Introduction: SAD is a precursor and key feature of chronic obstructive pulmonary disease (COPD). The lower limit of normal (LLN) and fixed ratio definition of FEV1/FVC may be discordant in up to 54% of cases, where there is potential for COPD misdiagnosis(1). Therefore, there is a clinical need to assess SAD in older people and determine whether this is pathological or part of normal aging. Methods: Healthy controls (n = 29) and mild to moderate COPD patients over 60 years old underwent lung function once within a prospective cohort study SAFFRON (IRAS ID 253739). COPD patients were classified as discordant (FEV1/FVC >LLN; disCOPD; n =14) or concordant (FEV1/FVC <LLN; conCOPD; n = 21). Analysis: one-way ANOVA or Kruskall-Wallis for parametric and non-parametric data respectively, categorical data using chi-squared test. Results: ConCOPD patients were younger (p=0.002) with mean TLco and Kco <80%pred (both p<0.001) and elevated TLC and FRC (both p=0.001) implying that emphysema and hyperinflation are confined to this group. Established SAD markers were more aberrant in COPD v health, with lower FEV1/FVC, lower MMEF25-75, raised X5Hz on impulse oscillometry and raised R5-19 on Forced Oscillation Technique (all p≤0.04). Notably disCOPD exhibited differences in oscillometry from health, and higher LCI (p=0.005). Discussion: There is no evidence of emphysema or hyperinflation on lung function in disCOPD patients, despite the presence of SAD, highlighting the potential for misdiagnosis of early COPD due to silent SAD. Radiology, blood biomarker and functional capacity data, collected as part of the SAFFRON study, will be of benefit. Ref 1: 10.1136/thx.2008.098483

Background The COVID-19 pandemic follows severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus epidemics. Some survivors of COVID-19 infection experience persistent respiratory symptoms, yet their cause and natural history remain unclear. Follow-up after SARS and MERS may provide a model for predicting the long-term pulmonary consequences of COVID-19. Methods This systematic review and meta-analysis aims to describe and compare the longitudinal pulmonary function test (PFT) and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19. Meta-analysis of PFT parameters (DerSimonian and Laird random-effects model) and proportion of CT features (Freeman-Tukey transformation random-effects model) were performed. Findings Persistent reduction in the diffusing capacity for carbon monoxide following SARS and COVID-19 infection is seen at 6 months follow-up, and 12 months after MERS. Other PFT parameters recover in this time. 6 months after SARS and COVID-19, ground-glass opacity, linear opacities and reticulation persist in over 30% of patients; honeycombing and traction dilatation are reported less often. Severe/critical COVID-19 infection leads to greater CT and PFT abnormality compared to mild/moderate infection. Interpretation Persistent diffusion defects suggestive of parenchymal lung injury occur after SARS, MERS and COVID-19 infection, but improve over time. After COVID-19 infection, CT features are suggestive of persistent parenchymal lung injury, in keeping with a post-COVID-19 interstitial lung syndrome. It is yet to be determined if this is a regressive or progressive disease.

Background: Half of acute exacerbations of COPD are due to bacterial infection, and the other half are likely influenced by microbial colonisation. The same organisms commonly cultured during acute exacerbations are often found in the sputum of patients during stability. A robust assessment of the prevalence of potentially pathogenic microorganisms (PPMs) in the sputum of stable COPD patients may help to inform the targeted prevention of exacerbation by these organisms. Methods: A systematic review and meta-analysis was carried out to determine the prevalence of PPMs in patients with COPD in the stable state. Meta-analysis of prevalence was carried out using the Freeman–Tukey double arcsine transformation random effects model, and sub-group analysis was performed for sputum modality. Prevalence of total and individual PPMs was calculated from patient-level data from individual studies. Results: Pooled prevalence of PPMs identified by sputum culture was found to be 41% (95% CI 36–47%). Significant heterogeneity was found across all studies, which can likely be attributed to inconsistent measuring and reporting of PPMs. The most commonly reported organisms were H. influenzae, M catarrhalis, S. pneumoniae, S. aureus, and P. aeruginosa. Declining lung function was weakly correlated with prevalence of PPMs. Conclusion: The airways of patients with COPD are colonised with PPMs during the stable state in almost half of patients. A complex relationship likely exists between the microbiome in the stable state and the phenotype of COPD patients. Targeted microbial therapy for preventing exacerbations of COPD should carefully consider the stable microbiome as well as the exacerbated.

