Histamine In Normal Subjects Research Articles

Reduction of allergic skin weal responses by sexual intercourse in allergic patients

Effect of sexual intercourse on allergen- and histamine-induced skin weal responses was studied. In normal subjects, house dust mite or Japanese cedar pollen allergen did not induce skin weal responses, while histamine induced skin weal responses. In contrast, in patients with allergic rhinitis or atopic dermatitis, who were allergic to Japanese cedar pollen and house dust mite, these allergens as well as histamine induced skin weal responses. Sexual intercourse had no effect on skin weal responses induced by histamine in normal subjects. In contrast, sexual intercourse significantly reduced skin weal responses induced by Japanese cedar pollen or house dust mite, while it did not reduce skin weal responses induced by histamine in allergic patients. This is the first report that sexual intercourse reduces specifically allergen-induced responses in allergic patients. These finding may have some implications for the pathophysiological effect of sexual intercourse on allergic diseases.

Topical Salmeterol Reduces Protein Content of Nasal Lavage Fluid in Response to Allergen and Histamine Challenge: Double-Blind Cross-over Placebo-Controlled Studies in Adults

We have studied the effects of topical intranasal β-2-adrenoceptor agonists on nasal airflow resistance (Rnaw) and secretions. Pretreatment with salmeterol (SM) and salbutamol (SB) was given in two double-blind, placebo-controlled studies. In Protocol 1, 15 patients with allergic rhinitis were challenged with a threshold dose of allergen. Rnawand lavage fluid total protein, albumin, mucin, lysozyme, tryptase, histamine, and eosinophil cationic protein (ECP) were measured. In Protocol 2, 20 normal subjects were challenged with ascending doses of histamine and Rnawand lavage fluid total protein and albumin were measured. After allergen challenge, there was a significant, increase in Rnawtotal protein, albumin, and tryptase. SM significantly attenuated the rise in total protein (post-allergen challenge mean 218 mcg/mL, 95% c.i. 16–447; SB 344, 45–641; placebo 365, 105–725: P = 0.036). SM significantly reduced albumin concentration at 30 minutes post-drug (post-histamine challenge geometric mean 17.1 mcg/mL, interquartile range 8.2–29.4; SB 25.1, 15.2–43.0; placebo 24.2, 16.6–37.8: P = 0.027). SM has acute effects on the nasal response to allergen in allergic rhinitis and to histamine in normal subjects. These results imply an effect on glands and blood vessels in vivo that may represent part of the drug's clinical activity.

Effect of inhaled leukotriene B4 alone and in combination with prostaglandin D2 on bronchial responsiveness to histamine in normal subjects.

Effect of inhaled leukotriene B4 alone and in combination with prostaglandin D2 on bronchial responsiveness to histamine in normal subjects.

Temperature and humidity modify airway response to inhaled histamine in normal subjects.

The airway response to inhaled histamine is known to be influenced by various stimuli (e.g., infection, ozone). Temperature (T) has been shown to affect it in vitro. We studied whether T and humidity (H) modify airway response to inhaled histamine in normal subjects. Twelve normal subjects 21 to 46 yr of age (mean age, 29 yr) performed two similar histamine inhalation tests, the only difference being the conditions of the inspired air. One test was done while breathing cold dry air (mean T +/- SEM, -17.3 +/- 1.8 degrees C; relative H, 0%), and the other while breathing warm humid air (mean T +/- SEM, 33.9 +/- 0.5 degrees C; relative H, 100%). Whereas the geometric mean histamine concentration required to produce a 15% fall in FEV1 in the warm humid tests was 22.7 mg/ml, it was 11.9 mg/ml in the cold dry test (p less than 0.01). It is concluded that the T and H of inspired air modify the airway response to inhaled histamine in normal subjects.

Effect of inhaled leukotriene B4 alone and in combination with prostaglandin D2 on bronchial responsiveness to histamine in normal subjects.

The effect of intradermal injection of leukotriene B4 alone and in combination with prostaglandin D2 and E2 and the effect of inhaled leukotriene B4 in combination with prostaglandin D2 were studied in six non-asthmatic men. The intradermal injection of leukotriene B4 (1 microgram) alone caused no immediate or late response in five of the six subjects but greatly potentiated the flare response to intradermal prostaglandin D2 (0.5 microgram) and E2 (0.5 microgram) in all subjects. In contrast, inhaled prostaglandin D2 (6 micrograms) alone and in combination with inhaled leukotriene B4 (12 micrograms) caused no change in the response to inhaled histamine, measured 30 minutes and three and six hours after the inhalation. These findings provide no support for the suggestion that leukotriene B4 has an important role in causing bronchial hyperresponsiveness. The possibility that higher doses of inhaled leukotriene B4 may alter bronchial responsiveness cannot, however, be ruled out.

