Aerogen

Jul 12, 2023

Disclosures: Barjaktarevic reports receiving grants from Amgen and Theravance/Viatris, and consulting fees from Aerogen, AstraZeneca, GlaxoSmithKline, Grifols, Inhibrx, Theravance/Viatris and Verona Pharma. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures. ADD TOPIC TO EMAIL ALERTS Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . Please try again later. If you continue to have this issue please contact customerservice@slackinc.com . Back to Healio Key takeaways: Patients with advanced COPD and blood eosinophils of 100 or less had more exacerbations and reduced lung function vs. those with blood eosinophils greater than 100. More of these patients had emphysema. An increase in exacerbations and worse lung function was found in those with advanced COPD and blood eosinophil counts less than or equal to 100 compared with those with higher counts, according to study results published in CHEST. Igor Barjaktarevic “Blood eosinophils represent an important biomarker in airway diseases and their increased counts are associated with a higher risk of exacerbations and better response to inhaled steroids,” Igor Barjaktarevic, MD, PhD, associate professor of medicine and medical director of the COPD program at the David Geffen School of Medicine at UCLA, told Healio. “Based on that, guidelines recommend the escalation of inhaled therapies. Nevertheless, having low blood eosinophils is currently seen as a reason to withhold certain therapeutic approaches, and specific cut-off thresholds are recommended to be guiding these decisions. Data were derived from LeMaster WB, et al. CHEST. 2023;doi:10.1016/j.chest.2022.10.029. “Our findings suggested that Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D COPD patients with low blood eosinophil counts (BECs) who are not treated with inhaled corticosteroids have greater emphysema, more exacerbations and greater lung function decline over time as compared with their peers with high BEC,” he added. “This should not come as a surprise as low blood eosinophils should by no means imply that these patients suffer less inflammation or less aggressive COPD, but rather distinct inflammatory pathways.” Using adults from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), Barjaktarevic and colleagues analyzed 185 patients with COPD in GOLD group D not taking inhaled corticosteroids to determine if there are changes in characteristics at baseline and clinical outcomes based on high or low blood eosinophil counts (BECs) . Researchers also evaluated 1,414 patients with COPD, which included the 185 patients in GOLD group D, also not on inhaled corticosteroids to account for all severity stages of COPD when assessing the impact BECs have on various outcomes. In order to find differences between those with high and low counts, researchers utilized multivariable mixed models and logistic regression. Within the cohort of all patients with COPD, 485 adults (mean age, 65.18 years; 55% men) had BECs less than or equal to 100, including 61 patients with COPD in GOLD group D, whereas 929 (mean age, 65.4 years; 62% men) had BECs greater than 100, including 124 patients in GOLD group D. Total cohort outcomes A few baseline demographics differed between the two sets of total patients, with more patients with low BECs being women and current smokers (39% vs. 33%) and fewer having a history of childhood asthma (6% vs. 10%) compared with patients with high BECs. Researchers observed no significant differences between the low and high BEC groups containing all COPD severity levels when assessing exacerbations (BEC 100 vs. BEC > 100, 0.4/year vs. 0.36/year), initiation of inhaled corticosteroid in follow-up (2.5% vs. 4.4%), reduced lung function (mean slope, –50 mL/year vs. –39 mL/year) and death (7.8% vs. 8.4%). GOLD group D outcomes Several outcomes changed when only including patients in GOLD group D. In terms of baseline characteristics, current smoking (47% vs. 31%) and emphysema (voxels < 950 Hounsfield units at total lung capacity, 7.46% vs. 4.61%; P = .029) were higher in those with lower BECs vs. those with higher counts. These patients also had significantly higher mean airway wall thickness (3.91; 95% CI. 3.87-3.96 vs. 3.85; 95% CI, 3.92-3.88). Compared with advanced COPD patients with BECs over 100, those with lower BECs experienced more exacerbations at 1 year (0.33/year vs. 0.62/year; P = .002) and in the 3-year follow-up (0.83/year vs. 1.16/year; P = .014), according to researchers. Notably, patients with lower counts also suffered with more exacerbations in