Digital quantification of p16-positive foci in fibrotic interstitial lung disease is associated with a phenotype of idiopathic pulmonary fibrosis with reduced survival.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with increased expression of cyclin-dependent kinase inhibitors such as p16 and p21, and subsequent induction of cell cycle arrest, cellular senescence, and pro-fibrotic gene expression. We sought to link p16-expression with a diagnosis of IPF or other fibrotic interstitial lung diseases (ILDs), radiographic pattern, senescent foci-specific gene expression, antifibrotic therapy response, and lung transplant (LTx)-free survival. METHODS: Eighty-six cases of fibrosing ILD were identified with surgical lung biopsy. Immunohistochemistry for p16 was performed on sections with the most active fibrosis. p16-positive foci (loose collection of p16-positive fibroblasts with overlying p16-positive epithelium) were identified on digital slides and quantified. Cases were scored as p16-low (≤ 2.1 foci per 100 mm2) or p16-high (> 2.1 foci per 100 mm2). Twenty-four areas including senescent foci, fibrotic and normal areas were characterized using in situ RNA expression analysis with digital spatial profiling (DSP) in selected cases. RESULTS: The presence of p16-positive foci was specific for the diagnosis of IPF, where 50% of cases expressed any level of p16 and 26% were p16-high. There was no relationship between radiographic pattern and p16 expression. However, there was increased expression of cyclin-dependent kinase inhibitors, collagens and matrix remodeling genes within p16-positive foci, and cases with high p16 expression had shorter LTx-free survival. On the other hand, antifibrotic therapy was significantly protective. DSP demonstrated that fibroblastic foci exhibit transcriptional features clearly distinct from that of normal-looking and even fibrotic areas. CONCLUSIONS: We demonstrated the potential clinical applicability of a standardized quantification of p16-positive fibroblastic foci. This method identifies an IPF phenotype associated with foci-specific upregulation of senescence-associated and matrix remodeling gene expression. While these patients have reduced LTx-free survival, good response to antifibrotic therapies was observed in those who were treated.

One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study.

BACKGROUND: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge. METHODS: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected. RESULTS: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up. CONCLUSION: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.

Lung ultrasound features predict admission to the neonatal intensive care unit in infants with transient neonatal tachypnoea or respiratory distress syndrome born by caesarean section.

We aimed to evaluate the reliability of lung ultrasound (LU) to predict admission to the neonatal intensive care unit (NICU) for transient neonatal tachypnoea or respiratory distress syndrome in infants born by caesarean section (CS). A prospective, observational, single-centre study was performed in the delivery room and NICU of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Term and late-preterm infants born by CS were included. LU was performed at 30' and 4 h after birth. LU appearance was graded according to a previously validated three-point scoring system (3P-LUS: type-1, white lung; type-2, black/white lung; type-3, normal lung). Full LUS was also calculated. One hundred infants were enrolled, and seven were admitted to the NICU. The 5 infants with bilateral type-1 lung at birth were all admitted to the NICU. Infants with type-2 and/or type-3 lung were unlikely to be admitted to the NICU. Mean full-LUS was 17 in infants admitted to the NICU, and 8 in infants not admitted. In two separate binary logistic regression models, both the 3P- and the full LUS proved to be independently associated with NICU admission (OR [95% CI] 0.001 [0.000-0.058], P = .001, and 2.890 [1.472-5.672], P = .002, respectively). The ROC analysis for the 3P-LUS yielded an AUC of 0.942 (95%CI, 0.876-0.979; P<.001), while ROC analysis for the full LUS yielded an AUC of 0.978 (95%CI, 0.926-0.997; P<.001). The AUCs for the two LU scores were not significantly different (p = .261).Conclusion: the 3P-LUS performed 30 min after birth proved to be a reliable tool to identify, among term and late preterm infants born to CS, those who will require NICU admission for transient neonatal tachypnoea or respiratory distress syndrome. What is known • Lung ultrasound (LU) has become an attractive diagnostic tool in neonatal settings, and guidelines on point-of-care LU in the neonatal intensive care unit (NICU) have been recently issued. • LU is currently used for diagnosing several neonatal respiratory morbidities and has been also proposed for predicting further intervention, such as NICU admission, need for surfactant treatment or mechanical ventilation in preterm infants. What is new • LU performed 30' after birth and evaluated through a simple three-point scoring system represents a reliable tool to identify, among term and late preterm infants born to caesarean section, those with transient neonatal tachypnoea or respiratory distress syndrome who will require NICU admission. • LU performed in the neonatal period confirms its potential role in ameliorating routine neonatal clinical management.

