Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Longitudinal study to assess impact of smoking at diagnosis and quitting on 1-year survival for people with non-small cell lung cancer.

OBJECTIVES: To update the prevalence of smoking in people as they were diagnosed with non-small cell lung cancer (NSCLC) and to see whether smoking status at baseline and quitting are independently associated with 1-year survival. DESIGN: A real-world cohort study following patients from diagnosis for up to 1 year or until death. SETTING: UK multi-centre study (28 sites) based in secondary and primary care. PARTICIPANTS: 1124 patients with newly diagnosed NSCLC between 2010-2016. MAIN OUTCOME MEASURES: Smoking status was validated at diagnosis and at every routine and emergency hospital visit. Cancer treatments were offered according to local multi-disciplinary team decisions following UK guidelines and smoking cessation treatments offered according to local practice /availability. Survival analysis and Cox Proportional Hazards Modelling examined the associations of a) smoking at baseline and b) quitting smoking, on survival at 1 year. RESULTS: 77% of never smokers, 60% of ex-smokers and 57% of current smokers, were alive at 1 year (p = 0.01). After adjusting for age, stage, EGOG, surgery and gender, ex smokers (adjusted HR 1.96, 95% CI 1.16-2.31) and current smokers (aHR 2.04, 1.19-3.48) were both more likely to die within one year. 23% of smokers with NSCLC quit within 3 months of diagnosis. At 1 year, 69% of those who quit were alive versus 53% of those who continued to smoke (p < 0.01). After adjusting the risk of dying was lower (aHR 0.75), in those who quit smoking, although this was not statistically significant (p = 0.23). CONCLUSIONS: This is the largest prospective study that validates smoking in NSCLC; it shows a third of people are smoking at the time of diagnosis. Smokers have lower 12-month survival than never and ex -smokers. Quitting smoking was associated with 25% reduction in mortality which may be clinically important although not statistically significant, after adjusting for other factors.

Prudent healthcare in emergency departments: a case study in Wales.

To deliver a patient-centred service, emergency departments (EDs) must be efficient, effective and meet the needs of the local population. This article describes a service redesign of unscheduled care in a hospital in Wales, which followed the principles of prudent healthcare to improve patient experiences. Extending the roles of nurse specialist practitioners was a major component of the redesign. Six working groups were established to guide the process, one of which was responsible for working cooperatively with the local community, which was concerned about perceived 'downgrading' of the ED. The service redesign was completed in 2016 and evaluation shows the target for patients being seen in under four hours improved from 88% to 96%, significantly more acute medical admission patients were discharged in less than 24 hours, and patient satisfaction increased overall.

The metabolomic detection of lung cancer biomarkers in sputum.

OBJECTIVES: Developing screening and diagnosis methodologies based on novel biomarkers should allow for the detection of the lung cancer (LC) and possibly at an earlier stage and thereby increase the effectiveness of clinical interventions. Here, our primary objective was to evaluate the potential of spontaneous sputum as a source of non-invasive metabolomic biomarkers for LC status. MATERIALS AND METHODS: Spontaneous sputum was collected and processed from 34 patients with suspected LC, alongside 33 healthy controls. Of the 34 patients, 23 were subsequently diagnosed with LC (LC(+), 16 NSCLC, six SCLC, and one radiological diagnosis), at various stages of disease progression. The 67 samples were analysed using flow infusion electrospray ion mass spectrometry (FIE-MS) and gas-chromatography mass spectrometry (GC-MS). RESULTS: Principal component analysis identified negative mode FIE-MS as having the main separating power between samples from healthy and LC. Discriminatory metabolites were identified using ANOVA and Random Forest. Indications of potential diagnostic accuracy involved the use of receiver operating characteristic/area under the curve (ROC/AUC) analyses. This approach identified metabolites changes that were only observed with LC. Metabolites with AUC values of greater than 0.8 which distinguished between LC(+)/LC(-) binary classifications where identified and included Ganglioside GM1 which has previously been linked to LC. CONCLUSION: This study indicates that metabolomics based on sputum can yield metabolites that can be used as a diagnostic and/or discriminator tool. These could aid clinical intervention and targeted diagnosis of LC within an 'at risk' LC(-) population group. The use of sputum as a non-invasive source of metabolite biomarkers may aid in the development of an at-risk population screening programme for lung cancer or enhanced clinical diagnostic pathways.

