Acute Bronchospasm Research Articles

Effect of a treatment protocol on the efficiency of care of the adult acute asthmatic

A treatment protocol for patients with acute bronchospasm was introduced to an adult emergency department in an attempt to decrease treatment time and potentially decrease need for admission. The charts of all patients seen in a control year (before any protocol was in place) and the first three years of the protocol were reviewed. All care was given by medical housestaff. The first year after the protocol was introduced showed no change in either admission rate or stay in the ED. During this time, however, the protocol was used only 33% of the time. In the following two years, the protocol was used 93% of the time, and the admission rate decreased from 36.4% to 23.3% (P less than .02). The length of stay for all patients seen fell from a mean of 3.6 hours to 2.8 hours (P less than .005). The length of stay for those discharged fell from an average of 4.3 hours to 3.6 hours (P less than .02). Among the patients admitted, there was also a less striking but similar decrease from 3.0 hours to 2.4 hours. An organized treatment protocol was effective in increasing the efficiency of care given by the housestaff. The routine use of the protocol was not immediate and required time for acceptance by the housestaff.

Reflex activation of the nonadrenergic noncholinergic inhibitory nervous system in feline airways.

Experiments were undertaken to learn if the nonadrenergic noncholinergic inhibitory nervous system (NANCIS) in feline airways could be activated reflexly either by mechanically stimulating the laryngeal mucosa or by inducing acute bronchospasm with boluses of 5-hydroxytryptamine (5HT) injected intravenously. Mechanical stimulation of the dorsal laryngeal mucosa evoked a biphasic bronchomotor response in anesthetized cats that had received intravenously an infusion of 5HT to raise their basal airway smooth muscle tone. The response consisted of a transient augmentation of bronchoconstriction followed by a prolonged bronchodilation. After muscarinic cholinergic receptor blockade with atropine, the constriction phase of the response disappeared, but the relaxation phase persisted. Bronchodilation elicited by laryngeal stimulation was resistant to beta-adrenergic receptor blockade with propranolol but was abolished by autonomic ganglionic blockade with hexamethonium and blocked reversibly by vagal cooling. The latter interventions, when imposed between successive dose-response curves generated by intravenous 5HT in animals pretreated with atropine and propranolol, did not alter the positions or slopes of the curves. These findings support the conclusion that mechanical stimulation of the larynx reflexly activates not only the well-known vagal cholinergic excitatory pathway to the airways but also the more recently described vagal, nonadrenergic noncholinergic inhibitory pathway. The results further indicate that bronchoconstriction is neither a prerequisite for the bronchodilator component of the laryngeal bronchomotor reflex nor an independent initiating stimulus for NANCIS-mediated reflex bronchodilation.

Immunopharmacology of Anaphylatoxin-Induced Bronchoconstrictor Responses

The complement anaphylatoxin peptides, C3a and C5a, are potential mediators of immediate hypersensitivity reactions, eliciting many of the same actions on isolated tissue and cell preparations as specific antigen. Instilled intratracheally in experimental animals, the peptides induce acute bronchospasms and are sometimes lethal. In vitro, they cause dose-dependent contraction of isolated lung tissue preparations, a response which correlates well with bronchospasms observed in vivo, and our current understanding of the cellular and molecular mechanisms of this action are reviewed here. C5a and its catabolic derivative, C5ades Arg, stimulate contraction of isolated guinea pig lung parenchymal strips in part by production of leukotrienes that constitute SRS-A, and by release of histamine. Leukotrienes in turn release thromboxane from lung tissue, and evidence indicates that at least part of the spasmogenic activity of these peptidolipids is mediated by this effect. C3a is considerably less potent than C5a in contracting lung tissues and appears to act primarily by causing the release of spasmogenic cyclooxygenase metabolites. Both peptides may additionally have direct action on contractile cells within the tissue. Platelet-activating factor (PAF), an unusual phospholipid mediator released from inflammatory cells stimulated with C5a and other agents, also contracts isolated lung parenchymal tissues. PAF stimulates release of significant quantities of thromboxane from guinea pig lung; however, indomethacin does not block contractile responses of the tissue. Recent evidence indicates that PAF may act on parasympathetic neurons in lung to release endogenous acetylcholine, and this action may be a major component of tissue responses to this mediator. Thus the complement anaphylatoxins stimulate release of many of the same mediators from lung tissues as are released by antigen challenge of sensitized tissue, and may, therefore, play an important role in the pathogenesis of allergic bronchospasms.

