naloxone and Asthma

This study examined the relationship between defensiveness, as measured by the Marlowe-Crowne Social Desirability Scale (MCSDS), and the perception of an externally applied respiratory resistance among people with asthma. Thirty asthmatic adults breathed through nine levels of inspiratory resistive load. Participants higher on the MCSDS were less accurate than others in psychophysical magnitude estimates of resistive load, and showed a reduced relationship between the physical load and the quality of respiratory sensations associated with exposure to the resistors. Defensive subjects also showed a differentially high increase in correlation between unpleasantness of respiratory sensations and resistance levels after receiving parenteral naloxone. These findings are consistent with the hypothesis that defensiveness may increase risk of asthma morbidity, due to inaccuracy in detecting sensations of dyspnea during asthma exacerbations. The inaccuracy may be caused by elevated endogenous opioids among defensive individuals.

Topics: Adult; Airway Resistance; Asthma; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Perceptual Defense; Self Concept; Sensation; Social Desirability

The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine (MCh). We studied six male asymptomatic asthmatics 18 to 35 yr of age. In a preliminary study we determined the concentration of MCh causing a 60% fall in FEV1 (PC60 FEV1). On two subsequent days, we measured breathing pattern, dyspnea sensation (Borg scale), mouth occlusion pressure (P0.1), and FEV1 before and 10 min after an intravenous injection of either naloxone (0.1 mg/kg) or saline according to a randomized double-blind crossover design. A MCh concentration equal to the PC60 FEV1 was then inhaled, and measurements were repeated 5 min later. Neither placebo nor naloxone affected baseline breathing pattern, P0.1, and FEV1. Naloxone pretreatment did not influence airway response to MCh; the mean percent fall in FEV1 was 65.9 +/- 1.3 and 64.7 +/- 1.2% (mean +/- 1 SE) on the placebo day and the naloxone day, respectively. After MCh inhalation no significant changes in VE, VT, and breathing frequency occurred when patients received placebo. However, P0.1 increased from 1.48 +/- 0.17 to 3.43 +/- 0.70 cm H2O (p less than 0.05), and VT/TI fell from 0.66 +/- 0.08 to 0.52 +/- 0.04 L/s (p less than 0.05). Naloxone pretreatment resulted in an increase in breathing frequency (from 18.2 +/- 1.7 to 22.8 +/- 2.6 breaths/min; p less than 0.05) and VT/TI (from 0.58 +/- 0.06 to 0.74 +/- 0.05 L/s; p less than 0.05) after MCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Adult; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Double-Blind Method; Dyspnea; Endorphins; Humans; Male; Methacholine Chloride; Middle Aged; Naloxone; Random Allocation; Respiration; Respiratory Mechanics

To determine whether morphine sulfate alters the bronchoconstrictive response to inhalation of distilled water, we gave 13 subjects with mild asthma 0.15 mg/kg morphine sulfate or normal saline intravenously, after which they inhaled increasing volumes of nebulized distilled water from an ultrasonic nebulizer. We constructed stimulus-response curves, and by interpolation determined the provocative output of the nebulizer that resulted in a 50% increase in SRaw from baseline (PO50). On a separate day the subjects inhaled 2.0 mg of atropine sulfate 30 min before they inhaled distilled water. We compared the bronchoconstrictive response after morphine and after atropine with the bronchoconstrictive response after saline by determining the ratio of the PO50 values. Atropine was considered effective in inhibiting bronchoconstriction in 7 of the 13 subjects in whom the ratio of PO50 after atropine to the PO50 after saline was greater than 2.0. By similar criteria, morphine was also considered effective in 5 of these 7 subjects. Neither atropine nor morphine was effective in the remaining 6 subjects. By chi-square analysis, we found a positive correlation between the inhibitory effects of morphine and those of atropine (p less than 0.05). In the 5 subjects in whom morphine was effective, naloxone reversed the inhibitory effect of morphine. Atropine caused significant baseline bronchodilation when compared with placebo (normal saline), whereas morphine did not. We conclude that opiate receptor stimulation by morphine causes inhibition of the vagally mediated component of water-induced bronchoconstriction.

Topics: Adult; Airway Resistance; Asthma; Atropine; Bronchi; Female; Humans; Lung Volume Measurements; Male; Morphine; Naloxone; Vagus Nerve; Water

To determine whether the endogenous opioid peptides play a part in the pathogenesis of asthmatic morning dipping, six patients with chronic asthma with a reproducible peak flow pattern of morning dipping were investigated in a double blind, randomised, crossover study of naloxone versus placebo. Naloxone was given as a loading dose of 8 mg followed by a continuous infusion of 5.6 mg/h from midnight until 10 am on two consecutive nights. Naloxone had no significant effect on PEFR, FEV1, or FVC at 6 am. There was, however, an improvement over placebo values in all these indices between the hours of 8 am and 8 pm on the day after the first naloxone infusion in all six patients. This effect was not observed after the second naloxone infusion.

