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Original Research

An Inhaled PI3Kδ Inhibitor Improves Recovery in Acutely Exacerbating COPD Patients: A Randomized Trial

, , , ORCID Icon, ORCID Icon, , , , , , , ORCID Icon, , , & ORCID Icon show all
Pages 1607-1619 | Published online: 03 Jun 2021

References

  • From the Global Strategy for the Diagnosis, Management and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020. Available from: http://goldcopd.org/. Accessed May 6, 2021.
  • Wedzicha JA, Seemungal TAR. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370(9589):786–796. doi:10.1016/S0140-6736(07)61382-8
  • Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184:662–671. doi:10.1164/rccm.201104-0597OC
  • Miravitlles M, Ferrer M, Pont À, et al.; IMPAC Study Group. Exacerbations impair quality of life in patients with chronic obstructive pulmonary disease. A two-year follow-up study. Thorax. 2004;59:387–395. doi:10.1136/thx.2003.008730
  • Niewoehner DE, Lokhnygina Y, Rice K, et al. Risk indexes for exacerbations and hospitalizations due to COPD. Chest. 2007;131:20–28. doi:10.1378/chest.06-1316
  • Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925–931. doi:10.1136/thx.2005.040527
  • Wilson R. Treatment of COPD exacerbations: antibiotics. Eur Respir Rev. 2005;14:32–38. doi:10.1183/09058180.05.00009404
  • Hunter MH, King DE. COPD: management of acute exacerbations and chronic stable disease. Am Fam Physician. 2001;64:603–613.
  • Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;16:1608–1613. doi:10.1164/ajrccm.161.5.9908022
  • Hurst JR, Donaldson GC, Quint JK, Goldring JJ, Baghai-Ravary R, Wedzicha J. Temporal clustering of exacerbations in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179:369–374. doi:10.1164/rccm.200807-1067OC
  • Suissa S, Dell’Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67:957–963. doi:10.1136/thoraxjnl-2011-201518
  • Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170:605–635.
  • Down K, Amour A, Baldwin IR, et al. Optimization of novel indazoles as highly potent and selective inhibitors of phosphoinositide 3-kinase δ for the treatment of respiratory disease. J Med Chem. 2015;58(18):7381–7399. doi:10.1021/acs.jmedchem.5b00767
  • Cahn A, Hamblin JN, Begg M, et al. Safety, pharmacokinetics and dose-response characteristics of GSK2269557, an inhaled PI3Kδ inhibitor under development for the treatment of COPD. Pulm Pharmacol Ther. 2017;46:69–77. doi:10.1016/j.pupt.2017.08.008
  • Milara J, Lluch J, Almudever P, Freire J, Xiaozhong Q, Cortijo J. Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2014;134(2):314–322. doi:10.1016/j.jaci.2014.02.001
  • To Y, Ito K, Kizawa Y, et al. Targeting phosphoinositide-3-kinase-delta with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182:897–904. doi:10.1164/rccm.200906-0937OC
  • Angulo I, Vadas O, Garçon F, et al. Phosphoinositide 3-kinase gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866–871. doi:10.1126/science.1243292
  • Stark AK, Chandra A, Chakraborty K, et al. PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner. Nat Commun. 2018;9:3174. doi:10.1038/s41467-018-05674-8
  • Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88–97. doi:10.1038/ni.2771
  • Sapey E, Stockley JA, Greenwood H, et al. Behavioral and structural differences in migrating peripheral neutrophils from patients with chronic obstructive pulmonary disease. AM J Respir Crit Care Med. 2011;183:1176–1186. doi:10.1164/rccm.201008-1285OC
  • Stark A-K, Sriskantharajah S, Hessel EM, Okkenhaug K. PI3K inhibitors in inflammation, autoimmunity and cancer. Curr Opin Pharmacol. 2015;23:82–91.
