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Anaphylaxis prevalence has increased within the last few years. This may be due to a marked increase in allergic sensitization to foods especially in the pediatric population, as well as to an increase in outdoor recreational habits and the availability of new biologic medications. Furthermore, guidelines for the diagnosis of anaphylaxis have been published, thus facilitating the recognition of this disorder. Diagnosis of anaphylaxis is mainly based on history and clinical criteria of organ system involvement. The serum tryptase assay is now commercially available and may be a helpful diagnostic tool in certain clinical situations involving hypotension, but not in the context of food-induced anaphylaxis. Treatment of anaphylaxis mainly involves the use of epinephrine as a first line medication for severe manifestations followed by symptomatic management of specific symptoms, such as antihistamines for urticaria and albuterol for wheezing. Although commonly practiced, treatment with systemic corticosteroids is not supported by evidence-based literature. Observation in a medical facility for 4-6 hours is recommended to monitor for late phase reactions, although these rarely occur. Education is an essential component of management of a patient with a previous history of anaphylaxis, emphasizing early use of epinephrine and providing a written action plan. Referral to a board-certified allergist/immunologist is recommended to determine the cause of the anaphylaxis as well as to rule out other potential conditions. In this review, our main focus will be on the treatment and prevention of anaphylaxis while providing our readers with a brief introduction to the diagnosis of anaphylaxis, its prevalence and its most common causes.
In addition to surfactant deficiency, increase of lung fluid content and secretion of fluid derived from the blood participate in the pathogenesis of RDS in newborns. We hypothesized that the administration of salbutamol (β-agonist) to increase lung fluid absorption would decrease the INSURE failure rate in newborns with respiratory distress syndrome (RDS) treated with intratracheal surfactant.
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No significant differences were seen between treatment groups in the degree of improvement in percent predicted FEV1 (P =.12), clinical score, respiratory rate, or O2 saturation. However, the nebulizer group had a significantly greater change in heart rate (P =.0001). Our study had 93% power to detect a mean difference in percent predicted FEV1 of 8 between the treatment groups.
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A randomised double-blind cross-over comparison was conducted. In Study 1, 27 adults with stable asthma who were currently using pressurised metered dose inhaler therapy attended for three study days. On each study day subjects inhaled doubling doses of histamine and were randomised to receive: (a) salbutamol 200 micrograms via Breath-A-Tech spacer and placebo 200 micrograms via Volumatic spacer; (b) placebo two puffs via Breath-A-Tech spacer and salbutamol 200 micrograms via Volumatic spacer; or (c) salbutamol 1 mg in 2 mL saline via jet nebuliser. FEV1 and FEF 25-75% were measured at two minute intervals for 20 minutes. In Study 2, subjects were randomised to use regular asthma medication by Volumatic or Breath-A-Tech spacers and recorded symptoms and peak expiratory flow (PEF) in a daily diary.
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Platelet-activating factor (PAF-acether) is a potent agonist (EC50: 3.2 x 10(-8) M) of isolated rat portal vein. BN 52063 (composed of BN 52020, BN 52021 and BN 52022; molar ratio 2:2:1) specifically inhibits PAF-acether (10(-7) M) induced tone (IC50: 3.9 x 10(-5) M). Salbutamol (IC50: 3.1 x 10(-7) M), forskolin (IC50: 3.1 x 10(-6) M) and theophylline (IC50: 2.25 x 10(-4) M) are also effective in inhibiting PAF-acether-induced contractile responses and all excepting forskolin, show a certain specificity in this action. The basal myogenic activity of the rat portal vein is dose-dependently decreased by salbutamol (IC50: 1.2 x 10(-7) M), forskolin (IC50: 2.6 x 10(-6) M) and theophylline (IC50: 2.3 x 10(-4) M) whereas BN 52063 has no effect. The data suggest that rat portal veins possess specific PAF-acether receptors sensitive to BN 52063 and that PAF-acether effects could be inhibited by compounds which can bypass these putative receptors and modulate cAMP levels.
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In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon γ at each study time point. The classification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol.
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This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study. Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 μg (via ELLIPTA(®) dry powder inhaler) or PBO for 12 weeks. The primary endpoint was St George's Respiratory Questionnaire (SGRQ) total score at day 84. Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1-12 and trough forced expiratory volume in 1 second on day 84. Adverse events were also assessed.
