- MeSH
- Epinephrine antagonists & inhibitors administration & dosage MeSH
- Allergens immunology adverse effects MeSH
- Anaphylaxis * etiology drug therapy immunology complications MeSH
- Histamine Antagonists administration & dosage MeSH
- Time-to-Treatment MeSH
- Hydrocortisone administration & dosage MeSH
- Humans MeSH
- SRS-A MeSH
- Check Tag
- Humans MeSH
A sensitive and precise method for simultaneous quantification of cysteinyl leukotrienes (=cys LTs) - leukotriene C4 (=LTC4), leukotriene D4 (=LTD4) and leukotriene E4 (=LTE4) - essential biomarkers of bronchial asthma present in exhaled breath condensate (=EBC) was developed. An immunomagnetic molecular probe was prepared by anchoring cysteinyl leukotrienes antibody on the surface of functionalized monodispersed magnetic particles and used to selectively isolate cys LTs from biological matrices - EBC, plasma and urine. Immobilization and the immunoaffinity capture procedures were optimized to maximize the amount of separated cys LTs, which were detected "off-beads" after acidic elution by UHPLC-ESI-MS/MS operated in a multiple reaction monitoring mode. The developed method was characterized with high precision ≤13.6% (intra-day precision determined as RSD) and ≤14.5% (inter-day precision determined as RSD), acceptable accuracy ≤18.5% (determined as RE), and high recovery of immunoseparation (≥93.1%) in aforementioned biological matrices. The applicability of the method was demonstrated on EBC, plasma and urine clinical samples of patients with various subtypes of bronchial asthma (occupational, steroid-resistant, moderate with and without corticosteroids therapy) and healthy subjects where reasonable differences in cys LTs concentration levels were found. Combining extremely selective immunomagnetic separation with highly sensitive and precise detection step, the developed method was used to aid diagnosis, predict the most effective therapy, and monitor the response to treatment. The detection of elevated inflammatory mediators (cys LTs) in EBC of subjects with relatively asymptomatic asthma and normal pulmonary function tests could offer a novel way for monitoring the lung inflammation and perhaps initiating treatment in an earlier stage.
- MeSH
- Asthma diagnosis drug therapy physiopathology MeSH
- Breath Tests MeSH
- Glucocorticoids therapeutic use MeSH
- Spectrometry, Mass, Electrospray Ionization methods MeSH
- Immunomagnetic Separation methods MeSH
- Leukotriene C4 analysis MeSH
- Leukotriene D4 analysis MeSH
- Leukotriene E4 analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Reproducibility of Results MeSH
- Sensitivity and Specificity MeSH
- Case-Control Studies MeSH
- Tandem Mass Spectrometry methods MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Controlled Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
Leukotrienes (LTs) are involved in the pathogenesis of lung fibrosis and were increased in exhaled breath condensate (EBC) of the patients with pneumoconiosis. However the possible influence of extra-pulmonary disorders on the EBC markers is not known. Therefore in parallel with EBC, LTs' levels in the plasma and urine were measured in patients with pneumoconiosis (45 × asbestos exposure, 37 × silica exposure) and in 27 controls. Individual LTs B4, C4, D4 and E4 were measured by liquid chromatography - electrospray ionization - tandem mass spectrometry (LC-ESI-MS/MS). In EBC, LT D4 and LT E4 were increased in both groups of patients (p<0.001 and p<0.05), comparing with the controls. Both LT B4 and cysteinyl LTs were elevated in asbestos-exposed subjects (p<0.05). Asbestosis with more severe radiological signs (s1/s2-t3/u2) and lung functions impairment has shown higher cysteinyl LTs and LT C4 in the EBC (p<0.05) than mild asbestosis (s1/s0-s1/s1). In addition, in the subjects with asbestosis, cysteinyl LTs in EBC correlated with TLC (-0.313, p<0.05) and TLCO/Hb (-0.307, p<0.05), and LT C4 with TLC (-0.358, p<0.05). In pneumoconioses, EBC appears the most useful from the 3 fluids studied.
