Skin prick test responses to codeine, histamine, and ragweed utilizing the Multitest device

Epicutaneous skin testing is a useful diagnostic tool in evaluating allergic disorders. Utilizing the Multitest device, skin prick test responses to codeine phosphate, histamine phosphate, and ragweed were examined in 56 human subjects. Relationships between the two positive controls, codeine and histamine, and their use as a reference denominator for ragweed reactions were assessed. Ragweed elicited detectable wheals in 15/56. Histamine phosphate (2.75 mg/mL) elicited a positive wheal response in 52/56 subjects, while codeine phosphate elicited a positive wheal in 39/56 and 30/56 subjects at 30 and 3 mg/mL, respectively. Wheal sizes for codeine phosphate at both 30 and 3 mg/mL showed significantly concordant relationships with histamine phosphate-induced wheal sizes (Spearman rho, P = .0084 and .0155, respectively); however the intersubject coefficient of variation was lower for histamine-induced wheal sizes (44%) than for codeine-induced wheal sizes (64% and 65%, respectively for 30 and 3 mg/mL). When a ratio of allergen to positive control reaction size was used to grade ragweed reactions, different patterns were observed using codeine compared with histamine. These results have implications in utilizing codeine phosphate as a positive skin prick test control for allergy testing.     

Relationship between atopy and bronchial responsiveness to histamine in a random population

Although there are theoretical reasons to suggest that atopy might predispose to non-allergic bronchial hyperresponsiveness, previous studies have yielded conflicting results. We assessed this by determining the atopic status and bronchial responsiveness to inhaled histamine in 400 randomly selected college students. An atopy score was determined as the number of "+"s from a standard battery of seven allergy prick skin tests each graded from + to +, and the atopic status was graded as non-atopic (no +'s) mildly atopic (1 to 4 +'s), moderately atopic (5 to 8 +'s), or markedly atopic (greater than 8 +'s). Non-allergic bronchial responsiveness to inhaled histamine was measured with a standardized histamine inhalation test from which the histamine provocation concentration producing a 20% FEV1 fall (PC20) was calculated. The prevalence of bronchial hyperresponsiveness to histamine (PC20 less than or equal to 8 mg/ml) was 10.3% in the entire population. There was a progressive increase from 6.1% in the non-atopic group to 33% in the markedly atopic group (p less than 0.001). In 43 subjects with both measurable atopy score (greater than or equal to 1) and PC20 (less than or equal to 16 mg/ml), a regression of atopy score vs. log PC20 produced a small (r = -0.36) but significant (p less than 0.02) correlation. These data indicate a significant relationship exists between atopic status and increased non-allergic bronchial responsiveness to histamine. Although cause and effect cannot be inferred from this study, it is hypothesized that atopy is one factor, among others, which predisposes to non-allergic bronchial hyperresponsiveness.     

The effect of inhaled nifedipine on bronchial reactivity to histamine in man

We have administered nifedipine by aerosol to six patients with mild asthma to determine whether local administration of a potent calcium channel blocker has any effect on resting airway tone or histamine reactivity. Subjects had their responsiveness to histamine measured and then received either nifedipine, 10 mg in 40% ethanol, or diluent alone in a randomized, double-blind fashion. Specific airway conductance, blood pressure, and heart rate did not change after either inhalation. Histamine reactivity was significantly reduced after the nifedipine aerosol, the geometric mean provocative concentration causing a 35% fall in specific airway conductance, rising from 5.0 to 10.9 mg/ml of histamine (p less than 0.05). In individuals this protective effect was variable but overall was no greater than that observed after sublingual nifedipine. Plasma nifedipine concentrations were measured in two subjects after administration of the aerosol and confirmed that inhaled nifedipine is absorbed across the bronchial mucosa.     

