IgE is associated with exacerbations and lung function decline in COPD

Background Both allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts. Methods COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD. Results Both in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12–2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32–3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy). Conclusion These data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-021-01847-0.


Table S1
Spirometric grades and clinical groups according to GOLD.

Spirometric grades
No. of patients Percentage  Shown are blood eosinophil concentrations (cells / µl blood) and percentages (% of all blood leukocytes) of patients with normal and elevated total IgE and allergen-specific serum IgE levels (SX1). All differences were statistically significant (p < 0.05).

Table S4A
Logistic regression analyses for the association between tertiles of total serum IgE at baseline and risk of declining FEV1 (group C) during follow-up. Tertiles of total IgE: tertile 1: ≤ 24.2 IU/ml, tertile 2: 24.3 -91.5 IU/ml, tertile 3: > 91.5 IU/ml. The minimal sufficient adjustment sets for estimating the total effect of total IgE on declining FEV1 comprises age and gender (according to DAG diagram analyses, www.dagitty.net). Therefore, we calculated logistic regression models adjusting for age and gender (model 1) and additional models with more potential confounders (model 2: adjusted for age, gender, BMI, initial FEV1 % predicted, smoking status; model 3: adjusted for age, gender, BMI, initial FEV1 % predicted, smoking status, history of asthma, history of allergy).

Table S4B
Logistic regression analyses for the association between tertiles of allergen-specific IgE (SX1) at baseline and risk of declining FEV1 (group C) during follow-up. Tertiles of SX-1: tertile 1: ≤ 0.08 IU/ml, tertile 2: 0.09 -0.19 IU/ml, tertile 3: > 0.19 IU/ml. The minimal sufficient adjustment sets for estimating the total effect of SX1 on declining FEV1 comprises age and gender (according to DAG diagram analyses, www.dagitty.net). Therefore, we calculated logistic regression models adjusting for age and gender (model 1) and additional models with more potential confounders (model 2: adjusted for age, gender, BMI, initial FEV1 % predicted, smoking status; model 3: adjusted for age, gender, BMI, initial FEV1 % predicted, smoking status, history of asthma, history of allergy).

Model
Tertile of SX1 OR 95% CI P Crude

Fig. S1
Correlation as measured using Spearman's correlation coefficient (r) between total IgE levels in serum (x-axis) and allergen-specific IgE in serum (y-axis, logarithmic scale) as measured using the SX assay, in the total group of 2280 patients. *** = p < 0.001.

Fig. S3
Restricted cubic splines to visualize the non-linear association between total IgE and the exacerbation history. Three knots of total or allergen-specific IgE were placed corresponding to the 10th, 50th, and 90th percentile of the IgE levels, respectively.
Increasing total IgE levels were associated with a higher risk of exacerbations in men (p = 0.004), but not in women (p = 0.135) with COPD.