EGPA should be considered in patients with severe asthma: Study
Rare AAV type diagnosed in 4% of those with uncontrolled asthma at hospital
Eosinophilic granulomatosis with polyangiitis (EGPA) should be considered in people with uncontrolled severe asthma and high blood levels of immune cells called eosinophils — a hallmark of the autoimmune disease — according to the findings of a study from Singapore.
This rare type of ANCA-associated vasculitis (AAV) was diagnosed in approximately 4% of the nearly 600 people with severe asthma seen in a single hospital in that country, and at a median of 10 years after an asthma diagnosis.
“Our study suggests that the prevalence of EGPA is higher in the severe asthma population,” the researchers wrote, calling on specialists to be vigilant in clinical settings.
“Pulmonologists should maintain high awareness of the disease with patients presenting with asthma, especially when they are uncontrolled or severe and have high blood eosinophil counts,” the team wrote.
The study, “Characteristics of Severe Asthma Clinic Patients with Eosinophilic Granulomatosis with Polyangiitis,” was published in The Journal of Allergy and Clinical Immunology: In Practice.
Singapore study analyzed records of nearly 600 patients with severe asthma
AAV is a group of autoimmune conditions characterized by inflammation and damage to small blood vessels, which affects several organs, including the lungs and kidneys. EGPA is also marked by high levels of eosinophils — immune cells that normally protect the body against disease-causing agents.
Asthma is a common feature of EGPA, typically occurring in its first stages, before the onset of other whole-body symptoms, like kidney, neurological, and skin manifestations.
However, “the relationship between the natural course of asthma and the other systemic [whole-body] manifestations of EGPA is not well defined,” the researchers wrote. In addition, “few studies have evaluated the prevalence and characteristics of EGPA in the group of patients with severe asthma (SA) with longitudinal follow-up.”
To find out more, the team of researchers retrospectively analyzed the medical records of 596 EGPA patients who were followed at the Singapore General Hospital’s multidisciplinary severe asthma clinic between 2011 and 2023.
Severe asthma was defined as having poor symptom control and/or having more than one episode of worsening symptoms in 12 months that required hospitalization, or more than two of such episodes requiring oral glucocorticoid treatment despite adherence to appropriate asthma treatment.
The EGPA diagnosis was based on a combination of factors: the presence of asthma, having eosinophil counts higher than one billion cells per liter of blood and/or eosinophils accounting for more than 10% of all immune cells, and having at least two other organs affected.
The patients’ median age at their asthma diagnosis was 45, but the range was a wide one, from 10 to 75 years. In all, 23 patients — 3.9% — were diagnosed with EGPA after a median of 10 years. Among them, 13 were women and 10 were men.
Severe asthma patients diagnosed with EGPA had a significantly lower body mass index, which is a ratio of height and weight, and less-controlled asthma compared with those without the disease. The EGPA patients also had higher peak eosinophil counts.
All but one of these 23 EGPA patients had a peak value of blood eosinophils higher than one billion cells/L; in the remaining patient, eosinophils accounted for 13.9% of immune cells. More than one-third — eight individuals — were positive for ANCAs, the self-reactive antibodies that drive most cases of AAV, but are detected less commonly among EGPA patients.
Over 40% of asthma patients diagnosed with EGPA first treated with Nucala
The EGPA patients all showed signs of mild lung obstruction, as assessed with a standard lung test measuring the amount of air individuals can force out of their lungs in one second.
After asthma, upper airway involvement was the most common disease manifestation, affecting 60.9%. This was followed by symptoms of damage to the nerves outside the brain and spinal cord, known as peripheral neuropathy, found in 52.2% of patients. Kidney involvement was seen for 47.9%, and skin manifestations affected 43.5%.
A total of 10 patients (43.5%) received biological therapies, or those derived from living organisms: Nucala (mepolizumab), an approved EGPA treatment that targets eosinophils, and dupilumab (sold as Dupixent), an eosinophil-targeting medication approved for other conditions marked by high eosinophil counts.
All 10 patients were given Nucala, but two later changed to dupilumab due to difficulty in controlling asthma and failure to achieve disease remission.
Overall, patients on biological medications were significantly younger at the EGPA diagnosis than those who were not on these therapies (55 vs. 68 years). They were also significantly more likely to have signs of pus, blood, or proteins in the lungs (70% vs. 23.1%), and less likely to have kidney involvement (10% vs. 76.9%).
Our study highlights the importance for clinicians treating [severe asthma patients] to remain at a high level of diagnostic awareness for signs of EGPA, … and to follow up with these patients for a prolonged time frame.
A significantly lower proportion of patients on biologic therapies remained on glucocorticoids relative to those not on those medications (30% vs. 76.9%), indicating a higher chance of discontinuing this class of medications; their long-term use is linked to severe side effects.
Treatment with the biologic agents was also significantly associated with less severe disease, as indicated by a lower Five Factor Score (FFS, 0.3 vs. 1.5). FFS is a measure of the likely course of the disease, with higher scores indicating worse disease and an increased risk of death.
“EGPA is a diverse and [variable] condition that necessitates a high clinical suspicion for diagnosis, multidisciplinary approach to its diagnosis and management, as well as prolonged period of ongoing clinical and therapeutic monitoring,” the team wrote. “Our study highlights the importance for clinicians treating [severe asthma patients] to remain at a high level of diagnostic awareness for signs of EGPA, … and to follow up with these patients for a prolonged time frame.”
Patients with severe asthma and high eosinophil counts should be evaluated for disease manifestations outside the lungs to allow early detection of EGPA, the researchers concluded.
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