Clinical effectiveness of budesonide/formoterol fumarate easyhaler for patients with poorly controlled obstructive airway disease: a real-world study of patient-reported outcomes

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Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation

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The alteration of irisin - brain-derived neurotrophic factor axis parallels severity of distress disorder in bronchial asthma patients

Distress disorder (a collective term for generalized anxiety disorder and major depressive disorder) is a well-known co-morbidity of bronchial asthma. The irisin—brain-derived neurotrophic factor (BDNF) axis is a pathway that influences several neurobehavioral mechanisms involved in the pathogenesis of distress disorder. Thus, the aim of the present study was to quantify the serum irisin and BDNF concentrations in order to investigate the possible link between the irisin/BDNF axis and distress disorder in an asthma patient cohort. Data of 167 therapy-controlled asthma patients were analyzed. Demographic, anthropometric, and anamnestic data were collected, routine laboratory parameters supplemented with serum irisin and BDNF levels were determined, pulmonary function test was performed using whole-body plethysmography, and quality of life was quantified by means of the St. George's Respiratory Questionnaire (SGRQ). Correlation analysis as well as simple and multiple linear regression were used to assess the relationship between the irisin level and the Impacts score of SGRQ, which latter is indicative of the presence and severity of distress disorder. We have found a significant, positive linear relationship between the Impacts score and the reciprocal of irisin level. This association was stronger in patients whose BDNF level was higher, and it was weaker (and statistically non-significant) in patients whose BDNF level was lower. Our results indicate that higher serum irisin level together with higher serum BDNF level are associated with milder (or no) distress disorder. This finding suggests that alteration of the irisin/BDNF axis influences the presence and severity of distress disorder in asthma patients

Exposure to inhomogeneous static magnetic field beneficially affects allergic inflammation in a murine model

Previous observations suggest that static magnetic field (SMF)-exposure acts on living organisms partly through reactive oxygen species (ROS) reactions. In this study, we aimed to define the impact of SMF-exposure on ragweed pollen extract (RWPE)-induced allergic inflammation closely associated with oxidative stress. Inhomogeneous SMF was generated with an apparatus validated previously providing a peak-to-peak magnetic induction of the dominant SMF component 389 mT by 39 T m(−1) lateral gradient in the in vivo and in vitro experiments, and 192 mT by 19 T m(−1) in the human study at the 3 mm target distance. Effects of SMF-exposure were studied in a murine model of allergic inflammation and also in human provoked skin allergy. We found that even a single 30-min exposure of mice to SMF immediately following intranasal RWPE challenge significantly lowered the increase in the total antioxidant capacity of the airways and decreased allergic inflammation. Repeated (on 3 consecutive days) or prolonged (60 min) exposure to SMF after RWPE challenge decreased the severity of allergic responses more efficiently than a single 30-min treatment. SMF-exposure did not alter ROS production by RWPE under cell-free conditions, while diminished RWPE-induced increase in the ROS levels in A549 epithelial cells. Results of the human skin prick tests indicated that SMF-exposure had no significant direct effect on provoked mast cell degranulation. The observed beneficial effects of SMF are likely owing to the mobilization of cellular ROS-eliminating mechanisms rather than direct modulation of ROS production by pollen NAD(P)H oxidases

Szenzoros neuropeptid felszabadulás farmakológiai gátlása, mint új gyógyszerhatás mechanizmus az asthma és a krónikus obstruktív légúti betegség terápiájában = Pharmacological inhibition of sensory neuropeptide release as a novel mechanism of action in the treatment of bronchial asthma and chronic obstructive airway disease

In vitro trachea perfúziós rendszerünkben 94 új szomatosztatin (SOM) agonistát (Biostatin Kft. Budapest) vizsgáltunk a kapszaicin-érzékeny afferensekből történő P-anyag (SP) felszabadulására, melyek közül 24 szignifikáns gátlást okozott. A legjobb 6 vegyületet in vivo is teszteltük, gyulladásmodellekben hatásosnak bizonyultak. A PACAP-38 és a szelektív sst4 receptor agonista peptidomimetikum J-2156 (Juvantia Pharma, Turku) e modellben koncentráció-függő módon gátolta az SP, CGRP és SOM felszabadulását. Specifikus RIA-t fejlesztettünk ki PACAP-38 mérésre, mellyel igazoltuk e peptid szenzoros rostokból történő felszabadulását. Endotoxinnal kiváltott szubakut légúti gyulladás egérmodellben funkcionális, morfológiai és biokémiai módszerekkel igazoltuk, hogy TRPV1 kapszaicin receptor génhiányos egerekben fokozott gyulladás és a következményes bronchialis hiper-reaktivitás alakult ki. SOM RIA és sst receptor antagonista kezeléssel biokémiai és funkcionális bizonyítékokat szolgáltattunk, hogy a gyulladás során TRPV1 receptor aktivációval SOM szabadul fel, amely gátolja a gyulladást és a bronchokonstrikciós hajlamot. A fenti eredményeink alapján szintetikus sst4 receptor agonisták, a heptapeptid TT-232 és peptidomimetikum J-2156, vizsgálata történt az előbbiekben ismertetett módszerekkel az LPS-indukálta pneumonitis és az ovalbuminnal kiváltott asztma modellekben egérben. E vegyületek mindkét modellben hatékonyan gátolták a légúti gyulladást és hiper-reaktivitást. | The effect of 94 novel somatostatin (SOM) agonists (Biostatin Ltd., Budapest) on substance P (SP) release from capsaicin-sensitive afferents were examined in our in vitro isolated trachea perfusion system. Among these 24 caused significant inhibition, the most effective 6 ligands diminished inflammation in vivo. PACAP-38 and the selective sst4 receptor agonist peptidomimetic J-2156 (Juvantia Pharma, Turku) concentration-dependently inhibited SP, CGRP and SOM release in this model. We have developed a specific RIA for measuring PACAP-38 and with its help the outflow of this peptide from capsaicin-sensitive afferents has been evidenced. Experiments using TRPV1 receptor gene-deficient mice provided functional, morphological and biochemical evidence for a novel type of counter-regulatory mechanism during endotoxin-induced airway inflammation. This is mediated by SOM released from sensory nerve terminals into the circulation in response to TRPV1 receptor activation. It inhibits inflammation and bronchial hyper-reactivity. Desensitization of capsaicin-sensitive afferents enhances inflammation which might be due to the lack of SOM released from these fibres. Based on the above described results, synthetic sst4 receptor agonists, the heptapeptide TT-232 and the peptidomimetic J-2156 have been studied in endotoxin-induced subacute pneumonitis and ovalbumin-evoked asthma models of the mouse and effectively inhibited airway inflammation and consequent hyper-reactivity