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Asthma is the most common chronic respiratory disease in the UK; however, the misdiagnosis rate is substantial. The lack of consistency in national guidelines and the paucity of data on the performance of diagnostic algorithms compound the challenges in asthma diagnosis. Asthma is a highly rhythmic disease, characterised by diurnal variability in clinical symptoms and pathogenesis. Asthma also varies day to day, seasonally and from year to year. As much as it is a hallmark for asthma, this variability also poses significant challenges to asthma diagnosis. Almost all established asthma diagnostic tools demonstrate diurnal variation, yet few are performed with standardised timing of measurements. The dichotomous interpretation of diagnostic outcomes using fixed cut-off values may further limit the accuracy of the tests, particularly when diurnal variability straddles cut-off values within a day, and careful interpretation beyond the ‘positive’ and ‘negative’ outcome is needed. The day-to-day and more long-term variations are less predictable and it is unclear whether performing asthma diagnostic tests during asymptomatic periods may influence diagnostic sensitivities. With the evolution of asthma diagnostic tools, home monitoring and digital apps, novel strategies are needed to bridge these gaps in knowledge, and circadian variability should be considered during the standardisation process. This review summarises the biological mechanisms of circadian rhythms in asthma and highlights novel data on the significance of time (the fourth dimension) in asthma diagnosis.

Patients suspected of ventilator-associated lower respiratory tract infections (VA-LRTIs) commonly receive broad-spectrum antimicrobial therapy unnecessarily. We tested whether exhaled breath analysis can discriminate between patients suspected of VA-LRTI with confirmed infection, from patients with negative cultures. Breath from 108 patients suspected of VA-LRTI was analysed by gas chromatography-mass spectrometry. The breath test had a sensitivity of 98% at a specificity of 49%, confirmed with a second analytical method. The breath test had a negative predictive value of 96% and excluded pneumonia in half of the patients with negative cultures. Trial registration number: UKCRN ID number 19086, registered May 2015.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated from Wuhan, China, at the end of 2019 and has rapidly spread to cause a global pandemic associated with substantial morbidity and mortality.1 By mid-April 2020, nearly two million confirmed cases of COVID-19 had been reported from 210 countries, resulting in over 100 000 deaths. Similar to previous novel coronavirus diseases (severe acute respiratory syndrome and Middle East respiratory syndrome), COVID-19 often leads to severe respiratory failure, and it might be assumed that patients with chronic respiratory diseases such as asthma would be at higher risk of developing severe illness. It is perhaps surprising then that, thus far, no clear association has been found2–5; asthma was reported in less than 1% of patients with COVID-19 from Wuhan,2 3 and chronic airway diseases, including asthma, in 10%–13% of nearly 2400 patients hospitalised in New York City.4 5 Although Williamson et al reported a modest increase in risk of COVID-19-related hospital deaths in asthma, this was mainly in patients recently receiving oral corticosteroids.6 It seems unlikely that respiratory comorbidities would be under-reported, so what other explanations may be offered? Shielding and self-isolation may be helping to reduce acquisition of SARS-CoV-2, but there is no reason to think this …

Variable airflow obstruction is a pathophysiological hallmark of asthma; however, the interactions between acute bronchoconstriction and the cough reflex are poorly understood. We performed a randomised, single-blind, placebo-controlled, crossover study to investigate the interaction between bronchoconstriction and cough in asthma. Capsaicin was administered to evoke coughs and methacholine to induce bronchoconstriction. We demonstrated that acute bronchoconstriction increased capsaicin-evoked coughs, which improved as airway calibre spontaneously resolved. However, capsaicin-evoked coughing had no impact on methacholine-induced bronchoconstriction. This study provides evidence that bronchoconstriction increases the activation of capsaicin-responsive airway nerves, but the precise mechanisms and mediators involved require further evaluation.TRIAL REGISTRATION NUMBER: ISRCTN14900082.

The first widely disseminated ‘asthma guideline’ came out of Australia and New Zealand in 1989,1 followed shortly by the British Thoracic Society (BTS) in 1990,2 the United States National Heart, Lung, and Blood Institute Expert Panel Report in 19913 and the Global Initiative for Asthma (GINA) strategy document in 1995.4 All have benefited from regular updates, the BTS collaborating with the Scottish Intercollegiate Guideline Network (SIGN) since 2003, most recently in 2016.5 Each new iteration of the asthma guidelines was written by experts in the field and based on best available evidence. It is not known whether these guidelines (or any others) have improved the care of people with asthma; asthma prevalence has continued to rise (although it may now have plateaued), and deaths overall have not fallen, although this statistic is driven entirely by an ageing population, as deaths in England from asthma in the young have in fact dropped dramatically.6 It is likely, however, that guidelines have reduced variation in diagnosis and treatment of this complex disease. In 2013, the National Institute for Health and Clinical Excellence (NICE) joined the guideline party, with a new approach that included consideration of health economics as well as clinical effectiveness. Their rationale included concerns that deaths were not falling, drug costs were rising and over-diagnosis and under-diagnosis still a significant issue. While the strength of evidence for each of these points varies (drug costs are rising across all areas of medicine, and over-diagnosis rates of 30% have been demonstrated repeatedly, even in recently diagnosed individuals7), all healthcare professionals involved in the care of people with asthma would recognise that each of these issues do need careful consideration. However, what had not been established was whether these failures were …

Background: With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLUHFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses. Methods: Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 µg/day followed by 1000 µg/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV1) of 20% or more (methacholine PD20) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC). Results: For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD20 compared with baseline. The improvement was not significantly greater with 1000 µg/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p

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.

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.

Overview Tracheobronchomalacia (TBM) is increasingly recognised as a significant diagnosis in patients diagnosed with “severe asthma”. Continuous Positive Airway Pressure (CPAP) is used as first line treatment to stent the airway in TBM patients in order to clear mucus and prevent irritation, inflammation and bacterial overgrowth thereby reducing the number of exacerbations experienced by patients. However, there is currently no published data which evaluates whether this intervention has an impact on outcomes in. This study describes a cohort of patients referred to a regional centre for severe asthma patients, who were subsequently diagnosed with TBM and analyses the impact of CPAP on exacerbations caused by TBM. Methods 20 TBM patients were identified at the North West Lung Centre in University Hospital South Manchester (UHSM) through clinics and department databases. Patient case notes and general practice medication prescriptions were used to obtain data on antibiotic and steroid prescriptions as well as hospital admissions (one year before and one after treatment). Exacerbations were analysed pre- and post-CPAP. Patient demographics were also recorded and compared to the cohort in the national severe asthma registry. Results TBM patients were found to have increased weight and BMI compared to the cohort described in the national severe asthma registry; weight 92.4 ± 28.8 in TBM compared to 81.2 ± 19.9 and BMI 35.5 ± 8.1 compared to 28.0. Analysis of CPAP data showed that with an average of 6 hours of CPAP daily at average pressures of 11 cm H2O significantly reduced the number of annual exacerbations experienced by over 50% for antibiotic and steroid prescriptions and significantly more for hospital admissions. Figure 1 shows the reduction in exacerbations in the year following the initiation of CPAP compared to the year before. Conclusions The severe asthma cohort with TBM are likely to have an increased weight and BMI. CPAP is an effective treatment option for TBM patients whilst awaiting the availability of more definitive surgical options and reduces antibiotic and steroid prescriptions as well as hospital admissions. It is recommended that all symptomatic TBM patients are considered for CPAP and monitored for exacerbations thereafter.

Background Vocal cord dysfunction (VCD) is often initially misdiagnosed as, or may coexist with, asthma. Identifying the differences between the types of triggers for each condition may help differentiate between these two conditions, and could give mechanistic insights. Aim The aim of this study is to identify and compare patient-reported triggers in VCD and asthma. Methods This was a two-part study. Part A – A retrospective case note review of the triggers of VCD from endoscopically-confirmed VCD patients was conducted. This information was used to generate a Breathlessness Triggers Survey with triggers recorded under the categories: scents, environmental factors, temperature, emotions, mechanical factors and daily activities. Part B – A prospective study which involved patients with VCD and/or asthma completing the Breathlessness Triggers Survey, rating the likelihood of each item triggering their symptoms using a five-point Linkert scale (strongly disagree to strongly agree). Chi-square test was performed to compare responses by cohort. Results Part A – Data from 202 patients with VCD (73.3% female, mean age 53.1yrs) were included in the retrospective study. The findings were used to create a 23-item Breathlessness Triggers Survey for Part B of the study. Part B – 38 patients with VCD-only (63.2% females, mean age 56.8 yrs), 39 patients with asthma-only (56.4% female, mean age 53.3 yrs) and 12 patients with both VCD and asthma (83.3% female, mean age, 56.8yrs) were recruited. The mean number of patient-reported triggers in the VCD and asthma cohort was 11 and 13 respectively. Mechanical factors such as talking (p ≤ 0.001), shouting (p = 0.004) and swallowing (p ≤ 0.001) were more common in the VCD cohort, whilst environmental factors such as pollen/flowers (p = 0.002) and damp air (p = 0.039) were more common in asthma. There were no differences between groups in frequency of reporting scents as triggers (except for vinegar, more common in VCD), temperature, emotions or daily activities. Conclusion There were notable differences and overlaps between patient-reported triggers of VCD and asthma, which could give clues to diagnosis during clinical assessment. Future work should focus on the mechanisms underlying these findings.