Value of oral provocation tests to aspirin and food additives in the routine investigation of asthma and chronic urticaria

Nonsteroidal anti-inflammatory drugs and certain food or drug additives are known to induce acute bronchospasms, angioneurotic edema, and urticaria in susceptible patients. Thirty-four patients (17 with asthma and 17 with urticaria), whose case history suggested such intolerance, were challenged orally with increasing doses of seven compounds: acetylsalicylic acid, glafenine, sodium benzoate, sulfur dioxide, potassium sorbate, sodium glutamate, and tartrazine. Among 162 oral provocation tests, 38 were positive (20% decrease in peak flow rate or appearance of acute urticaria/angioneurotic edema). Twenty-four of the 34 patients (nine with asthma and 15 with urticaria) were intolerant to at least one compound. However, no serious reaction was observed. In 20 of these 24 patients (six with asthma and 14 with urticaria), a diet free of additives and nonsteroidal anti-inflammatory drugs resulted, within 5 days, in a marked improvement of symptoms, which persisted 8 to 14 mo after starting the diet. Age, prevalence of IgE-mediated allergy, and nasal polyposis were similar in patients with or without reactions of intolerance. Under the conditions used, oral provocation tests proved to be feasible, safe, and useful in many patients not helped by existing methods.

Volume of Distribution of Theophylline in Acute Exacerbations of Reversible Airway Disease: Effect of Body Weight

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.

Inadequacy of FDA dosing guidelines for intravenous theophylline.

The ability of a dosing regimen of intravenous theophylline to achieve therapeutic serum theophylline concentrations was evaluated. Intravenous theophylline was administered to 25 adult patients with acute bronchospasm using dosing guidelines 20 percent higher than FDA recommendations. The dose of theophylline was determined by assignment to one of four clinical categories. Blood samples for determination of serum theophylline concentrations were collected 12 and 24 hours after initiation of a constant infusion. Differences between mean observed and target theophylline concentrations did not achieve statistical significance. All patients in categories 1 and 2 achieved therapeutic concentrations of theophylline. Most of those with subtherapeutic levels were smokers suffering from multiple diseases. We conclude that current FDA recommendations for dosing intravenous theophylline are unreliable for routine use in category 3 and 4 patients. Further work is necessary to evaluate these recommendations in pediatric and category 1 and 2 patients.

Response to Inhaled ß-Agonist in a Patient Receiving ß-Adrenergic Blockers

A 52-year-old man receiving long-term hemodialysis and a beta-adrenergic blocker for hypertension had symptoms of acute bronchospasm when exposed to a new hemodialyzer. Resistant to two doses of subcutaneous epinephrine (1 mL of 1:1000 dilution) and one intravenous dose of aminophylline (250 mg), the bronchospasm was rapidly relieved by metaproterenol sulfate given by inhalation one hour later.

Theophylline

This study was undertaken to evaluate a method of prospectively estimating appropriate aminophylline infusion rates in acutely ill, hospitalized patients with bronchospasm. Steady-state serum theophylline concentrations (Css), clearances (Cl), and half-lives (t1/2) were estimated by the Chiou method using serum concetrantions obtained 1 and 6 h after the start of a constant-rate intravenous aminophylline infusion in 10 male patients averaging 57 years of age. Using an enzyme-multiplied immunoassay (EMIT) system for theophylline analysis, pharmacokinetic estimations were excellent for Css (r = 0.9103, p less than 0.01) and Cl (r = 0.9750, p less than 0.01). The mean estimation errors were 9.4% (range 0.8-21.5) for Css and 12.3% (range 1.3-28.0) for Cl. There was no correlation between patient age and Cl. This method is useful for rapidly individualizing aminophylline therapy in patients with acute bronchospasm.

