Effectiveness and Safety of Argon Plasma Coagulation in Patients with Haemoptysis Caused by an Endobronchial Malignancy.

INTRODUCTION: Patients with central neoplasms and haemoptysis show low survival rates. Symptom control without recurrence 48 h after bronchoscopic interventions may improve the prognosis of these patients. Bronchoscopic argon plasma coagulation (APC) is a useful technique for endobronchial management of haemoptysis in patients with central malignancies. Nevertheless, limited data are available in the literature on its efficacy and safety and the main predictors of success are still unclear. METHODS: An observational, prospective, single-centre cohort study was carried out to assess the efficacy (i.e., immediate bleeding cessation without recurrence during the following 48 h) of bronchoscopic APC in the treatment of patients with haemoptysis caused by endobronchial malignancies and the main predictors of success. RESULTS: A total of 76 patients with median age 75 years (interquartile range: 65-79) were enrolled. 67 (88.2%) patients had bleeding cessation without recurrence 48 h after bronchoscopic APC. A low rate of non-serious adverse events (5.3%) was recorded and a low (7.6%) recurrence rate of haemoptysis at 3.5 months after the procedure was also shown. No clinical, demographic and endoscopic variables related to a successful procedure at 48 h were found. CONCLUSION: This study demonstrates that bronchoscopic APC is an effective procedure in the treatment of patients with haemoptysis caused by endobronchial malignancies, regardless of the clinical characteristics of the patients, the endoscopic and histological features of the neoplasm and the severity of the symptom. Furthermore, it shows a low rate of complications and long-term efficacy in bleeding control.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

PURPOSE: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. METHODS: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. RESULTS: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. CONCLUSIONS: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

A tailored approach to refractory severe Mepolizumab-associated headache: a case study.

INTRODUCTION: Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common. CASE STUDY: We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break. RESULTS: The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years. CONCLUSION: Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale.

Long-term outcomes of combination biologic therapy in uncontrolled severe asthma: a case study.

INTRODUCTION: Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies. CASE STUDY: Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019. RESULTS: The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic. CONCLUSION: Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale.

Does the severity of asthma affect exercise capacity and daily physical activity?

OBJECTIVE: Exercise capacity, daily physical activity, and psychological profile are crucial aspects in the management of asthmatic patients. Whether these features are expressed in a different way in mild-moderate (MMA) and severe asthma (SA) is unknown. METHODS: In this observational cross-sectional study, patients matching the American Thoracic Society/European Respiratory Society (ATS/ERS) definition for SA underwent incremental cardiopulmonary exercise testing (CPET), full lung function testing, and an evaluation of daily step count and physical activity. Questionnaires on quality of life, general fatigue, and presence of anxiety and depression traits (Hospital Anxiety and Depression Scale - HADS) were administered. Patients were compared with a cohort of age- and gender-matched MMA patients. RESULTS: We enrolled 16 SA, 17 MMA patients, and 16 healthy subjects. Compared to MMA, SA subjects showed a median (interquartile range) reduced peak oxygen consumption during CPET (20.4 (17.2-23.3) vs. 25.6 (18.5-30.3) ml/min/kg; p = 0.019), a reduced resting lung function (FEV1% of predicted 77 (67-84) vs. 96 (84-100); p < 0.001) and a pronounced anxiety trait at HADS (9.5 (3-11.7) vs. 4.0 (2.0-7.5); p = 0.023). In addition, SA patients showed a significantly higher reduction in inspiratory capacity from rest to peak (310 (160-520) vs. 110 (-65-325) ml; p = 0.031). We found no significant differences in mean daily step count or quality of life. CONCLUSIONS: Compared to MMA, SA patients present a reduced exercise capacity and a more pronounced anxiety trait, but not worse daily physical activity or quality of life. These aspects should be considered in the clinical management and research development of SA.

Bronchoscopy in the post-acute phase of COVID-19: an observational study.

BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19. METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled. RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer. CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.

QuantiFERON CMV Test and CMV Serostatus in Lung Transplant: Stratification Risk for Infection, Chronic and Acute Allograft Rejection.

The QuantiFERON CMV (QCMV) test evaluates specific adaptive immune system activity against CMV by measuring IFN-γ released by activated CD8+ T lymphocytes. We aimed to evaluate the QCMV test as a predictive tool for CMV manifestations and acute or chronic lung allograft rejection (AR and CLAD) in lung transplant (LTx) patients. A total of 73 patients were divided into four groups based on donor and recipient (D/R) serology for CMV and QCMV assay: group A low-risk for CMV infection and disease (D-/R-); group B and C at intermediate-risk (R+), group B with non-reactive QCMV and group C with reactive QCMV; group D at high-risk (D+/R-). Group D patients experienced higher viral replication; no differences were observed among R+ patients of groups B and C. D+/R- patients had a higher number of AR events and group C presented a lower incidence of AR. Prevalence of CLAD at 24 months was higher in group B with a higher risk of CLAD development (OR 6.33). The QCMV test allows us to identify R+ non-reactive QCMV population as the most exposed to onset of CLAD. This population had a higher, although non-significant, susceptibility to AR compared to the R+ population with reactive QCMV.

Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. METHODS: We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO2max <80%) at 18 months were analyzed. RESULTS: A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. CONCLUSIONS: Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function.

SARS-CoV-2 infection sequelae on exercise response: persistent or reversible? A 2-year perspective.

Post-COVID-19 exercise capacity sequalae on oxygen utilisation and ventilatory efficiency improve over time in most patients. Cardiopulmonary exercise testing is a valuable tool to identify those who may benefit from specific rehabilitative interventions. https://bit.ly/3qFd97x.

Vitamin D in SARS-CoV-2 patients with non-invasive ventilation support.

BACKGROUND: Vitamin D (VitD) deficiency has been reported to be associated with respiratory tract infection. In this work we evaluated the concentration of VitD in COVID-19 patients experiencing acute respiratory infections of different levels of severity excluding those who underwent invasive respiratory support. METHODS: The levels of serum VitD and C-reactive protein (CRP) were analyzed in 118 consecutive hospitalized COVID-19 patients (74 male, 44 female), confirmed with rRT-PCR. Of these patients with ventilation support 52 (44.1%) received oxygen via nasal cannula, oxygen mask or an oxygen mask with a reservoir, 48 (40.7%) were on a continuous positive airway pressure device (CPAP) and 18 (15,3%) on non-invasive mechanical ventilation (NIMV). RESULTS: The median values (range) of VitD and of CRP were 15.1 ng/mL (1.3-73.3) and 14.2 mg/L (5.0-151.2), respectively. A negative correlation from VitD levels and those of CRP (correlation coefficient: 0.259: P=0.005) was observed. VitD levels in O2 support patients were significantly higher than in both CPAP and NIMV patients. No statistical differences were found for CRP levels (P=0.834) among the three type of oxygen support. Fewer patients with O2 support had VitD <30 ng/mL and <20 ng/mL than CPAP and NIMV patients. There were no relationships between VitD and the three classes of IgM (P=0.419) and of IgG (P=0.862) SARS-CoV-2 antibodies values. The behavior was the same for CRP. CONCLUSIONS: Our study shows that a significant proportion of COVID-19 patients have a VitD deficiency and that this condition is more frequent in CPAP and in NIMV patients.

Early outcomes of "low-risk" patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing. Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period. Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery. Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.

Interventional pulmonology techniques in lung transplantation.

Lung transplantation is a key therapeutic option for several end-stage lung diseases. Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications. We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation. We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications. The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia). First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation. High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.

Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension.

BACKGROUND: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined. METHODS: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed. RESULTS: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO2 peak ≥14 ml/kg/min and SVI >30 ml/m2; Group 2, score between 2 and 5 (112 patients) with VO2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m2; Group 3, score >5 (46 patients) with VO2 peak <10 ml/kg/min and SVI <30 ml/m2. The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3. CONCLUSIONS: Combinations of VO2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH.

Patients With Coronavirus Disease 2019 Interstitial Pneumonia Exhibit Pancreatic Hyperenzymemia and Not Acute Pancreatitis.

