Knowledge on multiple interdependences between quality of life (QoL) and behavioural problems in relation to asthma severity and control is undetermined. The aims of the study were: (i) to assess the relationship of QoL and behavioural problems with asthma severity and control (ii) to predict children’s “abnormal/borderline” status with variation in QoL. For these purposes a multicenter case-control study on 47 Severe Asthma (SA) and 94 Moderate Asthma (MA) children was performed. The MIMIC approach was applied to investigate the effect of SA and non-controlled asthma (NC) on QoL and behavioural disorders. Logistic regression was used to estimate probabilities of having an “abnormal/borderline” status with variation in QoL. The MIMIC model showed that the magnitude of the effect of SA and NC was larger on QoL (β = −0.37 and β = −0.30, respectively) than on behavioural problems (β = 0.27). With regards to the probability of having a borderline status, in MA a QoL of 1 returned a probability of 0.81, whereas in SA a QoL of 1 returned a probability of 0.89. In conclusion, SA children are highly affected by impaired QoL and behavioural problems. The MIMIC model allowed us to obtain a comprehensive assessment of QoL and behavioural problems with asthma severity and control.

Asthma is the most frequent chronic inflammatory disease of the lower airways affecting children, and it can still be considered a challenge for pediatricians. Although most asthmatic patients are symptom-free with standard treatments, a small percentage of them suffer from uncontrolled persistent asthma. In these children, a multidisciplinary systematic assessment, including comorbidities, treatment-related issues, environmental exposures, and psychosocial factors is needed. The identification of modifiable factors is important to differentiate children with difficult asthma from those with true severe therapy-resistant asthma. Early intervention on modifiable factors for children with difficult asthma allows for better control of asthma without the need for invasive investigation and further escalation of treatment. Otherwise, addressing a correct diagnosis of true severe therapy-resistant asthma avoids diagnostic and therapeutic delays, allowing patients to benefit from using new and advanced biological therapies.

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.