Speaker- Alina Gherasim
The session emphasized on the importance of implementing bronchial and nasal allergen challenge tests in clinical practice. The primary challenge was the regulation of allergen extracts in Europe. For seven years, studies on environmental exposure to allergens and unitary tests revealed that allergic asthma remained underdiagnosed. In Strasbourg, an environmental exposure chamber was used to simultaneously expose patients to allergens in different sessions. In one study, the chamber was validated with birch allergen in a rhinitis population without known asthma. After medical history and tests, patients were exposed to 60 ng/m³ of Bet v1 for four hours. Surprisingly, 53% had an early asthmatic response (20% drop in FEV1) and 16% had a late response. Comparing with an asthma study, 62% had a late response (15% drop in FEV1 up to 24 hours post-exposure). Similar results were observed with grass pollen at higher doses (30 ng/m³ to 90 ng/m³), where half of the non-asthmatic population reacted. A double-blind placebo study confirmed no artificial drops in FEV1 or symptoms with placebo. The bronchial challenge usually induced a response in 20-30 minutes, while the chamber took around two hours.
Allergic asthma is defined by symptoms triggered by environmental allergens. The Yakiniu nomenclature identifies various asthma endotypes based on different hyperresponsiveness reactions, including the well-known types 1, 2, and 3, along with a T cell-mediated type important for immune response. The YACI further classifies types: 5 relates to epithelial barrier reactions releasing cytokines like IL25, IL33, and TSLP; 6 involves metabolic pathways, such as obesity; and 7 concerns chemical impacts from drugs affecting bronchial mucosa. The consensus aims to differentiate allergic asthma from asthma with sensitization for targeted treatments like allergen avoidance, immunotherapy, or biologics. Allergen exposure activates the epithelial barrier and cytokine release, influenced by gene and epigenetic factors, causing a switch between Th1 and Th2 responses, impacting microbiome dysbiosis and recruiting innate immune responses. Identifying immunologic and inflammatory cells is crucial for predicting treatment response, especially for expensive biologics. Comprehensive clinical history, environmental exposure, socioeconomic status, family history, phenotypic traits, and comorbidities are essential for diagnosis. Implementing nasal and bronchial allergen challenges helps endotype patients better. While nasal allergen challenges are widely accepted, bronchial allergen challenges remain debated. These diagnostic tools aim for accurate allergic asthma diagnosis and effective treatment targeting.
The stepwise approach for diagnosing asthma starts with a comprehensive clinical history. If the diagnosis remains unclear, a simple nasal allergen challenge can be performed. This involves applying a single dose in the nasal cavity to observe the clinical response. If the result is negative, patients should be referred to specialized centers for a short washout bronchial allergen challenge. A positive result confirms the diagnosis, while a negative result leads to an optimal washout bronchial challenge to confirm or rule out the diagnosis. The nasal allergen challenge methodology, including indications and contraindications, is well-established. Applying the allergen in the nasal cavity reveals prolonged inflammation. A rapid nasal provocation test involves two paths in each nostril with 50 microliters of allergen, assessing symptoms through subjective scores (such as the total nasal symptoms score and visual analog scale) and objective parameters (such as nasal potency using peak nasal inspiratory flow or rhinomanometry). Rhinomanometry, although expensive, is highly sensitive and specific. This test identifies rhinitis comorbidity in allergic asthma and uses both objective and subjective measures, with guidelines suggesting specific cutoffs for diagnosis. The bronchial allergen challenge, primarily a research tool, provides early asthmatic response data within two hours and requires special training and allergens. It involves early and late asthmatic responses, indicating safety concerns for patients but providing comprehensive endotyping information. Studies show an increase in chemokines (IL-33, IL-25, TSLP) and immunoreactivity in lung tissue after the bronchial allergen challenge, correlating with clinical aspects and spirometry results.
The stepwise approach to endotyping asthma follows familiar procedures. Diagnosis and the impact of Ig sensitization are prioritized initially, assessed through skin prick tests and serum-specific Ig. Positive results may lead to immunotherapy, particularly for moderate to severe patients. When these tests yield negative results, performing a basophil activation test is strongly recommended, usually in specialized centers. Positive results from this test can guide targeted treatment selection. While molecular diagnosis for patient selection is optimal but expensive, induced sputum analysis, though not essential during bronchial allergen challenges, can provide valuable insights, especially during asthma flare-ups. However, its utility may vary due to reimbursement limitations in different countries. Nasal and bronchial allergen challenges offer additional diagnostic benefits. Nasal challenges provide nasal secretions and serum IL-6 levels, indicating the Th1 pathway. Bronchial challenges yield sputum for Th2 assessment and can also reveal increased IL-17 levels, indicating the T3 pathway, particularly useful for diagnosing mixed asthma and guiding targeted treatment approaches.
The situation in Europe for allergen standardization is not very optimistic. While the U.S. does not allow certain practices, Europe has few companies that commercialize and standardize allergen solutions as required by agencies. These solutions must be standardized, with the most used bioequivalent allergen units employed for bronchial allergen challenges in research. However, the protein content varies, necessitating careful selection and complete analysis or certification. Glycated extracts are not recommended due to their mucosal irritant properties. European regulations demand control of allergen product potency, whereas the FDA has not approved nasal allergen challenges. Despite these challenges, the key message is the availability of tools to advance patient selection for targeted treatments, allergen avoidance, and immunotherapy. Effective management is possible with proper training provided by the IAC and national allergen societies for nasal, bronchial, and sputum-induced procedures. To address the underdiagnosis of allergic asthma, a registry of asthma is proposed for better patient management and targeted treatments.
European Academy of Allergy and Clinical Immunology (EAACI), 2024 31st May-3rd June, Valencia.