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IntroductionA biomarker-based approach to preschool (age 1–5 years) wheeze might be beneficial.1 Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) are potential biomarkers of inhaled corticosteroid (ICS) response, but stability in this population is unknown. We hypothesised that BEC and FeNO are stable in the short term in pre-school children with documented wheeze.MethodsThis was a prospective, year-long, observational study. We compared finger prick for BEC measurement, off-line FeNO measurement and skin prick testing (house dust mite, grass and tree pollen, cat, and dog hair) at baseline and on optional repeat occasion. Statistical methods: Intraclass correlation coefficient (ICC) test, chi-square test of independence. ICS treatment change (initiation, dose change, termination), ≥1 wheeze attack between tests, and atopic status (non-atopic, mono-sensitised, poly-sensitised) assessed as factors affecting stability.Results97 participants [median age: 35 months (IQR: 23–48 months, male=60). 47 completed the second testing 3–4 months later; BEC and FeNO were measured in 47 and 10 participants respectively. There was no difference between those who did and did not undergo a second test in age, atopic status, FeNO or BEC; a slightly higher proportion of males were re-tested, p=0.04. BEC measurements had poor repeatability (ICC=0.07, p>0.05,within-subject SD=269 cells/μl); FeNO measurements showed moderate repeatability (ICC=0.54,p<0.05, within-subject SD=3.2 ppb). Whatever BEC normal cut-off was examined (≥150, ≥200, ≥300, ≥400 and ≥500 cells/μl) switch in category (normal, abnormal) was equally likely (p>0.05), but stability was observed for both FeNO thresholds (≥5 and ≥ 10 ppb) (p<0.05). ICS treatment change, ≥1 wheeze attack between measurements or atopy had no association with change in either biomarker (p>0.05). BEC were not stable regardless of atopic status [mono-sensitised (n=11), polysensitised (n=12), non-atopics (n=24)] (p>0.05). Stability was not affected by ICS treatment change (n=12; n=8 initiation, n=2 each ICS stopped or increased dose), ≥1 wheeze attack between measurements (n=15) or atopy.ConclusionBEC but not FeNO were unstable over three to four months. Single BEC measurements may be an insufficient guide to preschool wheeze treatment. Due to the small sample size, FeNO results should be considered with caution.ReferenceJ Allergy Clin Immunol. 2016;138:1608–18

Introduction & ObjectivesThe prevalence of exercise induced laryngeal obstruction (EILO) is thought to be around 5–7% in the general adolescent population and can often be misdiagnosed as asthma.1 Continuous laryngoscopy during exercise (CLE) is the gold standard to confirm a diagnosis of EILO. However, EILO has limited availability in UK paediatric hospitals. Our aim was to evaluate the prevalence of confirmed EILO using CLE in a group of patients referred with exercise induced dyspnoea and to assess the ability of cardiopulmonary exercise testing (CPET) to diagnose these patients without the need for a CLE.MethodsRetrospective data were analysed from patients who had undergone CPET and CLE for suspected EILO. Evidence of stridor or dysfunctional breathing on the CPET was used to test the sensitivity and specificity of CPET to diagnose EILO. CPET was performed on a cycle ergometer with an incremental ramp protocol. CLE was also performed on the cycle ergometer with an ENT specialist citing and stabilising a nasal endoscope for the duration of the test. A shorter ramped supramaximal protocol was used for this.ResultsTwenty-three patients had a CPET and CLE between 2015–2023. Mean age: 12.6 years, 95% CI[11.5, 13.8]. A summary of CLE tests is shown (figure 1). Twenty were performed successfully and twelve had confirmed EILO. CPET had a sensitivity = 75.0%, 95% CI[42.8, 94.5%] and specificity = 90.9%, 95% CI[58.7, 99.8]Abstract S46 Figure 1ConclusionsThis study indicates that CPET has a low sensitivity and high specificity for EILO. Therefore, a normal CPET should not exclude a diagnosis of EILO, and a CLE should be performed. Evidence of dysfunctional breathing and/or stridor on CPET is highly specific for EILO in children and adolescents referred with exercise induced dyspnoea. We have also shown that CLE can be successfully performed in the majority patient’s aged between 7 and 18 years.ReferenceJohansson, et al. Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population. Thorax. 2015.

