Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling.

Background Asthma is a heterogeneous chronic inflammatory disease of the bronchi, the course of which is significantly influenced by extrinsic factors (specific and non‐specific). Methods The aim of this study was to evaluate the effect of these factors represented by nasal allergen challenge (specific factors) and methacholine challenge test (non‐specific) on changes in mRNA expression of genes encoding the TGF‐β (TGF‐β1 and TGF‐β3)‒Smad (mitogen‐activated protein kinase 1/3 [MPK1/3], Smad1/3/6/7) signaling pathway in asthmatic patients. Results Seventy‐five subjects were included in the study, of whom 27 were applied an intranasal allergen provocation and 48 a methacholine provocation. There were 9 men and 18 women in the intranasal provocation group, and 17 men and 31 women in the methacholine test group. We found that both examined the types of challenges contributed to changes in the relative expression of genes of the TGF‐β (TGF‐β1 and TGF‐β3)‒Smad (MPK1/3, Smad1/3/6/7) signaling pathway in asthmatic patients. A decrease was noted for MAPK1, MAPK3, Smad3, Smad6, and Smad7 genes and an increase of up to 2.5 times for TGF‐β1 gene. Conclusions Our experiment allows us to conclude that the change in the mRNA expression of the TGF‐β1–MPK1/3 and Smad3/6/7 genes occurs after an intranasal allergen and bronchial methacholine challenge.

Abstract. Transforming growth factor (TGF)-β1 has an essential role in bronchitis and the induction of bronchial remodelling, which are critical processes in the pathogenesis of asthma. However, the role of interleukin (IL)-15 in asthma inflammation remains unclear. The aim of the present study was to evaluate the effect of TGF-β1 mRNA expression on IL-15 mRNA expression in asthmatic patients and to assess the role of IL-15 in the clinical course of asthma. The study included 221 participants, comprising 130 patients with asthma and 91 healthy volunteers. The participants were subjected to testing using spirometry, as well as the Asthma Control Test™ and Borg Scale. The expression of TGF-β1 and IL-15 mRNA was analyzed in blood samples using reverse transcription-quantitative polymerase chain reaction. Statistical analysis indicated that IL-15 and TGF-β1 mRNA expression each differed significantly between the patient and control groups (P= 0.0016 and P= 0.033, respectively). A significant correlation was identified between IL-15 expression and TGF-β1 expression (R=0.41, P=0.0005). No correlation was observed between IL-15 expression and the degree of asthma severity, the results of spirometric examination or the frequency of asthma exacerbations. Further analysis revealed that IL-15 expression was elevated following the administration of inhaled glucocorticosteroids (iGCs; P=0.024), and reduced following methylxanthine treatment (P<0.001). The occurrence of dyspnoea differed between the study and control groups, and this was not found to be associated with IL-15 expression. Since IL-15 expression was correlated with TGF-β1 expression among asthmatic patients, and IL-15 expression was elevated following iGC administration, the results of the study suggest that IL-15 activity might be associated with the pathogenesis of asthma.

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Background Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers’ specialty and experience. Methods We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05). Conclusions Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice.