Methacholine In Subjects Research Articles

Elevation in lung volume and preventing catastrophic airway closure in asthmatics during bronchoconstriction.

BackgroundAsthma exacerbations cause lung hyperinflation, elevation in load to inspiratory muscles, and decreased breathing capacity that, in severe cases, may lead to inspiratory muscle fatigue and respiratory failure. Hyperinflation has been attributed to a passive mechanical origin; a respiratory system time-constant too long for full exhalation. However, because the increase in volume is also concurrent with activation of inspiratory muscles during exhalation it is unclear whether hyperinflation in broncho-constriction is a passive phenomenon or is actively controlled to avoid airway closure.MethodsUsing CT scanning, we measured the distensibility of individual segmental airways relative to that of their surrounding parenchyma in seven subjects with asthma and nine healthy controls. With this data we tested whether the elevation of lung volume measured after methacholine (MCh) provocation was associated with airway narrowing, or to the volume required to preventing airway closure. We also tested whether the reduction in FVC post-MCh could be attributed to gas trapped behind closed segmental airways.FindingsThe changes in lung volume by MCh in subjects with and without asthma were inversely associated with their reduction in average airway lumen. This finding would be inconsistent with hyperinflation by passive elevation of airway resistance. In contrast, the change in volume of each subject was associated with the lung volume estimated to cause the closure of the least stable segmental airway of his/her lungs. In addition, the measured drop in FVC post MCh was associated with the estimated volume of gas trapped behind closed segmental airways at RV.ConclusionsOur data supports the concept that hyperinflation caused by MCh-induced bronchoconstriction is the result of an actively controlled process where parenchymal distending forces on airways are increased to counteract their closure. To our knowledge, this is the first imaging-based study that associates inter-subject differences in whole lung behavior with the interdependence between individual airways and their surrounding parenchyma.

Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma

Airway hyperresponsiveness is a cardinal feature of asthma. Although the modulation of cholinergic neuroeffector transmission may play a role in airway responsiveness, in vivo evidence remains scarce. It is well known that histamine causes bronchoconstriction partly via vagal reflex, whereas methacholine does not. To investigate the significance of modulating neuroeffector transmission, we compared the effect of low-dose salbutamol-a β2-adrenoceptor agonist-on airway responsiveness to histamine with that to methacholine. We enrolled 12 subjects with stable asthma. After screening confirmed that inhalation of low-dose salbutamol (1μg) did not change their basic pulmonary function, subjects underwent measurement of airway responsiveness to inhaled histamine and methacholine with or without pretreatment with low-dose salbutamol, in a randomized, crossover fashion. Airway responsiveness was measured by an astograph by which respiratory conductance (Grs) was assessed by the forced oscillation method during continuous inhalation of histamine or methacholine in stepwise incremental concentrations. Airway responsiveness was calculated as the cumulative dose of bronchoconstrictors that induced a decrease of 35% in Grs. Inhalation of 1μg of salbutamol significantly attenuated airway responsiveness to histamine but not methacholine. This selective attenuation was observed irrespective of disease severity or phenotype, namely atopy or non-atopy. Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma. The present study may provide a novel insight into the bronchoprotective mechanism of β2-adorenoceptor agonist in clinical settings.

Asthma diagnosis and treatment: Filling in the information gaps

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment. Although the diagnosis of asthma is often based on clinical information, it is important to pursue objective criteria as well, including an evaluation for reversibility of airflow obstruction and bronchial hyperresponsiveness, an area with new diagnostic approaches. Furthermore, there exist a number of treatment gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease) in which new direction is needed to improve care. Amajor morbidity in asthmatic patients occurs with exacerbations and in patients with severe disease. Novel approaches to treatment for these conditions will be an important advance to reduce the morbidity associated with asthma.