OBJECTIVES: Gastrointestinal manifestations of coronavirus disease 19 (COVID-19) have been well established, but pancreatic involvement is under debate. Our aims were to evaluate the presence of acute pancreatitis in COVID-19 patients and to assess the frequency of pancreatic hyperenzymemia. METHODS: From April 1, 2020, to April 30, 2020, 110 consecutive patients (69 males, 41 females; mean age, 63.0 years; range, 24-93 years) met these criteria and were enrolled in the study. The clinical data and serum activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits. RESULTS: None of the patients studied developed clinical signs or morphological alterations compatible with acute pancreatitis. However, it was found that 24.5% of the patients had amylase values above 53 IU/L and 16.4% had lipase values above 300 IU/L. Only 1 patient (0.9%) had both amylase and lipase values in excess of 3-fold the upper normal limit without clinical signs of pancreatitis. CONCLUSIONS: The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results.

Distinct Mechanical Properties of the Respiratory System Evaluated by Forced Oscillation Technique in Acute Exacerbation of COPD and Acute Decompensated Heart Failure.

Discriminating between cardiac and pulmonary dyspnea is essential for patients' management. We investigated the feasibility and ability of forced oscillation techniques (FOT) in distinguishing between acute exacerbation of COPD (AECOPD), and acute decompensated heart failure (ADHF) in a clinical emergency setting. We enrolled 49 patients admitted to the emergency department (ED) for dyspnea and acute respiratory failure for AECOPD, or ADHF, and 11 healthy subjects. All patients were able to perform bedside FOT measurement. Patients with AECOPD showed a significantly higher inspiratory resistance at 5 Hz, Xrs5 (179% of predicted, interquartile range, IQR 94-224 vs. 100 IQR 67-149; p = 0.019), and a higher inspiratory reactance at 5 Hz (151%, IQR 74-231 vs. 57 IQR 49-99; p = 0.005) than patients with ADHF. Moreover, AECOPD showed higher heterogeneity of ventilation (respiratory system resistance difference at 5 and 19 Hz, Rrs5-19: 1.49 cmH2O/(L/s), IQR 1.03-2.16 vs. 0.44 IQR 0.22-0.76; p = 0.030), and a higher percentage of flow limited breaths compared to ADHF (10%, IQR 0-100 vs. 0 IQR 0-12; p = 0.030). FOT, which resulted in a suitable tool to be used in the ED setting, has the ability to identify distinct mechanical properties of the respiratory system in AECOPD and ADHF.

Link between serum lipid signature and prognostic factors in COVID-19 patients.

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including-among others-four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.

Severity does not impact on exercise capacity in COVID-19 survivors.

BACKGROUND: current data on the impact of acute illness severity on exercise capacity and ventilatory efficiency of COVID-19 survivors, evaluated at cardiopulmonary exercise test (CPET), are limited. METHODS: in this post-hoc analysis of our previous observational, prospective, cohort study on mechanisms of exercise intolerance in COVID-19 survivors, we aimed at evaluating the impact of acute COVID-19 severity on exercise capacity, pulmonary function testing (PFT) and chest computed tomography (CT) outcomes. RESULTS: we enrolled 75 patients (18 with mild-to-moderate disease, 18 with severe disease, and 39 with critical disease). Mean (standard deviation - SD) follow-up time was 97 (26) days. Groups showed a similar PFT and CT residual involvement, featuring a mildly reduced exercise capacity with comparable mean (SD) values of peak oxygen consumption as percentage of predicted (83 (17) vs 82 (16) vs 84 (15), p = 0.895) among groups, as well as the median (interquartile range - IQR) alveolar-arterial gradient for O2 in mmHg at exercise peak (20 (15-28) vs 27 (18-31) vs 26 (21-21), p = 0.154), which was in the limit of normal. In addition, these patients featured a preserved mean ventilatory efficiency evaluated through the slope of the relation between ventilation and carbon dioxide output during exercise (27.1 (2.6) vs 29.8 (3.9) vs 28.3 (2.6), p = 0.028), without a clinically relevant difference. CONCLUSIONS: Disease severity does not impact on exercise capacity in COVID-19 survivors at 3 months after discharge, including a ventilatory response still in the limit of normal.

Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019.

In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients' inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia.