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Rationale: Lung biopsy (LBx) has a relevant role in the prediction of prognosis of interstitial lung diseases (ILDs), but its impact on the clinical management of patients remains unexplored. Objectives: This study evaluates whether LBx may change the therapeutic strategy and assesses the effect of diagnostic reclassification after LBx on long-term prognosis. Methods: We evaluated the LBx of 426 consecutive patients with ILDs, without a definite usual interstitial pneumonia pattern on high-resolution computed tomographic imaging. A total of 266 patients underwent transbronchial lung cryobiopsy (TBLC), and 160 patients underwent surgical lung biopsy (SLB). The multidisciplinary team (MDT) determined a diagnosis with high or low confidence, and a management strategy, both before and after the LBx data. Results: Final MDT diagnoses were 189 idiopathic pulmonary fibrosis (IPF), 143 non-IPF fibrotic ILDs, and 94 nonfibrotic ILDs. LBx data changed the management strategy in 145 cases (34%), with similar results for TBLC and SLB (the treatment strategy changed in 31.5% of TBLC cases, 84/266, P

Background Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILAs are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral. Research Question Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs? Study Design and Methods Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement. Results Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System “S-modifier” [which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of FVC and diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD. Interpretation Guidance for identifying clinically relevant ILA, with subsequent referral and follow-up, was established. These results lay the foundation for developing practical guidance on managing patients with ILA.

Little is known about the light phenotype of SARS-CoV-2 pneumonia, which behaves in an unusual way, unlike other known respiratory diseases. We believe that the histopathological features of early COVID-19 could be considered the pathophysiological hallmark of this disease. Lung cryobiopsies show almost pristine alveoli, enlarged/hyperplasic alveolar capillaries along with dilatation of the post capillary pulmonary venules. Hypoxemia could therefore be explained by a reduction of the normal V/Q ratio, due to blood overflow around well ventilated alveoli. This could clarify typical manifestations of type L COVID-19, such as happy hypoxemia, response to awake prone positioning, response to PEEP/CPAP and platypnea orthodeoxia.

Purpose of review The evaluation of progression in fibrotic interstitial lung diseases (ILDs) may require a multidimensional approach. This review will cover the role and usefulness of lung biopsy in diagnosis and assessment of the progressive fibrotic phenotype. Recent findings The identification of specific findings and the balance between inflammation and fibrosis on lung biopsy may help distinguishing different disease entities and may likely determine the effect of treatment and possibly prognosis. The fibrotic morphological patterns potentially associated with a progressive phenotype include usual interstitial pneumonia (UIP), fibrotic nonspecific interstitial pneumonia, pleuroparenchymal fibroelastosis, desquamative interstitial pneumonia, fibrotic hypersensitivity pneumonitis and other less common fibrotic variants, with histopathological findings of UIP at the time of diagnosis being predictive of worse outcome compared with other patterns. The prognostic significance of lung biopsy findings has been assessed after both surgical lung biopsy (SLB) and transbronchial lung cryobiopsy (TBLC), the latter becoming a valid alternative to SLB, if performed in experienced centres, due to significantly lower morbidity and mortality. Summary Lung biopsy plays an important role in diagnosis and identification of the progressive fibrotic phenotype. The introduction of less invasive procedures could potentially expand the role of lung sampling, including for example patients with a known diagnosis of ILD or at an earlier stage of the disease.

Background: The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches. Objectives: To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia. Methods: Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset. Results: Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4+ T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1). Conclusions: Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.