The relative responsiveness to inhaled leukotriene E4, methacholine and histamine in normal and asthmatic subjects

The relative bronchoconstricting potencies of leukotriene E4 (LTE4) methacholine and histamine have been compared in asthmatic and normal subjects. LTE4 responsiveness in asthmatic subjects, as measured by the dose which produced a 35% fall in specific airways conductance (PD35), ranged from 0.06-24.4 nmol (geom mean 4.1 nmol, n = 20). This was significantly less than the PD35 in normal subjects (range 39.0-370 nmol, geom mean 105 nmol, n= 6; p less than 0.001). There was a correlation between LTE4 and methacholine responsiveness (r = 0.84, p less than 0.001) and between LTE4 and histamine responsiveness (r = 0.79, p less than 0.001). LTE4 was 73 times more potent than methacholine and 112 times more potent than histamine in asthmatic subjects. LTE4 was 20 times more potent than methacholine and 58 times more potent than histamine in normal subjects. LTE4 is a potent bronchoconstrictor agent, and LTE4 responsiveness correlates with both histamine and methacholine responsiveness.

Variability of airway responsiveness to histamine aerosol in normal subjects. Role of deposition.

The purpose of this investigation was to determine if the variability of bronchial responsiveness to inhaled histamine in normal subjects is related to the total dose of histamine deposited in the airways. To test this possibility, we used a new method of histamine challenge that permits calculating the histamine mass deposited in the airways in an attempt to correlate it with the magnitude of the response. Using a standardized breath-holding maneuver, 10 healthy nonsmokers and 10 healthy smokers with normal spirometry inhaled an aerosol generated from a solution containing a fixed ratio of histamine and a small quantity of hematoporphyrin serving as a fluorescent tracer. The mass of histamine deposited was calculated from the measured fluorescence of the inspired and expired aerosol. Forced expiratory volume in one second (FEV1) was measured before and 10 min after inhalation challenge. There was a negative correlation between percent decrease in FEV1 (delta FEV1) and histamine mass deposited in the nonsmokers (r = -0.83, p less than 0.005) and smokers (r = -0.82, p less than 0.005) without a difference between the 2 slopes. The range of delta FEV1 was 7 to 33% and of histamine mass deposited, 0.02 to 0.18 mg in the nonsmokers. The respective values in the smokers were 2 to 30% and 0.02 to 0.17 mg. In 6 subjects in whom dose-response curves were obtained, the mean deposited histamine mass required to decrease the FEV1 by 10% was 0.11 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of prior bronchoconstriction on the airway response to histamine in normal subjects.

We have examined the effect of prior bronchoconstriction on the bronchial responsiveness to inhaled histamine in nine normal subjects. The airway response to increasing concentrations of histamine aerosol was assessed by measurement of specific airways conductance (sGaw) in a body plethysmograph. The threshold provocative dose of histamine needed to cause a 35% fall in starting sGaw (PD35) and the steepest slope of the response were measured from cumulative log dose response curves. Histamine challenges were performed in duplicate after premedication with 0.9% sodium chloride (control) or methacholine aerosol on separate days. The mean starting sGaw did not change significantly after inhalation of 0.9% sodium chloride but methacholine caused a mean reduction in sGaw of 42%. Mean control PD35 values did not differ significantly from mean PD35 values after methacholine. The mean steepest slope of the response after methacoline was 47% lower than the mean control value. There was a significant linear relationship between starting sGaw and the steepest slope for the control and for the methacholine premedicated challenges. The reduction in slope after methacholine was accounted for by the fall in starting sGaw. Because histamine PD35 was not altered by prior bronchoconstriction, it is concluded that the bronchial hyperresponsiveness of asthmatic subjects to non-specific bronchoconstrictor stimuli is unlikely to be a direct consequence of their low starting airway calibre.

The Effect of H1 and H2 Receptor Antagonists on Bronchial Dose—Response Curves to Histamine in Normal Subjects

The Effect of H1 and H2 Receptor Antagonists on Bronchial Dose—Response Curves to Histamine in Normal Subjects