Breath analysis is a promising non-invasive approach for discovering biomarkers that may be able to detect early-stage lung cancer. However, previous studies in this area have had various limitations that have prevented them from being translated to clinical practice. The LuCID (Lung Cancer Indicator Detection) study aims to address these limitations by conducting the largest ever breath biomarker discovery study for lung cancer, using a state-of-the-art breath analysis approach.

Introduction and Objectives Health inequalities are associated with worse outcomes of COVID-19 illness.1 Health deprivation and disability is one domain within the Index of Multiple Deprivation (IMD). We investigated potential correlation between health deprivation and development of new fibrosis in COVID-19 survivors within a mixed catchment area in NW England in which 35% of neighbourhoods are within the 10% most deprived decile for health and disability. Methods Retrospective analysis of patients identified between March 2020 and January 2021 with either CVCX1 coded CXR or CVCX2 code with positive PCR test for COVID-19, who survived to follow-up at 3 months. Of 912 patients identified, 46 (5%) had new fibrotic changes on CT. Imaging was reviewed by a radiologist using suggested scoring system for COVID-19 follow-up 2 based on sum of 0–5 severity in 5 lobes (total 0–25) for markers of fibrosis. Deprivation decile was captured from patient postcode. Results 42/46 (91%) lived in a neighbourhood within the 50% most deprived for health and disability in England; 20 (43%) within the 10% most deprived. Comparison is shown in table 1. Conclusions We have shown patients surviving COVID-19 who developed new fibrosis are significantly more likely to live within a deprived postcode. Patients within the 10% most deprived postcodes for health and disability are more likely to be male and ex-smokers. We also noted patients developing fibrotic changes on CT within lowest 10% for deprivation had lower rates of ITU admission and required lower FiO2 (indicating less severe disease) but with equivalent radiological findings to those within less deprived areas. Severe deprivation may in itself increase risk of developing long-term respiratory complications from COVID-19, propagating the ongoing cycle of health and deprivation. References Marmot M, et al. Build Back Fairer: The COVID-19 Marmot Review. The Pandemic, Socioeconomic and Health Inequalities in England. [Internet] London: Institute of Health Equity; 2020. Available from https://www.health.org.uk/sites/default/files/upload/publications/2020/Build-back-fairer-the-COVID-19-Marmot-review.pdf Han X, et al. Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology 2021 Jan 26;299(1):E177–E186.

Introduction and Objectives BTS guidelines suggest radiological follow up at 12 weeks for patients with COVID-19 associated pneumonia. It is suggested development of post-covid fibrotic changes is more prevalent with severity of illness.1 We compared illness severity based on maximal respiratory support with non-resolving changes on CT imaging at >12 weeks. Smoking status at time of admission was also collected. Methods Retrospective analysis of COVID-19 patients surviving to follow up identified either by CVCX1 coded CXR or CVCX2 coded CXR and positive PCR between March 2020-January 2021. This identified 912 patients reviewed at 12 weeks with CXR ± CT imaging. 50/912 patients (5.5%) had evidence of either established fibrotic change or ongoing pneumonitis on CT. Imaging was reviewed by radiologist using suggested scoring system for Covid-19 follow-up 2 based on sum of 0–5 severity in 5 lobes (total 0–25) for markers of fibrosis/pneumonitis. Results Comparison is shown in table 1. All patients requiring more than 60% oxygen therapy received advanced respiratory support. 10/50 patients (20%) required no supplementary oxygen and 6/10 were not admitted to hospital. Comparison mean fibrosis score; IPPV-18.6, CPAP/HFNO-9.23, RA- 8.5. There were no current smokers in the follow-up cohort, 24 ex-smokers. Conclusions We noted significant risk for developing post-Covid pneumonic fibrotic changes even in clinically mild cases. With SpO2 at times of peak incidence being main indicator for CXR and/or admission we surmise there may be a significant unrecognized population without an initial CXR to prompt follow-up. It is not clear whether these patients will develop significant symptoms to prompt future investigations and what impact this might have. No patients developing ongoing CT changes were current smokers- a topic we suggest for further study and correlation. References McGroder CF, et al. Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length. Thorax29April 2021. doi:10.1136/thoraxjnl-2021-217031 Xiaoyu Han, et al. Six-month follow-up chest CT findings after severe COVID-19 pneumonia. Radiology 2021;299:1, E177–E186.