Background: Transbronchial lung cryobiopsy (TBLC) has been introduced recently in the diagnosis of interstitial lung diseases. We aimed to evaluate the prognostic significance of the distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases with the use of TBLC data in multidisciplinary team (MDT) diagnosis. Methods: In this single-centre, retrospective, investigator-initiated comparative study, we evaluated consecutive patients without a definite usual interstitial pneumonia pattern on high-resolution CT, who presented to the GB Morgagni Hospital (Forlì, Italy), and who underwent TBLC (Jan 1, 2011, to Dec 31, 2014) or surgical lung biopsy (SLB; Jan 1, 2002, to Dec 31, 2016). Three pathologists reviewed the specimens, masked to clinical information. MDT evaluation was done before and after biopsy. The primary endpoint was the prognostic significance of the MDT diagnostic separation between idiopathic pulmonary fibrosis and other interstitial lung diseases in patients undergoing TBLC. Mortality was evaluated by means of Cox regression analysis. Findings: We evaluated 500 consecutive cases, 426 of which were included: 266 had TBLC and 160 had SLB. 189 patients had idiopathic pulmonary fibrosis, 143 had other fibrotic interstitial lung diseases, and 94 had non-fibrotic interstitial lung diseases. Patients undergoing TBLC had more comorbidities and better preserved lung function compared with those undergoing SLB; among patients with a final MDT diagnosis of idiopathic pulmonary fibrosis, patients undergoing TBLC were older, had more comorbidities, and had a different post-biopsy treatment profile than those who received SLB. The distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases made by MDT diagnosis on the basis of TBLC biopsy had clear prognostic significance, with a 5-year transplant-free survival of 68% (95% CI 57–76) in patients with an MDT idiopathic pulmonary fibrosis diagnosis based on TBLC compared with 93% (87–96) in patients without an idiopathic pulmonary fibrosis diagnosis based on TBLC (hazard ratio 5·28, 95% CI 2·72–10·04; p

Bronchioles are noncartilaginous small airways with internal diameter of 2 mm or less, located from approximately the eighth generation of purely air conducting airways (membranous bronchioles) down to the terminal bronchioles (the smallest airways without alveoli) and respiratory bronchioles (which communicate directly with alveolar ducts and are in the range of 0.5 mm or less in diameter). Bronchiolar injury, inflammation, and fibrosis may occur in myriad disorders including connective tissue diseases, inflammatory bowel diseases, lung transplant allograft rejection, graft versus host disease in allogeneic stem cell recipients, neuroendocrine cell hyperplasia, infections, drug toxicity (e.g., penicillamine, busulfan), inhalation injury (e.g., cigarette smoke, nylon flock, mineral dusts, hard metals, Sauropus androgynous); idiopathic, common variable immunodeficiency disorder, and a host of other disorders or insults. The spectrum of bronchiolar disorders is wide, ranging from asymptomatic to fatal obliterative bronchiolitis. In this review, we discuss the salient clinical, radiographic, and histological features of these diverse bronchiolar disorders, and discuss a management approach.

Introduction: Lung biopsy in asthmatic patients is justified in case of atypical presentations of asthma, when other differential diagnoses, such as hypersensitivity pneumonitis or eosinophilic granulomatosis with polyangiitis, could be possible or for research purposes. Aim: We aim to describe the utility and the safety of TBLC (transbronchial lung cryobiopsy) in asthmatic patients, providing data on the pathological changes occurring in the airways and in the lung parenchyma. Methods: We reviewed asthmatic patients that underwent TBLC, that eventually had only a final diagnosis of asthma. Results: Three patients were detected. TBLC described pathological abnormalities in peribronchiolar and alveolar spaces already well identified with SLB (surgical lung biopsy); the pathological information provided could be useful to better understand the pathobiology of the disease. Finally, we had no complications, confirming a satisfactory safety profile of TBLC. Conclusion: We suggest the potential role of TBLC in asthmatic patients: its safety and its acceptable diagnostic accuracy lead to consider this procedure instead of SLB when histological changes in lung parenchyma are needed for the differential diagnosis. Furthermore, TLBC could be useful for research in the pathobiology of asthma and severe asthma.

A 60-years-old man, smoker, with bipolar disorder and history of hypertension, diabetes, and obesity, presented with a 5-days fever (38°C) and cough. His physical examination revealed exertional dyspnea and polypnea; saturation was 95% room air. He came from a protected nurse residence where some COVID positive subjects were already identified and his nasopharyngeal swab documented COVID infection positivity. CT scan showed patchy ground-glass nodules in the right upper lobe and a mild subpleural ground glass in the superior segment of left lower lobe. Numerous mediastinal and hilar lymphadenopathies, the biggest in 4R (short axis: 13mm), 7 (short axis: 14mm). The patient was treated with hydroxychloroquine, azithromycin and methylprednisolone. However, few days later he got worse in terms of gas exchange and laboratory tests (PaO2/FiO2 < 100; lymphocytes: 420/μl; IL-6: 56 pg/ml), so that he received a subcutaneous injection of tocilizumab and was intubated. After that, he showed a progressive improvement confirmed by CT scan with reduction in size of all the lymph nodes and complete disappearance of pulmonary infiltrates This article is protected by copyright. All rights reserved.

