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Introduction: A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA)., Methods and Analysis: This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6-17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models., Ethics and Dissemination: The study has been approved by the South Central-Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners., Trial Registration Number: ISRCTN12109108; EudraCT Number: 2019-004085-17., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies., Methods: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria., Results: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV 1 ) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately)., Conclusions: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma., Competing Interests: Conflict of interest: E. Khaleva and A. Rattu declare funding from 3TR European Union Innovative Medicines Initiative 2 to their institution for the present manuscript. C. Brightling declares grants from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic and 4DPharma; consulting fees from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic, 4DPharma and Teva; and support from the 3TR project. G.W. Clarke declares that he is an employee of AstraZeneca; and that he holds stock or stock options in AstraZeneca. M. van den Berge declares grants from GlaxoSmithKline, AstraZeneca, Roche, Genentech and Novartis paid to the university. A. Bossios declares honoraria for lectures from GlaxoSmithKline, AstraZeneca, Teva and Novartis; support for attending meetings from AstraZeneca and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Novartis and Sanofi; being a member of the Steering Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) of the European Respiratory Society; Vice-chair of the Nordic Severe Asthma Network (NSAN). V. Ramiconi and S. Romagosa Vilarnau declare unrestricted educational grants paid to the organisation from Novartis, Pfizer, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, AbbVie, LeoPharma, Boehringer Ingelheim, Sanofi, Regeneron, OM Pharma, MSD, Roche and DBV Technologies; support for attending meetings from Novartis. S-E. Dahlén declares a 3TR Innovative Medicines Initiative grant; consulting fees for AstraZeneca, Cayman Co., GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva; payment for lectures from AstraZeneca and Sanofi. S. Principe declares support for provision of study materials and medical writing. G. Hedlin declares participation in advisory boards of AstraZeneca and Sanofi. F. Singer reports grants from Lung League Bern, grants from the Swiss Cystic Fibrosis Society (CFCH), personal fees from Vertex Pharmaceuticals, personal fees from Novartis, outside the submitted work. A. Deschildre reports personal consulting fees from Sanofi-Regeneron, ALK, Novartis and GlaxoSmithKline; honoraria for lectures from ALK, Boehringer Ingelheim and Novartis; support for attending meetings from AstraZeneca, Stallergènes-Greer, MEDA, Nutricia, Sanofi and Novartis, outside the submitted work; and being on the scientific committee of SFA (Société Française d'Allergologie). L.J. Fleming declares participation in advisory boards and honoraria for lectures from Sanofi, Respiri UK, AstraZeneca, Novartis and Teva, outside of the scope of this publication; all payments were made to her institution. H. Staudinger reports that he is a salaried employee of Sanofi Genzyme and owns company stock of Sanofi and Merck & Co. K.C. Pike declares consultancy fees from Novartis, Adherium and Respiri, and honoraria for a lecture from Novartis. J. Grigg declares payments from GlaxoSmithKline, OM Pharma, Omron and Novartis (advisory boards), Sanofi (for lectures) and AstraZeneca (CI clinical trial). N. Rutjes reports personal fees for advisory board work from Sanofi. G.H. Koppelman reports receiving research grants from the Lung Foundation of the Netherlands, Ubbo Emmius Foundation, H2020 European Union, Teva, GlaxoSmithKline and Vertex, outside this work (money to institution); he reports memberships of advisory boards to GlaxoSmithKline and PURE-IMS, outside this work (money to institution). D. Cunoosamy holds shares in AstraZeneca and Sanofi. A.H. Maitland-van der Zee has received research grants outside the submitted work from GlaxoSmithKline, Boehringer Ingelheim and Vertex, she is the PI of a P4O2 (Precision Medicine for more Oxygen) public private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Roche, Smartfish, SODAQ, Thirona, TopMD and Novartis), and she has served in advisory boards for AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim with money paid to her institution. K.F. Chung has received honoraria for participating in advisory board meetings of GlaxoSmithKline, AstraZeneca, Roche, Novartis, Merck and Shionogi, regarding treatments for asthma, COPD and chronic cough, and has also been remunerated for speaking engagements for Novartis and AstraZeneca; received a MRC grant on Precision Medicine for severe asthma, EPSRC grant on air pollution and asthma, and a GlaxoSmithKline grant on mepolizumab and eosinophils in asthma. P. Nagakumar received speaker fees for talks on severe asthma from GlaxoSmithKline and Novartis. G. Brusselle declares payments from AstraZeneca, Novartis, Boehringer Ingelheim, Chiesi, Sanofi, GlaxoSmithKline and MSD, outside the submitted work. E. Hamelmann declares support from the German Ministry of Education and Research (BMBF) and German Asthma Net (GAN) eV; funding for research in severe asthma in children (CHAMP-01GL1742D) and for Severe Asthma Register. S. Vijverberg is PI of the PERMEABLE consortium. The PERMEABLE consortium is a research consortium focused on severe asthma and allergy and supported by ZonMW (456008004), the Swedish Research Council (2018-05619), the Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012), and the German Ministry of Education and Research (BMBF) FKZ01KU1909A), under the frame of the ERA PerMed JTC 2018 Call. In addition, S. Vijverberg has received research funding for a project on severe paediatric asthma from the Lung Foundation Netherlands (6.2.18.244JO). A-M.M. Schoos has participated on an advisory board for ALK. B. Dahlén reports personal fees for lectures from AstraZeneca, Novartis and Sanofi; and grants from Novartis and GlaxoSmithKline, outside the submitted work; participation on an advisory board for AstraZeneca and Sanofi. A. Exley declares being a minority shareholder in GlaxoSmithKline Plc. E.A. Gaillard reports consultancy work for Boehringer Ingelheim with money paid to the institution (University of Leicester); investigator-led research grants from Circassia Group, Gilead Sciences, Chiesi Limited and Propeller Health; and has a research collaboration with Medimmune. M. Pijnenburg declares payments to her institution from Sanofi Genzyme (advisory work) and Novartis (speakers fee). E. Melén declares consulting fees from AstraZeneca, Chiesi, Novartis and Sanofi, outside the submitted work. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis; sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi and GlaxoSmithKline, and a research grant to her institute from AstraZeneca for a UK multi-centre study. C. Pilette declares grants, consulting fees and honoraria for lectures (paid to institution) from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Mundipharma, Teva, Sanofi and ALK. C. Porsbjerg declares grants (paid to institution), consulting fees (paid to institution and personal honoraria) and honoraria for lectures (paid to institution and personal honoraria) from AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK; participation on an advisory board (paid to institution and personal honoraria) for AstraZeneca, Novartis, Teva, Sanofi and ALK. C. Coleman and C. Williams declare funding received to support this work by the European Lung Foundation (ELF) from the European Commission's Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 831434 (3TR), and are employees of the ELF. B. Ahrens, S. Kaul, D. Hartenstein and V. Mahler declare no conflict of interest for this article and state that the views expressed in this review are the personal views of the author and may not be understood or quoted as being made on behalf of or reflecting the position of the respective national competent authorities, the European Medicines Agency or one of its committees or working parties. L.G. Heaney declares support from the 3TR; grants from industrial pharma partners Amgen, AstraZeneca, Medimmune, Janssen, Novartis, Roche/Genentech, GlaxoSmithKline and Boehringer Ingelheim; project grant funding from Medimmune, Novartis UK, Roche/Genentech and GlaxoSmithKline, outside the submitted work; payments for lectures by AstraZeneca, Novartis, Roche/Genentech, GlaxoSmithKline, Chiesi and Teva, outside the submitted work; travel funding support to international respiratory meetings by AstraZeneca, Chiesi, Novartis, Boehringer Ingelheim, Teva and GlaxoSmithKline, outside the submitted work; advisory boards for AstraZeneca, Novartis, GlaxoSmithKline, Chiesi, Teva, Theravance and Vectura, outside the submitted work. R. Djukanovic declares funding from the European Respiratory Society, Teva, GlaxoSmithKline, Novartis, Sanofi and Chiesi for the SHARP Clinical Research Collaboration; consulting fees for Synairgen; honorarium for a lecture from GlaxoSmithKline; participation on a data safety monitoring board or advisory board for Kymab (Cambridge) and shares in Synairgen outside of the submitted work. A. Bourdin declares grants from Boehringer and AstraZeneca; consulting fees and payments from Boehringer, AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, Regeneron, Sanofi and Amgen outside of the submitted work. B. Karadag declares participation in a trial conducted by Sanofi (payment to institution) and attending advisory board meetings for GlaxoSmithKline (personal fees). K. Blumchen declares grants from Aimmune Therapeutics, DBV Technologies and Hipp GmbH; consulting fees from Aimmune Therapeutics, DBV Technologies and Allergy Therapeutics; payments for lectures from Aimmune Therapeutics, DBV Technologies, Novartis, Allergy Therapeutics, HAL, ALK, Allergopharma, Nutricia, Thermo Fisher Scientific, and Bausch and Lomb; personal fees for expert discussions from Novartis and Nestle; fees for attending meetings from Aimmune Therapeutics and DBV Technologies; being on data safety monitoring board of Charité, IIT. A. Gupta received speaker/advisory board fees from GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim; received research grants from GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim, paid to institution. L. Giovannini-Chami declares consulting fees from ALK, AstraZeneca and Novartis; honoraria for lectures, presentations from Novartis, ALK, Stallergènes, Sanofi and AstraZeneca; support for attending meetings from Stallergènes; participation on a data safety monitoring board or advisory board for Sanofi; being head of the Scientific Committee of the French Pediatric Pulmonology and Allergology Society. C.S. Murray has received lecture fees from GlaxoSmithKline and Novartis; received grants from Asthma UK and National Institute for Health Research; and has participated on an advisory board for Boehringer Ingelheim. G. Roberts declares European Union Innovative Medicines Initiative funding and AstraZeneca paid to the institution. Other co-authors declare no conflicts of interest for this article., (Copyright ©The authors 2023.)

