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Background: the antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19.Methods: this randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK. Eligible participants were adult (aged ≥18 years) outpatients with PCR-confirmed, mild-to-moderate SARS-CoV-2 infection who were within 5 days of symptom onset. Using permuted blocks (block size 2 or 4) and stratifying by site, participants were randomly assigned (1:1) to receive either molnupiravir (orally; 800 mg twice daily for 5 days) plus standard of care or matching placebo plus standard of care. The primary outcome was the time from randomisation to SARS-CoV-2 PCR negativity on nasopharyngeal swabs and was analysed by use of a Bayesian Cox proportional hazards model for estimating the probability of a superior virological response (hazard ratio [HR]>1) for molnupiravir versus placebo. Our primary model used a two-point prior based on equal prior probabilities (50%) that the HR was 1·0 or 1·5. We defined a priori that if the probability of a HR of more than 1 was more than 80% molnupiravir would be recommended for further testing. The primary outcome was analysed in the intention-to-treat population and safety was analysed in the safety population, comprising participants who had received at least one dose of allocated treatment. This trial is registered in ClinicalTrials.gov, NCT04746183, and the ISRCTN registry, ISRCTN27106947, and is ongoing.Findings: between Nov 18, 2020, and March 16, 2022, 1723 patients were assessed for eligibility, of whom 180 were randomly assigned to receive either molnupiravir (n=90) or placebo (n=90) and were included in the intention-to-treat analysis. 103 (57%) of 180 participants were female and 77 (43%) were male and 90 (50%) participants had received at least one dose of a COVID-19 vaccine. SARS-CoV-2 infections with the delta (B.1.617.2; 72 [40%] of 180), alpha (B.1.1.7; 37 [21%]), omicron (B.1.1.529; 38 [21%]), and EU1 (B.1.177; 28 [16%]) variants were represented. All 180 participants received at least one dose of treatment and four participants discontinued the study (one in the molnupiravir group and three in the placebo group). Participants in the molnupiravir group had a faster median time from randomisation to negative PCR (8 days [95% CI 8-9]) than participants in the placebo group (11 days [10-11]; HR 1·30, 95% credible interval 0·92-1·71; log-rank p=0·074). The probability of molnupiravir being superior to placebo (HR>1) was 75·4%, which was less than our threshold of 80%. 73 (81%) of 90 participants in the molnupiravir group and 68 (76%) of 90 participants in the placebo group had at least one adverse event by day 29. One participant in the molnupiravir group and three participants in the placebo group had an adverse event of a Common Terminology Criteria for Adverse Events grade 3 or higher severity. No participants died (due to any cause) during the trial.Interpretation: we found molnupiravir to be well tolerated and, although our predefined threshold was not reached, we observed some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this evidence is not conclusive.Funding: Ridgeback Biotherapeutics, the UK National Institute for Health and Care Research, the Medical Research Council, and the Wellcome Trust.

SARS-CoV-2 is the causative virus responsible for the COVID-19 pandemic. This pandemic has necessitated that all professional and elite sport is either suspended, postponed or cancelled altogether to minimise the risk of viral spread. As infection rates drop and quarantine restrictions are lifted, the question how athletes can safely resume competitive sport is being asked. Given the rapidly evolving knowledge base about the virus and changing governmental and public health recommendations, a precise answer to this question is fraught with complexity and nuance. Without robust data to inform policy, return-to-play (RTP) decisions are especially difficult for elite athletes on the suspicion that the COVID-19 virus could result in significant cardiorespiratory compromise in a minority of afflicted athletes. There are now consistent reports of athletes reporting persistent and residual symptoms many weeks to months after initial COVID-19 infection. These symptoms include cough, tachycardia and extreme fatigue. To support safe RTP, we provide sport and exercise medicine physicians with practical recommendations on how to exclude cardiorespiratory complications of COVID-19 in elite athletes who place high demand on their cardiorespiratory system. As new evidence emerges, guidance for a safe RTP should be updated.

Background: Targeting the immunoglobulin E pathway and the interleukin‐5 pathway with specific monoclonal antibodies directed against the cytokines or their receptors is effective in patients with severe asthma. However, there are patients who have suboptimal responses to these biologics. Since interleukin‐4 and interleukin‐13, signalling through the interleukin‐4 receptor, have multiple effects on the biology of asthma, therapies targeting interleukin‐4 and ‐13 (both individually and combined) have been developed.\ud \ud Objectives: To assess the efficacy and safety of anti‐interleukin‐13 or anti‐interleukin‐4 agents, compared with placebo, anti‐immunoglobulin E agents, or anti‐interleukin‐5 agents, for the treatment of children, adolescents, or adults with asthma.\ud \ud Search methods: We identified studies from the Cochrane Airways Trials Register, which is maintained by the Information Specialist for the Group and through searches of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The search was carried out on the 16 October 2020.\ud \ud Selection criteria: We included parallel‐group randomised controlled trials that compared anti‐interleukin‐13 or ‐4 agents (or agents that target both interleukin‐13 and interleukin‐4) with placebo in adolescents and adults (aged 16 years or older) or children (younger than 16 years), with a diagnosis of asthma; participants could receive their usual short‐ or long‐acting medications (e.g. inhaled corticosteroids (ICS), long‐acting beta adrenoceptor agonists (LABA), long‐acting muscarinic antagonists (LAMA), and/or leukotriene receptor antagonists) provided that they were not part of the randomised treatment.\ud \ud Data collection and analysis: We used standard methods expected by Cochrane.\ud \ud Main results: We identified and included 41 RCTs. Of these, 29 studies contributed data to the quantitative analyses, randomly assigning 10,604 people with asthma to receive an anti‐interleukin‐13 (intervention) or anti‐interleukin‐4 agent (intervention), or placebo (comparator). No relevant studies were identified where the comparator was an anti‐immunoglobulin agent or an anti‐interleukin‐5 agent. Studies had a duration of between 2 and 52 (median 16) weeks. The mean age of participants across the included studies ranged from 22 to 55 years. Only five studies permitted enrolment of children and adolescents, accounting for less than 5% of the total participants contributing data to the present review. The majority of participants had moderate or severe uncontrolled asthma. Concomitant ICS use was permitted or required in the majority (21 of 29) of the included studies. The use of maintenance systemic corticosteroids was not permitted in 19 studies and was permitted or required in five studies (information not reported in five studies). Regarding the most commonly assessed anti‐interleukin‐13/‐4 agents, four studies evaluated dupilumab (300 mg once every week (Q1W), 200 mg once every two weeks (Q2W), 300 mg Q2W, 200 mg once every four weeks (Q4W), 300 mg Q4W, each administered by subcutaneous (SC) injection); eight studies evaluated lebrikizumab (37.5 mg Q4W, 125 mg Q4W, 250 mg Q4W each administered by SC injection); and nine studies (3259 participants) evaluated tralokinumab (75 mg Q1W, 150 mg Q1W, 300 mg Q1W, 150 mg Q2W, 300 mg Q2W, 600 mg Q2W, 300 mg Q4W, each administered by SC injection; 1/5/10 mg/kg administered by intravenous (IV) injection); all anti‐interleukin‐13 or‐4 agents were compared with placebo.\ud \ud The risk of bias was generally considered to be low or unclear (insufficient detail provided); nine studies were considered to be at high risk for attrition bias and three studies were considered to be at high risk for reporting bias.\ud \ud The following results relate to the primary outcomes. The rate of exacerbations requiring hospitalisation or emergency department (ED) visit was probably lower in participants receiving tralokinumab versus placebo (rate ratio 0.68, 95% CI 0.47 to 0.98; moderate‐certainty evidence; data available for tralokinumab (anti‐interleukin‐13) only). In participants receiving an anti‐interleukin‐13/‐4 agent, the mean improvement versus placebo in adjusted asthma quality of life questionnaire score was 0.18 units (95% CI 0.12 to 0.24; high‐certainty evidence); however, this finding was deemed not to be a clinically relevant improvement. There was likely little or no difference between groups in the proportion of patients who reported all‐cause serious adverse events (anti‐interleukin‐13/‐4 agents versus placebo, OR 0.91, 95% CI 0.76 to 1.09; moderate‐certainty evidence).\ud \ud In terms of secondary outcomes, there may be little or no difference between groups in the proportion of patients who experienced exacerbations requiring oral corticosteroids (anti‐interleukin‐13/‐4 agents versus placebo, rate ratio 0.98, 95% CI 0.72 to 1.32; low‐certainty evidence). Anti‐interleukin‐13/‐4 agents probably improve asthma control based on asthma control questionnaire score (anti‐interleukin‐13/‐4 agents versus placebo, mean difference ‐0.19; 95% CI ‐0.24 to ‐0.14); however, the magnitude of this result was deemed not to be a clinically relevant improvement. The proportion of patients experiencing any adverse event was greater in those receiving anti‐interleukin‐13/‐4 agents compared with those receiving placebo (OR 1.16, 95% CI 1.04 to 1.30; high‐certainty evidence); the most commonly reported adverse events in participants treated with anti‐interleukin‐13/‐4 agents were upper respiratory tract infection, nasopharyngitis, headache and injection site reaction. The pooled results for the exploratory outcome, the rate of exacerbations requiring oral corticosteroids (OCS) or hospitalisation or emergency department visit, may be lower in participants receiving anti‐interleukin‐13/‐4 agents versus placebo (rate ratio 0.71, 95% CI 0.65 to 0.77; low‐certainty evidence).\ud \ud Results were generally consistent across subgroups for different classes of agent (anti‐interleukin‐13 or anti‐interleukin‐4), durations of study and severity of disease. Subgroup analysis based on category of T helper 2 (TH2) inflammation suggested greater efficacy in patients with higher levels of inflammatory biomarkers (blood eosinophils, exhaled nitric oxide and serum periostin).\ud \ud Authors' conclusions: Based on the totality of the evidence, compared with placebo, anti‐interleukin‐13/‐4 agents are probably associated with a reduction in exacerbations requiring hospitalisation or ED visit, at the cost of increased adverse events, in patients with asthma. No clinically relevant improvements in health‐related quality of life or asthma control were identified. Therefore, anti‐interleukin‐13 or anti‐interleukin‐4 agents may be appropriate for adults with moderate‐to‐severe uncontrolled asthma who have not responded to other treatments. These conclusions are generally supported by moderate or high‐certainty evidence based on studies with an observation period of up to one year.