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49–0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Background Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. Methods We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. Results We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. Conclusions HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. Trial registration NCT04411459.

Objectives: The purpose of this observational retrospective study was to evaluate, in patients with a severe acute respiratory syndrome coronavirus 2 infection, the association between the severity of coronavirus disease 2019 (COVID-19) respiratory illness and the risk of infected patients to develop obstructive sleep apnea (OSA). Methods: Ninety-six patients with confirmed COVID-19 infection were enrolled in the study. The STOP-BANG questionnaire to investigate the risk of the OSA syndrome was filled in by the patients at admission. The enrolled patients were divided into 2 groups according to the respiratory disease: group 1 (72 patients), hospitalized patients undergoing conventional oxygen therapy; group 2 (24 patients), patients requiring enhanced respiratory support. STOP-BANG results of these 2 groups were compared to observe whether patients with high OSA risk more frequently presented a severe form of COVID-19. Results: 41.6% of the patients in group 2 had a STOP-BANG score between 5 and 8 (high risk of having apnea); in contrast, 20.8% of the patients in group 1 had a STOP-BANG score between 5 and 8, with a statistically significant difference between the 2 groups ( P = .05). A complementary trend was observed regarding the proportion of patients in the range 0 to 2, which classifies patients at a low risk of OSA (48.6% vs 20.8% for groups 1 and 2, P = .01). Conclusions: According to our data, the chances of having a severe case of COVID-19 should be considered in patients at high risk of OSA. Current Knowledge/Study Rationale: Emerging research suggests that OSA could represent a potentially important risk factor for the severe forms of COVID-19. The purpose of this observational retrospective study was to evaluate the potential association between OSA and the severity of COVID-19 disease. Study Impact: According to our data, the likelihood of contracting a severe form of COVID-19 disease should be considered in patients at high risk of OSA.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Current understanding of the complex pathogenesis of COVID-19 interstitial pneumonia pathogenesis in the light of biopsies carried out in early/moderate phase and histology data obtained at postmortem analysis is discussed. In autopsies the most observed pattern is diffuse alveolar damage with alveolar-epithelial type-II cell hyperplasia, hyaline membranes, and frequent thromboembolic disease. However, these observations cannot explain some clinical, radiological and physiopathological features observed in SARS-CoV-2 interstitial pneumonia, including the occurrence of vascular enlargement on CT and preserved lung compliance in subjects even presenting with or developing respiratory failure. Histological investigation on early-phase pneumonia on perioperative samples and lung biopsies revealed peculiar morphological and morpho-phenotypical changes including hyper-expression of phosphorylated STAT3 and immune checkpoint molecules (PD-L1 and IDO) in alveolar-epithelial and endothelial cells. These features might explain in part these discrepancies.

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in the overall COVID-19 population, but limited information is available on their roles in young and middle-aged adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics and role of selected prognostic predictors in a large cohort of young and middle-aged hospitalized patients. Nine pulmonology units, across north and center of Italy, were involved in this retrospective study. Comorbidities were classified according to their known or potential association with COVID-19. A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 27.7%, and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only independent, significant predictors for MV. Comorbidities, such as hypertension, diabetes, asthma, and increased D-dimer levels were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Obesity in young and middle-aged adults is a strong predictor of a more complicated COVID-19, without, however, evidence of a significant effect on in-hospital mortality. Selected comorbidities, including hypertension, diabetes and asthma, significantly impact survival even in a younger population, suggesting the need for prompt recognition of these conditions.

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0–30, IQR 4–11). Median PaO2/FiO2 increased from 160 (range 53–409, IQR 122–210) at baseline to 237 (range 72–533, IQR 158–331) at day 7 after treatment with canakinumab (p 9/L, respectively, p p

Background: Therapies that slow IPF progression are now available and recent studies suggest that the use of anti-fibrotic therapy may reduce IPF mortality. Our aim was to evaluate whether, to what extent and for which factors the survival of IPF in a real life setting has changed in the last 15 years. Methods: Historical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral centre for ILDs with prospective intention. Results: The study comprised 634 patients. The year 2012 identifies the time point of mortality shift ( HR 0.58, CI 0.46-0.63, p Conclusions: Antifibrotic drugs significantly impact hospitalizations, acute exacerbations and IPF survival. After the introduction of cryobiopsy and antifibrotic drugs the prognosis of IPF patients has significantly improved together with our ability to detect IPF at an earlier stage.

