Publications
1241 results found
Burgess JK, Weiss DJ, Westergren-Thorsson G, et al., 2024, Extracellular matrix as a driver of chronic lung diseases, American Journal of Respiratory Cell and Molecular Biology, Vol: 70, Pages: 239-246, ISSN: 1044-1549
The extracellular matrix (ECM) is not just a 3 dimensional scaffold that provides stable support for all cells in the lungs but is also an important component of chronic fibrotic airways, vascular, and interstitial diseases. It is a bioactive entity that is dynamically modulated during tissue homeostasis and disease, which controls structural and immune cell functions, drug responses, and which can release fragments that have biological activity and that can be used to monitor disease activity. There is a growing recognition of the importance of considering ECM changes in chronic airways, vascular, and interstitial diseases including (i) compositional changes, (ii) structural and organizational changes, and (iii) mechanical changes -and how these impact on disease pathogenesis. Since altered ECM biology is an important component of many lung diseases, disease models must incorporate this factor to fully recapitulate disease-driver pathways and to study potential novel therapeutic interventions. While novel models are evolving that capture some or all of the elements of the altered ECM microenvironment in lung diseases, opportunities exist to more fully understand cell-ECM interactions that will help devise future therapeutic targets to restore function in chronic lung diseases. In this perspective article, we review evolving knowledge about the ECM's role in homeostasis and disease in the lung.
Daines L, Donaghy E, Canny A, et al., 2024, Clinician views on how clinical decision support systems can help diagnose asthma in primary care: a qualitative study., J Asthma, Vol: 61, Pages: 377-385
OBJECTIVE: Asthma can be difficult to diagnose in primary care. Clinical decision support systems (CDSS) can assist clinicians when making diagnostic decisions, but the perspectives of intended users need to be incorporated into the software if the CDSS is to be clinically useful. Therefore, we aimed to understand health professional views on the value of an asthma diagnosis CDSS and the barriers and facilitators for use in UK primary care. METHODS: We recruited doctors and nurses working in UK primary care who had experience of assessing respiratory symptoms and diagnosing asthma. Qualitative interviews were used to explore clinicians' experiences of making a diagnosis of asthma and understand views on a CDSS to support asthma diagnosis. Interviews were audio-recorded, transcribed verbatim and analyzed thematically. RESULTS: 16 clinicians (nine doctors, seven nurses) including 13 participants with over 10 years experience, contributed interviews. Participants saw the potential for a CDSS to support asthma diagnosis in primary care by structuring consultations, identifying relevant information from health records, and having visuals to communicate findings to patients. Being evidence based, regularly updated, integrated with software, quick and easy to use were considered important for a CDSS to be successfully implemented. Experienced clinicians were unsure a CDSS would help their routine practice, particularly in straightforward diagnostic scenarios, but thought a CDSS would be useful for trainees or less experienced colleagues. CONCLUSIONS: To be adopted into clinical practice, clinicians were clear that a CDSS must be validated, integrated with existing software, and quick and easy to use.
Melén E, Faner R, Allinson JP, et al., 2024, Lung-function trajectories: relevance and implementation in clinical practice, The Lancet, ISSN: 0140-6736
Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.
Diaconu M, Bush A, Tan H-L, 2024, Home sleep studies in children with neurodisabilities: success rates and parental perception., ERJ Open Res, Vol: 10, ISSN: 2312-0541
Home sleep studies in children with neurodisabilities have a high success rate (85.4% in our cohort), particularly in patients with limited mobility, have the advantage of reducing the burden of hospital admissions and are the family preferred option https://bit.ly/46t8aWN.
Chatziparasidis G, Chatziparasidi MR, Kantar A, et al., 2024, Time-dependent gene-environment interactions are essential drivers of asthma initiation and persistence., Pediatr Pulmonol
Asthma is a clinical syndrome caused by heterogeneous underlying mechanisms with some of them having a strong genetic component. It is known that up to 82% of atopic asthma has a genetic background with the rest being influenced by environmental factors that cause epigenetic modification(s) of gene expression. The interaction between the gene(s) and the environment has long been regarded as the most likely explanation of asthma initiation and persistence. Lately, much attention has been given to the time frame the interaction occurs since the host response (immune or biological) to environmental triggers, differs at different developmental ages. The integration of the time variant into asthma pathogenesis is appearing to be equally important as the gene(s)-environment interaction. It seems that, all three factors should be present to trigger the asthma initiation and persistence cascade. Herein, we introduce the importance of the time variant in asthma pathogenesis and emphasize the long-term clinical significance of the time-dependent gene-environment interactions in childhood.
