Obesity impacts eosinophilia biomarker sensitivity
medwireNews: Markers of inflammation conventionally used to identify eosinophilic airway inflammation in patients with asthma may not be effective in obese individuals, research suggests.
“Reliance on peripheral markers to make decisions regarding therapies targeting eosinophilia should therefore be approached with caution in obese asthma,” say Njira Lugogo (Duke University Medical Center, Durham, North Carolina, USA) and colleagues.
They suggest that the unique influences of obesity, including higher levels of oxidative stress and adipokine-mediated alterations of eosinophil chemotaxis and survival could influence the accuracy of surrogate markers of eosinophilia.
Their secondary analysis of data from two Asthma Clinical Research Network trials showed that the sensitivity with which blood eosinophils, immunoglobulin (Ig)E, and fractional exhaled nitric oxide (FeNO) were able to characterize eosinophilia was significantly reduced in 243 patients with asthma who had a body mass index (BMI) of 30 kg/m2 or more compared with 211 lean (BMI≤24.9 kg/m2) and 198 overweight (BMI=25–29.9 kg/m2) patients.
Logistic regression models, adjusted for age, gender, race, and BMI, showed that across all the patients, the three markers significantly predicted high sputum eosinophils, with odds ratios (ORs) of 1.44 for blood eosinophils, 1.25 for IgE, and 2.06 for FeNo.
But when the researchers carried out the same analysis for each of the weight categories, they found that IgE was poorly predictive of eosinophilia regardless of weight, while FeNO was predictive of high sputum eosinophils only in lean asthma patients (OR=3.89; p=0.004). Blood eosinophils were most predictive in lean individuals (OR=1.67; p=0.059) followed by overweight individuals (OR=3.01; p=0.007), but were not predictive in obese individuals (OR=0.96; p=0.88).
“In fact, none of the inflammation biomarker[s] significantly predicted the presence of high sputum eosinophils in asthmatic obese patients,” the team highlights in the Journal of Allergy and Clinical Immunology.
Blood and sputum eosinophil levels were similar across the three BMI groups, whereas median FeNo and IgE levels were significantly lower in obese individuals compared with both their lean and overweight peers.
Obese patients had significantly worse lung function and a higher symptom burden than the other participants and a significantly lower prevalence of eosinophilic inflammation (sputum eosinophils above 2%), according to an FeNO threshold above 25 ppb (but not above 50 ppb), sputum eosinophils above 2%, and blood eosinophils above 300 cells/µL.
Lugogo and team performed further analyses to determine at what cutoff points the biomarkers might predict eosinophilia in obese patients with asthma.
Balancing maximum sensitivity and specificity, they calculated lower cutoff points of 268 IU for IgE, 14.5 ppb for FeNO, and 96 cells/µL for blood eosinophils.
“From the standpoint of precision medicine, these results suggest that obese patients could be inaccurately assigned to non-eosinophilic phenotypes and possibly be excluded from receiving therapies for their asthma that could facilitate improved outcomes,” the researchers write.
They conclude that more sensitive biomarkers need to be identified for obese individuals, and suggest serum periostin, dipeptidyl peptidase 4 or specific cytokine measurements as possible alternatives.
By Lucy Piper
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