Introduction: despite the accumulating data on clinical and imaging features of COVID-19, its pathogenesis is still poorly understood. The majority of data regarding morphology and molecular changes regards post-mortem analysis; however, the value of performing lung biopsy on live patients more than autopsies on deceased patients is significantly high, as they may provide an insight into the complexity of the disease pathophysiology. Objectives: we examine the morphologic and molecular features of patients affected by COVID-19 who underwent lung biopsy at different times in the course of the disease: either at an earlier or at a later stage. Methods: comparative, multicenter, prospective, observational study. 24 patients were recruited. Lung samples were obtained by either cryobiopsy or TBB or SLB. Results: in most “early” phases of pneumonia the morphological changes did not match with typical DAD pattern; the exudative phase with jaline membranes and alveolar collapse were absent. Alveolar damage was patchy, varying from focal AECII hyperplasia to extensive nodular proliferation. The involvement of linear AECI was only partial; in advanced cases consistent remnants of normally looking AECI were present. A wide panel of immunohistochemical markers were just applied in samples (cytokeratin-7, cytokeratin 5/6, TTF1, CD34, Tubulin beta-3, alfa-SMA, CD163, CD14, CD20, CD138, CD3, CD4, CD8, T-bet, FoxP3, Gata-3, PD1, TCF1). Molecules involved in cell signaling, cell proliferation and activation were also investigated (beta-Catenin, phospho-STAT3, PDL-1, IDO, HLA-DR, CD25, gamma-fibrinogen).

Objectives: We sought to evaluate the association between age and presentation of SARS-COV2 infection Methods: Clinical presentation and radiological data of all consecutive COVID19 patients admitted to our Hospital between 01-03-2020 and 30-04-2020 were analyzed SARS-CoV-2 positive patients were diagnosed by either swab test or bronchoalveolar lavage Patients without proved SARS-CoV-2 infection or without HRCT scan were excluded All HRCT were reviewed and classified according to RSNA Classification of SARS-CoV-2 pneumonia(l) Results: Over the study period, 179 patients met the inclusion criteria Mean age was 67 years (SD 15 1, range 19-96);55 8% (N= 100) were male Of them, 22 patients (12%) had atypical clinical presentation The more frequent atypical presentations were cardiovascular, including syncope (N= 5, 22%) and heart failure (N= 5, 22%) HRCT was Typical in 151 (84 4%) patients, Indeterminate in 14 (7 8%), Atypical in 12 (6 7%), and Negative in 2 (0 01%) Among elderly patients (>70 years old) accounting for 44% of the total population (N=80), HRTC was more frequently Atypical (11/80 patients, 13 75%) compared to younger patients (

BackgroundPathogenesis of Coronavirus disease 2019 (Covid-19) is poorly understood. Most histologic studies come from post-mortem analysis, with existing data indicating that histologic features of acute respiratory distress syndrome are typically present in fatal cases. However, this observation may be misleading, due to confounding factors in pre-terminal disease, including injury resulting from prolonged mechanical ventilation. Ante-mortem lung biopsy may provide major pathogenetic insights, potentially providing a basis for novel treatment approaches.AimThis comparative, multicenter, prospective, observational study was planned to identify ante-mortem histological profile and immunohistochemical features of lung tissue in patients with Covid-19 in early and late phases of the disease, including markers of inflammatory cells and major pathways involved in the cytokine storm triggering.MethodsEnrolled patients underwent lung biopsy, according to the study protocol approved by local Ethical Committee, either within 15 days of the first symptoms appearing (early phase) or after >15 days (more advanced disease). Key exclusion criteria were excessive or uncorrectable bleeding risk and cardiovascular disease with heart failure. Lung samples were obtained by conventional transbronchial biopsy, trans-bronchial lung cryobiopsy or surgical lung biopsy.Results23 patients were enrolled: 12 patients underwent lung biopsy within 15 days and 11 patients more than 15 days after the onset of symptoms. Early biopsies were characterized by spots of patchy acute lung injury (ALI) with alveolar type II cells hyperplasia and significant vascular abnormalities (disordered angiogenesis with alveolar capillary hyperplasia, luminal enlargement and thickened walls of pulmonary venules, perivascular CD4-T-cell infiltration), with no hyaline membranes. In the later stages, the alveolar architecture appeared disrupted, with areas of organizing ALI, venular congestion and capillary thromboembolic microangiopathy. Striking phenotypic features were demonstrated in hyperplastic pneumocytes and endothelial cells, including the expression of phospho-STAT3 and molecules involved in immunoinhibitory signals (PD-L1 and IDO-1). Alveolar macrophages exhibited macrophage-related markers (CD68, CD11c, CD14) together with unusual markers, such as DC-Lamp/CD208, CD206, CD123/IL3AR.ConclusionA morphologically distinct “Covid pattern” was identified in the earlier stages of the disease, with prominent epithelial and endothelial cell abnormalities, that may be potentially reversible, differing strikingly from findings in classical diffuse alveolar damage. These observations may have major therapeutic implications, justifying studies of early interventions aimed at mitigating inflammatory organ injury.

Background: PD-L1 immunohistochemistry is currently performed in patients with advanced non-small cell lung carcinoma (NSCLC) to identify responders to immune checkpoint inhibitors. Cell blocks from fine needle aspiration of NSCLC are frequently used for diagnostic purposes. The aims of the study are to analyze: (a) the distribution of PD-L1 in cell blocks, in comparison to biopsies and surgical specimens; (b) the concordance of PD-L1 in specimens of the same patients. Methods: PD-L1 analyses conducted in NSCLCs were retrieved. Cell blocks were prepared with the self-clotting method. PD-L1 was performed with Dako 22C3 on the Ventana BenchMark ULTRA platform. Results were divided by tumor proportion score (TPS) in 3 categories: 2 = 2.905; P =.574). In 50 samples from 25 patients, PD-L1 was carried out in two samples of the same patients, with moderate agreement (concordance rate: 68.0%, k = 0.469). Conclusion: (a) PD-L1 is similarly distributed in the different materials; (b) PD-L1 shows moderate concordance in different samples of the same patients. PD-L1 may be routinely tested in cell blocks, but interpreted with caution and repeated whenever possible.

Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.

Bronchiolitis manifests as a variety of histological features that explain the complex clinical profiles and imaging aspects. In the period between January 2011 and June 2015, patients with a cryobiopsy diagnosis of bronchiolitis were retrospectively retrieved from the database of our institution. Clinical profiles, imaging features and histologic diagnoses were analysed to identify the role of cryobiopsy in the diagnostic process. Twenty-three patients with a multidisciplinary diagnosis of small airway disease were retrieved (14 females, 9 males; age range 31–74 years old; mean age 54.2 years old). The final MDT diagnoses were post-infectious bronchiolitis (n = 5), constrictive bronchiolitis (n = 3), DIPNECH (n = 1), idiopathic follicular bronchiolitis (n = 3), Sjogren’s disease (n = 1), GLILD (n = 1), smoking-related interstitial lung disease (n = 6), sarcoid with granulomatous bronchiolar disorder (n = 1), and subacute hypersensitivity pneumonitis (n = 2). Complications reported after the cryobiopsy procedure consisted of two cases of pneumothorax soon after the biopsy (8.7%), which were successfully managed with the insertion of a chest tube. Transbronchial cryobiopsy represents a robust and mini-invasive method in the characterization of small airway diseases, allowing a low percentage of complications and good diagnostic confidence.

Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Transbronchial cryobiopsy, a new diagnostic procedure in patients with diffuse lung disease, provides larger and better-preserved lung specimens compared to forceps biopsy. The diagnostic yield of cryobiopsy is much better than that of forceps biopsy and slightly lower than that of surgical lung biopsy, but with a lower complication rate compared to the latter. Literature suggests that in the multidisciplinary approach to patients with diffuse lung disease cryobiopsy provides diagnostic and prognostic information similar to surgical lung biopsy. Cryobiopsy can also be performed in some patients unsuitable for surgical biopsy, yet in whom histologic input is needed.