Airways are More Reactive to Histamine than to Methacholine in Patients with Mild Airway Hyperresponsiveness, Regardless of Atopy

BackgroundThe airway muscles from allergen-sensitized animals in vitro show a heightened response to histamine, but not to carbachol. This study investigated whether the airway responsiveness to histamine in vivo is comparable to that of methacholine in human subjects with varying degrees of atopy.MethodsOne-hundred-and-sixty-eight consecutive adult asthma patients or volunteers underwent bronchoprovocation tests to both histamine and methacholine after determining their blood eosinophil counts, serum total IgE levels and skin test reactivity to 10 common aeroallergens.ResultsThe responsiveness to histamine was significantly related to that to methacholine (r=0.609, p<0.001), but many individuals with a negative methacholine test response showed a positive response to histamine. The histamine-bronchial reactivity index (BRindex) was significantly higher than the methacholine-BRindex in subjects with a positive response to none (n=69, p<0.01) or only one (n=42, p<0.001) of histamine and methacholine, while there was no significant difference in the subjects with positive responses to both of them (n=57). The histamine-BRindex was significantly higher than the methacholine-BRindex in the subjects with mild histamine hyperresponsiveness (n=58, 1.28±0.01 vs. 1.20±0.02, respectively, p<0.001). Both histamine and methacholine responsiveness was significantly related to the atopy markers. However, the histamine-BRindex/methacholine-BRindex ratio of the atopics was not significantly different from that of the non-atopics.ConclusionsThe airway responsiveness to histamine is comparable to that of methacholine in the subjects with positive responses to both histamine and methacholine, but the airway responsiveness to histamine is greater than that to methacholine in those subjects with mild airway hyperresponsiveness, regardless of atopy.

Interleukin-4 and Interleukin-13 Augment the Proliferative Effect of Dexamethasone on Distal Lung Fibroblasts

Airway remodeling in asthma patients has received a great deal of attention as a process whereby significant structural abnormalities of the bronchial wall occur and may lead to a state of fixed, or irreversible, airway obstruction. 1 Hudon C Turcotte H Laviolette M et al. Characteristics of bronchial asthma with incomplete reversibility of airflow obstruction. Ann Allergy Asthma Immunol. 1997; 78: 195-202 Abstract Full Text PDF PubMed Google Scholar Among these abnormalities, a thickening of the subepithelial basement membrane has been described repeatedly, and even has been shown in some studies to correlate with bronchial hyperresponsiveness. 2 Boulet LP Turcotte H Boutet M Correlations between airway inflammation and responsiveness to methacholine in subjects with asthma, rhinitis, reactive airways dysfunction syndrome (RADS), chronic laugh and normals [abstract]. Eur Respir J. 1993; 6: 265S Google Scholar This morphologic change is thought to be due primarily to increased collagen deposition beneath the bronchial epithelium by airway fibroblasts. 3 Brewster CE Howarth PH Djukanovic R et al. Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell Mol Biol. 1990; 3: 507-511 Crossref PubMed Scopus (616) Google Scholar

Relationship between airway sensitivity to adenosine 5′ monophosphate and the shape of the concentration–response curve to methacholine in subjects with allergic rhinitis

The objective of this study was to determine differences in airway sensitivity to adenosine 5′-monophosphate (AMP) between allergic rhinitis subjects with plateau and those without evidence of plateau on the concentration–response curves to methacholine.A total of 51 adults (38 subjects with allergic rhinitis and 13 healthy controls) were challenged with increasing concentrations of methacholine and AMP. The methacholine challenge was terminated when there was a 40% or more decrease in forced expiratory volume in 1 sec (FEV1), whereas the AMP challenge was stopped when FEV1had fallen by more than 20%.A plateau for methacholine was detected in all 13 healthy controls and in 27 patients with allergic rhinitis (AR-plateau group), whereas 11 subjects with allergic rhinitis did not exhibit a plateau (AR-non-plateau group). The median (range) PC20AMP (provocative concentration required to produce a 20% fall in FEV1) value for the AR-non-plateau group was 44·0 mg ml−1(3·3–400·0), compared with 400·0 mg ml−1(12·1–400·0) in the AR-plateau group (P=0·03) and 400·0 mg ml−1in the healthy control group (P=0·007). The proportion of subjects who showed bronchoconstriction in response to AMP was higher in the AR-non-plateau group (73%) than in the AR-plateau group (30%) (P=0·03). However, three subjects with allergic rhinitis who had normal sensitivity to methacholine and plateau showed bronchoconstriction in response to AMP.We conclude that, in subjects with allergic rhinitis, the absence of plateau on the concentration–response curves to methacholine is associated with a higher prevalence and degree of bronchoconstriction in response to AMP. However, the two bronchoconstrictor stimuli were not identifying the same abnormalities of the airways.