  • Rangelov BA, Young AL, Jacob J, et al. Thoracic imaging at exacerbation of chronic obstructive pulmonary disease: a systematic review. Int J Chron Obstruct Pulmon Dis. 2020;15:1751–1787. doi:10.2147/COPD.S250746
  • Vos W, Van Holsbeke C, Van Geffen W, et al. Changes in functional respiratory imaging (FRI) endpoints correlate with changes in patient reported outcomes (PRO) after recovering from acute COPD exacerbation. Eur Respir J. 2015;46(suppl 59):OA2948.
  • Vos W, Van Holsbeke C, De Backer J, De Backer WA. Correlation between changes in FEV1 and functional respiratory imaging biomarkers in a large population of asthma and COPD patients. Am J Respir Crit Care Med. 2015;191:A2266.
  • De Backer LA, Vos WG, Salgado R, et al. Functional imaging using computer methods to compare the effect of salbutamol and ipratropium bromide in patient-specific airway models of COPD. Int J Chron Obstruct Pulmon Dis. 2011;6:637–646. doi:10.2147/COPD.S21917
  • Lanclus M, Clukers J, Van Holsbeke C, et al. Machine learning algorithms utilizing functional respiratory imaging may predict COPD exacerbations. Acad Radiol. 2019;26:1191–1199. doi:10.1016/j.acra.2018.10.022
  • Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report working party standardization of lung function tests, European Community for steel and coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993;6(suppl 16):5–40. doi:10.1183/09041950.005s1693
  • Jones PW, Harding G, Berry P, Wiklund I, Chen W-H, Kline Leidy N. Development and first validation of the COPD assessment test. Eur Respir J. 2009;34:648–654. doi:10.1183/09031936.00102509
  • Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54:581–586. doi:10.1136/thx.54.7.581
  • van Geffen WH, Hajian B, Vos W, et al. Functional respiratory imaging: heterogeneity of acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:1783–1792. doi:10.2147/COPD.S152463
  • Barbosa E, Ferreira F, Vos W, et al. Quantitative functional respiratory imaging may predict the mechanism of FEV1 decline after lung transplantation. Eur Respir J. 2017;50:PA2465.
  • Vos W, Janssens A, Van Holsbeke C, et al. Functional respiratory imaging to predict post-operative FEV1 after lobectomy/pneumonectomy. Eur Respir J. 2014;44:P342. doi:10.1183/09031936.00011714
  • Lins M, Vandevenne J, Thillai M, et al. Assessment of small pulmonary blood vessels in COVID-19 patients using HRCT. Acad Radiol. 2020;27:1449–1455. doi:10.1016/j.acra.2020.07.019
  • Thillai M, Patvardhan C, Swietlik EM, et al. Functional respiratory imaging identifies redistribution of pulmonary blood flow in patients with COVID-19. Thorax. 2020. doi:10.1136/thoraxjnl-2020-215395
  • Watz H, Tetzlaff K, Magnussen H, et al. Spirometric changes during exacerbations of COPD: a post hoc analysis of the WISDOM trial. Respir Res. 2018;19:251–266. doi:10.1186/s12931-018-0944-3
  • Coutré SE, Barrientos JC, Brown JR, et al. Management of adverse events associated with idelalisib treatment: expert panel opinion. Leuk Lymphoma. 2015;56:2779–2786. doi:10.3109/10428194.2015.1022770
  • Sánchez-Alegría K, Flores-León M, Avila-Muñoz E, Rodríguez-Corona N, Arias C. PI3K Signaling in neurons: a central node for the control of multiple functions. Int J Mol Sci. 2018;19:3725. doi:10.3390/ijms19123725
  • Wilson R, Cahn A, Montembault M, et al. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single (SD) and repeat (RD) inhaled doses of a novel phosphoinositide 3-kinase δ inhibitor (PI3Kδ), GSK2269557, administered to healthy smokers. Eur Respir J. 2014;44(Suppl 58):3411.