Background: Idiopathic pulmonary fibroelastosis (iPPFE) is a rare lung lesion characterized by pleural and subpleural parenchymal thickening due to accumulation of fibroelastotic tissue. Only recently, a few cases with a peribronchiolar distribution of fibroelastotic tissue have been reported. These lesions are more prominent in the upper lobes. Even though high resolution computed tomography (HRCT) scan features are considered characteristic, a histological confirmation is suggested, mainly when the clinical setting is not clearly defined. However, due to non-negligible complications, a surgical lung biopsy is not often recommended. The prognosis is usually poor and currently, the only effective treatment is lung transplantation. Method: Patients with a multidisciplinary diagnosis of iPPFE or airway-centered fibroelastosis (airway-centered FE), with histological confirmation by transbronchial cryobiopsy, were identified from an ongoing interstitial lung disease registry. Data on patient demographics, HRCT patterns, size and number of biopsies, histology patterns and complications were registered. Results: Seven patients were diagnosed with iPPFE and one patient was diagnosed with airway-centered FE. Pneumothorax was documented in three cases, but none of them required a chest tube. No other complications during or after the procedure were observed. Conclusion: This study suggests that using cryobiopsies in the diagnostics of PPFE and airway-centered FE is safe and effective.

PURPOSE: Sleep Breathing Disorders (SBD) are frequently found in idiopathic pulmonary fibrosis (IPF) and they are associated with worse quality of sleep and life and with higher mortality. The study aimed at evaluating the impact of SBD on prognosis (mortality or disease progression) in 35 patients with mild to moderate IPF.METHODS AND RESULTS: Obstructive sleep apnea (OSA) was diagnosed in 25/35 patients with IPF: 14/35 mild, 7/35 moderate, and 4/35 severe. According to the American Academy of Sleep Medicine (AASM) definition, sleep-related hypoxemia was found in 9/35 patients with IPF. According to the presence/absence of SBD, IPF patients were divided into 4 groups: NO-SBD group (Group A, 25.7%), OSA without sleep-related hypoxemia (Group B, 48.5%), OSA with sleep-related hypoxemia group (Group C, 22.8%), and only 1/35 had sleep-related hypoxemia without OSA(Group D, 2.8%). Statistical analysis was focused only on group A, B, and C. Patients with OSAS and sleep-related hypoxemia (Group C) had the worse prognosis, both in terms of mortality or clinical deterioration. SBD were the only independent risk factor (Cox Proportional Hazards Multiple Regression Analysis) for mortality (HR 7.6% IC 1.2-36.3; p = 0.029) and disease progression (HR 9.95% IC 1.8-644.9; p = 0.007).CONCLUSIONS: SBD are associated with a worse prognosis, both in terms of mortality or clinical progression. The presence of SBD should be explored in all IPF patients.

Background: Therapies that slow IPF progression are now available and recent studies suggest that the use of anti-fibrotic therapy may reduce IPF mortality. Our aim was to evaluate whether, to what extent and for which factors the survival of IPF in a real life setting has changed in the last 15 years. Methods: Historical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral centre for ILDs with prospective intention. Findings: The study comprised 634 patients. The year 2012 identifies the time point of mortality shift ( HR 0.58, CI 0.46-0.63, p

Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.

Introduction Malignant lymphoproliferative disorders are rarely observed in the lung and, considering their clinical and radiological heterogeneity, diagnosis is often difficult and may require invasive methods. Transbronchial cryobiopsy has been confirmed as a new tool in the diagnosis of interstitial lung diseases, given its fewer risks and costs compared to surgical approach. This study is aimed at assessing the effectiveness of cryobiopsy in the diagnosis of lymphoproliferative disorders. Materials and methods Among 970 consecutive cryobiopsies, performed between January 2011 and June 2018 at Morgagni Hospital of Forlì, Italy, 13 cases of lymphoproliferative disorders were collected. Results In 12 out of 13 cases a precise pathological diagnosis could be reached with the support of immunohistochemistry (IHC) and molecular ancillary studies. In the only case in which cryobiopsy did not lead to a definitive diagnosis, the subsequent surgical biopsy also did not help to clarify the diagnosis. Severe bleeding or pneumothorax did not occur in any case. On average, five biopsies were obtained per case, with a mean total area of 1161 mm2, and only 5 out of 65 specimens were inadequate for diagnosis. Instant freezing did not produce tissue artefacts nor did it affect IHC and molecular tests. In all cases the amount of available tissue was sufficient for all ancillary studies. Conclusions Transbronchial lung cryobiopsy is safe and effective for diagnosis in patients with suspected pulmonary involvement by lymphoproliferative disorders and it should therefore be considered a valid alternative to surgical biopsy in such cases., Cryobiopsy is an effective method in the diagnosis of lymphoproliferative disorders. Transbronchial cryobiopsy allows immunohistochemical and molecular analysis. No severe bleeding or pneumothorax were observed in this study. https://bit.ly/2zdHPTn