Improving Survival in Lymphangioleio-myomatosis: A 16-Year Observational Study in a Large Cohort of Patients.

BACKGROUND: Over the last 2 decades, great progress has been made in the understanding of the clinical aspects and pathogenesis of lymphangioleiomyomatosis (LAM), leading to publication of guidelines and approval of an effective therapy. OBJECTIVES: Aim of our study was to describe how the management and the natural history of this rare disease have changed after the publication of the ERS and American Thoracic Society/Japanese Respiratory Society guidelines and the introduction of sirolimus. METHODS: We examined 162 LAM patients followed at our center between 2001 and 2017, reporting clinical characteristics and diagnostic approach. Response to sirolimus in patients undergoing long-term treatment and mortality risk, estimated in terms of cumulative incidence taking into account organ transplantation as a competing cause of the event, were evaluated. The difference in the cumulative incidence between the patients admitted to the observation before 2011 and after 2011, year of the publication of the MILES trial for the efficacy of sirolimus, has also been estimated. RESULTS: Sixty-one patients had a histological diagnosis (22 from 2010 onward). 101 patients received a radiological diagnosis according to the guidelines criteria. Pulmonary function tests remained stable over a 3-year treatment period in patients who received sirolimus for over 12 months. The cumulative incidence of mortality after 10 years in the whole population was 25.5%. The cumulative incidence of mortality after 5 years was significantly lower in patients who entered the study since 2011 (after publication of the MILES trial) than in patients who entered the study before. CONCLUSIONS: We provide the data supporting the long-term efficacy of sirolimus therapy in a large cohort of patients with functional impairment and other manifestations of the disease. Our results also suggest that the advent of sirolimus and the publication of international guidelines changed the natural history of the disease lowering the mortality and reducing the need of invasive diagnostic techniques.

Validation of the risk stratification score in idiopathic pulmonary fibrosis: study protocol of a prospective, multi-centre, observational, 3-year clinical trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by a poor prognosis, with a progressive decline in lung function and considerable variability in the disease's natural history. Besides lung transplantation (LTx), the only available treatments are anti-fibrosing drugs, which have shown to slow down the disease course. Therefore, predicting the prognosis is of pivotal importance to avoid treatment delays, which may be fatal for patients with a high risk of progression. Previous studies showed that a multi-dimensional approach is practical and effective in the development of a reliable prognostic score for IPF. In the RIsk Stratification scorE (RISE), physiological parameters, an objective measure of patient-reported dyspnea and exercise capacity are combined to capture different domains of the complex pathophysiology of IPF. METHODS: This is an observational, multi-centre, prospective cohort study, designed to reflect common clinical practice in IPF. A development cohort and a validation cohort will be included. Patients newly diagnosed with IPF based on the ATS/ERS criteria and multi-disciplinary discussion will be included in the study. A panel of chest radiologists and lung pathologists will further assess eligibility. At the first visit (time of diagnosis), and every 4-months, MRC dyspnea score, pulmonary function tests (FEV1, FVC and DLCO), and 6-min walking distance will be recorded. Patients will be prospectively followed for 3 years. Comorbidities will be considered. The radiographic extent of fibrosis on HRCT will be recalculated at a 2-year interval. RISE, Gender-Age-Physiology, CPI and Mortality Risk Scoring System will be calculated at 4-month intervals. Longitudinal changes of each variable considered will be assessed. The primary endpoint is 3-year LTx-free survival from the time of diagnosis. Secondary endpoints include several, clinically-relevant information to ensure reproducibility of results across a wide range of disease severity and in concomitance of associated pulmonary hypertension or emphysema. DISCUSSION: The objective of this study is to validate RISE as a simple, straightforward, inexpensive and reproducible tool to guide clinical decision making in IPF, and potentially as an endpoint for future clinical trials. TRIAL REGISTRATION: U.S National Library of Medicine Clinicaltrials.gov, trial n. NCT02632123 "Validation of the risk stratification score in idiopathic pulmonary fibrosis". Date of registration: December 16th, 2015.

Chest-CT mimics of COVID-19 pneumonia-a review article.

