Search

BackgroundTwo subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions.MethodsWe performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers.FindingsIn two cohorts from the Children’s Hospital of Philadelphia (n=333) and from a multicentre study based at the University of California San Francisco (n=293), LCA identified two subphenotypes defined by differential elevation of biomarkers reflecting inflammation and endotheliopathy. In both cohorts, hyperinflammatory subjects had greater illness severity, more sepsis and higher mortality (41% and 28% in hyperinflammatory vs 11% and 7% in hypoinflammatory). Both cohorts demonstrated overlap with adult subphenotypes when assessed using parsimonious classifiers.InterpretationWe identified hypoinflammatory and hyperinflammatory subphenotypes of paediatric ARDS from two separate cohorts with utility for prognostic and potentially predictive, enrichment. Future paediatric ARDS trials should identify and leverage biomarker-defined subphenotypes in their analysis.

IntroductionA new UK Lung Allocation Scheme (UKLAS) was introduced in 2017, replacing the previous geographic allocation system. Patients are prioritised according to predefined clinical criteria into a three-tier system: the super-urgent lung allocation scheme (SULAS), the urgent lung allocation scheme (ULAS) and the non-urgent lung allocation scheme (NULAS). This study assessed the early impact of this scheme on waiting-list and post-transplant outcomes.MethodsA cohort study of adult lung transplant registrations between March 2015 and November 2016 (era-1) and between May 2017 and January 2019 (era-2). Outcomes from registration were compared between eras and stratified by urgency tier and diagnostic group.ResultsDuring era-1, 461 patients were registered. In era-2, 471 patients were registered (19 (4.0%) SULAS, 82 (17.4%) ULAS and 370 (78.6%) NULAS). SULAS patients were younger (median age 35 vs 50 and 55 for urgent and non-urgent, respectively, p=0.0015) and predominantly suffered from cystic fibrosis (53%) or pulmonary fibrosis (37%). Between eras 1 and 2, the odds of transplantation within 6 months of registration were increased (OR=1.41, 95% CI 1.07 to 1.85, p=0.0142) despite only a 5% increase in transplant activity. Median time-to-transplantation during era-1 was 427 days compared with waiting times in era-2 of 8 days for SULAS, 15 days for ULAS and 585 days for NULAS patients. Waiting-list mortality (15% era-1 vs 13% era-2; p=0.5441) and post-transplant survival at 1 year (81.3% era-1 vs 83.3% era-2; p=0.6065) were similar between eras.ConclusionThe UKLAS scheme prioritises the critically ill and improves transplantation odds. The true impact on waiting-list mortality and post-transplant survival requires further follow-up.

BackgroundRisk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.MethodsWe undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19.ResultsWe recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0–30.0 kg/m2and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use.ConclusionsAfter rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds.Trial registration numberClinicalTrials.gov Registry (NCT04330599).

BackgroundInability to return to work (RTW) is common after acute respiratory distress syndrome (ARDS). Mismatch in an individual’s job workload and his or her functional ability, termed work ability imbalance, is negatively associated with RTW, but has not been evaluated in ARDS survivors.ObjectWe examine associations between work ability imbalance at 6 months and RTW at 6 months and 12 months, as well as the ability to sustain employment in ARDS survivors.MethodsPreviously employed participants from the ARDS Network Long-Term Outcomes Study (N=341) were evaluated. Pre-ARDS workload was determined based on the US Occupational Information Network classification. Post-ARDS functional ability was assessed using self-reported 36-Item Short Form Health Survey (SF-36) physical functioning, social functioning and mental health subscales, and Mini-Mental State Examination. ARDS survivors were categorised into four work ability imbalance categories: none, psychosocial, physical, and both psychosocial and physical.ResultsAlmost 90% of ARDS survivors had a physical and/or psychosocial work ability imbalance at both 6-month and 12-month follow-up. Compared with survivors with no imbalance at 6 months, those with both physical and psychosocial imbalance had lower odds of RTW (6 months: OR=0.33, 95% CI=0.13 to 0.82; 12 months: OR=0.22, 95% CI=0.07 to 0.65). Thirty-eight (19%) of those who ever RTW were subsequently jobless at 12 months.ConclusionInterventions aimed at rebalancing ARDS survivors’ work ability by addressing physical and psychosocial aspects of their functional ability and workload should be explored as part of efforts to improve RTW, maintain employment and reduce the financial impact of joblessness.

IntroductionAdult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961.MethodsData were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used.ResultsAt age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=−0.20 SD, 95% CI −0.38 to –0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score −0.26 SD (95% CI −0.38 to –0.13), p<0.001; functional residual capacity −0.16 SD (−0.34 to –0.08), p=0.001; and residual volume −0.18 SD (−0.31 to –0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively).DiscussionFor this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of ‘smaller lungs’ when in middle age.

RationaleWhile cross-sectional studies have shown associations between certain occupational exposures and lower levels of lung function, there was little evidence from population-based studies with repeated lung function measurements.ObjectivesWe aimed to investigate the associations between occupational exposures and longitudinal lung function decline in the population-based Tasmanian Longitudinal Health Study.MethodsLung function decline between ages 45 years and 50 years was assessed using data from 767 participants. Using lifetime work history calendars completed at age 45 years, exposures were assigned according to the ALOHA plus Job Exposure Matrix. Occupational exposures were defined as ever exposed and cumulative exposure -unit- years. We investigated effect modification by sex, smoking and asthma status.ResultsCompared with those without exposure, ever exposures to aromatic solvents and metals were associated with a greater decline in FEV1(aromatic solvents 15.5 mL/year (95% CI −24.8 to 6.3); metals 11.3 mL/year (95% CI −21.9 to – 0.7)) and FVC (aromatic solvents 14.1 mL/year 95% CI −28.8 to – 0.7; metals 17.5 mL/year (95% CI –34.3 to – 0.8)). Cumulative exposure (unit years) to aromatic solvents was also associated with greater decline in FEV1and FVC. Women had lower cumulative exposure years to aromatic solvents than men (mean (SD) 9.6 (15.5) vs 16.6 (14.6)), but greater lung function decline than men. We also found association between ever exposures to gases/fumes or mineral dust and greater decline in lung function.ConclusionsExposures to aromatic solvents and metals were associated with greater lung function decline. The effect of aromatic solvents was strongest in women. Preventive strategies should be implemented to reduce these exposures in the workplace.

BackgroundMechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe’s impact on inflammation mediators and infection in children with CF.MethodsSeventy-seven children with CF <10 years of age (35 infants <1 year; 42 children 1–10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed.ResultsHair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D2(PGD2) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD2and increased methicillin-resistant Staphylococcus aureussurvival in human CF macrophages.ConclusionsInfants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF.

BackgroundThe demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre.MethodsData were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height.ResultsOf the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were transplanted followed by 61% of patients with CF, 59% of other lung pathology patients and 48% of patients with PF, who also had the highest waiting list mortality (37%). The chance of transplantation also differed by height with taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to 1.04, p<0.001). Patients with blood group O had the highest waiting mortality at 3 years postregistration compared with all other blood groups (27% vs 20%, p<0.001).ConclusionsThe way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings.

Understanding the geographical distribution of COVID-19 through the general population is key to the provision of adequate healthcare services. Using self-reported data from 1 960 242 unique users in Great Britain (GB) of the COVID-19 Symptom Study app,we estimated that, concurrent to the GB government sanctioning lockdown, COVID-19 was distributed across GB, with evidence of ‘urban hotspots’. We found a geo-social gradient associated with predicted disease prevalence suggesting urban areas and areas of higher deprivation are most affected. Our results demonstrate use of self-reported symptoms data to provide focus on geographical areas with identified risk factors.

RationalePopulation-based studies have found evidence of a relationship between occupational exposures and Chronic Obstructive Pulmonary Disease (COPD), but these studies are limited by the use of prebronchodilator spirometry. Establishing this link using postbronchodilator is critical, because occupational exposures are a modifiable risk factor for COPD.ObjectivesTo investigate the associations between occupational exposures and fixed airflow obstruction using postbronchodilator spirometry.MethodsOne thousand three hundred and thirty-five participants were included from 2002 to 2008 follow-up of the Tasmanian Longitudinal Health Study (TAHS). Spirometry was performed and lifetime work history calendars were used to collect occupational history. ALOHA plus Job Exposure Matrix was used to assign occupational exposure, and defined as ever exposed and cumulative exposure unit (EU)-years. Fixed airflow obstruction was defined by postbronchodilator FEV1/FVC <0.7 and the lower limit of normal (LLN). Multinomial logistic regressions were used to investigate potential associations while controlling for possible confounders.ResultsEver exposure to biological dust (relative risk (RR)=1.58, 95% CI 1.01 to 2.48), pesticides (RR=1.74,95% CI 1.00 to 3.07) and herbicides (RR=2.09,95% CI 1.18 to 3.70) were associated with fixed airflow obstruction. Cumulative EU-years to all pesticides (RR=1.11,95% CI 1.00 to 1.25) and herbicides (RR=1.15,95% CI 1.00 to 1.32) were also associated with fixed airflow obstruction. In addition, all pesticides exposure was consistently associated with chronic bronchitis and symptoms that are consistent with airflow obstruction. Ever exposure to mineral dust, gases/fumes and vapours, gases, dust or fumes were only associated with fixed airflow obstruction in non-asthmatics only.ConclusionsPesticides and herbicides exposures were associated with fixed airflow obstruction and chronic bronchitis. Biological dust exposure was also associated with fixed airflow obstruction in non-asthmatics. Minimising occupational exposure to these agents may help to reduce the burden of COPD.

BackgroundAir pollution has been linked to increased morbidity and mortality associated with a number of chronic health conditions including asthma. We hypothesised that levels of ambient air pollution would be related to the number of hospital admissions with exacerbations of asthma.MethodsData on asthma admissions to a large acute NHS trust in the East Midlands were extracted using discharge diagnosis codes over a five-year period from April 2011 to March 2016. Ambient air pollution levels during this period were obtained from the website of the Department for Environment, Food and Rural Affairs. These data were based on a single monitoring station located in the centre of the City which recorded hourly readings of ozone, nitrogen oxides and small particulate matter (PM2.5). Daily mean data were utilised in the analysis. The effect of ambient air pollution on daily admissions for asthma was assessed using a generalised linear model in R version 3.3.1. Independent variables in the model were time, Ozone, NO, NOx and PM2.5. Fourier terms to capture any long-term trend or seasonality where also included in the model. Delayed exposure effects where investigated by fitting separate constrained lag models.ResultsDuring the period from April 2011 to March 2016 there were 4204 admissions due to asthma exacerbations (71% female, mean age 48 years). Admission numbers increased progressively from 726 in 2011/12 to 1043 in 2015/16. Admissions were most frequent in the month of December (2.9 per day) and least frequent in August (1.5 per day). None of Ozone, NO, NOx and PM2.5or their lagged terms were found to be independent predictors of daily admissions for asthma.ConclusionAmbient air pollution measured at a single fixed monitoring station within a city is not able to predict the frequency of admissions due to asthma. Further research on the health effects of air pollution should make use of more detailed assessments of city-wide exposure, for instance by utilising satellite imaging and geospatial mapping.

Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression.

Abstract Background Inhaled adenosine monophosphate (AMP) is thought to cause bronchoconstriction in asthmatic patients indirectly through mast cell mediator release. It may therefore be a more sensitive marker of airway inflammation in asthma and hence more specific for epidemiological surveys of asthma than challenges that act directly on airway smooth muscle such as histamine. There is some uncertainty as to how repeatable the measurement is and this is important if it is to be used for epidemiological studies. Methods The response to histamine and AMP challenges and the protection afforded by terbutaline (500 μg) against these two challenges was measured on two occasions two weeks apart in 20 subjects with asthma (19 completed the study). The response to histamine and AMP was measured as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD₂₀) and the protection afforded by terbutaline in doubling doses (DD). Repeatability was assessed as the limits of agreement. Results Although terbutaline had a slightly greater protective effect against AMP than histamine on both the first (ΔPD₂₀ =2.66 versus 2.11 DD) and second occasion (2.56 and 2.15 DD), the differences were not statistically significant. The limits of agreement for the two histamine and two AMP challenges after placebo were from 3.06 to −3.5 and from 3.78 to −4.54 DD respectively, and these values did not differ significantly. The agreement limits between the first PD₂₀ histamine and PD₂₀ AMP values after placebo were similar, being from 3.73 to −3.72 DD after allowing for the 17.8-fold higher PD₂₀ values for AMP compared with histamine. Conclusions Terbutaline caused a slightly greater inhibition of the bronchoconstrictor response to AMP than histamine but the differences were small and non-significant. Any differences in repeatability between AMP and histamine challenges are small and in this study were not significant. The fact that the agreement between histamine and AMP PD₂₀ values was similar to the agreement between repeat histamine or repeat AMP PD₂₀ values suggests that, within an asthmatic population, PD₂₀ AMP may not be providing different information from that provided by PD₂₀ histamine.

BackgroundPulmonary hypertension (PH) in pregnancy is associated with a high risk of maternal death (30%–50%). Despite risks, patients may actively plan pregnancy. Patients may also present whilst pregnant with previously undiagnosed PH.MethodsRetrospective review of patients presenting during pregnancy at a PH centre between 2001 and 2017.ResultsA total of 27 patients were identified over a 16 year period from 2001 till April 2017. Patients were classified as WHO group 1 (n=25) or group 4 (n=2). Eight of the 27 patients had 2 or more pregnancies and in total 36 pregnancies were managed during the study period. Of the 36 pregnancies, 20 resulted in live birth, 9 ended with medical termination and 7 resulted in a miscarriage. All patients were supervised by a multi-professional team (PH physicians, anaesthetists, obstetricians, intensivists and nurse specialists). 19 deliveries were by Caesarean section with 1 vaginal delivery and planned between 32 to 36 weeks; the earliest live birth was at 25+5 weeks post cardiorespiratory arrest at 25 weeks. Patients underwent epidural or combined spinal/epidural regional anaesthesia and were monitored peri-delivery in an intensive care environment with arterial and central venous access. Of 36 pregnancies, 2 women died within 6 months of delivery (3 and 28 days post-delivery) and none during pregnancy. Patients were followed until January 2017; mean follow up 64 months (range 0–174 months) after last pregnancy. The 5 year survival for all patients (n=27) from date of last pregnancy with PH was 92%.ConclusionMortality of PH in pregnancy in a setting of experienced and coordinated care is less than historical series but remains significant. Counselling women with PH of these risks remains an essential part of disease management. In the event of pregnancy, patients should be managed by a multiprofessional team with peripartum care in an intensive care environment.

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a smoking related lung disease characterised by airflow obstruction on spirometry. COPD patients are prone to acute exacerbations, frequently leading to health care utilisation. There are over 7500 people in Hull with COPD and it is estimated over 6000 patients are living with the condition without a diagnosis. Early identification of COPD with targeted smoking cessation and early initiation of treatment has potential to improve outcomes. We describe the early Results of a COPD screening initiative in Hull.MethodsA collaborative screening program was developed involving the acute hospital trust, community services, clinical commissioning group and city council. The initiative was supported by British Lung Foundation, branded under their ‘Love Your Lungs’ campaign. Screening was undertaken over 4 days in public venues in areas with high smoking prevalence. Individuals completed symptom and lifestyle questionnaires and FEV-1/FEV-6 assessment. Symptomatic individuals with FEV-1 ≤80% predicted and/or FEV-1/FEV-6 ratio <0.73 were invited to attend a one-stop clinic where they underwent diagnostic spirometry and saw a respiratory physician and smoking cessation specialist.Results253 individuals were screened (41% male, 25% current smokers). 67/253 screened positive and 60 were given a one-stop clinic appointment. Individuals not offered appointments either declined or lived outside the area. 31/60 individuals attended their appointment, 6/60 are awaiting review and 23/60 either cancelled or did not attend (DNA). 17/31 clinic attenders were diagnosed with COPD and 13/31 received an alternative diagnosis in addition to or instead of COPD. 57/60 were discharged for on-going care under their GP and 3/60 remain under specialist follow-up. The characteristics of screen positive individuals are presented in Table 1.ConclusionsIn this unselected screening program, the COPD diagnosis rate was 7% and would likely have been higher if all screen positive individuals had attended a one-stop clinic. This compares favourably with diagnosis rates in targeted COPD case finding trials reported previously. Engaging current smokers proved challenging with high DNA rates in this group. Further research is required to assess whether early COPD diagnosis through screening alters smoking behaviour or disease outcomes.Abstract P25 Table 1Characteristics of screen positive individuals

IntroductionMeasurement of fractional exhaled nitric oxide (FeNO) is an easy to perform non-invasive test and surrogate marker of eosinophilic airway inflammation. It has been suggested that suppression of FeNO following a week of directly observed inhaled corticosteroid (ICS) therapy provides objective evidence of non-adherence. Though guidelines for the prescription of novel steroid sparing agents recommend this strategy as part of evaluation, it has not been rigorously evaluated in routine clinical practice. We report the outcomes of using this strategy as part of standard clinical care in our centre.MethodsConsecutive consenting patients with FeNO levels greater than 45 ppb on two occasions who were adherent to prescribed therapy on the basis of clinical history, and meeting criteria for initiation of biological therapy undertook directly observed ICS therapy – supervised (DOTS) over 8 days. In this, patients existing ICS/LABA combination inhalers were changed to once daily fluticasone/vilanterol (Relvar 184/22). Inhaler technique was taught by a specialist nurse and inhaled therapy taken under direct supervision (in person or remotely via Skype). FeNO, spirometry, eosinophil count and the Asthma Control Questionnaire −7 (ACQ-7) were recorded on the first and last days. FeNO was also recorded on day 4. Data are presented as mean ±SD.ResultsSixteen subjects (7 males, age 43±18 years) completed assessments (1 did not have day 4 FeNO value). All but one had ≥80% prescription pick-up rates checked with GP records. FeNO levels decreased from 121±63 ppb to 71±36 ppb at day 4 and 66±43 ppb at day 8 (p<0.01). 10 subjects had significant FeNO suppression by day 4 (figure 1). ACQ-7 score improved from 2.7±1.2 to 1.7±1.1 (p<0.01). Eosinophil count (0.65±0.51) and percent predicted FEV1 (79±19) did not change significantly.ConclusionCombining the use of once a day therapy with remote assessment using appropriate technology, FeNO suppression is a feasible objective test of adherence in the routine clinical setting. Despite appropriate refill collection rates over half of subjects were identified as non-adherent to inhaled therapy. Although these individuals did not commence biological therapy, improvements have been sustained. We recommend routine use of this assessment in severe asthma services.[Figure]

BackgroundAs part of a collaborative 100 day rapid testing programme with NHS England and Stockport Together, we aimed to improve the way patients with breathlessness are assessed, diagnosed and treated. Between June 2015 and June 2016 5.2% and 9.1% of cardiology and respiratory patients seen at Stockport NHS Foundation Trust respectively were subsequently referred to the other specialty causing delays in diagnosis and multiple clinic attendances. Breathlessness is a common reason for unscheduled presentation to ED and primary care.AimsTo provide a one stop multidisciplinary clinic to step down 75% patients presenting with breathlessness in 2 visits or less to primary care or appropriate specialist community teams, with clear diagnoses and patient led management plans.MethodsA clinic consisting of a cardiologist, respiratory physician, cardiac and respiratory physiologists and a member of The Prevention Alliance (TPA) was set up initially in the community and then in Stepping Hill Hospital. Primary care referrals on existing outpatient waiting lists were used and a GP referral template was also created. In a single day patients had CXR, ECG, ECHO and spirometry prior to seeing both consultants together. TPA supported the patient to explore and develop their own plan and signposted to appropriate 3rd sector or self-help organisations.ResultsBetween June 2016 and May 2017 62 patients were seen in the clinic (28/34 male/female; mean age 67.7±1.5). To date, 43.5% patients have been stepped down and a further 19.4% are awaiting investigations and pending step down within 2 visits. The rest require further follow up with respiratory (22.6%), cardiology (9.6%) or both specialties (4.8%). Patient feedback was extremely positive; with a median rating of 1 (range 1–3) in overall helpfulness (1 being most helpful; 5 least helpful) and multiple comments in favour of the multi-speciality clinic.ConclusionThis multi-disciplinary approach to breathlessness has successfully led to a significant number of patients being stepped down from secondary care quickly and efficiently, within 2 visits and with appropriate management plans and education. This model will hopefully prevent these patients being referred to cardiology/respiratory services in the future, reduce attendances to ED and primary care and ensure patient led management.

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is potentially curable by pulmonary endarterectomy (PEA). Despite this a significant proportion of patients offered PEA decline surgery.ObjectiveTo compare long term survival and prognostic indicators in patients with technically operable CTEPH who underwent PEA and those who declined surgery.MethodsData were collected for consecutive, treatment-naive patients diagnosed with CTEPH between 2001 and 2014 identified from the ASPIRE-pulmonary-hypertension-registry.ResultsOf 588 patients with CTEPH, 368 patients were offered surgery. Seventy six percent (n=281) underwent PEA, 20% (n=72) declined surgery and 4% (n=15) were planned to undergo surgery. Five year survival was superior in patients undergoing PEA at 83% compared to patients who declined surgery at 56% (p=0.001, log-rank test). In patients who were offered surgery, mixed venous oxygen saturation (SvO2) (p=0.003), gas transfer (DLco) (p=0.042), history of coronary artery disease (p=0.031) and patient choice (declining surgery) (p<0.001) were independent predictors of mortality. For patients who declined surgery a median threshold of DLco 62%, right atrial pressure 11 mmHg, and SvO262% the positive and negative predictive values for 3 year survival were 31% and 100%, 32% and 95% and 30% and 97%, respectively.[Figure]ConclusionIn a cohort of consecutive patients with CTEPH the long-term survival of patients undergoing PEA is excellent and superior to patients declining surgery and strongly favours surgical intervention in eligible patients. More work is required to understand factors influencing decision making in CTEPH and to ensure that patients are counselled and supported to make informed decisions.

BackgroundTraumatic pneumothoraces are a common consequence of major trauma. Despite this, there is a paucity of literature regarding their optimal management, including the role of conservative treatment. The aim of this study was to assess the treatment, complications and outcomes of traumatic pneumothoraces in patients presenting to a Major Trauma Centre.MethodsThe prospectively collected Trauma Audit :and Research Network (TARN) database was used to identify all patients presenting with traumatic pneumothoraces to a UK Major Trauma Centre from April 2012 to December 2016. Demographics, mechanism of injury, injury severity score (ISS), management and outcomes were analysed.Results602 patients were included in study period. Mean age 48 (SD 22) with 73% male. Mean ISS was 26 and inpatient mortality 9%. Of the 602 traumatic pneumothoraces, 277/602 (46%) were initially treated conservatively. 252/277 (90%) of this cohort did not require subsequent chest tube insertion, including the majority, 56/62 (90%), of patients on admission positive pressure ventilation (PPV). Hazard ratio for failure of conservative management showed no difference between the ventilated and non-ventilated patients (HR 1.1 p 0.84). Only the presence of large hemothorax was associated with increased likelihood of failure of conservative management.ConclusionsIn the largest observational study of traumatic pneumothoraces published to date, over 90% of patients whose pneumothorax was managed conservatively never required subsequent tube drainage. Importantly, this also applies to patients requiring PPV, with no significant increased risk of failure of expectant management. This data supports a role for conservative management in traumatic pneumothoraces.

IntroductionEvidence has implicated neutrophil elastase (NE), a proteolytic enzyme, as a key driver of the pulmonary vascular remodelling that underlies pulmonary arterial hypertension (PAH). Moreover, studies using animal models and explanted human lung tissue have demonstrated that inhibition of NE attenuates pulmonary hypertension. However, there has been little investigation into neutrophil function in PAH patients even though their azurophilic granules are the main physiological reservoir of NE. We investigated neutrophil phenotypes in patients with PAH versus healthy controls, with a focus on neutrophil degranulation.MethodsNeutrophils were isolated from venous blood of PAH patients and healthy controls (HC) and treated with LPS; viability was assessed at 20 hours by morphology. Cell surface receptor expression was determined by flow cytometry. To evaluate degranulation, neutrophils were treated with priming agents, platelet activating factor (PAF, 1 µM) or tumour necrosis factor-α (TNF, 20 ng/ml), and subsequently stimulated with N-formylmethionyl-leucyl-phenylalanine (fMLP; 100 nM). NE release was measured by ELISA and released NE activity and myeloperoxidase (MPO) activity were determined by fluorogenic (Enzchek) and colorimetric (o-dianisidine oxidation) assays respectively.ResultsNeutrophil apoptosis 20 hours following stimulation with LPS was significantly lower in PAH (25.4%+/-2.2, n=12) versus HC samples (44.9%+/-4.7, n=9), p<0.001. There were no differences in TLR2 or TLR4 expression between PAH and HC neutrophils. PAH neutrophils released greater amounts of NE following stimulation (e.g., TNF-α priming: PAH 675.2 ng/ml+/-77 vs. HC 277 ng/ml +/−18.4, p<0.0001) but there was no increase in NE activity in the same supernatants, nor any difference in released MPO activity compared to healthy controls.ConclusionsOur Results indicate that neutrophil phenotype is altered in PAH, with a prolonged lifespan in response to a pro-inflammatory stimulus and increased release of NE. However, we did not detect a corresponding increase in NE activity, suggesting a concomitant increase in NE inhibitor release from PAH neutrophils. The potential role of this altered neutrophil phenotype in vascular remodelling requires further investigation.