Monogenic type I interferonopathies are inherited heterogeneous disorders characterised by early onset of systemic and organ specific inflammation, associated with constitutive activation of type I interferons (IFNs). In the last few years, several clinical reports identified the lung as one of the key target organs of IFN-mediated inflammation. The major pulmonary patterns described comprise children's interstitial lung diseases (including diffuse alveolar haemorrhages) and pulmonary arterial hypertension but diagnosis may be challenging. Respiratory symptoms may be either mild or absent at disease onset and variably associated with systemic or organ specific inflammation. In addition, associated extrapulmonary clinical features may precede lung function impairment by years, and patients may display severe/endstage lung involvement, although this may be clinically hidden during the long-term disease course. Conversely, a few cases of atypical severe lung involvement at onset have been reported without clinically manifested extrapulmonary signs. Hence, a multidisciplinary approach involving pulmonologists, paediatricians and rheumatologists should always be considered when a monogenic interferonopathy is suspected. Pulmonologists should also be aware of the main pattern of presentation to allow prompt diagnosis and a targeted therapeutic strategy. In this regard, promising therapeutic strategies rely on Janus kinase-1/2 (JAK-1/2) inhibitors blocking the type I IFN-mediated intracellular cascade.

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.

Background: Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in overall COVID-19 population, but limited information are available on their specific roles in young adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics, and role of selected prognostic predictors, in particular obesity, in a large cohort of young hospitalized patients with COVID-19 pneumonia. Methods: Nine Pulmonology Units, across North and Centre of Italy, were involved in this retrospective study. Demographic and clinical characteristics as well as radiological features were registered for all cases. Comorbidity were classified according to their known or potential association with COVID-19. Findings: A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 73 patients (27.7%), and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only significant predictors for MV in a full model adjusted for comorbidities and markers of severity. Pre-existing comorbidities, such as hypertension, diabetes and asthma, and increased D-dimer level were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Interpretation: Obesity in young adults is, per se, a strong, independent, predictor of a more complicated COVID-19, without, however, influencing in-hospital mortality. On the other hand, selected comorbidities, mainly hypertension, diabetes and asthma, significantly impact survival even in a young population, and prompt recognition of these conditions as well as a closer surveillance of this subgroup are highly recommended. Funding: none. Declaration of Interests: Prof. Bonifazi reports speaker fees from Boehringer Ingelheim and Roche, outside the submitted work; Dr. Harari reports personal fees from Roche, grants and personal fees from Actelion and Boehringer Ingelheim, outside the submitted work. Ethics Approval Statement: Anonymized data of patients included in the study cohort were retrospectively collected from electronic medical records. The study protocol complies to the ethical guidelines of the 1975 Declaration of Helsinki and it was notified and approved by the coordinator ethics committee (n. 2020131) and by each local ethics committee and the need for patient’s informed consent was waived.

IntroductionThe accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD), surgical lung biopsy is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy.MethodsThis prospective, multicentre, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic interstitial pneumonia by a central MDTD board (two clinicians, two radiologists, two pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps, as follows: 1) clinicoradiological data alone; 2) addition of bronchoalveolar lavage (BAL) findings; 3) addition of TBLC interpretation; and 4) surgical lung biopsy findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis.ResultsTBLC led to a significant increase in the percentage of cases with confident diagnoses or provisional diagnoses with high confidence (likelihood ≥70%) from 60.2% to 81.2%. In 32 out of 52 patients nondiagnostic after BAL, TBLC provided a diagnosis with a likelihood ≥70%. The percentage of confident diagnoses (likelihood ≥90%) increased from 22.7% after BAL to 53.9% after TBLC. Pneumothoraces occurred in 16.4% of patients, and moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days.InterpretationTBLC increases diagnostic confidence in the majority of ILD patients with an uncertain noninvasive diagnosis, with manageable side-effects. These data support the integration of TBLC into the diagnostic algorithm for ILD.