Topics: Adolescent; Adult; Asthma; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Naloxone; Peak Expiratory Flow Rate; Respiration; Vital Capacity

Although respiratory heat loss with cooling of the tracheobronchial mucosa is responsible for the airway obstruction that develops after inhalation of subfreezing air in asthmatics, the mechanism by which airway cooling results in bronchoconstriction is not known. In order to test whether release of endogenous opiate peptides might play a role in mediating this response, asthmatic subjects were studied before and after isocapnic hyperventilation of subfreezing air after the administration of placebo or naloxone, given in a double-blind fashion. Five asthmatic subjects were tested with low-dose (0.8 mg) and 5 with high-dose (10 mg) naloxone given intravenously. Pretreatment with naloxone at either dose did not attenuate the decrease in FVC, FEV1, or FEF25--75 after cold air in comparison with placebo pretreatment. A slightly greater decrease in FEV1 and FEF25--75 after low-dose naloxone than placebo pretreatment can be partially explained by a difference in the temperature achieved during cold air inhalation. We conclude that endogenous opiate peptides are not involved in mediating the bronchoconstrictor response to cold air inhalation in asthmatics.

Topics: Adult; Asthma; Bronchi; Bronchial Spasm; Cold Temperature; Endorphins; Female; Humans; Hyperventilation; Lung Volume Measurements; Male; Naloxone; Premedication; Pulmonary Ventilation; Spirometry

A 6-year-old boy is brought to the emergency department of a level 1 trauma center by emergency medical services (EMS) for presumed asthma exacerbation with subsequent unresponsiveness and transient bradycardia. The initial physician exam was remarkable for an unresponsive child, with diffusely diminished breath sounds bilaterally, accompanied by diffuse wheezing, as well as pinpoint pupils. This last observation led to the recommendation to attempt a dose of naloxone for a possible overdose prior to proceeding with intubation for the altered mental status. The child had a brisk response to the naloxone, was subsequently placed on a naloxone drip, and admitted to the hospital. Initial provider thoughts were that the naloxone had worked on an accidental overdose of over-the-counter dextromethorphan containing medication. These suspicions were later proven incorrect after mass spectrometry yielded a positive methadone presence in the urine. The child was ultimately discharged home with ongoing input from child protective services, without further medical complications. The increased utilization of methadone for the treatment of both opioid withdrawal, as well as for chronic pain management demands, heightened awareness of the clinicians, as cases such as this will continue to appear.

Topics: Asthma; Bradycardia; Child; Diagnosis, Differential; Drug Overdose; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Respiratory Insufficiency

Topics: Administration, Inhalation; Asthma; Heroin; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Adult; Asthma; Codeine; Humans; Hypertension; Male; Naloxone; Narcotic Antagonists; Travel

To determine whether a mu opiate agonist can constrict the human airways, the dose of codeine (C) or histamine (H) producing a 40% decrease (PD40) in specific airway conductance (SGAW) was measured in 17 asthmatic and 14 normal subjects. Then, the subjects were skin tested with C and H, and the effect of naloxone (N) and chlorpheniramine (CP) on PD40-C was assessed. In five asthmatic subjects responding to less than 5 mg (16.6 mumol) inhaled C, SGAW was also recorded after oral administration (30 mg) and pharyngeal spraying (5 mg) of C. PD40-C could be determined in 11 of the 17 asthmatics but in none of the normal subjects. This constrictor effect lasted less than 15 min, was unrelated to resting airway caliber, and required a relatively high bronchial sensitivity to H (PD40-H usually less than 0.2 mumol) and high doses of C (11.93 +/- 12.0 mumol). However, in C responders, PD40-C and PD40-H were unrelated. C-induced bronchoconstriction was blunted by N in a dose-dependent fashion and to a mild and inconsistent degree, by CP. Pharyngeal spraying or oral challenge with C failed to change SGAW. Skin sensitivity to H and C was similar in C-responders and non-responders. In conclusion, large doses of inhaled C constrict the airways of asthmatic subjects highly sensitive to H. This effect seems mediated through (mu?) opiate receptors located bronchially rather than centrally, pharyngeally or in the skin. In C-induced bronchoconstriction H liberation plays a contributory but minor role. Skin and bronchial sensitivity to C are unrelated.

Topics: Adolescent; Adult; Asthma; Bronchi; Bronchoconstriction; Bronchoconstrictor Agents; Codeine; Histamine; Humans; Middle Aged; Naloxone; Receptors, Opioid, mu; Time Factors

We wanted to determine whether 10 mg naloxone inhaled quantitatively could modulate the resting bronchial tone and respiratory response in exercise-induced asthma (EIA). In 11 asthmatic subjects, we measured specific airway conductance (SGaw) and forced expiratory flow (FEF) before and after the inhalation of naloxone or saline. In another 10 asthmatic subjects, we measured SGaw, FEF, and the ventilatory gas exchange, heart rate, and blood pressure responses produced by a treadmill exercise during 3 separate days: without any pretreatment (Day 1) or preceded by the inhalation of either 10 mg naloxone (Day 2) or saline (Day 3). We found that after 10 mg inhaled naloxone only one of 11 subjects bronchodilated, displaying an isolated, reproducible delta SGaw greater than 40% at 30 and 60 min. In the EIA protocol, the cardiopulmonary responses during exercise remained similar on all experimental days, but in seven of 10 subjects (all with %FEV1/FVC greater than or equal to 70% delta SGaw was -60 +/- 11%, + 1 +/- 40%, and -52 +/- 7% during no treatment, naloxone, and saline days, respectively (p less than 0.05). FEF changes were comparable on all days (p greater than 0.05).. (1) consistent with the general role of endogenous opioids, these neurotransmitter/neuromodulators can modulate a stress-related bronchoconstrictor response (EIA), but only very seldom the resting bronchial tone. (2) Naloxone does not blunt EIA through a decrease in the asthmogenic stimulus (i.e., ventilation) or airway caliber change, but presumably through competition with the endogenous opioids released during exercise.

Topics: Administration, Inhalation; Adolescent; Adult; Airway Resistance; Asthma; Asthma, Exercise-Induced; Bronchi; Humans; Naloxone; Pulmonary Ventilation; Rest

Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma.

Topics: Adult; Asthma; Asthma, Exercise-Induced; beta-Endorphin; Double-Blind Method; Endorphins; Enkephalin, Methionine; Female; Humans; Male; Naloxone; Random Allocation

Two female patients revived from fulminant attacks of asthma are described. Ventilatory responses to asphyxia in these patients were 0.70 +/- 0.10 l min-1 % SaO2-1 and 0.64 +/- 0.21 l min-1 % SaO2-1 (mean +/- SEM), respectively. These values were significantly less than the responses of seven normal female subjects (1.54 +/- 0.11 l min-1 % SaO2-1 mean +/- SEM; p less than 0.01). Ventilatory responses to hypercapnia of the two patients were in the low normal range. Dopamine-receptor blockade with prochlorperazine significantly increased the ventilatory response to asphyxia in normal subjects (p less than 0.05 or less for each subject) but did not alter the depressed responses in the asthmatic patients. In one patient, naloxone in a dose of 400 micrograms reversed the decreased ventilatory responsiveness; the response to asphyxia was increased from 0.72 l min-1 % SaO-1 to 1.80 l min-1 % SaO2-1 (p less than 0.01) and the response to hypercapnia was increased from 0.90 l min-1 mmHg-1 to 4.80 l min-1 mmHg-1 (p less than 0.01). Naloxone had no effect in the second asthmatic patient nor in five normal subjects. Defective chemoreceptor responses to chemical stimuli may play a role in sudden death from asthma; endogenous opioids may mediate this disorder of ventilatory control.

Topics: Adult; Asphyxia; Asthma; Bronchodilator Agents; Endorphins; Female; Heart Rate; Humans; Hypercapnia; Male; Middle Aged; Naloxone; Prochlorperazine; Pulmonary Ventilation; Receptors, Dopamine; Respiratory Insufficiency; Resuscitation; Spirometry

Topics: Adult; Angioedema; Asthma; Female; Humans; Middle Aged; Naloxone; Pruritus

A total of 291 diabetics were studied to see whether an asthmatic reaction was associated with facial flushing induced by chlorpropamide and alcohol. Of these patients, 191 reported facial flushing, of whom 12 reported breathlessness as well. Of these 12, five also described wheezing, and respiratory function tests showed them to have asthma. Three of these five patients underwent further tests, which showed that the asthmatic reaction could be prevented by giving disodium cromoglycate and the specific opiate antagonist naloxone. One patient developed wheezing when given an enkephalin analogue with opiate-like activity. Asthma induced by chlorpropamide and alcohol was concluded to be mediated by endogenous peptides with opiate-like activity such as enkephalin.

Topics: Asthma; Chlorpropamide; Drug Synergism; Enkephalins; Ethanol; Forced Expiratory Volume; Humans; Male; Middle Aged; Naloxone