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The goal of the present study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in asthmatic patients, and to evaluate the NO response to maintenance fluticasone 250 microg/salmeterol 50 microg (F/S) and add-on montelukast 10 mg (M).
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Spirometry is an important component of the National Asthma Education and Prevention Program guidelines for asthma, yet published data show variable associations between forced expiratory volume in 1 second percentage (FEV1%) predicted, symptoms and health care utilization. The objective of this analysis was to examine the association between FEV1% and future risk of exacerbations among a well-characterized population of children with asthma.
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In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.
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The mass median diameter (MMD) for the tgAAVCF was 2.78 +/- 0.43 microm. If the system works ideally and the patient only receives aerosol on inspiration, the patient would receive 47 +/- 0% of the initial dose placed in the nebulizer, with 72 +/- 0.73% of this being deposited beyond the vocal cords.
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Twenty patients took part in the trial. Compared with the placebo, the inhalation of salmeterol significantly increased the FEV(1). Even in the 9 patients treated with high-dose ICSs plus theophylline plus a leukotriene receptor antagonist, the FEV(1) increased significantly more after salmeterol than after the placebo.
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The objective of the article was to perform a predictive analysis, based on quantitative structure-property relationships, of the dissociation constants (pK(a)) of different medicinal compounds (e.g., salicylic acid, salbutamol, lidocaine). Given the importance of this property in medicinal chemistry, it is of interest to develop theoretical methods for its prediction. The descriptors selection from a pool containing more than a thousand geometrical, topological, quantum-mechanical, and electronic types of descriptors was performed using the enhanced replacement method. Genetic algorithm and the replacement method (RM) techniques were used as reference points. A new methodology for the selection of the optimal number of descriptors to include in a model was presented and successfully used, showing that the best model should contain four descriptors. The best quantitative structure-property relationships linear model constructed using 62 molecular structures not previously used in this type of quantitative structure-property study showed good predictive attributes. The root mean squared error of the 26 molecules test set was 0.5600. The analysis of the quantitative structure-property relationships model suggests that the dissociation constants depend significantly on the number of acceptor atoms for H-bonds and on the number of carboxylic acids present in the molecules.
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This paper describes a series of stability and redistribution studies aimed at understanding the presence and significance of beta 2-agonists in asthma deaths. Salbutamol and terbutaline were shown to be stable in postmortem blood at 23 degrees C for 1 week, 4 degrees C for 6 months and -20 degrees C for 1 to 2 years. However, fenoterol was shown to degrade at 23 degrees C (83% loss), 4 degrees C (93% loss) and -20 degrees C (66% loss) over the same time. Salbutamol concentrations detected in blood taken at the time of body admission to the mortuary were not significantly different from the concentrations detected in blood taken from the same cases at the time of autopsy (45 h later). This suggests that significant postmortem redistribution of salbutamol is unlikely to occur during this period. Postmortem blood concentrations of at least salbutamol are likely to reflect the concentration of these drugs in the body at the time of death.
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Sensitivity and exposure to indoor allergens constitutes a risk factor for the development and persistence of asthma in children.
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We measured the uptake of the soluble inert gas dimethyl ether (DME) from a segment of the conducting airways to estimate mucosal blood flow (Qaw) noninvasively. The subjects inhaled, from the functional residual capacity position, a 300-ml gas mixture containing 35% DME, 8% helium, 35% oxygen, and the balance nitrogen; they held their breath for 5 s and then exhaled into a spirometer. During exhalation, the instantaneous concentrations of DME and helium were recorded together with expired gas volume. The maneuver was repeated with breathhold times of 5, 10, 15, and 20 s. We calculated Qaw using the time-dependent decrease in DME concentration in relation to the helium concentration in an expired volume fraction between 80 and 130 ml (representing an anatomic dead-space segment distal to the glottis) and the mean DME concentration. In 10 healthy nonsmokers, mean (+/- SE) Qaw was 8.0 +/- 1.3 ml/min, or 8 +/- 2 microliters/min/cm2 mucosal surface. We obtained a value of 12 +/- 3 microliters/min/cm2 in a validation experiment in sheep. Inhaled methoxamine (nebulized dose 10 mg) caused a 65 +/- 19% decrease (p < 0.05), and albuterol (nebulized dose 2.5 mg) a 92 +/- 17% increase (p < 0.05), in mean Qaw in seven subjects, with the maximum changes occurring immediately or 15 min postinhalation. We conclude that the DME uptake method is an acceptable noninvasive means of estimating airway mucosal blood flow in humans and its modification by vasoactive substances.