Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma
Introduction/Aim Lung inhomogeneity measures obtained using computed cardiopulmonography (CCP) are sensitive to small-airways disease. Here, we assessed changes in lung inhomogeneity in patients with type-2 high asthma treated with biological therapy and explored the relationship between inhomogenei...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-02-01
|
| Series: | BMJ Open Respiratory Research |
| Online Access: | https://bmjopenrespres.bmj.com/content/12/1/e002721.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823864509389864960 |
|---|---|
| author | Nayia Petousi Nick P Talbot Ian Pavord Peter A Robbins Nicholas M J Smith Graham Richmond Asma Alamoudi Lorenzo Petralia Haopeng Xu Dominic Sandhu Grant AD Ritchie |
| author_facet | Nayia Petousi Nick P Talbot Ian Pavord Peter A Robbins Nicholas M J Smith Graham Richmond Asma Alamoudi Lorenzo Petralia Haopeng Xu Dominic Sandhu Grant AD Ritchie |
| author_sort | Nayia Petousi |
| collection | DOAJ |
| description | Introduction/Aim Lung inhomogeneity measures obtained using computed cardiopulmonography (CCP) are sensitive to small-airways disease. Here, we assessed changes in lung inhomogeneity in patients with type-2 high asthma treated with biological therapy and explored the relationship between inhomogeneity measures and conventional asthma disease markers.Methods This was an observational study of 91 severe type-2 high asthma patients recruited from a tertiary asthma clinic, of whom 67 subsequently started anti-IL5 or anti-IL5R biologics. Patients were evaluated at baseline and, 54 of those commencing biologics, at their fourth injection with either mepolizumab or benralizumab. Assessments included prebronchodilator and postbronchodilator CCP and spirometry, and measurements of blood eosinophil count (BEC), fractional exhaled nitric oxide and Asthma-Symptom Questionnaire (ACQ-5).Results Bronchodilation significantly reduced σlnCl, a novel CCP-derived ventilation inhomogeneity index, (ΔσlnCl −0.08, 95% CI (−0.10 to –0.05), p<0.001). Baseline σlnCl, but not forced expiratory volume in 1 s (FEV1) % predicted, was significantly associated with BEC (linear mixed-effects (LME) regression coefficient for BEC 0.18, 95% CI (0.04, 0.32), p=0.01). Following biologics, improvements in σlnCl were significantly dependent on BEC (LME regression coefficient +0.19, 95% CI (0.11, 0.27), p<0.001) whereas improvements in FEV1 % predicted related to both BEC and ACQ-5 responses (LME coefficients: BEC −10.8 % pred, 95% CI (−16.1,–5.5); ACQ-5 –3.5 % pred, 95% CI (−5.1 to –1.9), p<0.001). Following biologics, the change in σlnCl followed a bimodal distribution that dichotomised patients into σlnCl-Responders and σlnCl-Non-Responders. Responders, unlike Non-Responders, experienced significant improvements in symptoms and FEV1 % predicted (Δ pre-BD FEV115±15% pred, p<0.001) and included a higher proportion of patients in clinical remission at 1 year.Conclusion σlnCl is strongly associated with systemic eosinophilic inflammation in severe type-2 high asthma. An early σlnCl response following anti-IL5 biologics identifies patients more likely to experience improvements in symptoms and lung function when systemic eosinophils are depleted. σlnCl may provide a sensitive route for tracking inflammation involving the small airways. |
| format | Article |
| id | doaj-art-919444da43964d6caa6c0fc1a70f7ead |
| institution | Kabale University |
| issn | 2052-4439 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Respiratory Research |
| spelling | doaj-art-919444da43964d6caa6c0fc1a70f7ead2025-02-09T04:45:09ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392025-02-0112110.1136/bmjresp-2024-002721Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthmaNayia Petousi0Nick P Talbot1Ian Pavord2Peter A Robbins3Nicholas M J Smith4Graham Richmond5Asma Alamoudi6Lorenzo Petralia7Haopeng Xu8Dominic Sandhu9Grant AD Ritchie10Nuffield Department of Medicine, University of Oxford, Oxford, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UKNuffield Department of Medicine, University of Oxford, Oxford, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UKDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UKDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UKDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UKNuffield Department of Medicine, University of Oxford, Oxford, UKDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UKDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UKIntroduction/Aim Lung inhomogeneity measures obtained using computed cardiopulmonography (CCP) are sensitive to small-airways disease. Here, we assessed changes in lung inhomogeneity in patients with type-2 high asthma treated with biological therapy and explored the relationship between inhomogeneity measures and conventional asthma disease markers.Methods This was an observational study of 91 severe type-2 high asthma patients recruited from a tertiary asthma clinic, of whom 67 subsequently started anti-IL5 or anti-IL5R biologics. Patients were evaluated at baseline and, 54 of those commencing biologics, at their fourth injection with either mepolizumab or benralizumab. Assessments included prebronchodilator and postbronchodilator CCP and spirometry, and measurements of blood eosinophil count (BEC), fractional exhaled nitric oxide and Asthma-Symptom Questionnaire (ACQ-5).Results Bronchodilation significantly reduced σlnCl, a novel CCP-derived ventilation inhomogeneity index, (ΔσlnCl −0.08, 95% CI (−0.10 to –0.05), p<0.001). Baseline σlnCl, but not forced expiratory volume in 1 s (FEV1) % predicted, was significantly associated with BEC (linear mixed-effects (LME) regression coefficient for BEC 0.18, 95% CI (0.04, 0.32), p=0.01). Following biologics, improvements in σlnCl were significantly dependent on BEC (LME regression coefficient +0.19, 95% CI (0.11, 0.27), p<0.001) whereas improvements in FEV1 % predicted related to both BEC and ACQ-5 responses (LME coefficients: BEC −10.8 % pred, 95% CI (−16.1,–5.5); ACQ-5 –3.5 % pred, 95% CI (−5.1 to –1.9), p<0.001). Following biologics, the change in σlnCl followed a bimodal distribution that dichotomised patients into σlnCl-Responders and σlnCl-Non-Responders. Responders, unlike Non-Responders, experienced significant improvements in symptoms and FEV1 % predicted (Δ pre-BD FEV115±15% pred, p<0.001) and included a higher proportion of patients in clinical remission at 1 year.Conclusion σlnCl is strongly associated with systemic eosinophilic inflammation in severe type-2 high asthma. An early σlnCl response following anti-IL5 biologics identifies patients more likely to experience improvements in symptoms and lung function when systemic eosinophils are depleted. σlnCl may provide a sensitive route for tracking inflammation involving the small airways.https://bmjopenrespres.bmj.com/content/12/1/e002721.full |
| spellingShingle | Nayia Petousi Nick P Talbot Ian Pavord Peter A Robbins Nicholas M J Smith Graham Richmond Asma Alamoudi Lorenzo Petralia Haopeng Xu Dominic Sandhu Grant AD Ritchie Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma BMJ Open Respiratory Research |
| title | Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma |
| title_full | Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma |
| title_fullStr | Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma |
| title_full_unstemmed | Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma |
| title_short | Effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type-2 high asthma |
| title_sort | effects of biologic therapy on novel indices of lung inhomogeneity in patients with severe type 2 high asthma |
| url | https://bmjopenrespres.bmj.com/content/12/1/e002721.full |
| work_keys_str_mv | AT nayiapetousi effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT nickptalbot effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT ianpavord effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT peterarobbins effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT nicholasmjsmith effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT grahamrichmond effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT asmaalamoudi effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT lorenzopetralia effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT haopengxu effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT dominicsandhu effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma AT grantadritchie effectsofbiologictherapyonnovelindicesoflunginhomogeneityinpatientswithseveretype2highasthma |