Severe asthma exacerbations have high morbidity and mortality. The management can be challenging, and the optimal strategy for patients admitted to the intensive care unit (ICU) with life-threatening and near-fatal asthma has not been fully defined. An interesting area of research is represented by the rescue or compassionate use of biological drugs when all treatments fail, including advanced interventions such as extracorporeal membrane oxygenation. This systematic review analyzes the cases described in the literature and discusses characteristics, treatments, and outcomes of patients who received asthma-approved monoclonal antibodies as rescue therapy following admission to the ICU due to near-fatal asthma exacerbations or status asthmaticus refractory to conventional treatments. A total of 14 studies (13 case reports and 1 case series) were included according to the prespecified inclusion and exclusion criteria. Various monoclonal antibodies were administered, most commonly benralizumab and omalizumab. Treatment was generally initiated within the first week of ICU admission, with nearly half of the patients receiving therapy within 5 days. Further research, including randomized controlled trials, is required to assess if this therapeutic option impacts ICU outcomes, which specific biologics could be used, and their eventual optimal timing and dosage.

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six groups to distinguish profiles of symptomatic resilience from biological insensitivity to corticosteroids. Methods: Real-world study of 292 patients stratified into six groups based on BEC (≥250 cells/microL), FeNO (≥25 ppb), and IgE (≥100 kU/L). ACT, BMI, FEV1, comorbidities, and therapeutic burden were analyzed. Results: The EoS+ IgE+ group showed “symptomatic resilience”: apparent clinical control (54.5% ACT ≥ 20) supported by a critical pharmacological burden (90% salbutamol, 80% OCS ≥ 7.5 mg). The Triple Positive and EoS+ FeNO+ groups depicted “Maximum Steroid Insensitivity,” characterized by poor control despite maximal ICS/OCS regimens. FeNO could appear like the primary driver of instability, reflecting a trajectory of oxidative stress not altered by steroids. Conclusions: T2 biomarkers provide a unique prognostic value unidentifiable by standard clinical assessment. FeNO monitoring unmasks silent distress in resilient patients and identifies the “therapeutic wall” in refractory profiles. Therefore biological remission could represents the only effective target to modify the natural history of the disease.