Emotional content of dreams in obstructive sleep apnea hypopnea syndrome patients and sleepy snorers attending a sleep-disordered breathing clinic.

STUDY OBJECTIVES: To assess prospectively the emotional content of dreams in individuals with the obstructive sleep apnea hypopnea syndrome (OSAHS) and sleepy snorers. METHODS: Prospective observational study. Forty-seven patients with sleepiness and snoring attending a sleep-disordered breathing clinic, completed a morning diary concerning pleasantness/unpleasantness of their dreams for 10 days, and then had AHI assessed by a limited-channel home sleep study. Participants and groups: Sleepy snorers, AHI < 5: n = 12 (mean age = 51.00 years [SD 7.01], 7 males); AHI 5 -14.9, n = 14 (mean age = 49.71 y [9.73], 12 males); AHI ≥ 15, n = 21 (mean age = 56.33 [11.24], 16 males). RESULTS: All groups reported similar numbers of dreams and nightmares during the diary period. The AHI ≥ 15 group were significantly higher on dream unpleasantness than were the sleepy snorers (p < 0.05); and when only males were analyzed, this difference was also significant (p = 0.01). As AHI increased across the 3 groups, there was a significant decrease in variability of dream emotions (Levene test for homogeneity of variance between the 3 groups, p = 0.018). Mean daytime anxiety and daytime depression were significantly correlated with mean dream unpleasantness and with mean number of nightmares over the diary period. CONCLUSIONS: Patients with AHI ≥ 15 had more emotionally negative dreams than patients with AHI < 5. The variation in mean dream emotion decreased with increasing AHI, possibly because sleep fragmentation with increasing AHI results in fewer and shorter dreams, in which emotions are rarer.

Evaluation of FTIR spectroscopy as a diagnostic tool for lung cancer using sputum.

BACKGROUND: Survival time for lung cancer is poor with over 90% of patients dying within five years of diagnosis primarily due to detection at late stage. The main objective of this study was to evaluate Fourier transform infrared spectroscopy (FTIR) as a high throughput and cost effective method for identifying biochemical changes in sputum as biomarkers for detection of lung cancer. METHODS: Sputum was collected from 25 lung cancer patients in the Medlung observational study and 25 healthy controls. FTIR spectra were generated from sputum cell pellets using infrared wavenumbers within the 1800 to 950 cm-1 "fingerprint" region. RESULTS: A panel of 92 infrared wavenumbers had absorbances significantly different between cancer and normal sputum spectra and were associated with putative changes in protein, nucleic acid and glycogen levels in tumours. Five prominent significant wavenumbers at 964 cm-1, 1024 cm-1, 1411 cm-1, 1577 cm-1 and 1656 cm-1 separated cancer spectra from normal spectra into two distinct groups using multivariate analysis (group 1: 100% cancer cases; group 2: 92% normal cases). Principal components analysis revealed that these wavenumbers were also able to distinguish lung cancer patients who had previously been diagnosed with breast cancer. No patterns of spectra groupings were associated with inflammation or other diseases of the airways. CONCLUSIONS: Our results suggest that FTIR applied to sputum might have high sensitivity and specificity in diagnosing lung cancer with potential as a non-invasive, cost-effective and high-throughput method for screening. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00899262.

Infectious mononucleosis complicated by acute hepatitis and myocarditis: a response to corticosteroids.

Infectious mononucleosis, or glandular fever, is a viral illness which commonly affects young adults. Symptoms can vary from sore throat, enlarged lymph glands, lethargy and weight loss to more serious clinical manifestations such as myocarditis or hepatitis. Treatment is usually conservative although there has been significant debate over the role of oral corticosteroids, especially in more serious cases. Evidence based medicine suggests that there is little to no role for steroids, but there are enough published case reports where steroid therapy has been potentially life saving that the debate continues. We present a case of a fit and well man who had significant multi-organ involvement secondary to infectious mononucleosis, and our experience of oral corticosteroid treatment.