance (PVR) was the strongest predictor of 6MWD on both univariate and stepwise regression analyses, and remained so considering only patients with normal wedge pressure (< 15 mm Hg) (n = 61). HRCT fibrosis score and pulmonary function tests did not significantly correlate with 6MWD. Conclusions: In patients with FIP, PVR is a significant contributor of 6MWD, independently from the extent of fibrosis on HRCT. These results strengthen both the rationale to use 6MWD as endpoint in FIP and to target APH with specific therapies.

Staged unilateral lung volume reduction surgery: from mini-invasive to minimalist treatment strategies

Lung volume reduction surgery (LVRS) entailing unilateral or bilateral non-anatomical resection of severely damaged emphysematous tissue carried out by thoracoscopic or open surgical approaches, under general anesthesia with single-lung ventilation, has resulted in significant and long-lasting clinical and functional benefit. Unfortunately, the morbidity rates reported by simultaneous bilateral resectional LVRS has led to raise criticism regarding its cost-effectiveness and has stimulated in recent years the development of less invasive bronchoscopic and surgical non-resectional methods of treatment that are preferentially performed in a staged unilateral fashion. We had previously proposed an innovative LVRS modality, which did not entail any resection of lung tissue and was electively carried out according to a staged unilateral strategy by a multiport thoracoscopic access, through thoracic epidural anesthesia in conscious, spontaneously ventilating patients (awake LVRS). The awake LVRS resulted in significant clinical benefit paralleling that achieved by the resectional method with lower morbidity rates and shorter hospital stay. Moreover, the awake LVRS proved also suitable to be employed in stringently selected patients to perform redo procedures following previous successful bilateral LVRS. More recently, in order to minimize the global surgery- and anesthesia-related traumas, we have modified our original non-resectional method by adopting a single thoracoscopic access as well as an anesthesia protocol entailing use of a simple intercostal block with target control sedation, to realize an ultra-minimally invasive or minimalist LVRS. Hence, a deeper investigation of the pros and cons of staged unilateral LVRS strategies as well as of the novel surgical non-resectional and redo LVRS is warranted in order to verify, the optimal strategies of treatment, which will prove to reduce the typical LVRS-related morbidity while assuring the most durable benefit in patients with advanced emphysema.

Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored.