Predictors of Pulmonary Hypertension and Right Ventricular Dysfunction in Patients with Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that occurs in susceptible individuals in response to various inhaled antigens. The fibrotic phenotype of HP is characterized by disease progression and can lead to pulmonary hypertension (PH). The aim of this study was to estimate the prevalence of PH and to identify predictors of PH in patients with chronic HP. METHODS: We conducted an observational longitudinal study that included 85 patients with an established diagnosis of HP. Clinical examination, quality of life questionnaires, high-resolution computed tomography (HRCT) of the chest, arterial blood gases analyses, six-minute walking test (6-MWT), pulmonary function tests, and echocardiography were performed. RESULTS: Patients were divided into groups with fibrotic (71.8%) and nonfibrotic phenotype (28.2%). PH was detected in 41 (48.2%) patients. Patients with PH had the predominant fibrotic phenotype of HP, were older, more symptomatic, and had a higher FVC/DLco ratio. The most significant predictors of PH were CT signs of fibrosis, finger clubbing, FVC/DLco, decreased distance, and SpO2 at the end of 6-MWT, as well as the presence of cardiovascular diseases. CONCLUSIONS: PH is a common condition in patients with chronic HP, especially with the fibrotic phenotype. Early detection of the PH predictors is necessary for the timely diagnosis of this complication of HP.

Predictors of Progression and Mortality in Patients with Chronic Hypersensitivity Pneumonitis: Retrospective Analysis of Registry of Fibrosing Interstitial Lung Diseases.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) resulting from an immune-mediated response in susceptible and sensitized individuals to a large variety of inhaled antigens. Chronic HP with a fibrotic phenotype is characterized by disease progression and a dismal prognosis. The aim of this study was to identify predictors of progression and mortality in patients with chronic HP in real clinical practice. MATERIALS AND METHODS: This retrospective, multicenter, observational study used data from a registry of 1355 patients with fibrosing ILDs. The study included 292 patients diagnosed with chronic HP based on the conclusion of a multidisciplinary discussion (MDD). RESULTS: The patients were divided into groups with progressive (92 (30.3%) patients) and nonprogressive pulmonary fibrosis (200 (69.7%) patients). The most significant predictors of adverse outcomes were a DLco < 50% predicted, an SpO2 at the end of a six-minute walk test (6-MWT) < 85%, and a GAP score ≥ 4 points. CONCLUSION: Pulmonary fibrosis and a progressive fibrotic phenotype are common in patients with chronic HP. Early detection of the predictors of an adverse prognosis of chronic HP is necessary for the timely initiation of antifibrotic therapy.

Breathing pattern, accessory respiratory muscles work, and gas exchange evaluation for prediction of NIV failure in moderate-to-severe COVID-19-associated ARDS after deterioration of respiratory failure outside ICU: the COVID-NIV observational study.

BACKGROUND: Data on the efficacy of non-invasive ventilation (NIV) after progression of respiratory failure in patients who have already received oxygen therapy, or CPAP outside ICU is limited. The study aimed to find predictors of NIV failure based on breathing pattern, gas exchange, and accessory respiratory muscles evaluation in patients who progressed to moderate-to-severe COVID-19 ARDS. METHODS: This was a prospective observational study in patients with moderate-to-severe COVID-19-ARDS on NIV (n = 80) admitted to COVID-ICU of Sechenov University. The combined success rate for conventional oxygen and CPAP outside ICU was 78.6% (440 of 560 patients). The primary endpoints were intubation rate and mortality. We measured respiratory rate, exhaled tidal volume (Vte), mean peak inspiratory flow (PIF), inspiratory time (Ti), PaO2, SpO2, end-tidal carbon dioxide (PETCO2), and Patrick score, and calculated ROX index, PaO2/FiO2, ventilatory ratio, and alveolar dead space (Vdalv/Vt) on Days 1, 3, 5, 7, 10, and 14. For all significant differences between NIV success and failure groups in measured data, we performed ROC analysis. RESULTS: NIV failure rate in ICU after deterioration of respiratory failure outside ICU was 71.3% (n = 57). Patients with the subsequent NIV failure were older at inclusion, more frail, had longer duration of disease before ICU admission, and higher rate of CPAP use outside ICU. ROC-analysis revealed that the following respiratory parameters after 48 h of NIV can serve as a predictors for NIV failure in moderate-to-severe COVID-19-associated ARDS: PaO2/FiO2 < 112 mmHg (AUROC 0.90 (0.93-0.97), p < 0.0001); PETCO2 < 19.5 mmHg (AUROC 0.84 (0.73-0.94), p < 0.0001); VDalv/VT > 0.43 (AUROC 0.78 (0.68-0.90), p < 0.0001); ROX-index < 5.02 (AUROC 0.89 (0.81-0.97), p < 0.0001); Patrick score > 2 points (AUROC 0.87 (0.78-0.96), p = 0.006). CONCLUSION: In patients who progressed to moderate-to-severe COVID-19-ARDS probability of NIV success rate was about 1/3. Prediction of the NIV failure can be made after 48 h based on ROX index < 5.02, PaO2/FiO2 < 112 mmHg, PETCO2 < 19.5 mmHg, and Patrick score > = 2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667923 , registered on 16/12/2020.

Potential for the lung recruitment and the risk of lung overdistension during 21 days of mechanical ventilation in patients with COVID-19 after noninvasive ventilation failure: the COVID-VENT observational trial.

BACKGROUND: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. METHODS: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum¼ positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. RESULTS: The «optimum¼ PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). CONCLUSION: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate¼ PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.

A 61-Year-Old Woman With Insidious Dyspnea and Diffuse Cystic Lung Disease.

A 61-year-old woman, an ex-smoker with a 10 pack year smoking history, was referred to our clinic for the evaluation of insidious dyspnea and diffuse, bilateral infiltrates on a chest radiograph. She reported that she had been experiencing dyspnea on exertion and dry cough for the past 1.5 years. She denied fevers, chills, hemoptysis, or weight loss. Aside from a smoking history, there were no comorbidities or environmental exposures. She had no family history of lung diseases or other disorders. She worked as a school teacher and had no occupational exposures. There were no pets in the home and no prior occupational exposures.

Anti-IL-17 monoclonal antibodies in hospitalized patients with severe COVID-19: A pilot study.

BACKGROUND: One of the main pathophysiological mechanisms underlying the severe course of COVID-19 is the hyper-inflammatory syndrome associated with progressive damage of lung tissue and multi-organ dysfunction. IL-17 has been suggested to be involved in hyper-inflammatory syndrome. OBJECTIVE: To evaluate the efficacy and safety of the IL-17 inhibitor netakimab in patients with severe COVID-19. STUDY DESIGN: In our retrospective case-control study we evaluated the efficacy of netakimab in hospitalized patients with severe COVID-19 outside the intensive care unit (ICU). Patients in the experimental group were treated with standard of care therapy and netakimab at a dose of 120 mg subcutaneously. RESULTS: 171 patients with severe COVID-19 were enrolled in our study, and 88 of them received netakimab. On the 3 day of therapy, body temperature, SpO2/FiO2, NEWS2 score, and CRP improved significantly in the netakimab group compared to the control group. Other clinical outcomes such as transfer to ICU (11.4% vs 9.6%), need for mechanical ventilation (10.2% vs 9.6%), 28-day mortality (10.2% vs 8.4%), did not differ between the groups. CONCLUSION: In hospitalized patients with severe COVID-19, anti-IL-17 therapy might mitigate the inflammatory response and improve oxygenation, but do not affect the need for mechanical ventilation and mortality.

Beneficial effects of inhaled surfactant in patients with COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: We have investigated the use of nebulized surfactant as a potential therapeutic option for the patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) undergoing non-invasive ventilation. METHODS: The patients were divided into 2 groups: surfactant (n = 33) and control (n = 32). The subjects in the surfactant group received the inhaled surfactant at daily dose of 150-300 mg. The oxygenation parameters and several clinical outcomes were analyzed. RESULTS: On the 5 day of therapy, PaO2/FiO2 improved significantly in the surfactant group compared to the control group (184 (155-212) mmHg vs 150 (91-173) mmHg, p = 0.02). The inhaled surfactant significantly reduced the need for transfer of patients to intensive care units (24.2% vs 46.9%, p = 0.05) and invasive mechanical ventilation (18.2% vs 40.6%, p = 0.04). Even more, the nebulized surfactant shortened the length of non-invasive ventilation (7 (3-13) days vs 11 (5-22) days, p = 0.02) and time spent in hospital (18 (16-27) days vs 26 (21-31) days, p = 0.003) in patients suffering from COVID-19-linked ARDS. CONCLUSIONS: Our preliminary data provided indications that inhaled surfactant therapy may represent a promising option for patients with COVID-19-associated ARDS. However, larger clinical trials are crucially needed.

Recombinant tissue plasminogen activator treatment for COVID-19 associated ARDS and acute cor pulmonale.

Existing literature highlights the fact that patients with COVID-19 exhibit alterations in the coagulation process and are associated with respiratory and cardiovascular diseases, including acute respiratory distress syndrome and acute cor pulmonale. In this report, we describe the effects of systemic thrombolysis on acute cor pulmonale in a patient suffering from COVID-19. We demonstrated that systemic thrombolysis successfully improved the hemodynamics of our patient and resulted in a prominent reduction in hypercapnia, alveolar dead space, and ventilatory ratio.

Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19.

AIM: Noninvasive ventilation (NIV) is known to reduce intubation in patients with acute hypoxemic respiratory failure (AHRF). We aimed to assess the outcomes of NIV application in COVID-19 patients with AHRF. MATERIALS & METHODS: In this retrospective cohort study, patients with confirmed diagnosis of COVID-19 and AHRF receiving NIV in general wards were recruited from two university-affiliated hospitals. Demographic, clinical, and laboratory data were recorded at admission. The failure of NIV was defined as intubation or death during the hospital stay. RESULTS: Between April 8 and June 10, 2020, 61 patients were enrolled into the final cohort. NIV was successful in 44 out of 61 patients (72.1%), 17 patients who failed NIV therapy were intubated, and among them 15 died. Overall mortality rate was 24.6%. Patients who failed NIV were older, and had higher respiratory rate, PaCO2, D-dimer levels before NIV and higher minute ventilation and ventilatory ratio on the 1-st day of NIV. No healthcare workers were infected with SARS-CoV-2 during the study period. CONCLUSIONS: NIV is feasible in patients with COVID-19 and AHRF outside the intensive care unit, and it can be considered as a valuable option for the management of AHRF in these patients.