Quantitative skin prick testing

Dose-response curves of histamine- and allergen-induced wheal areas were evaluated in seven normals (defined as negative skin prick test (SPT) to inhalant allergens and no clinical signs of allergy), seven latent allergics (positive SPT without allergic symptoms), and 20 manifest allergics (positive SPT and allergic symptoms). Three concentrations of histamine HCl (1, 10 and 100 mg/ml) and three 10-fold concentrations of nine inhalant allergens (birch, timothy, mugwort, horse, dog, cat, house dust mite, Cladosporium and Alternaria) in concentrations 1,000 10,000 and 100,000 BU/ml were used and linear regression was performed on the skin reactions. Only tests with an SD% less than 40%, a log slope greater than 0.1, and a correlation coefficient greater than 0.95 were accepted. In normals a significantly higher concentration of histamine was needed to elicit a wheal reaction of 2 mm2 (end-point) compared with allergics. Likewise, normals had a significantly higher slope i.e. steeper dose-response curve of histamine than manifest allergics. The slope of the allergen-induced wheal area was significantly higher than the histamine slope. No relation between corresponding slope of histamine and allergens was found (Rho = 0.15). The skin sensitivity equivalent to histamine calculated as the allergen concentration eliciting a wheal equal to histamine showed a median increase of 5-6 fold in allergen concentration by a 10-fold increase of histamine concentration. The highest correlation between the wheal area of a single allergen concentration and the skin sensitivity was found for allergen concentration 100,000 BU.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone

We have studied a 50-year-old white man with chronic urticaria and angioedema who has responded to treatment with cimetidine alone for over 2 yr. In a double-blind, placebo-controlled study, cimetidine alone was at least as effective as chlorpheniramine in relief of urticaria and angioedema. Additionally, cimetidine significantly inhibited (p less than 0.01) the wheal response to histamine when it was compared to placebo. The inhibition of wheal response to histamine by cimetidine was significantly higher (p less than 0.05) than chlorpheniramine. The presence of predominantly H2- rather than H1-histamine receptors in the cutaneous blood vessels may be responsible for the therapeutic effects of cimetidine in this patient.     

Effect of skin pigmentation on the response to intradermal histamine

The effects of injecting histamine phosphate, in serial 10-fold dilutions ranging from 0.0001 to 0.1 mg/ml histamine base, intradermally into three groups of nonatopic healthy volunteers with varying degrees of skin pigmentation were studied. The wheal sizes in the 30 Negroid subjects with darkly pigmented skins were consistently greater than those in both the 30 Caucasian subjects with light skin pigmentation and the 15 mixed Caucasian/Negroid subjects with light brown skins. The overall wheal response was the smallest in the Caucasian subjects. The differences in wheal sizes were greatest between the Negroid and Caucasian subjects for all dilutions, and these differences were statistically significant (p less than 0.005). From this study it appears that skin pigmentation has a profound effect on the wheal response to intradermally injected histamine. It is speculated that this difference in response may be related to the melanin pigment in the skin.     

Skin test reactivity and clinical allergen sensitivity in infancy

We examined the development of skin test reactivity and clinical allergen sensitivity in infancy. Seventy-eight infants of atopic parents were skin prick tested every 4 mo from 4 to 16 mo and an additional 57 of these infants were tested at 20 mo. Wheal diameters were recorded for histamine (1 mg/ml) and specific allergen reactions by use of cow's milk, egg albumen, wheat, and Dermatophagoides pteronyssinus. The histamine mean wheal diameter was significantly lower at 4 and 8 mo compared to the older infants. Infants at 20 mo also had significantly smaller wheals than adult controls. Histamine reactivity was greater in atopic infants at 4 mo compared to nonatopic infants. Reactions to ingested allergens occurred early in infancy but were usually transient. There was a good correlation between skin sensitivity and clinical immediate-food hypersensitivity to the food concerned. In contrast, reactions to the inhaled allergen, D. pteronyssinus, occurred later in infancy, were persistent, and increased in size with age. Although we found no relationship between the acquisition of skin reactivity to D. pteronyssinus and development of the respiratory symptoms of atopic disease during the period of the study, it is possible that inhaled allergen reactivity may be related to respiratory symptoms at later ages. Despite the decreased histamine reactivity in early infancy, skin tests proved reliable markers of clinical disease in ingested but not inhalant allergen sensitivity.     

Reproducibility of Histamine Skin Prick Test

The reproducibility of skin prick test using histamine dihydrochloride 1, 5, and 10 mg/ml was tested by three nurses in five non-atopics in a double-blind trial. The variations day-to-day, within-day, between and for the same tester were calculated. Seventy-five percent of wheal reactions obtained by histamine 1 mg/ml were less than 15 mm2. With histamine 5 mg/ml there were only a few wheals less than 15 mm2 and none at all with histamine 10 mg/ml. The mean coefficient of variation of wheals greater than 15 mm2 was between 20-30%, in contrast to figures between 30-60% with wheals less than 15 mm2. No significant day-to-day or within-day variation was shown concerning histamine wheal areas. It is suggested that histamine dihydrochloride 10 mg/ml should replace histamine dihydrochloride 1 mg/ml as the positive reference in routine skin prick tests and biological standardization.     