Introduction and Objectives Patients with Inducible laryngeal obstruction (ILO) and Breathing pattern disorder (BPD) can mimic severe asthma. ILO and/or BPD can co-exist in patients with severe asthma. Therefore a multidisciplinary team (MDT) approach from Respiratory Physicians, Respiratory specialist nurses, Speech and Language therapists, Physiotherapists and Psychologists to accurately diagnose and manage these conditions is essential. The MDT optimises the patient outcomes as well as reducing healthcare utilisation and costs of pharmacotherapy. Methods Eighty six patients who attended Bolton complex breathlessness clinic between Apr2017 - July 2019 were involved in this service evaluation. Hospitalisations, Emergency departmental (ED) visits, oral steroid and antibiotic courses 12 months before and after review in the clinic were analysed using paired t-testing with p value Conclusions Accurate diagnosis and appropriate interventions for ILO and BPD undertaken from Specialist Complex breathlessness clinic resulted in significant reduction of hospitalisations, booster courses of oral steroids and antibiotics in our cohort of patients.

Prior to the COVID‐19 pandemic, laryngoscopy was the mandatory gold standard for the accurate assessment and diagnosis of inducible laryngeal obstruction. However, upper airway endoscopy is considered an aerosol‐generating procedure in professional guidelines, meaning routine procedures are highly challenging and the availability of laryngoscopy is reduced. In response, we have convened a multidisciplinary panel with broad experience in managing this disease and agreed a recommended strategy for presumptive diagnosis in patients who cannot have laryngoscopy performed due to pandemic restrictions. To maintain clinical standards whilst ensuring patient safety, we discuss the importance of triage, information gathering, symptom assessment and early review of response to treatment. The consensus recommendations will also be potentially relevant to other future situations where access to laryngoscopy is restricted, although we emphasize that this investigation remains the gold standard.

Introduction The differential diagnosis of refractory breathlessness can be challenging, involving a systematic assessment of potential causes and aggravating co-morbidities. The index of suspicion for referral for specialist assessment of conditions such as Inducible Laryngeal Obstruction (Ilo) may be heightened using available clinical assessment tools, for example, the Inspiratory arm of the flow volume loop (FVL). Sterner (2009) found Ilo to be the most common diagnosis in patients with a consistently abnormal inspiratory loop. Morris & Christopher (2013) found 52% of patients with Ilo had flattened inspiratory loop. The current gold standard for objectively assessing for Ilo is Laryngoscopy. Aims and objectives To investigate the presence of an abnormal inspiratory FVL in a sample of patients with symptoms of breathlessness, and to analyse whether this is a predictor of specific causes of breathlessness. Methods Patient notes and FVL results were reviewed according to characteristic abnormalities of the inspiratory curve (flattened, absent and truncated) for people referred to a tertiary airways service for symptoms of breathlessness over a 22 month period. Assessment information was collated for patients (n=324) diagnosed with asthma, Ilo or both. Patient demographics and detailed assessment information were compared across these groups to look for potential patterns and predictors. Results 59% of patients with Ilo (with or without asthma) had an abnormal inspiratory FVL, compared to 42% of patients without Ilo. For patients with Ilo as their sole diagnosis, 62% had an abnormal FVL. A chi-square analysis showed that an abnormal inspiratory FVL was significantly more common in patients with a diagnosis of Ilo (χ2= 4.47; p≤0.05) compared to patients without. A binary logistic regression assessed the relationship between an abnormal inspiratory FVL and Ilo diagnosis. The model was significant (χ 2 =5.1 (1, N=324) p=0.02) indicating that FVL was a significant predictor of Ilo, and odds ratios suggested that patients with Ilo were twice as likely to have an abnormal loop. Conclusions In patients with breathlessness symptoms that are refractory to optimal medical treatment, observation of the FVL may indicate the potential for further specialist assessment for Ilo with provocation videolaryngoscopy.

Introduction Symptoms of breathlessness in people referred to a Tertiary Airways and Severe Asthma service may be due to a variety of treatable conditions, including asthma, inducible laryngeal obstruction (Ilo) and breathing pattern disorder (BPD). Previous research has shown overlap between asthma and Ilo (Low et al, 2011), and between asthma and BPD (Boulding et al., 2016). In clinical practice, overlap between Ilo and BPD is also common, but this has not been consistently shown in research. Aims and objectives To explore the incidence of Ilo, asthma and BPD and the overlap between these conditions in a sample of patients referred to a tertiary airways service, and to investigate patient characteristics associated with each condition. Methods Patient notes were reviewed for people referred to a tertiary airways service for symptoms of breathlessness over an 18 month period. Assessment information was collated for patients (n=306) diagnosed with asthma, Ilo and/or BPD. Results Of the 306 patients, 235 (77%) were diagnosed with Ilo via videolaryngoscopy, 177 (58%) were diagnosed with asthma, and 83 (27%) were diagnosed with BPD. There was significant overlap between the three conditions, with 186 patients (52%) having at least two conditions. The most common overlap was between asthma and Ilo (30% of patients), followed by Ilo and BPD (11%). In contrast, only 3% of patients in this sample had both asthma and BPD. All three conditions were seen in 9% of patients. A visual representation of overlap is presented in figure 1 below: Of the three conditions, Ilo most commonly co-occurred with asthma, whilst BPD most commonly co-occurred with Ilo. When BPD co-occurred with asthma, this was most commonly seen together with Ilo. Conclusions This study showed high levels of overlap between conditions that can contribute to symptoms of breathlessness. This emphasises the importance of a multi-professional assessment and optimisation of comorbid treatable traits, such as Ilo and BPD. It may also serve as a reminder for a timely referral for specialist assessment and management of treatable traits to avoid the potential of morbidity, increased healthcare utilisation and over-medication in severe and difficult to treat asthma.

BACKGROUND: Frequent exacerbations are an important cause of morbidity in patients with severe asthma.OBJECTIVE: Our aim was to identify factors associated with frequent exacerbations in a large well-characterized severe asthma population and determine whether factors differed in patients treated with and without maintenance oral corticosteroids (OCS).METHODS: Adults with severe asthma from specialized asthma centers across the United Kingdom were recruited to the UK Severe Asthma Registry. Demography, comorbidities and physiological measurements were collected. We conducted univariable and multivariable logistic regression analyses to identify factors associated with frequent exacerbations, defined as 3 or more exacerbations treated with high-dose systemic corticosteroids in the past year.RESULTS: Of 1,592 patients with severe asthma from the UK Severe Asthma Registry, 1,137 (71%) were frequent exacerbators and 833 (52%) were on maintenance OCS. The frequent exacerbators were more likely to be ex-smokers, have gastroesophageal reflux disease, higher Asthma Control Questionnaire-6 (ACQ-6) score, and higher blood eosinophilia. Multivariable regression analyses showed ACQ-6 score greater than 1.5 (odds ratio [OR] 4.25; P < .001), past smoking history (OR 1.55; P = .024), and fractional exhaled nitric oxide greater than 50ppb (OR 1.54; P = .044) were independently associated with frequent exacerbations. Past smoking history correlated with frequent exacerbations only in patients on maintenance OCS (OR 2.25; P = .004), whereas ACQ-6 score greater than 1.5 was independently associated with frequent exacerbations in those treated with and without maintenance OCS (OR 2.74; P = .017 and OR 6.42; P < .001, respectively).CONCLUSIONS: Several factors were associated with frequent exacerbations in a large UK severe asthma registry population. High ACQ-6 score had the strongest association with frequent exacerbations irrespective of maintenance OCS status.

BACKGROUND: Cough both protects and clears the airway. Cough has three phases: breathing in (inspiration), closure of the glottis, and a forced expiratory effort. Chronic cough has a negative, far‐reaching impact on quality of life. Few effective medical treatments for individuals with unexplained (idiopathic/refractory) chronic cough (UCC) are known. For this group, current guidelines advocate the use of gabapentin. Speech and language therapy (SLT) has been considered as a non‐pharmacological option for managing UCC without the risks and side effects associated with pharmacological agents, and this review considers the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of SLT in this context. OBJECTIVES: To evaluate the effectiveness of speech and language therapy for treatment of people with unexplained (idiopathic/refractory) chronic cough. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, trials registries, and reference lists of included studies. Our most recent search was 8 February 2019. SELECTION CRITERIA: We included RCTs in which participants had a diagnosis of UCC having undergone a full diagnostic workup to exclude an underlying cause, as per published guidelines or local protocols, and where the intervention included speech and language therapy techniques for UCC. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of 94 records. Two clinical trials, represented in 10 study reports, met our predefined inclusion criteria. Two review authors independently assessed risk of bias for each study and extracted outcome data. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs) or geometric mean differences. We used standard methods recommended by Cochrane. Our primary outcomes were health‐related quality of life (HRQoL) and serious adverse events (SAEs). MAIN RESULTS: We found two studies involving 162 adults that met our inclusion criteria. Neither of the two studies included children. The duration of treatment and length of sessions varied between studies from four sessions delivered weekly, to four sessions over two months. Similarly, length of sessions varied slightly from one 60‐minute session and three 45‐minute sessions to four 30‐minute sessions. The control interventions were healthy lifestyle advice in both studies. One study contributed HRQoL data, using the Leicester Cough Questionnaire (LCQ), and we judged the quality of the evidence to be low using the GRADE approach. Data were reported as between‐group difference from baseline to four weeks (MD 1.53, 95% confidence interval (CI) 0.21 to 2.85; participants = 71), revealing a statistically significant benefit for people receiving a physiotherapy and speech and language therapy intervention (PSALTI) versus control. However, the difference between PSALTI and control was not observed between week four and three months. The same study provided information on SAEs, and there were no SAEs in either the PSALTI or control arms. Using the GRADE approach we judged the quality of evidence for this outcome to be low. Data were also available for our prespecified secondary outcomes. In each case data were provided by only one study, therefore there were no opportunities for aggregation; we judged the quality of this evidence to be low for each outcome. A significant difference favouring therapy was demonstrated for: objective cough counts (ratio for mean coughs per hour on treatment was 59% (95% CI 37% to 95%) relative to control; participants = 71); symptom score (MD 9.80, 95% CI 4.50 to 15.10; participants = 87); and clinical improvement as defined by trialists (OR 48.13, 95% CI 13.53 to 171.25; participants = 87). There was no significant difference between therapy and control regarding subjective measures of cough (MD on visual analogue scale of cough severity: −9.72, 95% CI −20.80 to 1.36; participants = 71) and cough reflex sensitivity (capsaicin concentration to induce five coughs: 1.11 (95% CI 0.80 to 1.54; participants = 49) times higher on treatment than on control). One study reported data on adverse events, and there were no adverse events reported in either the therapy or control arms of the study. AUTHORS' CONCLUSIONS: The paucity of data in this review highlights the need for more controlled trial data examining the efficacy of SLT interventions in the management of UCC. Although a large number of studies were found in the initial search as per protocol, we could include only two studies in the review. In addition, this review highlights that endpoints vary between published studies. The improvements in HRQoL (LCQ) and reduction in 24‐hour cough frequency seen with the PSALTI intervention were statistically significant but short‐lived, with the between‐group difference lasting up to four weeks only. Further studies are required to replicate these findings and to investigate the effects of SLT interventions over time. It is clear that SLT interventions vary between studies. Further research is needed to understand which aspects of SLT interventions are most effective in reducing cough (both objective cough frequency and subjective measures of cough) and improving HRQoL. We consider these endpoints to be clinically important. It is also important for future studies to report information on adverse events. Because of the paucity of data, we can draw no robust conclusions regarding the efficacy of SLT interventions for improving outcomes in unexplained chronic cough. Our review identifies the need for further high‐quality research, with comparable endpoints to inform robust conclusions.

Introduction Inducible laryngeal obstruction (Ilo) is defined as an inappropriate adduction of the larynx on inspiration. Speech and language therapy (SLT) is viewed as the cornerstone of treatment of Ilo. Clinical consensus indicates that the optimal number of SLT sessions is between four and six. Our previous research has shown that% Forced Vital Capacity (% FVC) is a reliable predictor of Ilo in patients with breathlessness referred to our tertiary airways service (ERS Congress, 2017). In our current research, we aimed to investigate whether% FVC and other patient factors can predict improvement in Ilo symptoms following SLT intervention. Methods Data were analysed from 59 patients presenting to our service with symptoms of breathlessness. All had a diagnosis of Ilo via videolaryngoscopy and received SLT treatment. Analyses investigated relationships between improvement on Ilo symptoms and% FVC as well as other patient details. The VCDQ, a validated questionnaire measuring Ilo symptoms and response to SLT, was used pre- and post-therapy to assess improvement. Results VCDQ scores decreased following SLT for forty (68%) patients, demonstrating improvement. Of patients who improved, the mean number of SLT sessions was four, with the majority (60%) attending three to five sessions. No relationships were found between post-SLT improvement on the VCDQ and patient factors including age, gender, and potential co-morbidities such as asthma, GORD and rhinitis. There was a significant relationship between% FVC and VCDQ improvement (r=0.346, n=51, p=0.01). A binary logistic regression assessed the impact of% FVC on VCDQ improvement. The model was significant (χ 2=6.337 (1, n=59) p=0.012), and explained between 12% and 16% of the variance in improvement, correctly classifying 69% of cases. Patients with higher% FVC were five times more likely to show improvement on the VCDQ following SLT. Conclusions In line with clinical consensus, 3 to 5 sessions of SLT were sufficient to lead to improvements on VCDQ scores for the majority of patients. Patient demographic data did not predict improvements in Ilo following SLT, however% FVC may be a predictor of good treatment response to SLT for Ilo.

Background Asthma is a heterogenous disease characterised by chronic airway inflammation and variable airflow obstruction. We use surrogate markers of inflammation and evidence of atopy to help aid the diagnosis and monitor disease. The aim of this project was to explore the relationship of markers of eosinophilia to asthma symptoms in new patients presenting to difficult asthma clinics. To date, there is very limited data linking eosinophilic inflammation and the severity of asthma symptoms. Objective To investigate the relationship between sputum and blood eosinophilia, exhaled nitric oxide and asthma symptoms as measured using asthma control test (ACT). Method This was a prospective cohort study. Data was collected from patients attending difficult asthma clinics fulfilling the following criteria: New patients, a diagnosis of asthma and a complete data set from initial clinic work-up (FeNO, Blood and sputum eosinophils, ACT on the same day). Patients were excluded if they were on oral steroids at the time of presentation. Results A total of 25 patients were included in the study. The ratio of female to male was 4:1. The mean age of the patients was 39. All patients were step 4+of the BTS asthma management. The was no correlation between any of the markers of eosinophilic inflammation and ACT scores. Discussion The lack of robust data looking into the relationship between markers of eosinophilia and symptom control poses a question as to whether we are measuring the right outcomes. With the known adverse effects of steroids, a degree of certainty that driving down markers of eosinophilia provides benefit to the patient is crucial. Asthma is such a clinical disease with a broad spectrum of symptoms. Therefore, the patients’ subjective level of symptom control should be paramount in managing the disease and tailoring their treatment. Work is ongoing to expand across multiple sites to explore this further.

Background The 2013 NHS England service specifications for severe asthma aimed to develop a limited number of high volume specialist hub centres. These centres would have a multi-disciplinary team (MDT) working to improve patient outcomes and reduce healthcare costs. In the North West we have developed a networked approach to specialised severe asthma services; the first Operation Delivery Network (ODN) for a chronic disease. Representatives from 11 NHS Trusts and a central hub undertake a monthly virtual MDT meeting with physicians, nurses, pharmacists, physiotherapists, clinical psychologists, speech and language therapists, and radiologists represented. All patients being considered for specialised treatments undergo MDT discussion for consensus approval of treatment. Aim To summarise the experience and case-mix encountered during the first 4 years of operation of our regional virtual severe asthma MDT. Methods We reviewed all cases discussed at the MDT between January 2015 and June 2018. Proformas are submitted via nhs.net accounts and data entered into a central database by MDT coordinator. All biologic proformas are pre-assessed by the ODN Pharmacist and Specialist nurse to ensure compliance with the NICE guidelines. Results During this period 41 meetings were held, with 933 cases discussed. Omalizumab was approved in 78% of cases submitted, BT in 39%, mepolizumab in 84% and reslizumab in 94%. The most common reasons for non-approval of omalizumab were insufficient steroid requirement, poor adherence and lack of allergy to perennial allergen. The most common reasons for non-approval to mepolizumab and reslizumab were poor adherence and lack of evidence of raised eosinophil levels within the stated 12 month period. The potential 5 year cost saving of high cost therapies not approved at the Central hub is estimated to be £7.5 million. Conclusion A multi-site virtual severe asthma MDT meeting facilitates expert care across a wide geographical area, ensures governance in the use of novel and expensive therapies, strengthens collaboration and aims to improve patient care. Reference Ryan D, et al. The UK’s largest severe asthma multidisciplinary team meeting; experience from the first 18 months. ThoraxDec 2016:71(3);A5.

Introduction Inducible laryngeal obstruction (Ilo) is defined as inappropriate adduction of the vocal cords on inspiration. Currently, there is no agreed aetiology for Ilo described in literature. Exploration of relationships between patient-reported onset factors and Ilo classification on video laryngoscopy may further understanding of the nature and causes of Ilo. Previous research by our Tertiary Airways service described patient-reported Ilo onset factors in a five category taxonomy: Respiratory, Medical, Psychological, Irritant and Exercise (BTS Winter Meeting, 2017), and classified laryngeal presentation of Ilo on videolaryngoscopy according to the ERS/ACCP (2014) International Consensus nomenclature (BTS Winter Meeting, 2017), including speed of initiation of Ilo symptoms (i.e. fast or slow). Aims and objectives To explore possible relationships between Ilo onset factors and observed speed of Ilo initiation as seen on laryngoscopy. Methods Self-reported Ilo onset factors for 102 patients were compared with videolaryngoscopy classification of initiation timing of Ilo. Results There were significant relationships between Ilo initiation speed and certain onset factors. ‘Slow’ initiation was associated with Medical (e.g. surgery, medication) onset factors (χ 2=4.627, df=1, p=0.031). ‘Fast’ initiation was associated with Respiratory (e.g. Asthma, chest infection) onset factors (χ 2=7.976; df=1; p=0.005). A binary logistic regression assessed the impact of these onset factors on initiation speed. The model was significant (χ2=12 (2, n=102) p=0.002), and explained between 11% and 16% of the variance in onset timing, correctly classifying 74% of cases. Patients with Medical onset factors were five times more likely to have fast Ilo initiation, whilst patients with Respiratory onset factors were two and a half time as likely to have slow Ilo initiation. Conclusions Comparing Ilo onset factors with initiation speed highlighted associations which may help to elucidate relationships between onset factors and subsequent Ilo presentation. The ‘slow’ pattern associated with Medical onset factors may suggest a steady-state physiological or neuropathic aetiology, whereas the ‘fast’ pattern, associated with Respiratory onset factors may indicate mechanisms related to airway hyper-responsiveness.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of anti-interleukin-13 or anti-interleukin-4 agents, compared with placebo, anti-Immunoglobulin E agents, or anti-interleukin-5 agents, for the treatment of children, adolescents, or adults with asthma.

Introduction and Objectives Inducible Laryngeal Obstruction (Ilo) is poorly understood, in terms of aetiology and onset by patients and clinicians. Patients presenting to our Tertiary Airways service commonly seek an understanding of the causes and triggers of their Ilo episodes. This study aims to develop a taxonomy of categories of patient-reported onset factors for Ilo from a sample of patients with confirmed Ilo on laryngoscopy, referred to our service. Method Within a nine month period, 103 patients referred to the Airways service (76% female, 24% male; age range 15–86 years (median=52)) with endoscopically-confirmed Ilo were asked to report historical factors contemporaneous with the initial onset of Ilo symptoms. A retrospective analysis of patient notes was also conducted to identify co-morbidities and additional onset factors. Single or multiple onset factors for each patient were collected, which were coded into initial themes. From these themes, second-order onset categories were developed which incorporated factors reported by all participants. Results Thirteen initial onset themes were developed. These included psychological factors (25% of patients), upper respiratory tract infections (23%), reflux (17%), chest infections (14%), medical conditions (12%) and surgery (10%). These were then refined into a taxonomy of five categories of onset factors: Respiratory Tract Infections and Viruses (40% of patients) Underlying Medical Conditions, e.g., rhinitis with post nasal drip, reflux (34%) Psychological difficulties (25%) Irritants, e.g., medication (23%) Exercise (7%) Only one patient had onset factors in multiple categories, indicating that these categories are largely independent of each other. The prevalence of certain onset factors was mediated to some degree by age, e.g., medical conditions were more frequent factors for older participants, whereas exercise was a more common factor in younger participants. Conclusions This study demonstrates patient-reported onset factors for Ilo can be usefully translated into a detailed taxonomy based on specific conditions/triggers. This understanding may be useful in furthering our understanding, both of common trigger and onset factors that can be communicated to patients, and may help to inform therapeutic interventions aimed at the active self-management of Ilo.

Introduction: Home mechanical ventilation (HMV) is a recognised evidence-based intervention for patients in chronic respiratory failure (CRF). However there is a paucity of evidence on the adherence to this treatment. Modern technological advances in healthcare have allowed the exploration of remote monitoring. This study examined the adherence of HMV and evaluated the clinical outcomes associated with adherence in a variety of patient populations. Methods: A retrospective study was carried out between May to June 2016. Adherence data was downloaded through remote monitoring on 62 patients. Primary outcomes included changes in blood gases at 3 and 6 months, and hospital admissions 12 months pre- and post-ventilation. Qualitative outcomes were obtained through a questionnaire conducted via telephone interviews. Results: Patients undertaking remote monitoring of HMV demonstrated an adherence rate of 90.3% (mean [SD] = 7h17min [2h53min]). No significant difference in adherence was found between patients of different aetiologies. The blood gases improved significantly at 3 months compared to baseline (p Conclusion(s): This study has demonstrated that contrary to existing evidence, the adherence to HMV was extremely good across all diseases and we hypothesise remote monitoring may play a role in this increased adherence.

Background: Differential diagnosis of asthma and VCD can be challenging. Previous research (e.g. Newman, Mason & Schmaling, 1995) has suggested a number of risk factors for VCD. Aims and Objectives: To compare co-morbidity characteristics of patients with complex breathlessness referred to a tertiary Airways service. To analyse whether specific factors are associated with an increased likelihood of confirming a diagnosis of VCD. Methods: Descriptive and correlational statistics were used to analyse patient characteristics and co-morbid factors in a sample of 155 patients, of whom 83 had confirmed VCD. A logistic regression analysis was used to identify significant predictor variables for VCD. Results: The majority of patients diagnosed with VCD were female (72%). A high proportion of these patients had reflux (49%), rhinitis (41%) and/or co-morbid asthma (33%). Partial correlations showed that Forced Vital Capacity percent (FVC%) within lung function tests was significantly correlated with a diagnosis of VCD (rs= 0.329, n=73, p=0.005). Age, gender, reflux, rhinitis and Forced Expiratory Volume 1 percent were not significantly correlated with VCD diagnosis. A logistic regression was performed to assess the impact of FVC% on diagnosis of VCD. The model was significant: χ 2 (1, N=73) =10.38, p=0.001. The model explained between 13.3% and 21.8% of the variance in VCD diagnosis, and correctly classified 83.6% of cases. Conclusions: A number of possible co-morbid factors were identified. Lung function, as described by FVC%, was found to be a significant predictor for VCD diagnosis in a sample of patients with complex breathlessness. This measure may be useful in the differential diagnosis of asthma and VCD.

Background: There is strong emerging evidence on the devastating effect of anthropogenic climate change on lung health. In England, the NHS accounts for 30% of the public sector carbon footprint, with patient travel being accountable for 8% of overall travel (17%). Purpose: The Lancashire and South Cumbria Long Term Ventilation Service (LSCLTVS) invested in a remote monitoring system (EncoreAnywhere TM) for patient9s dependant on home mechanical ventilation. This study investigated the potential impact on carbon footprint within our regional service and if any benefits were seen as a secondary impact of remote motioning. Methods: Over a 3 month time period 138 telephone consultations were recieved by the LSCLTVS. Patients or carers that called reporting deterioration in a clinical condition that could not be rectified over the telephone were identified. A ventilator review was indicated in 29 patients which would normally necessitate either a hospital clinic visit or home consultation. Results: In a 3 month time period 29 return journeys were prevented through the use of remote monitoring. This equated to 1029.3km (623miles), 249kgCO2e (0.24tCO2e)*saved over 28 hours in commuting time and £255 in mileage costs (40p per mile). It also had a positive impact on patient experience and no hospital admissions or clinic visits were necessary. *Emission factors from DEFRA 2012 show for an average petrol car the value is 0.24234kgCO2e per km Conclusion: The use of remote monitoring within the LSCLTVS has reduced the carbon footprint of the service on average 6.6kgCO2e per patient. Patients also reported improved satisfaction and compliance

Introduction: Our specialist multidisciplinary Airways Service manages patients with vocal cord dysfunction (VCD), principally with respiratory speech and language therapy (rSLT). The VCDQ (Fowler 2015) is the first validated questionnaire for use in VCD, with 12 statements covering a broad range of impacts and symptoms. Aim: To determine the effect of treatment on each VCDQ statement and establish where rSLT has most impact. Methods: We included retrospective (Sept 2015 - Jan 2016) data from patients who had i) endoscopically diagnosed VCD; ii) completed rSLT treatment; and iii) pre & post VCDQ data. Results: Sixteen patients had full data sets. All patients reported clinical improvements. There was overall improvement in VCDQ from median (range) 46 (20-60) pre to 38 (12-50) post rSLT (Wilcoxon9s signed rank p=0.017). Of the 12 statements, items 10 (I am frustrated that my symptoms have not been understood correctly) and 12 (the attacks impact on my social life) improved the most [3.0 (1-5) to 1.0 (1-4), p=0.001] and [4.0 (1-5) to 3.0 (1-5), p=0.001 respectively]. Improvements in item 2 (I feel I can9t get breath past a certain point in my throat/upper chest because of restriction) and 3 (my breathlessness is usually worse when breathing in) were nearly statistically significant [4.0 (1-5) to 3.0 (1-5), p=0.062] and [4.0 (1-5) to 3.0 (1-5), p=0.077 respectively]. Conclusions: Management of VCD with rSLT is beneficial. This preliminary analysis suggests it has the most significant impact on psychosocial issues and may also have physical benefits for symptoms. We acknowledge larger numbers are required to guide future therapeutic refinements.

Mutations in nuclear genes involved in the maintenance of mitochondrial DNA (mtDNA) are associated with an extensive spectrum of clinical phenotypes, manifesting as either mtDNA depletion syndromes or multiple mtDNA deletion disorders.(1.)

Rationale: Some patients with severe asthma are immunologically sensitized tooneormorefungi, a clinical entity categorized as severe asthma with fungal sensitization (SAFS). It is not known whether SAFS responds to antifungal therapy. Objectives: To evaluate the response of SAFS to oral itraconazole. Methods: Patients with severe asthma sensitized to at least one of seven fungi by skin prick or specific IgE testingwererecruited. Allhad total IgE less than 1,000 IU/ml and negative Aspergillus precipitins. They were treated with oral itraconazole (200 mg twice daily) or placebo for 32 weeks, with follow-up for 16 weeks. Measurements and Main Results: The primary end point was change in the Asthma Quality of Life Questionnaire (AQLQ) score, with rhinitis score, total IgE, and respiratory function as secondary end points. Fifty-eight patients were enrolled, of whom 41% had been hospitalized in the previous year. BaselinemeanAQLQscorewas4.13 (range, 1-7). At 32 weeks, the improvement (95% confidence interval) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with a -0.01 (-0.43, 0.42) change in the placebo group (P = 0.014). Rhinitis score improved (-0.43) in the antifungal, and deteriorated (+0.17) in the placebo group (P = 0.013). Morning peak flow improved (20.8 L/minute, P = 0.028) in the antifungal group. Total serum IgE decreased in the antifungal group(-51 IU/ml) but increased in placebo group (+30 IU/ml) (P = 0.001). No severe adverse events were observed, but seven patients developed adverse events requiring discontinuation, five in the antifungal group. Conclusions: SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients. Clinical trial registeredwithwww.controlled-trials.com (ISRCTN61552714).

Introduction: Our tertiary airways service offers specialist speech and language therapy (SLT) for vocal cord dysfunction and refractory chronic cough, face-to-face or via Skype™. Analysis of the Skype™ pilot suggested that the response to therapy was equivalent to face-to-face.We have reviewed patient satisfaction with both methods. Methods: A tailored patient satisfaction questionnaire was sent to all patients discharged from respiratory SLT between January and June 2014. Patients were invited to complete the questionnaire anonymously and return by post in a pre-paid envelope. Results: Twenty-six of 61 questionnaires were returned (response rate 43%). Patient satisfaction was very favourable with 96% pleased with the overall service provided. Further, 96% were happy to have engaged with SLT as a treatment option and felt they had been given enough information about why they had been referred. We compared data from those receiving traditional clinician-facing appointments (n=18) with those having virtual consultations (n=8). Approximately a third found traditional clinic appointment times inconvenient compared to 0% over Skype™. Of the Skype™ cohort 100% patient satisfaction was reported for all questions compared with 84% from the traditional treatment delivery mode. Conclusions: Listening to patients9 views is essential to providing a patient -centred health service. Identifying such a favourable patient satisfaction response emphasises the importance of respiratory SLT. Based on the feedback received virtual SLT consultations are now routinely offered to patients who struggle to attend traditional clinic appointments.

Laryngopharyngeal reflux (LPR) can induce laryngeal hyper-responsiveness, a unifying feature underlying chronic cough and vocal cord dysfunction. The diagnosis of LPR currently relies on invasive oesophageal pH impedance testing. We compared symptoms, laryngeal signs and salivary pepsin as potential diagnostic methods for identifying LPR in patients with upper airway symptoms.Symptoms were assessed using the Reflux Symptom Index (RSI) and signs of laryngeal inflammation quantified using the Reflux Finding Score (RFS) during laryngoscopy. Saliva samples were analysed for the presence of pepsin. A sub-group of patients with severe symptoms and signs of LPR were investigated with oesophageal pH monitoring and impedance study.Seventy eight patients with chronic cough and/or suspected vocal cord dysfunction were recruited, mean (SD) age, 54.6 (15.6) years. The majority (87%) had significant symptoms of reflux (RSI13). There were clinical signs of LPR (RFS7) in 51% of cases. Pepsin was detected in the saliva of 63% of subjects and 78% of those with a high RFS. Salivary pepsin had a sensitivity of 78% and specificity of 53% for predicting a high RFS. There was a correlation between the RSI and RFS (r = 0.51, p 0.001) and between the severity of laryngeal inflammation and the concentration of pepsin (r = 0.28, p = 0.01). All cases investigated with pH-impedance study had objective evidence of proximal reflux.Salivary pepsin may be used as a screening adjunct to supplement the RFS in the clinical workup of patients with extra-oesophageal symptoms and upper respiratory tract presentations of reflux.

BACKGROUND:\ud Vocal Cord Dysfunction (VCD) typically involves abnormal adduction of the vocal cords during inspiration, mimics the symptoms of asthma and leads to the prescription of ineffective medications.\ud \ud OBJECTIVE:\ud We aimed to develop a clinical tool to monitor symptoms and response to treatment in confirmed VCD.\ud \ud METHODS:\ud We collated symptoms of VCD from focus groups comprising patients and healthcare-professionals; phrases describing these symptoms were assessed for face validity and internal correlation, and rated for importance. The resultant 12 item questionnaire (VCDQ) rated the impact of each on a 5-point Likert scale (total score range 12 to 60), and was tested for reliability, concurrent validity and performance in 31 patients with endoscopically confirmed VCD (± asthma), 29 asthmatics with no history of VCD, and 14 healthy controls. We assessed response to speech and language therapy and the minimal important difference by measuring the VCDQ pre- and post- therapy in a 20 new patients.\ud \ud RESULTS:\ud The VCDQ had excellent test-retest reliability, and differentiated VCD versus healthy (Mann-Whitney test: z = -5.390, P < 0.001) and asthma (z = -5.730, p < 0.001). All patients improved post-therapy, assessed both by a global rating of change score (GRCS) and by the VCDQ [median (IQR) score pre-therapy 50.5 (48.0 - 54.8), post therapy 35.0 (29.3 - 41.8), p < 0.001]. The minimal important difference in the VCDQ associated with a rating of "minimally better" on the GRCS was 4 points.\ud \ud CONCLUSIONS AND CLINICAL RELEVANCE:\ud The VCDQ is a valid and responsive tool suitable for measuring changes in symptoms in patients with VCD. It also gives insight into which symptoms are important to patients, and could guide future therapy refinements. Future assessments of novel therapies for this condition should use an appropriately validated tool such as the VCDQ to measure response.

Background Patients that have chronic respiratory disease (CRD) and breathing pattern disorders (BPD) have a higher prevalence of anxiety and depression than the general population. These patients have worse respiratory health outcomes and in addition, their psychological problems are often left undiagnosed and untreated. Little is known about how anxiety and depression varies between CRD and BPD. Methods This prospective study involved screening patients attending secondary and tertiary respiratory clinics over an eight-week period. Patients were asked to complete the Hospital Anxiety and Depression Scale (HADS), Short Form-12 (SF-12) and St. George’s Respiratory Questionnaire (SGRQ). Demographical data and spirometry were also collected. Our primary outcome measure was the difference in these scores between patients with CRD (asthma, bronchiectasis and chronic obstructive pulmonary disease) compared to BPD (vocal cord dysfunction and dysfunctional breathing). Results 43 patients (21 with CRD and 22 with BPD) completed questionnaires; mean (SD) age 55 (17) yrs, 32 female. The overall prevalence of borderline anxiety was 17% and clinically significant anxiety 37%. The overall prevalence of borderline depression was 15% and clinically significant depression 29%. Of the patients with CRD, 29% had anxiety and 29% depression. In the BPD cohort, anxiety and depression were found in 45% and 30% of patients respectively. The difference between these groups was not statistically significant (anx: P = 0 .42; dep P = 0 .19). Independent predictors for anxiety and depression were higher SGRQ (anx: P = 0 .001; dep: P < 0 .0001), lower SF-12 Mental (anx: P < 0 .0001; dep: P < 0 .0001) and Physical (anx: P = 0 .042; dep: P = 0 .0027) Health Composite Scores, and lower FEV 1 % predicted (anx: P = 0 .0043; dep: P = 0 .016). Conclusions Anxiety and depression are present in a significant numbers of individuals in both CRD and BPD, with no difference between these groups, so efforts should be made to screen for psychological problems in patients with both CRD and BPD. Worse respiratory function and more symptoms are important contributing factors to patients’ risk of anxiety and depression.

Introduction There is strong emerging evidence on the devastating effect of anthropogenic climate change on lung health. In England, the NHS accounts for 30% of the public sector carbon footprint, with patient travel being accountable for 8% of overall travel (17%). The climate change act (2008) resulted in the government and NHS committing to an 80% reduction in carbon emissions by 2050. Methods There are many studies detailed the benefit of telemonitoring in reducing carbon footprint within NHS services. Within the Lancashire and South Cumbria Long Term Ventilation Service (LSCLTVS) we have invested in a ventilator remote monitoring system (EncoreAnywhereTM). Over a 3 month time period we analysed the telephone consultations of all 138 patients under the care of the LSCLTVS (80 patients on remote monitoring systems). Patients or carers that called reporting deterioration in a clinical condition that could not be rectified over the telephone were identified. The normal intervention that would follow would be a visit from the GP or community respiratory team, hospital admission, clinic visit or home visit from the ventilation team. A ventilator review was indicated in 29 patients which would normally necessitate either a clinic visit to Royal Preston Hospital or a consultation at home. However as these patients had remote ventilator monitoring we were able to review data and make changes remotely. Results In a 3 month time period 29 return journeys were prevented through the use of remote monitoring. This equated to 1029.3 km (623 miles), 249 kgCO2e (0.24 t CO2e)*saved over 28 hours in commuting time and £255 in mileage costs (40 p per mile). It also had a positive impact on patient experience and no hospital admissions or clinic visits were necessary after remote consultation. 62% (n = 18) patients required use of rescue packs including antibiotics and mucolytics as well as remote ventilator changes. *Emission factors from DEFRA 2012 show for an average petrol car the value is 0.24234 kg CO2e per km Discussion The use of remote monitoring within the LSCLTVS has reduced the carbon footprint of the service on average 6.6 kg CO2e per patient. Patients also reported improved satisfaction and compliance.

Background and aim Many patients presenting to our complex breathlessness service appear to have breathing pattern disorders (BPDs). When suspected clinically, they are referred to a specialist respiratory physiotherapist for assessment and treatment. Here we describe the prevalence of identifiable breathing patterns and their clinical characteristics Methodology We performed a retrospective review of our clinical database including patients seen for initial physiotherapy assessment between December 2015 and June 2016. Patients underwent a standardised diagnostic assessment (clinical history, physiotherapy assessment, lung function and Nijmegan questionnaire). Results Data from 43 patients with confirmed BPD were included, 77% female, mean age 58 yrs. Relevant respiratory comorbidities included chronic cough (33%), asthma (30%) and vocal cord dysfunction (30%), with no comorbidity in 23%. Other associated conditions included musculoskeletal conditions (47%), chronic pain (44%), obesity (44%), nasal blockage (42%) and anxiety (31%). Four categories of breathing patterns were identified: thoracic dominant (58%), irregular/crescendo (51%), forced abdominal expiration (30%), and thoraco-abdominal asynchrony (2%). More than one BPD was seen in 35% of patients; only forced abdominal expiration and thoracic dominant didn’t co-exist. Conversely all pattern types could be found in isolation, although irregular/crescendo was more likely to co-exist with another pattern type. Conclusion Four separate breathing pattern types were identified, in isolation or in combination. Although anxiety was fairly common, many other associated disease and conditions were seen, especially relating to biomechanical factors. This preliminary data may enable clinicians to identify breathing pattern types, lead to the development of targeted treatment options and promote screening of particular conditions associated with BPD.

Introduction Home mechanical ventilation (HMV) is a recognised evidence-based intervention for patients in chronic respiratory failure (CRF). However there is a paucity of evidence on the adherence to this treatment. This study examined the adherence of HMV and evaluated the clinical outcomes associated with adherence in a variety of patient populations – namely neuromuscular disease, chest wall disease, obesity hypoventilation syndrome and chronic obstructive pulmonary disease (COPD). Methods A retrospective study was carried out between May to June 2016. Adherence data was downloaded through remote monitoring. Primary outcomes included changes in blood gases at 3 and 6 months, and hospital admissions 12 months pre- and post-ventilation. Qualitative outcomes were obtained through a questionnaire conducted via telephone interviews. Results 62 patients were included in this study. Patients undertaking remote monitoring of HMV demonstrated an adherence rate of 90.3%, defined as more than 4 hours of ventilator use/night (mean [SD] = 7h 17min [2h 53min]). No significant difference in adherence was found between patients of different aetiologies. The blood gases improved significantly at 3 months compared to baseline (p Conclusion This study has demonstrated that contrary to existing evidence, the adherence to HMV was extremely good across all diseases. Remote monitoring may play a role in this increased adherence. Although HMV contributed to improvements in blood gases at 3 months, there was a universal trend for these parameters to return to baseline at 6 months in all disease states despite good adherence. Our data therefore suggests that early follow-up is essential to detect deterioration and support the need for palliation. Nevertheless HMV remains an effective treatment to reduce hospital admissions and improve quality of life, if patients are adherent to the intervention.

Background Severe asthma comprises 5% of all asthma, but over 50% of the asthma healthcare burden. With multi-disciplinary team (MDT) working there is potential to improve patient outcomes and reduce healthcare costs. In 2013 NHS England produced service specifications for severe asthma aiming to develop a limited number of high volume specialist centres. In the North West we have developed a networked approach to specialised severe asthma services; the first Operation Delivery Network for a chronic disease. Representatives from 11 NHS Trusts and a central hub undertake a monthly virtual MDT meeting, with physicians, nurses, physiotherapists, clinical psychologists, speech and language therapists, allergists, pathologists and radiologists represented. All patients being considered for specialised treatments undergo MDT discussion for consensus approval of treatment. Aim To summarise the experience and case-mix encountered during the first 18 months of operation of our regional virtual severe asthma MDT Methods We reviewed all cases discussed at the MDT between January 2015 and June 2016. Cases were submitted online via nhs.net accounts, and data entered into a central database managed by two MDT coordinators for MDT discussion. Results During this period 17 meetings were held, with 208 case-submissions representing 185 patients, mean (SD) 12 (7) discussions per meeting. Indications for case submission included proposals for use of omalizumab, bronchial thermoplasty (BT), and steroid-sparing therapies, and for the discussion of patients with complex clinical issues, often managed across multiple sites. Omalizumab was approved in 81% of cases submitted, and BT in 39%, with more of the latter requiring multiple discussions (30% versus 2%) The most common reasons for non-approval of omalizumab were insufficient steroid requirement, poor adherence, and lack of allergy to a perennial allergen. Thermoplasty was not approved or listed for re-discussion for a variety of reasons, including 10 (43%) that required further investigation. Conclusion We describe our early experience of a multi-site virtual severe asthma MDT meeting facilitating expert care across a wide geographical area. This ensures governance in the use of novel and expensive severe asthma therapies, strengthens regional collaborations and ultimately aims to provide better patient care.

OBJECTIVES—To find the nature and incidence of symptoms experienced by a large sample of hospital endoscopy nurses. To find whether nurses in endoscopy units develop asthma under current working conditions in endoscopy units. To obtain analytically reliable data on exposure concentrations of glutaraldehyde (GA) vapour in endoscopy units, and to relate them to individual hygiene and work practices. To characterise any exposure-response relations between airborne GA and the occurrence of work related symptoms (WRSs). Due to the growing concern about the perceived increase in WRSs among workers regularly exposed to biocides, all of whom work within a complex multiexposure environment, a cross sectional study was designed. METHODS—Current endoscopy nurses (n=348) from 59 endoscopy units within the United Kingdom and ex-employees (who had left their job for health reasons (n=18) were surveyed. Symptom questionnaires, end of session spirometry, peak flow diaries, skin prick tests (SPTs) to latex and common aeroallergens, and measurements of total immunoglobulin E (IgE) and IgE specific to GA and latex were performed. Exposure measurements included personal airborne biocide sampling for peak (during biocide changeover) and background (endoscopy room, excluding biocide changeover) concentrations. RESULTS—All 18 ex-employees and 91.4% of the current nurses were primarily exposed to GA, the rest were exposed to a succinaldehyde-formaldehyde (SF) composite. Work related contact dermatitis was reported by 44% of current workers exposed to GA, 56.7% of those exposed to SF composite, and 44.4% of ex-employees. The prevalence of WRSs of the eyes, nose, and lower respiratory tract in current workers exposed to GA was 13.5%, 19.8%, and 8.5% respectively and 50%, 61.1%, and 66.6% in the ex-employees. The mean percentage predicted forced expired volume in 1 second (ppFEV1) for ex-employees (93.82, 95% confidence interval (95% CI) 88.53 to 99.11) was significantly lower (p

Introduction The Airways Service at Royal Preston Hospital receives tertiary referrals from across the UK. When a diagnosis of vocal cord dysfunction (VCD) or chronic cough is made and speech and language therapy (SLT) required, patients undergo weekly therapy (minimum four sessions), which some may struggle to attend due to pre-existing commitments and/or travel time. As SLT typically does not require ‘hands-on’ therapy we felt that Skype™ videoconferencing may be a useful mode of treatment delivery. We present our initial experience of this service. Methods A six-month pilot was completed whereby patients were offered SLT over Skype. Prior to therapy all patients were seen by the respiratory consultant and speech and language therapist for assessment and flexible laryngoscopy. Patients required confidential webcam access and proficiency. Symptom questionnaires were completed pre and post therapy (for VCD the 12 item VCDQ; for chronic cough the 19-item LCQ), and patient satisfaction questionnaires and flexible laryngoscopy performed post therapy. Results Eleven people have completed SLT over Skype™ to date, and all demonstrated improvement in symptoms following therapy. Patients with VCD showed a decrease in score on the VCDQ from median (range) 48 (12–53) pre therapy to 40 (7–42) post therapy [minimal clinical important difference (MCID) 5]. Patients with chronic cough showed an increase on the LCQ from median (range) 6.4 (4.6–8.2) pre therapy to 12.2 (10–14.6) post therapy (MCID 1.3). Improvements in laryngeal tension and sensitivity were noted in all cases. All patients gave positive feedback in their patient satisfaction questionnaire scoring “very satisfied” or greater. On three occasions Skype connection problems delayed sessions by a few days. Conclusions Virtual consultations provide the opportunity to treat patients in a more time efficient and practical way, and improvements in patient-reported symptoms and laryngeal appearances were similar to those of patients attending therapy sessions in chest clinic. This data gives support to pursue formalised tariffs for a specialised telehealth service. We feel that Skype should continue as a regular therapy option for patients and other members of the multi-disciplinary team (MDT) should consider this method of therapy delivery.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide and there are concerns that end-of-life care for these patients is inadequate. Advance care planning is encouraged, with the hope that it will improve communication and avoid unwanted interventions, which have been particular concerns; in practice, these discussions rarely occur. We have little knowledge of the views of patients with COPD on advance care planning. Understanding this could help integrate advance care planning into the routine management of patients with COPD. Aim: To explore the views of people with severe COPD about advance care planning. Design: Qualitative design, with data collection incorporating audio recorded semi-structured interviews. Analysis followed a grounded theory approach. Setting/participants: Patients with severe COPD ( n =10, Gold Standards Framework criteria) were recruited from primary and secondary care settings. Results: Participants felt they had not been given enough information about their diagnosis and prognosis, and were keen for more discussion with healthcare professionals. They wanted more involvement in decisions about their treatment when those decisions were required. Participants were happy to discuss their general views about future care, but felt uncomfortable with the traditional model of binding ‘advance directives’. Conclusions: Considering advance care planning as a repeated process of discussion of prognosis, concerns and probable preferences for care would be more useful than encouraging binding advance decisions. Further research should assess the effectiveness of this approach. Local coordination of who is responsible for information provision is needed, and greater involvement of patients with COPD in management decisions as they arise.

Introduction Vocal cord dysfunction (VCD) typically involves abnormal vocal cord movement during inspiration. The recognised gold standard for diagnosis is fibreoptic laryngoscopy (FOL) during a symptomatic attack. Despite this there are no reported VCD FOL assessment scales to facilitate agreement in presentation, disease severity and treatment monitoring. Our VCD tertiary airways clinic receives over 300 referrals a year. We run a weekly diagnostic FOL list and identified the need for a VCD FOL classification for optimal care. Aims To gain consensus for a VCD FOL appearance scale and identify its interrater reliability. Methods An expert consensus group was convened comprising two respiratory consultant physicians and two respiratory speech and language therapists (SLTs). All have significant experience in VCD FOL interpretation. The group met, discussed and agreed on the VCD FOL appearance scale (Table 1). Two assessment teams were identified, each comprising a respiratory physician and a respiratory SLT. Each team rated patients, referred for FOL with a clinical suspicion of VCD, in three consecutive diagnostic FOL lists. All procedures were recorded and then blindly re-rated during playback by the other assessment team. Results Eighteen patients received ratings; the mean (range) age was 51(19–80) and 78% were female. The assessing teams agreed on the rating for seven patients. For nine patients there was disagreement but adjacent classifications. Interrater agreement was performed using a weighted kappa (1 = complete agreement in classification; 0.5 = disagreement but adjacent classifications; 0 = disagreement and non-adjacent classifications). There was moderate agreement between the teams; 0.44 with a 95% confidence interval of 0.18–0.70. There was no bias between the assessment teams, as each had mean ratings for all patients of 2.4. Conclusions The VCD FOL appearance scale is a promising clinical assessment tool for the VCD population. We expected further interrater agreement; interestingly the majority of disagreement would not have changed management as classification still yielded a positive diagnosis. The differential maybe attributed to whether ratings were performed live or in playback, and this should be investigated. With further development, standardisation of application and robust validation it will be a useful assessment to direct appropriate management and facilitate accurate and consistent diagnosis.

Introduction Heliox21 reduces the work of breathing in patients with extra-thoracic airway obstruction, is not curative or intended to replace other treatments. In our specialist service we have significant numbers of patients whom have history of regular hospitalisations, relating to poorly controlled vocal cord dysfunction (VCD). The gold standard for treatment is respiratory speech and language therapy (rSLT). We increasingly value Heliox21 as an early adjunct to rSLT in severe patients who are establishing management strategies. Aims To assess the impact of Heliox21 on patient admission rate and self-reported experience, for patients with severe VCD. Methods We retrospectively reviewed the rSLT caseload from June–December 2014. All patients with endoscopically confirmed VCD, greater than five VCD related hospitalisations prior to the commencement of VCD treatment and who were prescribed Heliox21 for use in the community were included. We requested hospital admission data (from patient’s GP and secondary care physicians) between June 2013–June 2015, and reviewed medical and rSLT notes for demographic information/co-morbidity data/opinions of Heliox21. Results Five patients met the inclusion criteria, three were available for analysis; one male and two female (aged 23,43,57 years). All had treated co-morbidities of asthma (BTS step 5) and reflux. One patient had treated nasal disease. Six-months prior to community Heliox21 administration the mean (range) number of hospital admissions was 11 (8–13); after instigation, during the same follow-up period, this reduced by 81% (2 admissions) and two patients had no hospitalisations. In all patients rSLT occurred simultaneously. Patient opinions included, ‘heliox gives me time to start my therapy and means I don’t ring 999 straight away,’ and, ‘heliox stops me from going to A&E all the time.’ Two patients, who had completed rSLT, had Heliox21 removed as it was no longer needed. Conclusions Heliox21 has a positive impact on reducing VCD hospital admissions and is a low cost short-term solution (£160 set-up, £8.50 month). This retrospective review has limitations; the impact of rSLT alone on admission rates needs to be compared. Further investigation is needed to examine the worth of Heliox21 as an initial adjunct to rSLT, with consideration of how to prevent reliance.