Albuterol: an adrenergic agent for use in the treatment of asthma pharmacology, pharmacokinetics and clinical use.

Albuterol is a long-acting beta 2-adrenergic receptor-selective drug that relaxes airway smooth muscle. It is currently available in the United States in oral and metered-dose inhaler forms. Nebulizer solutions and parenteral preparations are likely to be marketed here in the future. The chemical modifications that make albuterol beta 2-selective also promote oral bioavailability and increased duration of action by decreasing sensitivity to degradative enzymes. Albuterol can also produce undesirable dose-related effects: metabolic effects including decreased levels of plasma potassium, phosphate, calcium and magnesium; increased levels of plasma glucose, insulin, renin, lactate and ketones; peripheral vasodilation and perhaps some direct cardiac stimulation resulting in decreased systemic and pulmonary vascular resistance, increased pulse pressure and tachycardia; and skeletal muscle tremor. These side effects are most common with parenteral administration and much less prominent with aerosol administration, which yields lower systemic concentrations. Limited pharmacokinetic data suggest a long distribution phase, a terminal half-life of 3-8 hours, and 10-20% oral bioavailability. Aerosolization of albuterol or a similar agent with a compressed-air nebulizer appears to be best first-line management of the patient with acute dyspneic asthma, but appropriate preparations for this kind of therapy are currently missing from the United States market. Intravenous albuterol has also been employed in acutely dyspneic patients, but produces more side effects than carefully administered intravenous theophylline, is impaired by lack of sufficient pharmacokinetic information to guide dosing, and is of uncertain efficacy in the asthmatic with respiratory failure. However, it appears to lack the potentially life-threatening side effects that can result when theophylline is used carelessly . In the ambulatory patient, aerosolized albuterol (or a similar agent) administered by metered-dose inhaler is an excellent agent for treatment as needed and/or for prevention of acute bronchospasm triggered by exercise or other predictable cause. Advantages include a high degree of efficacy, rapid onset and long duration of effect, and minimal side effects. Regularly scheduled administration of albuterol by metered-dose inhaler is a widely used and effective maintenance medication for patients requiring long-term prophylactic therapy. However comparisons of the ability of this regimen and the other common maintenance regimens (cromolyn and theophylline) to control chronic symptoms of asthma are needed.

Long-term management of diaphragmatic paralysis complicating prosthetic valve replacement.

The exact incidence of diaphragmatic paralysis complicating secondary heart procedures is not known. The postoperative period can be complicated by difficulty in weaning from mechanical ventilation and misinterpretation of the clinical signs of respiratory muscle fatigue for congestive heart failure and acute bronchospasm. We present 3 patients, all of whom had right diaphragmatic paralysis and recurrent respiratory failure after a second mitral valve replacement. Long-term management with night-time ventilation in 2 patients resulted in no further episodes of respiratory failure and physical rehabilitation with exercise tolerance significantly greater than the preoperative state.