Functional depression of H2 histamine receptors in sheep with experimental allergic asthma

We tested the hypothesis that airway hyperresponsiveness to histamine in the allergic sheep is related to functional depression of H2 histamine receptors. Thirteen of 32 sheep responded with bronchoconstriction to inhaled Ascaris suum antigen (allergic sheep), and the remainder served as controls (nonallergic sheep). In the allergic sheep, 50 and 100 breaths of 5% histamine solution increased mean pulmonary resistance (RL) to 235% and 438% of baselines, respectively. The corresponding values in nonallergic sheep were 200% and 211%, indicating a greater response to the higher dose of histamine in allergic sheep. Selective H1-receptor stimulation with 50 breaths of histamine (pretreatment with the H2-receptor antagonist metiamide) failed to enhance the effect of histamine in allergic sheep (mean RL increased to 239% of baseline) whereas it enhanced the histamine response in nonallergic sheep (RL increased to 438% of baseline). Selective H2-receptor stimulation (pretreatment with the H1-receptor antagonist chlorpheniramine) caused histamine to decrease RL by 31% in the nonallergic sheep group; it blocked but did not reverse the histamine effect in the allergic sheep. Similar observations were made in a different group of animals when selective H1- or selective H2-receptor stimulation was produced by 100 breaths of histamine. The cutaneous wheal response to intradermal histamine dilutions of 0.0001. 0.001, 0.01, and 1 mg/ml was similar in both groups. In nonallergic sheep, both chlorpheniramine and metiamide blunted the cutaneous wheal response. In allergic animals, only chlorpheniramine blunted the cutaneous wheal response, whereas metiamide was without effect. We conclude that airway hyperresponsiveness to histamine in allergic sheep is related to a functional depression of H2 receptors and that such a defect is observed both in the airways as well as in the skin.     

Efficacy of ebastine, cetirizine, and loratadine in histamine cutaneous challenges.

BACKGROUND: Few studies have compared the antihistaminic effect of ebastine at 20 mg/day (maximal recommended daily dose) with the effect found for other antihistamines in human pharmacologic models. OBJECTIVE: To compare the inhibition of the histamine-induced skin reaction produced by ebastine (20 mg/day) with that produced by cetirizine (10 mg/day), loratadine (10 mg/day), or placebo in a double-blind, randomized, crossover, placebo-controlled clinical trial. METHODS: Twenty volunteers (10 men and 10 women) received the four treatments once daily for 7 days, with a mean 7-day washout period between treatments. Three intradermal histamine challenges (0.05 mL of a 100 microg/mL histamine solution at 4, 8, and 24 hours after drug administration) were performed at baseline, day 1 (single dose), and day 7 (multiple doses). Wheal and flare areas were measured after 15 minutes. RESULTS: All treatments yielded significant reductions of histamine-induced wheal in comparison to placebo (P < 0.001). Analysis of covariance revealed significant differences between treatments (P < 0.05). Ebastine had a significantly greater antihistaminic effect than did cetirizine or loratadine, except at 4 hours after a single dose versus cetirizine. Further, the effect of cetirizine was similar with single or multiple doses after both 4 and 24 hours, whereas the effect of ebastine showed significant increases in wheal reduction with multiple doses (P < 0.05). No serious adverse events or withdrawals occurred during the study. CONCLUSION: This study shows that ebastine in a 20-mg dose is an effective once-daily antihistamine. Superior efficacy was found in comparison to cetirizine (10 mg) or loratadine (10 mg) on the overall skin wheal response after single and multiple doses.     

Skin reactivity to histamine and codeine in unselected 9-year-old children from Italy, Poland and Libya

BACKGROUND: Previous studies have shown that histamine skin reactivity (the dimensions of a skin wheal elicited by a prick with histamine 10 mg/ml) in unselected school children has increased in Italy during the past two decades and is higher in Italy than in Poland. Hence this variable can probably be influenced by a changing or different lifestyle. The aim of this study was to compare skin reactivity to histamine and codeine (a marker of histamine releasability from mast cells) in schoolchildren from countries with different lifestyles. METHODS: Six previously unstudied unselected populations of 9-year-old schoolchildren (two each from Poland, Italy, and Libya; n = 863 subjects; 49.0% males) were pricked with two concentrations of histamine (10 and 1 mg/ml) and codeine (90 and 9 mg/ml). RESULTS: The higher concentrations of both pharmacologic agents tested yielded significantly different wheal areas in the three countries: Poland < Italy < Libya (histamine, 11.8, 16.1 and 20.7 mm2; codeine, 9.2, 13.2 and 16.2 mm2; p < 0.001 for all comparisons). The lower concentrations elicited almost matching results. Histamine wheal areas correlated closely with areas elicited by codeine in the same individual: angular coefficients of the histamine to codeine regression lines were 0.535, Italy; 0.551, Libya; 0.612, Poland; and 0.581 for the whole population. More histamine was needed to produce a wheal in Poland than in Libya: a 20-mm2 wheal required an injected histamine concentration of about 8.8 mg/ml in Libya, 29.5 mg/ml in Italy and 102.1 mg/ml in Poland. CONCLUSION: More studies are necessary to explain the observed international differences in skin histamine reactivity and their effect on the prevalence of positive allergen skin tests.     

Reliability of allergy skin testing

Background

Percutaneous allergen skin testing remains an established benchmark for diagnosing atopic disease. The reliability of skin testing depends greatly on the performance of allergen extracts used, methods used, and the presence of antihistamine medications.

In vivo airway eosinophil accumulation induced by polymyxin-B reduces bronchial responsiveness in guinea pigs

BACKGROUND: Chronic desquamative eosinophilic bronchitis and bronchial hyperresponsiveness have been considered essential for bronchial asthma. However, it has not been studied whether airway eosinophils enhance or inhibit bronchial responsiveness in vivo. OBJECTIVE: This study was conducted to elucidate the influence of airway eosinophil accumulation on bronchial responsiveness in vivo. MATERIALS AND METHODS: Guinea pigs were transnasally treated with 75 microg/kg of polymyxin-B or vehicle twice a week for a total of 3 weeks. Guinea pigs were surgically cannulated and artificially ventilated 24 h after the last administration of polymyxin-B or vehicle. Ten minutes after the installation of artificial ventilation, ascending doses of methacholine, acetylcholine or histamine were inhaled for 20 s at intervals of 5 min. Subsequent study was conducted 20 min after treatment of 60 mg/kg of indomethacin in the same manner. Final study was conducted in naive guinea pigs after single inhalation of 75 microg/mL of polymyxin B. RESULTS: The proportion of eosinophils in bronchoalveolar lavage fluid significantly increased in guinea pigs treated with polymyxin-B compared with vehicle. Bronchial responsiveness to inhaled methacholine, acetylcholine and histamine was significantly decreased by the polymyxin-B treatment. This protective effect induced by polymyxin B was abolished by pretreatment of indomethacin. A significant increase in bronchial responsiveness was observed after a single inhalation of polymyxin B. CONCLUSION: These results suggest that in vivo airway eosinophils may reduce non-specific bronchial responsiveness through inhibitory or bronchoprotective prostanoids.     

Relative potency of fexofenadine HCl 180 mg, loratadine 10 mg, and placebo using a skin test model of wheal-and-flare suppression.

BACKGROUND: H1-receptor antagonists differ in their ability to produce peripheral H1-blockade. Suppression of histamine-induced flares and wheals is a useful objective test for measuring these differences. OBJECTIVE: To evaluate the relative potency of fexofenadine HCI 180 mg, loratadine 10 mg, and placebo (PBO) in suppressing histamine-induced flares and wheals and compare the onset, duration, and maximum suppression of histamine achieved with each agent. METHODS: Thirty healthy volunteers were enrolled in this randomized, double-blind, single-dose, crossover study. Flares and wheals induced by skin-prick testing with histamine 1.8 mg/mL were measured before treatment, every 20 minutes during the first hour after dosing, and thereafter hourly between 2 and 12 hours and between 23 and 25 hours postdose. RESULTS: Fexofenadine was significantly more effective than loratadine in suppressing the histamine-induced flare response at hours 2 through 7 and 10 through 12 and produced greater flare suppression than did PBO at hours 2 through 25. Onset of flare suppression occurred 2 hours after dosing with fexofenadine and 4 hours after dosing with loratadine. Likewise, fexofenadine was superior to loratadine in suppressing the wheal response from hours 1 through 12 and was more effective than PBO at hours 1 through 12, 24, and 25. Throughout the 25-hour measurement interval, the magnitude of difference in both wheal and flare suppression consistently favored fexofenadine over loratadine. CONCLUSIONS: In a skin test model of wheal-and-flare suppression, fexofenadine showed rapid distribution into the skin compartment with faster onset of action and greater potency vs loratadine.     

Effect of beta adrenergic stimulation and blockade on cutaneous reactivity to histamine.

It has been previously demonstrated that iontophoresis of beta adrenergic agents will alter the size of immediate hypersensitivity skin tests. It was unclear whether this alteration was due to an effect on the dermal mast cell (inhibition of histamine release) or on the cutaneous vasculature (inhibition of capillary permeability). For this reason isoproterenol, propranolol, diphenhydramine as a positive control, and saline as a negative control were iontophoresed onto the forearm of 10 atopic and 10 nonatopic adult subjects. In order to bypass histamine release from mast cells the patients were then challenged directly with histamine by the "prick" technique. The size of the resultant wheals was noted. The data obtained allowed the following conclusions: (1) The atopic group responded to histamine with greater wheal size than the nonatopic group. (2) Iontophoresis of diphyenhydramine effectively reduced the magnitude of the histamine wheal in both groups. (3) Isoproterenol decreased the wheal size in both groups. (4) Propranolol increased the wheal size in only the nonatopic group. (5) The successful modulation of the histamine-induced wheal and flare indicated that these drugs, regardless of their effect on the dermal mast cell, exert a measurable effect on the target organ (vasculature).     

Late asthmatic reactions and changes in histamine responsiveness provoked by occupational agents

The temporal and quantitative relationship between increases in airway responsiveness and late asthmatic reactions provoked by inhalation challenge with occupational agents was studied in nine individuals who underwent a total of thirteen active inhalation challenge tests with one of the following agents: toluene diisocyanate (TDI), maleic anhydride (MA), trimellitic anhydride (TMA), carmine, or colophony (pine wood resin). Airway responsiveness to inhaled histamine (histamine PC20) was measured before and at approximately 3 and 24 h after control and active challenge exposure, when, on all but four occasions, FEV1 was within 10% of pre-challenge values. Significant increases (p less than 0.02) in histamine responsiveness were present at 3 h following challenge exposures which subsequently provoked a definite late asthmatic reaction (FEV1 decrease greater than 15% 3-11 h post challenge). These increases in histamine responsiveness were significantly greater than those at 3 h following the challenges which provoked an isolated early (FEV1 decrease less than 6% 3-11 h post-challenge) or equivocal late asthmatic reaction (FEV1 decrease 6-15% 3-11 h post-challenge) (p less than 0.03). Although histamine responsiveness remained high at 24 h after challenges provoking late asthmatic reactions (p less than 0.05), this was less than the increase at 3 h and not significantly different from the PC20 at 24 h after challenges provoking either single early or equivocal late asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppressive effects of histamine skin reactivity by a nonsedating antihistamine-mequitazine.

The suppressive activity of mequitazine (MQZ) on histamine skin reactivity was evaluated in 29 healthy subjects (age 22-25 years) in a single-blind study. Fifteen subjects received MQZ, at a dosage of 5 mg BID, for 7 days while 14 served as controls. A prick skin test with saline or histamine hydrochloride (1 mg/ml and 10 mg/ml) was performed in duplicate, on both forearms, starting from the baseline day and continuing for 4 days after medication had been discontinued (total of 11 days). The skin-test subject and the reader was unaware of the randomization process. Mean diameters of wheal and flare as well as the skin index scores (after Voorhost) were used in the analysis. Maximal flare suppression (as compared to the baseline values) was observed on day 6 (97% suppression for 1 mg/ml and 54% suppression for 10 mg/ml, p less than 0.01). Suppression of wheal size was significant (19% for 1 mg/ml and 28% for 10 mg/ml) but was not clinically relevant. Suppression of skin index scores was maximal on day 6 (71% for 1 mg/ml and 43% for 10 mg/ml, p less than 0.01). After MQZ had been discontinued, all measurements gradually returned to baseline values and were not different therefrom within 3 days. However, final measurements of wheal and flare were smaller than baseline values (60-94% of baselines). We conclude that MQZ, at the manufacturers's recommended dose of 5 mg BID, significantly suppressed flare size of histamine skin tests and recommend that MQZ be discontinued for at least 3 days prior to performing allergy skin tests.     

Skin Prick Testing and the Use of Histamine References

The skin prick test is a fundamental test in biological allergen standardization and in evaluation of changes in skin sensitivity due to treatment. The allergen concentration eliciting a wheal equal to that produced by histamine 1 mg/ml is generally accepted as the skin sensitivity. Using a standardized quantitative skin prick test, 25 mould allergic patients were tested with quadruplicate determinations of five 10-fold allergen concentrations of highly purified and standardized extracts. Histamine 1 and 10 mg/ml were used as positive references. The 10-fold increase of histamine resulted in a doubling of the histamine reaction and increased the mean wheal diameter from 4 to 7 mm. The correlation between skin sensitivity estimated by histamine 1 and 10 mg/ml is significant, but with a dissociation between the two ways of estimating the sensitivity of 0.25 log step in the low sensitivity range and 1.8 log step in the high sensitivity range (the difference at median sensitivity is 1 log step). No correlation was found between histamine- and allergen-induced wheal area increase, and the discrepancy might be caused by a difference in the endogenous histamine release and/or difference in the number of histamine receptors at different degrees of sensitivity. With the use of median values it is possible to perform biological standardization with histamine 10 mg/ml and interpolate to histamine 1 mg/ml. However, the response in individual patients varies, and because of the small wheal area and the low reproducibility with histamine 1 mg/ml we recommend the exchange of histamine 1 mg/ml to histamine 10 mg/ml as an international positive reference.     

Inhibition of allergen-induced asthma by three forms of sodium cromoglycate

The effect of three forms of sodium cromoglycate (SCG), 20 mg, on allergen-induced early asthmatic responses was examined in ten stable asthmatics. Dose response allergen inhalation tests were performed on five occasions at intervals of from 1 to 2 weeks to determine the provocation concentration producing a 20% reduction (PC20 allergen) in FEV₁. Placebo was given before the first and the last tests to determine the reproducibility of responses to allergen over the study period; reduced responsiveness was observed in eight of the ten subjects. Major changes in levels-of specific serum antibodies of the IgE and IgG classes did not serve to explain the changes in bronchial responses although there was a trend which suggested IgG-related desensitization. The observed changes in bronchial responses and antibody levels illustrate the requirement for tests of reproducibility of responses by the use of placebo controls at the beginning and end of a series of allergen inhalation challenges. SCG as (i) a micronized powder with lactose, (ii) micropellets without lactose, or (iii) an aerosol, were inhaled double-blind, in random order, 5 min before the additional three allergen inhalation tests. PC₂₀ allergen was reduced following SCG in seven subjects; the differences were statistically significant for the group. There was no observed difference in efficacy between the different forms of SCG. In this study, the efficacy of SCG could not be related to age, atopic status, the initial level of allergen-specific IgE antibody, baseline FEV₁, level of bronchial responsiveness to inhaled histamine or an effect of SCG on responsiveness to histamine.     

Prediction of late asthmatic responses to inhaled allergen

Relationships between cutaneous and bronchial responses to allergen were examined in nineteen atopic asthmatics. Allergen inhalation tests elicited an isolated early asthmatic response (EAR) in ten subjects and a dual asthmatic response (DAR) in nine subjects. Ragweed IgE RAST, performed with the sera of those patients tested with ragweed antigen, yielded higher values in all but one patient who experienced DAR than any of the patients with EAR. In one patient with annual symptoms in the ragweed season, positive skin tests with ragweed antigen and DAR to inhaled ragweed extracts, the IgE RAST was entirely negative and the serum IgE concentration was low. Dilutions of the allergen used in each individual for inhalation were also used in skin-prick tests. Early cutaneous allergic response (ECAR) mean wheal diameters were obtained at 10 min and late cutaneous allergic response (LCAR) mean diameters at 6-8 hr. Early asthmatic response (EAR) subjects differed modestly from DAR subjects in the relationships between ECAR and LCAR; in the EAR group, a significantly larger wheal diameter (P < 0.01) was required before an LCAR ensued, however there was some overlap. Once LCAR developed, there was no difference between EAR and DAR groups in the magnitude of the LCAR. There was a trend (not significant) towards a requirement for a higher antigen concentration in the EAR group to elicit an LCAR. In conclusion, correlates of an isolated EAR from inhaled antigen include: (i) a low positive IgE RAST result with the antigen, (ii) ECAR 6 mm or greater with the antigen which does not proceed to a LCAR, and (iii) a high concentration of antigen is needed in skin tests to elicit an LCAR. Correlates of a DAR include:(i) a high IgE RAST result with the antigen, (ii) an ECAR wheal diameter less than 5 mm with the antigen proceeds to a LCAR, and (iii) a low antigen concentration in skin tests elicits an LCAR. The observed correspondence between the tendency to late skin and late airway responses is evidence of a common immunologic basis.