Fractional exhaled nitric oxide non-suppression in asthma
<p><strong>Background:</strong> Factional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of the higher risk type-2 inflammatory phenotype in asthma.</p> <p><strong>Objectives:</strong> 1) To assess if patients who fail to suppress FeNO aft...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2021
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| _version_ | 1826316244799717376 |
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| author | Couillard Castonguay, S |
| author2 | Hinks, T |
| author_facet | Hinks, T Couillard Castonguay, S |
| author_sort | Couillard Castonguay, S |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Factional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of the higher risk type-2 inflammatory phenotype in asthma.</p>
<p><strong>Objectives:</strong> 1) To assess if patients who fail to suppress FeNO after monitored therapy exhibit corticosteroid resistance. 2) To translate non-suppression of type-2 biomarkers to inflammatory mediators in the airway and peripheral blood in severe asthma. 3) To develop a prototype risk scale predicting asthma attacks based on FeNO and blood eosinophils.</p>
<p><strong>Methods:</strong> 1) Induced sputum eosinophils and 11 sputum supernatant plus 9 serum inflammatory proteins were analysed in a paired before/after analysis of FeNO suppression tests conducted in Oxford, compared on the basis of a positive/negative test (i.e.: ≥42/% decrease in FeNO following monitored high-intensity corticosteroid therapy). 2) These inflammatory mediators were also correlated to the FeNO and blood eosinophil levels at the point of maximum treatment intensity in a cross-sectional study pooling the Oxford FeNO suppression cohort and the RASP-UK trial cohort. 3) Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of 8 randomised clinical trials. These were used to derive rate ratios and the predicted asthma attack rate for different patient groups.</p>
<p><strong>Results:</strong> 1) Thirty-four FeNO suppression tests were analysed. The 19 patients failing to suppress FeNO were older, more intensely treated, and had little or no trends for improvement in clinical nor sputum/serum measurements compared to those who suppressed. 2) In 74 patients with severe asthma, FeNO correlated with airway type-2 cytokine, chemokine, alarmin and eosinophilia, whilst blood eosinophils correlated with serum interleukin-5. 3) The trial-derived (n=3051) prototype risk scale showed feasibility and potential to predict asthma attacks which can be prevented by anti-inflammatory therapy.</p>
<p><strong>Conclusion:</strong> FeNO non-suppression carries significant translational, prognostic and theragnostic utility as a biomarker of type-2 airway inflammation in asthma – especially when used in combination with blood eosinophils.</p> |
| first_indexed | 2024-03-07T07:11:58Z |
| format | Thesis |
| id | oxford-uuid:3312c52e-e5a0-4a5d-ac6d-15df48d44f5c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:41:22Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:3312c52e-e5a0-4a5d-ac6d-15df48d44f5c2024-12-07T12:26:18ZFractional exhaled nitric oxide non-suppression in asthmaThesishttp://purl.org/coar/resource_type/c_bdccuuid:3312c52e-e5a0-4a5d-ac6d-15df48d44f5cAsthmaMedicineEnglishHyrax Deposit2021Couillard Castonguay, SHinks, TPavord, I<p><strong>Background:</strong> Factional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of the higher risk type-2 inflammatory phenotype in asthma.</p> <p><strong>Objectives:</strong> 1) To assess if patients who fail to suppress FeNO after monitored therapy exhibit corticosteroid resistance. 2) To translate non-suppression of type-2 biomarkers to inflammatory mediators in the airway and peripheral blood in severe asthma. 3) To develop a prototype risk scale predicting asthma attacks based on FeNO and blood eosinophils.</p> <p><strong>Methods:</strong> 1) Induced sputum eosinophils and 11 sputum supernatant plus 9 serum inflammatory proteins were analysed in a paired before/after analysis of FeNO suppression tests conducted in Oxford, compared on the basis of a positive/negative test (i.e.: ≥42/% decrease in FeNO following monitored high-intensity corticosteroid therapy). 2) These inflammatory mediators were also correlated to the FeNO and blood eosinophil levels at the point of maximum treatment intensity in a cross-sectional study pooling the Oxford FeNO suppression cohort and the RASP-UK trial cohort. 3) Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of 8 randomised clinical trials. These were used to derive rate ratios and the predicted asthma attack rate for different patient groups.</p> <p><strong>Results:</strong> 1) Thirty-four FeNO suppression tests were analysed. The 19 patients failing to suppress FeNO were older, more intensely treated, and had little or no trends for improvement in clinical nor sputum/serum measurements compared to those who suppressed. 2) In 74 patients with severe asthma, FeNO correlated with airway type-2 cytokine, chemokine, alarmin and eosinophilia, whilst blood eosinophils correlated with serum interleukin-5. 3) The trial-derived (n=3051) prototype risk scale showed feasibility and potential to predict asthma attacks which can be prevented by anti-inflammatory therapy.</p> <p><strong>Conclusion:</strong> FeNO non-suppression carries significant translational, prognostic and theragnostic utility as a biomarker of type-2 airway inflammation in asthma – especially when used in combination with blood eosinophils.</p> |
| spellingShingle | Asthma Medicine Couillard Castonguay, S Fractional exhaled nitric oxide non-suppression in asthma |
| title | Fractional exhaled nitric oxide non-suppression in asthma |
| title_full | Fractional exhaled nitric oxide non-suppression in asthma |
| title_fullStr | Fractional exhaled nitric oxide non-suppression in asthma |
| title_full_unstemmed | Fractional exhaled nitric oxide non-suppression in asthma |
| title_short | Fractional exhaled nitric oxide non-suppression in asthma |
| title_sort | fractional exhaled nitric oxide non suppression in asthma |
| topic | Asthma Medicine |
| work_keys_str_mv | AT couillardcastonguays fractionalexhalednitricoxidenonsuppressioninasthma |