Optimization of bronchial asthma treatment according to polymorphism in the leukotriene-C4 synthase gene

The aim of the study was to investigate the effectiveness of different schemes of basic asthma therapy depending on the polymorphism of the LTC4 gene. Materials and methods. 181 patients with asthma were recruited to participate in the study. All patients included in the study underwent a general clinical study, spirometry, the level of asthma control was determined by Asthma control questionnaire 5 (ACQ-5), by studying the polymorphism of the LTC4 gene, it was determined that patients belong to the A/A, A/C and C/C genotypes. Results. Allelic -444C polymorphism of the LTC4-S gene (rs 730012) had the following genotype frequency among asthma patients: A/A – 77 people (42.6 %), A/C – 73 people (40.3 %) and C/C – 31 people (17.1 %). In groups of patients with genotypes A/A and A/C, during treatment with a low dose of ICS and montelukast, there was a significant improvement in FEV1 and the score according to the ACQ-5 questionnaire (asthma control level). However, in the group of patients with the C/C genotype, there were no significant changes in FEV1 and the score according to the ACQ-5 questionnaire. In the groups of patients with genotypes A/A and C/C on the background of increasing the dose of ICS to medium in a fixed combination with LABA compared with the results of treatment with low-dose ICS and montelukast, there was a significant improvement in FEV1 and asthma control – ACQ- 5. At the same time, in the group of patients with genotype A/C, there were no reliable indicators of FEV1 and ACQ-5 score changes. Conclusions. The frequency of genotypes A/A, A/C and C/C for LTC4S polymorphism in the studied population are 42.6 %, 40.3 % and 17.1 %, respectively. Patients with genotypes A/A and C/C have a significant response to treatment with a low dose of ICS and montelukast in the form of an improvement in FEV1 and ACQ-5 score. Increasing the dose of ICS up to moderate in a fixed combination with β2-LABA in groups of patients with genotypes A/A and C/C leads to a significant improvement in the FEV1, as well as in the asthma control level - ACQ-5

Airway Compliance Measurements in Mouse Models of Respiratory Diseases

The quantification of airway compliance (Caw) is essential to the study of airway alterations in disease models. However, the required measurements of airway pressure and volume are difficult to acquire in mice. We hypothesized that the inflation limb of full-range pressure-volume (PV) curves could be used to quantify Caw, as it contains a segment where only the airway tree is distended. The study objective was to assess the feasibility of the approach by analysis of full-range PV curves previously collected in three mouse models: an elastase model of emphysema, a genetic model spontaneously developing emphysema (leukotriene C4 synthase knock-out; LTC4S-KO) and a bleomycin model of lung fibrosis. Attempts to validate results included Caw change relative to respiratory system compliance (ΔCaw/ΔC), the minute work of breathing (mWOB) and the elastance at 20.5 Hz (Ers_20.5) from prior respiratory mechanics measurements in the same subjects. Caw was estimated at 3% of total compliance in healthy mice or 2.3 ± 1 μL/cmH2O (n=17). The technique detected changes in models of respiratory obstructive and restrictive diseases relative to control mice as well as differences in the two emphysema models studied. The changes in Caw were consistent with those seen in ΔCaw/ΔC, mWOB or Ers_20.5, with some variations according to the model, as well as with results reported in the literature in humans and mice. Direct Caw measurements in subjects as small as mice could prove useful to further characterize other respiratory disease models associated with airway remodeling or to assess treatment effects.