Hyperimmune plasma infusion in an immunocompromised Covid-19 patient previously treated for follicular lymphoma.

Covid-19 in immunocompromised patients shows a prolonged course and may lead to a poor prognosis. Although data on hyperimmune plasma for treatment of Covid-19 suggest an improved outcome in immunocompetent patients, limited data are currently available in immunocompromised patients. We present the case of a 62-year-old Caucasian woman, who was previously treated with obinutuzumab and bendamustine for follicular lymphoma and showed a prolonged positive test for Covid-19. Since no improvement was observed with standard of care (including remdesivir), the possibility of hyperimmune plasma infusion was discussed. A first dose of hyperimmune plasma was administered, with subsequent onset of fever, increasing inflammatory indexes and worsening radiological findings. Three days later a second dose of plasma was administered. Within twelve hours cough and fever disappeared, and oxygen at rest was discontinued. The patient was discharged 5 days later, and nasopharyngeal swabs resulted negative 16 days after discharge.

Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome.

OBJECTIVES: The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC). METHODS: In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction). RESULTS: Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) vs 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk. CONCLUSION: This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.

Change in pulmonary mechanics and the effect on breathing pattern of high flow oxygen therapy in stable hypercapnic COPD.

: We studied the effects of high flow oxygen therapy (HFOT) versus non-invasive ventilation (NIV) on inspiratory effort, as assessed by measuring transdiaphragmatic pressure, breathing pattern and gas exchange. Fourteen patients with hypercapnic COPD underwent five 30-min trials: HFOT at two flow rates, both with open and closed mouth, and NIV, applied in random order. After each trial standard oxygen therapy was reinstituted for 10 min. Compared with baseline, HFOT and NIV significantly improved breathing pattern, although to different extents, and reduced inspiratory effort; however, arterial carbon dioxide oxygen tension decreased but not significantly. These results indicate a possible role for HFOT in the long-term management of patients with stable hypercapnic COPD. TRIAL REGISTRATION NUMBER: NCT02363920.

Methods for Measuring Lung Volumes: Is There a Better One?

BACKGROUND: Accurate measurement of lung volumes is of paramount importance to establish the presence of ventilatory defects and give insights for diagnostic and/or therapeutic purposes. OBJECTIVES: It was the aim of this study to measure lung volumes in subjects with respiratory disorders and in normal controls by 3 different techniques (plethysmographic, dilutional and radiographic methods), in an attempt to clarify the role of each of them in performing such a task, without any presumptive 'a priori' superiority of one method above others. Patients andMethods: In different groups of subjects with obstructive and restrictive ventilatory defects and in a normal control group, total lung capacity, functional residual capacity (FRC) and residual volume were measured by body plethysmography, multi-breath helium (He) dilution and radiographic CT scan method with spirometric gating. RESULTS: The 3 methods gave comparable results in normal subjects and in patients with a restrictive defect. In patients with an obstructive defect, CT scan and plethysmography showed similar lung volumes, while on average significantly lower lung volumes were obtained with the He dilution technique. Taking into account that the He dilution technique does primarily measure FRC during tidal breathing, our data suggest that in some patients with an obstructive defect, a number of small airways can be functionally closed at end-expiratory lung volume, preventing He to reach the lung regions subserved by these airways. CONCLUSION: In all circumstances, both CT scan with spirometric gating and plethysmographic methods provide similar values of lung volumes. In contrast, the He dilution method can measure lower lung volumes in some patients with chronic airflow obstruction.

Predictors of exercise-induced bronchoconstriction in subjects with mild asthma.

