Biomarker strategies for perioperative hypersensitivity reactions and severe eosinophilic asthma

Asthma is a significant global health concern impacting up to 235 million people worldwide. It is a non-communicable and chronic inflammatory disease marked by periodical or persistent respiratory symptoms (eg shortness of breath, wheezing, chest tightness and cough) and airflow limitation due to bronchoconstriction, airway wall thickening and increased mucus production.1, 2 Asthma frequently commences in early childhood and affects more boys than girls. Children with asthma are at higher risk of depression and anxiety, negatively impacting asthma control and management. Recent studies have suggested that asthmatic children might also be burdened by poor mental health, including attention-deficit hyperreactivity (ADHD) and autism spectrum disorder (ASD). (ref3 bow Shaws). Uncontrolled asthma can have a wide-ranging effect on the lives of young people, including on their health, sleep, academic performance, social interactions, school attendance and overall quality of life. Limited studies have evaluated the influence of asthma on adolescents completing high school and on academic performance. Notably, most of these studies have yielded inconclusive findings. Mitchell and Colleagues (ref4) (ref 4) have compared scholastic performance and high school completion of young people hospitalized with asthma to matched peers not hospitalized with asthma. The authors conducted a population-based matched case-comparison cohort study of young people aged ≤18 years hospitalized for asthma during 2005–2018 in New South Wales, Australia, using linked birth, health, education and mortality records. Mitchell and Colleagues identified a relationship between young males hospitalized with asthma and a higher risk of not attaining minimum standards for numeracy and reading in national school-based assessments compared to their matched peers. Moreover, both young males and females hospitalized with asthma had a higher risk of not completing high school than matched peers. Educational attainment was more impaired for young people hospitalized with asthma than peers with no asthma-related hospitalizations. This suggests the need to develop and evaluate intervention strategies to maintain and enhance the academic performance of young students with asthma. Perioperative hypersensitivity reactions (POH) are infrequent but severe and potentially life-threatening, with an incidence between 1:1,250 and 1:13,000. It is reported that the severity of POH is usually higher than for other causes of anaphylaxis, with increased morbidity and mortality.5, 6 The combination of simultaneous administration of several drug agents, the surgical procedure, unreported or unknown exposures, and numerous differential diagnoses makes the evaluation of perioperative events challenging. Additionally, pharmacological properties of specific drugs agents or surgical management of patients may induce symptoms mimicking POH. Non-specific histamine release, which can be explained by MRGPRX2 stimulation, may lead to POH symptoms. Serum tryptase increases during acute allergic reactions. Its diagnostic value to distinguish mast-cell-mediated reactions in POH allergy workup has not been fully defined. Srisuwatchari and colleagues7 evaluated the acute (TA) and baseline (TB) tryptase levels in all patients who presented with suspected POH and underwent complete drug allergy workup at the university hospital of Montpellier and Strasbourg between March 2011 and December 2019. The authors reported that the optimal cut-off point for TA was 9.8 μg/L to discriminate patients in whom a specific allergic trigger was or was not identified during suspected POH workup. TA value of 33 μg/L or higher was required to achieve a PPV >90%. When TA increases above this 90% PPV level without allergy tests identifying a specific cause, the authors recommend a multidisciplinary approach to diagnosis including anaesthetists, surgeons and allergists in order to identify other potential hidden allergic causes of POH (Figure 1). Allergic asthma is heterogeneous in both phenotypes and endotypes.7 Benralizumab is an effective biological treatment in most but not all patients with severe eosinophilic asthma (SEA). Randomized controlled trials (RCTs) have revealed a decrease in exacerbation rate, oral corticosteroid (OCS) use, improved lung function and quality of life. A multifactorial effect conceivably contributes to the heterogeneous treatment response seen in SEA.8 Di Bona and colleagues9 have identified SEA sub-phenotypes with differential responsiveness to benralizumab. The authors performed a hierarchical cluster analysis in 105 SEA patients who received benralizumab for six months. They analysed clinical variables, particularly age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1% predicted, nasal polyposis and bronchiectasis status. The authors confirmed that benralizumab was clinically effective in most severe eosinophilic asthma. They further demonstrated the presence of 4 different clusters within the homogeneous severe eosinophilic asthma Type 2 phenotype (Figure 2). Most importantly, clusters were characterized by differential expression of type 2 biomarkers, and distinct clinical features showed differential benralizumab responsiveness. Given the multifactorial nature of clinical responses in chronic inflammatory disease, novel computational approaches such as machine learning and artificial intelligence are warranted to analyse and interpret complex data sets in RCT and real-world evidence studies to improve patient management.