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Background Chest radiography (CR) patterns for the diagnosis of COVID-19 have been established. However, they were not ideated comparing CR features with those of other pulmonary diseases. Purpose To create the most accurate COVID-19 pneumonia pattern comparing CR findings of COVID-19 and non-COVID-19 pulmonary diseases and to test the model against the British Society of Thoracic Imaging (BSTI) criteria. Material and Methods CR of COVID-19 and non-COVID-19 pulmonary diseases, admitted to the emergency department, were evaluated. Assessed features were interstitial opacities, ground glass opacities, and/or consolidations and the predominant lung alteration. We also assessed uni-/bilaterality, location (upper/middle/lower), and distribution (peripheral/perihilar), as well as pleural effusion and perihilar vessels blurring. A binary logistic regression was adopted to obtain the most accurate CR COVID-19 pattern, and sensitivity and specificity were computed. The newly defined pattern was compared to BSTI criteria. Results CR of 274 patients were evaluated (146 COVID-19, 128 non-COVID-19). The most accurate COVID-19 pneumonia pattern consisted of four features: bilateral alterations (Expß=2.8, P=0.002), peripheral distribution of the predominant (Expß=2.3, P=0.013), no pleural effusion (Expß=0.4, P=0.009), and perihilar vessels’ contour not blurred (Expß=0.3, P=0.002). The pattern showed 49% sensitivity, 81% specificity, and 64% accuracy, while BSTI criteria showed 51%, 77%, and 63%, respectively. Conclusion Bilaterality, peripheral distribution of the predominant lung alteration, no pleural effusion, and perihilar vessels contour not blurred determine the most accurate COVID-19 pneumonia pattern. Lower field involvement, proposed by BSTI criteria, was not a distinctive finding. The BSTI criteria has lower specificity.

Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

High flow nasal cannula (HFNC) is used to treat acute hypoxemic respiratory failure (AHRF) even outside the ICU and the ROX index (pulse oximetry/fraction of inspired oxygen/respiratory rate) may predict HFNC failure. OBJECTIVE: The purpose of this investigation was therefore to verify whether the ROX index is an accurate predictor of HFNC failure for COVID-19 patients treated outside the intensive care unit (ICU) and to evaluate the validity of the previously suggested threshold. DESIGN: Multicenter study. Retrospective observational analysis of prospectively collected data. SETTING: 3 centres specialized in non-invasive respiratory support (Buenos Aires, Argentina; Bolzano and Treviso, Italy). Patients treated outside the ICU were analysed MEASUREMENTS: The variables to calculate the ROX index were collected during the first day of therapy at 2, 6, 12 and 24 hours and then recorded every 24 hours. HFNC failure was defined as escalation of respiratory support to invasive mechanical ventilation (IMV) or death. MAIN RESULTS: A total of 35 (29%) patients failed HFNC and required intubation. ROC analysis identified the 12-hour ROX index as the best predictor of intubation with an AUC of 0.7916[CI 95% 0.6905-0.8927] and the best threshold to be 5.99[Specificity 96% Sensitivity 62%]. In the survival analysis, a ROX value

Coronavirus disease 2019 (COVID-19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID-19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS-CoV-2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS-CoV-2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID-19 pneumonia.

Pneumothorax (PNX) and pneumomediastinum (PNM) are potential complications of COVID-19, but their influence on patients’ outcomes remains unclear. The aim of the study was to assess incidence, risk factors, and outcomes of severe COVID-19 complicated with PNX/PNM. Methods: A retrospective multicenter case-control analysis was conducted in COVID-19 patients admitted for respiratory failure in intermediate care units of the Treviso area, Italy, from March 2020 to April 2021. Clinical characteristics and outcomes of patients with and without PNX/PNM were compared. Results: Among 1213 patients, PNX and/or PNM incidence was 4.5%. Among these, 42% had PNX and PNM, 33.5% only PNX, and 24.5% only PNM. COVID-19 patients with PNX/PNM showed higher in-hospital (p = 0.02) and 90-days mortality (p = 0.048), and longer hospitalization length (p = 0.002) than COVID-19 patients without PNX/PNM. At PNX/PNM occurrence, one-third of subjects was not mechanically ventilated, and the respiratory support was similar to the control group. PNX/PNM occurrence was associated with longer symptom length before hospital admission (p = 0.005) and lower levels of blood lymphocytes (p = 0.017). Conclusion: PNX/PNM are complications of COVID-19 associated with a worse prognosis in terms of mortality and length of hospitalization. Although they are more frequent in ventilated patients, they can occur in non-ventilated, suggesting that mechanisms other than barotrauma might contribute to their presentation.