Tian K, Dangarh P, Zhang H, et al., 2024, Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection., Clin Exp Allergy, Vol: 54, Pages: 109-119
BACKGROUND: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain. METHODS: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity. RESULTS: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised. CONCLUSIONS: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.
Levy ML, Beasley R, Bostock B, et al., 2024, A simple and effective evidence-based approach to asthma management: ICS-formoterol reliever therapy., Br J Gen Pract, Vol: 74, Pages: 86-89
Makrinioti H, Bush A, 2024, Can We Test the Function of the Small Airways in Children Outside the Laboratory?, Chest, Vol: 165, Pages: 241-242
Bush A, 2024, Strip searching by the police: potential for abuse?, Arch Dis Child, Vol: 109
Khalaf Z, Bush A, Saglani S, et al., 2024, Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma, Thorax, Vol: 79, Pages: 112-119, ISSN: 0040-6376
Background Asthma trials and guidelines often do not distinguish between adolescents and younger children. Using a large English data set, we evaluated the impact of age on asthma characteristics, management and exacerbations.Methods Primary care medical records, 2004–2021, were linked to hospital records. Children were categorised by age at diagnosis and followed until the next age bracket. Ages (based on management guidelines) were 5–8 years, 9–11 years and adolescents (12–16 years). Characteristics evaluated included body mass index, allergies and events before and after diagnosis (symptoms, medication). Exacerbation incidence was calculated. Multivariable Cox proportional hazards determined associations with exacerbations.Results 119 611 children were eligible: 61 940 (51.8%) 5–8 years, 32 316 (27.7%) 9–11 years and 25 355 (21.2%) adolescents. Several characteristics differed by age; children aged 5–8 years had the highest proportion with eczema, food/drug allergy and cough, but adolescents had the highest proportion with overweight/obesity, aeroallergen sensitisation, dyspnoea and short-acting-beta-agonist only use. Exacerbation rates were highest in the youngest children (per 100 person-years (95% CI): 5–8 years =13.7 (13.4–13.9), 9–11 years =10.0 (9.8–10.4), adolescents =6.7 (6.5–7.0)). Exacerbation risk factors also differed by age; 5–8 years: male, eczema and food/drug allergy were strongly associated, but for children ≥9 years old, obesity and aeroallergen sensitisation were strongly associated. For all children, higher socioeconomic deprivation was significantly associated with having an exacerbation. Delayed diagnosis was most common in children aged 5–8 years and was associated with increased exacerbations across all ages.Conclusion Children’s baseline characteristics and exacerbation rates varied according to their age group. Clinica
Baugh A, Buhr RG, Bush A, et al., 2024, Strategies to Classify Lung Function: It's Not Black and White., Am J Respir Crit Care Med, Vol: 209, Pages: 19-20
Chang AB, Boyd J, Bush A, et al., 2024, A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study., Lancet Respir Med, Vol: 12, Pages: 78-88
Improving the treatment of non-cystic fibrosis bronchiectasis in children and adolescents requires high-quality research with outcomes that meet study objectives and are meaningful for patients and their parents and caregivers. In the absence of systematic reviews or agreement on the health outcomes that should be measured in paediatric bronchiectasis, we established an international, multidisciplinary panel of experts to develop a core outcome set (COS) that incorporates patient and parent perspectives. We undertook a systematic review from which a list of 21 outcomes was constructed; these outcomes were used to inform the development of separate surveys for ranking by parents and patients and by health-care professionals. 562 participants (201 parents and patients from 17 countries, 361 health-care professionals from 58 countries) completed the surveys. Following two consensus meetings, agreement was reached on a ten-item COS with five outcomes that were deemed to be essential: quality of life, symptoms, exacerbation frequency, non-scheduled health-care visits, and hospitalisations. Use of this international consensus-based COS will ensure that studies have consistent, patient-focused outcomes, facilitating research worldwide and, in turn, the development of evidence-based guidelines for improved clinical care and outcomes. Further research is needed to develop validated, accessible measurement instruments for several of the outcomes in this COS.
Papiris SA, Veith M, Papaioannou AI, et al., 2024, Alpha1-antitrypsin deficiency in Greece: Focus on rare variants., Pulmonology, Vol: 30, Pages: 43-52
PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis
Bush A, 2023, MULTIDISCIPLINARY MANAGEMENT OF THE CHILD WITH ASTHMA NOT RESPONDING TO TREATMENT, Current Allergy and Clinical Immunology, Vol: 36, Pages: 220-225, ISSN: 1609-3607
Most children with asthma respond well to low-dose inhaled corticosteroids, sometimes with the addition of a long-acting β-2 agonist. Failure to respond is usually because either the diagnosis is wrong or they are not taking their treatment. If the diagnosis truly is asthma and the child is not responding, then, instead of prescribing ever more and higher doses of medications, a complete review to determine what it is about the child and their asthma which is making treatment response suboptimal should be undertaken. The factors to be considered in such a review include adherence, adverse environmental factors and psychosocial influences, and relevant co-morbidities such as obesity and exercise-induced laryngeal obstruction. Such a review means that most children referred for the consideration of biological therapy can in fact be managed with standard treatment approaches. Adherence may be improved by simplifying the regime – for example, the single inhaler for reliever and treatment approach or a once-daily treatment combined with directly observed therapies. In the rare cases of children with true therapy-resistant asthma, a range of expensive injectable biologicals may help, but the need for these is the exception. Sadly, the most common cause of non-responsive asthma globally remains that the medications are either inaccessible or too expensive.
White D, Bush A, Smyth AR, et al., 2023, Why and how should children be protected from the deluge of vaping related media and marketing overexposure?, Breathe (Sheff), Vol: 19, ISSN: 1810-6838
E-cigarettes are products delivering nicotine via inhalation and are devised to mimic tobacco smoking. While they were initially introduced as a device putatively to aid with smoking cessation, their use is now far broader than that. Use by children is significantly increasing. There is growing evidence of the potential harms of vaping. E-liquids used for e-cigarettes contain a wide range of harmful substances, and the clinical consequences of this are now being increasingly demonstrated, such as the rise in cases of e-cigarette- or vaping-associated lung injury. In addition, early use may result in long-term nicotine addiction. Vaping companies utilise marketing methods that distinctly target young people, and weak legislation in the UK allows them free rein to expose children to vaping. In this review we demonstrate why children must be protected from vaping. We must have stringent legislation to prevent easy access to e-cigarettes, including banning the convenience and affordability disposable vapes provide, and prevent marketing that does not warn about the potential health effects. The Australia approach of prescription or pharmacy only access for smoking cessation should be considered to limit exposure of children and minimise use by nonsmokers.
Bush A, 2023, Learning from cystic fibrosis: How can we start to personalise treatment of Children's Interstitial Lung Disease (chILD)?, Paediatr Respir Rev
Cystic fibrosis (CF) is a monogenic disorder cause by mutations in the CF Transmembrane Regulator (CFTR) gene. The prognosis of cystic fibrosis has been transformed by the discovery of highly effective modulator therapies (HEMT). Treatment has changed from reactive therapy dealing with complications of the disease to pro-active correction of the underlying molecular functional abnormality. This has come about by discovering the detailed biology of the different CF molecular sub-endotypes; the development of biomarkers to assess response even in mild disease or young children; the performance of definitive large randomised controlled trials in patients with a common mutation and the development of in vitro testing systems to test efficacy in those patients with rare CFTR mutations. As a result, CF is now an umbrella term, rather than a specific diagnostic label; we have moved from clinical phenotypes to molecular subendotypes. Children's Interstitial Lung Diseases (chILDs) comprise more than 200 entities, and are a diverse group of diseases, for an increasing number of which an underlying gene mutation has been discovered. Many of these entities are umbrella terms, such as pulmonary alveolar proteinosis or hypersensitivity pneumonitis, for