Aspirin and allergic diseases: A review

Aspirin intolerance manifests itself as an acute urticaria-angioedema, bronchospasm, severe rhinitis, or shock occurring within three hours of aspirin ingestion. Aspirin intolerance occurs most commonly in patients with chronic urticaria (23 percent), in whom it is mostly manifested by the urticarial type of aspirin intolerance, and in asthmatic persons (4 to 19 percent), in whom it is mostly manifested by the bronchospastic type. The frequency of aspirin intolerance in patients with nasal polyps is about 23 percent, and consists of the bronchospastic type of intolerance. There is no definite evidence that aspirin intolerance is mediated by an immunologic reaction. In the bronchospastic type, an association between prostaglandins and the slow-reacting substance of anaphylaxis seems likely. The pathogenic mechanism for the urticarial type of aspirin intolerance is unknown. Under carefully controlled conditions, a transient desensitization to aspirin is possible. Various drugs, most of which are prostaglandin inhibitors, cross-react with aspirin in intolerant persons. They are, in decreasing order of frequency, as follows: indomethacin (100 percent), ibuprofen, mefenamic acid, phenylbutazone, sodium benzoate, tartrazine and acetaminophen (5 percent). Aspirin is an efficacious drug with increasing therapeutic use. In order to minimize its risk and increase its safety, physicians should familiarize themselves with those high-risk conditions where aspirin therapy should be avoided, or at least used cautiously.

Analgesic‐induced asthma

The reported incidence of acute bronchospasm in patients with asthma who take aspirin varies from 2% to 28%, depending on the methods used to obtain data. Earlier surveys were conducted among adults, and recent studies have shown a similar incidence in children. Immunological mechanisms are unlikely to be responsible. A current hypothesis for the development of analgesic-induced asthma is based upon the inhibitory effect of aspirin on the cyclo-oxygenase pathway for the metabolism of arachidonic acid. This theory is supported by the observation that any non-steroidal anti-inflammatory drug which inhibits cyclo-oxygenase activity may precipitate attacks in subjects with asthma who are sensitive to aspirin. Since most of these drugs are structurally dissimilar to aspirin, any immunological crossreactivity is unlikely. It is possible that the bronchospasm which follows inhibition of cyclo-oxygenase activity is due either to decreased formation of cyclo-oxygenase products with bronchodilator properties and inhibitory effects on mediator release, or to increased formation of lipoxygenase products with bronchoconstrictor properties.

Acknowledgments in Cimetidine Report

Letters and Corrections1 November 1982Acknowledgments in Cimetidine ReportBERTRAND M. BELL, M.D.BERTRAND M. BELL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-5-790_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the acknowledgments to a brief report by Knapp and associates (1) I am listed among others and thanked for "many thoughtful suggestions." I would like it known that "thoughtful suggestions" were that it was both medically and morally wrong to rechallenge this patient who had had a severe attack of acute bronchospasm when he was initially treated and, for a variety of reasons, it would be impossible to obtain informed consent from this patient....Reference1. KNAPPGRIMSHAWGOLDFARBFARKASRUBINROSENSTREICH ARJPMD. Cimetidine-induced anaphylaxis. Ann Intern Med. 1982;97:374-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bronx Municipal Hospital Center Bronx, NY 10461 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1982Volume 97, Issue 5Page: 790-790 Issue Published: 1 November 1982 PDF DownloadLoading ...

A review of solvent abusers and their management by a child psychiatric out-patient service.

1 This study reviews 45 solvent abusers referred, over a 3-year period, to the Departments of Child Psychiatry attached to a large postgraduate teaching hospital. 2 Abusers are considered in 3 defined groups: chronic, periodic, experimental. 3 Boys predominate mainly in the group of chronic abusers, where a strong association is seen with delinquent behaviour and disrupted family backgrounds. 4 Many chronic users report transient symptoms of a toxic psychosis. A marked affective component may be evident, often depressive in character. 5 Systemic physical symptoms are common, especially amongst chronic users. Weight loss, nausea and vomiting, acute bronchospasm, cardiac arrhythmias have all been reported. 6 Other illicit drug use is widespread through the whole sample, but of little significance. Most children report alcohol and cigarette consumption, use of which can be very heavy. 7 Treatment was offered to most children, and comprised mainly family and individual work. A favourable outcome was correlated with high motivation, at least 6 months' duration of out-patient attendance, or with residential care and therapy. Approximately half the children who were chronic or periodic users had improved at follow-up. 8 Recommendations for more systematic recording of solvent abuse have been made as a result of these findings. All cases in the future will be separately registered, and their progress followed prospectively.

Use of a pharmacokinetic method for establishing doses of aminophylline to treat acute bronchospasm

A pharmacokinetic method of establishing individualized doses of aminophylline in patients with acute bronchospasm was evaluated. Patients admitted to a hospital who required intravenous aminophylline for bronchodilation were studied. Blood samples were drawn before treatment for theophylline-content measurement. Loading doses were administered intravenously and half-lives and volumes of distribution were determined. Individualized constant-rate infusions based on pharmacokinetic data were then begun. Heart rate, nausea, vomiting, seizures, and serum theophylline content were monitored during the study. The mean age of the 55 patients in the study was 54.3 years (range: 7 to 87). Patients with congestive heart failure or liver disease numbered 32; 30 patients were smokers. At approximately 24 hours after the calculated constant-rate infusion was begun, 85% of the patients had therapeutic serum levels of theophylline; 11% of the patients had subtherapeutic levels and 4% had toxic levels. All measured concentrations were between 7.5 and 23.0 microgram/ml. The study method produced significantly more patients in the therapeutic range than would have occurred if previously reported standardized methods had been used (p less than 0.05). Most patients had a decreased heart rate after treatment. No other adverse effects occurred that were attributable to i.v. aminophylline. It is concluded that, for patients in acute bronchospasm, individualizing i.v. aminophylline doses with patient-specific pharmacokinetic data can increase significantly the number of patients who rapidly attain therapeutic serum theophylline levels.

Bronchodilator activity of a PGE 2 analog in animals and in man

A C-11 substituted PGE 2 analog, DHET-PGE 2 [ ℓ -11-deoxy-11α-(2-hydroxyethylthio)-PGE 2 methyl ester], was demonstrated to exert potent bronchodilator activity in three in vivo models of augmented airway resistance: (1) acute bronchospasms, induced by 5-hydroxytryptamine, histamine and acetylcholine in the anesthetized guinea pig, (2) acute bronchospasm, induced by pilocarpine, in the anesthetized dog, and (3) chronic bronchospasm, induced by SO 2 exposure, in the unanesthetized dog. In acute and 30-day toxicological studies in the dog, no cardiovascular, respiratory or gastrointestinal side effects were observed at aerosol doses at least 1,000 times those required for efficacy. In vitro , DHET-PGE 2 effectively relaxed isolated preparations of dog bronchus that had been contracted with carbachol. In clinical studies, human asthmatics and bronchitics responded consistently to β-agonist bronchodilators but variably to DHET-PGE 2. Overall, increases in pulmonary resistance or decreases in FEV 1 were observed with DHET-PGE 2. Subsequent evaluation in isolated carbachol-contracted human bronchus revealed that, in contrast to the bronchodilator activity of PGE 1 and β-agonists, DHET-PGE 2 and PGE 2 induced contraction. Considered along with results from previous clinical studies on other PGs, these data underscore the difficulties in making extrapolations on this class of compounds from animal models to humans and suggest that human bronchial tissue may provide the only appropriate preclinical test system for predicting the clinical efficacy of PG bronchodilators.

Adverse reactions of aspirin and related drugs.

The term "aspirin intolerance" is defined as acute urticaria-angioedema, bronchospasm, severe rhinitis, or shock occurring within three hours of aspirin ingestion. Aspirin intolerance occurs most commonly in patients with chronic urticaria (23%), in whom it is mostly manifested by the urticaria type of aspirin tolerance, and in asthmatic individuals (4%), in whom it is mostly manifested by the bronchospastic type. There is no definite evidence that aspirin intolerance is mediated by an immunologic reaction. In the bronchospastic type, an association between prostaglandins and the slow-reacting substance of anaphylaxis (SRS-A) seems likely. It is possible that aspirin causes a preponderance of prostaglandin F2 alpha (PGF2 alpha), resulting in bronchospasm. The effect of aspirin on blood histamine is controversial. The two major types of aspirin intolerance seem to be mediated by different mechanisms.

Cefoperazone in the treatment of severe or complicated infections.

We report the use of cefoperazone in 62 cases of serious infection, most of which occurred in patients with renal impairment. 43 severe or complicated urinary tract infections, 11 cases of pneumonia and 8 with other severe sepsis were treated with cefoperazone 1 to 2 g twice daily usually for 5 to 10 days. Of the patients with urinary tract infection, all who were symptomatic showed a rapid clinical response; 26 (61%) were cured including 11 of 16 with chronic renal failure; 12 relapsed and 5 were reinfected with a different pathogen. All of these patients were infected by organisms sensitive to cefoperazone by disc testing but in 5 of those who relapsed the cefoperazone MIC was in fact greater than or equal to 50 microgram/ml. Ten of 11 cases with radiologically confirmed pneumonia were cured with cefoperazone. 7 episodes of pneumonia were in patients with end-stage chronic renal failure (6 were on dialysis) and 1 was in a patient with acute renal failure. Seven of 8 cases with severe sepsis were cured with cefoperazone. 1 patient was withdrawn from the study when acute bronchospasm followed a 2 g intravenous dose. 2 of the successfully treated patients had functioning renal transplants, 2 of 3 with severe chronic renal failure were on dialysis and 1 had acute renal failure. Side effects included minor disturbances of liver function in 6 patients (11%), diarrhoea in 7 (13%) and marked alcohol intolerance in one, 4 patients with chronic renal failure developed a coagulation disorder which was corrected with vitamin K. None of the patients showed deterioration in renal function while receiving cefoperazone. Cefoperazone promises to be an effective drug for the treatment of a wide spectrum of severe infections in hospitalised patients including those with impaired renal function.

Airway anesthesia and respiratory response to methylcholine induced bronchoconstriction

P 0.1 and breathing pattern in response to acute methylcholine induced bronchoconstriction were studied with and without previous airway anesthesia in 6 normal subjects. In a randomized cross-over study, on two successive days, the subjects inhaled either 4% lidocaine hydrochloride or isotonic saline for 12 min, and then methylcholine for 3 min. FEV 1, P 0.1, and breathing patterns were measured at baseline and following each inhalation. Baseline values were changed neither by saline, nor by lidocaine, and methylcholine induced the same 18% decrease in FEV 1 after each agent. Bronchospasm was not accompanied by a change in PACO 2. After saline, methylcholine bronchospasm was associated with an increase of P 0.1 from 1.0±0.2 (SEM) to 1.8 cm H 2O±0.3 (SEM) ( P<0.05). During bronchospasm following airway anesthesia, P 0.1 was increased from 1.1±0.2 (SEM) to 1.3 cm H 2O±0.3 (SEM), which was not significant. Comparing bronchospasm after saline to that after xylocaine we observed an increase in Ti after xylocaine, which was correlated with the decrease in P 0.1, suggesting that both were affected by airway anesthesia. We concluded that vagal airway receptors contribute to the increase in inspiratory drive accompanies acute bronchospasm and also may contribute to the regulation of resting breathing pattern during bronchospasm in humans.

Pulmonary Effects of Topical Timolol

Timolol, a beta-adrenergic blocking agent, recently became available for the treatment of glaucoma. We report the occurrence of acute bronchospasm in a previously asymptomatic asthmatic patient following topical use of timolol. Therapy with the drug was discontinued, and four weeks later the patient was challenged with two drops of 0.5% timolol. A 25% decrease in forced expiratory volume at one second (FEV1) was demonstrated at one hour. The fall in FEV1 was even greater (47%) when the patient was rechallenged with four drops. We emphasize the need to avoid topical beta-adrenergic blocking agents in asthmatic patients.