Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.

Patients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO2R) on outcome in these patients has not been explored in randomised trials. Open-label randomised trial comparing NIV (NIV arm) with ECCO2R (ECCO2R arm) in patients with AECOPD at high risk of NIV failure (pH < 7.30 after ≥ 1 h of NIV). The primary endpoint was time to cessation of NIV. Secondary outcomes included device tolerance and complications, changes in arterial blood gases, hospital survival. Eighteen patients (median age 67.5, IQR (61.5–71) years; median GOLD stage 3 were enrolled (nine in each arm). Time to NIV discontinuation was shorter with ECCO2R (7:00 (6:18–8:30) vs 24:30 (18:15–49:45) h, p = 0.004). Arterial pH was higher with ECCO2R at 4 h post-randomisation (7.35 (7.31–7.37) vs 7.25 (7.21–7.26), p < 0.001). Partial pressure of arterial CO2 (PaCO2) was significantly lower with ECCO2R at 4 h (6.8 (6.2–7.15) vs 8.3 (7.74–9.3) kPa; p = 0.024). Dyspnoea and comfort both rapidly improved with commencement of ECCO2R. There were no severe or life-threatening complications in the study population. There were no episodes of major bleeding or red blood cell transfusion in either group. ICU and hospital length of stay were longer with ECCO2R, and there was no difference in 90-day mortality or functional outcomes at follow-up. There is evidence of benefit associated with ECCO2R with time to improvement in respiratory acidosis, in respiratory physiology and an immediate improvement in patient comfort and dyspnoea with commencement of ECCO2R. In addition, there was minimal clinically significant adverse events associated with ECCO2R use in patients with AECOPD at risk of failing or not tolerating NIV. However, the ICU and hospital lengths of stay were longer in the ECCO2R for similar outcomes. Trial registration The trial is prospectively registered on ClinicalTrials.gov: NCT02086084. Registered on 13th March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084?cond=ecco2r&draw=2&rank=8

Introduction: Septic patients undergoing mechanical ventilation (MV) often experience difficulty in weaning. Th aim of this study was to determine whether inflammatory biomarkers of sepsis could be indicative of the failure or success of spontaneous breathing trial (SBT) in these patients. Methods: Sixty-five patients on MV (42 septic and 23 intubated for other reasons) fulfilling the criteria for SBT were included in the study. Blood samples were collected right before, at the end of (30 min) and 24 h after the SBT. Serum inflammatory mediators associated with sepsis (IL-18, IL-18BP, TNF) were determined and correlated with the outcome of SBT. Results: A successful SBT was achieved in 45 patients (69.2%). Septic patients had a higher percentage of SBT failure as compared to non-septic patients (85% vs. 15%, p = 0.026), with an odds ratio for failing 4.5 times (OR = 4.5 95%CI: 1.16–17.68, p 0.022). IL-18 levels and the relative mRNA expression in serum were significantly higher in septic as compared to non-septic patients (p < 0.05). Sepsis was independently associated with higher serum IL-18 and TNF levels in two time-point GEE models (53–723, p = 0.023 and 0.3–64, p = 0.048, respectively). IL-18BP displayed independent negative association with rapid shallow breathing index (RSBI) (95% CI: −17.6 to −4, p = 0.002). Conclusion: Sustained increased levels of IL-18 and IL-18BP, acknowledged markers of sepsis, were found to be indicative of SBT failure in patients recovering from sepsis. Our results show that, although subclinical, remaining septic inflammation that sustaines for a long time complicates the weaning procedure. Biomarkers for the estimation of the septic burden and the right time for weaning are needed.

Chronic obstructive pulmonary disease (COPD) is a common cause of chronic respiratory failure and its course is punctuated by a series of acute exacerbations which commonly lead to hospital admission. Exacerbations are managed through the application of non-invasive ventilation and, when this fails, tracheal intubation and mechanical ventilation. The need for mechanical ventilation significantly increases the risk of death. An alternative therapy, extracorporeal carbon dioxide removal (ECCO2R), has been shown to be efficacious in removing carbon dioxide from the blood; however, its impact on respiratory physiology and patient outcomes has not been explored. A randomised controlled open label trial of patients (12 in each arm) with acute exacerbations of COPD at risk of failing conventional therapy (NIV) randomised to either remaining on NIV or having ECCO2R added to NIV with a primary endpoint of time to cessation of NIV. The change in respiratory physiology following the application of ECCO2R and/or NIV will be measured using electrical impedance tomography, oesophageal pressure and parasternal electromyography. Additional outcomes, including patient tolerance, outcomes, need for readmission, changes in blood gases and biochemistry and procedural complications, will be measured. Physiological changes will be compared within one patient over time and between the two groups. Healthcare costs in the UK system will also be compared between the two groups. COPD is a common disease and exacerbations are a leading cause of hospital admission in the UK and worldwide, with a sizeable mortality. The management of patients with COPD consumes significant hospital and financial resources. This study seeks to understand the feasibility of a novel approach to the management of patients with acute exacerbations of COPD as well as to understand the underlying physiological changes to explain why the approach does or does not assist this patient cohort. Detailed respiratory physiology has not been previously undertaken using this technique and there are no other randomised controlled trials currently in the literature. ClinicalTrials.gov, NCT02086084.