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Two hundred patients aged 18-60 yr, undergoing elective laparoscopic cholecystectomy were randomized into four groups of 50 each. Group I served as control, while Groups II, III and IV received an aerosol inhalation of salbutamol, beclomethasone or sodium chromoglycate 15 min prior to entering the operating room. Following iv fentanyl (2 micro g x kg(-1)) the incidence of cough was recorded and graded as mild (1-2), moderate (3-5) and severe (> 5) depending on the number of coughs observed. Results were analyzed using 'z' and Fischer's Exact test. A P value of < or = 0.05 was considered significant.
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Correct performances (minimum and maximum of the six steps) were noticed after one demonstration in 92-98% of the adults, 87-99% of the elderly, 81-96% of the children and 83-99% of the adolescents. These figures had markedly increased at the last visit. Repeat instructions were necessary in 26% of the cases. Investigators found Easyhaler(®) easy to teach in 87% of the patients and difficult in only 0.5%. Patients found Easyhaler(®) easy to learn and use, and the patients' (and parents') satisfaction with the inhaler was very high. Lung function values [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)] improved statistically significantly during the studies, indicating good inhaler competence and treatment adherence.
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We examined the use of partial expiratory flow-volume (PEFV) curves to obtain dose-response curves to an inhaled beta 2-adrenoceptor agonist (salbutamol) in eight normal subjects. Maximum expiratory flow at low lung volumes increased on both PEFV and full expiratory flow-volume curves, but the increase was always considerably greater on PEFV (28.4%) than on full (14.5%) curves. The percent increase in flow on the PEFV curve was not significantly influenced by the preceding volume history being 90-120 s of tidal breathing, forced expiration to residual volume, or breath holding after a full inflation. These results suggest that normal tone during tidal breathing is temporarily reduced but not abolished by a full inflation, and once basal tone has been restored it is not enhanced by a full expiration. In seven of the eight subjects a satisfactory cumulative dose-response curve to inhaled salbutamol was obtained with a plateau value of maximum flow at a dose of 110 microgram. The relatively good reproducibility of PEFV curves and the considerable bronchodilator signal obtained (29-70% increase in flow above base line in different individuals) suggest that such dose-response curves may be useful in studying normal bronchial pharmacology in vivo.
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There is no difference between groups regarding clinical score and variation of forced expiratory volume in one second. There was a major variation in the heart rate response to the nebulizer (35%) compared to the commercially available spacer and dry powder inhaler (15 and 17%) and between the homemade spacer and the commercially available spacer (28 and 15%) (p = 0.004). The nebulizer and homemade spacer caused more tremor (p = 0.02). The cost of treatment was higher for the nebulizer and commercially available spacer (p = 0.0001).
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Excitation of muscle often leads to a net loss of cellular K + and a rise in extracellular K+([K+]o), which in turn inhibits excitability and contractility. It is important, therefore, to determine how this K+ is cleared by diffusion into the surroundings or by reaccumulation into the muscle cells. The inhibitory effects of the rise in [K+] o may be assessed from the time course of changes in tetanic force in isolated muscles where diffusional clearance of K+ is eliminated by removing the incubation medium and allowing the muscles to contract in air. Measurements of tetanic force, endurance, and force recovery showed that in rat soleus and extensor digitorum longus (EDL) muscles there was no significant difference between the performance of muscles contracting in buffer or in air for up to 8 min. Ouabain-induced inhibition of K+ clearance via the Na+,K+ pumps markedly reduced contractile endurance and force recovery in air. Incubation in buffer containing 10 mM K+ clearly inhibited force development and endurance,and these effects were considerably reduced by stimulating Na+,K+ pumps with the 2 -agonist salbutamol. Following 30-60 s of continuous stimulation at 60 Hz, the amount of K + released into the extracellular space was assessed from washout experiments. The release of intracellular K+ per pulse was fourfold larger in EDL than in soleus,and in the two muscles, the average [K+] o reached 52.4 and 26.0 mM, respectively, appreciably higher than previously detected. In conclusion, prevention of diffusion of K+ from the extracellular space of isolated working muscles causes only modest interference with contractile performance. The Na+,K+ pumps play a major role in the clearance of K+ and the maintenance of force. This new information is important for the evaluation of K+ -induced inhibition in muscles, where diffusional clearance of K+ is reduced by tension development sufficient to suppress circulation.
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Thirty children with a median gestational age of 25-29 weeks and median postnatal age of 13 months.
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Ten patients with chronic bronchitis (Medical Research Council definition) completed a double-blind placebo-controlled study comparing 400 micrograms, 1 mg, 1.6 mg and 2 mg salbutamol powder. Response was measured by spirometry, peak expiratory flow rate, heart rate and tremor at intervals up to 4 hours post-inhalation. Pulmonary function results showed a trend towards higher doses producing improved response and a longer duration of action, with bronchodilatation following 2 mg significantly greater than 400 micrograms. Seven patients developed or had an increase in tremor following a single dose of 2 mg and in one this was considered to be severe. No adverse effects were recorded on ECG.
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Overall, the rate of hospitalization was lower in the ipratropium group (59 of 215 children [27.4 percent]) than in the control group (80 of 219 [36.5 percent], P=0.05). For patients with moderate asthma (indicated by a peak expiratory flow rate of 50 to 70 percent of the predicted value or an asthma score of 8 to 11 on a 15-point scale), hospitalization rates were similar in the two groups (ipratropium: 8 of 79 children [10.1 percent]; control: 9 of 84 [10.7 percent]). For patients with severe asthma (defined as a peak expiratory flow rate of <50 percent of the predicted value or an asthma score of 12 to 15), the addition of ipratropium significantly reduced the need for hospitalization (51 of 136 children [37.5 percent], as compared with 71 of 135 [52.6 percent] in the control group; P=0.02).
Twenty adults with clinically stable asthma.
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114 steroid-naive current or former smokers with moderate to severe COPD.
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The aim of this study was to determine whether the effects of inhaled beclomethasone dipropionate and budesonide dry powder on pulmonary function correlate with those on measurement of serum eosinophil cationic protein (sECP). Thirty-two asthmatic adults in a stable phase, treated daily with 1,000 micrograms beclomethasone dipropionate metered-dose inhaler, completed a 2-week wash-out period and were then randomized to receive a 200 micrograms/dose q.i.d. of either drug, over an 8-week period. Pulmonary function tests (FEV1, FVC, PEFR, FEF25-75% and MEF50) were measured at study entry, before and after every 2 weeks of treatment, while PEFR (morning and evening), symptom scores and salbutamol use PRN were recorded daily on a dairy card. sECP was measured at baseline and after 4 and 8 weeks of treatment. Safety variables included adverse reactions, morning serum cortisol and vital signs (heart rate and blood pressure). FEV1, FVC, PEFR, FEF25-75%, MEF50 and morning PEFR significantly increased (p < 0.05) over baseline in the beclomethasone group, while only FEV1 at week 6 and evening PEFR significantly increased (p < 0.05) in the budesonide group; no significant differences between groups were reported. sECP significantly decreased (p < 0.01) in the beclomethasone group at week 4 and 8 (p < 0.05 between groups). Evidence of statistically significant negative correlation between the FEV1 percent predicted and sECP was assessed at baseline (correlation coefficient r = -0.60, p < 0.05) in the total patient sample, and in the results, expressed as percent change over baseline, obtained at both week 4 and 8 (p < 0.01). A significant decrease in salbutamol use PRN, symptom score and number of daily bronchospasm attacks was also reported in the beclomethasone group (p < 0.05). No adverse reactions or relevant changes in morning cortisol and vital signs were reported in either group. It was concluded that sECP proved to be a reliable marker for monitoring inflammatory events in asthma; inhaled beclomethasone dipropionate dry powder was at least as effective as budesonide in improving lung function and the underlying asthma inflammation.
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To determine whether circadian variation in adrenoceptor function might underlie the 'morning dip' in peak expiratory flow (PEF) rate and its abolition by salbutamol we measured indices of beta-adrenoceptor function (Bmax. and Kd), the ratio FEV1/FVC, and plasma cortisol at 08.00 and 18.00 hours on and off salbutamol (4 mg given orally every 4 h) in five extrinsic asthmatic patients and five normal volunteers. There was a significant circadian variation in receptor numbers (Bmax.) in both the control and asthmatic groups which was not abolished on treatment with salbutamol. Both groups appeared to compensate for loss of receptor number induced by salbutamol administration by increasing receptor affinity. For comparable combinations of drug/time, there was no significant difference between the control and asthmatic groups. We conclude that the 'morning dip' observed in asthmatic patients cannot simply be explained by changes in cell receptor number or affinity, as our results suggest that both groups have intact beta-adrenoceptor function. Nevertheless, our observations of the normal circadian rhythm has important implications for future studies of beta-adrenoceptors in asthmatic patients.
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Our pilot study suggests that the use of nebivolol in hypertensive patients with stable mild to moderate COPD was safe during a 2-week trial. Evaluation of longer time periods, larger patient numbers with more severe COPD or during exacerbations is warranted.
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The reported data for compound screening with the bioluminescence resonance energy transfer (BRET2) assay is very limited, and several questions remain unaddressed, such as the behavior of agonists. Eleven beta2 adrenergic receptor (beta2-AR) agonists were tested for full or partial agonism in an improved version of the receptor/beta-arrestin2 BRET2 assay and in 2 cyclic adenosine monophosphate (cAMP) assays (column cAMP assay and ALPHAscreen cAMP assay). Tested in the highly sensitive ALPHAscreen cAMP assay, all selected agonists behaved as full agonists, using isoproterenol as a reference compound. In the less sensitive column cAMP assay, ephedrine and dopamine had a clear partial response. For the BRET2 assay, a highly graded picture was obtained. Moreover, beta2-AR antagonists were tested for inverse agonism. Pronounced inverse agonism was detected in the ALPHAscreen cAMP assay. Only marginal inverse agonistic responses were seen for alprenolol and pindolol in the column cAMP assay, and no inverse agonism was seen in the BRET2 assay. For the beta2-AR, the BRET2 assay may be superior for secondary screening of agonists where a separation of full and partial agonists is needed and the ALPHAscreen cAMP assay may be preferred for primary screening of agonists where all receptor activating compounds are desired.
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Patients had a significant decrease in plasma potassium concentrations that was evident by 30 minutes and sustained for at least 2 hours after albuterol treatment. After the administration of 10- and 20-mg doses of albuterol, the maximal decrease in the plasma potassium levels was 0.62 +/- 0.09 and 0.98 +/- 0.14 mmol/L (SE), respectively. Nebulized saline administration did not produce a significant change in the plasma potassium concentrations. Patients did not develop symptoms or significant changes in blood pressure or heart rate with albuterol treatment.
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A prospective, open, multi-centre study was performed to evaluate the efficacy and safety of a fixed combination of inhaled Fluticasone (250 microgram BID) and Salmeterol (50 microgram BID) in a single inhaler device (Diskus). 3345 patients (48 % male, mean age 52 years, range 17 - 90 years) with mild to moderate asthma were treated over a period of 8 weeks. Lung function, quality of life and adverse events were evaluated as primary outcome variables.
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Six healthy volunteers.
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To investigate the effects of methacholine (MTH) challenge on spirometry, lung mechanics, respiratory gases, and ventilation-perfusion (VA/Q) distributions, 16 subjects 16 to 58 yr of age with stable mild asthma (FEV1, 92 +/- 5% [SEM] predicted; FEF25-75, 71 +/- 7% predicted; respiratory system resistance (Rrs) at 4 Hz, 4.6 +/- 0.4 cm H2O/L-1 s; PaO2, 88 +/- 3 mm Hg; AaPO2, 23 +/- 3 mm Hg) were recruited. Baseline VA/Q distributions were unimodal and relatively narrow in 12 patients and modestly bimodal in the other four. The dispersion of pulmonary blood flow (log SD Q) was slightly enlarged (0.71 +/- 0.09) and that of ventilation (log SD V) was normal (0.57 +/- 0.04) (normal range, 0.3 to 0.6); an index of overall VA/Q heterogeneity (DISP R-E*) was also mildly abnormal (5.3 +/- 0.8) (normal values less than 3.0). After MTH challenge, FEV1, FEF25-75, and PaO2 fell (to 62 +/- 3 and 35 +/- 3% predicted, and to 71 +/- 1 mm Hg, respectively), whereas Rrs (p less than 0.001 each), minute ventilation (p less than 0.02), heart rate (p less than 0.01), and AaPO2 increased (p less than 0.001). VA/Q relationships mildly to moderately worsened (log SD Q increased to 0.98 +/- 0.04 [p less than 0.01], log SD V to 0.79 +/- 0.04, and DISP R-E* to 9.8 +/- 0.6 [p less than 0.001 each]). Qualitatively, the pattern of blood flow distribution was broadly unimodal in 13 patients and modestly bimodal in three, of whom only one had a bimodal baseline distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
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Bronchiolitis is a common respiratory infection in infants that is sometimes treated with albuterol. Response to albuterol is determined by clinical assessment, but this subjective determination is potentially unreliable. In this study, we compared providers' clinical assessment of response to albuterol with the measurement of response by pulmonary mechanics in intubated, sedated, and ventilated infants.
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This population-based, prospective, observational cohort included children aged 2 to 16 years, hospitalized for asthma at an urban pediatric facility and followed for greater than or equal to 12 months. The primary outcome was asthma-related emergency revisit within 12 months of discharge. Revisits were identified by billing codes, respiratory chief complaints, and medications administered (eg, albuterol, systemic corticosteroids), dispensed, or prescribed. Predictors and covariates include demographic, socioeconomic, access, and environmental exposure variables collected during index admission. Multivariable logistic regression was used to evaluate the association between predictors and odds of asthma-related revisit.
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Thirty COPD patients were randomized to receive inhaled Tio (18 µg once daily) or inhaled SFC (50/250 µg twice daily) plus Tio for 12 weeks. Spirometry and CT were performed, and the St. George's Respiratory Questionnaire (SGRQ) was completed, before and after the trial. Airway dimensions were assessed by a validated CT technique, and airway wall area (WA) corrected for body surface area (BSA), percentage wall area (WA%), absolute wall thickness T/√BSA, and luminal area Ai/BSA at the right apical segmental bronchus, were measured.
Nocturnal cough and wheeze are common in asthma and often treated with beta2 agonists or theophyllines. As nocturnal asthma and these therapies may affect sleep and cognition, we compared 50 microg salmeterol inhaled every 12 h with individually dose-titrated sustained-release oral theophylline on sleep quality and cognitive performance in 15 patients with stable nocturnal asthma (overnight peak expiratory flow rate [PEFR] fall > or = 15%, > or = 1 asthmatic awakening/week) using a double-blind, double-dummy, crossover design with 14-d therapy limbs. Cognitive testing and polysomnography were performed on Nights 13 and 14. Trough plasma theophylline concentration after Night 14 on theophylline was median 11.1 (interquartile range 8.3, 15.2) microg/ml. Overnight PEFR falls were similar [salmeterol 2.3 (0, 10.6), theophylline 3.5 (-0.3, 9.6)%, p = 0.4] but on salmeterol there were more nights without awakenings [median difference 1 (0, 2), p < 0.01], fewer nocturnal arousals [difference -3 (-7, 2) h(-1), p < 0.05] and improved quality of life (p = 0.05). Sleep architecture did not otherwise differ. Visual vigilance improved on salmetrol (p < 0.05), but otherwise daytime cognition was unaffected. There was no patient preference for either therapy. Hence in patients with nocturnal asthma, we demonstrate no major clinical advantage, but a small benefit in sleep quality, quality of life, and daytime cognitive function with salmeterol.
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Lactic acidosis is a recognised event in adult patients with status asthmaticus, particularly in the setting of intensive care. However, it has been infrequently studied in patients attending the emergency departments (ED).
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The mean area under the curve of improvement for scaling/hypertrophy, pain, itching and global patient assessment was significantly better for the actively treated patients as compared with placebo (scaling/hypertrophy, P = 0.0262; pain, P = 0.0238; itching, P = 0.0135; global patient assessment, P = 0.045). Moreover, the percentage of patients without induration was significantly higher in the active group compared with the placebo group (P = 0.013), and a statistically significantly greater decrease in the size of the lesional area was also seen in the overall analysis of the R-salbutamol-treated patients (P = 0.0197). No serious adverse events were reported.
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The goal of this study was to examine the impact of a multidisciplinary intervention designed to improve appropriate albuterol inhaler utilization among patients with asthma.
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Randomized, double-blind, crossover clinical trial.