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Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA.

Abstract

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.

Authors+Show Affiliations

FLUIDDA nv, Groeningenlei, Kontich, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.Department of Respiratory Medicine, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.FLUIDDA nv, Groeningenlei, Kontich, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.FLUIDDA nv, Groeningenlei, Kontich, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.FLUIDDA nv, Groeningenlei, Kontich, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.Department of Respiratory Medicine, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.Department of Respiratory Medicine, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.Department of Radiology, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.Department of Respiratory Medicine, ZNA Middelheim Hospital, Antwerp, Belgium.Department of Respiratory Medicine, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26917956

Citation

Vos, Wim, et al. "Functional Respiratory Imaging to Assess the Interaction Between Systemic Roflumilast and Inhaled ICS/LABA/LAMA." International Journal of Chronic Obstructive Pulmonary Disease, vol. 11, 2016, pp. 263-71.
Vos W, Hajian B, De Backer J, et al. Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2016;11:263-71.
Vos, W., Hajian, B., De Backer, J., Van Holsbeke, C., Vinchurkar, S., Claes, R., Hufkens, A., Parizel, P. M., Bedert, L., & De Backer, W. (2016). Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA. International Journal of Chronic Obstructive Pulmonary Disease, 11, 263-71. https://doi.org/10.2147/COPD.S93830
Vos W, et al. Functional Respiratory Imaging to Assess the Interaction Between Systemic Roflumilast and Inhaled ICS/LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2016;11:263-71. PubMed PMID: 26917956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA. AU - Vos,Wim, AU - Hajian,Bita, AU - De Backer,Jan, AU - Van Holsbeke,Cedric, AU - Vinchurkar,Samir, AU - Claes,Rita, AU - Hufkens,Annemie, AU - Parizel,Paul M, AU - Bedert,Lieven, AU - De Backer,Wilfried, Y1 - 2016/02/04/ PY - 2016/2/27/entrez PY - 2016/2/27/pubmed PY - 2016/10/8/medline KW - FRI KW - aerosol distribution KW - modeling KW - physiology KW - ventilation SP - 263 EP - 71 JF - International journal of chronic obstructive pulmonary disease JO - Int J Chron Obstruct Pulmon Dis VL - 11 N2 - 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. SN - 1178-2005 UR - https://www.unboundmedicine.com/medline/citation/26917956/Functional_respiratory_imaging_to_assess_the_interaction_between_systemic_roflumilast_and_inhaled_ICS/LABA/LAMA_ L2 - https://dx.doi.org/10.2147/COPD.S93830 DB - PRIME DP - Unbound Medicine ER -