each of which there are multiple and very different endotypes. Even those chILDs for which a specific gene mutation has been discovered comprise, as with CF, different molecular subendotypes likely mandating different therapies. For most chILDs, current treatment is non-specific (corticosteroids, azithromycin, hydroxychloroquine). The variability of the different entities means that there is little evidence for the efficacy of any treatment. This review considers how some of the lessons of the success story of CF are being applied to chILD, thus opening the opportunities for truly personalised medicine in these conditions. Advances in knowledge in the molecular biology of surfactant protein C and Adenosine triphosphate binding cass
Bush A, 2023, Going Down, Dooby Doo Down, Down: Identifying Rapid Spirometry Decline., Am J Respir Crit Care Med, Vol: 208, Pages: 1014-1015
Hine J, Fleming L, Judah G, et al., 2023, M17 PATIENT ENGAGEMENT WITH ADHERENCE TECHNOLOGY: LEARNINGS FROM THE ‘FINANCIAL INCENTIVES TO IMPROVE ASTHMA’ (FINA) STUDY, Pages: A269-A270, ISSN: 0040-6376
Background Digital interventions are acceptable and often effective for improving short-term medication adherence for children and young people (CYP) with asthma. Interventions using electronic monitoring devices (EMDs) can be supported by behaviour change techniques such as reminders and financial incentives. Most digital interventions require patient engagement; however, it is important to understand how patients engage to maximise effectiveness. As part of the feasibility assessment of the FINA study, a pilot RCT of a digital financial incentives intervention, patient engagement with EMDs and smartphone app was explored. Methods During the FINA study, CYP (aged 11–17 years old) with asthma monitored their adherence for 24-weeks using an EMD. Participants randomised to financial incentives intervention viewed their adherence (table and bar-graph) and their reward progress (totaliser, traffic-light calendar, and weekly notifications) through a smartphone app. Financial reward was delivered regularly (at 4-, 8- and 12-weeks) and relied upon real-time data; participants were advised to sync their EMD and app daily. Control group viewed their sensor syncing history only and were advised to sync their EMD and app weekly. All participants were requested to promptly report any problems to the research team. Patient engagement was explored using syncing data, technical issue reporting and research team involvement. Results 32 participants are enrolled in on-going trial (intervention, n=16); 84% have completed first 12-weeks. Technical problems were experienced by 13/16 intervention and 8/16 control participants; 12 of whom did not report these until research visit 2 (12-weeks, post-intervention). 7/16 intervention participants did not sync their EMD and app as advised and were reminded by research team at least once ahead of reward delivery; 1 participant only synced once throughout intervention. 14/16 control participants did not sync weekly. Discussion Limited pat
Versi A, Ivan FX, Abdel-Aziz MI, et al., 2023, Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation, Allergy, Vol: 78, Pages: 2906-2920, ISSN: 0105-4538
BACKGROUND: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. METHODS: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). RESULTS: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year. CONCLUSIONS: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.
McGinn EA, Mandell EW, Smith BJ, et al., 2023, Dysanapsis as a Determinant of Lung Function in Development and Disease., Am J Respir Crit Care Med, Vol: 208, Pages: 956-963
Bush A, Ramsey B, Shteinberg M, et al., 2023, Phoenix from the Ashes: Celebrating the 2023 North American Cystic Fibrosis Conference., Am J Respir Crit Care Med, Vol: 208, Pages: 909-910
Gappa M, Bush A, Ersu RH, et al., 2023, Children and the European Respiratory Society: from silos to synergies., Eur Respir J, Vol: 62
Edmondson C, Westrupp N, Short C, et al., 2023, Unsupervised home spirometry is not equivalent to supervised clinic spirometry in children and young people with cystic fibrosis: results from the CLIMB-CF study, Pediatric Pulmonology, Vol: 58, Pages: 2871-2880, ISSN: 1099-0496
BACKGROUND: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested. METHODS: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes. RESULTS: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV1 data pairs. The mean (SD) FEV1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread. CONCLUSION: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately.
Chatziparasidis G, Bush A, Chatziparasidi MR, et al., 2023, Airway epithelial development and function: A key player in asthma pathogenesis?, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 47, Pages: 51-61, ISSN: 1526-0542
Warraich S, Bush A, Levy ML, et al., 2023, Regular (up to 10 puffs 4-hourly) inhaled salbutamol should be prescribed at discharge after an asthma attack: myth or maxim?, Breathe (Sheff), Vol: 19, ISSN: 1810-6838
Over the past 20 years, the concept of asthma weaning plans on discharge after an attack has crept into common practice, although the precise origin of these plans is unclear. High use of short-acting β2-agonists (SABAs) may result in tolerance to their bronchodilator effects, thus diminishing their efficacy, particularly when they are most needed at the time of an acute attack. Furthermore, key warning signs of a deterioration in asthma control may be masked and the weaning plan may encourage the over-use and over-reliance on SABAs. Side-effects from over-use may also occur, including lactic acidosis, downregulation of the β2-adrenoreceptor, increased allergen response and pro-inflammatory effects. The need for asthma education at discharge, a personal asthma action plan and vigilance about prescribing and ensuring adherence to maintenance therapy are definitely important. However, the current authors conclude that the benefit of prescribing regular salbutamol (up to 10 puffs every 4 h) at discharge after an acute asthma attack is a myth, and a very dangerous one.
Mazulov O, Powell Z, Powell E, et al., 2023, World Bronchiectasis Day: It is time for global action to promote equity of care, PEDIATRIC PULMONOLOGY, Vol: 58, Pages: 2183-2186, ISSN: 8755-6863
Fleming L, Hine J, Bush A, et al., 2023, Patient financial incentives to improve asthma management: a systematic review, BMJ Open, Vol: 13, Pages: 1-9, ISSN: 2044-6055
Objectives The objectives of this systematic review are to identify studies that assess the effectiveness of patient-directed financial incentive interventions to improve asthma management behaviours, determine overall effectiveness of financial incentives, identify design characteristics of effective interventions and assess the impact on longer-term outcomes in the context of asthma.Design Systematic review with narrative synthesis.Data sources Electronic databases (MEDLINE, Embase, Global Health, PsycINFO, CINAHL, PubMed and Web of Science) and grey literature sources (NHS Digital, CORE, ProQuest, Clinical Trials Register and EU Clinical Trials Register) were searched in November 2021 and updated March 2023.Eligiblity criteria Eligible articles assessed financial incentives to improve asthma management behaviours (attendance at appointments, medication adherence, tobacco smoke/allergen exposure, inhaler technique and asthma education) for patients with asthma or parents/guardians of children with asthma. Eligible study design included randomised controlled, controlled or quasi-randomised trials and retrospective/prospective cohort, case-controlled or pilot/feasibility studies.Synthesis A narrative synthesis was conducted; eligible studies were grouped by asthma management behaviours and financial incentive framework domains.Results We identified 4268 articles; 8 met the inclusion criteria. The studies were from the USA (n=7) and the UK (n=1). Asthma management behaviours included attendance at appointments (n=4), reduction in smoke exposure (n=1) and medication adherence (n=3). Five studies demonstrated positive behaviour change, four of which were significant (attendance at appointments (n=3) showed significant differences between intervention and control: 73% and 49% in one study, 46.3% and 28.9% in another, and 35.7% and 18.9%, respectively; medication adherence (n=1) showed significant change from 80% during intervention to 33% post intervention). These four
Abdel-Aziz MI, Thorsen J, Hashimoto S, et al., 2023, Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 208, Pages: 142-154, ISSN: 1073-449X
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Brandsma J, Schofield JPR, Yang X, et al., 2023, Stratification of asthma by lipidomic profiling of induced sputum supernatant, Journal of Allergy and Clinical Immunology, Vol: 152, Pages: 117-125, ISSN: 0091-6749
BACKGROUND: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features. OBJECTIVE: To perform a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as healthy controls. METHODS: Induced sputum supernatant was collected from 211 asthmatic adults and 41 healthy individuals enrolled in the U-BIOPRED study. Sputum lipidomes were characterised by semi-quantitative shotgun mass spectrometry, and clustered using topological data analysis to identify lipid phenotypes. RESULTS: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of nine molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthmatics and healthy controls, but within the asthmatic population as well. Matching clinical, pathobiological, proteomic and transcriptomic data informed on the underlying disease processes. Sputum lipid phenotypes with higher levels of non-endogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts. CONCLUSION: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthmatics, resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator. CLINICAL IMPLICATION: Immunomodulation of extracellular vesicle secretion in the lungs may provide a novel therapeutic target for severe asthma.
Ramsey B, Bush A, 2023, Cystic Fibrosis: From Tragedy to Triumph, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 208, Pages: 9-10, ISSN: 1073-449X
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