Background and Objectives: Transbronchial lung cryobiopsy(TBLC) has recently been proposed as an alternative to surgical lung biopsy(SLB), avoiding surgery in more than 80% of ILDs cases. Our study aims to evaluate impact of TBLC in real life setting of a referral ILDs center. Methods: Retrospective review of 634 patients referred to our center(2002-2016). We analyzed time trends of biopsies methods and num of IPF diagnosis per year; complications, hospitalization days and mortality rates related to TBLC and SLB were evaluated. Results: 288(36%) had histological UIP/IPF diagnosis. 133 underwent TBLC and 95 SLB (8 had TBLC before SLB). Since TBLC has been introduced in 2011, the amount of lung biopsy triplicated and TBLC has significantly increased over time (Fig1). Hospitalization time was significantly lower for TBLC compared to SLB(2.39 vs 4.88days, p Conclusions: After 2011 the number of overall IPF diagnosis increased, along with the number of histologic confirmation of UIP/IPF by TBLC, whereas SLB significantly decreased. Compared to SLB we observed lower rates of complications, hospitalization and mortality with TBLC in IPF patients.

Background: IPAF (interstitial lung disease with autoimmune features) is a research category recently introduced with limited data on prognosis and natural history. The aim of this study was to evaluate the characteristics of patients meeting IPAF criteria in a cohort of patients previously diagnosed with IPF. Methods: We retrospectively analyzed the medical records of IPF diagnoses at or center from 2002 until 2016. We reassigned IPF diagnoses according to the 2018 ATS/ERS guidelines and IPAF diagnoses according to ERS statement. We extracted data regarding demographics, medications, smoking history, laboratory results (autoimmunity) and pulmonary function. Results: Among 360 IPF-diagnoses, we identified: Group A composed of 289 IPF-only patients; Group B composed of 49 IPF patients with positive auto-antibodies (including anti-thyroid); Group C (IPF/IPAF) composed of 22 patients meeting IPAF criteria. IPF/IPAF patients were more frequently female (40%) (compared respectively to 17%females in group A and 30% in group B, p= 0.005). Conclusions: Reflux and arthralgia were the most frequent clinical manifestations in the IPAF group (respectively 23% and 55%), whereas in IPF-only group reflux was described in 26%(p 0.0065) and arthralgia in 2% of cases (p

Due to the increasing role of endosonography [endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and esophageal ultrasound-guided fine needle aspiration (EUS-FNA)] in the diagnosis of several lung diseases, the knowledge of technical aspects is mandatory to optimize the success of the procedure. Among those technicalities related to the procedure, the choice of a needle over another one-either in terms of dimension and type-may have a role in the diagnostic process, especially in some diseases such as lymphoproliferative disorders. In this review, we analyze the current knowledge about the biopsy needle for endosonography, providing also some hints for the future.

Background: Prognostic evaluation in idiopathic pulmonary fibrosis (IPF) may be important as it can guide management decisions, but the potential role of honeycomb changes in providing information about outcome and survival of patients with IPF, particularly if diagnosed using cryobiopsy, has not been evaluated. Aim of this study was to determinate whether a relationship exists between honeycombing on cryobiopsy and clinical/radiological picture and outcome in patients with IPF and to assess whether the same pathologic criteria that have been used to define the UIP pattern (usual interstitial pneumonia) for surgical biopsy can also be applied to cryobiopsy. Methods: Sixty-three subjects with a multidisciplinary diagnosis of IPF and a UIP pattern on cryobiopsy were evaluated. Patients were classified into two sub-groups depending on the presence of honeycombing on histology. Results: The presence of honeycombing on cryobiopsy did not identify a specific phenotype of patients as it did not correlate with radiological and clinical picture and it was not associated neither with the risk of death (p = 0. 1192) or with the event-free survival (p = 0.827); a higher number of samples and the presence of pleura on biopsy were instead associated with an increase in the finding of honeycombing. Conclusions: The same pathologic criteria that have been used to define the UIP pattern in surgical biopsies (with honeycombing changes considered as non-mandatory for the definition of the pattern itself) can be applied to cryobiopsy samples, as the presence of these changes do not define different clinical or radiological phenotypes of patients with IPF.