Aerodigestive eosinophilia may be an endotype of severe uncontrolled asthma
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Key takeaways:
- 45% of children with airway eosinophils had endobronchial biopsy eosinophils without bronchoalveolar lavage eosinophils.
- 48% of the patients had positive bacterial bronchoalveolar lavage cultures.
WASHINGTON — Children with severe uncontrolled asthma commonly have eosinophilic airway inflammation, according to data presented at the American Thoracic Society International Conference.
This inflammation makes endobronchial biopsy an important tool in characterizing airway eosinophils, Jessica Lee Erkman, CPNP, of the pediatric pulmonology department at Hassenfeld Children’s Hospital at NYU Langone, and colleagues wrote.
“We have been caring for children with severe asthma for many years,” Erkman told Healio.
Erkman said that she and her colleagues have seen patients who are on combination therapy including high-dose inhaled corticosteroids and long-acting beta agonists, whose adherence has been addressed and whose allergy workups have been completed but continue to have poorly controlled asthma.
“This results in a certain degree of frustration for both the provider and patient,” Erkman said. “We realized that the next step has to be a thorough characterization of lower airway inflammation and addressing complicating factors in their poor asthma control.”
This approach allows for the creation of a more precise personalized treatment plan, Erkman said, adding that a comprehensive aerodigestive evaluation would provide the needed information.
“We are concerned that ‘noninvasive’ phenotyping of asthma is not accurate and may not correlate with invasive methods at all,” she continued. “This may potentially lead to sub-optimal selection of biological medications and reduce the success of this expensive treatment.”
Study design, results
The researchers conducted a retrospective analysis of children with severe uncontrolled asthma who had bronchoscopy with bronchoalveolar lavage (BAL), endobronchial biopsy (EBB) and esophagoscopy with biopsy (EsB).
There were 64 patients who had a bronchoscopy, including 40 patients whose procedure was combined with esophagoscopy. Of the 47 patients with airway eosinophils, 21 (45%) had EBB eosinophils but not BAL eosinophils.
The researchers also called the relationship between severe airway eosinophilia and EsB eosinophils significant (chi square, 8.8; P = .003), with 84% specificity.
Further, the researchers said 35 of the patients (55%) had severe BAL neutrophilia (≥ 42%), 25 (39%) had neutrophilic infiltrates based on EBB, and 31 (48%) had positive bacterial BAL cultures (≥ 104 colony-forming unit per mL).
Positive bacterial BAL cultures were related to severe BAL neutrophilia (chi square, 4.3; P = .037) and to the presence of EBB neutrophilic infiltrates (chi square, 4; P = .046).
The researchers additionally reported that 34 patients (53%) had reticular basement membrane thickening. Although there was no relationship between this thickening and the presence of EBB eosinophils, severe airway eosinophilia or neutrophilic infiltrates in EBB, the researchers wrote, it had a significant relationship with EsB eosinophils (chi square, 4.8; P = .03).
Finally, the researchers found that the 40 patients with EsB included 14 (35%) with reflux esophagitis and nine (23%) with eosinophilic esophagitis.
Conclusions, next steps
Calling eosinophilic airway inflammation common among children with severe uncontrolled asthma, the researchers said EBB was important in properly assessing and characterizing airway eosinophils. Noting that bacterial infection in the lower airway may drive neutrophilic airway inflammation, the researchers also said that esophageal eosinophils frequently are present and relate to severe airway eosinophilia in children with severe uncontrolled asthma.
“We feel this is a very important finding,” Erkman said. “It almost seems like the neutrophilic phenotype of asthma, which has never been clearly defined in pediatrics, could be explained by overlap of asthma with bacterial lower airway infection. We think it may provide a key to future management.”
As they are present in half of children with severe uncontrolled asthma, the researchers added, features of airway remodeling relate to the presence of esophageal eosinophils and may define aerodigestive eosinophilia as an endotype of severe uncontrolled asthma.
And, in more than 50% of cases, the researchers concluded, esophagitis further complicates severe uncontrolled asthma.
“Larger asthma centers should adapt the aerodigestive approach to asthma comorbidities and characterization of airway inflammation,” Erkman said. “Consideration shall be given to the attempts to personalize treatment plans based on the findings of this workup.”
Erkman called this the task of future research.
“We need to conduct prospective studies and show how phenotyping/endotyping of asthma using methods of bronchoalveolar lavage and endobronchial and esophageal biopsy may lead to more precise selection of treatments and increased treatment efficacy,” she said.