Aim: Using a non-invasive lung function technique (interrupter resistance, Rint), we aimed to determine whether a dose-response to salbutamol could be detected in wheezy preschool children and if so, which dose of salbutamol should be administered to routinely evaluate bronchial reversibility., Method: Wheezy children (3 to <7 years) were enrolled in a prospective multicenter study. Rint was measured at baseline, and after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol. Data were analyzed using mixed modeling approach with an inhibitory maximal effect (I max ) model, to account for a sparse sampling design. Simulations were performed to predict the percentage of children with significant Rint reversibility at several doses., Results: Final results were available in 99 children out of 106 children included. The model adequately fitted the data, showing satisfactory goodness-of-fit plots and a low residual error of 8%. Children with uncontrolled symptoms had lower I max (ie, showed less reversibility) compared to children with totally/partly controlled symptoms (0.23 vs. 0.31, P < 0.001). Dose to reach 50% of I max (D 50 ) was 51 μg. According to simulations, 88.1% of children with significant reversibility at dose 800 μg would already show significant reversibility at 400 μg., Conclusion: Interrupter resistance was able to measure a dose-response curve to salbutamol in wheezy preschool children, which was similar to that of older patients. Young children require a high dose of salbutamol to correctly assess airway bronchodilator response, especially these with poor symptom control., (© 2018 Wiley Periodicals, Inc.)

