Exacerbations in allergic bronchopulmonary aspergillosis (ABPA) are predicted by elevated peripheral blood eosinophil count (BEC) and the severity of bronchiectasis, and most commonly occur within 3 years of stopping glucocorticoid treatment, according to a post hoc analysis published in Mycoses.
Researchers sought to characterize the long-term outcomes of ABPA and to identify exacerbation predictors. Primary outcomes included the incident rate and frequency of exacerbations. ABPA exacerbation prediction factors and changes in serum total immunoglobulin E (IgE) during glucocorticoid treatment were secondary outcomes of interest.
Investigators conducted a retrospective post hoc analysis of a study of 182 treatment-naïve patients (mean, 38 years of age; 53.3% women; mean [SD] asthma duration, 12 [9.3] years) with acute stage ABPA-complicating asthma from 3 randomized trials conducted between 2014 and 2017. Patients in those trials were monitored every 6 weeks for 6 months, then every 6 months after receiving oral prednisolone for 4 months (0.5, 0.25, and 0.125 mg/kg/day for 4 weeks each; then tapered by 5mg every 2 weeks until discontinuation at 4 months). Mean follow-up duration was 2.8 years.
Patients with concomitant use of omalizumab, voriconazole, or other biological agents or taking systemic glucocorticoids for more than 3 weeks in the previous 6 months were excluded. More than 95% of patients had bronchiectasis with mean involvement of 8 bronchopulmonary segments.
In the current post hoc analysis, the investigators defined response to treatment as more than 75% improvement from baseline cough and dyspnea and at least 50% clearance of chest radiographic opacities. ABPA exacerbation was defined as the appearance of radiological opacities consistent with APBA and the persistent worsening of patient symptoms.
The investigators found 81 patients (44.5%) experienced 120 exacerbations during follow-up of 512 patient-years (ABPA exacerbation incident rate, 234/1000 patient-years). Exacerbations were experienced by 90.1% of patients within 3 years of stopping therapy. Mean time to first ABPA exacerbation was 608 days after stopping prednisolone therapy. Investigators noted exacerbations were exceedingly rare after 5 years.
After adjusting for serum total IgE and high-attenuation mucus, ABPA exacerbation was independently predicted by a peripheral BEC of at least 1000 cells/μL (adjusted odds ratio [aOR], 2.43; 95% CI, 1.26-4.67); female sex (aOR, 2.16; 95% CI, 1.10-4.24); extent of bronchiectasis (aOR, 1.10; 95% CI, 1.03-1.18); and age (aOR, 0.97; 95% CI, 0.94-0.99), on multivariate logistic regression analysis.
After 6 weeks, the best cut-off for identifying treatment response was a 20% decline for serum total IgE; the cut-off for identifying ABPA exacerbations was a 50% increase for serum total IgE.
Post hoc analysis limitations include no description of the type of bronchiectasis, lack of uniformity in follow-up duration, and the potential for disease course to be altered by therapy variation.
“ABPA exacerbations were common within 3 years of stopping treatment,” investigators concluded, adding, “Age, female sex, peripheral blood eosinophilia and the extent of bronchiectasis predicted ABPA exacerbations.” Investigators further concluded that “The optimal serum total IgE cut-off for defining ABPA response and exacerbations is a 20% decline and a 50% increase, respectively.”
References:
Agarwal R, Sehgal IS, Muthu V, et al. Long-term follow-up of allergic bronchopulmonary aspergillosis treated with glucocorticoids: A study of 182 subjects. Mycoses. Published online August 9, 2023. doi:10.1111/myc.13640