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.

Introduction The potential of exhaled breath condensate (EBC) as a non-invasive indicator of airways disease has been studied for three decades or more. 8-isoprostane is a product of lipid peroxidation which can be detected within EBC. Studies have reported this as a potential objective indicator of oxidative stress in asthma. We therefore aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma. Design A systematic review and meta-analysis of EBC 8-isoprostane in asthma. Methods We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I2. Study quality and risk of bias was assessed using QUADAS-2 and GRADE. Results We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane concentrations in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies had results appropriate for inclusion in a random effects meta-analysis of mean difference between asthma and controls (see Figure 1). This found a statistically significant between-groups difference of +22 pg/ml in asthma. Confidence in the result is limited by the small number of studies; by substantial methodological and statistical heterogeneity (I 2 = 94); and by an inability to assess the risk of bias in key domains of the quality assessment tool. Conclusion The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It will be essential to develop accurate, reliable and standardised methods of both EBC collection and 8-isoprostane analysis if its use as a biomarker in asthma is to be evaluated.

Objectives Measure bone turnover markers (BTM) CTx, P1NP and bone-specific alkaline phosphatase (BsALP) in a severe asthma population using systemic corticosteroids (SCS). Assess bone mineral density (BMD) change in regional severe asthma clinics. Background Severe asthma often requires regular SCS use. SCS cause several adverse effects including reduced bone metabolism; resorption is increased and formation is decreased resulting in osteoporosis. DXA scans monitor BMD in the hip and spine every 3–5 years. BMD decrease is treated with bone sparing medication (BSM), but treatment is retrospective and response takes years to assess. BTM represent markers of systemic bone metabolism and may offer a more efficient alternative. CTx is a resorption marker, P1NP and BsALP are formation markers. Method Patients attending Manchester or Belfast severe asthma clinic with two or more DXA scans were identified from case files. We measured BTM in Manchester severe asthma patients and a control group of Manchester severe asthma patients requiring less than 3 courses of steroids per year. Using case files we collected data including DXA scan results, SCS use and osteoporosis risk factors. Results BMD change and BTM did not correlate overall (patients n = 78, controls n = 18) but correlated negatively in patients where the most recent DXA was Conclusion This study has confirmed that BTM may be potentially used as a surrogate for BMD measurement; however a more a prospective study where BTM are measured at the time of two DXA scans which are years apart is required.

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.

Introduction Patients with asthma are prone to recurrent infective exacerbations, due to viral or bacterial infections. We have previously presented retrospective data, demonstrating significantly reduced lung function in severe asthma patients with specific antibody deficiency. The prevalence and impact of specific antibody deficiency in this patient group is not known. Aim We aimed to determine the prevalence of specific antibody deficiency and its association with markers of disease severity. Methods We prospectively collected data from all new patients attending the regional severe asthma clinic. We recorded demographic details and markers of disease severity including: BTS treatment step, inhaled corticosteroid (ICS) dose, spirometry, blood and sputum eosinophil count, radiological findings such as bronchiectasis and bronchial wall thickening, exacerbations in the last year and ITU admissions. Specific antibody levels to Haemophilus Influenzae (Streptococcus Pneumoniae ( Results Data for 53 patients (39F), mean (SD) age 49.6 (15.9) years were available. Mean (SD) FEV1 was 69 (22)% predicted, ICS dose 1914 (1337) micrograms, and BMI 31.5 (8.6) kg/m 2 . All were at BTS step 3–5. Information on specific antibody levels was available for 43 and 45 patients for H Influenzae and S pneumoniae respectively and for both in 42 patients. Overall out of the 42 patients 35 (83%) were deficient to one or both the organisms. Of these 13 (31%) were deficient to H Influenzae alone, 5(12%) to S pneumoniae alone, and 17 (40.5%) to both. Looking at each organism separately 30 (70%) out of 43 were deficient to H Influenzae and 23 out of 45 (51%) were deficient to S pneumoniae . Of the 32 patients for whom data were available 20 (63%) had 7 or more exacerbations in the preceding year and two thirds of these had bronchial wall thickening on their CT scans. A third of patients (30%) reported at least one ITU admission. The presence of specific antibody deficiency did not correlate with any clinical or radiological findings. Conclusion Specific antibody deficiency to H influenza and S pneumoniae is remarkably common in moderate to severe asthma. Further studies are required to determine the clinical significance of this finding.