Introduction and objectives Traditional entry to the lung cancer pathway was via NICE urgent referral criteria, with an option for patients to be referred urgently with normal CXR and high suspicion (outside strict NICE guidance for urgent review). The National Optimal Lung Cancer Pathway (NOLCP) changed entry criteria to either abnormal CXR prompting CT or direct access to 72 hour CT scan with normal CXR but high clinical suspicion 'as per NICE guidance'. Current NICE guidance revolves around CXR indications and suggests primary care investigation in cases of normal CXR/absence of haemoptysis. Wirral Lung Unit (WLU) adopted NOLCP in Oct 2017 via paperless system using radiology requests linking primary care with radiology, respiratory and outpatient departments. Referral form for direct access CT included equivalent criteria to traditional faxed referrals however we encountered capacity issues with numbers of requests. We aimed to investigate the PPV for methods of entry to NOLCP and potentially triage primary care referrals appropriately to the accepted standard of 3%. Methods Review of indications and results of CXR/CT for all patients between January to March 2018 referred into WLU from primary care. Results- Total- 210 patients. Table 1 shows the outcomes from the two referral routes. Conversion rate to malignancy in the 'flagged CXR' patients was 35% and 15% in those fulfilling NICE urgent criteria referred via primary care CT. 2/56 of the requests were outside strict NICE criteria with low conversion rates to malignancy- one oesophageal and one lung (where no CXR was done pre scan- which would have been abnormal). In this group conversion to all malignancy was 1.8% and lung 0%. Conclusion NICE promotes urgent referral with a risk threshold PPV above 3% (unexplained haemoptysis/abnormal CXR) but contains no specific guidance for direct CT criteria with normal CXR and absence of haemoptysis. We found these criteria to be similarly applicable to urgent CT requests and suggest 72 hour scans are limited to these cases. We have introduced a separate CT stream for 'concerning symptoms only' (<3 weeks), accepting importance of investigation to aid small numbers of potentially early stage diagnoses in this group.

No previous trials of immune modulators (IMs) to treat non-small cell lung cancer (NSCLC) have included ‘cytology’ specimens, dispersed cells aspirated from a tumour deposit or body cavity, for immunochemical assessment of PD-L1, a useful complementary or compulsory companion diagnostic test. This has led to the widely-held view that, in the absence of such ‘validation’, cytology specimens cannot be used to assess it. In many centres, endobronchial ultrasound (EBUS)-guided aspiration of the tumour or intra-thoracic lymph nodes is the preferred means of diagnosis and staging of NSCLC and such specimens account for the majority received for analysis. Failure to asses them has serious implications for appropriate management and might deny patients effective therapy. Much of this reluctance centres on the alleged effect of fixation in alcohol-based fixatives, the preferred method of cytopathologists, rather than formalin, the standard fixation medium for tissue specimens, on the expression of PD-L1 on the cell surface. We compared expression of PD-L1 in 50 paired specimens of NSCLC, one fixed in an alcohol-based fixative and one in neutral-buffered formalin, taken from the same tumour deposit or lymph node during the same procedure. All were spun down and formed into a cell block before assessment for PD-L1 expression, which was by two appropriately-trained pathologists with extensive experience in its interpretation. In none of the 50 pairs studied was there any significant difference, qualitative or quantitative, in the pattern or extent of PD-L1 expression and, in the great majority, it was identical irrespective of fixation. There is no evidence from this study that the use of alcohol-based fixatives has any effect on the expression of PD-L1 or its interpretation. Notwithstanding the general challenges in accurately assessing such expression, which are common to specimens of tissue as well as dispersed cells, pathologists should feel able to interpret cytology specimens with confidence and clinicians able to rely on the results.

There is an urgent need for methods to detect lung cancer earlier. If detected early, over half of lung cancer patients could be cured with existing treatments. Therefore, our greatest opportunity lies in increasing rates of early diagnosis through improved cancer screening. Exhaled breath contains over 1,000 Volatile Organic Compounds (VOCs), which are the products of metabolic activity, hence they directly reflect the current state of cells and represent a valuable source of information about the health of an individual. As the earliest stages of tumor development are characterized by profound changes in cellular metabolic activity, VOCs are potential non-invasive biomarkers for early detection of lung cancer. The LuCID study aims to collect breath samples and evaluate VOCs in exhaled breath as non-invasive biomarkers for early detection of lung cancer.

Background: Fat free mass (FFM) depletion is reported in cystic fibrosis (CF) patients and is not detected by BMI. Objectives: To investigate the association between whole or regional body composition indices and hospitalization or pulmonary function in adult CF patients. Methods: A historical cohort study was carried out. Data of DXA scans performed between January 2007 and June 2012 in 85 adults with CF (44 males, mean age 23±4 years) were collected. Whole body, arm, leg and trunk FFM were divided by height squared to obtain FFM index (FFMI). The decline of FEV1 and the number and days of hospitalization per year was computed from time of DXA scan to end of follow-up. Results were adjusted for age, pancreatic function, diabetes and lung infections. Results: Median follow-up was 2 years (IQR: 1−2.5 years). Patients with low whole body or limbs FFMI had higher risk of spending more than 14 days per year in hospital compared to patients with normal FFMI (adjusted OR: whole body 3.91, 95%CI 1.05–14.52, P = 0.042; arm 3.55, 95%CI 1.11–11.31, P = 0.032; leg 3.87, 95%CI 1.19; 12.57, P = 0.024). Whole body, arm and leg FFMI positively correlated with FEV1 at time of DXA scan (r = 0.55, P< 0.0001; r = 0.40, P< 0.05 and r = 0.55, P< 0.0001). No association was observed between relative rate of FEV1 decline and body composition indices. Conclusions: In adult patients with CF, low whole body and limbs FFMI, derived from DXA body composition analysis, are associated with more time spent in hospital. The gender dependent relationship between whole body or limbs FFMI and pulmonary function, needs to be further investigated.

