Effect of different albuterol dosing regimens in the treatment of acute exacerbation of chronic obstructive pulmonary disease

There is substantial evidence for an activation of the sympathetic nervous system in man as well as in genetic models of hypertension, such as the spontaneously hypertensive rat (SHR), but we are only beginning to understand the central mechanisms that generate changes in sympathetic activity and elevate blood pressure (BP). Significant recent advances have been made in defining the neural pathways involved in BP regulation and in identifying the neurotransmitters these neurones utilise. In this overview, we describe the neural pathways within the medulla oblongata and spinal cord that participate in BP control and examine the role of amino acid neurotransmitters within these pathways. We demonstrate how alterations in these pathways explain the sympathetic activation observed in the SHR and contribute to hypertension in this model. Lastly, we examine the application of modern molecular biological approaches to further our understanding of the neural regulation of the circulation. In these studies, we used the administration of antisense oligonucleotides to interrupt gene expression.     

Behavioral and environmental factors associated with acute exacerbation of asthma

Micellar catalysis plays a crucial role in NO metabolism because media in vivo are heterogeneous and the concentration of NO in different phases at different levels of solubility differs by degrees of magnitude. The relative volumes of the hydrophobic phases are usually small. At small volumes (which are calculated) of these phases the reaction rates of NO metabolism change. The dependence on the relative volumes is resonance-like. Not only regulation, but bifurcations and catastrophes are possible in vivo as a result of this changing due to the small change of effectiveness of micellar catalysis.     

Language of dyspnea in assessment of patients with acute asthma treated with nebulized albuterol

To investigate whether the language of dyspnea provides relevant clinical information in addition to that provided by ratings of overall dyspnea intensity when assessing subjective response to therapy, we conducted a prospective study in a cohort of 25 patients with acute asthma presenting to the emergency department of a tertiary care hospital. Patients received nebulized albuterol treatments every 20 min with a maximum of three doses. At presentation and after each treatment, patients completed spirometry, rated overall dyspnea intensity on a modified Borg scale, and selected phrases that described qualities of breathlessness from a 15-item questionnaire. Paired Student's t tests revealed significant improvements in FEV1 (from 1.39 +/- 0.66 L to 1.80 +/- 0.76 L, p < 0. 001) and reductions in dyspnea intensity (from 5.12 +/- 2.08 to 2.82 +/- 1.59, p < 0.001) after the first albuterol treatment. Dyspnea intensity continued to decrease significantly in response to the second treatment, modified Borg rating 2.26 +/- 1.52, although there was no positive bronchodilator response. The results from Cochran Q tests revealed that the frequency of the experience of "chest tightness" decreased significantly across the phases of treatment. However, the sensations of "work" or "breathing effort" persisted at the same time that the FEV1 revealed ongoing airways obstruction. We conclude that attention to the language of dyspnea would alert health care providers to residual air flow obstruction despite decreases in overall dyspnea intensity.     

Observations on the effects of aerosolized albuterol in acute asthma

To determine the dose of albuterol required to terminate acute episodes of asthma, 92 acutely ill subjects received three doses of 2.5 mg each by nebulization every 20 min. Peak expiratory flow rates (PEFR) and signs and symptoms were serially monitored. A dose-response increase in pulmonary function was found, but only 66% of the subjects improved sufficiently to be sent home. Of these, 56% required < or = 5.0 mg of drug to reach the discharge threshold, whereas the remainder needed 7.5 mg. In 34% of participants, albuterol was ineffectual. These individuals were characterized by more severe obstruction at presentation, and after three doses of medication their PEFR still did not exceed 40% of the expected value. Further treatment in the emergency department (ED) or hospital was not immediately helpful, and these patients ultimately required 3.8 +/- 0.4 d of inpatient care to become asymptomatic. There were no discernible differences between responders and nonresponders in the type or quantity of medications used. However, the nonresponders had more severe disease as measured by recurrent hospitalizations and ED visits. This study demonstrates that, in emergency situations, albuterol does not relieve acute airway obstruction in all asthmatic individuals with equal efficacy. Two-thirds of patients are sensitive, and in these patients 5 to 7.5 mg of albuterol provides optimal treatment. In the remainder, albuterol, even in high doses, has little effect for days.     

Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthma

Monoamines, including both dopamine and serotonin, synapse onto prefrontal cortical interneurons. Dopamine has been shown to activate these GABAergic interneurons, but there are no direct data on the effects of serotonin on GABA release in the prefrontal cortex. We, therefore, examined the effects of the 5-HT2a/c agonist 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) on extracellular GABA levels in the prefrontal cortex of the rat. Local infusions of DOI dose-dependently increased cortical extracellular GABA levels. In addition, systemic DOI administration resulted in Fos protein expression in glutamic acid decarboxylase67-immunoreactive interneurons of the prefrontal cortex. These data indicate that serotonin, operating through a 5-HT2 receptor, acutely activates GABAergic interneurons in the prefrontal cortex. These data further suggest that there may be convergent regulation of interneurons by dopamine and serotonin in the prefrontal cortex.     

Airway and lung tissue mechanics in asthma. Effects of albuterol

We examined the partitioning of total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti) in patients with mild to moderate asthma (baseline FEV1, 54 to 91% of predicted) before and after albuterol inhalation. An optimal ventilator waveform was used to measure RL and lung elastance (EL) in 21 asthmatics from approximately 0.1 to 8 Hz during tidal excursions. Analysis of the RL and EL provided separate estimates of airway and lung tissue properties. Eleven subjects, classified as Type A asthmatics, displayed slightly elevated RL but normal EL. Their data were well described with a model consisting of homogeneous airways leading to viscoelastic tissues before and after albuterol. The other 10 subjects, classified as Type B asthmatics, demonstrated highly elevated RL and an EL that became highly elevated at frequencies above 2 Hz. These subjects required the inclusion of an airway wall compliance in the model prealbuterol but not postalbuterol. This suggests that the Type B subjects were experiencing pronounced constriction in the periphery of the lung, resulting in shunting of flow into the airway walls. Spirometric data were consistent with higher constriction in Type B subjects. Both groups demonstrated significant (p < 0.05) decreases in Raw and tissue damping after albuterol, but tissue elastance decreased only in the Type B group. The percent contributions of Raw and Rti to RL were similar in both groups and did not change after albuterol. We conclude that in asthma, Raw comprises the majority (> 70%) of RL at breathing frequencies. The relative contributions of Raw and Rti to RL appear to be independent of the degree of smooth muscle constriction.     

Increase of chemokine levels in sputum precedes exacerbation of acute asthma attacks

Basophils and eosinophils can be activated in vitro by several chemokines such as RANTES, monocyte chemotactic and activating factor (MCAF/MCP-1), macrophage inflammatory peptide-1 alpha (MIP-1 alpha), and interleukin-8 (IL-8). To explore the clinical relevance of the in vitro observations, we measured here the concentrations of these chemokines in sputa from asthmatic patients during acute attacks. Before the onset of a late-phase exacerbation, sputum MCAF/MCP-1, MIP-1 alpha, and IL-8 levels transiently but markedly increased from the basal levels in all of the patients with exacerbation, whereas the sputum levels of these chemokines remained unchanged during the course in the patients without a late-phase exacerbation. These results suggest the involvement of these chemokines in the late-phase exacerbation of asthma.     

Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma

OBJECTIVE: To compare the efficacy and safety of inhaled salmeterol xinafoate, a long-acting beta 2-adrenoceptor agonist, with that of albuterol, a short-acting inhaled beta 2-agonist, in the treatment of asthma. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Eleven outpatient clinical centers. SUBJECTS: A total of 322 male and female patients at least 12 years of age with chronic symptomatic asthma requiring daily therapy. INTERVENTION: Patients were treated with salmeterol xinafoate (42 micrograms inhaled twice daily), albuterol (180 micrograms inhaled four times daily), or placebo (four times a day) for 12 weeks; patients in all three groups could use inhaled albuterol as backup medication for breakthrough symptoms. MAIN OUTCOME MEASURES: Serial 12-hour forced expiratory flow in 1 second (FEV1), peak expiratory flow (PEF), asthma symptoms, nocturnal awakenings due to asthma, episodes of asthma exacerbations, and electrocardiography. RESULTS: The mean area under the curve for FEV1 throughout each 12-hour period was consistently greater after a single dose of salmeterol than after two doses of albuterol administered 6 hours apart (P < .001), with the difference ranging from 3.1 to 4.3 L.h. Salmeterol produced an average increase in morning and evening PEF of 26 and 29 L/min, respectively, over pretreatment values compared with decreases of -13 and -3 L/min, respectively, in the albuterol group and -2 L/min both in the morning and evening in the placebo group (P < .001). Patients in the salmeterol group had significantly fewer days and nights with symptoms than did either the albuterol or placebo group (P < .001). Responses to salmeterol were similar at day 1 and at week 12. Adverse events in all treatment groups were equally infrequent, and no clinically significant change in cardiac rhythm was observed with salmeterol treatment. CONCLUSION: Salmeterol inhaled twice daily is more effective than albuterol inhaled four times a day (or as needed) in patients with asthma requiring maintenance therapy. No deterioration of asthma control was observed with the use of salmeterol over a 3-month period.     

The correlational analysis assessment of exacerbation in bronchial asthma and treatment efficacy

Blood and sputum eosinophils, eosinophilic cation protein (ECP) in the serum and OPV1 were measured in 30 patients with atopic bronchial asthma (BA) of moderate severity showing eosinophilia at the beginning and the end of treatment week 1 and 4, respectively. In exacerbation of BA relative number of blood eosinophils averaged 10.4 + -1.4%, sputum 35.2 + -5.6%. Serum concentration of ECP, OPV1, IgE averaged 42.6% + -11.9%, 66.8 + -6.3%, 753.7 + -114 IU/ml, respectively. In exacerbation a strong correlation is noted between relative number of eosinophils in the blood and sputum, between the levels of IgE and ECP. At the end of the treatment OPV1 was higher while ECP level in the serum went down. Reduced eosinophilia in the blood and sputum correlated with OPV1 increment. In BA patients with high blood and sputum eosinophilia function of the lungs depends on eosinophilic number, while in normalization of blood eosinophil concentration and in a sharp fall of sputum eosinophil number OPV1 changes correlation with changes in ECP in the course of treatment. A close correlation between changes in eosinophil count, FVD indices, IgE and ECP levels during the treatment indicate relief of inflammation in BA patients.     

Effects of an acute exacerbation on nutritional and metabolic profile of patients with COPD

In this study, we investigated the influence of an acute disease exacerbation on the nutritional and metabolic status of patients with chronic obstructive pulmonary disease (COPD). The study group consisted of 23 patients acutely admitted to the hospital for standardized medical treatment. Dietary intake (dietary records and diet history), resting energy expenditure (ventilated hood), body composition (bioelectrical impedance spectroscopy) and disease symptoms (visual analogue scale) were assessed on admission, daily throughout the hospitalization period, at discharge and 3 months thereafter in stable clinical condition. Dietary intake, since aggravation of disease symptoms, prior to admission, (5,640+/-2,671 kJ) was significantly lower than habitual intake (7,863+/-2,005 kJ). The balance between dietary intake with measured resting energy expenditure and estimated diet-induced thermogenesis was severely impaired during the first 3 days of hospitalization, stabilizing thereafter to 145+/-24% at discharge. Resting energy expenditure decreased from 6,812+/-900 kJ (123+/-11%) on admission to 6,196+/-795 kJ (113+/-14%) at discharge (p<0.001). During treatment, no significant shift in water compartments, fat-free mass and body weight was seen. Follow-up data were obtained from 10 out of 23 patients. Three months after admission, dietary intake was not significantly different from usual dietary intake (8,512+/-2,290 and 8,415+/-2,600 kJ, respectively), resting energy expenditure was similar to the value at discharge, and a significant body weight gain was seen. We conclude that an acute exacerbation of chronic obstructive pulmonary disease is accompanied by an impaired energy balance due to a decreased dietary intake and an increased resting energy expenditure.     

Use of glycopyrrolate in the treatment of Meniere's disease

OBJECTIVES/HYPOTHESIS: The objective of this study was to determine whether glycopyrrolate is useful as a vestibular suppressant in patients with Meniere's disease. The tested hypotheses were that glycopyrrolate would decrease the perception of dizziness measured by the Dizziness Handicap Inventory in patients with Meniere's disease and that placebo would cause no such decrease. STUDY DESIGN: Randomized, prospective. METHODS: Thirty-seven subjects with a diagnosis of Meniere's disease were administered either 2 mg of glycopyrrolate or placebo twice daily as needed for vertigo. All were also administered the regimen of 1500 mg sodium/day diet and diuretic. The following indices were examined: Dizziness Handicap Inventory, Tinnitus Handicap Inventory, Modified Somatic Perception Questionnaire, Beck Depression Inventory, hearing examination, and electronystagmography. After 4 to 6 weeks of the drug regimen, Dizziness Handicap Inventory, Tinnitus Handicap Inventory, Modified Somatic Perception Questionnaire, and Beck Depression Scale were reexamined. Paired t tests were performed to verify the significance of improvement before and after treatment. RESULTS: Subjects who received glycopyrrolate had statistically significant reduction in Dizziness Handicap Inventory, Beck Depression Score, and Modified Somatic Perception Score. In the placebo group, no improvement in any index was found. CONCLUSIONS: The hypothesis that glycopyrrolate is a useful vestibular suppressant in patients with Meniere's disease was statistically verified.     

Treatment of severe acute exacerbation of asthma and chronic obstructive lung disease. An interview study

A telephone survey was conducted of all the 71 Danish hospitals with the capacity to receive acutely ill medical patients. The purpose was to register treatment regimes used in acute asthma and exacerbations in chronic obstructive pulmonary disease (COPD). The house officer on duty was interviewed and questioned about the use of nebulizers, oxygen therapy, bronchodilators, steroids, theophyllins and monitoring of the patient's condition. The physician survey was supplemented by a smaller survey among emergency room nurses about nebulizing systems. The answers showed inadequate knowledge of nebulizing systems. There was a noticeable variation in the dosing of oxygen and in the dosing of bronchodilators and steroids. beta 2-agonist treatment by nebulizer differed with a factor 14 in dose. The majority of the physicians had no specific parameters for monitoring severity of disease. CONCLUSION: There is a need for improvement of the knowledge of nebulizing systems, including specific knowledge of the appropriate use of propellant gasflow and time of nebulizing for optimum performance of the used nebulizer. Divergent answers from the nurses and the physicians show the need for interdisciplinary instruction. The noticeable variation in treatment in this Danish survey displays a need for quality control in terms of concise guidelines for medical therapy in acute exacerbations of asthma and COPD and guidelines for monitoring of the response to the treatment. A suggestion for a treatment regime is proposed.     

Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid

STUDY OBJECTIVE: To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma. DESIGN: Randomized, prospective, placebo-controlled, double-blind trial. SETTING: Tertiary-care children's hospital. PATIENTS: Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment. INTERVENTIONS: All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone. MEASUREMENTS AND MAIN RESULTS: Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups. CONCLUSION: When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified.     

Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network

This in vitro study investigated the temperature changes experienced during electric welding of titanium to determine if the welding heat presented a potential danger to pulpal vitality. Welds were applied to cast titanium simulations of a three-unit fixed partial denture containing two thermocouples measuring temperature changes. Mean maximal temperature changes were 127.4 degrees F near the weld and 68.6 F degrees at the axial wall. The mean times for the temperature to drop to within 10.0 degrees F of the starting temperature ranged from 84.1 to 133.7 seconds. The relatively low temperatures recorded in this study suggest that further investigation is warranted into the use of the welder intraorally.     

High serum albuterol levels and tachycardia in adult asthmatics treated with high-dose continuously aerosolized albuterol

To study the feasibility of using high-dose continuously aerosolized albuterol aerosol in adults, seven adult asthmatic patients were treated eight times with 0.4 mg/kg/h albuterol delivered by continuous nebulization over 4 h. One patient withdrew at 3 h after supraventricular tachycardia developed. This subsided promptly on discontinuing albuterol therapy. Heart rate increases were observed in six of eight treatments and serum albuterol levels at the end of treatment were greater than 25.0 ng/ml in all but one treatment. A mean increase in heart rate of 16.3 percent was observed for the entire group. Of the treatments with elevated (> 25.0 ng/ml) serum albuterol levels, a significant cumulative increase in heart rate was observed with time. A significant improvement of FEV1 was observed (p = 0.0025) with a net increase of 36.8 percent. These data suggest that high-dose continuously aerosolized albuterol treatment in some adult asthmatics can result in markedly elevated serum albuterol levels and potential cardiac stimulation despite spirometric improvement.