Background: The literature shows that delayed or erroneous diagnosis of respiratory conditions may be common in primary care due to underuse of spirometry or poor spirometric technique. The Community Respiratory Assessment Unit (CRAU) was established to optimise diagnosis and treatment of respiratory disease by providing focused history-taking, quality-assured spirometry, and evidence-based guideline-derived management advice.

Clinical characteristics and 28-day mortality of medical patients admitted with COVID-19 to a central London teaching hospital Dear Editor, Clinical Characteristics and 28-day mortality of COVID-19 in London We read with interest the article by Galloway et al. describing a clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death. 1 We undertook a prospective cohort study of adult patients (≥ 18 years old) with laboratoryconfirmed COVID-19 admitted to the Chelsea & Westminster Hospital during a one-month period between 7th March and 7th April 2020 to identify predictors of survival at 28-days. Methods We excluded patients who were diagnosed with nosocomialacquired COVID-19 and those who had received novel agents as part of concurrently running research trials to minimise confounding and avoid duplication of findings. We collected clinical characteristics: age, sex, gender, ethnicity, smoking status, duration of symptoms, comorbidities, observations, laboratory results, radiology, pharmacological treatments administered, use of continuous positive airways pressure (CPAP), non-invasive ventilation (NIV), requirement for intubation, and outcome (survival to discharge or death). Discharged patients, or if unreachable, their primary care physicians were contacted by telephone to confirm vital status at 28-days. Copies of death certificates were acquired. Predictors were computed from baseline characteristics using multivariable analyses. The final date of follow-up was the 8th May 2020. COVID-19 infection was confirmed using nucleic acid real-time reverse transcriptase polymerase chain reaction (RT-PCR) on combined nasal and oropharyngeal swabs. The study was approved by the research governance committee.

Lung cancer is the leading cause of cancer-related deaths in the world. The most prevalent subtype, accounting for 85% of cases, is non-small-cell lung cancer (NSCLC). Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the most common subtypes. Despite recent advances in treatment, the low 5-year survival rate of NSCLC patients (approximately 13%) reflects the lack of early diagnostic biomarkers and incomplete understanding of the underlying disease mechanisms. We hypothesized that integration of metabolomic, transcriptomic and genetic profiles of tumours and matched normal tissues could help to identify important factors and potential therapeutic targets that contribute to tumorigenesis. We integrated omics profiles in tumours and matched adjacent normal tissues of patients with LUSC (N = 20) and LUAD (N = 17) using multiple system biology approaches. We confirmed the presence of previously described metabolic pathways in NSCLC, particularly those mediating the Warburg effect. In addition, through our combined omics analyses we found that metabolites and genes that contribute to haemostasis, angiogenesis, platelet activation and cell proliferation were predominant in both subtypes of NSCLC. The important roles of adenosine diphosphate in promoting cancer metastasis through platelet activation and angiogenesis suggest this metabolite could be a potential therapeutic target.Abbreviations ADP, adenosine diphosphate; HMDB, Human Metabolome Database; LC/MS, liquid chromatography/mass spectrometry; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; NSCLC, non-small-cell lung cancer; WGCNA, weighted gene co-expression network analysis.

Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40–10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.