Rationale Apoptotic cell uptake (efferocytosis) by airway macrophages (AMs) is critical for lung immune homeostasis and is defective in chronic lung diseases, including asthma,1 although the molecular mechanism behind this remains unknown. The TAM (Tyro3, Axl, MerTK) receptor tyrosine kinases are one of the main receptor classes that mediate efferocytosis but little is known about their regulation and function in inflammatory lung diseases. Aim To investigate expression profile of TAM receptors and their ligand Gas6 in human AMs and analyse potential defects in TAM receptor expression in chronic lung inflammation. Methods AMs from the sputum of patients with asthma (BTS step 3–5) (n = 30) or healthy donors (HD) (n = 12) were enriched by plastic adhesion. Monocytes were isolated from matched whole blood samples by CD14 positive selection and differentiated into monocyte-derived macrophages (MDMs). Total RNA was extracted from all purified cell populations and mRNA expression analysed by qPCR. HD MDMs were stimulated with Th2 cytokines in vitro and TAM receptor expression was analysed using qPCR and ELISA. ![Abstract S130 Figure 1][1] Abstract S130 Figure 1 mRNA expression of Axl in airway macrophages of healthy donors and patients with asthma Main results Axl was the dominant TAM receptor expressed in HD AMs whereas monocytes and MDMs predominantly expressed MerTK. Axl expression was significantly reduced in AMs from patients with asthma compared to HD (p < 0.0001), while mRNA levels of MerTK and Gas6 was similar in both groups. We found no differences in Axl and MerTK expression in monocytes and MDMs from HD and patients with asthma, indicating that the observed differences were restricted to the site of inflammation. In vitro , MDM stimulation with IL-4 or IL-13 downregulated Axl mRNA and protein expression in a time-dependent manner. Conclusions We have shown for the first time that Axl is the principal TAM receptor expressed in human AMs. Significant reduction of Axl expression in AMs from patients with asthma might be responsible for inefficient clearance of apoptotic cells from the inflamed airways and contribute to persistent airway inflammation. Strategies aimed at restoration of Axl expression or activity may represent a novel therapeutic strategy in asthma and other chronic lung diseases. Reference 1 Simpson JL, Gibson PG, Yang IA et al . Impaired macrophage phagocytosis in non-eosinophilic asthma. Clin Exp Allergy . 2013; 43 :29–35 [1]: pending:yes

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 Detection of peripheral pulmonary lesions (PPLs) is on the rise but an accurate means of obtaining a tissue diagnosis without high risk of complications is lacking. 1 Virtual bronchoscopic navigation (VBN) guides the bronchoscope under direct vision and, in combination with radial endobronchial ultrasound (R-EBUS) or ultrathin bronchoscopy, may enhance the diagnostic yield of PPLs with a minimal complication rate. 2 Aims To pilot the use of VBN in the diagnosis of PPLs. To identify patient and lesion characteristics that predict successful VBN. Methods Images from chest CT (slice width 1–1.25 mm) were acquired from patients, and lesion features, including location and presence of a bronchus sign (bronchus contained within PPL), were recorded. CT images were transferred to a portable workstation and Lungpoint Broncus © was used to create a virtual pathway to the PPL. Bronchoscopy was performed with VBN followed by R-EBUS guidance, under conscious sedation, and biopsies obtained. Pre-procedure characteristics, biopsy adequacy, biopsy outcome, 30-day follow up and complications were recorded. Results The median age of our cohort (n = 7) was 79 and all patients had one or more comorbidities. PPL median size was 28 mm and all were located in sub-segmental bronchi. VBN guided the operator to the correct site in six cases. Adequate biopsies were taken from five patients; four had a positive bronchus sign. Three adequate biopsies received a diagnosis of primary lung cancer; those remaining were negative. One patient with inadequate biopsies underwent transthoracic needle biopsy (TTNB) and was diagnosed with primary lung cancer. No complications occurred in spite of the significant co-morbidity of this patient cohort. Discussion Our preliminary data suggest that in a selected patient cohort with a bronchus sign, VBN may be a useful and safe adjunct to R-EBUS to obtain a tissue diagnosis from PPLs. In contrast, TTNB has a high diagnostic sensitivity but is tarnished by a high complication rate and is not suitable in patients with significant co-morbidity. Therefore, VBN and R-EBUS are particularly useful where TTNB carries a high risk. References 1 Kikuchi E, Yamazaki K, Sukoh N, et al . Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions. Eur Respir J 2004; 24 :533–7 2 Ishida T, Asano F, Yamazaki K, et al . Virtual bronchoscopic navigation combined with endobronchial ultrasound to diagnose small peripheral pulmonary lesions: a randomised trial. Thorax 2011; 66 :1072–7

Introduction/aim Omalizumab (Xolair) is a recombinant humanised monoclonal antibody licensed for the treatment of severe allergic asthma patients with IgE mediated disease. The mechanism of action of omalizumab is to bind to IgE preventing interaction with FCERI (high affinity receptors) upon the surface of mast cells and basophils, thereby reducing the activation of the inflammatory cascade and associated clinical symptoms. Although blood eosinophilia is a useful measure of airway inflammation, the correlation between blood eosinophils and omalizumab treatment has not been described outside clinical trial. Therefore, our aims were to identify whether the introduction of omalizumab is associated with a change in the blood eosinophil count within our cohort of patients with severe asthma. Methods We collected measurements of blood eosinophils in patients maintained on omalizumab for periods 12 months pre and post, and (where available) 24 months pre and post initiation of therapy. We also investigated any correlation between blood eosinophils pre and post treatment versus clinical parameters including total IgE and omalizumab dose. Results Complete data sets including 12-month blood eosinophil data were available for 49 of our current cohort of 92 patients on treatment. The mean blood eosinophil count dropped from 0.33 × 10 9 cells/l (IQR 0.37) × 10 9 cells/l pre-treatment to 0.22 × 10 9 cells/l (IQR 0.30) post treatment ( p = Additionally, we widened the window to 24 months pre and post initiation of treatment, if blood eosinophil data was not available at 12 months. Data for 59 patients demonstrated similar significant reduction in mean blood eosinophil, 0.34 × 10 9 cells/l (IQR 0.34) pre-treatment to 0.23 × 10 9 cells/l (IQR 0.29) ( p = 0 .003). No association was seen between the changes in mean blood eosinophil counts post treatment versus total monthly omalizumab dose and baseline total IgE. Conclusion Our data demonstrates a significant reduction in blood eosinophils in patients who are receiving omalizumab treatment when comparing blood eosinophils at 12 and 24 months pre and post treatment. Future work should investigate whether this is a direct result of omalizumab therapy, due to confounding by other treatment, or a marker of improved asthma control.

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.

Background Inhaled anti-inflammatory therapy is fundamental to asthma management, but adherence is very poor. This increases the risk of exacerbations and poor symptom control. Currently there is no direct way of assessing adherence to inhaled steroids accurately. The primary aim of this project was to determine whether liquid chromatography tandem mass spectrometry could be used to detect fluticasone propionate (FP) in human serum as a potential aid to therapeutic monitoring. The secondary aim was to relate serum levels of FP to markers of asthma severity. Methods We collected blood samples over an 8 hr period from inpatients with severe asthma on a stable dose of inhaled FP. Following baseline (trough) sampling, patients were observed using their inhaler, with inhaler technique documented. Subsequent samples were obtained 1, 2s, 4 and 8 hrs post inhalation. Demographic details and spirometry were also recorded. Results Thirteen patients were recruited: 8 males, 5 females; age range 22–64 yrs; FEV1 range 53–101% predicted; 10 patients on 1000 mcg/day, and three on 2000 mcg/day FP. The mean concentration of FP at 1 hr post inhaler (peak in 7/13 patients) was 95.5 (SD 89.1) ng/L. The mean pre-dose trough concentration was 32.9 (SD 41.5) ng/L. Two patients were noted to have poor inhaler technique; these patients had some of the lowest serum FP levels recorded. The FEV1% predicted was found to be strongly correlated with the peak serum FP concentration (Pearson’s r = 0.8, p = 0.001). Conclusion We have demonstrated that FP can be detected in the blood of patients with severe asthma following directly observed therapy; this could have a potential future application as a direct measure of adherence and perhaps inhaler technique. We also demonstrated a profound effect of reduced lung function predicting low serum FP levels. Future work will explore whether poor absorption reflects relatively poor efficacy in the most severe patients.

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.

Background Vocal cord dysfunction (VCD) is a debilitating condition characterised by paroxysmal episodes of dyspnoea, typically resulting from abnormal adduction of the vocal cords during breathing. Diagnosis is complicated by its self-limiting nature and significant overlap in symptoms with other respiratory conditions such as asthma, and referral for further investigation therefore requires a high index of suspicion from non-specialist physicians. Our aim is to design a questionnaire with a high positive predictive value for VCD, which would hopefully lead to earlier identification and treatment and also reduce the levels of iatrogenic morbidity associated with misdiagnosis. Methods 15 subjects with a confirmed diagnosis of VCD were recruited from the outpatient respiratory department. Semi-structured interviews in four focus groups were conducted to capture each sufferer9s subjective experience. Concurrently, two focus groups were held with nine healthcare professionals with specialist and non-specialist interest to gather professional opinion on VCD symptoms. The collated data were used to generate a preliminary questionnaire that was tested for face validity in ten patients and healthcare professionals. Results (1) Item generation: symptom profiles varied markedly, however certain characteristics did emerge with commonalities between most of the subjects or within a specific subset of individuals. These were grouped into the following themes—location, onset, sensations, breathing/voice changes, triggers, exacerbating factors and psychosocial impact. 17 items were generated for the preliminary questionnaire and expressed as positive or negative statements. (2) Face validity: general response was positive towards the comprehensibility of the statements and relevance to each subject. Based on user comments the number of items was reduced to twelve, all items were modified to positive statements to improve comprehensibility and a 5-point analogue scale will be used for scoring responses. Conclusions A preliminary diagnostic tool has been generated and tested for face validity in patients with VCD. Initial feedback indicates a high relevance of the questionnaire items to the subject. At this stage, modifications have been made to eliminate ambiguity and repetition. We will now test concurrent validity, specificity and test-retest variability of the questionnaire in healthy volunteers, and respiratory patients with and without VCD.

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.

Introduction Severe Asthma, characterised by persistent symptoms despite maximal medical therapy, represents 5% of asthma cases. Bronchial Thermoplasty (BT) is a novel therapy, NICE approved for Severe Asthma patients uncontrolled despite step 4/5 of British Guideline on Asthma Management. BT delivers radiofrequency thermal energy to airways distal to the main-stem bronchi, permanently reducing airway smooth muscle mass. It is unknown whether treatment of smooth muscle hypertrophy impacts persistently upon systemic signs of allergic inflammation. Peripheral blood eosinophils (PBEs) are a marker of allergic inflammation in asthma. We asked: does BT modify signs of allergic inflammation as measured by PBEs and if so, does this effect persist over time? Method A retrospective review of 15 consecutive Severe Asthma cases treated with BT was performed. Serial PBEs measured before and up to 1 year after BT were compared. Blood eosinophil levels taken peri-procedure were excluded from analysis due to standard protocol concomitant steroid therapy. For time to first detectable high PBE all available post-BT PBE levels were assessed. Results 13 patients had PBE data before and after BT, with an average of 9 and 12 serial PBE levels pre and post-BT respectively. Mean PBE 1 year pre-BT was 0.33 × 109/L falling to a mean of 0.16 × 109/L 1 year post-BT (p 0.4 × 109/L) was 7 months (range 1–13 months). In 5 patients (38%) PBE remained within normal range persistently post BT. Conclusion Severe Asthma patients undergoing BT had a significant reduction in average peripheral blood eosinophil levels from baseline. In over 1/3 of cases this effect was persistent 1 year post procedure. These findings support the concept that BT not only reduces asthma-associated smooth muscle hypertrophy but impacts upon systemic markers of allergic inflammation. ![Abstract S96 Figure 1][2] Abstract S96 Figure 1 [1]: #F1 [2]: pending:yes

