Anna Dor-Wojnarowska

The G/G genotype of transforming growth factor beta 1 (TGF-β1) single nucleotide (+915G/C) polymorphism coincident with other host and environmental factors is associated with irreversible bronchoconstriction in asthmatics

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)‐β1 gene polymorphism despite established role that TGF‐β1 plays in airway remodelling. We tested TGF‐β1 single‐nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case–control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00–19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF‐β1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.

Fractioned exhaled nitric oxide (FENO) is not a sufficiently reliable test for monitoring asthma in pregnancy

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial. The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy. We monitored 72 pregnant asthmatics aged 18-38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled. FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2 ppb; 9.5 ppb-188.3 ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6 ppb; 6.2 ppb-103.4 ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameters considerable intrasubject variability, regardless of the degree of asthma control.

Sex-related clinical aspects in insect venom anaphylaxis.

Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects’ venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable.