952 results found
Ring AM, Carlens J, Bush A, et al., 2020, Pulmonary function testing in children's interstitial lung disease., Eur Respir Rev, Vol: 29
The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.
de Benedictis FM, Guidi R, Bush A, 2020, Reflux-Aspiration in Chronic Lung Disease, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 17, Pages: 1030-1030, ISSN: 1546-3222
Trucco F, Carruthers E, Davies JC, et al., 2020, Inflammation in children with neuromuscular disorders and sleep disordered breathing, SLEEP MEDICINE, Vol: 72, Pages: 118-121, ISSN: 1389-9457
Andersson CK, Iwasaki J, Cook J, et al., 2020, Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze, ALLERGY, ISSN: 0105-4538
Bingham Y, Sanghani N, Cook J, et al., 2020, Electronic adherence monitoring identifies severe preschool wheezers who are steroid responsive., Pediatric Pulmonology, Vol: 55, Pages: 2254-2260, ISSN: 1099-0496
Little is known about adherence to inhaled corticosteroids (ICS) in preschool children with troublesome wheeze. Children with aeroallergen senitization, or those reporting multiple trigger wheeze (MTW), are more likely to respond to ICS. We hypothesized that adherence to ICS and symptom control are only positively related in atopic children, or those reporting MTW. Patients aged 1 to 5 years with recurrent wheeze prescribed ICS were recruited from a tertiary respiratory clinic. Clinical phenotype and aeroallergen senitization were determined, and adherence assessed using an electronic monitoring device (Smartinhaler). Symptom control (test for respiratory and asthma control in kids [TRACK]), quality of life (PACQLQ), airway inflammation (offline exhaled nitric oxide) were assessed at baseline and follow-up. Forty-eight children (mean age 3.7 years; SD, 1.2) were monitored for a median of 112 (interquartile range [IQR], 91-126) days. At baseline n = 29 reported episodic viral wheeze and n = 19 reported MTW. Twenty-four out of 48 (50%) wheezers had suboptimal ICS adherence (<80%). Median adherence was 64% (IQR, 38-84). There was a significant increase in TRACK and PACQLQ in the group as a whole, unrelated to adherence. In subgroup analysis only atopic wheezers with moderate or good adherence ≥ 60% had a significant increase in TRACK. There was no relationship between clinical phenotype, and adherence or TRACK. In this pilot study, overall adherence to ICS was suboptimal and was positively related to symptom control in atopic wheezers only. Assessments of adherence are important in preschool troublesome wheezers before therapy escalation to help identify those with an ICS responsive phenotype.
Bédard A, Antó JM, Fonseca JA, et al., 2020, Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air® App, Allergy, Vol: 75, Pages: 1672-1688, ISSN: 0105-4538
BACKGROUND: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. METHODS: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. RESULTS: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. CONCLUSIONS: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.
Rubin GD, Ryerson CJ, Haramati LB, et al., 2020, The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic A Multinational Consensus Statement From the Fleischner Society, CHEST, Vol: 158, Pages: 106-116, ISSN: 0012-3692
Pifferi M, Bush A, Marani F, et al., 2020, Lung Function Longitudinal Study by Phenotype and Genotype in Primary Ciliary Dyskinesia, CHEST, Vol: 158, Pages: 117-120, ISSN: 0012-3692
Gupta A, Bush A, Nagakumar P, 2020, Asthma in children during the COVID-19 pandemic: lessons from lockdown and future directions for management., Lancet Respir Med
Abdel-Aziz MI, Brinkman P, Vijverberg SJH, et al., 2020, eNose breath prints as a surrogate biomarker for classifying patients with asthma by atopy., J Allergy Clin Immunol
BACKGROUND: Electronic noses (eNoses) are emerging point-of-care tools that may help in the subphenotyping of chronic respiratory diseases such as asthma. OBJECTIVE: We aimed to investigate whether eNoses can classify atopy in pediatric and adult patients with asthma. METHODS: Participants with asthma and/or wheezing from 4 independent cohorts were included; BreathCloud participants (n = 429), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adults (n = 96), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes pediatric participants (n = 100), and Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory Effects 2 participants (n = 30). Atopy was defined as a positive skin prick test result (≥3 mm) and/or a positive specific IgE level (≥0.35 kU/L) for common allergens. Exhaled breath profiles were measured by using either an integrated eNose platform or the SpiroNose. Data were divided into 2 training and 2 validation sets according to the technology used. Supervised data analysis involved the use of 3 different machine learning algorithms to classify patients with atopic versus nonatopic asthma with reporting of areas under the receiver operating characteristic curves as a measure of model performance. In addition, an unsupervised approach was performed by using a bayesian network to reveal data-driven relationships between eNose volatile organic compound profiles and asthma characteristics. RESULTS: Breath profiles of 655 participants (n = 601 adults and school-aged children with asthma and 54 preschool children with wheezing [68.2% of whom were atopic]) were included in this study. Machine learning models utilizing volatile organic compound profiles discriminated between atopic and nonatopic participants with areas under the receiver operating characteristic curves of at least 0.84 and 0.72 in the training and validation sets, respectively. The unsupervised approach revealed t
Makrinioti H, Bush A, Griffiths C, 2020, What are patient-reported outcomes and why they are important: improving studies of preschool wheeze, ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION, Vol: 105, Pages: 185-+, ISSN: 1743-0585
Verger N, Arigliani M, Raywood E, et al., 2020, Limitations of regional ventilation inhomogeneity indices in children with cystic fibrosis, PEDIATRIC PULMONOLOGY, Vol: 55, Pages: 2315-2322, ISSN: 8755-6863
Bush A, Pabary R, 2020, Pulmonary alveolarproteinosis in children., Breathe (Sheff), Vol: 16, ISSN: 1810-6838
Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations. Educational aims: To understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation.To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey.To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children.To discuss when to treat PAP with whole-lung lavage and/or granulocyte-macrophage colony-stimula
Davies G, Stanojevic S, Raywood E, et al., 2020, An observational study of the lung clearance index throughout childhood in cystic fibrosis: Early years matter., Eur Respir J
Bush A, Levy M, Fleming L, 2020, Steroid-filled rant: or another fashion accessory?, Arch Dis Child
Bush A, 2020, Kids, Difficult Asthma and Fungus, Journal of Fungi, Vol: 6, ISSN: 2309-608X
Fungi have many potential roles in paediatric asthma, predominantly by being a source of allergens (severe asthma with fungal sensitization, SAFS), and also directly damaging the epithelial barrier and underlying tissue by releasing proteolytic enzymes (fungal bronchitis). The umbrella term 'fungal asthma' is proposed for these manifestations. Allergic bronchopulmonary aspergillosis (ABPA) is not a feature of childhood asthma, for unclear reasons. Diagnostic criteria for SAFS are based on sensitivity to fungal allergen(s) demonstrated either by skin prick test or specific IgE. In children, there are no exclusion criteria on total IgE levels or IgG precipitins because of the rarity of ABPA. Diagnostic criteria for fungal bronchitis are much less well established. Data in adults and children suggest SAFS is associated with worse asthma control and greater susceptibility to asthma attacks than non-sensitized patients. The data on whether anti-fungal therapy is beneficial are conflicting. The pathophysiology of SAFS is unclear, but the epithelial alarmin interleukin-33 is implicated. However, whether individual fungi have different pathobiologies is unclear. There are many unanswered questions needing further research, including how fungi interact with other allergens, bacteria, and viruses, and what optimal therapy should be, including whether anti-neutrophilic strategies, such as macrolides, should be used. Considerable further research is needed to unravel the complex roles of different fungi in severe asthma.