Background: Safety and efficacy of benralizumab (BEN) for severe eosinophilic asthma (SEA) have been demonstrated in Phase III clinical trials. Obesity is a risk factor for SEA and might affect the beneficial effect of asthma medication. ANANKE is part of AstraZeneca’s global XALOC real-world evidence program for benralizumab. Aims: To explore whether benralizumab efficacy is affected by body mass index (BMI) in SEA patients. Methods: Post-hoc analysis of an observational, multicenter, retrospective Italian study of SEA patients with at least 12 weeks of BEN treatment. Patients were stratified according to BMI: normal/underweight (Nr) (BMI Results: 182 patients were included, Nr=70 (68.6% female, mean age 55±12.8, median BEN duration 9.2 months), OW=79 (48.1% female, mean age 56.6±12.9, median BEN duration 9.4 months), Ob=33 (75.8% female, mean age 56.5±14.7, median BEN duration 10.2 months). Any AER passed from 4.49 to 0.18 (-96%) in Nr (N=66), from 3.99 to 0.32 (-92%) in OW (N=76) and from 3.72 to 0.34 (-90.9%) in Ob (N=30). Severe AER changed from 1.32 to 0.04 (-97%) in Nr, from 1.12 to 0.10 (-91.1%) in OW and from 1.13 to 0.08 (-92.9%) in Ob. ACT increased from a median of 15 in Nr (N=57), 14 in OW (N=61) and 13 in Ob (N=25) to 22 in Nr (N=29) and Ob (N=11) and 23 in Ow (N=35) at week 48. Conclusions: In an Italian real-world setting, the efficacy of BEN in SEA patients seems not to be affected by obesity, leading to asthma control al >90% reduction of AER and severe AER regardless of BMI.

Background: The widespread use of rapid on-site evaluation is hampered by constraints related to time and resources, inadequate reimbursement, and evidence from randomized trials that show a lack of increase in diagnostic yield and specimen adequacy associated with its usage. Objective: We aimed to verify whether a pulmonologist can assess endosonography-derived lymph node samples after a comprehensive and reproducible training provided by a specialist pathologist. Methods:Prospective, observational trial structured in three phases. In the first (training) phase, a pathologist critically evaluated the smears from 150 archival endosonography cases with a pulmonologist. In the second (test) phase, the pulmonologist was asked to assess 50 archival endosonography-derived samples. In the last (real-life) phase, the pulmonologist classified the samples from 200 patients during the endosonography. The overall agreement between pulmonologist and pathologist (gold standard), assessed through κ-statistics, was the primary outcome. The agreement for the identification of specific cytological categories was the secondary outcome. Results: The overallagreement between pulmonologist and pathologist was 84% (κ0.765, 95% CI 0.732–0.826) in the test phase and 89.7% (κ 0.844, 95% CI 0.799–0.881) in the real-life phase. The agreement for specific cytological categories was 92.7% (95% CI 0.824–0.980) for inadequate samples, 90.3% (95% CI 84.5–94.5%) for reactive lymphadenopathies, 90.5% (95% CI 0.845–0.946) for malignancy, and 73% (95% CI 0.515–0.897) for granulomatous samples. Conclusions: A trained pulmonologist can reliably assess adequacy and malignancy for endosonography-derived samples, which could be useful in institutions where a cytopathologist/cytotechnician is not available regularly.

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Background: The Suppressor of Cytokine Signalling (SOCS) proteins, particularly SOCS3, and its regulation by TNF-α, have been originally described in animal and in vitro studies as inhibitors of cytokine-signalling in response to a chronic inflammation. However, more recently, the suppressive role of SOCS3 has been questioned by other animal studies, which suggested an important proinflammatory role for this protein. Aim: To investigate in a human inflammatory disease, COPD, the expression of SOCS3 and its inducer TNF-α in alveolar macrophages (AM). Methods: SOCS3 and TNF-α expression was quantified in alveolar macrophages (SOCS3+AM%, TNF-α+AM%) in lungs from 19 smokers with COPD (COPD) [FEV1: 60±31(%)], 16 smokers without COPD (noCOPD) and 9 nonsmokers (NS) using immunochemistry. Results: The percentage of SOCS3+AM was higher in COPD [68(31-95)%] than in noCOPD [48(22-78)% p=0.04] and NS [10(4-56)% p=0.005]. This pattern was paralleled by the expression of TNF-α in AM, that was higher in COPD [90(52-97)%] than in noCOPD [32(17-60)%] and in NS [1(0-15)% p Conclusions: The increased expression of SOCS3 and its modulator TNF-α in alveolar macrophages of COPD, a chronic inflammatory disease, casts some doubts about SOCS3 suppressor function and rather favours a role for SOCS3 as a proinflammatory mediator.

