COPD sputum eosinophils: relationship to blood eosinophils and the effect of inhaled PDE4 inhibition

Abstract

Patients with COPD who have higher eosinophil numbers in the airways and peripheral blood demonstrate a greater clinical response to inhaled corticosteroids (ICS) [1–3]. Furthermore, the effect of the oral phosphodiesterase-4 (PDE4) inhibitor roflumilast on exacerbations in severe COPD patients with chronic bronchitis, who are treated with ICS and long-acting bronchodilators, also appears to be greater at higher blood eosinophil counts [4]. The mechanisms responsible for these differential drug effects remain to be defined, but may relate to increased type-2 inflammation and/or decreased presence of colonising airway bacteria in COPD patients with more eosinophils [5, 6], leading to different responses to anti-inflammatory drugs. An association between blood and sputum eosinophils has been observed in some, but not all studies [7–12]. Accurate sputum eosinophil count measurement requires good quality samples to make cytospins where eosinophils can be clearly counted; variable quality of sputum samples, particularly in multicentre studies, will affect the ability to show a relationship with blood eosinophil counts.

COPD patients with chronic bronchitis and higher sputum eosinophil counts show increased type‐2 and PDE4 gene expression in sputum

“…4,10 Furthermore, we recently showed that tanimilast significantly reduced sputum eosinophil numbers in the eosinophilhigh group. 12 These previous results coupled with our current data strongly suggest that differential responses to PDE4 inhibition may relate to an increased presence of features of T2 inflammation and PDE4-related pathways in the eosinophilic COPD phenotype.…”

<p>Ultra Long-Acting β-Agonists in Chronic Obstructive Pulmonary Disease</p>

“…Elevated blood eosinophil counts predict the clinical response to inhaled corticosteroid treatment in individuals with COPD. 118 This relationship appears to start at a level of 100 eosinophils/µl and the clinical response becomes more robust as the eosinophil count increases. 123 , 124 Although only a small proportion of individuals with COPD have alpha-1-antitrypsin deficiency, recognition of the genetic mutations that cause reduced functional alpha-1-antitrypsin within the lung and increased risk of emphysema leads to specific therapy with alpha-1-antitrypsin replacement.…”

“…Serum or sputum eosinophil counts may be used to classify and hierarchize patients with COPD based upon their response to inhaled corticosteroids. 118 Plasma fibrinogen concentration is an FDA qualified biomarker for all-cause COPD mortality and COPD exacerbations. 119 One of the major goals of determining these COPD traits is to develop individualized precision medicine treatment strategies that will provide both prognostic and therapeutic guidance for the management of each person with COPD.…”

Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist

“…In contrast to the latter study, a recent study in a larger population of COPD patients revealed a consistent reduction in the eosinophil counts (but not the neutrophil count) in both bronchial biopsy and sputum samples after 16 weeks of treatment with roflumilast - particularly when the drug was combined with a LABA ( Rabe et al, 2018 ). The inhaled PDE4 inhibitor (CHF6001) was also shown to reduce sputum eosinophil counts in COPD patients with a higher sputum eosinophil count (≥3%) ( Singh et al, 2020 ). This reduction in the eosinophil count might be due (at least in part) to the inhibition of CCL5 release in bronchial explants (as seen in the present study), which might contribute to the reduction in moderate-to-severe exacerbations of COPD ( Martinez et al, 2018 ).…”