Ramphul M, Bush A, Chang A, et al., 2020, The role of the pediatrician in caring for children with tracheobronchomalacia, EXPERT REVIEW OF RESPIRATORY MEDICINE, Vol: 14, Pages: 679-689, ISSN: 1747-6348
Hogg C, Bush A, 2020, CON: Primary Ciliary Dyskinesia diagnosis: Genes are all you need!, Paediatr Respir Rev
Bayfield KJ, Alton E, Irving S, et al., 2020, “Nitrogen offset in N2 multiple washout method”. Katie J. Bayfield, Eric Alton, Samantha Irving, Andrew Bush, Jane C. Davies. ERJ Open Res 2019; 6: 00043-2020, ERJ Open Research, Vol: 6, Pages: 1-1, ISSN: 2312-0541
This article was originally published with the sentence “Thank you for the opportunity to respond to the correspondence by J.G. Nielsen from Innovision about our recent paper”. The authors have since been made aware that J.G. Nielsen sold Innovision ApS (Glamsbjerg, Denmark) prior to the submission of his correspondence and, at the time of writing, has no financial interests in any business relating to lung clearance index technologies. This sentence has now been changed to “Thank you for the opportunity to respond to the correspondence by J.G. Nielsen about our recent paper” in the article itself.
Trucco F, Rosenthal M, Bush A, et al., 2020, The McGill score as a screening test for obstructive sleep disordered breathing in children with co-morbidities, SLEEP MEDICINE, Vol: 68, Pages: 173-176, ISSN: 1389-9457
Bush A, 2020, Azithromycin is the answer in paediatric respiratory medicine, but what was the question?, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 34, Pages: 67-74, ISSN: 1526-0542
de Benedictis FM, Bush A, 2020, Janus looks both ways: How do the upper and lower airways interact?, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 34, Pages: 59-66, ISSN: 1526-0542
Jochmann A, Artusio L, Sharifian H, et al., 2020, Fluctuation-based clustering reveals phenotypes of patients with different asthma severity, ERJ OPEN RESEARCH, Vol: 6
Bush A, 2020, Which Child with Asthma is a Candidate for Biological Therapies?, JOURNAL OF CLINICAL MEDICINE, Vol: 9
Broadbent L, Manzoor S, Zarcone MC, et al., 2020, Comparative primary paediatric nasal epithelial cell culture differentiation and RSV-induced cytopathogenesis following culture in two commercial media, PLoS One, Vol: 15, Pages: 1-12, ISSN: 1932-6203
The culture of differentiated human airway epithelial cells allows the study of pathogen-host interactions and innate immune responses in a physiologically relevant in vitro model. As the use of primary cell culture has gained popularity the availability of the reagents needed to generate these cultures has increased. In this study we assessed two different media, Promocell and PneumaCult, during the differentiation and maintenance of well-differentiated primary nasal epithelial cell cultures (WD-PNECs). We compared and contrasted the consequences of these media on WD-PNEC morphological and physiological characteristics and their responses to respiratory syncytial virus (RSV) infection. We found that cultures generated using PneumaCult resulted in greater total numbers of smaller, tightly packed, pseudostratified cells. However, cultures from both media resulted in similar proportions of ciliated and goblet cells. There were no differences in RSV growth kinetics, although more ciliated cells were infected in the PneumaCult cultures. There was also significantly more IL-29/IFNλ1 secreted from PneumaCult compared to Promocell cultures following infection. In conclusion, the type of medium used for the differentiation of primary human airway epithelial cells may impact experimental results.
Jolliffe DA, Stefanidis C, Wang Z, et al., 2020, Vitamin D Metabolism is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease., Am J Respir Crit Care Med
RATIONALE: Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. OBJECTIVE: To determine whether vitamin D metabolism is altered in asthma or COPD. METHODS: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation in 93 adults with asthma, COPD or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls. MEASUREMENTS AND MAIN RESULTS: The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where statistically significant. CONCLUSIONS: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.
Roberts G, Fontanella S, Selby A, et al., 2020, Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749
BACKGROUND: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. OBJECTIVE: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. METHODS: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma. RESULTS: Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups. CONCLUSIONS: The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.
Davies G, Thia LP, Stocks J, et al., 2020, Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year., J Cyst Fibros
BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.
Irving S, Fleming L, Ahmad F, et al., 2020, Lung clearance index and steroid response in pediatric severe asthma, PEDIATRIC PULMONOLOGY, Vol: 55, Pages: 890-898, ISSN: 8755-6863
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.