- MeSH
- Asbestosis metabolism radiography MeSH
- Breath Tests * MeSH
- Leukotriene B4 analysis blood urine MeSH
- Leukotriene C4 analysis blood urine MeSH
- Leukotriene D4 analysis blood urine MeSH
- Leukotriene E4 analysis blood urine MeSH
- Leukotrienes analysis blood urine MeSH
- Middle Aged MeSH
- Humans MeSH
- Respiratory Function Tests MeSH
- Aged MeSH
- Silicosis metabolism radiography MeSH
- Severity of Illness Index MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
A method was developed for rapid and accurate determination of cysteinylleukotrienes (LTC4, LTD4, LTE4), essential biomarkers of bronchial asthma, in exhaled breath condensate. The method consists of an immunoseparation procedure combined with selective and sensitive detection by LC-ESI-MS in the multiple reaction monitoring mode (MRM) and using a stable-isotopedilution assay. The precision of the method was around 94 %. The mean accuracy was higher than 90 % for the content of cysteinylleukotrienes in the concentrate up to 250 pg ml-1. The method was tested on patients with occupational bronchial asthma and compared with healthy subjects. The differences between the two groups were significant.
Hlavním cílem léčby astmatu je kontrola nad astmatem. Pro kontrolu nad astmatem lze v monoterapii použít inhalační kortikosteroidy nebo antileukotrieny. Cílem AIRSTUDY bylo ověřit účinnost, snášenlivost a bezpečnost montelukastu u částečné a nedostatečné kontroly astmatu. V neintervenční studii byl hodnocen výsledek u 5438 pacient ů (2006) a u 4049 pacient ů (2008). Zařazení montelukastu do léčby mělo významný pozitivní účinek, nežádoucí ú č inky nebyly zaznamenány.
The main goal of asthma treatment is asthma control.Inhaled corticosteroids (ICS) are the most effective asthma controllers. IC S and antileucot- rienes (ALT) can be used as monotherapy. AIRSTUDY was a nonintervention study to demonstrate efficacy,tolerance and safety of m ontelucast in patients with partly controlled or uncontrolled asthma. Montelucast was used in 5438 (2007) and 4049 (2008) subjects. Montel ucast as add- on-treatment has been shown a significant effect with a good tolerance and without side-effects.
- MeSH
- Acetates administration & dosage MeSH
- Leukotriene Antagonists administration & dosage MeSH
- Asthma drug therapy MeSH
- Quinolines administration & dosage MeSH
- Child MeSH
- Adult MeSH
- Drug Evaluation MeSH
- Leukotriene D4 antagonists & inhibitors MeSH
- Humans MeSH
- Disease Management MeSH
- Patient-Centered Care MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
Účel prehľadu Účelom tohto prehľadu je upozorniť na zásadné články súčasnej literatúry, ktoré ovplyvnili naše poznanie využiteľnosti biomarkerov pri astme, a to v klinickej praxi, ako aj vo výskume. Biomarkery pochádzajú z mnohých zdrojov [bronchoalveolárna laváž (BAL), spútum, vydychovaný vzduch a krv] a majú veľké spektrum rôznych vlastností aj uplatnenia. Nové poznatky V súčasnosti je stále väčšia pozornosť venovaná biomarkerom vo vydychovanom vzduchu, a to plynným časticiam (vydychovaný oxid dusnatý), ako aj molekulám s vyššou molekulovou hmotnosťou [kondenzát vydychovaného vzduchu (exhaled breath condensate, EBC)]. Súčasný výskum v oblasti analýzy EBC sa zameriava na hodnotenie, štandardizáciu a technické podmienky, zatiaľ čo výskum v oblasti vydychovaného oxidu dusnatého (exhaled nitric oxide, ENO) sa presunul k overovaniu jeho predikčnej hodnoty v konkrétnych klinických situáciách. Využitie veľmi dômyselných bioštatistických metód a kombinatórnych analýz vedie k ďalšiemu pokroku vo zmysle využitia biomarkerov. Súhrn Pre klinickú prax diagnostiky a liečby astmy sú zatiaľ zrejme najviac overenými a aj najspoľahlivejšími biomarkermi parametre zápalu v indukovanom spúte a hodnoty ENO. Niektoré štúdie, v ktorých sa vyšetroval ENO, sa zdajú byť obzvlášť sľubné z hľadiska skorého využitia v praxi. Výsledky meraní EBC sú na použitie pre klinické účely v súčasnosti ešte príliš nejednoznačné. Nie všetky otázky významné pre klinickú prax alebo výskum je však možné zodpovedať pomocou vyšetrenia spúta a merania EBC alebo ENO, a preto si dôležité miesto v oblasti výskumu stále ponechávajú BAL, bronchiálna biopsia a snáď i stanovenie EBC.
The purpose of this review is to highlight seminal and current literature that informs our understanding of the clinical and investigative utility of biomarkers in asthma. Biomarkers derive from a variety of sources [bronchiolar lavage (BAL), sputum, exhaled breath, and blood], and have widely variant performance characteristics, and applicability. RECENT FINDINGS: Increasing attention is given to biomarkers in exhaled breath, both gaseous (exhaled nitric oxide) and higher molecular weight moieties [in exhaled breath condensate (EBC)]. Current research in EBC analysis has focused on validation, standardization, and technical considerations, whereas research on exhaled nitric oxide (ENO) has moved to testing its predictive value in clinical situations. The use of advanced biostatistical techniques, and combinatorial analyses has led to additional advances in the utility of biomarkers. SUMMARY: To date, the best validated, and best performing biomarkers for clinical asthma appear to be measures of inflammation in induced sputum, and measures of ENO. Some trials using ENO appear particularly promising for early clinical use. EBC metrics are at present too inchoate for clinical purposes. However, not all important clinical and research questions can be addressed with sputum, EBC, or ENO metrics, leaving an important place for BAL, bronchial biopsy, and perhaps EBC measurements in the research arena.
- MeSH
- Biomarkers metabolism MeSH
- Asthma metabolism MeSH
- Bronchoalveolar Lavage MeSH
- Breath Tests MeSH
- Leukotriene E4 urine MeSH
- Humans MeSH
- Nitric Oxide metabolism MeSH
- Sputum cytology MeSH
- Exhalation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Allergic rhinitis and bronchial asthma can coexist and affect each other. OBJECTIVE: To investigate the relationship between the postseasonal increase in the concentration of leukotriene (LT) B4 and LTE4 in exhaled breath condensate (EBC) and bronchial responsiveness to methacholine (BRM) in patients with seasonal allergic rhinitis (SAR). METHODS: In 28 patients with SAR and 50 healthy study patients, the leukotrienes were measured in EBC during and after the pollen season by gas chromatography/mass spectrometry. The BRM was determined after the pollen season. RESULTS: In 7 patients with SAR, significantly increased concentrations of both the leukotrienes were found in EBC during and 5 months after the pollen season. The following seasonal and postseasonal median values were measured in patients with SAR in comparison with control patients: LTB4: 131 and 90 pg/mL vs 80 and 79 pg/mL, P < .001 and P = .03, respectively; LTE4: 122 and 86 pg/mL vs 76 and 74 pg/mL, P < .001 and P = .02, respectively. Five months after the pollen season, the concentrations of LTB4 and LTE4 decreased with respect to their seasonal values (90 and 86 pg/mL, respectively, P < .001, for both leukotrienes). In 7 patients with SAR and leukotriene levels exceeding the reference limits, significantly increased BRM was also found (LTB4: P = .02; LTE4: P = .002). CONCLUSIONS: The seasonal and postseasonal increases in LTB4 and LTE4 concentrations in EBC of the patients with SAR correlated significantly with the later increase in BMR. This relationship could provide a useful predictive parameter for early inflammatory processes in the lower airways of patients with allergic rhinitis.
- MeSH
- Anti-Asthmatic Agents therapeutic use MeSH
- Asthma drug therapy MeSH
- Bronchi drug effects MeSH
- Adult MeSH
- Financing, Organized MeSH
- Leukotriene B4 analysis MeSH
- Leukotriene E4 analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Methacholine Chloride pharmacology therapeutic use MeSH
- Young Adult MeSH
- Reference Standards MeSH
- Rhinitis, Allergic, Seasonal drug therapy MeSH
- Exhalation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal adverse effects therapeutic use MeSH
- Aspirin adverse effects therapeutic use MeSH
- Asthma chemically induced immunology physiopathology MeSH
- Arachidonic Acid metabolism MeSH
- Leukotriene C4 immunology MeSH
- Rhinitis chemically induced immunology physiopathology MeSH
1st ed. xxv, 336 s. : il. ; 26 cm
- MeSH
- Autacoids physiology MeSH
- Leukotrienes biosynthesis metabolism therapeutic use MeSH
- SRS-A antagonists & inhibitors MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Farmacie. Farmakologie
- NML Fields
- pneumologie a ftizeologie
- farmacie a farmakologie
- biochemie