Interrupter resistance (R(int)) is a widely used measure of airway caliber, but concerns remain about repeatability and sensitivity. Some R(int) variability may derive from the linear back-extrapolation algorithm (LBE 30/70) usually used to estimate driving pressure. To investigate whether other methods of estimating driving pressure could improve repeatability and sensitivity, we studied 39 children with asthma. Two measurements of R(int)-each the median of 10 interruptions-were made 5 min apart, and 14 children had a third measurement after bronchodilator (R(int)BD). Mouth pressure transients were analyzed using several algorithms, to compare the magnitude, repeatability, and sensitivity to bronchodilator change of R(int) values yielded. Algorithms taking driving pressure from later in the transient, predictably, yielded higher values of R(int) than those which back-extrapolated to time of valve closure. Algorithms which did not rely on back-extrapolation, including mean oscillation pressure (MOP) and mean plateau pressure (MP 30/70) had better repeatability. Sensitivity to detect change, calculated as ratio of bronchodilator response to repeatability coefficient (DeltaR(int)/CR), was also better for non-extrapolating algorithms: MP 30/70 1.67, LBE 30/70 1.28 (P = 0.0004). Measuring R(int) using techniques other than conventional back-extrapolation may give more consistent and clinically useful results, and these approaches merit further exploration., ((c) 2007 Wiley-Liss, Inc.)

