Corrigendum: Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

[This corrects the article DOI: 10.3389/fmed.2022.1083264.].

Eosinopenia as a Prognostic Biomarker for Noninvasive Ventilation Use in COPD Exacerbations.

BACKGROUND: In recent years, blood eosinophils have been evaluated as a surrogate biomarker for eosinophilic airway inflammation and as a prognostic indicator of the outcomes of hospitalized COPD subjects. During an exacerbation of COPD, eosinopenia has been proposed as a prognostic marker of adverse outcomes. OBJECTIVES: The aim of the present post hoc analysis was to elucidate the effectiveness of blood eosinophils for predicting the need of NIV in subjects with COPD exacerbation. METHODS: Consecutive subjects admitted to a hospital for COPD exacerbation were included in the analysis. The eosinophil count from the first complete blood count was used to designate the eosinophil groups. The relationship between the clinical characteristics and blood eosinophil counts, as dichotomized using 150 cells/µL, was evaluated. Results Subjects with blood eosinophil number < 150 k/µL had a more severe disease on admission compared to subjects with ≥150 k/µL, regarding pH 7.400 (7.36, 7.44) vs. 7.42 (7.38, 7.45), p = 0.008, PO2/FiO2 levels 238.1 (189.8, 278.6) vs. 276.2 (238.2, 305.6), p < 0.001, CRP (mg/L) levels 7.3 (3.1, 19.9) vs. 3.5 (0.7, 7.8), p < 0.001 and required a longer hospital stay (days) 10.0 (8.0, 14.0) vs. 5.0 (3.0, 7.0) p < 0.001 respectively. The number of blood eosinophils correlated with the levels of CRP upon admission (p < 0.001, r = -0.334), with arterial pH upon admission (p < 0.030, r = 0.121), with PO2/FiO2 (p < 0.001, r = -0.248), and with duration of hospital stay (p < 0.001, r = -0.589). In the multinomial logistic regression analysis, blood eosinophil count < 150 k/µL was an independent predictor of the use of NIV during hospital stay. CONCLUSION: During COPD exacerbation, low blood eosinophil levels upon admission are related to more severe disease and can be used as a predictor of the need of NIV. Further prospective studies are needed to identify the use of blood eosinophil levels as a predictor of unfavorable outcomes.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.

Predictors of Mortality in Tocilizumab-Treated Severe COVID-19.

Purpose: Tocilizumab is associated with positive outcomes in severe COVID-19. We wanted to describe the characteristics of nonresponders to treatment. Methods: This was a retrospective multicenter study in two respiratory departments investigating adverse outcomes at 90 days from diagnosis in subjects treated with tocilizumab (8 mg/kg intravenously single dose) for severe progressive COVID-19. Results: Of 121 subjects, 62% were males, and 9% were fully vaccinated. Ninety-six (79.4%) survived, and 25 died (20.6%). Compared to survivors (S), nonsurvivors (NS) were older (median 57 versus 75 years of age), had more comorbidities (Charlson comorbidity index 2 versus 5) and had higher rates of intubation/mechanical ventilation (p < 0.05). On admission, NS had a lower PO2/FiO2 ratio, higher blood ferritin, and higher troponin, and on clinical progression (day of tocilizumab treatment), NS had a lower PO2/FiO2 ratio, decreased lymphocytes, increased neutrophil to lymphocyte ratio, increased ferritin and lactate dehydrogenase (LDH), disease located centrally on computed tomography scan, and increased late c-reactive protein. Cox proportional hazards regression analysis identified age and LDH on deterioration as predictors of death; admission PO2/FiO2 ratio and LDH as predictors of intubation; PO2/FiO2 ratios, LDH, and central lung disease on radiology as predictors of noninvasive ventilation (NIV) (a < 0.05). The log-rank test of mortality yielded the same results (p < 0.001). ROC analysis of the above predictors in a separate validation cohort yielded significant results. Conclusions: Older age and high serum LDH levels are predictors of mortality in tocilizumab-treated severe COVID-19 patients. Hypoxia levels, LDH, and central pulmonary involvement radiologically are associated with intubation and NIV.

State-of-the-Art Treatments for Sarcoidosis.

Sarcoidosis is a heterogeneous disease with various treatment indications. Although it affects mainly the lungs, sarcoidosis can affect every organ, especially when the disease course is chronic and protracted. Regular patient follow-up is recommended for early recognition of active, ongoing organ-specific granulomatous inflammation to avoid progression to irreversible fibrosis. In this review, we elaborate on treatment indications and various anti-sarcoidosis regimens proven useful in clinical trials. We also review specialized treatment of specific disease manifestations, with a focus on cardiac sarcoidosis. We also report on treatment for special conditions such as fatigue and small fiber neuropathy. Treatment for sarcoidosis is an emerging landscape, with new data complementing the existing knowledge.

Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

Introduction: Post-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD). Methods: In this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1. Results: Two hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and <60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and <60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and <5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5-29% and <5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic. Conclusion: Post-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are "immature." Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.

Reduction in Hospitalizations for Respiratory Diseases during the First COVID-19 Wave in Greece.

