ICS Use May Modify FEV₁ Decline in α₁-Antitrypsin Deficiency Patients with Relatively High Blood Eosinophils

Abstract

Background: α 1 -Antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease (COPD). In COPD unrelated to AATD, the role of a higher blood eosinophil count in disease and subsequent personalization of therapy has recently received much attention. We sought to investigate this concept in patients with AATD-associated COPD. Objectives: The study aims to evaluate eosinophilia status against outcomes including mortality and FEV 1 decline in patients with AATD. Methods: All patients with PiSZ and PiZZ genotypes were identified from the UK AATD registry. The participants were substratified according to inhaled corticosteroid (ICS) use. Blood eosinophil counts were assessed from baseline and annually during follow-up (range 1-18 years). Eosinophilia was defined as a level >0.2 × 10 9 /L, and classified by the frequency of such counts into "always," "intermittent," or "never present." Univariate and multivariate analyses were conducted. Results: In total, 646 participants were included, 53.9% of whom demonstrated intermittent and 7.4% persistent eosinophilia. Survival did not differ according to eosinophilic group (p > 0.05). Those with persistent eosinophilia showed a slower FEV 1 decline (p < 0.001). There was no clear association with exacerbation frequency. Patients on ICS at baseline were more likely to be eosinophilic (p = 0.002) and having a lower FEV 1 (p < 0.001) and greater pack-year exposure (16.5 vs. 7.8 pack-years, p < 0.001). When the multivariate analyses of FEV 1 decline were stratified for baseline ICS use, the association of persistent eosinophilia with slower decline persisted in those on ICS. Conclusions: Blood eosinophil levels persistently >0.2 × 10 9 /L may be an indication for ICS use in PiZZ AATD in order to reduce FEV 1 decline.

<p>Obstacles to Early Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency: Current Perspectives</p>

“…Inhaled therapies are prescribed according to the degree of breathlessness and inhaled corticosteroids have been shown to reduce FEV1 decline in PiZZ AATD patients with persistent eosinophilia. 56…”

Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*

“…In one large study, implementation of a management plan associated with increased adherence to pharmacological therapy was shown to reduce exacerbations and unscheduled healthcare use and improve health‐related quality of life . A post hoc analysis of another study suggested that inhaled corticosteroid could be useful in patients with AATD‐associated COPD who have persistent peripheral blood eosinophilia . Prescription of inhaled therapy, oxygen and treatment of exacerbations in AATD should be considered using similar principles to other patients with COPD …”

“…105 A post hoc analysis of another study suggested that inhaled corticosteroid could be useful in patients with AATDassociated COPD who have persistent peripheral blood eosinophilia. 106 Prescription of inhaled therapy, oxygen and treatment of exacerbations in AATD should be considered using similar principles to other patients with COPD. [94][95][96] Extrapulmonary manifestations: Management of liver complications AATD causes chronic hepatitis and its sequelae including liver fibrosis, cirrhosis and hepatocellular carcinoma.…”

<p>The Value of Inflammatory Biomarkers in Differentiating Asthma–COPD Overlap from COPD</p>

“…ICS can reduce the FEV 1 decline in patients with higher blood eosinophils counts at baseline. 51 Although many previous studies have demonstrated the value of inflammatory markers in ACO diagnosis, [15][16][17][18][19] the results remain highly controversial. 20 Kobayashi et al 15 found that 156.2/mm 3 was the best diagnostic cut-off level of EOS for ACO diagnosis, with the sensitivity and specificity being 49.5% and 83.8%, respectively.…”