Background: Xanthines have been used in the treatment of asthma as a bronchodilator, though they may also have anti-inflammatory effects. The current role of xanthines in the long-term treatment of childhood asthma needs to be reassessed., Objectives: To determine the efficacy of xanthines (e.g. theophylline) in the maintenance treatment of paediatric asthma., Search Strategy: A search of the Cochrane Airways Group Specialised Register was undertaken with predefined search terms. Searches are current to May 2005., Selection Criteria: Randomised controlled trials,lasting at least four weeks comparing a xanthine with placebo, regular short-acting beta-agonist (SABA), inhaled corticosteroids (ICS), cromoglycate (SCG), ketotifen (KET) or leukotriene antagonist, in children with diagnosed with chronic asthma between 18 months and 18 years old., Data Collection and Analysis: Two reviewers independently selected each study for inclusion in the review and extracted data. Primary outcome was percentage of symptom-free days., Main Results: Thirty-four studies (2734 participants) of adequate quality were included. Xanthine versus placebo (17 studies): The proportion of symptom free days was larger with xanthine compared with placebo (7.97% [95% CI 3.41, 12.53]). Rescue medication usage was lower with xanthine, with no significant difference in symptom scores or hospitalisations. FEV1 , and PEF were better with xanthine. Xanthine was associated with non - specific side-effects. Data from behavioural scores were inconclusive. Xanthine versus ICS (four studies) : Exacerbations were less frequent with ICS, but no significant difference on lung function was observed. Individual studies reported significant improvements in symptom measures in favour of steroids, and one study reported a difference in growth rate in favour of xanthine. No difference was observed for study withdrawal or tremor. Xanthine was associated with more frequent headache and nausea. Xanthine versus regular SABA (10 studies): No significant difference in symptoms, rescue medication usage and spirometry. Individual studies reported improvement in PEF with beta-agonist. Beta-agonist treatment led to fewer hospitalisations and headaches. Xanthine was associated with less tremor. Xanthine versus SCG (six studies ): No significant difference in symptoms, exacerbations and rescue medication. Sodium cromoglycate was associated with fewer gastro-intestinal side-effects than xanthine. Xanthine versus KET (one study): No statistical tests of significance between xanthine and ketotifen were reported. Xanthine + ICS versus placebo + same dose ICS (three studies) : Results were conflicting due to clinical/methodological differences, and could not be aggregated., Authors' Conclusions: Xanthines as first-line preventer alleviate symptoms and reduce requirement for rescue medication in children with mild to moderate asthma. When compared with ICS they were less effective in preventing exacerbations. Xanthines had similar efficacy as single preventative agent compared with regular SABA and SCG. Evidence on AEs (adverse effects) was equivocal: there was evidence for increased AEs overall, but no evidence that any specific AE (including effects on behaviour and attention) occurred more frequently than with placebo. There is insufficient evidence from available studies to make firm conclusions about the effectiveness of xanthines as add-on preventative treatment to ICS, and there are no published paediatric studies comparing xanthines with alternatives in this role. Our data suggest that xanthines are only suitable as first-line preventative asthma therapy in children when ICS are not available. They may have a role as add-on therapy in more severe asthma not controlled by ICS, but further studies are needed to examine this, and to define the risk-benefit ratio compared with other agents.

Electronic devices are now available to measure and store lung function parameters in the home. Before adopting a device for clinical or research use, it is important to validate it in the target patient group. The aim of this study was to assess a low-cost, portable, logging spirometer, the VM Plus (VM), against a standard laboratory Jaeger spirometer (JS) for use in children with respiratory disease. Seventy children with stable asthma or cystic fibrosis performed spirometry on the two devices, and results for peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) were compared. Comparison was made both using the two devices separately (separate method) and with the devices connected in series (series method). Reproducibility of the VM measurements was also assessed. Correlation between measurements was close (R values: separate, PEF, 0.91; FEV(1), 0.94; series, PEF, 0.97, FEV(1), 0.99), but PEF readings on the VM Plus were substantially higher than with the JS (mean difference: separate, 54.8 L/min; series, 28.2 L/min). This reflects well-reported differences in PEF measurements between the Mini-Wright PEF meter, on which the VM Plus spirometer is based, and conventional spirometers. Limits of agreement (series method) were: PEF, -13.2 to +69.6 L/min; FEV(1), -0.03 to +0.19 L. Reproducibility of VM Plus measurements was acceptable: coefficient of variation for PEF was 4%; for FEV(1), 4.3%; coefficient of reproducibility for PEF, 39 L/min; for FEV(1), 0.26 L. The VM Plus provides reasonably accurate, reproducible measurements of PEF and FEV(1), but intrinsic bias, particularly in PEF measurement, needs to be taken into account. Its potential to document longitudinal changes in lung function in children with respiratory disease at home merits further study.

Background: The role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear., Aim: To investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma., Methods: A total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 microg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period., Results: Thirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD., Conclusion: Improvement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.

Aim: To determine whether asthmatic children who present to hospital with hypoxia perceive breathlessness less well than non-hypoxic presenters., Methods: A total of 27 children aged 5-16 years (mean age 10) admitted with acute asthma had recordings of oxygen saturation (SaO(2)), clinical score, forced expiratory volume in one second (FEV(1)), and breathlessness score (HMP) at admission and at 5, 10, 24, 48, and 72 hours after admission. Those defined as hypoxic (SaO(2) <92%) at admission were compared with a non-hypoxic group., Results: Twelve children were hypoxic at admission. Compared with the non-hypoxic group they were younger (8.6 (SD 2.8) v 11.2 (2. 8) y, p = 0.02), and had greater airway obstruction (FEV(1) 32.5 (10)% v 54.3 (26)%, p = 0.0073, 95% confidence interval (CI) -36.9 to -6.6) yet had a trend towards less breathlessness (median HMP 4 v 3, p = 0.062, CI -0.001 to 2.00) at admission. The hypoxic group had a smaller change in breathlessness from admission to discharge, despite a similar improvement in FEV(1), reflected in a lower ratio of change in HMP to change in FEV(1) (DeltaHMP/DeltaFEV(1)) (median DeltaHMP/DeltaFEV(1) 0.021%(-1) v 0.073%(-1), p = 0.0081, CI -0.075 to -0.016). Linear regression analysis showed a strong relation between DeltaHMP/DeltaFEV(1) and initial SaO(2) (p = 0.004, r = 0. 54)., Conclusions: Asthmatic children who present to hospital hypoxic tend to perceive themselves as less breathless than non-hypoxic children. This may predispose to a future life threatening attack.

Children with acute asthma account for a significant proportion of paediatric hospital admissions, and clear guidelines exist for their care. The aim of this study was to determine their management in the UK. Over 1 year (February 1995 to January 1996), children aged 1-14 yrs admitted with acute asthma were studied in both teaching and district general hospitals. An admission pro forma was used to collect data prospectively, with a computer-based information management system for the input of admissions in each centre. Ten centres collected data prospectively, with 1,578 admissions involving 1,352 children (median age 3.6 yrs). Sixty two per cent of children were <5 yrs of age. Sixty three per cent of admissions had initial arterial oxygen saturation (Sa,O2) recorded, and, in those older than 5 yrs, 36% had their initial peak expiratory flow rate recorded. Systemic steroids were given to 78%. An initial Sa,O2 of <92% was associated with a longer stay in hospital, and also with intravenous treatment. Preventative treatment increased from 42% on admission to 53% on discharge. The rates of documented education were low. This is the largest UK study following publication of national guidelines and shows that there is still room for improvement in the management of children admitted with acute asthma.

Branhamella catarrhalis has been associated with exacerbations of chronic bronchitis and asthma in adults. To investigate the possible role of B. catarrhalis in asthma of early childhood, we took posterior pharyngeal swabs from 24 normal children, 20 well asthmatics, and 20 acutely wheezy asthmatics, all between 1 and 4 years of age. On culture, 33% of the normal children were colonized with B. catarrhalis; colonization rates in the well asthmatics (70%) and in the wheezy asthmatics (75%) were significantly higher than in normals. The nature of this association requires further study.

Over a 25 year period, 31 asthmatic children received artificial ventilation for acute asthma at Alder Hey Children's Hospital on 48 occasions. Altogether 47 episodes occurred from 1971-89, with no decline in the number of episodes per year (mean 2.5) over this period. Eight children died during intermittent positive pressure ventilation (IPPV), and of the 23 survivors, three further children had subsequently died from asthma. Seventeen children were followed up for more than a year after IPPV. Sixteen still had symptoms of asthma and over half had symptoms every day. Ten cooperated with pulmonary function tests: mean forced expiratory volume in one second was 83% of predicted and geometric mean provocative histamine concentration (PC20) was 2.1 mg/ml. Since the follow up study a fourth patient had died from asthma. IPPV continues to be required for a small number of asthmatic children each year. The survivors remain a high risk group with significant continuing morbidity and mortality.

Asthma is a multifactorial disease of the airways characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. Conventional MHC class II–restricted CD4+ T cells are considered a key cell in asthma pathogenesis because they have a broad T-cell receptor repertoire, providing specificity and reactivity to diverse protein allergens. This notion was challenged when a study found that invariant Natural Killer (NK) T cells were the predominant T cells in the lung and bronchoalveolar lavage fluid of all asthmatic subjects studied. This finding was provocative because invariant NKT cells have a very limited T-cell receptor repertoire and are specific for a restricted set of lipid antigens that bind to CD1d, a nonpolymorphic MHC-like molecule. However, multiple subsequent studies failed to replicate the initial study and instead found that invariant NKT cells are present as a small fraction of the total T cells in the asthmatic lung. Thus, we believe that although CD1d-restricted NKT cells might play a role in modulating the asthmatic phenotype, they are not the critical drivers of the asthmatic response, a role we believe is still held by conventional MHC class II–restricted CD4+ T cells. [Copyright &y& Elsevier]