Coronavirus disease 2019 (COVID-19) emerged in early December 2019 in China, as an acute lower respiratory tract infection and spread rapidly worldwide being declared a pandemic in March 2020. Chest-computed tomography (CT) has been utilized in different clinical settings of COVID-19 patients; however, COVID-19 imaging appearance is highly variable and nonspecific. Indeed, many pulmonary infections and non-infectious diseases can show similar CT findings and mimic COVID-19 pneumonia. In this review, we discuss clinical conditions that share a similar imaging appearance with COVID-19 pneumonia, in order to identify imaging and clinical characteristics useful in the differential diagnosis.

An unusual case of painless type A aortic dissection.

The pathogenesis of acute aortic dissection (AAD) is not fully elucidated yet, but it was recently shown that inflammation contributes to the occurrence and development of both Stanford type A and type B AAD. We describe a rare case of a painless type A aortic dissection that occurred in an 85-year-old male, with moderate calcified aortic stenosis and a moderately dilated ascending aorta in 6-month clinical and echocardiographic follow-up. A chronic calculous cholecystitis with neutrophilic leukocytosis and severely increased C reactive protein was diagnosed in the last 3 months. In this patient, a chronic systemic inflammatory state might have contributed to generate the intimal entry tear in the aortic root. In particular, a neutrophil mobilization might have played a causative role in aortic rupture.

Longitudinal functional changes with clinically significant radiographic progression in idiopathic pulmonary fibrosis: are we following the right parameters?

BACKGROUND: Progression of the disease in idiopathic pulmonary fibrosis (IPF) is difficult to predict, due to its variable and heterogenous course. The relationship between radiographic progression and functional decline in IPF is unclear. We sought to confirm that a simple HRCT fibrosis visual score is a reliable predictor of mortality in IPF, when longitudinally followed; and to ascertain which pulmonary functional variables best reflect clinically significant radiographic progression. METHODS: One-hundred-twenty-three consecutive patients with IPF from 2 centers were followed for an average of 3 years. Longitudinal changes of HRCT fibrosis scores, forced vital capacity (FVC), total lung capacity and diffusing lung capacity for carbon monoxide were considered. HRCTs were scored by 2 chest radiologists. The primary outcome was lung transplant (LTx)-free survival after the follow-up HRCT. RESULTS: During the follow-up period, 43 deaths and 11 LTx occurred. On average, the HRCT fibrosis score increased significantly, and a longitudinal increase > 7% predicted LTx-free survival significantly, with good specificity, but limited sensitivity. The correlation between radiographic and functional progression was moderately significant. HRCT progression and FVC decline predicted LTx-free survival independently and significantly, with better sensitivity, but worse specificity for a ≥ 5% decline of FVC. However, the area under the curve towards LTx-survival were only 0.61 and 0.62, respectively. CONCLUSIONS: The HRCT fibrosis visual score is a reliable and responsive tool to detect clinically meaningful disease progression. Although no individual pulmonary function test closely reflects radiographic progression, a longitudinal FVC decline improves sensitivity in the detection of clinically significant disease progression. However, the accuracy of these methods remains limited, and better prognostication models need to be found.

The CALIPER-Revised Version of the Composite Physiologic Index is a Better Predictor of Survival in IPF than the Original Version.

CALIPER is a computer-based quantitative algorithm to accurately characterize and quantify pulmonary fibrosis, and a revised version of composite physiologic index (CPI) has been developed against this new algorithm. The prognostic capabilities of the original and CALIPER-revised versions of CPI were compared in a cohort of 185 patients with IPF prospectively followed in 2 centers. CALIPER-revised CPI was a significant risk factor towards lung transplant (LTx)-free survival, with enhanced hazard ratio (5.68) compared to the original CPI (5.36). Accuracy of LTx-free survival was substantially improved with CALIPER-revised CPI (area under the curve [AUC] 0.75 vs. 0.66), with much better specificity (83% vs. 55%). Six-month changes of CALIPER-revised CPI predicted survival significantly (AUC 0.65). CALIPER-revised CPI is a better predictor of LTx-free survival in patients with IPF. Since CALIPER technology is not available to all centers, this simple and easy to obtain tool may be used to guide management decisions in IPF.

Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases.

Rationale: The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. Objectives: To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. Methods: A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Measurements and Main Results: Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5-8 mm). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: κ = 0.22 (95% confidence interval [CI], 0.01-0.44), percentage agreement = 38% (95% CI, 18-62%); MDA2 versus TBLC: κ = 0.31 (95% CI, 0.06-0.56), percentage agreement = 48% (95% CI, 26-70)%; MDA2 versus SLB: κ = 0.51 (95% CI, 0.27-0.75), percentage agreement = 62% (95% CI, 38-82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Conclusions: Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.