Introduction Our specialist service manages patients with vocal cord dysfunction (VCD), chronic cough (CC) and dysfunctional breathing (DB), and referrals have grown exponentially since we introduced this novel multi-disciplinary (MDT) model in 2006. The team comprises two severe asthma specialist physicians, two respiratory speech and language therapists (rSLT), a severe asthma nurse specialist, respiratory physiotherapist and clinical psychologist. Aims To describe the clinical characteristics of those referred and assess utilisation of the multi-disciplinary structure. Methods Patient demographics and clinical data were retrospectively collated from clinical records of patients referred between January and December 2014. Results The service received 249 referrals. Excluding patients still in treatment or who failed to attend initial assessment, 141 complete data sets were available for analysis: 71% female; mean (range) age 55 (18–79) years. Assessment requests were for VCD (71%), CC (28%) or both (1%) and over half were from NW severe asthma centres or extra-regional specialist centres. The majority of referrals were from hospital consultants (72%), with the remainder from GPs (17%) and AHPs (11%). For VCD there was 73% agreement between the clinical suspicion on referral and nasendoscopic assessment. Approximately half had evidence of co-existent reflux (52%) and a third (29%) had nasal disease. The majority were seen by more than one member of the MDT team; all by a specialist physician and a rSLT, 43% by respiratory physiotherapy, and 7% clinical psychology. In the VCD cohort 64% had a previous asthma diagnosis and this was confirmed in the majority (93%) – 49(82%) were ≥Step 3 on BTS/SIGN guidelines; 43% were additionally referred for DB assessment; 78 flow volume loops were available and 31 (40%) were suggestive of extra thoracic inspiratory airway obstruction. Sixty-seven patients (48%) received rSLT management [median (range) 4(1–8) sessions] with a further 16(11%) scheduled to receive it post medical intervention. Of those who completed treatment, 63% had clinically improved presentation on discharge nasendoscopy. Conclusions A large proportion of patients referred to a specialist service for patients with complex breathlessness require multi-disciplinary intervention. There is a significant incidence of VCD and DB in patients with severe complex asthma. Of those receiving rSLT interventions, outcome was extremely effective at reducing symptoms.

Introduction Pulmonary rehabilitation (PR) programs use multidisciplinary teams to optimise physical and social functioning of patients with chronic respiratory impairment. Such patients demonstrate an increased prevalence of oropharyngeal dysphagia as a consequence of impaired co-ordination between respiration and swallowing function. Often patients will not be aware of the warning signs of dysphagia and unfortunately will not be seen by a speech and language therapist until they are admitted to hospital. We report the outcomes of a pilot scheme whereby such patients underwent education, assessment and treatment for dysphagia as part of their PR programme.. Methods The pilot scheme ran between June 2013 and May 2014. Intervention consisted of: (1) a one hour group education session on the signs, symptoms and risks of dysphagia; (2) screening for oropharyngeal dysphagia; and (3) individual outpatient management in Airways Clinic. The majority of patients attending the education sessions had a diagnosis of Chronic Obstructive Pulmonary Disease (COPD). Results The education programme was delivered to 72 patients, and resulted in a significant improvement in dysphagia knowledge. The average score pre education was 3/11 and post education was 8/11. Fourteen patients (19%) exhibited or reported symptoms of dysphagia. Of these two patients were overtly aspirating and required food/fluid modification and seven patient’s required instrumental assessment in the form of fibre endoscopic evaluation of swallowing (FEES). During FEES, three patients showed penetration of food/ fluids and were at risk of silent aspiration. These patients attended for further SLT where diet/ fluids were modified, posture was assessed and dysphagia therapy was introduced. Conclusions Dysphagia education and management of patients in PR can contribute the early identification, patient awareness and self-management of dysphagia. We have confirmed that undiagnosed but clinically important dysphagia is present in patients undergoing PR. We are investigating whether improved dysphagia knowledge and early identification of dysphagia symptoms leads to reduced exacerbations and improved quality of life.

Background Laryngopharyngeal reflux (LPR) is implicated in inducing laryngeal hyper-responsiveness which is a unifying feature underlying chronic cough and vocal cord dysfunction. A lack of response to standard anti-reflux therapy in patients with LPR may be due to persistence of non-acid-reflux and pepsin causing ongoing laryngeal epithelial inflammation. We investigated: (a) the prevalence of pepsin reflux in respiratory patients requiring nasendoscopy for the investigation of upper airway symptoms; (b) the performance of commonly used clinical LPR-diagnostic tools in predicting the presence of salivary pepsin. Methods Subjects had symptoms and signs of laryngeal inflammation quantified using, the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS). Salivary pepsin was measured with a lateral flow device using monoclonal antibody labelling (Peptest, RDBiomed). Patients with severe signs of laryngeal inflammation were referred for impedance-pH oesophageal studies to assess for objective evidence of reflux. Results Of the 78 subjects recruited, 76% were female, mean age 55 (range 17–82). Ten were undergoing investigation for chronic cough, and 68 for possible vocal cord dysfunction (confirmed in 45). 30 had concomitant asthma, and 42 were prescribed anti-reflux treatment. 87% had a high RSI, and 51% a high RFS. Pepsin was detected in the saliva of 49/78 subjects (63%), and prevalence did not vary significantly between treatment group. There was a weak correlation between the RFS and pepsin concentration (r=0.28, p=0.01) and the positive and negative predictive values for pepsin detection for those with a high RFS were 63% and 69% respectively. To date all 8 patients tested have had significant proximal reflux on impedance study, of which 6 had a positive pepsin assay. Conclusion Salivary pepsin was frequently present in patients with upper airway symptoms, but only weakly related to clinical findings of reflux, suggesting a high prevalence of LPR that is not associated with typical laryngeal findings. The significance of such sub-clinical reflux remains to be seen however the use of pepsin assay in patients with upper airway symptoms may be most valuable in directing diagnosis in milder cases where symptoms and signs lack specificity and the condition may otherwise be missed.

Background Advance care planning is recommended for patients with chronic obstructive pulmonary disease (COPD), aiming to reduce unwanted interventions, improve communication and influence place of death. Currently this is rarely done. Healthcare professionals9 perspectives on the reasons for this have been sought, but there is little information about patients9 views. Aims To explore the views of patients with severe COPD on advance care planning and how they feel it could be best integrated into their care. Method A qualitative interview strategy was adopted, drawing from grounded theory. Patients with severe COPD (gold standards framework criteria) were recruited from primary and secondary care until saturation was reached (n=10, 9M, 1F). Interviews using a broad topic guide were conducted in participants9 homes, audio recorded and transcribed verbatim. Analysis was inductive, generating themes using techniques of constant comparison. Results Participants wanted to discuss their future preferences and concerns with healthcare professionals, but did not feel comfortable making binding advance decisions and wanted to revisit these discussions regularly. Participants were not distressed by these discussions. Some participants felt more comfortable discussing future preferences with healthcare professionals they knew, others were comfortable with any healthcare professional involved in their care. Participants identified wanting more information about their diagnosis including prognosis early in their illness, but thought advance care planning would be more appropriate later. They expected their healthcare practitioner to initiate advance care planning discussions. Conclusions Advance care planning discussions could have a useful role in the care of patients with severe COPD, and fit with what patients expect from their healthcare team. Distress could be minimised by sensitive exploration, ideally within an established healthcare relationship. Regular discussion of disease status and likely progression, identified as being wanted from an early stage, could establish a good background to later discussion of advance care planning.

Background Vocal Cord Dysfunction (VCD) is typically reported to affect young females and has been associated with a psychiatric history. We run a multidisciplinary-based service for VCD patients with input from specialist speech and language therapy, physiotherapy and psychology. We investigated the demographics of our patient cohort with VCD, its association with anxiety and depression and whether this affected treatment response. Methods All patients referred for specialist speech and language therapy at the Royal Preston Hospital Airways Clinic between June 2006 and May 2011 with VCD confirmed by endoscopy were included. During routine clinical care data were collected including demographic details and comorbidities. Patients were also asked to complete the Hospital Anxiety and Depression (HAD) questionnaire. Subjective symptomatic improvement was recorded at patient follow-up visits. Results A total of 95 patients were eligible for study inclusion: 73.7% were female with a median age of 53 (17–83) years while men were older at 59 (37–80) years. Medical comorbidities included asthma (56.8%), reflux (47.4%), chronic cough (17.9%), nasal disease (16.8%) and neurological disease (12.6%). A history of confirmed psychiatric disease was noted in 38.9%. In 43 patients who completed HAD scores, moderate or severe anxiety was found in 41.8% and depression in 23.3%. Response to treatment was excellent (67% showing clinical improvement) and this was independent of medical or psychological comorbidity. Conclusions Our data suggest that VCD affects a wide range of patients, in terms of age, gender, comorbidities and HAD scores which do not impact on treatment response, as a result of the multidisciplinary approach and this success is comparable to most asthma therapies when patient compliance and education are accounted for. It challenges many previously held concepts and supports a multidisciplinary approach to treating VCD.