hyperreactivity Dotaz Zobrazit nápovědu
The airway hyperreactivity (AHR) is a symptom occurring in various diseases of the respiratory system. It is defined as an abnormal bronchoconstriction response to a different spectrum of biological, chemical and pharmacological stimuli. Pathogenesis of airway hyperreactivity is not well understood. The available literature data shows that in the AHR pathogenesis is important not only genetic predisposition or influence of combination environmental and genetic factors, but also the presence and activity of various inflammatory mediators and other endogenous factors (growth factors, nuclear transcription factors). In this process is also important role of neural regulation and release of pro-inflammatory neurotransmitters. Our aim was to provide a comprehensive overview of knowledge about the symptoms--from the risk factors and pathogenesis through the clinical importance to the need for better understanding new options in therapeutic interventions.
- MeSH
- bronchiální hyperreaktivita diagnóza patofyziologie terapie MeSH
- lidé MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
Oxygen therapy provides an important treatment for preterm and low-birth-weight neonates, however, it has been shown that prolonged exposure to high levels of oxygen (hyperoxia) is one of the factors contributing to the development of bronchopulmonary dysplasia (BPD) by inducing lung injury and airway hyperreactivity. There is no effective therapy against the adverse effects of hyperoxia. Therefore, this study was undertaken to test the hypothesis that natural phytoalexin resveratrol will overcome hyperoxia-induced airway hyperreactivity, oxidative stress, and lung inflammation. Newborn rats were exposed to hyperoxia (fraction of inspired oxygen - FiO2>95 % O2) or ambient air (AA) for seven days. Resveratrol was supplemented either in vivo (30 mg·kg-1·day-1) by intraperitoneal administration or in vitro to the tracheal preparations in an organ bath (100 mikroM). Contractile and relaxant responses were studied in tracheal smooth muscle (TSM) using the in vitro organ bath system. To explain the involvement of nitric oxide in the mechanisms of the protective effect of resveratrol against hyperoxia, a nitric oxide synthase inhibitor - Nomega-nitro-L-arginine methyl ester (L-NAME), was administered in some sets of experiments. The superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and the tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in the lungs were determined. Resveratrol significantly reduced contraction and restored the impaired relaxation of hyperoxia-exposed TSM (p<0.001). L-NAME reduced the inhibitory effect of resveratrol on TSM contractility, as well as its promotion relaxant effect (p<0.01). Resveratrol preserved the SOD and GPx activities and decreased the expression of TNF-alpha and IL-1beta in hyperoxic animals. The findings of this study demonstrate the protective effect of resveratrol against hyperoxia-induced airway hyperreactivity and lung damage and suggest that resveratrol might serve as a therapy to prevent the adverse effects of neonatal hyperoxia. Keywords: Bronchopulmonary dysplasia, Hyperoxia, Airway hyperreactivity, Resveratrol, Pro-inflammatory cytokines.
- MeSH
- antioxidancia farmakologie MeSH
- bronchiální hyperreaktivita prevence a kontrola metabolismus patofyziologie chemicky indukované MeSH
- bronchopulmonální dysplazie * prevence a kontrola metabolismus MeSH
- hyperoxie komplikace metabolismus MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech * MeSH
- novorozená zvířata * MeSH
- oxidační stres * účinky léků MeSH
- pneumonie * prevence a kontrola metabolismus chemicky indukované MeSH
- potkani Sprague-Dawley MeSH
- resveratrol * farmakologie MeSH
- stilbeny farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia MeSH
- resveratrol * MeSH
- stilbeny MeSH
The investigation of bronchial hyperreactivity (b.h.) represents the basic diagnostic test in asthmatics. In 515 asymptomatic pediatric and adolescent asthmatics (age 6-23 years) divided into various subgroups according to the study purposes, b.h. as an induced airway obstruction was assessed after inhalations of a single dose of acetylcholine (3 mg), histamine (3 mg), hypotonic and hypertonic solutions with jet nebulizer. B.h. was also studied following inhalations of distilled and mineral water, physiologic solution with ultrasonic nebulizer, and 5 min. free running outdoors. The induced airway obstruction was assessed by parameters measured from maximum expiratory flow-volume curve. The most potent stimuli were the inhaled acetylcholine (3 mg) and 5 min. free running outdoors. By the latter two tests similar incidence and magnitude of b.h. were revealed in our asthmatics without airway obstruction as well as with a mild obstruction (MEF50 and MEF25 below lower limits of predicted before both tests). For both tests (acetylcholine and 5 min. free running), recommended in practice, were given the expected limits of lung function parameters before starting the tests. The values of the parameters before the onset of provocation tests were unreliable predictors of the induced airway obstruction in our asthmatics. B. h. was also assessed in 426 healthy 9-years old children by inhalation of 1% carbachol (mean dose: 2.57 +/- 0.7 mg). Various lung function parameters showed different incidence of b.h. in the latter children. Both values of one- second vital capacity and respiratory resistance (interruption technique) revealed b.h. in 46% of our healthy children (decline of parameters more than 20%). Other parameters measured, except peak expiratory flow, proved b.h. more frequently. In the article the problems of respiratory resistance measured by interruption technique and higher incidence of b.h. in the studied healthy children are outlined.
The prevalence was assessed in a randomized group of 18-year-old and older inhabitants of Prague 8. A total of 8458 internationally tested questionnaires were sent out to a population of 90,458; information was obtained on 7605 (89.9%), 1274 were given a detailed examination by standardized methods. Cumulative prevalence of bronchial asthma (B): 2.3% +/- 0.3% (same in M and F). The highest values at the age of 18-20 years were 3.5%; 3.6% in the age group 21-30 years, the absolutely highest values--4.6%--were recorded in 18-year-old men. Contemporary prevalence of BA: 1.99%. In BA bronchial obstructions were found in 51%, bronchial hyperreactivity in 75%, positive skin tests in 71%, an increase of IgE in 36%. Prevalence of chronic bronchitis (CHB): 14.1%; men 17.6% women--11.3%, highest value--18.9%--in the age group 70-80 years; absolutely highest values were recorded in men aged 70-80 years--20.9%. In CHB there was a bronchial obstruction in 55% and this obstruction was reversible in 40%. In the group CHB bronchial asthma was recorded in 20%. Prevalence of bronchial hyperreactivity (BHR) was estimated from results of broncho-provocative tests and from the calculation according to prevalence of BHR in respiratory diseases. The thus calculated figure was 13.7%. The incidence of bronchial asthma in chronic bronchitis in 1/6 and of bronchial hyperreactivity in more than 1/10 of the adult population are striking facts. It is essential to find the causes of these findings and make effective provisions to counteract them.
- MeSH
- bronchiální astma epidemiologie MeSH
- bronchiální hyperreaktivita epidemiologie MeSH
- bronchitida epidemiologie MeSH
- chronická nemoc MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- prevalence MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Geografické názvy
- Československo epidemiologie MeSH
Prevalence of bronchial asthma and bronchial hyperreactivity (BH) was studied in a randomized sample of Prague 8 inhabitants aged 19 and over. The number of adults living in Prague 8 had been 90 458 by December 31, 1987. 8458 questionnaires had been sent to 5 randomly selected districts. Information mainly concerned with respiratory diseases was received from 89.9% persons. Cumulative prevalence (i.e. both contemporary and past) of bronchial asthma was 2.3% +/- 0.3% in both sexes. The cumulative prevalence calculated by way of direct standardization was slightly higher - 2.33% +/- 0.33% (men 2.33% +/- 0.5%, women 2.32% +/- 0.45%). The highest value of 3.6% was found at the age of 21-30 years. Evidence of BH was found in 75% cases of bronchial asthma by means of the inhalation histamine test. In adult population, the BH value was calculated on the basis of distribution of incidence in the healthy population and in persons with respiratory disease and the BH prevalence was found in each group. The BH in total adult population of Prague 8 was 13.7%. This is an alarming figure.
- MeSH
- bronchiální astma epidemiologie MeSH
- bronchoprovokační testy MeSH
- bronchy patofyziologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Geografické názvy
- Československo epidemiologie MeSH
- MeSH
- bronchoprovokační testy * MeSH
- bronchy patofyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Ozone and nitrogen oxides are environmental pollutants especially present in smog. They are oxidants potent to cause bronchial hyperreactivity, lung fibrosis, and emphysema. Other occupational hazards are mineral dust particles (asbestos, silica) which may cause the development of inflammation and fibrosis in the lungs. Inflammatory cells (neutrophils, eosinophils, monocytes, macrophages) become activated during inflammation and produce superoxide anion radicals. Reactive oxygen species developed e.g. in smog have been recognized--at least partly--to be responsible for the observed pulmonary tissue damage. Several mechanisms leading to toxicity, including disbalance of vegetative nervous control, damage of bronchial epithelium, role of mediators of inflammation and other issues are discussed. (Fig. 1, Ref. 32.)
- MeSH
- bronchiální hyperreaktivita etiologie metabolismus MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- plíce metabolismus patologie MeSH
- plicní fibróza etiologie metabolismus MeSH
- prach škodlivé účinky MeSH
- smog škodlivé účinky MeSH
- volné radikály metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- látky znečišťující vzduch MeSH
- mediátory zánětu MeSH
- prach MeSH
- smog MeSH
- volné radikály MeSH
INTRODUCTION: ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR). AIM: The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children. METHODS: One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents. RESULTS: We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013). CONCLUSION: ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.
- MeSH
- bronchiální astma genetika MeSH
- bronchiální hyperreaktivita genetika MeSH
- dítě MeSH
- epigeneze genetická * MeSH
- genomový imprinting MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- otcové MeSH
- proteiny ADAM genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ADAM33 protein, human MeSH Prohlížeč
- proteiny ADAM MeSH
We studied the effects of hydrogen peroxide, hypochlorous acid and ozone on muscarinic and beta-adrenergic receptor responses in guinea pig tracheal tissue. Pretreatment of the tracheal strips with hydrogen peroxide (up to 10 mM) did not affect the muscarinic or beta-adrenergic receptor responses after stimulation with methacholine or (-)-isoprenaline respectively. In contrast to hydrogen peroxide, hypochlorous acid (1 mM and 10 mM) decreased the maximal contraction and the pD2-value after stimulation with the muscarinic agonist methacholine. Comparable effects were observed after stimulation with the beta-adrenoceptor agonist (-)-isoprenaline but the beta-adrenoceptor response seemed to be more susceptible to hypochlorous acid treatment than the muscarinic response. In other words, hypochlorous acid changes the balance between muscarinic and beta-adrenergic receptor responses of guinea pig tracheal strips in favour of the muscarinic receptor responses. In vivo exposure of the guinea pigs to 3 ppm ozone for two hours resulted in a hyperreactivity (increase in maximal contraction) after stimulation of the muscarinic receptor with methacholine. No effects were observed in the pD2-value. The beta-adrenergic receptor response was also affected after ozone exposure. No effects were seen in the maximal (-)-isoprenaline induced relaxation but there was an increase (hypersensitivity) in the pD2-value. Our data suggest that oxidative stress modulates receptor responses. Moreover, the type of oxidant seems to differentially affect various receptor responses. This may be of importance to further understand the influence of an oxidative effect (either directly via ozone or through inflammation) in lung tissue.
- MeSH
- beta-adrenergní receptory fyziologie MeSH
- bronchiální hyperreaktivita patofyziologie MeSH
- bronchokonstrikce fyziologie MeSH
- kultivační techniky MeSH
- kyselina chlorná farmakologie MeSH
- morčata MeSH
- oxidační stres fyziologie MeSH
- ozon farmakologie MeSH
- peroxid vodíku farmakologie MeSH
- receptory muskarinové fyziologie MeSH
- trachea metabolismus MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-adrenergní receptory MeSH
- kyselina chlorná MeSH
- ozon MeSH
- peroxid vodíku MeSH
- receptory muskarinové MeSH
Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals, and by mechanical stimulation of airway mucosa in anesthetized animals just after the end of the experiment. In contrast to 50 % oxygen, 100 % oxygen breathing leads to significant decrease in chemically induced cough in guinea pigs with allergic inflammation. No significant changes were present in cough induced by mechanical stimulation of airways.
- MeSH
- alergie imunologie MeSH
- bronchiální hyperreaktivita imunologie MeSH
- hyperoxie imunologie MeSH
- kašel chemicky indukované imunologie MeSH
- kyselina citronová MeSH
- kyslík farmakologie MeSH
- mechanika dýchání MeSH
- morčata MeSH
- ovalbumin imunologie MeSH
- reflex fyziologie MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyselina citronová MeSH
- kyslík MeSH
- ovalbumin MeSH