which antibiotics were necessary (0.71 vs. 0.5; P = .02). Additionally, researchers observed larger reductions in lung function per year in patients with lower BECs in GOLD group D when put against those with higher counts (mean slope, –68 mL/year vs. –23 mL/year; P = .036). “A lot of new therapeutic approaches have been developed targeting patients with high eosinophils while much less has been made available for those with low eosinophils — in fact, we’ve taken inhaled corticosteroids off the table for many of them,” Barjaktarevic told Healio. “Therefore, it is for clinicians to recognize the particular vulnerability of the latter group of patients and understand the need for a tailored personalized approach to considering escalating pharmacologic and non-pharmacologic therapies. Simply put, a cutoff of 100 cells/µL, which is mentioned in the GOLD guidelines as a threshold below which the use of inhaled corticosteroids has ‘low likelihood of treatment benefit,’ needs to be taken as a warning that the risk-benefit relationship needs to be well-addressed rather than a reason not to proceed with escalation of therapeutic approaches and automatic withholding of therapeutic options that would otherwise be offered to those above this threshold.” Exacerbation predictors, inhaled corticosteroids use Researchers included all patients when evaluating predictors of exacerbations and found a higher risk for this outcome in both BECs groups with white race (BEC 100, P = .038; BEC > 100, P = .043) and a history of previous exacerbations (P < .001 for both), along with a lower risk with postbronchodilator FEV1 (P = .002; P < .001). Notably, only patients with high counts had a heightened risk for exacerbations with a history of asthma (P = .02). Lastly, in a separate assessment, researchers evaluated the 61 patients with low BECs in GOLD group D against 27 patients in the same BEC and COPD severity group but with baseline inhaled or oral corticosteroid use. Exacerbations over 1 year and initial lung function were not significantly linked to inhaled corticosteroid use. When interpreting the results, several limitations should be considered, Barjaktarevic told Healio. “Our data are based on a retrospective analysis of a cohort not designed specifically to examine the clinical implications of a low BEC,” he said. “Other limitations include the relatively small number of participants with low blood eosinophils in our cohort and the fact that the decisions to use or not to use different therapeutic approaches during the course of the study were not in the control of our study team. Consequently, our conclusions need to be taken cautiously, suggesting the need for dedicated prospective studies to be conducted in the future to further address the clinical implications of low eosinophils in COPD. “The search for reliable biomarkers in a heterogeneous disease such as COPD needs to continue, and understanding the endotypic characteristics of inflammatory pathways is crucial for further development of pharmacotherapies,” Barjaktarevic added. “While we have made much progress in understanding the Th-2 cellular immunity pathways recently, more effort is required in understanding non-eosinophilic COPD.” This study by Barjaktarevic and colleagues adds to growing literature on COPD management depending on severity level and clinical characteristics; however, it challenges the emphasis the GOLD guidance places on patients with high BECs with its findings, according to an accompanying editorial by Timothy H. Harries, MBBS, PhD, of the department of public health and primary care, and Richard E. K. Russell, MD, PhD, of the department of immunobiology at King’s College in London. “Although the [GOLD guidance’s] focus is on those patients with raised BEC, clearly we also need to consider those with BEC [equal to or less than] 100 cells/mL,” Harries and Russell wrote. “These COPD patients may benefit from close monitoring after the clinical course and an assessment to detect bacterial colonization of the airways, thus allowing appropriate treatment. “Much remains to be discovered about the role of both high and low blood eosinophils in COPD, and this will be a rich vein for research from the molecular level to the epidemiology of these patients,” they added. “Both low and high blood eosinophil levels present challenges to patients and opportunities for researchers and clinicians. Is there an optimum blood eosinophil level in COPD? From our current knowledge and this new data mandate, clearly we need to look both ways!” For more information: Reference: