1004 results found
Tanner N, Saglani S, Li AM, et al., 2021, Airway inflammation in severe asthmatics with acid gastro-oesophageal reflux., Thorax
The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma.
Bush A, Pavord ID, 2021, Challenging the paradigm: moving from umbrella labels to treatable traits in airway disease, BREATHE, Vol: 17, ISSN: 1810-6838
Makhecha S, Jamalzadeh A, Irving S, et al., 2021, Paediatric severe asthma biologics service: from hospital to home, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 106, Pages: 900-902, ISSN: 0003-9888
Chen Y-H, Cheadle CE, Rice L, et al., 2021, The Induction of Alpha-1 Antitrypsin by Vitamin D in Human T Cells Is TGF-beta Dependent: A Proposed Anti-inflammatory Role in Airway Disease, FRONTIERS IN NUTRITION, Vol: 8, ISSN: 2296-861X
Bush A, 2021, Growing, Growing Gone: The Double Whammy of Early Deprivation and Impaired Evolution of Lung Function., Am J Respir Crit Care Med
Levy ML, Fleming L, Goldring S, et al., 2021, Piling Pelion upon Ossa: surely we already have enough non-evidence based ways of treating acute asthma?, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 106, Pages: 730-731, ISSN: 0003-9888
Chang AB, Fortescue R, Grimwood K, et al., 2021, European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936
Chang AB, Boyd J, Bell L, et al., 2021, Clinical and research priorities for children and young people with bronchiectasis: an international roadmap, ERJ OPEN RESEARCH, Vol: 7
Bush A, Pabary R, Allinson J, et al., 2021, They SHALL grow old: a UK rare disease clinical network for adult congenital thoracic malformations, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 106, Pages: 625-626, ISSN: 0003-9888
Jochmann A, Artusio L, Usemann J, et al., 2021, A 3-month period of electronic monitoring can provide important information to the healthcare team to assess adherence and improve asthma control, ERJ OPEN RESEARCH, Vol: 7
Alahmadi FH, Simpson AJ, Gomez C, et al., 2021, Medication adherence in patients with severe asthma prescribed oral corticosteroids in the U-BIOPRED cohort, Chest, Vol: 160, Pages: 53-64, ISSN: 0012-3692
BACKGROUND: Whilst estimates of sub-optimal adherence to oral corticosteroids in asthma range from 30 to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. RESEARCH QUESTIONS: 1. What is the prevalence of suboptimal adherence detected using self-reporting and direct measures? 2. Is suboptimal adherence associated with disease activity? STUDY DESIGN AND METHODS: Data were included from individuals with severe asthma taking part in the U-BIOPRED study prescribed daily oral corticosteroids. Participants completed the MARS, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid-chromatography mass spectrometry. RESULTS: Data from 166 participants were included in this study, mean (SD) age 54.2 (11.9) years, FEV1 65.1 (20.5) % predicted, 58% female. 37% completing the MARS reported sub-optimal adherence, and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 35% participants who had both performed; adherence detection did not match between methods in 53%. Self-reported high-adherers had better asthma control and quality of life, whereas directly-measured high-adherers had lower blood eosinophils. INTERPRETATION: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.
Pifferi M, Bush A, Mule G, et al., 2021, Longitudinal Lung Volume Changes by Ultrastructure and Genotype in Primary Ciliary Dyskinesia, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 18, Pages: 963-970, ISSN: 1546-3222
Bush A, 2021, COVID-19 and Children, HIC Setting: What Did We Have to Change?, Publisher: WILEY, Pages: S34-S35, ISSN: 8755-6863
Custovic A, Bush A, 2021, Pediatric Asthma - Diagnosis and Assessment of Future Risk., Publisher: WILEY, Pages: S24-S26, ISSN: 8755-6863
Bush A, 2021, Impact of early life exposures on respiratory disease., Paediatr Respir Rev
The antecedents of asthma and chronic obstructive pulmonary disease (COPD) lie before school age. Adverse effects are transgenerational, antenatal and in the preschool years. Antenatal adverse effects impair spirometry by causing low birth weight, altered lung structure and immune function, and sensitizing the foetus to later insults. The key stages of normal lung health are lung function at birth, lung growth to a plateau age 20-25 years, and the phase of decline thereafter; contrary to perceived wisdom, accelerated decline is not related to smoking. There are different trajectories of lung function. Lung function usually tracks from preschool to late middle age. Asthma is driven by antenatal and early life influences. The airflow obstruction, emphysema and multi-morbidity of COPD all start early. Failure to reach a normal plateau and accelerated decline in lung function are risk factors for COPD. Airway disease cannot be prevented in adult life; prevention must start early.
Saglani S, Robinson P, Fontanella S, et al., 2021, Recurrent severe preschool wheeze: From pre-specified diagnostic labels to underlying endotypes, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X
Rationale: Preschool wheezing is heterogeneous, but the underlying mechanisms are poorly understood. Objectives: To investigate lower airway inflammation and infection in preschool children with different clinical diagnoses undergoing elective bronchoscopy/bronchoalveolar lavage-BAL. Methods: We recruited 136 children aged 1-5 years (105 recurrent severe wheeze-RSW; 31 non-wheeze respiratory disorders-NWRD). RSW were assigned as episodic viral-EVW or multiple trigger wheeze-MTW. We compared lower airway inflammation/infection in different clinical diagnoses and undertook data-driven analyses to determine clusters of pathophysiological features, and investigated their relationships with pre-specified diagnostic labels. Measurements and Main Results: Blood eosinophils and allergic sensitization were significantly higher in RSW than NWRD. Blood neutrophils, BAL eosinophils and neutrophils, and positive bacterial culture and virus detection rates were similar between groups. However, pathogen distribution differed significantly, with higher detection of rhinovirus in RSW and Moraxella in sensitized RSW. EVW and MTW did not differ in blood/BAL inflammation, or bacterial/virus detection. Partition Around Medoids algorithm revealed 4 clusters of pathophysiological features: (1) Atopic (17.9%); (2) Non-atopic, low infection rate, high inhaled corticosteroids-ICS (31.3%); (3) Non-atopic, high infection rate (23.1%); and (4) Non-atopic, low infection rate, no ICS (27.6%). Cluster allocation differed significantly between RSW and NWRD (RSW evenly distributed across clusters, 60% of NWRD assigned to cluster 4, p<0.001). There was no difference in cluster membership between EVW and MTW. Cluster 1 was dominated by Moraxella detection (p=0.04) and Cluster 3 by Haemophilus/Staphylococcus/ Streptococcus (p=0.02). Conclusions: We identified four clusters of severe preschool wheeze distinguished using sensitization, peripheral eosinophilia, lower airway neutrophilia and bacteriolog
Bloom C, Franklin C, Bush A, et al., 2021, Burden of preschool wheeze and progression to asthma in the UK: population-based cohort 2007 to 2017, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 1949-1958, ISSN: 0091-6749
BackgroundWheeze is one of the most common symptoms of preschool children (age 1 to 5 years), yet we have little understanding of the burden in the UK.ObjectivesDetermine prevalence and pattern of physician-confirmed preschool wheeze, related healthcare utilisation, and factors associated with progression to school-age asthma.MethodsWe used nationally representative primary and secondary care electronic medical records between 2007-2017 to identify preschool children with wheeze. Factors associated with asthma progression were identified in a nested cohort of children with follow-up from 1-2 years of age, until at least 8 years of age.ResultsFrom 1,021,624 preschool children, 69,261 were identified with wheeze. Prevalence of preschool wheeze was 7.7% in 2017. Wheeze events were lowest in August and highest in late-autumn/early-winter. During median follow-up of 2.0 years (IQR 1.2-4.0), 15.8% attended an emergency department, and 13.9% had a hospital admission, for a respiratory disorder. The nested cohort with prolonged follow-up identified 15,085 children; 35.5% progressed to asthma between 5-8 years old. Of children with preschool wheeze, without an asthma diagnosis, 34.9% were prescribed inhaled corticosteroids, and 15.6% oral corticosteroids. The factors most strongly associated with progression to asthma were wheeze frequency and severity, atopy, prematurity, maternal asthma severity and first reported wheeze event occurring in September.ConclusionsPreschool wheeze causes considerable healthcare burden, a large number of children are prescribed asthma medication and have unplanned secondary care visits. Multiple factors influence progression to asthma, including first wheeze event occurring in September.
Bush A, 2021, Control pollution, protect children, save lives, BMJ-BRITISH MEDICAL JOURNAL, Vol: 373, ISSN: 1756-1833
Ullmann N, Allegorico A, Bush A, et al., 2021, Effects of the COVID-19 pandemic and lockdown on symptom control in preschool children with recurrent wheezing, Pediatric Pulmonology, Vol: 56, Pages: 1946-1950, ISSN: 1099-0496
INTRODUCTION: Preschool wheezers are at high risk of recurrent attacks triggered by respiratory viruses, sometimes exacerbated by exposure to allergens and pollution. Because of the COVID-19 infection, the lockdown was introduced, but the effects on preschool wheezers are unknown. We hypothesized that there would be an improvement in outcomes during the lockdown, and these would be lost when the lockdown was eased. MATERIALS AND METHODS: Patients underwent medical visits before and after the COVID-19 lockdown. We recorded the childhood Asthma Control Test (cACT) and a clinical questionnaire. Data on symptoms, the need for medications and the use of healthcare resources were recorded. We compared these data with retrospective reports from the preceding year and prospectively acquired questionnaires after lockdown. RESULTS: We studied 85 preschool wheezers, mean age 4.9 years. During the lockdown, cACT score was significantly higher (median 25 vs. 23); families reported a dramatic drop in wheezing episodes (51 vs. none), significant reductions in the day and nighttime symptoms, including episodes of shortness of breath (p < .0001); the use of salbutamol and oral corticosteroids (OCS) dropped significantly (p < .0001) and 79 (95%) patients needed no OCS bursts during the lockdown. Finally, patients had significantly fewer extra medical examinations, as well as fewer Emergency Room visits (p < .0001). All were improved compared with the same time period from the previous year, but outcomes worsened significantly again after lockdown (cACT median: 22). CONCLUSIONS: During the national lockdown, children with persistent preschool wheeze showed a significant clinical improvement with reduction of respiratory symptoms, medication use for exacerbations, and use of healthcare resources. This trend reversed when lockdown restrictions were eased.
Koucky V, Pohunek P, Vasakova M, et al., 2021, Transition of patients with interstitial lung disease from paediatric to adult care, ERJ OPEN RESEARCH, Vol: 7
Lucchetti D, Santini G, Perelli L, et al., 2021, Detection and characterization of extracellular vesicles in exhaled breath condensate and sputum of COPD and severe asthma patients., European Respiratory Journal, ISSN: 0903-1936
Devaney R, Simpson T, Bush A, et al., 2021, Fructose 1,6-bisphosphatase deficiency as a cause of childhood interstitial lung disease, PEDIATRIC PULMONOLOGY, Vol: 56, Pages: 2362-2365, ISSN: 8755-6863
Schmidt A, Kenia P, Morgan C, et al., 2021, Hereditary pulmonary alveolar proteinosis as collateral damage from a large chromosomal deletion, PEDIATRIC PULMONOLOGY, Vol: 56, Pages: 1687-1689, ISSN: 8755-6863
Meghji J, Mortimer K, Agusti A, et al., 2021, Improving lung health in low-income and middle-income countries: from challenges to solutions, LANCET, Vol: 397, Pages: 928-940, ISSN: 0140-6736
Bush A, Levy M, Fleming L, 2021, Steroid-filled rant: or another fashion accessory?, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 106, Pages: 211-+, ISSN: 0003-9888
Hogg C, Bush A, 2021, Pro-Con Debate CON: Primary Ciliary Dyskinesia diagnosis: Genes are all you need!, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 37, Pages: 34-36, ISSN: 1526-0542
Bousquet J, Anto JM, Czarlewski W, et al., 2021, Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19, Allergy, Vol: 76, Pages: 735-750, ISSN: 0105-4538
Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.
Nagakumar P, Chadwick C-L, Bush A, et al., 2021, Collateral impact of COVID-19: why should children continue to suffer?, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 180, Pages: 1975-1979, ISSN: 0340-6199
Gidaris DK, Stabouli S, Bush A, 2021, Beware the inhaled steroids or corticophobia?, Swiss Med Wkly, Vol: 151
Inhaled corticosteroids have been the cornerstone of atopic, allergic asthma management for more than half a century. They have side effects (as does every medication), but they have transformed the control of asthma and saved many lives since their introduction. The current review revisits local and systemic side effects of inhaled corticosteroids and explores the prevalence and nature of parental fears (“corticophobia”) in different parts of the world. The empathetic physician treating asthma should bear in mind the impact of parental concerns on the management of this potentially life-threatening disease and try to dispel myths at every opportunity by emphasising the well-established benefits and excellent safety profile of inhaled corticosteroids.
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