Background: Coexistent emphysema and usual interstitial pneumonia (UIP) on CT is increasingly recognised. It is unclear if combined pulmonary fibrosis and emphysema syndrome (CPFE) is a distinct clinical entity with an impact on survival. Aim: To compare survival rates of patients with idiopathic pulmonary fibrosis (IPF), CPFE and emphysema. Methods: Retrospective cohort study of 509 patients with COPD or IPF and a CT scan performed between 2009-2020 from 4 UK NHS sites. Demographic and clinical data was extracted from electronic medical records, including initial CT scan report and date, initial pulmonary function tests (ANOVA test - * denotes p<0.05 across groups) and date of death/ follow-up censor point. Patients were grouped from CT reports as IPF, CPFE or Emphysema. Kaplan Meier Survival Estimates were performed using STATA v16. Results: Patients were grouped as: -IPF (n=317. At CT: mean age 73.3 years [SD 9.2]; 64.4% male; mean FEV1 2.16L [SD 0.66]*, mean FVC 2.68L [SD 0.84]*). 43.2% received antifibrotic therapy. -CPFE (n=109. At CT: mean age 72.2 years [SD 9.3]; 67.9% male; mean FEV1 2.13L [SD 0.73]*; mean FVC 3.00L [SD 1.00]*). -Emphysema (n=83. At CT: mean age 65.6 years [SD 10.6]; 66.3% male; mean FEV1 1.61L [SD 0.67]*; mean FVC 3.12L [SD 0.86]*). Figure 1 shows Kaplan Meier Survival Estimates. Conclusion: Co-existent emphysema and fibrosis is associated with worse survival than emphysema alone - CPFE has a survival trajectory comparable to IPF.

Aim To undertake a prospective study of the accuracy of two models (LACE and BOOST) in predicting unplanned hospital readmission in older patients (>75 years). Methods Data were collected from a single centre prospectively on 110 patients over 75 years old admitted to the acute medical unit. Follow-up was conducted at 30 days. The primary outcome was the c-statistic for both models. Results The readmission rate was 32.7% and median age 82 years, and both BOOST and LACE scores were significantly higher in those readmitted compared with those who were not. C-statistics were calculated for both tools with BOOST score 0.667 (95% CI 0.559-0.775, P = .005) and LACE index 0.685 (95% CI 0.579-0.792, P = .002). Conclusion In this prospective study, both the BOOST and LACE scores were found to be significant yet poor, predictive models of hospital readmission. Recent hospitalisation (within the previous 6 months) was found to be the most significant contributing factor.

"Designing undergraduate neurosurgical e-learning: medical students' perspective." British Journal of Neurosurgery, 33(1), p. 79

Nerve growth factor (NGF) levels increase in response to inflammation of the mammalian colon. The precise cellular sources of colonic NGF synthesis, however, remain elusive. Using lines of transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the NGF promoter, we found a subpopulation of adendritic EGFP(+) neurons in the myenteric plexus. These colonic EGFP(+) neurons display positive immunostaining for calretinin but not nitric oxide synthase 1 (NOS1) two biomarkers of mouse myenteric neurons. A loss of NGF expression in null mutant postnatal mice does not affect the survival of these EGFP(+) neurons. Induction of colonic inflammation confirms local increases in NGF mRNA/protein levels, which coincide with heightened detection of EGFP by myenteric neurons. Though NOS1(+) myenteric neurons display positive immunostaining for trkA (the receptor required for NGF binding/signaling), transgenic overexpression of NGF by smooth muscle cells in the colon does not alter the survival, somal size, or axonal density of trkA-expressing NOS1(+) myenteric neurons. Mice lacking functional p75NTR (the second receptor required for NGF binding) exhibit significantly less axonal damage among NOS1(+) myenteric neurons, in response to chemically induced colonic inflammation. Likewise, trkA-expressing sympathetic axons that innervate the myenteric ganglia display less damage in the absence of p75NTR. These data are the first to implicate calretinin(+) myenteric neurons as a source of NGF in the murine colon, and that in response to colonic inflammation, increases in NGF can exaggerate damage of intrinsic NOS1(+) axons and extrinsic sympathetic axons that co-express trkA and p75NTR.