Abstract
In chronic obstructive pulmonary disease (COPD), the effects of inhaled corticosteroids are predicted by blood eosinophil counts. We previously briefly reported increased immunoglobulin (Ig)A and IgM levels in bronchoalveolar lavage (BAL) of COPD patients with higher (eosinophilhigh) compared to lower (eosinophillow) blood eosinophils (>250/μL versus < 150/μL), suggesting differences in adaptive immune function. An inverse relationship exists between eosinophil counts and airway pathogenic bacteria levels. The mechanistic reasons for these associations between eosinophils, corticosteroids and pathogenic bacteria are unclear. IgA, IgM and IgG levels were assessed in BAL, bronchial biopsies and epithelium collected from eosinophilhigh (n = 20) and eosinophillow (n = 21) patients. Bronchial B‐cell numbers were measured by immunohistochemistry. B‐cell activity was assessed in bronchial samples and following exposure to BAL from eosinophilhigh and eosinophillow patients. BAL levels of non‐typeable Haemophilus influenza (NTHi)‐specific immunoglobulins were quantified. Results showed airway expression of IgA, IgG1 and IgM were lower in eosinophillow compared to eosinophilhigh patients, with lower levels of NTHi‐specific IgA and IgM. Bronchial B‐cell numbers were similar in both groups, but B‐cell activity was lower in eosinophillow patients. In conclusion, COPD eosinophillow patients show differences in adaptive immune function compared to COPD eosinophilhigh patients. These differences may cause different microbiomes in these COPD phenotypes.
Highlights
Randomized controlled trials have shown that blood eosinophil counts are a biomarker that predict the effects of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) patients at increased exacerbation risk.[1,2]
We present bronchoalveolar lavage (BAL) immunoglobulin results normalized to patient-specific BAL urea levels (Figure 1A); BAL IgA and IgM protein levels remained higher in eosinophilhigh compared to eosinophillow patients
The results showed that approximately twice as many bacteria were opsonized with IgA and IgM using BAL fluid from eosinophilhigh compared to eosinophillow patients (Figure 5), indicating lower levels of non-typeable Haemophilus influenza (NTHi)-specific IgA and IgM antibodies in eosinophillow patients
Summary
Randomized controlled trials have shown that blood eosinophil counts are a biomarker that predict the effects of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) patients at increased exacerbation risk.[1,2] The Global initiative for the management of Obstructive Lung Disease (GOLD) report recommends the use of blood eosinophil measurements to. We previously performed a bronchoscopy study in 21 blood eosinophil low (250 eosinophils/μl; eosinophilhigh) COPD patients to investigate biological differences associated with eosinophil counts.[3] We reported higher lung eosinophil numbers, thicker reticular basement membrane and differences in the levels of various inflammatory mediators including IL-5, IL-13, CCL24 and CCL26 in eosinophilhigh compared to eosinophillow patients.[3,4] Such findings are observed in patients with asthma,[5] providing insights into potential reasons for differential ICS responses associated with blood eosinophil counts in COPD. We investigated IgA, IgM and IgG levels using different samples and techniques, and measured B-cell activation and bacterial opsonization
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