Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples

Thwaites, Ryan S.; Jarvis, Hannah; Singh, Nehmat; Jha, Akhilesh; Pritchard, A.J.; Fan, Hailing; Tunstall, Tanushree; Nanan, Joan; Nadel, Simon; Kon, Onn Min; Openshaw, Peter; Hansel, Trevor T.

doi:10.3791/56413

Cited by 34 publications

(31 citation statements)

References 45 publications

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“…Reasons for exclusion are described in detail in Figure E2, the commonest being lack of ICS therapy. [20][21][22][23][24] (ACT 25 point scale -score 20-24 well controlled, less than 20 not well controlled).…”

Section: Resultsmentioning

confidence: 99%

“…Concentrated nasal lining fluid was collected by applying synthetic absorptive matrices to the nasal mucosa for 1 minute and stored at -80 o C until analysis 21 . Fluid was eluted by adding 100µL Luminex assay buffer, supernatant was clarified by centrifugation for 10 minutes, and 30 cytokines and immune proteins were analysed as per manufacturer's protocol as we previously described 9,19 .…”

Section: Mucosal Cytokine Levelsmentioning

confidence: 99%

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Mechanisms and kinetics of bacterial clearance after experimental colonisation in adults with asthma

Zaidi

Jochems

Reiné

et al. 2020

Preprint

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Background Pneumococcal pneumonia is a leading cause of death, particularly affecting those with chronic respiratory disease. Observational studies suggest increased nasopharyngeal colonisation rates with S.pneumoniae in asthma, and lower specific antibody levels. Objectives Using experimental human pneumococcal challenge, we examined the acquisition and kinetics of nasopharyngeal colonisation of Streptococcus pneumoniae serotype 6B. We also aimed to dissect associated mucosal and systemic immune responses and immunizing effect of carriage. Methods Fifty participants with asthma well-controlled on moderate inhaled corticosteroid doses were challenged with pneumococcus, and a subset of colonized individuals were re-challenged 6-11 months later with the same pneumococcal isolate . Colonisation rates (from nasal wash), systemic antibody levels and mucosal cellular and cytokine responses were compared to 151 healthy controls. Measurements and Main Results Colonisation rates were 28/50 (56%) and 68/151 (45%) in those with asthma and controls respectively, p=0.17. Duration of colonisation was shorter in people with asthma (median 14 days vs 29 days, p=0.03) but of similar density. Body mass index was higher in colonised compared with non-colonised asthma individuals (median 24.7 [IQR 24.1-29.0] and 23.5 [20.1-26.4] respectively, p=0.019). Despite an increase in pneumococcal capsular and protein antibodies after colonisation, 4/12 asthmatic individuals became colonised again upon re-challenge. Nasal neutrophil and T cell levels, in particular mucosa associated invariant T (MAIT) cells were decreased in people with asthma compared to healthy controls (median 9.4, [IQR 5.0-13.3 %] of CD8+ T cells) vs median 15.8, [IQR 9.9-25.9 %] of CD8+ T cells respectively (p=0.0047). Most nasal cytokines were also reduced in asthmatics. In both groups, colonisation led to recruitment of monocytes and granulocytes to the nasal mucosa. Conclusions: Nasopharyngeal colonisation was of shorter duration in those with asthma compared to controls, although acquisition rates were not different. Rates of colonisation were higher with increasing BMI in individuals with asthma. Despite a baseline reduction in mucosal immune cells and cytokines in asthmatics with corticosteroids, colonisation led to cellular recruitment in both groups. Colonisation was not associated with protection from homologous re-challenge in individuals with asthma, in contrast to healthy volunteers. Clinical Implication: People with asthma on inhaled corticosteroids have an increased likelihood of pneumococcal infection secondary to reduced mucosal immune responses from nasopharyngeal colonisation and a lack of protection from re-exposure.

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Section: Resultsmentioning

confidence: 99%

Section: Mucosal Cytokine Levelsmentioning

confidence: 99%

Mechanisms and kinetics of bacterial clearance after experimental colonisation in adults with asthma

Zaidi

Jochems

Reiné

et al. 2020

Preprint

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“…We collect unstimulated nasal secretion samples (nasosorption samples) using methods described by Thwaites et al 40. This collection is brief, minimally invasive and a minimally distressing process.…”

Section: Methods and Analysismentioning

confidence: 99%

Impact of preterm birth on brain development and long-term outcome: protocol for a cohort study in Scotland

et al. 2020

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IntroductionPreterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data.Methods and analysisTheirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at <33 weeks of gestational age (GA) and 100 healthy control infants born after 37 weeks of GA. Multiple domains are assessed: maternal and infant clinical and demographic information; placental histology; immunoregulatory and trophic proteins in umbilical cord and neonatal blood; brain macrostructure and microstructure from structural and diffusion MRI (dMRI); DNA methylation; hypothalamic–pituitary–adrenal axis activity; social cognition, attention and processing speed from eye tracking during infancy and childhood; neurodevelopment; gut and respiratory microbiota; susceptibility to viral infections; and participant experience. Main analyses include creation of novel methods for extracting information from neonatal structural and dMRI, regression analyses of predictors of brain maldevelopment and neurocognitive outcome associated with preterm birth, and determination of the quantitative predictive performance of MRI and other early life factors for childhood outcome.Ethics and disseminationEthical approval has been obtained from the National Research Ethics Service (NRES), South East Scotland Research Ethics Committee (NRES numbers 11/55/0061 and 13/SS/0143 (phase I) and 16/SS/0154 (phase II)), and NHS Lothian Research and Development (2016/0255). Results are disseminated through open access journals, scientific meetings, social media, newsletters anda study website (www.tebc.ed.ac.uk), and we engage with the University of Edinburgh public relations and media office to ensure maximum publicity and benefit.

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“…Data from these four devices and an embedded asthma symptom diary will be recorded in the STIFLE application through an integrated approach (figure 3). ∼30 patients who agree to participate in a nasal biomarker substudy of STIFLE will be shown how to collect a nasal absorption sample (synthetic absorptive matrix (SAM) [28]), and will be provided with a kit and instructions for collecting the samples at home. These patients will collect daily morning nasal samples for the first 30 days of randomised treatment for the evaluation of inflammatory biomarkers.…”

Section: Design Of the Stifle Studymentioning

confidence: 99%

Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design

et al. 2020

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Asthma is a chronic inflammatory airway disease. Increase in airway inflammation is hypothesised to contribute to worsening of asthma symptoms and deterioration in lung function, resulting in the use of reliever medication. Short-acting β2-agonists only treat the symptoms, whereas an anti-inflammatory reliever is believed to treat both symptoms and the underlying inflammation, thereby arresting the progression to an exacerbation. As-needed budesonide/formoterol as an anti-inflammatory reliever reduces the risk of severe exacerbations. However, supporting mechanistic evidence has not yet been described, specifically the temporal dynamics of parameters including airway inflammation, over time and during asthma worsening.The STIFLE study aims to characterise daily variability in airway inflammation, symptoms, lung function and reliever use in people with asthma. This phase IV, open-label, parallel-group, multicentre, exploratory study will enrol 60–80 adult patients with asthma receiving low- or medium-dose inhaled corticosteroids/long-acting β2-agonists (EudraCT identifier number 2018-003467-64). Participants will be randomised 1:1 to either as-needed budesonide/formoterol dry-powder inhaler or salbutamol reliever for 24 weeks, in addition to their maintenance therapy. Daily data will be captured for fractional exhaled nitric oxide, spirometry, asthma symptoms and medication use using devices connected to a smartphone via the STIFLE application. STIFLE will thereby enable not only characterisation of the variability of airway inflammation and clinical outcomes in relation to asthma worsening, but also elucidate the effect of as-needed budesonide/formoterol on airway inflammation against a background of daily maintenance therapy.

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Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples

Cited by 34 publications

References 45 publications

Mechanisms and kinetics of bacterial clearance after experimental colonisation in adults with asthma

Mechanisms and kinetics of bacterial clearance after experimental colonisation in adults with asthma

Impact of preterm birth on brain development and long-term outcome: protocol for a cohort study in Scotland

Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design

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