Age-dependency of sensitization to aero-allergens in asthmatics

Skin reactivity (intracutaneous test) to histamine and allergens was studied cross-sectionally in a Dutch asthmatic patient population from childhood to old age (4–75 years). It was found that the histamine skin reactivity rose significantly (p<0.05) during childhood, was significantly higher in the 10–15-year age group, and was constant between 20 and 75 years of age. The mean wheal index (histamine ratio) of all allergens was constant during childhood, and decreased after the age of 25 for grass pollen and house-dust mite and after the age of 15 for the other allergens. The prevalence of a positive skin test decreased with age, except for grass pollen. During childhood the indoor allergens, cat dander and house-dust mite, were the most important, while after the age of 15 sensitivity to an outdoor allergen, grass pollen, increased markedly. At all ages house-dust mite was the most important allergen. After the age of 25 the prevalence of every allergen declines. The prevalence of a positive skin test to Cladosporium was unexpectedly high in childhood (10–40%). It can be concluded that the prevalence of a positive skin test declines with age, except for grass pollen. The degree of sensitization in asthmatics peaked in the age groups between 20 and 40 and sensitivity to indoor allergens developed earlier than sensitivity to outdoor allergens. Clinical aspects Skin tests producing immediate wheal and flare reactions are widely used for the detection of allergy in patients referred for asthmatic prohlems. For good evaluation of a skin test it is important to know the influence of age on skin reactivity. In this study we evaluated the wheal index (histamine ratio) of the skin test and the prevalence of a positive skin test using a set of 6 standardized common aero-allergens and one non-standardized, cross-sectionally, in a Dutch asthmatic patient population (4–75 years). Since standardized allergens were used, the prevalences hetween the different allergens could be compared. It was found that the histamine skin reactivity peaked at the age of 15 and was lower in all other age groups. Therefore, when comparing skin test results in different age groups, it may be important to use wheal indices instead of absolute values. Except for grass pollen the prevalence of a positive skin test decreased with age. During childhood indoor allergens are the most important, while after the age of 15 sensitivity towards outdoor allergens increases. Honse-dust mite is the most important allergen at all ages. Surprisingly, a fungal allergen (Cladosporium herharuni) was found to he of significance in young children (prevalence 10–40%). The prevalence of at least one positive skin test in asthmatics declined with age, while the degree of sensitization (expressed as the mean wheal index) peaked in young adults (20–40 years of age).     

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.     

Increase of skin reactivity to histamine in patients after lung cancer surgery

In 16 patients with lung cancer submitted to radical surgery skin reactivity was studied. Skin prick test was done in all patients with histamine concentration--10 mg/ml and negative control before and after surgery. The longest wheal diameter was measured after 15 min and 30 min. The wheal size was determined as a difference between histamine wheal diameter and negative control diameter (before surgery--after 15 min. 1.53 +/- 1.43 mm., after 30 min. 2.31 +/- 1.77 mm. vs after surgery--after 15 min 3.44 +/- 1.06; p < 0.001, after 30 min 4.25 +/- 1.20; p < 0.001. In patients with lung cancer the significant increase in histamine wheal size was observed as compared with its size before surgery. The lower expression of histamine wheal receptors (mainly H1 skin receptors) is probably caused by cancer suppression. The expression of these receptors increased after tumor excision.     

Changes over 13 years in skin reactivity to histamine in cohorts of children aged 9-13 years

BACKGROUND: Several studies report substantial differences in the prevalence of skin test reactivity to allergens in children from adjacent geographic areas; others report an increased prevalence over time. To find out whether these differences depend on variations in skin reactivity to histamine, we determined the time trend of histamine wheal sizes in successive cohorts of unselected children living in the same area (Viterbo, Italy). METHODS: We conducted three epidemiologic surveys, each including children aged 9 and 13 years. The 1983-7 study investigated 170 children (150 were tested twice); the 1992 study, 158 children; and the 1996 study, 208 children. RESULTS: In both age groups, the mean diameter of the wheal induced by histamine skin prick tests (10 mg/ml) increased significantly over time (9-year-olds: 3.25 mm in 1983, 4.68 in 1992, and 5.89 in 1996; 13-year-olds: 3.89 mm in 1987, 5.18 in 1992, and 6.50 in 1996) (P < 0.001 between subsequent studies). The distribution of the wheal diameters for both ages showed a trend to a right shift in the three successive studies (P < 0.001). The dose-response curves for three histamine concentrations (0.2, 1, and 10 mg/ml) had significantly steeper slopes in 1996 than in 1983-7 (P < 0.001). CONCLUSION: The marked time-related increase in the size of the histamine wheals could help to explain the trend toward an increased prevalence of positive allergen skin test reactions reported during the past years. The causes of increased skin reactivity to histamine remain conjectural.     