Borg scores before and after challenge with adenosine 5'-monophosphate and methacholine in subjects with COPD and asthma.

Dyspnoea differs between subjects with chronic obstructive pulmonary disease (COPD) and asthma, partly because the underlying mechanisms for bronchoconstriction differ. This study investigated the possible role of inflammation and the contribution of clinical variables on dyspnoea in subjects with COPD and asthma. Forty-eight smoking subjects with COPD and 21 nonsmoking subjects with asthma, were challenged with adenosine 5'-monophosphate (AMP) and methacholine. The Borg score was assessed before and after each challenge. Mean increases in Borg score (per percentage decrease in baseline forced expiratory volume in one second (FEV1)) were significantly smaller in COPD than in asthma (p<0.01), values being 0.055 and 0.045 in COPD and 0.122 and 0.093 in asthma respectively. This difference was largely due to the fact that one-third of the subjects with COPD did not increase their Borg score during bronchoconstriction. The increase in Borg tended to be larger during AMP than during methacholine challenge, both in asthma and COPD. Changes in Borg scores were explained by age in COPD and by the Borg score before AMP challenge in asthma. The authors conclude that perception of dyspnoea during adenosine 5'-monophosphate and methacholine induced bronchoconstriction is lower in chronic obstructive pulmonary disease than in asthma and that age contributes to this difference. As adenosine 5'-monophosphate is regarded as an indirect marker of airway inflammation, the results suggest that inflammation is not important because both groups showed similar responses on such provocations.

Effect of Mild Hypoxia on Airway Responsiveness to Methacholine in Subjects With Airway Hyperresponsiveness

The inhalation of hypoxic gas has been reported to enhance the airway responsiveness to methacholine in some animal models. However, the data on humans have so far been conflicting. We attempted to examine the effect of hypoxic gas inhalation on the airway responsiveness to methacholine. We evaluated the airway responsiveness to methacholine by continuously measuring respiratory conductance with the forced oscillation method under normoxia or hypoxia in a single-blind, randomized, crossover fashion (2 days for each). Twelve asymptomatic male volunteers (mean +/- SD age, 27 +/- 4 years) with airway hyperresponsiveness to methacholine. Two of the 12 volunteers had a history of bronchial asthma. The participants inhaled either normoxic or hypoxic gas with continuous inhalation of aerosolized methacholine in incremental doses with a sustained respiratory rate of 15 breaths/min. The arterial oxygen saturation was kept to 90% on the hypoxic days. There were no significant differences in any indexes of airway responsiveness to methacholine (the cumulative dose of methacholine at the threshold and the point of 35% decrease of the respiratory conductance, and the slope factor of the dose-response curve) between the hypoxic days and the normoxic days. The inhalation of mildly hypoxic gas does not enhance the airway responsiveness to methacholine in humans with airway hyperresponsiveness.

Non-specific airway hyperresponsiveness in mono-sensitive Sicilian patients with allergic rhinitis. Its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season.

Initial attempts to evaluate the association between allergic rhinitis and non-specific bronchial responsiveness has produced conflicting results. In fact, some studies showed a strong correlation and other failed to find an association. However, little is known about the effect of natural specific allergen exposure on the bronchial reactivity of mono-sensitive patients with rhinitis in the southern Mediterranean area, in relation to skin reactivity to allergens, total serum IgE levels and blood eosinophils. The significance of the association between allergic rhinitis, and abnormal airway responsiveness with regard to the pathogenesis of asthma is unclear. For this reason, we have studied non-specific bronchial hyperreactivity, in patients with seasonal allergic rhinitis, with reference to the responsible allergen. The aim of the study was to correlate the responsiveness to bronchoprovocation with methacholine in subjects a with allergic rhinitis during and out of the pollen season with total serum IgE and blood eosinophils. Fourty-nine non-smoking patients with clinical diagnosis of allergic rhinitis and mono-sensitive skin-prick tests to pollen allergens were enrolled in the study. Twenty patients suffered from seasonal rhinitis to Parietaria pollen, 15 patients to Gramineae pollen and 14 patients to Olea pollen. In all patients lung function measurements (assessed as response to methacholine), total serum IgE and blood eosinophil counts were measured during and out of the pollen season. During pollen season, 16 out of 49 rhinitis patients demonstrated values of bronchial responsiveness measured as response to inhaled methacholine in the asthmatic range whereas out of the pollen season only eight patients were in the asthmatic range. By analysing the results with reference to the responsible allergen, during the pollen season 15 out of 16 patients were Parietaria-sensitive and out of the pollen season seven out of eight patients. Finally, in Parietaria-sensitive rhinitis bronchial responsiveness significantly correlated, during and out of the pollen season, with total serum IgE and with blood eosinophil counts. Our results are consistent with the hypothesis that Parietaria is more important than Olea and Gramineae as a risk for developing non-specific bronchial hyperresponsiveness. On the whole, present observations provide further evidence that there is an interrelationship of allergen kind, total serum IgE, eosinophil and bronchial hyperresponsiveness suggesting that they may play a role in the development of bronchial asthma in rhinitis patients.

Airway Hyperresponsiveness to Methacholine in Subjects with Spinal Cord Injury

Previously, we found that never-smokers with quadriplegia were hyperresponsive to aerosolized methacholine. To further explore the phenomenon, we compared responsiveness to methacholine in never-smokers with that of smokers and ex-smokers. We also evaluated responsiveness in subjects with high paraplegia (lesions at T-1 to T-6) or low paraplegia (lesions at T-7 and below). We found that smokers and ex-smokers with quadriplegia were hyperresponsive to methacholine (provocative concentration causing a 20% fall in FEV1 = 1.9 mg/mL), and that the response was comparable to that found in never-smokers, revealing that hyperresponsiveness among never-smokers cannot be attributed to preinjury airway hyperreactivity that precluded cigarette use. In contrast, subjects with low paraplegia were not hyperresponsive to methacholine. Among subjects with high paraplegia, the three subjects demonstrating airway hyperresponsiveness had significantly lower FEV1 (percent predicted). The findings support the hypothesis that airway hyperresponsiveness in subjects with quadriplegia represents loss of sympathetic innervation of the lung, thereby leaving intact unopposed bronchoconstrictor cholinergic activity. However, reduced lung volumes in these subjects also suggest the possibility that airway hyperresponsiveness is due to loss of ability to stretch airway smooth muscle by deep breathing.

Magnitude and determinants of short-term tachyphylaxis to methacholine in subjects with symptomatic or asymptomatic airway hyperresponsiveness and in normal controls.

Tachyphylaxis to methacholine has been reported in nonasthmatic subjects. In a recent study on the prevalence of airway hyperresponsiveness (AHR) and atopy, we performed duplicate methacholine inhalation tests at a 60-min interval, in subjects with symptomatic asthma (n = 33), asymptomatic AHR (AAHR) (n = 72) and in a group of normal subjects (n = 130); 135/235 subjects were atopic. All subjects had a respiratory questionnaire, allergy skin prick tests, blood eosinophil counts and determination of total serum IgE level. In asthmatic subjects, PC20 just failed to be significantly higher on a second methacholine challenge (p = 0.09); when they were stratified according to severity of AHR and use of inhaled corticosteroids, we observed a significant increase in PC20 on the second test in asthmatic subjects with mild AHR not using corticosteroids (p < 0.01). In normal controls, PC20 methacholine was slightly increased on rechallenge (p < 0.01) as it was in those with AAHR (p < 0.01). There was no relationship between the magnitude of the change in PC20 and age, sex, baseline airway responsiveness, percent fall in FEV1 on the first challenge, atopic score, blood eosinophil counts and serum IgE levels. In conclusion, tachyphylaxis to methacholine is observed in normal or mild asthmatic subjects not using inhaled corticosteroids and in subjects with AAHR; however, in most subjects this change is of a small magnitude.

Variability of the plateau response to methacholine in subjects without respiratory symptoms.

Interpretation of measurements of limited maximal airway narrowing, or plateau response, requires knowledge of its variability within subjects and between methods. The repeatability of the plateau response to inhaled methacholine with a dosimeter (D) method (maximal dose 210 mumol) and a tidal breathing (T) method (730 mumol), and the agreement of the two methods, were measured in 16 subjects with mild or no asthma. Two tests by each method (D1,D2,T1,T2) were performed in random order over four consecutive days, with a third dosimeter (D3) test one week later. The dose producing a decrease in forced expiratory volume in one second (FEV1) of 10% (PD10) and the plateau were calculated from each dose-response curve. A plateau was reached in all five tests in 12 subjects and in all tests except D3 in 14 subjects. PD10 was inversely related to the plateau (r = -0.95 for D, r = -0.77 for T). The 95% ranges for differences between two determinations of the plateau in a subject were +/- 11.9% (change in FEV1), +/- 19.2%, and +/- 20.3%, estimated from D1-2 and 1-3, and T1-2 tests, respectively. From the same tests the 95% ranges for the difference of a single determination from an individual's true mean value were +/- 8.3%, +/- 13.6%, and +/- 14.3%. The limits of agreement between methods indicated that 95% of the measurements of the plateau by tidal breathing ranged from 15.2% below to 13.3% above those obtained by dosimeter. There was no significant bias between methods. Tachyphylaxis over 24 hours occurred with PD10 but not with the plateau response. The plateau response is a subject characteristic which is independent of the method of inhalation challenge testing. Repeatability of the plateau is low in this group of subjects with low airway responsiveness.

Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma.

To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 +/- 0.2 cm H2O/L/s in RL, 1.5 +/- 0.1 cm H2O/L/s in RC, and 0.8 +/- 0.1 cm H2O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose-response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC35) and a 50% decrease (PC50) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (delta RL), central (delta RC), and peripheral (delta Rp) airways from the baseline values at either PC35 or PC50.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a thromboxane A 2 receptor antagonist (AA-2414) on bronchial hyperresponsiveness to methacholine in subjects with asthma

Bronchial hyperresponsiveness (BHR) to various stimuli is one of the major clinical features of bronchial asthma. In this study, the effect of a thromboxane A 2 (TXA 2) receptor antagonist, AA-2414, on BHR to methacholine was evaluated in 15 patients with asthma. The methacholine inhalation test was performed before and after oral administration of AA-2414 for 4 days (20 or 40 mg/day). The provocative concentration of methacholine producing a 20% fall in FEV 1 (PC 20) was measured as an index of BHR. There was a significant increase in PC 20 ( p < 0.01) from 0.43 (geometric SEM, 1.42) mg/ml to 0.93 (geometric SEM, 1.43) mg/ml after 40 mg/day of AA-2414, whereas baseline values of FVC and FEV 1 were not changed by the treatment. Twenty milligrams per day of AA-2414 did not alter the PC 20 value nor the parameter of baseline pulmonary functions. These findings might support our hypothesis that the subthreshold concentration of TXA 2 in the bronchial tissues, which has no effect on bronchomotor tone per se, may be involved in BHR in asthma. Further studies with more potent and specific TXA 2 receptor antagonists are needed to confirm the conclusion.

Bronchial Hyperresponsiveness to Inhaled Methacholine in Subjects with Chronic Left Heart Failure at a Time of Exacerbation and After Increasing Diuretic Therapy

Cough and wheezing are common findings in left heart failure. However, it is still questionable whether nonallergic bronchial hyperresponsiveness, the hallmark of asthma, is also associated with this condition. In 12 subjects with acute decompensation of chronic postischemic LV failure, we assessed the PC20 methacholine during an episode of acute LV failure and after five to 15 days of intensive diuretic therapy. Weight, arterial blood gases, plethysmographic lung volumes, and expiratory flows were also measured on both visits. Extravascular lung water was estimated indirectly with a radiologic score. During acute decompensation, six subjects had significant airway obstruction and eight had a PC20 less than or equal to 16 mg/ml (significant bronchial hyperresponsiveness). After diuretic therapy, subjects improved significantly, losing an average of 2.2 kg, but they still had chronic LV failure and evidence of an obstructive breathing defect. Although mean PC20 was unchanged, three subjects had significantly improved PC20 after treatment. We conclude that: (1) left ventricular failure is often associated with mild bronchial hyperresponsiveness, although it is not excluded that smoking and the resulting possibility of bronchial obstruction can also play some role; and (2) acute treatment does not generally alter bronchial responsiveness to methacholine, suggesting that chronic LV failure can cause chronic changes to the airways.

Nasal response to substance P and methacholine in subjects with and without allergic rhinitis

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.

Cromolyn sodium inhibits the increased responsiveness to methacholine that follows ultrasonically nebulized water challenge in patients with asthma

We have previously reported that airway responsiveness to inhaled methacholine in subjects with asthma is increased 40 to 60 minutes after challenge with ultrasonically nebulized water. This study reveals that increased responsiveness to methacholine is abolished by administration of cromolyn sodium before the water challenge. The mean dose of methacholine (95% confidence limits) inducing a 20% fall in FEV1 (PD20) was 1.10 mumol (0.43 to 2.80). The PD20 after water challenge was 0.42 mumol (0.17 to 1.01) that was significantly lower (p less than 0.005) than that observed for the initial challenge. Administration of cromolyn before the water challenge abolished this increased responsiveness to methacholine. The mean PD20 was 1.32 mumol (0.47 to 3.68) that was not significantly different from that measured for the initial methacholine challenge. Methacholine responsiveness was unchanged when challenge was performed 40 to 60 minutes after cromolyn alone or after methacholine itself. We conclude that cromolyn abolishes the increased responsiveness to methacholine and probably does so by inhibiting the release of mediators.

Effect of aerosol fenoterol on the severity of bronchial hyperreactivity in patients with asthma.

Beta adrenergic agents given by aerosol decrease the responsiveness of the airways to histamine and methacholine in subjects with asthma, causing a shift of the dose response curve to the right. To find out whether the shift is related to the dose of beta adrenergic agent given and to determine the duration of the reduced responsiveness, eight subjects with asthma were given histamine inhalation tests after inhaled saline and after increasing doses of inhaled fenoterol on different days. The histamine inhalation tests were repeated at hourly intervals for five hours after a selected dose of fenoterol. Fenoterol caused a dose related shift to the right of the histamine dose response curve in each subject and in some the dose response relationship reached the "non-symptomatic range." The shift in the dose response curve was short lived and had returned towards the control position within three hours in all subjects. There was no change in shape of the curves at the time of maximal shift. The results show that inhaled fenoterol greatly reduces the airway responsiveness to histamine, but up to 400 micrograms of fenoterol every four to five hours may be needed to keep the responsiveness of the airways in the non-symptomatic range.

217 The diagnostic significance of increased bronchial responsiveness to methacholine in subjects with rhinitis

217 The diagnostic significance of increased bronchial responsiveness to methacholine in subjects with rhinitis

23. Effect of disodium chromoglycate on inhalation challenge with allergen, histamine, and methacholine in subjects with bronchial asthma: Ung Yun Ryo, M.D., Ph.D., Bann Kang, M.D., and Robert G. Townley, M.D., Omaha, Neb.

23. Effect of disodium chromoglycate on inhalation challenge with allergen, histamine, and methacholine in subjects with bronchial asthma: Ung Yun Ryo, M.D., Ph.D., Bann Kang, M.D., and Robert G. Townley, M.D., Omaha, Neb.