Introduction: With survival increasing in CF, CF-related diabetes (CFRD) and its assocated complications are more common.Achieving optimal glycaemic control can be particularly difficult despite traditional management methods.CGM provides greater insight into glycaemic trends through the day, and helps determine the benefits of treatment changes.We routinely use CGM for optimisation of diabetic control at our large CF centre (n = 282; 40% CFRD), and have explored its utility in the management of this CF complication.Method: We evaluated CGM traces in 29 CFRD patients over a 20 month period, along with any subsequent changes in weight, pulmonary function, HBA 1 C and antibiotic treatment.Food and exercise diaries completed during CGM were also evaluated. Results: See Table [Mean (SD)]: 69% gained weight, 72% improved their lung function (p < 0.0001) and 62% improved HBA 1 C (p < 0.0001).Overall, 45% required less IV antibiotic therapy (p < 0.0001) and 34% required fewer oral antibiotic courses.90% of subjects had dietary adjustments following review of food and exercise diaries.34% had a change in the type of insulin prescribed following CGM. Conclusion:This study demonstrates the utility of CGM to improve clinical status and optimize treatment including the dosage and type of insulin therapy.CGM used in conjunction with good education, support and the concurrent mapping of food and exercise diaries is of educational benefit allowing the fine-tuning of any adjustments of treatment.Group FEV1 (%) Weight (kg) HBA1C (IFCCmmol/mol) Oral Antibiotics (n courses) IV Antibiotics (n courses) Pre-CGM 56 (29) 58 (12) 63 (28) 0.69 1.

This study was designed to compare the measured consumption of eight high‐fiber snack foods (cookies, muffins, crackers and cheese, pretzels, dry cereal, applesauce, chocolate pudding, carrots and ranch dip) with the level of liking of the food in children attending a local daycare center. Snacks were served in the mornings of eight different days to a sample of 2–5 year old children (n=42). Food intake was calculated with pre‐and post consumption plate weighing. Liking of the foods was estimated using a 3‐point likert scale (yummy, so‐so, yucky) for the following characteristics: appearance, taste, texture, sweetness, and overall liking; non‐parametric test (p‐value<0.05) was used to determine statistical significance. Results showed that amount consumed and liking of food were not associated except for increased intakes with higher ratings for the appearance and overall liking of the applesauce (p‐value<0.001), the taste of cookies (p‐value<0.04), and the appearance of the ready‐to‐eat cereal (p‐value<0.02). Our results indicate that in these preschool‐age children consuming a morning snack at daycare, food consumption is not predicted by the liking of the food. Further studies to determine the predictors of food intake behavior in this age group are needed.

Alteration of the membrane fatty acyl composition modulates the fusion of myoblasts into multinucleate myotubes. The rate of fusion after addition of calcium to 50–52 hour cultures of chick pectoral myoblasts is markedly inhibited in cells possessing acyl chains enriched in elaidate and is enhanced in those enriched in oleate. The modulations appear to occur after the cells have recognized one another and adhered strongly but before the membranes have united. These observations lead to a hypothesis for membrane union (fusion) in which the lipids participate directly perhaps by a mechanism analogous to that proposed for the fusion of lipid vesicles.

We have cultured myogenic cells derived from primary explants and a cell line (L6) in a lipid-depleted medium (LDM) and produced large alterations of the fatty acyl and polar headgroup composition and of the cellular sterol levels. These alterations were produced by altering the composition of the media as follows: removing biotin and providing exogenous fatty acid; removing choline and providing exogenous ethanolamine or choline analogues; and by adding 25-OH cholesterol, an inhibitor of 3-hydroxy-3-methylglutarate (HMG)-CoA reductase. Relatively small, secondary alterations of other lipid classes accompany the large primary alteration. In general, they are not obviously compensatory for the primary alteration by retaining some physical property. We have explored the influence of these lipid alterations on myoblast proliferation and fusion into myotubes. In general, considerable variability appears tolerated, but there also appear to be limits. Long-term cultures grown in media containing a single fatty acid do not proliferate indefinitely, and the fatty acid does not become the sole fatty acyl component of the phospholipids. This phenomenon is also observed for cultures enriched in phosphatidylethanolamine (PE) or phosphatidyldimethylethanolamine (PDME). The influence of the lipid alterations on fusion is particularly interesting. The inclusion of 25-OH cholesterol inhibits fusion. Enrichment of the fatty acyl chains with elaidate or the polar headgroups with PE also inhibits fusion, but in contrast to that by 25- OH cholesterol, a significant fraction of the myoblasts are aligned and interacting with each other. Oleate enrichment enhances the rate of fusion.