Clinical Remission by a Comprehensive Severe Asthma Management Strategy Guided by Airway Inflammometry and Bioimaging
Bibliographic record
Abstract
Abstract RATIONALE: Clinical remission is a recently introduced multicomponent treatment goal in severe asthma. Several studies have shown that about 20-40% of patients achieve remission when treatment decisions are based on the currently recommended biomarkers (blood eosinophils and FeNO). Here, we report clinical remission in severe asthma following 24 months of treatment using a comprehensive, individualized strategy involving the use of anti-inflammatory therapy, biologics, antibiotics, immunomodulators, and bronchial thermoplasty, guided by clinical assessment, airway physiology, sputum inflammometry, and airway imaging. METHODS: Clinical characteristics—including exacerbations, oral corticosteroid (OCS) requirements, symptoms (ACQ-5), and lung function—were assessed over the 2 years prior to the commencement of the strategy and compared to outcomes after 2 years of strategy-guided treatment. The proportion of patients who met clinical remission—defined as the absence of exacerbations, no OCS use, and good asthma control (ACQ-5 <1.5), with or without lung function decline (FEV1% decline <5% from baseline)—was evaluated. RESULTS: A total of 178 patients [median age 56 years (IQR 44.8-64); 57.3% women] were evaluated. All subjects were treated with high doses of inhaled corticosteroids (and requiring 2-3 short courses of prednisone/year); 66.9% were on maintenance prednisone. Overall, 157 of 178 patients (88.2%) were treated with biologics alone or in combination with other strategies. Thirty-six patients (20.2%) had immunodeficiencies leading to airway infections contributing to asthma exacerbations and were treated with antibiotics, hypertonic saline, and/or immunoglobulins. Sixteen patients (9%) whose symptoms were driven by airway hyperresponsiveness (PC20 methacholine <0.5mg/mL) received bronchial thermoplasty guided by functional MRI after controlling the inflammatory component. Compared to outcomes over the 2 years prior to assessment, all outcomes improved significantly (Figure 1A). Notably, after 24 months 89.9% (160/178) of patients were exacerbation-free, 83.1% (148/178) were OCS-free, 78.1% (139/178) had well-controlled asthma, and 84.8% (128/151) had preserved lung function (Figure 1B). Clinical remission was achieved by 66.3% (118/178) of patients based on the three primary criteria [absence of exacerbations, no OCS use, and controlled symptoms (ACQ-5 <1.5)], and by 60.9% (92/151) when including no lung function decline. Residual symptoms and clinical disease were driven by airway infections and airway hyperresponsiveness, and not by T2 immune mechanisms (Figure 1B). CONCLUSION: Using a comprehensive set of biomarkers and management strategy tailored to the pathobiology of the individual patient, it is realistic to achieve clinical remission in up to 70% of patients. Recurrent airway infections, mucus and airway hyperresponsiveness remain unmet needs in severe asthma.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".