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1.
Eur Respir Rev ; 31(164)2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1928158

ABSTRACT

The incidental discovery of pre-clinical interstitial lung disease (ILD) has led to the designation of interstitial lung abnormalities (ILA), a radiological entity defined as the incidental finding of computed tomography (CT) abnormalities affecting more than 5% of any lung zone. Two recent documents have redefined the borders of this entity and made the recommendation to monitor patients with ILA at risk of progression. In this narrative review, we will focus on some of the limits of the current approach, underlying the potential for progression to full-blown ILD of some patients with ILA and the numerous links between subpleural fibrotic ILA and idiopathic pulmonary fibrosis (IPF). Considering the large prevalence of ILA in the general population (7%), restricting monitoring only to cases considered at risk of progression appears a reasonable approach. However, this suggestion should not prevent pulmonary physicians from pursuing an early diagnosis of ILD and timely treatment where appropriate. In cases of suspected ILD, whether found incidentally or not, the pulmonary physician is still required to make a correct ILD diagnosis according to current guidelines, and eventually treat the patient accordingly.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Disease Progression , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/epidemiology , Incidental Findings , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/epidemiology , Lung Diseases, Interstitial/therapy , Tomography, X-Ray Computed
2.
Eur Respir J ; 2022 Mar 17.
Article in English | MEDLINE | ID: covidwho-1753102

ABSTRACT

Several patients experience pulmonary sequelae after Sars-Cov-2 infection, ranging from self-limited abnormalities to major lung diseases. Morphological analysis of lung tissue may help in understanding pathogenic mechanisms and provide consistent personalised management. Aim of the study was to ascertain morphologic and immuno-molecular features of lung tissue. Transbronchial lung cryobiopsy was carried out in patients with persistent symptoms and computed tomography suggestive of residual lung disease after recovery from Sars-CoV-2 infection. 164 patients were referred for suspected pulmonary sequelae after COVID-19; 10 patients with parenchymal lung disease extent >5% underwent lung biopsy. Histological pattern was not homogeneous, as three different case clusters could be evidenced, which were mirrored in clinical and radiological features: cluster one ("chronic fibrosing") characterised by post-infection progression of pre-existing interstitial pneumonias; cluster two ("acute/subacute injury") characterised by different types and grades of lung injury, ranging from organising pneumonia and fibrosing NSIP to diffuse alveolar damage; cluster three ("vascular changes") characterised by diffuse vascular increase, dilatation and distortion (capillaries and venules) within otherwise normal parenchyma. Clusters two and three were characterised by immunophenotypical changes similar to those observed in early/mild covid-19 pneumonias (abnormal expression of STAT3 in hyperplastic pneumocytes and PD-L1, IDO and STAT3 in endothelial cells). This is the first study correlating histological/immunohistochemical patterns with clinical and radiological pictures of patients with post-COVID lung disease. Different phenotypes with potential different underlying pathogenic mechanisms have been identified.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307124

ABSTRACT

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.

5.
Radiol Med ; 127(2): 162-173, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1626023

ABSTRACT

PURPOSE: COVID-19-related acute respiratory distress syndrome (ARDS) is characterized by the presence of signs of microvascular involvement at the CT scan, such as the vascular tree in bud (TIB) and the vascular enlargement pattern (VEP). Recent evidence suggests that TIB could be associated with an increased duration of invasive mechanical ventilation (IMV) and intensive care unit (ICU) stay. The primary objective of this study was to evaluate whether microvascular involvement signs could have a prognostic significance concerning liberation from IMV. MATERIAL AND METHODS: All the COVID-19 patients requiring IMV admitted to 16 Italian ICUs and having a lung CT scan recorded within 3 days from intubation were enrolled in this secondary analysis. Radiologic, clinical and biochemical data were collected. RESULTS: A total of 139 patients affected by COVID-19 related ARDS were enrolled. After grouping based on TIB or VEP detection, we found no differences in terms of duration of IMV and mortality. Extension of VEP and TIB was significantly correlated with ground-glass opacities (GGOs) and crazy paving pattern extension. A parenchymal extent over 50% of GGO and crazy paving pattern was more frequently observed among non-survivors, while a VEP and TIB extent involving 3 or more lobes was significantly more frequent in non-responders to prone positioning. CONCLUSIONS: The presence of early CT scan signs of microvascular involvement in COVID-19 patients does not appear to be associated with differences in duration of IMV and mortality. However, patients with a high extension of VEP and TIB may have a reduced oxygenation response to prone positioning. TRIAL REGISTRATION: NCT04411459.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/therapy , Microvessels/diagnostic imaging , Respiration, Artificial/methods , Tomography, X-Ray Computed/methods , Aged , Female , Humans , Intensive Care Units , Italy , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Prospective Studies , SARS-CoV-2
6.
Mod Pathol ; 34(8): 1444-1455, 2021 08.
Article in English | MEDLINE | ID: covidwho-1196829

ABSTRACT

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.


Subject(s)
COVID-19/pathology , Cell Communication , Endothelial Cells/pathology , Epithelial Cells/pathology , Lung/pathology , B7-H1 Antigen/metabolism , Biopsy , COVID-19/metabolism , COVID-19/mortality , COVID-19/virology , Cytokines/metabolism , Endothelial Cells/metabolism , Endothelial Cells/virology , Epithelial Cells/metabolism , Epithelial Cells/virology , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Lung/metabolism , Lung/virology , Phosphorylation , Prognosis , STAT3 Transcription Factor/metabolism , Signal Transduction
7.
J Clin Med ; 10(6)2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1136514

ABSTRACT

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.

8.
Respiration ; 100(6): 488-498, 2021.
Article in English | MEDLINE | ID: covidwho-1136133

ABSTRACT

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.


Subject(s)
COVID-19 , Lung Diseases, Interstitial , Autopsy , Endothelial Cells , Humans , Lung , SARS-CoV-2 , Tomography, X-Ray Computed
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