Immediate skin test reactivity to common aeroallergens in patients with respiratory allergies: a comparative analysis of allergen-induced skin reactions and their histamine controls

The results of the immediate skin test response to a panel of 16 common aeroallergens performed in a group of 659 consecutive patients with symptoms suggestive of a respiratory allergy were analyzed. A group of 108 healthy individuals served as control subjects. Ninety-four percent of the patients and 87% of the control subjects had at least one allergen-induced reaction (wheal greater than or equal to 2 by 2 mm). The prevalence of positive skin reactions to each aeroallergen was equally high in both groups. However, if a skin reaction is considered as positive only when an allergen-induced wheal is equal or larger compared to the 50% of the wheal obtained with the histamine control in that individual, 70% of the patients had positive skin reactions and only 38% of the control subjects were positive (p less than 0.05). Similarly, the prevalence rates to five aeroallergens (pollen, Fusarium, Mucor, Pullularia, and Curvularia) in the patient group were reduced to those levels observed with the control group, suggesting they are clinically less important. The age and not the sex influenced both the prevalence rates (p less than 0.001) and the mean size (p less than 0.01) of allergen and histamine-induced skin reactions. Lower prevalence rates and mean size values were observed in the youngest group (0 to 9 years). Moreover, there was an inverse relationship between lower skin reactivity with more younger subjects in our patient population. These results indicate that patients and healthy individuals have similar mechanisms for skin reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen

The purpose of this study was to examine the possible influence of the phases of the menstrual cycle on dermal reactivity to skin-prick testing. We studied 15 atopic, menstruating women with seasonal rhinoconjunctivitis and/or asthma, with known sensitivity to olive and parietaria (mean age 25.2 years) and 15 non-atomic, healthy, female controls (mean age 24.7 years). Skin-prick tests with histamine, morphine, and in the atopic group with parietaria/and/or olive, were repeated three times during the same menstrual cycle, corresponding to bleeding (day 1–4), midcycle (day 12–16) and the late progesterone phase (day 24–28). None of the patients had received oral antihistamines or exogenous hormones for at least 1 month prior to testing. Results indicate a significant increase in weal-and-flare size to histamine, morphine, and parietaria on days 12–16 of the cycle, corresponding to ovulation and peak oestrogen levels. This was observed in both atopic and non-atopic women. Differences in skin reactivity to histamine and morphine between the groups were not significant. Therefore, in women, the phase of the menstrual cycle is another factor that may influence skin-test results.     

Circadian variations of histamine binding to lymphocytes and neutrophils and skin reactivity to histamine in atopic and healthy subjects

Introduction Numerous pathophysiological conditions change during 24-hour periods. Histamine, the main mediator in allergic reactions, exerts a multiplicity of pathophysiological actions through binding to specific receptors on effector cells. Nocturnal exacerbation of symptoms occurs in many atopic diseases in which histamine is an important mediator. Nocturnal wheezing is a very common symptom of asthma. The aim of this study was to determine whether the binding of (fluorescein-labeled) histamine to cells participating in allergic-inflammatory processes (lymphocytes, neutrophils) and skin reactivity to histamine undergo circadian changes and to compare these phenomena in atopic asthmatic and healthy subjects. Materials and Methods Blood samples were collected at 8 am, 2 pm, 8 pm, 2 am, and 8 am the next day. Histamine skin-prick tests were performed at the same times. Results It was found that skin reactivity to histamine (wheal, erythema) in healthy subjects underwent significant circadian changes with acrophase at 8 am (wheal) or 8 pm (erythema), the lowest values being at night (2 am, p = 0.017), in contrast to atopics, in whom the highest reactivity was found at night (2 am, p = 0.002). Significant differences in the binding of fluorescein-labeled histamine between day (8 am–2 pm) and night (2 am) were observed for lymphocytes (p = 0.006) and neutrophils (p = 0.018). Conclusions In the asthmatic group these changes were not significant. Circadian changes in both the binding of histamine by effector cells and skin reactivity to histamine were different in healthy and asthmatic subjects, and this may play a role in the pathomechanism, course, and chronopharmacotherapy of atopic diseases.     

Skin prick test to egg white provides additional diagnostic utility to serum egg white-specific IgE antibody concentration in children

BACKGROUND: Levels of IgE antibody to egg white of greater than 7 kIU/L are highly predictive of clinical reactivity to egg, and lower levels often require evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs have inherent risks, and diagnostic criteria indicating high likelihood of passing would be clinically useful. OBJECTIVE: We sought to determine whether the size of the skin prick test (SPT) to egg white adds diagnostic utility for children with low egg white-specific IgE antibody levels. METHODS: A retrospective analysis of clinical history, egg white-specific IgE antibody levels, SPT responses, and egg OFC outcomes was performed. RESULTS: Children who passed (n = 29) egg OFCs and those who failed (n = 45) did not differ significantly in age, clinical characteristics, or egg white-specific IgE levels. There were, however, significant differences between both egg white SPT wheal response size and egg/histamine SPT wheal index. Children who failed egg OFCs had a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P = .003). Children who failed egg OFCs had a median egg/histamine index of 1.00; those who passed had a median index of 0.71 (P = .001). For egg white-specific IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index of 0.65 was associated with a 50% chance of passing. CONCLUSION: In children with low egg white-specific IgE levels, those with smaller SPT wheal responses to egg were more likely to pass an egg OFC than those with larger wheal responses. The size of the egg white SPT response might provide additional information to determine the timing of egg OFC. CLINICAL IMPLICATIONS: The size of the egg white SPT wheal response might provide the clinician with additional information to determine the timing of egg OFC in children with low egg white-specific IgE antibody levels.     

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).     

Interleukin-4-positive mast cells are highly associated with the extent of immediate allergic wheal reaction in the skin

BACKGROUND: In addition to histamine, mast cells contain other potent mediators which can contribute to the allergic wheal reaction in the skin. METHODS: To study the association of tryptase-, chymase-, and interleukin-4 (IL-4)-positive mast cells with the size of the prick-test wheal reaction, 50 sensitive atopic subjects were prick-tested with the cow-dander allergen on the forearm skin, and the wheal area was measured. A corresponding site of intact healthy-looking skin was biopsied and examined enzyme-histochemically for tryptase and chymase. A double-staining method was used to demonstrate the immunoreactivity of IL-4 and chymase inhibitors (alpha1-proteinase inhibitor and alpha1-antichymotrypsin) in mast cells. The levels of total and cow-specific immunoglobulin E (IgE) were measured in serum. RESULTS: The number of tryptase- and chymase-positive mast cells or those containing chymase inhibitors revealed no correlation with the wheal reaction. In contrast, both the percentage and the number of IL-4-positive mast cells showed significant positive correlation with the wheal size per se (P<0.0001), as well as with the ratio of the wheal size by cow allergen to that by histamine control (P<0.003). In addition, tryptase-, chymase-, and IL-4-positive mast cells correlated with total IgE, but not with specific IgE, levels, and they showed no relation to the clinical manifestation of atopic disease, asthma or atopic dermatitis. CONCLUSIONS: The novel finding was that IL-4-positive, but not tryptase- and chymase-positive, mast cells are intimately associated with the extent of the prick-test wheal.     

The effect of food and exercise on the skin response to compound 48/80 in patients with food-associated exercise-induced urticaria-angioedema

Food-associated, exercise-induced urticaria-angioedema is increasingly being recognized. We studied five atopic individuals in whom ingestion of food was followed by exercise-induced urticaria-angioedema. The combined effect of food and exercise on skin wheal response to compound 48/80 and histamine was studied. Symptoms could be reproduced in only four of the patients who performed strenuous exercise after ingestion of food to which they were skin sensitive. When symptoms appeared, that is, after a combination of food and exercise challenge, there was a marked increase in the wheal response to compound 48/80 (greater than 200%) and not to histamine. Food or exercise challenge alone did not induce any significant change in the skin reactivity to compound 48/80 or to histamine. It was concluded that mast cell releasability could be increased when the patient was subjected to combined factors.     

A controlled study of the effect of corticosteroids on immediate skin test reactivity

Limited uncontrolled studies in the past have yielded conflicting results as to the ability of corticosteroids to suppress the immediate wheal-and-flare test. This double-blind controlled study, using 15 atopic volunteers, demonstrated that a one-week course of steroids exerted no significant effect, compared to placebo, on reactivity to ragweed wheal size and the threshold dilution measurements. Reactivity to compound 48–80 and histamine was also unaffected. In vivo effects of the steroid in these subjects was demonstrated by significant eosinopenia.     

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.     

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.     

Increased releasability of skin mast cells after exercise in patients with exercise-induced asthma

The role of lung mast cells in exercise-induced asthma (EIA) is controversial. To investigate whether the skin mast cell releasability is increased after exercise in EIA, 49 young atopic men with or without asthma took part in a free-running test for 6 min and were given skin prick tests using morphine, a mast cell secretagogue, before and after the exercise. The mean diameters of the wheal induced by morphine in patients with EIA were not significantly different from those in patients without EIA before exercise, although the baseline lung function was significantly lower and the airway hyperresponsiveness, the peripheral blood eosinophil count, and the size of the wheal in response to Dermatophagoides pteronyssinus were significantly higher in patients with EIA. However, the differences of the morphine-induced wheal diameter between patients with EIA and those without EIA became significant at 120 min after exercise (p<0.05), while the responses to histamine were not significantly different. These results suggest that exercise increases the releasability of skin mast cells in EIA patients whose asthma/allergy are relatively severe.     

Skin reactivity to codeine and histamine during prolonged corticosteroid therapy

Corticosteroids, used in low to moderate doses for short time intervals, do not suppress immediate percutaneous skin test responses to allergens, compound 48/80, or histamine. During routine skin testing, in our clinic, intradermal injection of codeine (1 mg/ml) and histamine (0.02 mg/ml) are used as positive controls. We had noted that responses to codeine but not histamine are decreased in some patients with asthma who had been receiving prolonged corticosteroid therapy. Therefore, we retrospectively compared skin test responses to codeine and histamine between 25 adult subjects with asthma receiving steroids (group I) and 25 age-matched control subjects (group II). In group I, the mean wheal diameters, induced by codeine but not histamine, were significantly less than diameters in group II. This decreased skin test reactivity to codeine was not due to effects of theophylline also taken by group I subjects, since the skin test reactions of other subjects with asthma, treated with theophylline but not steroids (group III), were not significantly different from reactions in group II. We conclude that prolonged courses of corticosteroids do not appear to alter histamine-induced vascular reactivity in skin but may affect cutaneous mast cell responses by an undefined mechanism.     

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.     

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.     

Correlations of in vivo mediator release with late cutaneous allergic responses in humans : I. Kinetics of histamine release

To evaluate the contribution of mast cell-derived mediators in the late cutaneous allergic response, the duration and quantity of antigen-induced histamine release was compared to the intensity of the antigen-induced skin reactions in atopic volunteers. Chambers containing either pollen extract or buffer were appended to denuded bases for 1 hr and were replaced hourly with buffer for 3 additional hr. These were compared to the extinction dilution skin test titer and to the mean diameters of the 20-minute wheal and induration at 6 and 8 hr after intradermal injection of antigen. Chamber-fluid histamine levels were significantly higher at antigen than at buffer sites throughout the 4 hr. The hourly histamine levels correlated with the size of the induration at 6 and 8 hr but not with the wheal size or skin test titer. We conclude that (1) histamine is released for at least 4 hr at skin sites of antigen challenge as a consequence of prolonged release either from individual or sequentially activated mast cells, and (2) the quantity of histamine released correlates with the intensity of the late-phase skin response. We hypothesize that histamine might be a marker for prolonged release from the mast cell of other mediators that are responsible for the late-phase response.     

Bronchial allergen challenge in subjects with low levels of allergic sensitization to indoor allergens

BACKGROUND: Low skin reactivity to common inhalant allergens is frequently found in asymptomatic individuals as well as in patients with respiratory complaints. However, most studies on bronchial allergen challenge concern patients with high levels of allergic sensitization. The present study was directed to bronchial reactions after allergen challenge in subjects with low skin reactivity to Dermatophagoides pteronyssinus or cat dander. METHODS: Titrated intracutaneous skin tests, skin prick tests, specific IgE assays, histamine release on washed leukocytes, and bronchial histamine and allergen-challenge tests were performed in 20 subjects with an intracutaneous skin test threshold for cat dander (Felis domesticus) or D. pteronyssinus above 0.1 BU/ml (mean wheal diameter in skin prick test with 10000 BU/ml: 4.4mm). Ten of the 20 patients had specific IgE below the detection limit in at least one of the three IgE assays which were done. Fifteen patients had a specific IgE level below 2 kU/I in all three tests. As a positive control group, the same parameters were studied in seven moderately sensitized patients with an intracutaneous skin test threshold below 0.1 BU/ml (mean wheal diameter with 10000 BU/ml: 7.2mm). RESULTS: The 20 subjects with low levels of allergic sensitization had an early decrease in FEV1 of 8.6% (P<0.01) and a mean late decrease of 6.3% (P<0.05). There was a trend for decrease in PC20 histamine 24h after allergen challenge (-0.4 doubling doses, P=0.09). CONCLUSIONS: In this group of subjects with low levels of allergic sensitization, a statistically significant early and late decrease in FEV1 was found. However, the decrease in lung function was small and unnoticed by most patients. The increase in nonspecific bronchial hyperresponsiveness after bronchial allergen challenge did not reach statistical significance in the study group. The results indicate that allergen exposure in patients with low levels of allergic sensitization may lead to airways changes in the absence of acute symptoms.