ERS statement on chest imaging in acute respiratory failure.

Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other.

Management of incidental pulmonary nodule in CT: a survey by the Italian College of Chest Radiology.

OBJECTIVES: The aim of this study is to present the results of the Italian survey on the management of pulmonary nodules incidentally identified at computed tomography (CT). MATERIALS AND METHODS: An online electronic survey, consisting of 23 multiple-choice questions, was created using the SurveyMonkey web-based tool. The questionnaire was developed by the Board of the Italian College of Chest Radiology of the Italian Society of Medical and Interventional Radiology (SIRM) and by an experienced group of Italian Academic Chest Radiologists. The link to the online electronic survey was submitted by email to all the SIRM members. RESULTS: A total of 767 radiologists, corresponding to 7.5% of all the SIRM members, participated in the online survey. The majority of participants (92%) routinely describe the attenuation of pulmonary nodules in the report, and 84.1% recommend the further follow-up, with 92.7% of respondents taking CT nodule morphological features into consideration. The 57.7% of participants adhere to the Fleischner Society guidelines for the management of incidental pulmonary nodules. However, 56.6% and 75.6% of respondents have a more cautious approach than that recommended by the guidelines and tend to use a shorter follow-up for both solid and ground-glass nodules, respectively. Finally, 94.5% of participants favor congresses and refresher courses dedicated to insights on lung nodule diagnosis and management. CONCLUSIONS: This survey demonstrates that the management of pulmonary nodules incidentally detected on CT is still complex and controversial. The majority of SIRM members express a need for an update on this topic.

Lung Cryobiopsy for the Diagnosis of Interstitial Lung Diseases: A Series Contribution to a Debated Procedure.

Introduction: Transbronchial cryobiopsy is an alternative to surgical biopsy for the diagnosis of fibrosing interstitial lung diseases, although the role of this relatively new method is rather controversial. Aim of this study is to evaluate the diagnostic performance and the safety of transbronchial cryobiopsy in patients with fibrosing interstitial lung disease. Materials and methods: The population in this study included patients with interstitial lung diseases who underwent cryobiopsy from May 2015 to May 2018 at the Division of Pneumology of San Giuseppe Hospital in Milan and who were retrospectively studied. All cryobiopsy procedures were performed under fluoroscopic guidance using a flexible video bronchoscope and an endobronchial blocking system in the operating room with patients under general anaesthesia. The diagnostic performance and safety of the procedure were assessed. The main complications evaluated were endobronchial bleeding and pneumothorax. All cases were studied with a multidisciplinary approach, before and after cryobiopsy. Results: Seventy-three patients were admitted to this study. A specific diagnosis was reached in 64 cases, with a diagnostic sensitivity of 88%; 5 cases (7%) were considered inadequate, 4 cases (5%) were found to be non-diagnostic. Only one major bleeding event occurred (1.4%), while 14 patients (19%) experienced mild/moderate bleeding events while undergoing bronchoscopy; 8 cases of pneumothorax (10.9%) were reported, of which 2 (2.7%) required surgical drainage. Conclusions: When performed under safe conditions and in an experienced center, cryobiopsy is a procedure with limited complications having a high diagnostic yield in fibrotic interstitial lung disease.

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.

Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist.

OBJECTIVES: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). METHODS: The writing committee selected the HRCT criteria-the Delphi items-for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as "essential", "optional", or "not relevant". The items rated "essential" by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. RESULTS: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated "essential" by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated "essential" by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. CONCLUSIONS: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists.

Integrated Use of Lung Ultrasound and Chest X-Ray in the Detection of Interstitial Lung Disease.