INTRODUCTION: During the first COVID-19 wave, a considerable decline in hospital admissions was observed worldwide. AIM: This retrospective cohort study aimed to assess if there were any changes in the number of patients hospitalized for respiratory diseases in Greece during the first CO-VID-19 wave. METHODS: In the present study, we evaluated respiratory disease hospitalization rates across 9 tertiary hospitals in Greece during the study period (March-April 2020) and the corresponding period of the 2 previous years (2018-2019) that served as the control periods. Demographic data and discharge diagnosis were documented for every patient. RESULTS: Of the 1,307 patients who were hospitalized during the study period, 444 (35.5%) were males with a mean (±SD) age of 66.1 ± 16.6 years. There was a 47 and 46% reduction in all-cause respiratory morbidity compared to the corresponding periods of 2018 and 2019, respectively. The mean incidence rate for respiratory diseases during the study period was 21.4 admissions per day, and this rate was significantly lower than the rate during the same period in 2018 (40.8 admissions per day; incidence rate ratio [IRR], 0.525; 95% confidence interval [CI], 0.491-0.562; p < 0.001) or the rate during 2019 (39.9 admissions per day; IRR, 0.537; 95% CI, 0.502-0.574; p < 0.001). The greatest reductions (%) in the number of daily admissions in 2020 were observed for sleep apnoea (87% vs. 2018 and 84% vs. 2019) followed by admissions for asthma (76% vs. 2018 and 79% vs. 2019) and chronic obstructive pulmonary disease (60% vs. 2018 and 51% vs. 2019), while the lowest reductions were detected in hospitalizations for pulmonary embolism (6% vs. 2018 and 23% vs. 2019) followed by tuberculosis (25% vs. both 2018 and 2019). DISCUSSION/CONCLUSION: The significant reduction in respiratory admissions in 2020 raises the reasonable question of whether some patients may have avoided seeking medical attention during the COVID-19 pandemic and suggests an urgent need for transformation of healthcare systems during the pandemic to offer appropriate management of respiratory diseases other than COVID-19.

Glycated Hemoglobin (HbA1c) as a Predictor of Outcomes during Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Systemic inflammation may be the common denominator between COPD and type 2 diabetes and may explain the correlation in both diseases' development and progress. The aim of this prospective observational study is to examine the prognostic value of glycated hemoglobin levels (HbA1c) and HbA1c-adjusted glycemic variables (glycemic gap, stress hyperglycemia ratio και modified stress hyperglycemia ratio) in an acute exacerbation of COPD (AECOPD) as well as in COPD disease's morbidity and mortality during the following year. We evaluated patients hospitalized only for COPD exacerbations. Levels of HbA1c and HbA1c-adjusted glycemic variables were recorded upon admission. The study outcomes included duration of hospital stay, need for mechanical ventilation and exacerbation outcome. All subjects were followed up for one year. A total of 156 patients were included in the study (74.4% men, age [mean ± SD] 72 ± 7 years). Patients (21.8%) had type 2 diabetes and 67.9% of patients were receiving ICS treatment. The median value of HbA1c was 5.9 (IQR: 5.4, 6.5). Necessity for mechanical ventilation was significantly higher for patients with lower values of HbA1c [median: 5.3 (IQR 5.02, 6.3) vs. 5.9 (IQR 5.5, 6.5), p = .038]. However, duration of hospitalization, death during hospitalization as well as the number of new exacerbation events, time to next exacerbation and mortality during the following year did not differ significantly. Moreover, none of the HbA1c-adjusted glycemic variables examined, demonstrated any statistical significance. In conclusion neither the preceding nor the present glycemic state exhibit a predictive value regarding short- or long-term outcomes of an AECOPD.

Blood eosinophils as predictor of outcomes in patients hospitalized for COPD exacerbations: a prospective observational study.

PURPOSE: In the present prospective multicentre observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations. MATERIAL AND METHODS: Consecutive patients >40 years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in three groups (<50, 50-149 and ≥150 cells/µL). Patients received standard care and were followed up for a year. RESULTS: A total of 388 patients were included (83.5% male, mean age 72 years). Patients with higher blood eosinophils had less dyspnoea (Borg scale), lower C-reactive protein (CRP) and higher PaO2/FiO2 (partial pressure for oxygen/fraction of inhaled oxygen), and were discharged earlier (median 11 vs. 9 vs. 5 days for patients with <50, 50-149 and ≥150 cells/µL, respectively). Patients with <50 cells/µL presented higher 30-day and 1-year mortality, whereas there were no differences in moderate/severe COPD exacerbations between the three groups. In a post hoc analysis, treatment with inhaled corticosteroids as per physicians' decision was associated with better exacerbation prevention during follow-up in patients with ≥150 cells/µL. CONCLUSIONS: Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.

Cardiac sarcoidosis: diagnosis and management.

Sarcoidosis is a chronic inflammatory disease of unknown etiology characterized by multi-organ involvement. End-organ disease consists of granulomatous inflammation, which if left untreated or not resolved spontaneously, leads to permanent fibrosis and end-organ dysfunction. Cardiac involvement and fibrosis in sarcoidosis occur in 5-10% of cases and is becoming increasingly diagnosed. This is due to increased clinical awareness among clinicians and new diagnostic modalities, since magnetic resonance imaging and positron-emission tomography are emerging as "gold standard" tools replacing endomyocardial biopsy. Despite this progress, isolated cardiac sarcoidosis is difficult to differentiate from other causes of arrhythmogenic cardiomyopathy. Cardiac fibrosis leads to congestive heart failure, arrhythmias and sudden cardiac death. Immunosuppressives (mostly corticosteroids) are used for the treatment of cardiac sarcoidosis. Implantable devices like a cardioverter-defibrillator may be warranted in order to prevent sudden cardiac death. In this article current trends in the pathophysiology, diagnosis and management of cardiac sarcoidosis will be reviewed focusing on published research and latest guidelines. Lastly, a management algorithm is proposed.

An unusual disease with an interesting sign.

Acute interstitial pneumonias mimic infectious pneumonias. Radiology signs point to, but usually don't establish, diagnosis. http://bit.ly/3b3P1iK.