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Effect of deep inspiration on airway conductance in subjects with allergic rhinitis and allergic asthma.

We measured specific airway conductance (Gaw/Vtg) in a body plethysmograph before and after a deep inspiratory maneuver in 8 subjects with allergic rhinitis and 8 subjects with allergic asthma. In hay fever subjects deep inspiration had no effect on Gaw/Vtg if it was performed in the control state; however, when methacholine-induced bronchoconstriction was present, deep inspiration transiently increased Gaw/Vtg. In asthmatic subjects deep inspiration was followed by a transeint fall in baseline Gaw/Vtg in the control state; however, when bronchoconstriction was present, deep inspiration was followed by small and variable changes in Gaw/Vtg in 7 subjects and marked improvement in Gaw/Vtg in 1 subject. In asthmatic subjects the bronchoconstrictor response to deep inspiration performed in the control state is thought to be due to reflex changes in bronchomotor tone mediated by cholinergic (vagal) nerve pathways. Like asthmatic subjects, hay fever subjects, hay fever subjects also possess cholinergic-mediated airway hyperreactivity compared with normals. Our results indicate that, in spite of their increased airway reactivity, hay fever subjects respond more like normal subjects than like asthmatic subjects after a deep inspiratory maneuver.

Adult↗

Toluene diisocyanate pulmonary disease: immunopharmacologic and mecholyl challenge studies.

Selected workers exhibiting clinical "sensitivity" to toluene diiosocyanate (TDI) (wheezing, cough, and dyspnea upon entering a TDI-containing area) were studied for : (1) in vitro TDI-induced leukocyte histamine release; (2) determination of cyclic 3',5' adenosine monophosphate (cAMP) levels of lymphocytes exposed to TDI; (3) effect of TDI on the isoproterenol-induced increase of lymphocyte cAMP levels: and (4) acetyl-beta-methylcholine (mecholyl) inhalation challenge. TDI did not induce histamine release from leukocytes of "sensitive" or "nonsensitive" individuals, nor were lymphocyte cAMP levels affected by in vitro TDI exposure, TDI did, however, diminish in vitro stimulation of cAMP by isoproterenol. This effect, seen with cells of "sensitive" and "nonsensitive" individuals, appeared to be dose-dependent; there were no significant differences between the two groups. When challenged with mecholyl, 7 of 10 "sensitive" but only 1 of 10 "nonsensitive" individuals showed a greater than 20% decrease in FEV1. These results suggest that TDI-induced obstructive airways disorders may be associated with altered beta-adrenergic function.

Administration, Intranasal↗

Effect of histamine and methacholine on nasal airway resistance in atopic and nonatopic subjects. Comparison with bronchial challenge and skin test responses.

Serial nasal, intracutaneous, or bronchial challenges were carried out with solutions containing 2- or 3-fold increments in histamine (H) or methacholine (Meth) concentration until nasal airway resistance (NAR) increased by more than 100%, a large intracutaneous reaction was elicited, or FEV1 decreased by 20% or more. Thirty nonatopic and 48 asymptomatic atopic subjects were studied, the latter group divided into rhinitic patients with and without asthma. Several types of data analysis demonstrated there was no significant difference in the nasal or cutaneous effects of H or Meth between the atopic and nonatopic groups. Comparable results were obtained in a subgroup of 39 subjects (13 normal, 13 atopic, and 13 atopic with asthma) who underwent all six test sequences (i.e., nasal, cutaneous, and bronchial with both drugs). As expected, the asthmatics showed significantly increased bronchial reactivity to both agents. In comparison with Meth, H had a much greater effect on the nasal mucosa and skin than on the bronchi. It is concluded that, contrary to bronchial responses, but in accord with cutaneous reactivity, the nasal responses of nonatopic subjects, atopic persons with allergic rhinitis alone, and subjects with both allergic rhinitis and asthma show no intergroup differences on testing with H or Meth.

Airway Resistance↗

Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate.

Nine asthmatic patients with a mean age of 14 yr received bronchial challenges with histamine and methacholine. The challenges were repeated after inhalation of 80 microgram of SCH 1000 (ipratropium bromide) and 5 mg of chlorpheniramine maleate. The provocation doses which produced a 20% fall in forced expiratory volume in 1 sec (FEV1) and the slopes of the dose-response curves were analyzed. SCH 1000 prevented methacholine-induced bronchoconstriction and chlorpheniramine prevented methacholine-induced bronchoconstriction. There was no significant change in the dose-response curve of histamine after SCH 1000 or in the dose-response curve of methacholine after chlorpheniramine. The findings indicate that the mechanisms and receptor sites involved in bronchial provocation by histamine and methacholine are distinctly different. The histamine response is unlikely to be vagally mediated because histamine-induced bronchoconstriction was not prevented by SCH 1000. Both SCH 1000 and chlorpheniramine caused significant bronchodilatation, suggesting the presence of both histamine- and vagal-dependent bronchomotor tone.

Adolescent↗

Measurements of responsiveness in bronchoprovocation testing.

The relative sensitivity and usefulness of FEV1 and SGaw measurements in determining airway responsiveness to stimuli causing changes in bronchomotor tone depend to a great extent on the population studied. Though neither test provides a great deal of information regarding the site of airway obstruction, when used together they provide a reliable and sensitive indicator of airway responsiveness.

Airway Resistance↗

Inhalation challenge and pharmacologic studies of toluene diisocyanate (TDI)-sensitive workers.

Workers with "sensitivity" to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.

Aerosols↗

Relationship between airways response to allergens and nonspecific bronchial reactivity.

Bronchial inhalation challenges to histamine, methacholine, and at least one antigen were performed on 183 asthmatic patients who previously had received skin tests to at least 16 different antigens. Individuals with a positive skin test and a positive antigen inhalation challenge to the same antigen had lower thresholds of response to both histamine and methacholine. This pattern was statistically significant for mixed trees, mixed grasses, mixed molds, and house dust but not for mixed ragweed. For those individuals who had a negative antigen inhalation challenge, skin test reactivity (positive or negative) alone was not associated with a different threshold of response to histamine or methacholine. Also, a higher percentage of positive antigen inhalation challenges were seen in the group of individuals with a low threshold of response to both histamine and methacholine than in groups with either a moderate or high threshold of response to these chemical agents. The results imply that at least two factors are associated with a positive bronchial inhalation challenge to a specific antigen: nonspecific airways hyperreactivity, as indexed by a methacholine or histamine inhalation challenge, and a positive skin test.

Adolescent↗

Nasal methacholine challenge. A test for the measurement of nasal reactivity.

The aim of this study was to develop a test for the measurement of nasal reactivity. Different concentrations of methacholine were sprayed intranasally, and the nasal secretion and blockage were measured in normal subjects. The simple collection and measurement of secretion was found to be a valuable parameter of mucosal reactivity, while measurement of nasal airway resistance was unreliable, due in part to the presence of secretion in the nasal cavity. The methacholine test had a fairly good reproducibility when the amount of secretion was used as the only parameter. It caused a significantly stronger reaction in women than in men. Patients with perennial rhinitis had a more vigorous response than the controls. It is concluded that the methacholine test may prove useful as a sign of perennial rhinitis and also for the objective evaluation of medication, but further studies are warranted.

Adolescent↗

Evaluation of a patient with cold and cholinergic urticaria.

A-20-year-old male Army paratrooper presented with a history of inducible urticaria associated with exercise as well as cold exposure. Upon evaluation, he not only had a positive ice cube test, but also had a positive mecholyl skin test with numberous satellite lesions and generalized punctate urticaria following exercise challenge. Thus, he appeared to have combined cold and cholinergic urticaria. When mediator release was examined during cold and exercise challenge, histamine release was observed in each instance; a rapid rise and fall of plasma histamine was seen after cold challenge, while a lag phase followed by sustained elevation of plasma histamine was associated with exercise challenge. This represents the fourth reported case of combined cold and cholinergic urticaria and is the first in whom mediator release was assessed. The time-course of histamine release was characteristic of each disorder.

Adult↗

A comparison of the asthmatic response to methacholine and exercise.

The airway responses to methacholine and to exercise challenges were compared in 45 young adults with asthma. The spirometric response to five minutes of treadmill exercise was first documented. On a separate day methacholine dose-response relationships were determined. All asthmatics had an abnormal response to methacholine, and 36 had an abnormal response to exercise. Methacholine sensitivity and exercise-induced asthma were significantly related (r = 0.69, p less than 0.001), but the relationship was nonlinear; the increased response to exercise related to the logarithm of the methacholine response. Between asthmatics with generally unreactive airways, small variation in methacholine sensitivity was associated with large variations in the severity of exercise-induced asthma; between more responsive asthmatics, there was a smaller effect. It is suggested that exercise-induced asthma is dependent on two factors: a stimulus generated during exercise and a response from abnormal bronchi. The bronchial response may be a limiting factor in asthmatics with less responsive airways.

Adolescent↗

Comparison of plasma histamine and cyclic nucleotides after antigen and methacholine inhalation in man.

Serial determinations of plasma histamine and cyclic nucleotides (adenosine monophosphate [AMP] and guanosine monophosphate [GMP]) were performed after inhalation of antigen and methacholine in four groups of subjects. In the first group, consisting of six antigen-sensitive subjects exhibiting bronchospasm after inhalation of ragweed or grass antigen, plasma histamine was elevated within 2 min and persisted for 30 min after inhalation of antigen. Peak histamine levels were between 18 to 80 ng/ml. In the second group, consisting of four nonatopic subjects, neither bronchospasm nor histamine was observed, despite inhalation of the same or 10-fold increased concentrations of antigen. In the third group, consisting of six subjects (three atopic and three nonatopic) exhibiting bronchospasm after inhalation of 2.5 to 10 mg of methacholine, sustained increases of histamine began at 1 min and persisted for 60 min after inhalation of methacholine. In the fourth group, seven subjects (two atopic, five nonatopic) without demonstrable bronchospasm despite inhalation of 2.5- to 10-fold increased doses of methacholine, no histamine was detected in the plasma at any time after inhalation of methacholine. Serial measurements of cyclic nucleotides showed no consistent changes in serum levels of cyclic AMP or cyclic GMP following inhalation challenge. We conclude that serum levels of histamine but not cyclic nucleotides change during bronchospasm induced by either antigen or methacholine.

Adult↗