BACKGROUND: Physical effort is capable of triggering airway obstruction in asthmatics, the so-called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma, aiming to find predictors for developing EIBa. METHODS: In 20 subjects with mild asthma, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day. A maximal, symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed the day after, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV1 change at 1,3,5,7,10 and 15 min after the end of the exercise. RESULTS: 19 subjects completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise. In asthmatics with EIBa, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH), as documented by their progressive increase of end-expiratory lung volume. This subgroup, showing earlier post-exercise FEV1 fall, had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) at rest (p < 0.05) and higher airways responsiveness, expressed as PD20FEV1 (p < 0.05) as compared with other asthmatics with EIBa. CONCLUSIONS: No functional respiratory parameters seem to predict EIBa in mild asthmatics. However, in those with EIBa, a subgroup developed DH during exercise, and this was associated with a baseline reduced forced expiratory flow rates at lower lung volumes and higher airway hyperresponsiveness, suggesting a prominent small airways impairment.

Respiratory function, autonomic dysfunction, and systemic inflammation are closely linked in patients with COPD and tidal flow limitation: An exploratory study.

RATIONALE: The study aimed to investigate the interplay among respiratory function, autonomic dysfunction, and systemic inflammation in COPD patients. METHODS: In 19 COPD patients, functional respiratory parameters, heart rate variability (HRV), and plasma high-sensitivity-C-reactive-protein (hs-CRP) were assessed. Forced oscillation technique (FOT) was used to detect the absence (NFL) or presence (FL) of resting tidal expiratory flow limitation. Subsequently, patients underwent an incremental shuttle walking test (ISWT). Twenty healthy subjects were also shown as controls. RESULTS: FEV1, DLCO, and lung volumes displayed significant correlations with LH/FH ratio (0.56 < r2<0.27,p < 0.01). A significant relationship was found between LH/FH ratio with IC/TLC ratio% (r2 = 0.29,p < 0.05) and hs-CRP (r2 = 0.26,p < 0.05). Patients with FL had greater hs-CRP plasma levels (p < 0.05), lower IC/TLC% (p < 0.05), and higher LH/FH ratio (p<0.001). CONCLUSIONS: Worse airflow obstruction was associated with a higher LH/HF ratio, directly related, to hs-CRP and indices of dynamic hyperinflation. The presence of resting tidal FL with dynamic pulmonary hyperinflation is a strong driver of systemic inflammation and autonomic dysfunction.

Dyspnea During Night-Time and at Early Morning in Patients with Stable COPD is Associated with Supine Tidal Expiratory Flow Limitation.

Rationale: Patients with chronic obstructive pulmonary disorder (COPD) complain of various COPD-related symptoms with different daily frequencies. During the night-time and at early morning, dyspnea is often reported and may predict an increased risk of COPD exacerbation and hospitalization and all-cause mortality. The aim of the study was to assess the underlying mechanisms of this symptom, seeking functional biomarkers of its occurrence. Methods: Stable COPD patients with moderate-to-severe airflow obstruction and without confounding comorbidities underwent extensive baseline function respiratory tests. Spirometry, maximal flow-volume curves, lung volumes, and lung diffusion capacity parameters were obtained. Inspiratory capacity was also measured both in seated and supine positions. Forced oscillation technique (FOT) and negative expiratory pressure (NEP) method were used to establish the presence of tidal expiratory flow limitation (EFL) during recumbency. Questionnaires for recording COPD-related symptoms were administered. Sleep-related disturbances reported by the patients were also registered. Results: Forty-two consecutive COPD patients aged 65±9 completed the protocol. They were divided, according to the absence (NFL) or presence (FL) of supine EFL, in NFL group (n=17) and FL group (n=25). FL COPD patients had more severe airflow obstruction (FEV1= 46.4±19.4 vs 65.1±12.5% pred., p<0.01) and they showed no increase of supine IC in contrast with NFL COPD patients (ΔIC= 0.080±0.18 vs 0.390±0.28 L, p<0.01). Dyspnea either during night-time and at early morning was significantly more reported in FL COPD patients than in NFL COPD patients (p<0.05) and in those with less than 10% increase in supine IC (p<0.05). Conclusion: Supine EFL is frequently associated with both night-time and early morning dyspnea, suggesting that the development of recumbent dynamic pulmonary hyperinflation, heralded by the lack of increment of IC in supine position, is a pivotal mechanism of this symptom. No or trivial increase in supine IC may indicate the occurrence of dyspnea under these conditions.