Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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Background: Pulse oximetry is widely used in the clinical setting. The purpose of this validation study was to investigate the level of agreement between oxygen saturations measured by pulse oximeter (SpO 2) and arterial blood gas (SaO 2) in a range of oximeters in clinical use in Australia and New Zealand. Methods: Paired SpO 2 and SaO 2 measurements were collected from 400 patients in one Australian and two New Zealand hospitals. The ages of the patients ranged from 18 to 95 years. Bias and limits of agreement were estimated. Sensitivity and specificity for detecting hypoxaemia, defined as SaO 2 < 90%, were also estimated. Results: The majority of participants were recruited from the Outpatient, Ward or High Dependency Unit setting. Bias, oximeter-measured minus arterial blood gas-measured oxygen saturation, was − 1.2%, with limits of agreement − 4.4 to 2.0%. SpO 2 was at least 4% lower than SaO 2 for 10 (2.5%) of the participants and SpO 2 was at least 4% higher than the SaO 2 in 3 (0.8%) of the participants. None of the participants with a SpO 2 ≥ 92% were hypoxaemic, defined as SaO 2 < 90%. There were no clinically significant differences in oximetry accuracy in relation to clinical characteristics or oximeter brand. Conclusions: In the majority of the participants, pulse oximetry was an accurate method to assess SaO 2 and had good performance in detecting hypoxaemia. However, in a small proportion of participants, differences between SaO 2 and SpO 2 could have clinical relevance in terms of patient monitoring and management. A SpO 2 ≥ 92% indicates that hypoxaemia, defined as a SaO 2 < 90%, is not present. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12614001257651). Date of registration: 2/12/2014.

Background and objective: Hypercapnia is associated with worse clinical outcomes in exacerbations of COPD. The present study aimed to determine the effects of nasal high flow (NHF) therapy on transcutaneous partial pressure of carbon dioxide (PtCO 2 ) in stable COPD patients. Methods: In a single-blind randomized controlled crossover trial, 48 participants with COPD were allocated in random order to all of four 20 min interventions: NHF at 15 L/min, 30 L/min and 45 L/min or breathing room air with each intervention followed by a washout period of 15 min. The primary outcome measure was PtCO 2 at 20 min, adjusted for baseline PtCO 2 . Secondary outcomes included respiratory rate at 20 min, adjusted for baseline. Results: The mean (95% CI) change in PtCO 2 at 20 min was −0.6 mm Hg (−1.1 to 0.0), P = 0.06; −1.3 mm Hg (−1.9 to 0.8), P < 0.001; and −2.4 mm Hg (−2.9 to −1.8), P < 0.001; for NHF at 15 L/min, 30 L/min and 45 L/min compared with room air, respectively. The mean (95% CI) change in respiratory rate at 20 min was −1.5 (−2.7 to −0.3), P = 0.02; −4.1 (−5.3 to −2.9), P < 0.001; and −4.3 (−5.5 to −3.1), P < 0.001; breaths per minute compared with room air, respectively. Conclusion: NHF results in a small flow-dependent reduction in PtCO 2 and respiratory rate in patients with stable COPD.

BackgroundFluticasone furoate/Vilanterol trifenatate (FF/VI) is an inhaled corticosteroid/long-acting beta-agonist combination with a prolonged bronchodilator duration of action. We characterised the time-course of onset and offset of airway anti-inflammatory action of FF/VI, as assessed by fraction of exhaled nitric oxide (FeNO), and compared this to the bronchodilator duration of action.MethodsA single-centre, randomised, double-blind, placebo-controlled, two-period, crossover study was undertaken in 28 steroid-naïve adults with asthma. Participants with an FEV1 ≥ 60% predicted, reversible airway disease, and FeNO > 40 ppb received FF/VI 100/25 mcg or placebo once daily for 14 days. FeNO and peak expiratory flow were measured twice-daily during treatment and during a 21-day washout period. FEV1 was measured for five days from treatment cessation. The primary outcome measure was FeNO change from baseline ratio for 21 days following treatment cessation.ResultsIn the 27 subjects who completed the study, median (range) baseline FeNO was 87 ppb (42–212). FF/VI 100/25 mcg reduced FeNO by day 3, ratio FF/VI versus placebo 0.72 (95% confidence interval 0.61–0.86) with the maximum reduction occurring at day 14, 0.32 (0.27–0.37). Following cessation of treatment FeNO remained suppressed for 18 days, ratio on day 18 0.77 (0.59–1.00), whereas improvements in FEV1 and peak flow were maintained for 3 to 4 days post-treatment.ConclusionsThe anti-inflammatory duration of action of FF/VI is consistent with the high glucocorticoid receptor affinity and long lung retention of fluticasone furoate. The anti-inflammatory effect of FF/VI was of greater duration than its bronchodilator effect in adults with mild asthma.Funding GlaxoSmithKline (201499).Trial registrationProspectively registered on ClinicalTrials.gov registry number NCT02712047.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0836-6) contains supplementary material, which is available to authorized users.

Objective: To compare the effects on transcutaneous carbon dioxide tension (Ptco2) of high concentration and titrated oxygen therapy in medical inpatients with morbid obesity who were not selected for a pre‐existing diagnosis of obesity hypoventilation syndrome. Design: A randomised, crossover trial undertaken between February and September 2015. Setting: Internal medicine service, Wellington Regional Hospital, New Zealand. Participants: 22 adult inpatients, aged 16 years or more, with a body mass index exceeding 40 kg/m2. Interventions: Participants received in random order two 60‐minute interventions, with a minimum 30‐minute washout period between treatments: titrated oxygen therapy (oxygen delivered, if required, via nasal prongs to achieve peripheral oxygen saturation [Spo2] of 88–92%), and high concentration oxygen therapy (delivered via Hudson mask at 8 L/min, without regard to Spo2). Ptco2 and Spo2 were recorded at 10‐minute intervals. Main outcome measure: Ptco2 at 60 minutes, adjusted for baseline. Results: Baseline Ptco2 was 45 mmHg or lower for 16 participants with full data (73%). The mean difference in Ptco2 between high concentration and titrated oxygen therapy at 60 minutes was 3.2 mmHg (95% CI, 1.3–5.2 mmHg; P = 0.002). Conclusion: High concentration oxygen therapy increases Ptco2 in morbidly obese patients. Our findings support guidelines that advocate oxygen therapy, if required in patients with morbid obesity, be titrated to achieve a target Spo2 of 88–92%. Clinical trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12610000522011.