Objectives To determine whether Mycophenolate mofetil (MMF) is an effective steroid sparing agent in a single centre cohort of severe asthma patients. Background MMF is a powerful inhibitor of purine and pyrimidine synthesis via the de novo pathway, upon which lymphocyte production is dependent. It is currently licensed for use in transplant rejection prophylaxis. Other immunosuppressant therapies have been used off licence in difficult-to-treat asthma patients under specialist supervision in an effort to reduce corticosteroid use. MMF is currently a third line immunosuppressant after methotrexate and azathioprine at the North West Lung Centre. Methods A retrospective data analysis was performed including all patients under specialist asthma care at UHSM that were previously or currently treated with MMF. Annualised average daily steroid dose was calculated from the available data in patient case notes. This was calculated for 12 months prior to commencing any immunosuppressant therapy and during MMF treatment. Exacerbation and hospital admission rates were also recorded. Results A total of 34 patients were identified as being on MMF for severe asthma for at least 8 weeks. 11 did not tolerate MMF or had no response and subsequently stopped. The primary analysis was carried out on 23 patients and a secondary post hoc analysis was performed on all patients who had been on treatment for a minimumof 6 months at the time of the study (N=12). The average yearly steroid sparing impact of MMF was 5.9 mg per day, (p 6 months (Δ 3.9 p = 0.20). There was no statistically significant reduction in admission or exacerbation rates. Conclusion MMF has shown a small steroid sparing effect in this retrospective analysis, although the effect appeared less positive in the sub-group of those analysed after being on treatment for at least 6 months further analysis of the potential benefits of MMF in this patient population is required.

Objectives To determine if specific clinical questions could reliably predict the ultimate inflammatory phenotype of patients attending a severe asthma service. The severe asthma clinic at University Hospital of South Manchester now routinely ask the desert island question (DIQ)…. “If you were on a desert island and could only have steroids or antibiotics which would you choose?” Background It is widely accepted that asthma is the result of complex pathological processes giving rise to a variety of different phenotypes, including eosinophilic and non- eosinophilic inflammatory patterns. Phenotype is determined by investigations e.g. baseline blood/sputum eosinophil level and clinical response to treatments including steroid augmentation/withdrawal. Investigations include antibody status to Haemophilus Influenza and Streptococcus Pneumonia. Methods New patients referred to the severe asthma service were asked the DIQ during their first appointment, prior to any investigations. We collected data from first clinic letters and case notes. Data collected included DIQ answer, phenotype, additional diagnoses, historical steroid and antibiotic use, sputum data and all asthma treatments trialled. Results A total of 59 patients were identified. 71% answered steroids and 29% answered antibiotics. Of those that answered steroids, 83% had eosinophilic asthma, 14% had non-eosinophilic asthma. The breakdown of the different phenotypes within the different answer groups is illustrated in Figure 1. The positive predictive value (PPV) of the answer “steroids” was 86% and “antibiotics” 47% (χ 2 =7.182 p= Conclusion This small pragmatic study has shown that the answer “steroids” to the DIQ has a high PPV for eosinophilic airway inflammation. The “antibiotic” response is much less useful in predicting inflammatory phenotype, but it does identify a high likelihood of antibody deficiency.

Introduction Refractory chronic cough has a significant negative impact on HRQoL. There are currently limited effective antitussive therapies. Few studies have explored the effectiveness of nonpharmacological interventions for refractory chronic cough. This study investigated the efficacy of PSALTI on HRQoL for people with refractory chronic cough in a multi-centred RCT. Methods Participants were recruited across five NHS hospitals trusts. 76 participants were randomised to PSALTI or placebo (equal attention) intervention. PSALTI consisted of education, laryngeal hygiene and hydration advice, cough control techniques and psycho-educational counselling. Placebo consisted of general education on exercise, diet, stress and relaxation. Both groups attended 4 weekly sessions of 1:1 therapy. HRQoL was measured at baseline, four weeks (end of treatment) and 3 month follow up by Leicester cough questionnaire (LCQ). Cough reflex sensitivity was assessed at baseline and four weeks by capsaicin cough challenge (C2, C5, concentration that caused first urge to cough (Cu)) and was analysed by geometric means (GM). Outcomes between groups were analysed using ANCOVA. Results The PSALTI (n = 35) and Placebo groups (n = 41) were well matched (p > 0.05) for age [mean (SD)] 58(15) vs. 56(11) years; gender 71% vs 63% females; cough duration [median (IQR)] 60(30 to 126) vs 48(24 to 126) months and baseline LCQ [mean (SD)] 10.4(3.6) vs 11.9(3.5). At four weeks HRQoL improved in both groups, mean LCQ increase in PSALTI was 3.4 (95% CI 2.26 to 4.55) vs placebo 1.7 (95% CI 0.78 to 2.54); difference in LCQ change between groups was 1.5 (95% CI 0.27 to 7.31, p = 0.02) points more on average in the PSALTI group. This effect is greater than the MCID for LCQ and was sustained at 3 months (mean difference change between groups after 4 weeks to 3 months was -0.28 (95% CI -1.83 to 1.38). There was a significant increase in Cu in the PSALTI group compared to placebo (GM(SD) change 2 µm (5.07) vs 0.612 µm (3.26), p = 0.02). There was no significant difference in cough reflex sensitivity between the groups (C2, p = 0.46; C5, p = 0.74). Conclusions PSALTI significantly improved HRQoL compared with equal attention placebo intervention and this improvement was sustained at three months. PSALTI also significantly increased Cu compared to placebo.

Background Methotrexate (MTX) immunosuppressive therapy is selectively used to assist with the reduction of the oral corticosteroid demand thereby decreasing the risk of potential side effects in individuals with steroid dependant asthma. Previous reported data has demonstrated similar significant reduction in corticosteroid load, asthma exacerbation and hospital admission rate. This study aims to compare similar variables collated from UK severe asthma specialist centres to further generate evidence for the continued use of MTX as an effective aid in the reduction of corticosteroid burden in a severe asthma cohort. Methods A retrospective data collection was performed across two UK severe asthma centres with data from a third pending. Patients included had a confirmed diagnosis of severe asthma and had been treated with MTX for at least 12 months to allow sufficient analysis. Variables assessed included mean average daily corticosteroid dose, overall percentage reduction of corticosteroid, exacerbation frequency and acute admission events both twelve months prior to and post commencement of MTX therapy. Data collection was examined for each individual centre then combined and examined for consistency of results. Results N = 29 (21/8) Average daily corticosteroid dose was reduced by 6 mg combined across both centres [p = 0.004] (6.4 mg/5 mg) a percentage of overall reduction of corticosteroid equated to 34.8% jointly across both centres and 39.3% and 30.0% individually. Exacerbation frequency decreased from 4.8 to 2.5 annually combined across both centres [p = 0.003] although conflict in result is identified as one centre reports a 1.0 increase in exacerbations compared to 3.4 decrease in the other centre. Combined admission decreased from 1.3 to 0.3 annually [p = 0.004] 1.1 and 0.4 decrease in each individual centre. Conclusion When monitored and supervised in the correctly chosen severe asthma patient, MTX can significantly reduce the demand for corticosteroids and consequently reduce steroid related side effects, admission and exacerbation this has been demonstrated across two specialist centres with correlating data.

Introduction We present a series of cases referred to our severe asthma clinic that symptomatically appear like asthma, yet physiology demonstrated one of the more uncommon types of severe Small Airway Disease (SAD), including: Allergic Bronchopulmonary Aspergillosis (ABPA), Obliterative Bronchiolitis (OB), follicular bronchiolitis and Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). These diseases represent a diagnostic challenge. We have also reviewed cases of tracheomalacia and horseshoe lung, which in our report shared similar physiology to SAD. Methods Our findings in these SAD patients are compared with randomly identified cases of genuine severe asthma. Results ABPA, OB, follicular bronchiolitis and DIPNECH shared similar physiology in this project and are compared together as Non-Asthmatic SAD (NASAD). When compared to asthmatic SAD (ASAD), NASAD demonstrated a lower FEF 25–75% (NASAD range 4–26%, median 9%, 7 out of 8 120% v. ASAD range 66–121%, median 97.5%, 2 out of 6 > 120%). All patients, except one, demonstrated normal gas transfers strongly suggesting an absence of emphysema. HRCT alone did not provide any diagnostic benefit. Only asthma demonstrated significant and consistent bronchodilator reversibility. Tracheomalacia mimicked SAD, demonstrating an inconsistent pattern of FEF 25–75% and a small degree of variation of RV around normal. Horseshoe lung demonstrated similar physiology to NASAD. Conclusions Clinicians need to consider the above mentioned diseases as an alternative diagnosis to emphysema and asthma in those with a characteristically SAD flow volume loop, a high RV and normal gas transfers.

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 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.