Despite the considerable progress in the classification of the idiopathic interstitial pneumonias (IIPs), the lack of an international standard has resulted in variable and confusing diagnostic criteria and terminology. The advent of high-resolution computerized tomography, the narrowed pathologic definition of usual interstitial pneumonia (UIP) and recognition of the prognostic importance of separating UIP from other IIP patterns have profoundly changed the approach to the IIPs. This is an international Consensus Statement defining the clinical manifestations, pathology, and radiologic features of patients with IIP. The major objectives of this statement are to standardize the classification of the idiopathic interstitial pneumonias (IIPs) and to establish a uniform set of definitions and criteria for the diagnosis of IIPs. The targeted specialties are pulmonologists, radiologists, and pathologists. A multidisciplinary core panel was responsible for review of background articles and writing of the document. In addition, this group reviewed the clinical, radiologic, and pathologic aspects of a wide spectrum of cases of diffuse parenchymal interstitial lung diseases to establish a uniform and consistent approach to these diseases and to clarify the terminology, definitions, and descriptions used in routine clinical practice. The final statement was drafted after a series of meetings of the entire committee. The level of evidence for the recommendations made in this statement is largely that of expert opinion developed by consensus. This classification of IIPs includes seven clinico-radiologic-pathologic entities: idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. The need for dynamic interaction between pathologists, radiologists, and pulmonologists to accurately diagnose these disorders is emphasized. The level of evidence for the recommendations made in this Statement is largely that of expert opinion developed by consensus. This Statement is an integrated clinical, radiologic, and pathologic approach to the classification of the IIPs. Use of this international multidisciplinary classification will provide a standardized nomenclature and diagnostic criteria for IIP. This Statement provides a framework for the future study of these entities. Key Messages * Unclassifiable interstitial pneumonia : Some cases are unclassifiable for a variety of reasons (see text). † This group represents a heterogeneous group with poorly characterized clinical and radiologic features that needs further study. ‡ COP is the preferred term, but it is synonymous with idiopathic bronchiolitis obliterans organizing pneumonia.

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Another interesting finding of this case series is that hypertension was the most common chronic comorbidity among patients who died. A previous 2020 case series 1 also reported a higher rate of hypertension among patients with COVID-19 who were admitted to intensive care units than among patients with COVID-19 who were not admitted to intensive care units. However, hypertension usually is not an independent risk factor associated with mortality in patients with sepsis. 5 According to a study from earlier this year, 6 severe acute respiratory syndrome coronavirus 2 infects the lungs through the angiotensin-converting enzyme II receptor. Further research is needed to find the mechanism of COVID-19. In addition, clinical studies are also needed to confirm whether angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could be beneficial for patients with COVID-19.Our study has some limitations. One limitation is that our data were from patients who died during late January 2020, and they may not be representative of later cases of COVID-19.This case series found that delayed intubation was common in the early stage of the COVID-19 epidemic in Wuhan. Potential reasons for the delay include lack of invasive mechanical ventilators and lack of specific clinical training for respiratory support.

The JmjC-domain-containing histone demethylases (JHDMs) can remove histone lysine-methylation and thereby regulate gene expression. The JmjC-domain uses iron Fe (II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl-lysine. We hypothesize that reactive oxygen species will oxidize Fe (II) to Fe (III), thereby attenuating the activity of JmjC-domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3 hours) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3 hours, exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; pre-incubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2′, 7′-dichlorofluorescein (DCF), GSH/GSSG ratio and protein carbonyl content. A cell free system indicated H2O2 inhibited histone demethylase activity where increased Fe (II) rescued this inhibition. TET protein also showed a decreased activity under oxidative stress. Cells exposed to a low dose and long term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate>30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P<0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.

Purpose An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. Methods We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. Results Of the 733 patients included in the study, the median (IQR) age was 65 (56–73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high d -dimer level, low PaO 2 /FiO 2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. Conclusion In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources. Electronic supplementary material The online version of this article (10.1007/s00134-020-06211-2) contains supplementary material, which is available to authorized users.

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