Control of airway inflammation maintained at a lower steroid dose with 100/50 microg of fluticasone propionate/salmeterol

BACKGROUND: Inhaled corticosteroids (ICSs) have been shown to reverse epithelial damage and decrease lamina reticularis thickness in patients with asthma. OBJECTIVE: This study investigated whether clinical asthma control and airway inflammation could be maintained after switching therapy from medium-dose fluticasone propionate (FP) to low-dose FP administered with the long-acting beta2-agonist (LABA) salmeterol. METHODS: Eighty-eight subjects (age, > or =18 years) who, during open-label screening, demonstrated improved asthma control after an increase from 100 microg of FP twice daily to 250 microg of FP twice daily were randomized to receive 100/50 microg of FP/salmeterol through a Diskus inhaler (GlaxoSmithKline, Research Triangle Park, NC) twice daily or continue 250 microg of FP twice daily through a Diskus inhaler for 24 weeks. Clinical outcomes were monitored, and bronchial biopsy specimens and bronchoalveolar lavage fluid were obtained before and after 24 weeks of treatment. RESULTS: There were no significant differences between treatments with respect to eosinophils in the bronchial mucosa and bronchoalveolar lavage fluid; mucosal mast cells, neutrophils, or CD3+, CD4+, CD8+, or CD25+ T lymphocytes; or concentration of mediators (GM-CSF, IL-8, and eosinophil cationic protein). The 2 treatments were not different with respect to lamina reticularis thickness. Consistent with the airway inflammatory measures, clinical and physiologic measures of asthma control were also similar. CONCLUSION: This study demonstrates that control of asthma and airway inflammation is maintained over the 24-week treatment period when patients requiring a medium-dose ICS are switched to a lower-dose ICS with a LABA. CLINICAL IMPLICATIONS: A lower-dose ICS with a LABA is effective in controlling inflammation and providing clinical asthma control, confirming current guideline recommendations

Disconnect between sputum neutrophils and other measures of airway inflammation in asthma

No abstract available

Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts

Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.6 month embargo; published online: 26 April 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]