BACKGROUND: Current data have shown that lung ultrasound (LUS) may be useful in the detection of interstitial lung disease (ILD) by the evaluation of B-lines, the sonographic marker of pulmonary interstitial syndrome. Nevertheless, no prospective study has compared LUS to chest X-ray (CXR) for ILD assessment, and there is no general agreement on the specific echographic diagnostic criteria for defining ILD. OBJECTIVES: The aims of this study were (1) to compare the accuracy of LUS and CXR in the detection of ILD using high-resolution CT (HRCT) as the gold standard and (2) to compare the accuracy of different echographic diagnostic criteria for ILD diagnosis. METHODS: LUS was performed on 104 patients undergoing HRCT for suspected ILD. In 49 patients, a CXR scan performed within 3 months of HRCT was analyzed. ILD was defined as the presence of ≥5 B-lines in ≥3 chest areas. A total B-line score (TBLS) was also calculated, as in previous studies. The observers evaluating LUS and CXR were blinded to the HRCT results and clinical data. RESULTS: On HRCT, ILD was assessed in 50 patients. CXR was specific (91%; 95% CI 80-100) but not sensitive (48%; 95% CI 28-67). Conversely, LUS showed high sensitivity (92%; 95% CI 84-99) and low specificity (79%; 95% CI 69-90). Using a TBLS, sensitivity did not change, while specificity decreased. CONCLUSIONS: LUS could be a sensitive tool for ILD detection. CXR and LUS have different but complementary features, and their combined use could reduce the need for HRCT. The use of different diagnostic criteria for defining ILD does not affect sensitivity but influences specificity.

Persistent fever with chills and an endocardial mass in a child: an unusual presentation of Hughes-Stovin syndrome.

A 12-year-old boy with a right atrium endocardial mass was initially diagnosed as having Lemierre's syndrome on the basis of previous mastoiditis and jugular vein and cerebral venous thrombosis. Lack of response to antibiotics, persistent high fever with chills, acute-phase reactants, and peripheral arterial pseudoaneurysms made us reconsider the diagnosis. Only after the late appearance of radiological pulmonary lesions and recognition of pulmonary artery aneurysms, Hughes-Stovin syndrome was diagnosed. Hughes-Stovin syndrome is an exceedingly rare vasculitis, especially in childhood, consisting of multiple pulmonary artery aneurysms and deep venous thromboses. The lack of formal diagnostic criteria and the rarity of the disease make the diagnosis very challenging, especially when respiratory complaints are not present at onset, as in the presented case. The treatment aims to reduce inflammation, although there is debate about anticoagulation therapy because of the risk of pulmonary haemorrhage.

Bronchial artery embolization for the treatment of haemoptysis in pulmonary hypertension.

PURPOSE: To test the efficacy of bronchial artery embolization (BAE) to treat haemoptysis in pulmonary hypertension (PH). METHODS: 33 patients were treated by BAE for haemoptysis associated with PH (PH group = 21) or non-associated with PH (control group = 12). The details of procedure, outcome, and rate of relapse were compared between the two groups. Within the PH group, the comparison was operated between subjects with congenital heart disease-associated pulmonary artery hypertension (CHD-APAH subgroup = 12) and non-CHD (non-CHD-APAH subgroup = 9). RESULTS: The rate of relapse at 30 and 90-days was similar between the PH group and control group. BAE in the PH group was more challenging (median 2 arteries embolized per procedure) compared to the control group (median 1 artery embolized per procedure; p = 0.001). Bleeding arteries were more heterogeneous in the PH group, while a single right bronchial artery was the only clinical finding in 66.7% of controls (p = 0.001). Within the PH group, the CHD subgroup showed higher survival rate compared to the non-CHD-APAH group (p = 0.007). CONCLUSION: BAE is effective and safe for the treatment of haemoptysis in PH, yet more challenging than other conditions. In PH-associated haemoptysis, BAE provides higher survival rate for subjects with PH associated with CHD.

A new CT-score as index of hemodynamic changes in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: The aim of this study was to retrospectively assess the relationship between radiological and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We introduced a new CT-score to evaluate hemodynamic changes, only employing CT-pulmonary angiography (CTPA). MATERIALS AND METHODS: 145 patients affected by CTEPH underwent hemodynamic and CTPA evaluation. Among these 145 patients, 69 underwent pulmonary endarterectomy (PEA) and performed a CTPA evaluation even after surgery. Hemodynamic assessment considered the values of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), obtained through right heart catheterization (RHC). Radiological evaluation included CTPA signs of pulmonary hypertension. RESULTS: A highly significant statistical correlation was observed between the new CT-score and both mPAP and PVR (p < 0.000) in the whole sample and also in the subgroup who underwent PEA. In addition, mPAP and PVR showed an important association with the severity of mosaic perfusion (p < 0.000). mPAP also correlated with main pulmonary artery diameter (p < 0.01); a significant association was found in both between PVR and tricuspid regurgitation(p < 0.000) and with PVR and presence of unilateral or bilateral pulmonary thromboembolic occlusion (p < 0.05). CONCLUSION: Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible.