Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA
Wim Vos,1 Bita Hajian,2 Jan De Backer,1 Cedric Van Holsbeke,1 Samir Vinchurkar,1 Rita Claes,2 Annemie Hufkens,2 Paul M Parizel,3 Lieven Bedert,4 Wilfried De Backer2 1FLUIDDA nv, Groeningenlei, Kontich, 2Department of Respiratory Medicine, 3Department of Radiology, University Hospital Antwerp, Wilri...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2016-02-01
|
| Series: | International Journal of COPD |
| Subjects: | |
| Online Access: | https://www.dovepress.com/functional-respiratory-imaging-to-assess-the-interaction-between-syste-peer-reviewed-article-COPD |
| _version_ | 1828422748859269120 |
|---|---|
| author | Vos W Hajian B De Backer J Van Holsbeke C Vinchurkar S Claes R Hufkens A Parizel PM Bedert L De Backer W |
| author_facet | Vos W Hajian B De Backer J Van Holsbeke C Vinchurkar S Claes R Hufkens A Parizel PM Bedert L De Backer W |
| author_sort | Vos W |
| collection | DOAJ |
| description | Wim Vos,1 Bita Hajian,2 Jan De Backer,1 Cedric Van Holsbeke,1 Samir Vinchurkar,1 Rita Claes,2 Annemie Hufkens,2 Paul M Parizel,3 Lieven Bedert,4 Wilfried De Backer2 1FLUIDDA nv, Groeningenlei, Kontich, 2Department of Respiratory Medicine, 3Department of Radiology, University Hospital Antwerp, Wilrijkstraat, Edegem, 4Department of Respiratory Medicine, ZNA Middelheim Hospital, Antwerp, Belgium Background: Patients with COPD show a significant reduction of the lobar hyperinflation at the functional residual capacity level in the patients who improved >120 mL in forced expiratory volume in 1 second (FEV1) after 6 months of treatment with roflumilast in addition to inhaled corticosteroids (ICSs)/long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs).Methods: Functional respiratory imaging was used to quantify lobar hyperinflation, blood vessel density, ventilation, aerosol deposition, and bronchodilation. To investigate the exact mode of action of roflumilast, correlations between lobar and global measures have been tested using a mixed-model approach with nested random factors and Pearson correlation, respectively.Results: The reduction in lobar hyperinflation appears to be associated with a larger blood vessel density in the respective lobes (t=−2.154, P=0.040); lobes with a higher percentage of blood vessels reduce more in hyperinflation in the responder group. Subsequently, it can be observed that lobes that reduce in hyperinflation after treatment are better ventilated (t=−5.368, P<0.001). Functional respiratory imaging (FRI)-based aerosol deposition showed that enhanced ventilation leads to more peripheral particle deposition of ICS/LABA/LAMA in the better-ventilated areas (t=2.407, P=0.024). Finally, the study showed that areas receiving more particles have increased FRI-based bronchodilation (t=2.564, P=0.017), leading to an increase in FEV1 (R=0.348, P=0.029).Conclusion: The study demonstrated that orally administered roflumilast supports the reduction of regional hyperinflation in areas previously undertreated by inhalation medication. The local reduction in hyperinflation induces a redistribution of ventilation and aerosol deposition, leading to enhanced efficacy of the concomitant ICS/LABA/LAMA therapy. FRI appears to be a sensitive tool to describe the mode of action of novel compounds in chronic obstructive pulmonary disease. Future studies need to confirm the enhanced sensitivity and the potential of FRI parameters to act as surrogates for clinically relevant, but more difficult to measure, end points such as exacerbations. Keywords: modeling, physiology, ventilation, aerosol distribution, FRI |
| first_indexed | 2024-12-10T15:51:33Z |
| format | Article |
| id | doaj.art-61bb47d01790437d98187b671921fbe8 |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-12-10T15:51:33Z |
| publishDate | 2016-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-61bb47d01790437d98187b671921fbe82022-12-22T01:42:47ZengDove Medical PressInternational Journal of COPD1178-20052016-02-012016default26327125491Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMAVos WHajian BDe Backer JVan Holsbeke CVinchurkar SClaes RHufkens AParizel PMBedert LDe Backer WWim Vos,1 Bita Hajian,2 Jan De Backer,1 Cedric Van Holsbeke,1 Samir Vinchurkar,1 Rita Claes,2 Annemie Hufkens,2 Paul M Parizel,3 Lieven Bedert,4 Wilfried De Backer2 1FLUIDDA nv, Groeningenlei, Kontich, 2Department of Respiratory Medicine, 3Department of Radiology, University Hospital Antwerp, Wilrijkstraat, Edegem, 4Department of Respiratory Medicine, ZNA Middelheim Hospital, Antwerp, Belgium Background: Patients with COPD show a significant reduction of the lobar hyperinflation at the functional residual capacity level in the patients who improved >120 mL in forced expiratory volume in 1 second (FEV1) after 6 months of treatment with roflumilast in addition to inhaled corticosteroids (ICSs)/long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs).Methods: Functional respiratory imaging was used to quantify lobar hyperinflation, blood vessel density, ventilation, aerosol deposition, and bronchodilation. To investigate the exact mode of action of roflumilast, correlations between lobar and global measures have been tested using a mixed-model approach with nested random factors and Pearson correlation, respectively.Results: The reduction in lobar hyperinflation appears to be associated with a larger blood vessel density in the respective lobes (t=−2.154, P=0.040); lobes with a higher percentage of blood vessels reduce more in hyperinflation in the responder group. Subsequently, it can be observed that lobes that reduce in hyperinflation after treatment are better ventilated (t=−5.368, P<0.001). Functional respiratory imaging (FRI)-based aerosol deposition showed that enhanced ventilation leads to more peripheral particle deposition of ICS/LABA/LAMA in the better-ventilated areas (t=2.407, P=0.024). Finally, the study showed that areas receiving more particles have increased FRI-based bronchodilation (t=2.564, P=0.017), leading to an increase in FEV1 (R=0.348, P=0.029).Conclusion: The study demonstrated that orally administered roflumilast supports the reduction of regional hyperinflation in areas previously undertreated by inhalation medication. The local reduction in hyperinflation induces a redistribution of ventilation and aerosol deposition, leading to enhanced efficacy of the concomitant ICS/LABA/LAMA therapy. FRI appears to be a sensitive tool to describe the mode of action of novel compounds in chronic obstructive pulmonary disease. Future studies need to confirm the enhanced sensitivity and the potential of FRI parameters to act as surrogates for clinically relevant, but more difficult to measure, end points such as exacerbations. Keywords: modeling, physiology, ventilation, aerosol distribution, FRIhttps://www.dovepress.com/functional-respiratory-imaging-to-assess-the-interaction-between-syste-peer-reviewed-article-COPDModelingPhysiologyVentilationAerosol DistributionInhaled Therapy |
| spellingShingle | Vos W Hajian B De Backer J Van Holsbeke C Vinchurkar S Claes R Hufkens A Parizel PM Bedert L De Backer W Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA International Journal of COPD Modeling Physiology Ventilation Aerosol Distribution Inhaled Therapy |
| title | Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA |
| title_full | Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA |
| title_fullStr | Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA |
| title_full_unstemmed | Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA |
| title_short | Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA |
| title_sort | functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ics laba lama |
| topic | Modeling Physiology Ventilation Aerosol Distribution Inhaled Therapy |
| url | https://www.dovepress.com/functional-respiratory-imaging-to-assess-the-interaction-between-syste-peer-reviewed-article-COPD |
| work_keys_str_mv | AT vosw functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT hajianb functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT debackerj functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT vanholsbekec functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT vinchurkars functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT claesr functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT hufkensa functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT parizelpm functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT bedertl functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama AT debackerw functionalrespiratoryimagingtoassesstheinteractionbetweensystemicroflumilastandinhaledicslabalama |