Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis

Objective The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. Method This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. Results A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. Conclusions Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment

Excess ventilation and ventilatory constraints during exercise in patients with chronic obstructive pulmonary disease.

We assessed the relationship between minute ventilation/carbon dioxide output (VE/VCO2) and ventilatory constraints during an incremental cardiopulmonary exercise testing (CPET) in patients with chronic obstructive pulmonary disease (COPD). Slope and intercept of the VE/VCO2 linear relationship, the ratios of inspiratory capacity/total lung capacity (IC/TLC) and of tidal volume (VT) over vital capacity (VTpeak/VC) and IC (VTpeak/IC) and over forced expiratory volume at 1st second (VTpeak/FEV1) at peak of exercise were measured in 52 COPD patients during a CPET. The difference peak-rest in end-tidal pressure of CO2 (PETCO2) was also measured. VE/VCO2 intercept showed a negative correlation with IC/TLC peak (p < 0.01) and a positive one with VTpeak/FEV1 (p < 0.01) and with PETCO2 peak-rest (p < 0.01). VE/VCO2 slope was negatively related to VTpeak/VC, VTpeak/IC and VTpeak/FEV1 (all correlations p < 0.05) and to PETCO2 peak-rest (p < 0.01). In COPD, VE/VCO2 slope and intercept provide complementary information on the ventilatory limitation to exercise, as assessed by changes in the end-expiratory lung volume and in tidal volume excursion

Fat Free Mass Depletion is Associated to Poor Exercise Capacity Irrespective of Dynamic Hyperinflation in COPD Patients.

BACKGROUND: In patients with COPD, we investigated the effect of the fat-free mass (FFM) on maximal exercise capacity and the relationship with changes in operational lung volumes during exercise. METHODS: In a cross-sectional study fifty-seven patients (16 females; age 65 \ub1 8 yrs) were consecutively assessed by resting lung function, symptom-limited cardiopulmonary exercise test, and body composition by means of bioelectrical impedance analysis to measure the FFM index (FFMI, kg/m2). RESULTS: Patients were categorized as depleted (n = 14) or non depleted (n = 43) according to FFMI. No significant difference in gender, age and in resting lung function was found between depleted and non depleted patients. When compared with non depleted, the depleted COPD patients had a significantly lower O2 uptake at peak of exercise and at anaerobic threshold as well as peak O2 pulse, O2 uptake efficiency slope (OUES) and heart rate recovery (HRR) (p < 0.05 for all comparisons), but similar inspiratory capacity/total lung capacity ratio at peak of exercise. Moreover, they also reported significantly higher leg fatigue (p < 0.05), but not dyspnea on exertion. In all patients, significant correlations (p < 0.01) were found between FFMI and peak O2Pulse, OUES, HRR and leg fatigue. CONCLUSIONS: This study shows that FFM depletion per se plays a part in the reduction of exercise capacity of COPD patients, regardless of dynamic hyperinflation, and is strictly associated to poor cardiovascular response to exercise and to leg fatigue, but not to dyspnoea

Ventilatory Response to Carbon Dioxide Output in Subjects with Congestive Heart Failure and in Patients with COPD with Comparable Exercise Capacity.

Patients with congestive heart failure or COPD may share an increased response in minute ventilation (V˙ E) to carbon dioxide output (V˙ CO2) during exercise. The goal of this study was to ascertain whether the V˙ E/V˙ CO2 slope and V˙ E/V˙ CO2 intercept can discriminate between subjects with congestive heart failure and those with COPD at equal peak oxygen uptake (V˙ O2). METHODS: We studied 46 subjects with congestive heart failure (mean age 61 9 y) and 46 subjects withCOPD(mean age 648 y) who performed a cardiopulmonary exercise test. RESULTS: TheV˙ E/V˙ CO2 slope was significantly higher in subjects with congestive heart failure compared with those with COPD (39.5 9.5 vs 31.8 7.4, P < .01) at peak V˙ O2 < 16 mL/kg/min, but not > 16 mL/kg/min (28.3 5.3 vs 28.9 6.6). TheV˙ E/V˙ CO2 intercept was significantly higher in both subgroups of subjects with COPD compared with the corresponding values in the subjects with congestive heart failure (3.60 1.7 vs 0.16 1.7 L/min, P < .01; 3.63 2.7 vs 0.87 1.5 L/min, P < .01). According to receiver operating characteristic curve analysis, when all subjects with peak V˙ O2 < 16 mL/kg/min were considered, subjects with COPD had a higher likelihood to have the V˙ E/V˙ CO2 intercept > 2.14 L/min (0.92 sensitivity, 0.96 specificity). Regardless of peak V˙ O2, the end-tidal pressure of CO2 (PETCO2) at peak exercise was not different in subjects with congestive heart failure (P .42) and was significantly higher in subjects with COPD (P < .01) compared with the corresponding unloaded PETCO2. CONCLUSIONS: The ventilatory response toV˙ CO2 during exercise was significantly different between subjects with congestive heart failure and those with COPD in terms of the V˙ E/V˙ CO2 slope with moderate-to-severe reduction in exercise capacity and in terms of theV˙ E/V˙ CO2 intercept regardless of exercise capacity. Key words: congestive heart failure; COPD; exercise; ventilatory response