Introductions: Safety and efficacy of benralizumab for severe eosinophilic asthma (SEA) have been demonstrated in Phase III clinical trials. However real-word evidence in Italy is limited. ANANKE is part of AstraZeneca’s global XALOC RWE program for benralizumab. Objects: To describe the clinical impact of benralizumab on adult patients with SEA in a real-life setting. Methods: This is an ongoing observational, multicentre, retrospective study of the clinical characteristics and asthma exacerbations for SEA patients in Italy with at least 12 weeks of benralizumab treatment. Clinical (including comorbidities and atopic status) and laboratory (blood eosinophil count and total IgE) data have been collected. Annualized exacerbation rates (AER) before and after the first benralizumab injection (index date) were analysed. Results: 61 patients were included in this interim analysis [70.5% female, mean age 52.8 ± 13.9, median duration of disease 9.5 years (IQR 3.7-23.1), median eosinophil count (N=41) 410/mm3 (IQR 300-680/mm3), median total IgE (N=39) 215 IU/L (IQR 83-477 IU/L), atopic status 55.7%]. Comorbidities were frequent (44/61 patients, 72.1%), and 34.4% reported chronic rhinosinusitis with nasal polyps (CRSwNP) in the past year. Patients were treated with benralizumab for a median of 9.3 months (IQR 6.1-11.7).During the year prior to index date, AER was 4.98 for any exacerbation and 1.25 for severe exacerbations (N=52). After index date, AER was reduced to 0.38 for any exacerbation(92.4% reduction) and 0.08 for severe exacerbations (93.6% reduction). Conclusion: benralizumab has been prescribe to adult-onset SEA patients, with high prevalence of CRSwNP, indipendent of atopy. Benralizumab led to 93.6% reduction in severe AER

BACKGROUND The effect of chronic use of renin–angiotensin–aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients. METHODS A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020. RESULTS All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09–0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17–1.83, P = 0.341). CONCLUSIONS Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality.

Background In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. Methods We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. Results Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24–0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12–0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). Conclusion In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592., This multicenter observational study gave the first evidence that prolonged, low-dose methylprednisolone treatment is associated with a significantly lower hazard of death, reduced ICU burden and decreased ventilator dependence without affecting viral clearance in patients with severe COVID-19 pneumonia/ARDS.

Lung surface photos show wounds/haemorrhages caused by transbronchial lung cryobiopsy (TBLC). TBLC bleeding can extensively soil airways with consequences for lung function, stressing the need for bleeding prevention and more research via registries.https://bit.ly/34wWAeR

Introduction and Objectives: Endosonography has become standard of care in the diagnostic work-up of mediastinal lymphadenopathy and peribronchial lung lesions, but its success rate in some specific settings/conditions may be hampered by limited needle flexibility and size. We report on our initial experience with the 19G Flex needle, characterized by larger size and greater flexibility as compared with the currently available cytology needles. Methods: Retrospective review of prospectively collected data on the first 13 consecutive patients submitted to endosonography with the 19G Flex needle. Patients were included if they had: a) suspicion of a histologically complex disease (i.e. lymphoma); b) suspicion of an advanced lung cancer possibly requiring extensive genotyping; c) a lesion whose sampling with a 22G needle had failed due to lack of visibility when the needle was loaded into the scope. Results: the 13 patients enrolled had a mean age of 58.15±17 years and a male to female ratio of 8:5. Target lesions (mean size 18.6±6.4 mm) were lymphadenopathies (9 patients), lung lesions (3 patients), and a pleural nodule (1 patient). Histology core/s and a definite diagnosis (adenocarcinoma, 4 cases; lymphoma, 2; mesothelioma, 2, metastases from extrathoracic tumors, 2; non-small-cell lung cancer not otherwise specifiable, 1; small cell carcinoma, 1; sarcoidosis, 1) were obtained in 100% of patients. A single case of self-resolving bleeding was the only complication we observed. Conclusions: Preliminary results obtained with the dedicated Flex 19G needle are promising, as sample size/quality is satisfactory and the needle influence on scope flexibility is minimal. This article is protected by copyright. All rights reserved.

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Pleuroparenchymal fibroelastosis (PPFE) is a very rare lung disease characterized by dense fibrous thickening of the visceral pleura and intraalveolar fibrosis containing prominent elastosis, with typical upper lobe predominance. PPFE usually shows progressive restrictive ventilatory impairment refractory to medical treatment; bilateral lung transplantation currently remains the only available therapeutic option. In this report, we describe a case of suspected PPFE relapse after lung transplantation that, to our knowledge, has never been described in the medical literature. A 48-year-old male with idiopathic pleuroparenchymal fibroelastosis underwent a bilateral lung transplant in our department. 8 months later, he presented with progressively worsening clinical condition, his respiratory state gradually deteriorated. High-resolution CT again showed bilateral diffused parenchymal consolidations, with prevalence in the upper lobes and subpleural regions. A PPFE relapse was therefore suspected, so he was listed for lung retransplantation, which was performed ten months after the first transplant. Histopathological analysis of the second explanted lung again confirmed the diagnosis of PPFE. The case highlights the possibility of PPFE relapse after lung transplantation, that may add to the increasing evidence of an underlying auto-immune mechanism contributing to its pathogenesis.

Over the last decade transbronchial lung cryobiopsy (TBLC) has proven to be an "innovative application" of an "old procedure" for the histologic diagnosis of diffuse interstitial lung diseases (DILDs). Thus, the technique of TBL cryobiopsy is now adopted for diagnostic purposes, transbronchially in peripheral airways to sample lung parenchyma, whereas this same technique was traditionally employed in the past for therapeutic purposes, essentially for the management of malignant obstruction of central airways. When patients with interstitial lung diseases (ILDs) need histopathological data in their diagnostic pathway, this bioptic approach could be a valid alternative to surgical lung biopsy, that is still the gold standard at the moment. TBL cryobiopsy has a good safety profile, its sensitivity and specificity appear good overall in idiopathic pulmonary fibrosis. In the last ten years, many papers have been published about this procedure defining modalities by which cryobiopsy should be performed. These studies have shown that TBL cryobiopsy is feasible, it allows to obtain larger lung parenchymal specimens (3 times larger than "classic" transbronchial biopsies), characterized by unaltered and artefact-free morphology, and it represents a safe and poorly invasive diagnostic tool for the histologic diagnosis of ILDs. The technical aspects are really important, and they still need a complete standardization. TBL cryobiopsy should be part of an equipment of the modern interventional pulmonologist, who should know indications and contraindications of this methodic and the technical aspects of the procedure. This is a complex procedure requiring to be performed by endoscopists working in specialized centers with specific knowledge of DILDs, and a multidisciplinary approach, which represent pre-requisites for admission to training in this procedure.

International audience; 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

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Endobronchial ultrasound (EBUS) has revolutionized the field of bronchoscopy because it allows to observe peribronchial structures and distal peripheral lung lesions. The use of EBUS was first described by Hurte and Hanrath in 1992. EBUS technology exists in two forms: radial and convex transducer probes. The radial EBUS probe has a 20-MHZ (12-30 MHz available) rotating transducer that can be inserted together with or without a guide sheath through the working channel (2.0-2.8 mm) of a standard flexible bronchoscope. The transducer rotates and produces a 360-degree circular image around the central position of the probe. There are two types of radial EBUS probes: "peripheral" probes, used to identify parenchymal lung lesions, and "central" probes, with balloon sheaths, used for the assessment of airway walls and peribronchial lymph nodes.

This atlas is designed as an easy-to-use reference guide that identifi es and illustrates the key patterns of diffuse lung diseases observed on high-resolution computed tomography (HRCT). This atlas documents in great detail each pattern’s signs with close Rad-Path correlations. This book also allows a rapid view of HRCT characteristics and appearances of the individual diseases grouped on the basis of their prevalent radiological pattern.

A non-invasive test to facilitate the diagnosis of non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) is still not available and represents an important goal. Forty-eight patients with stage I NSCLC, 45 with IPF, 30 with other idiopathic interstitial pneumonias (IIPs) including idiopathic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (HP), 35 with diffuse non-malignant disease and 30 healthy donors were enrolled onto the study. Free circulating (fc)DNA and MMP-7 levels were evaluated by Real Time PCR and ELISA, respectively. Median fcDNA levels were similar in NSCLC (127 ng/mL, range 23.6–345 ng/mL) and IPF (106 ng/mL, range 22–224 ng/mL) patients, and significantly lower in IIPs patients, in individuals with other diseases and in healthy donors (p &lt, 0.05). Conversely, median MMP-7 values were significantly higher in IPF patients (9.10 ng/mL, range 3.88–19.72 ng/mL) than in those with NSCLC (6.31 ng/mL, range 3.38–16.36 ng/mL, p &lt, 0.0001), NSIP (6.50 ng/mL, range 1.50–22.47 ng/mL, p = 0.007), other diseases (5.41 ng/mL, range 1.78–15.91, p &lt, 0.0001) or healthy donors (4.35 ng/mL, range 2.45–7.23, 0.0001). Serum MMP-7 levels seem to be capable of distinguishing IPF patients from those with any other lung disease. fcDNA levels were similar in NSCLC and IPF patients, confirming its potential role as a biomarker, albeit non-specific, for the differential diagnosis of NSCLC.

Pulmonary pathologists were aware of cases of idiopathic interstitial pneumonia (IIP) that morphologically did not fit Liebow's classification scheme. These cases were labeled as "cellular interstitial pneumonia" or "chronic interstitial pneumonia not otherwise specified." The term nonspecific interstitial pneumonia (NSIP) was first used in relation to a pattern of lung interstitial inflammation seen in association with human immunodeficiency virus (HIV) infection. In 1994 NSIP was used to indicate a group of subacute or chronic interstitial pneumonias characterized morphologically by interstitial inflammation or fibrosis or both, with preservation of the lung architecture and the absence of typical findings for any of the other main categories of IIP (mainly usual interstitial pneumonia, desquamative interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia). Although these patients presented with "nonspecific" lung histology (categorized as cellular and fibrotic variants), and with a broad spectrum of associated clinical conditions, such as connective tissue diseases (CTDs), environmental exposure, and previous acute lung injury, they showed some peculiar clinical aspects, including favorable response to corticosteroid treatment and overall good prognosis.The clinical and radiographic profiles were better defined in the last decade. The NSIP pattern is the histological background of a subacute/chronic interstitial pneumonitis that may be observed in many conditions, including CTD, drug-induced lung disease, hypersensitivity pneumonitis, slowly healing diffuse alveolar damage (DAD), relapsing organizing pneumonia, occupational exposure, immunodeficiency (mainly HIV infection), graft versus host disease (GVHD), familial pulmonary fibrosis, immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlap features with Rosai-Dorfman disease, multicentric Castleman disease, and myelodysplastic syndrome. Rarely, NSIP is the histology recognized in patients with idiopathic interstitial pneumonitis, in whom efforts to find potential causative exposures are futile. This entity occurs mostly in middle-aged, never-smoker women, with a likely association with an autoimmune background. High-resolution computed tomographic (HRCT) scans typically demonstrate ground-glass attenuation with a bibasilar distribution, or in the fibrotic variant, ground-glass attenuation along with reticular lines and traction bronchiectasis. The prognosis is good compared with idiopathic pulmonary fibrosis (IPF), and therapeutic options include mainly corticosteroids and immunosuppressive agents. Recently a more precise definition of clinical profiles and radiographic findings of idiopathic NSIP allows consideration of less invasive diagnostic procedures (bronchoalveolar lavage, transbronchial lung biopsy). Better understanding of pathogenetic mechanisms might widen the therapeutic horizon giving a role to new therapeutic options in more severe cases.

Background: Pleural empyema can be subdivided into 3 stages: exudative, multiloculated, and organizing. In the absence of clear septation, antibiotics plus simple drainage of pleural fluid is often sufficient treatment, whereas clear septation often requires more invasive treatment. Objectives: The aim of this study was to report our experience and analyze the safety and efficacy of medical thoracoscopy in patients with multiloculated and organizing empyema. Methods: We performed a retrospective study reviewing the files of patients referred for empyema and treated by medical thoracoscopy at our department from July 2005 to February 2011. Results: A total of 41 patients with empyema were treated by medical thoracoscopy; empyema was free flowing in 9 patients (22%), multiloculated in 24 patients (58.5%), and organized in 8 patients (19.5%). Medical thoracoscopy was considered successful without further intervention in 35 of 41 patients (85.4%): all of the 9 patients with free-flowing fluid, 22 of the 24 patients with multiloculated empyema (91.7%), and only 4 of the 8 patients with organizing effusion (50%). Conclusions: Our study confirms that multiloculated pleural empyema could safely and successfully be treated with medical thoracoscopy while organizing empyema can be resistant to drainage with medical thoracoscopy, requiring video-assisted thoracic surgery or open surgical decortications; among this population, the presence of separate ‘pockets’ not in apparent communication with each other often leads to a surgical approach.

Introduction: Transbronchial needle aspiration (TBNA) is an established method to diagnose hilar/mediastinal lymphadenopathies and/or masses. Real-time endobronchial ultrasound (EBUS) is a method that involves TBNA, and has been shown to increase the diagnostic yield in this context. Objectives: A descriptive study has been conducted to test real-time EBUS in the diagnosis of hilar-mediastinal lymphadenopathies/masses with a shorter diameter less then 2.5 cm or with a previous negative ‘blind’ TBNA. Methods: Consecutive patients referred for EBUS-TBNA of hilar/mediastinal lymph nodes were included in the study, when a node or mass was detected on a chest computed tomography scan. The primary end point was the number of successful biopsy specimens. Lymph node stations were classified according to the American Thoracic Society scheme. Results: Ninety-four patients (66 males, 28 females) of mean age 62 years (range: 17–86) underwent EBUS-TBNA: EBUS-TBNA could be performed in all patients. The procedure was diagnostic in 80 patients (89.4%); positive samples were 73 (52 lung cancer, 18 sarcoidosis and 3 tuberculosis), negative samples were 17, inadequate specimens were obtained in four patients (4.25%) and surgically proven false negative results were found in six cases (6.38%). Biopsy specimens were taken from lymph nodes in region 2L (1 case), 2R (5 cases), 4R (20 cases), 4L (7 cases), 7 (47 cases), 10R (9 cases), 10L (2 cases), 11R (6 cases) and 11L (3 cases). Sensitivity was 92.4%, and specificity was 100%. No complications occurred. Conclusions: EBUS-TBNA is a safe and reliable method for sampling mediastinal lymph nodes. Please cite this paper as: Gurioli C, Ravaglia C, Romagnoli M, Casoni G, Tomassetti S, Nanni O, Poletti V. EBUS-TBNA in mediastinal/hilar lymphadenopathies and/or masses: an Italian case series. Clin Respir J 2012; 6: 3–8.

This study compared the results of high-resolution computed tomography (HRCT) and cytohistology after transbronchial biopsy in the evaluation of drug-related interstitial lung disease (DR-ILD).Patients with a clinical and imaging diagnosis of DR-ILD were prospectively included in a study protocol lasting 5 years. All patients were evaluated by bronchoscopy with transbronchial biopsy or bronchoalveolar lavage (BAL) following an HRCT examination that raised a suspicion of DR-ILD. Two radiologists (one senior and one junior), unaware of the diagnosis, reported the single HRCT findings, their distribution and predominant pattern. In the event of disagreement, the diagnosis was subsequently reached by consensus. Cytohistological examination was considered the gold standard in the diagnosis of DR-ILD. Patients who were unable to undergo the endoscopic procedure were excluded from the study.The study included 42 patients (25 men, 17 women; age range 20-84 years). Transbronchial biopsy was performed in all but four patients (one case of alveolar haemorrhage and three cases of lipoid pneumonia) in whom the diagnosis was established with BAL. Assessment of the HRCT images revealed the following patterns: noncardiogenic pulmonary oedema (n=13); organising pneumonia (OP) (n=9); hypersensitivity pneumonitis (HP) (n=2); alveolar haemorrhage (AH) (n=2); nonspecific interstitial pneumonia (NSIP) (n=5); lipoid pneumonia (LP) (n=1); sarcoid-like pattern (n=1). Cytohistological diagnosis revealed diffuse alveolar damage (DAD) in 11 patients, OP in seven, HP in three, AH in three, chronic interstitial pneumonia (CIP) in eight, LP in three and pseudosarcoidosis in one. Subdivision of the drugs into antineoplastic and nonantineoplastic agents showed that the most common patterns were CIP (n=6), DAD (n=2) and OP (n=2) in the antineoplastic group and DAD (n=9) and OP (n=5) in the nonantineoplastic group. Sensitivity and specificity of the radiological analysis was excellent, especially for patterns such as OP and DAD (sensitivity 0.86 and specificity 0.88 for OP; sensitivity 1 and specificity 0.93 for DAD).HRCT demonstrated excellent sensitivity and specificity. In cases in which its specificity was low, HRCT was nonetheless useful for biopsy planning and clinical-radiological monitoring after discontinuation of the drug treatment.

Background Asbestosis is characterized by lung and pleural fibrosis and by immune system dysregulation, with autoantibody production and systemic immune-mediated disease. No specific therapies are available for asbestosis. Recently, the pivotal pathogenic role exerted by interleukin-1beta has been recently reported. Case presentation We treated with anti-interleukin 1 beta targeted antibody canakinumab a 67 year old man with asbestosis and long lasting systemic autoimmune features. A dramatic improvement in clinical manifestations was observed at 1 week after the first injection, with complete clinical remission at 4 months. Conclusion This case suggests new perspectives for the treatment of asbestosis and its systemic features.

Interstitial lung diseases (ILD), also defined as diffuse parenchymal lung diseases (DPLD) include a heterogeneous group of pulmonary disorders. They may be caused by an underlying connective tissue disease (CTD), Rheumatoid Arthritis (RA) or ANCA-associated Vasculitis (AAV). Pulmonary manifestations of these conditions may also precede systemic onset and therefore, pulmonologists may be confronted with diagnosing a systemic rheumatic disease. For the discrimination of CTD-related ILD and idiopathic interstitial pneumonia (IIP), serological testing is recommended. After careful reviewing the available literature, we suggest a serologic diagnostic algorithm for pulmonologists dealing with ILD-patients. This algorithm depicts the consensus for antibody testing that was reached amongst authors. Obviously this consensus approach requires further validation in everyday practice and leaves room for local adaption of the diagnostic strategy depending on the availability of diagnostic capacity and cost. It is our hope, however, that the rational and stepwise approach of serological testing for ILD will ultimately save unnecessary expenses associated with general laboratory screening. Finally a broader consensus on the strategy for laboratory testing in ILD in general might also improve the detection level of these relatively rare diseases and this will ultimately improve management and care of patients suffering from these complex disorders.

Lipoid pneumonia (LP) is due to the accumulation of either endogenous or exogenous lipids in the alveoli. The exogenous LP (ELP) results from the chronic aspiration or inhalation of animal, vegetable, or mineral oils or fatty substances that by reaching the pulmonary alveoli cause a foreign body-type inflammatory reaction of lung parenchyma, associated with fibrosis, necrosis, and possible cavitation. Pulmonary reaction is characterised by symptoms and radiological findings that are common to other pulmonary diseases. The radiologic presentation of ELP includes lung consolidations and ground-glass opacities, with predominant involvement of the lower lobes. Thickening of interlobular septa, adipose or not adipose single mass, and poorly marginated nodules may also occur. Cavitation, when present, is mainly associated with infection by non-tuberculous mycobacteria or fungi. Thus in patients exposed to lipoid aspiration presenting with cavitated mass on CT scan, possible infection should be thoroughly ascertained, and adequate treatment promptly initiated. Hereby, we report three cases of non-infectious cavitary exogenous lipoid pneumonia. In all three patients, one with acute onset and two with chronic recurrent form, the ELP diagnosis was confirmed by both cytological and histological findings, whereas microbiological examination gave negative results. Moving from these three cases, we review the pathogenesis, clinical and radiological manifestation of ELP.

Among the nonpharmacological therapies, pulmonary rehabilitation (PR) is particularly appropriate for patients with chronic respiratory impairment who, despite any optimal drug management, are still symptomatic and experience restriction in every day activities. Pulmonary rehabilitation performed in inpatient, outpatient, or home settings demonstrates short–and long–term clinical efficacy. Although disease severity does not inherently dictate candidacy for exercise training, the degree of physiological and functional impairment may influence setting in which the training should occur. Therefore, inpatient rehabilitation is generally best–suited for the most sick and most disabled patients. The overall results from the literature confirm that the inpatient setting for a PR program is a feasible option and does not necessarily result in higher direct costs when balanced against duration and effectiveness in terms of improved outcomes.