Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

RATIONALE: Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker-signature to predict sputum eosinophilia in asthma. METHODS: VOCs emitted into the space above sputum samples (headspace) from severe asthmatics (n=36) were collected onto sorbent tubes and analysed using thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ≥3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: (I) acute asthmatics according to blood eosinophilia ≥0.3x109cells/L or sputum eosinophilia of ≥ 3% in the UK EMBER consortium (n=65) and U-BIOPRED-IMI consortium (n=42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analysed by gas-chromatography-mass spectrometry (GC×GC-MS -EMBER or GC-MS -U-BIOPRED). MAIN RESULTS: The in vitro headspace identified 19 VOCs associated with sputum eosinophilia and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ≥ 3% in headspace (AUROC (95% CI) 0.90(0.80-0.99), p<0.0001), correlated inversely with sputum eosinophil % (rs= -0.71, p<0.0001) and outperformed FeNO (AUROC (95% CI) 0.61(0.35-0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89(0.76-1.0) (EMBER cohort) with sputum eosinophilia and 0.90(0.75-1.0) in U-BIOPRED - again outperforming FeNO in U-BIOPRED 0.62 (0.33-0.90). CONCLUSIONS: We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point of care clinical sensors.

Lessons of the month 1: Mesenteric ischaemia secondary to infective endocarditis.

A 60-year-old woman presented with sudden-onset epigastric pain, vomiting and small volume rectal bleeding. She had a history of mechanical mitral valve replacement, for which she was on warfarin. Computed tomography (CT) angiography of the abdomen showed gallstones, a fluid-filled stomach and faecal loading. She subsequently deteriorated with worsening abdominal pain and haemodynamic instability. Non-contrast CT showed small bowel ischaemia and infarction. She rapidly deteriorated and a decision was made that surgery was likely to be futile. She died soon afterwards. On review of the initial CT angiography, an occlusion within the superior mesenteric artery (SMA) was visualised. The post mortem showed small bowel infarction due to embolic occlusion of the SMA secondary to bacterial endocarditis of the prosthetic mitral valve. This case should prompt awareness among clinicians that acute mesenteric ischaemia secondary to septic embolisation should be considered in patients with risk factors for infective endocarditis presenting with acute abdominal pain.

Cardiovascular outcomes in patients with COPD-OSA overlap syndrome: A systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory conditions that are independently associated with increased cardiovascular disease (CVD). It is not clear from current evidence whether COPD-OSA overlap syndrome confers an additive risk. This systematic review and meta-analysis investigated whether CVD was more prevalent in patients with overlap syndrome compared to either condition alone. We searched four electronic databases, screened 1826 records against the inclusion criteria. After screening, 18 retrospective, observational studies involving 4613 overlap patients, 16,046 OSA patients and 1679 COPD patients met the inclusion criteria. A random-effects meta-analysis of five studies (I2 = 61%) showed that overlap was associated with a significantly higher risk of hypertension compared to patients with COPD alone (OR = 1.68, 95%CI 1.21-2.35). Overlap was also associated with an increased risk of peripheral vascular disease compared to OSA alone (OR = 3.30 95%CI 2.66-4.10), with a subset of studies also suggesting an increased risk of ischaemic heart disease, heart failure, and cerebrovascular disease. However, it is worth noting that the findings are limited by the considerable heterogeneity of the studies, all of which were observational and retrospective in nature. This review highlights that patients with overlap syndrome have a high prevalence of CVD with some suggestion of an increased risk compared to patients with either condition alone.

Treatment of COVID-19: a review of current and prospective pharmacotherapies.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread and have grave health and socioeconomic consequences worldwide. Researchers have raced to understand the pathophysiological mechanisms underpinning the disease caused by SARS-CoV-2 so that effective therapeutic targets can be discovered. This review summarises the key pharmacotherapies that are being investigated for treatment of COVID-19, including antiviral, immunomodulator and anticoagulation strategies.

COVID-19 vaccines: what happened to evidence-based medicine?

The UK government recently decided to extend the interval between the first dose of the Pfizer BioNTech and AstraZeneca COVID-19 vaccines from 3 weeks to 12 weeks to maximise the number of people receiving the initial dose, despite the trials only providing vaccine efficacy data based on a schedule of 21 days between doses. This editorial discusses whether there is evidence to support this policy change.