Evolving Disease Phenotypes in Pediatric Severe Asthma: A Report of Dual Biologic Therapy for Comorbid Systemic Inflammatory Disease
Bibliographic record
Abstract
Abstract Introduction: Identification of disease phenotypes in pediatric severe asthma allows for targeted treatment strategies, but data on their evolution during childhood is limited. We present a case of severe eosinophilic asthma, in a child with new onset features of a systemic inflammatory disease, prompting augmentation of biologic therapy. Case Description: A 12-year-old patient with severe eosinophilic, atopic asthma, and a history of multiple PICU admissions, was escalated in treatment to high-dose ICS/LABA therapy, montelukast, and chronic oral steroids. Spirometry revealed moderate obstruction with a 26% bronchodilator response, and phenotyping showed elevated serum eosinophils, with peak of 4730cells/µL, IgE 145 IU/ml, fractional exhaled nitric oxide (FeNO) at 57ppb, and multiple aeroallergen sensitizations. Initiation of omalizumab allowed for cessation of oral steroids and reduction to moderate dose ICS/LABA. Serum eosinophils decreased to 0.30cells/µL and FeNO to 7ppb. Within 12 months of initiation of omalizumab, the patient had new onset fatigue, weight loss and hematochezia. Despite ongoing respiratory symptom control, eosinophils increased to 2440cells/µL and FeNO to 37ppb. Further testing revealed iron deficiency anemia, elevated fecal calprotectin to 758µg/g, and newly positive pACNA 1:80 with weakly positive anti-PR3 antibodies at 24.7CU. The patient was diagnosed with ulcerative colitis (UC) based on isolated chronic colitis on colonoscopy. Refractory response to mesalamine prompted escalation to vedolizumab, a gut-selective anti-integrin monoclonal antibody. Without meeting criteria for EGPA or another unifying diagnosis, the patient continues to be followed closely by GI, rheumatology and respirology for UC and severe asthma, on dual biologic therapy. Discussion: We present a pediatric patient with classic eosinophilic, atopic asthma, with good response to anti-IgE therapy. However, during early adolescence developed signs of an alternative systemic inflammatory disease, prompting initiation of dual biologic therapy. With the introduction of novel biologic therapies, and our growing understanding of evolving disease phenotypes in asthma, it is crucial to develop refined, multidisciplinary approaches to targeting evolving inflammatory pathways involved. Conclusion: Vigilant monitoring of patients with severe asthma is crucial to detect changes in disease phenotype, which may herald the evolution of a patient's disease. Recognition allows for accurate, timely, and targeted adjustments to treatment regimens.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".