IntroductionNational Institute for Health and Care Excellence (NICE) guideline (NG80) aims to aid asthma diagnosis in children and suggests sequential lung function testing. We compared diagnostic outcomes using NG80 to that of an ‘expert panel’ of respiratory consultants within the Rapid Access Diagnostics for Asthma (RADicA) study.MethodThe RADicA study recruited children aged 5–16 years with symptoms suggestive of asthma. Clinical history, physical examination, and lung function [fractional exhaled nitric oxide (FeNO), spirometry, bronchodilator reversibility, peak expiratory flow variability, methacholine challenge] were assessed before and after inhaled corticosteroid treatment. The ‘expert panel’ reviewed results from all visits and assigned diagnostic categories of ‘asthma’, ‘not asthma’, ‘possible asthma’, or ‘insufficient evidence’.The NG80 algorithm was used to categorise participants into the same categories using results from the first study visit. If a child was unable to perform a test they were classed as insufficient evidence and stopped from progressing through the NG80 algorithm at that point. This process was then repeated allowing children a second attempt at spirometry and FeNO from study visit 2. Children in whom a diagnosis of ‘asthma’ was not confirmed, were reassessed with their methacholine challenge results. A positive challenge (PD20 < 0.2 mg) was used to confirm ‘asthma’; negative challenge resulted in no change in category and if no challenge was performed classed as ‘Insufficient evidence’.Results127 children [mean age (SD) 9 (3) yrs] were enrolled into the study and completed visit 1; 112 children attended visit 2. Diagnostic categories are shown for each method in the table 1 below.Expert panel gave 56% of children a diagnosis of ‘asthma’ and 20% ‘not asthma’. Allowing children, a second attempt at spirometry and FeNO increased the number with confirmed ‘asthma’ and reduced those classed as insufficient evidence, compared with one attempt. A methacholine challenge in those without a confirmed asthma diagnosis following NG80 recommended testing, significantly increased the number of children with a diagnosis of asthma.Abstract S42 Table 1Shows the number of children categorised as asthma, not asthma, possible asthma or insufficient evidence by expert panel, NG80 and its modified versions Expert Panel NG80 first attempt NG80 allowing 2 attempts at FeNO and Spirometry NG80 with Methacholine challenge Asthma 71 (56%) 20 (16%) 24 (19%) 56 (44%) Not asthma 25 (20%) 38 (30%) 42 (33%) 28 (22%) Possible asthma 4 (3%) 16 (12%) 21 (17%) 3 (2%) Insufficient evidence 27 (21%) 53 (42%) 40 (31%) 40 (31%) ConclusionRepeating simple tests in primary care may improve diagnosis and reduce the number requiring further referral. Methacholine challenge further improved the number with confirmed ‘asthma’.Please refer to page A283 for declarations of interest related to this abstract.

IntroductionWe previously conducted a systematic review of outcome measures for severe asthma and found that existing quality of life (QoL) tools fail to fully capture the deficits experienced by paediatric patients. While the Severe Asthma Questionnaire (SAQ) has been developed for adults, its suitability for children and adolescents remained unexplored. Our aim was to assess the appropriateness of the SAQ for paediatric use and develop a prototype Paediatric SAQ (PSAQ).MethodsWe conducted qualitative interviews with children, adolescents, parents, and Healthcare Professionals (HCPs) caring for severe asthma patients. Participants’ perspectives on the relevance, comprehensibility, and comprehensiveness of the SAQ for the paediatric population were sought. The interviews were analysed thematically, and the findings informed development of a prototype PSAQ.ResultsA total of 26 patients and parents of children with severe asthma aged 7–17 years were interviewed. The majority were female and had experience with biologics. The 20 HCPs interviewed had ≥10 years’ experience practicing at a severe asthma centre. Participants represented 11 countries. The majority of SAQ items were deemed relevant with suggestions to remove adult-related examples and edits to improve comprehensibility. For instance, a parent commented their adolescent ‘may not be able to do housework if she’s feeling that she’s not having a good day’, and the adolescent echoed that if they ‘had a big flare-up of my asthma, I’m not going to be cleaning’, and suggested using the term ‘chores’. However, examples such as ‘home maintenance’ and ‘gardening’ were considered irrelevant, a sentiment shared by HCPs who noted the limited familiarity of patients with such adult-related activities. Participants recommended enhancing the PSAQ’s comprehensiveness by addressing environmental triggers, pets, and treatment burden. Several patients mentioned they ‘want a pet but can’t because of my asthma’ while others expressed ‘I think it’s been one of the issues throughout my life with asthma um making sure to take the medication’.ConclusionsWe have developed the prototype PSAQ for assessing QoL impairments specific to paediatric severe asthma. Further research will validate the PSAQ, which will be valuable for patient monitoring in clinic and evaluating treatment effectiveness in clinical trials.Please refer to page A283 for declarations of interest related to this abstract.

Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional dyspnoea in young people. We have previously shown that subjects with EILO have a breathing pattern disorder (BPD).1 2 AimsTo determine if large tidal volumes beyond physiological capacity at peak exercise cause EILO symptoms.MethodWe retrospectively analysed cardiopulmonary exercise test (CPET) data in children with exercise induced dyspnoea and identified two cohorts of 20 patients each (A) EILO with BPD and (B) BPD only. EILO: stridor or feeling of throat constriction during CPET. BPD: evidence of hyperventilation (increased breathing frequency (BF) or large tidal volumes (VT)), stunted increase in tidal volume or an erratic breathing pattern in response to exercise on the CPET plots. To further characterise the two groups, the Empey Index (ratio of FEV1 (ml): PEFR (l/min)) was compared pre- and post-exercise between and within groups.ResultsDemographic data were similar between groups (table 1). There was no difference in tidal volumes at peak exercise between the EILO and BPD groups on unadjusted T-tests (table 1) and univariate and multivariate logistic regression analysis (p=0.14). There was no difference in the Empey index between the two groups at either time point. There was no relationship between the post-exercise and baseline Empey index in either group.Abstract S47 Table 1Demographics, Spirometry and CPET data Difference Between Medians P-value P-value Summary Age 0 0.9685 ns Height (m) 0.008 0.9947 ns Weight (kg) 4.9 0.2084 ns Peak VO2/kg (ml/min/kg) 3.8 0.2677 ns VE Peak (L/min) -4.18 0.9097 ns VT at Peak (L) 0.3435 0.0773 ns FEV1 (L) Pre-exercise (EILO vs BPD) -0.065 0.9307 ns FEV1 (L) Post-exercise (EILO vs BPD) -0.05 0.9502 ns PEF (L) Pre-exercise (EILO vs BPD) -0.445 0.2236 ns PEF (L) Post-exercise (EILO vs BPD) 0.13 0.6819 ns FEV1 (L) Pre- vs post-exercise (EILO) -0.025 0.8778 ns FEV1 (L) Pre- vs post-exercise (BPD) 0.155 0.6063 ns PEF (L) Pre- vs post-exercise (EILO) -0.01 0.9387 ns PEF (L) Pre- vs post-exercise (BPD) 0.73 0.2271 ns Empey Index (Pre) 0.3146 0.3307 ns Empey Index (Post) 0.1146 0.9285 ns Empey Index (Pre vs Post EILO) -0.2456 0.4612 ns Empey Index (Pre vs Post BPD) -0.4456 0.1415 ns ConclusionsWe found no difference in tidal volumes at peak exercise and the Empey index between EILO and BPD groups. Further work is needed to establish why some subjects with augmented tidal volumes at peak exercise have symptoms of EILO while others (BPD group) do not.ReferencesWells C, et al. Paediatr Respir Rev. 2023;46:37–48.Makariou I, et al. European Respiratory Journal Sep 2022;60(suppl 66):2982

BackgroundPreschool wheeze affects about one in three children aged under 5 years in the UK and may be associated with sensitization to aeroallergens. Little is known about the effect of preschool wheeze and atopy on airway mechanics. Forced oscillometry technique (FOT) is a non-invasive, effort-independent lung function technique, which measures airway mechanics expressed as respiratory impedance and is composed of resistance (Rrs) and reactance (Xrs). We sought to; 1) assess the feasibility of FOT in children with preschool wheeze, 2) establish baseline and bronchodilator reversibility (BDR) for FOT measurement in preschool wheezers and relate results to symptom control, quality of life and atopic status.MethodsA prospective, cross-sectional study was undertaken in 35 children aged 1–5 years old with doctor-diagnosed recurrent preschool wheeze attending a paediatric respiratory clinic. A pseudorandom FOT device was used to examine Rrs and Xrs at a frequency of 8 Hz and then repeated after bronchodilator administration. Symptoms and quality of life were assessed using the Test for Respiratory and Asthma Control in Kids (TRACK) and Paediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) to correlate symptoms with FOT baseline measurements.Results12/35 children had aeroallergen sensitisation. 18/35 (51%) children successfully completed FOT measurement, median age= 4 (3–5). (63%) of those who completed the test were ≥ 4 years. Atopic and non-atopic preschool wheezers had raised Rrs and impaired Xrs, with atopic wheezers having significantly worse Rrs, p= 0.04. Acceptable BDR studies were achieved in 16/35 of the children tested. Significant BDR was seen in Rrs and Xrs in atopic and non-atopic children, figure 1. However, the levels of bronchodilator responsiveness were similar in atopic and non-atopic wheezers. There was no correlation between baseline FOT measurements and TRACK or PACQLQ scores.Abstract S45 Figure 1Bronchodilator response identified by forced oscillometry technique. Shown: a) respiratory resistance before and after bronchodilator, b) respiratory reactance before and after bronchodilator[Figure omitted. See PDF]DiscussionFOT was only feasible in clinical settings in children with preschool wheeze ≥4 years of age. Rrs is raised and Xrs is impaired in children with preschool wheeze and these parameters improve in response to bronchodilator. Further studies are needed to relate FOT in atopic and non-atopic wheezers to other objective measures i.e., bronchial samples to better understand the differences between groups.Please refer to page A284 for declarations of interest related to this abstract.

This brief paper summarizes a mixed method review of over 500 neuroscientific reports investigating the proposition that general intelligence (g or IQ) and multiple intelligences (MI) can be integrated based on common and unique neural systems. Extrapolated from this interpretation are five principles that inform teaching and curriculum so that education can be strengths-based and personalized to promote academic achievement. This framework is proposed as a comprehensive model for a system of educational cognitive neuroscience that will serve the fields of neuroscience as well as educators. Five key principles identified are culture matters, every brain is unique—activate strengths, know thyself, embodied cognition/emotional rudder, and make it mean something.

Abstract I argue that Aristotle's arguments in passages regarding chance in the Physics and in passages about ignorance in action in the Nicomachean and Eudemian Ethics presuppose two different uses of 'for the sake (ἕνεκα) of something', which are able to explain respectively the wish or thought of agents and the type or nature of what they actually do. In my view, however, this does not commit Aristotle, in the 'ignorance' passages from the two Ethics, to holding that the type or nature of what the agents actually do is for the sake of killing or wounding.

One of the central problems of any phenomenological account concerning alienness is that the phenomenon itself seems to constantly avoid both our gaze as well as our theoretical grasp. Characterized by Edmund Husserl as that which is accessible in its fundamental inaccessibility and by Bernhard Waldenfels as that which perpetually surpasses any sense-horizon, alienness (as distinguished from the mere difference of otherness) reveals the limits of our experience and reveals the limits of our theoretical discourse. In this context, I investigate the relation between radical alienness and the universality of meaning from the standpoint of Waldenfels’s account of responsivity and Heidegger’s method of formal indication. While Waldenfels’s project of overcoming intentionality as the basic structure of sense-giving toward a more original dimension of responsivity avoids the pitfalls of logification and egocentrism that lead to the appropriation of the alien, this move beyond intentionality also transgresses the limits of experience. How can we then speak from a phenomenological standpoint about the demand and the basic response that always already precede sense-giving? I contend that a possible way to tackle this issue can be found in Heidegger’s early account of formal indicative conceptuality. By highlighting a series of three central similarities with Waldenfels’s responsive phenomenology, I show that a formal indicative rethinking of responsivity is possible and that it manages to avoid the appropriation of the alien, i.e., integrating it into a preestablished order and completely determining it, while it still maintains a connection with the original lived-experience and the world.

Cinematic spaces are defined by their ability to create new spaces through reorganizing physical environments, a process facilitated by cinema. Directors use unique spaces in their films to convey specific themes and emotions. In Pelin Esmer's İşe Yarar Bir Şey (Something Useful, 2017), the train serves as the setting for the film's initial segment, offering views of external lives from within through the window. This prompts individuals to reflect, question their existence, and experience diverse emotional states. The objective of this study, which examines the 2017 film Something Useful, is to analyze the spaces utilized and the spatial experiences of the protagonists at the threshold by examining them through the lenses of Gaston Bachelard's (1994) concepts of home, Stavros Stavrides's (2010) notion of the threshold, and Michel Foucault's (2008) concept of heterotopia. The train, as an example of heterotopia, facilitates a transition to the protagonists' inner worlds while observing the external world. This space is characterized by a different experience of time, functioning as a transitional space that is both physical and metaphorical. It is marked by threshold elements, such as glass, which delineate and symbolize the space's function as a conduit between inner and outer realms. The house is an uncanny space for existential inquiries and suicide. It is a mix of cosmos and chaos.