# The Late Asthmatic Reaction Is in Part Independent from the Early Asthmatic Reactions

## TL;DR

Some asthma patients experience a late reaction to allergens without an early reaction, leading to more severe symptoms and lung inflammation.

## Contribution

This study shows that late asthmatic reactions can occur independently of early reactions in some patients.

## Key findings

- A late asthmatic reaction (LAR) can occur without a significant early asthmatic reaction (EAR) in some patients.
- Distinct miRNAs correlate with increased bronchial inflammation and lung function decline in patients with LAR.
- Low allergen doses can induce LAR without triggering EAR in 35% of patients.

## Abstract

House dust mites (HDM) are the world’s most important cause of allergic asthma. It is unclear why some patients with HDM allergy develop an early asthmatic reaction (EAR) only, whereas others react with a dual asthmatic reaction—EAR plus late asthmatic reaction (LAR). In patients with LAR, the symptoms and bronchial inflammation are more severe, and the current knowledge suggests that the EAR always precedes the LAR. The aim of the present study was to investigate whether a LAR can occur separately even without a significant EAR. In a pilot study of 20 patients with asthma and HDM allergy, a bronchial allergen challenge (BAC) was performed on three separate occasions with a tapered allergen dose. Before and 24 h later, exhaled NO (eNO), eosinophils and miRNAs were measured as markers of bronchial inflammation. Compared to BAC1, at BAC2 there was a significant decrease in the EAR from mean 39.25 ± 13.37% to mean 33.55 ± 5.25% (p < 0.01), whereas the LAR remained unchanged: mean 28.10 ± 10.95% to mean 30.31 ± 7.77% (n.s.). At BAC3, both the EAR and the LAR were significantly attenuated compared to the first and second BAC. In 3 (15%) patients, even the tapered allergen dose induced a dual asthmatic reaction. In 10 (50%) patients, the allergen dose was too low to trigger a significant EAR and LAR. In 7 (35%) patients, there was no EAR, but a significant LAR (mean max fall FEV1 20.5 + 4.7%) recorded. Significant correlations (p < 0.05) were found between distinct miRNAs (miR-15a-5p, miR-15b-5p and miR-374a-p5), eNO, and the decline in lung function and the presence of a LAR (p < 0.01). We can demonstrate that a LAR is induced in some patients without an EAR to low allergen exposure. This leads to a strong inflammatory reaction with an increase in eNO and a decrease in FEV1 and distinct miRNAs. Accordingly, these individuals are at greater risk of asthmatic symptoms and remodeling with loss of lung function than patients who do not have a LAR.