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Quillaja bark (soapbark)--induced asthma.

A 24-yr-old man developed sensitization to Quillaja bark (soapbark) dust at his work place. Within 3 mo of being employed in a factory processing Quallaja bark to produce saponin, he experienced asthma symptoms while handling the bark but only nasal symptoms on being exposed to the purified saponin. Bronchial provocation using Quillaja bark dust resulted in immediate bronchoconstriction as well as faintness, diffuse erythema, and hypotension. Radioallergosorbent test (RAST) using the pulverized crude Quillaja bark was markedly positive, and cross-reactivity between gum acacia and gum tragacanth was demonstrated using this technique.

Adult↗

Tachyphylaxis to inhaled isoproterenol and the effect of methylprednisolone in dogs.

Acute tachyphylaxis can be induced to inhaled isoproterenol (ISO) in anesthetized, closed-chested mongrel dogs. The responsiveness to ISO measured as the percent reduction in methacholine-induced bronchoconstriction was decreased significantly (p less than 0.01) after a 1-hr period of repeated ISO inhalations (ISO-loading). Intravenous administration of methylprednisolone (1 mg/kg) reversed the decrease in responsiveness to ISO.

Animals↗

Bronchial response to methacholine and histamine in monkeys with beta adrenergic blockade.

The possibility has been investigated that propranolol administration could alter bronchial reactivity to methacholine and histamine in monkeys (Macaca fuscata and Macaca fascicularis). The impedance of the total respiratory system was measured by the forced 3-HZ oscillation method through an endotracheal tube. Methacholine and histamine dose-dependently increased the impedance in monkeys irrespective of the route of administration (inhalation of aerosol or intravenous injection). Propranolol treatment increased the bronchial response to intravenously injected methacholine and caused no significant change in the bronchial response to aerosolized methacholine. No marked difference was observed in the bronchial response to histamine due to treatment with propranolol regardless of whether administered by intravenous injection or aerosol challenge.

Adrenergic beta-Antagonists↗

Standardization of inhalation provocation tests: influence of nebulizer output, particle size, and method of inhalation.

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 micrometer aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 micrometer AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV1) by 20% (PC20). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC20. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.

Aerosols↗

Nonallergic rhinitis with eosinophilia (NARES syndrome). Clinical and immunologic presentation.

Fifty-two patients with perennial nasal symptoms of sneezing paroxysms, profuse watery rhinorrhea, and pruritus of the nasopharyngeal mucosa in an "on-again-off-again" symptomatic pattern have been clinically and immunologically characterized. Historically, age at onset of symptoms showed equal distribution from the first through the fifth decades, and the duration of symptoms at diagnosis ranged from 3 mo to 40 yr (mean 9 yr). Trigger factors associated by the 52 patients with the acute onset of nasal symptoms were none or unknown in 22 (42%), weather changes in 16 (31%), odors in eight (15%), and noxious or irritating substances in six (12%). No patients had a history or physical examination consistent with nasal polyposis, bronchial asthma, current sinusitis, nor otitis media. Fifty percent had a negative family history for either chronic rhinitis or bronchial asthma. Nasal secretion smears revealed marked eosinophilia during symptomatic periods. Intradermal skin tests were negative in 49 patients. Serum radioallergosorbent test (RAST) confirmed immediate hypersensitivity skin tests in two of the three patients with positive skin tests. Mean total eosinophil count was 218/mm3. Quantitative immunoglobulins were normal in all patients. Mean serum IgE was 74 IU/ml. Methacholine bronchial challenge was negative in 37 of 37 patients tested. An open aspirin challenge was negative in 13 of 13 patients tested. Spontaneously collected nasal secretions or 0.9% saline nasal washes were analyzed for percent eosinophils, total protein, IgG, IgA, IgE, and RAST to six perennial aeroallergens in 31 of the 52 patients. Neither elevated total IgE nor evidence of specific IgE was found in the study patients' nasal secretions. This report describes 52 patients with symptoms similar to those seen in perennial allergic rhinitis. A characteristic pattern of symptomatic presentation and a paucity of the in vivo and in vitro findings associated with IgE-mediated nasal disease distinguishes this homogeneous disorder from perennial allergic rhinitis.

Bronchial Provocation Tests↗

Differential effects of methacholine and antigen challenge on gas exchange in allergic subjects.

In order to better characterize the differential effects of nonspecific and specific (antigen) bronchial challenge on gas exchange, seven ragweed-sensitive subjects with a history of asthma underwent progressive inhalation challenge with methacholine and ragweed extract on two different days. For comparable severity of bronchospasm (mean specific airway conductance 0.05 sec-1cm-1H2O for methacholine and 0.06 sec-1cm-1H2O for ragweed), there was a greater decrease in mean arterial oxygen saturation after ragweed (4.7%) than after methacholine challenge (2.7%) (p less than 0.05). While this was not accompanied by differences in static lung volumes, the density-dependent index decreased by 19% after ragweed (p less than 0.001) but remained unchanged after methacholine challenge. These results suggest that a greater involvement of peripheral airways in the bronchospastic response is, at least in part, responsible for the greater decrease in arterial oxygen saturation after ragweed challenge.

Adult↗

Bronchial hyperreactivity to methacholine in farmers' lung disease.

Methacholine inhalation challenges were performed in five groups: 14 patients with history of farmers' lung disease (FLD), nine well farmers with precipitating antibodies to Micropolyspora faeni antigen, II normal subjects, 12 asthmatic patients, and 10 patients with interstitial lung disease (ILD) other than hypersensitivity pneumonitis. After calculating the mean areas under the dose-response curves, FLD patients had a significantly greater degree of methacholine sensitivity than did well farmers with M. faeni antibody and normals. However, the methacholine sensitivity of FLD patients was indistinguishable from a group of patients with ILD and significantly less than the asthmatic group. Fifty percent of patients with FLD had positive methacholine challenges (greater than or equal to 20% decrease in their 1-sec forced vital capacity [FEV1] from the control FEV1). Hyperirritable airways was a common finding in FLD.

Antibodies, Fungal↗

Effects of ascorbic acid and indomethacin on the airways of healthy male subjects with and without induced bronchoconstriction.

We have investigated the effects of ascorbic acid (1.0 gm orally) and indomethacin (50 mg orally) on airway tone in the basal state in six health nonsmoking male adults. Airway tone was assessed from measurements of specific airway conductance and flow rates interpolated from partial expiratory flow-volume curves by means of whole-body plethysmography and spirometry, respectively. Neither ascorbic acid nor indomethacin alone produced a significant change in basal tone. However, both the duration and intensity of the bronchoconstriction induced by methacholine aerosol (10 mg/ml for 30 sec) were significantly reduced by prior administration of ascorbic acid. This ameliorating action of ascorbic acid was blocked by ingestion of indomethacin. The results suggest that ascorbic acid exerts its effects by altering the production of a bronchodilator prostaglandin.

Airway Resistance↗

Effect of an inhaled corticosteroid on methacholine airway reactivity.

Methacholine airway reactivity was studied in seven asthmatic patients before and at the end of 4 mo of beclomethasone dipropionate therapy, as well as in a control group. There was no statistically significant change in reactivity in either group, suggesting that a change in airway cholinergic receptor activity is not part of the mechanism of action of corticosteroids in asthma.

Administration, Intranasal↗

Comparison of bronchial responses to prostaglandin F2 alpha and methacholine.

We examined bronchial responsiveness to prostaglandin (PG) F2 alpha to determine its applicability in clinical practice and to compare it with bronchial responsiveness to the pharmacologically dissimilar agent, methacholine. Inhalation tests with two fold increasing concentrations of the two agents were carried out in 19 asthmatic and four normal subjects. The results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 sec (PC20). The range of concentrations required to determine the PC20 was greater with PGF2 alpha (0.0001 to less than 5 mg/ml) than that with methacholine (0.07 to 30.96 mg/ml). Side effects of cough, retrosternal irritation, and expectoration of sputum were more frequent after PGF2 alpha. Repeat measurements in the same subjects showed that response to PGF2 alpha were as highly reproducible (r = 0.98, p less than 0.001) as previously reported with methacholine, and there was a cumulative dose effect (p less than 0.001). PC20PGF2 alpha correlated with PC20 methacholine (r = 0.5, p less than 0.01), but to a lesser degree than was previously demonstrated between histamine and methacholine. The poorer correlation was explained by the results of four subjects tolerant to PGF2 alpha relative to methacholine, three of whom were aspirin (ASA) intolerant; the correlation was much stronger when these subjects were excluded from analysis (r = 0.91, p less than 0.001). The results suggests that (1) PGF2 alpha is not a suitable agent to use in clinical practice to measure nonspecific bronchial responsiveness because of the wide dose range and unpleasant side effects, (2) the bronchial responsiveness of different individuals to PGF2 alpha and methacholine is usually well correlated and is thus unrelated to specific receptor activity, and (3) there is a relative reduction in responsiveness to PGF2 alpha in some asthmatics, particularly those with ASA intolerance.

Adult↗

Development and loss of toluene diisocyanate reactivity: immunologic, pharmacologic, and provocative challenge studies.

Toluene diisocyanate (TDI) sensitivity accompanied by nonspecific bronchial hyperresponsiveness occurs in approximately 5% of occupationally exposed workers. We report the case of a 32-yr-old worker followed longitudinally after removal from isocyanate exposure. TDI reactivity was lost 11 mo after removal from exposure and nonspecific bronchial hyperresponsiveness resolved after 17 mo. Bronchial reactivity to radishes (Raphanus sativus), which developed concurrently with TDI reactivity, was lost 2 yr later. Immunopharmacologic results show that the worker's initial decreased ability of lymphocytes to produce cyclic AMP returned to near normal after 2 yr. IgE antibodies to a human serum albumin tolyl monoisocyanate conjugate were still present at this time.

Adult↗

Methacholine-induced cutaneous flare response: bivariate analysis of responsiveness and sensitivity.

Cutaneous reactions to allergens exhibit a sigmoid dose-response relationship. Available methods for evaluating the allergen skin-test response do not adequately account for the sigmoid curve. Methodologic factors handicap quantitative studies of allergens based on skin-test reactivity. This problem was evaluated with a pharmacologic agonist that mimics cutaneous reactivity. Epicutaneous tests with appropriate concentrations of methacholine were used to provoke flare responses in 84 healthy subjects. A novel hyperbolic tangent model of the sigmoid dose-response curve was used to estimate responsiveness (R) as the midpoint of the sigmoid curve. Sensitivity (C) was estimated as the agonist concentration yielding a flare response equivalent to R. Estimates of sensitivity were independent of estimates of responsiveness (r=-0.0565, p=0.6642). The geometric mean methacholine sensitivity among health subjects was 287 mM/L, and average methacholine responsiveness was 4.9 mm. The mathematic model used in these studies fitted observations surprisingly well (X2(84)=37.044, p greater than 0.95). Differences in methacholine sensitivity and responsiveness related to race, sex, and allergic and/or vasomotor tendencies were detected but were subtle and did not account for a significant portion of the variation among healthy subjects. This model may provide a useful method for quantifying cutaneous immediate hypersensitivity reactions in patients.

Adolescent↗

Methacholine bronchial challenge in children.

Methacholine sensitivity was evaluated in 166 young subjects who had normal resting spirometric values but who presented problems suggesting lower airways hyperreactivity. Fifty-eight patients (35%) did not have significant sensitivity. The diagnosis of asthma was excluded in this subgroup. Forty-one patients (25%) had mild methacholine sensitivity, 49 (30%) had moderate sensitivity, and 18 (11%) had extreme methacholine sensitivity. Many patients who reacted had chief complaints of cough, bronchitis, or other low respiratory-tract symptoms and did not complain of wheezing. Methacholine challenge helped to clarify appropriate therapy in these individuals. One-year follow-up of these patients showed most patients to be continuing the therapeutic regimen that had been prescribed initially. Methacholine bronchoprovocation was a useful adjunct to management of this large outpatient population of children and young adults and deserves attention as a procedure relevant to patients care, not solely as an investigational test.

Adolescent↗

Prolonged asthmatic responses to inhaled methacholine.

The pattern of asthmatic response after inhalation of atropine and methacholine was studied in six adult asthmatics. After pretreatment with atropine, the provocation concentration of methacholine to cause a fall in FEV1 of 20% was increased from 0.66 +/- 2.09 to 94.90 +/- 1.78 mg/ml. In the subsequent 7 hr, four subjects developed prolonged asthmatic responses. These occurred after concentrations of methacholine higher than those used clinically but did not directly relate to the dose of methacholine or to the increase in dose after atropine. In one subject the prolonged response was not accompanied by increased methacholine responsiveness and was not prevented by pretreatment with cromolyn sodium (40 mg). These results show that high doses of methacholine inhaled after pretreatment with atropine can induce prolonged asthmatic responses but the mechanism is unclear.

Adult↗

Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure.

Serial measurements of symptoms, peak flow rates, methacholine bronchial responsiveness, and ragweed-specific IgE antibodies were made before and during the ragweed pollen season in 13 sensitized subjects. Allergen inhalation tests were carried out with aerosols of pollen extract out of season in nine subjects; isolated early asthmatic responses were provoked in four, and dual responses (early followed by late) were provoked in five. During the pollen season all subjects developed hay fever and eight had symptoms of asthma. There was a real increase in methacholine responsiveness during the ragweed season. This increase appeared before or after the occurrence of asthma symptoms and changes in flow rates and was greater in subjects with symptoms in the pollen season, dual responses after allergen inhalation tests, and higher levels of ragweed-specific IgE antibodies. The results confirm the occurrence of seasonal asthma and increases in nonallergic (nonspecific) bronchial responsiveness to methacholine from seasonal pollen exposure. They suggest that the occurrence of symptoms is closely linked to the allergic inflammatory reaction and the induction of increased nonallergic responsiveness.

Adolescent↗

Effect of atropine on the bronchial response of asthmatic subjects to the inhalation of ultrasonically nebulized distilled water.

To determine whether atropine provides protection against the bronchoconstriction that develops in asthmatic subjects after inhalation of ultrasonically nebulized distilled water, we exposed six asthmatic patients to this stimulus with and without pretreatment with atropine (0.04 mg/kg). The mean FEV1 decreased from 3.32 to 2.39 L (-28%) without and from 3.49 to 3.18 L (-9%) with atropine. This protective effect was statistically significant (p less than 0.05), suggesting that cholinergic pathways are involved in the obstructive response to the inhalation of ultrasonically nebulized distilled water.

Adult↗

Relationship between types of asthmatic reaction, nonspecific bronchial reactivity, and specific IgE antibodies in patients with red cedar asthma.

We studied the relationship between specific IgE antibodies, nonspecific bronchial reactivity to methacholine, and the type of asthmatic reaction in patients with red cedar asthma. The level of circulating specific IgE antibodies (expressed as RAST ratios) was not related to the type of asthmatic reaction, the degree of nonspecific bronchial hyperreactivity [expressed by the provocative concentration of methacholine producing a 20% decrease in the forced expiratory volume in 1 sec (PC20)] or the index of reactivity to plicatic acid. On the other hand, methacholine PC20 was found to correlate with the index of reactivity to plicatic acid in the late asthmatic reaction (LAR) and both the immediate and late components of the dual asthmatic reaction (DAR). Development of the LAR is associated with increase in nonspecific bronchial hyperreactivity. Repeated inhalation challenge with plicatic acid in eight patients with LAR resulted in DAR in all. The results suggest that the mechanism responsible for the LAR is associated with an increase in nonspecific bronchial reactivity; furthermore, the immediate component of DAR could also be related to heightened bronchial hyperreactivity.

Adult↗