Background: This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β-agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function.
Methods: Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siV) and resistance (siR) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siV and siR changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siV and siR at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV) and COPD Assessment Test (CAT) were also assessed.
Results: There were no significant changes in pre-dose siV or siR at TLC from baseline to V3, although at FRC there was a significant decrease in mean siR in the distal airways (- 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siV and siR (siV: 39.8% and 62.6%; siR: - 51.1% and - 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siV: 77.9%; siR: - 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV was 62.2 mL (p = 0.0690), and in CAT total score was - 3.30 (p < 0.0001).
Conclusions: In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021.
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http://dx.doi.org/10.1186/s12931-023-02549-5 | DOI Listing |
Respir Res
October 2023
Departments of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Cell Host Microbe
March 2016
Department of Medicine, University of Miami Miller School of Medicine, FL 33133, USA,. Electronic address:
Lentiviruses have a long-documented association with macrophages. Abundant evidence exists for in vitro and, in a tissue-specific manner, in vivo infection of macrophages by the primate lentiviruses HIV-1 and SIV. However, macrophage contribution to aspects of HIV-1 and SIV pathogenesis, and their role in viral persistence in individuals on suppressive antiretroviral therapy, remains unclear.
View Article and Find Full Text PDFVaccine
April 2015
Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX, USA; Southwest National Primate Research Center, San Antonio, TX, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:
Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.
View Article and Find Full Text PDFJ Immunol
June 2014
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden;
Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2014
McGill University AIDS Centre, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montréal, Québec, Canada.
Objectives: HIV-1 generates swarms of similar, but genetically distinct, variants termed quasispecies and many of these variants can be defective. A relevant question is whether such defective species can contribute to viral pathogenesis. Indeed, we previously reported that a presumed recombination of defective proviral DNA with other complementary defective proviral DNA or with wild-type viral DNA in the aftermath of superinfection could lead to the rescue of defective provirus and the production of replication-competent virus.
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