Comparison of outdoor allergenic particles and allergen levels.

INTRODUCTION: Spore and pollen counts have been used traditionally to determine aeroallergen exposure. Using a liquid based collector and enzyme immunoassays, we have developed methods for measuring airborne allergen concentrations. In this work we test the hypothesis that airborne allergen concentrations are directly related to spore and pollen counts. METHODS: Test samplers used included a high-volume cyclonic liquid impinger (SpinCon) and a standard spore trap (Burkard). Samples were collected on a weekly basis from May to October and were analyzed microscopically for spores and pollen grains. The liquid samples were analyzed by enzyme-linked immunoassay for the presence of allergens from Alternaria, Cladosporium, Aspergillus, oak, fescue, ragweed, and plantain. Specific Alternaria allergens Alt al and GP70 also were measured. RESULTS: Pollen counts for the SpinCon and Burkard collectors were similar, though spore counts were lower with the SpinCon. Detectable amounts of three of the seven allergenic species including fescue, ragweed, and Alternaria were present in air samples. Concentrations of pollens were seen in their respective seasons while fungal allergen levels varied throughout the period. Allergen levels generally agreed with particle counts, however peak allergen levels and peak particle counts for individual species did not correlate well. CONCLUSIONS: At flow rates of 236 L/min, the SpinCon is comparable to the Burkard for counting airborne pollen and spores. Samples collected by the SpinCon permit quantitative determination of allergen levels in outdoor air. The poor correlation between measured airborne allergen and related particles indicates the potential for significant allergen exposure in the absence of identifiable particles in air.     

Immunochemical estimations of allergenic activities from outdoor aero-allergens, collected by a high-volume air sampler

To quantify airborne allergens in amorphus and morphological particles, a survey with collection of aero-allergens on glass fibre filters by means of a high-volume air-sampler (HIVOL) was conducted. In preliminary laboratory experiments we compared various filter elution techniques, and the pulverizing elution technique was found to be optimal with regard to yield and convenience. When a surfactant, Tween 20 (0.5% v/v), was added to the elution buffer, a recovery of 80% could be obtained. Allergens in eluates were analysed by means of an IgG-subclass RAST inhibition assay. This immunochemical method for quantification of airborne allergens was validated, as a high recovery of timothy grass pollen allergens was eluted from air filters, and eluates were shown specific by RAST inhibition. The amount of immunochemically measured airborne timothy and birch allergens collected by means of the HIVOL sampler was highly correlated with pollen counts obtained with a Burkard sampler (pollen trap) situated in the same place.     

Airborne ragweed allergens: association with various particle sizes and short ragweed plant parts

These investigations were undertaken to size airborne particles by use of a high-volume sampler and to measure the short ragweed allergen activity of airborne particles of different sizes. We found both in vitro and in vivo short ragweed allergen activity in particles of all size ranges including greater than 6, 3 to 6, 1.8 to 3, 1 to 1.8, and 0.3 to 1.0 micron in diameter. Furthermore, we investigated various parts of the short ragweed plant as possible sources of allergen. Plant parts collected before, during, and after the pollination season demonstrated significant in vitro and in vivo allergen activities. We demonstrated allergen activity in various plant parts, especially the inflorescence, as late as November 30. Appreciable ragweed allergenic activity was also associated with particles less than 1 micron in diameter. Collectively, these observations suggest persistent ragweed plant debris in different sized particles as a source of allergen in the air before and after the ragweed pollination season. This may contribute to out-of-season symptoms observed in highly ragweed-sensitive individuals.     

Rapidly released allergens from short ragweed pollen: I. Kinetics of release of known allergens in relation to biologic activity

Study of the kinetics of in vitro release of known antigens from short ragweed pollen revealed a slow release of AgE (1.5% to 4% release after 16 min) but a rapid release of other highly allergenic components. The rapidly released allergens in 16-min pollen extracts were found to be mainly highly basic proteins including the well-characterized Ra5 molecule along with several hitherto uncharacterized components. Considering previous data that suggest that particles of a similar size to ragweed pollen grains remain in the nose only about 6 to 8 min following inhalation, it is difficult to explain the apparent anomaly between the high biologic potency of 16-min extracts and their low AgE content. Increase in the pH of the extracting buffer from the physiologically normal nasal pH of 5.5 to 6.5 to about pH 8.0 to 8.5 (characteristically found in rhinitis) increased the proportion of AgE released after 16-min extraction by about 10-fold, suggesting that response to allergens in ragweed and other inhalants may enhance AgE release and thereby aggravate allergic symptoms. Detailed comparison of the allergenic activity of AgE and of 16-min and 4-day ragweed extracts in 38 ragweed-sensitive subjects suggested that allergens other than AgE were together more important than AgE in causing ragweed allergy in most patients, although large patient-to-patient differences in relative response were observed. Our data emphasize the need to reevaluate materials used in both diagnosis and treatment of ragweed allergy. The importance of AgE relative to other ragweed pollen components with respect to induction of allergic symptomatology deserves to be placed in a more balanced perspective.     

Shared allergenic and antigenic determinants in Alternaria and Stemphylium extracts

To develop a model for mold allergen extract standardization, we studied eight commercial Alternaria extracts from various suppliers by a variety of immunochemical and physicochemical techniques, including measurement of Alt-I, a purified allergenic fraction of Alternaria. Wide variations were noted in the allergenic and antigenic potencies of these extracts. Estimates of Alt-I content measured by Alt-I RAST inhibition and by radioimmunoassay correlated significantly (p < 0.05), but Alt-I activity by either method could not be correlated with allergenic potency as measured by RAST inhibition using solid-phase Alternaria. Each test extract produced unique and differing patterns of Coomassie blue-stained bands in isoelectrofocusing gels and in crossed immunoelectrophoresis gels using rabbit antibodies to Alternaria. The optimal method for mold allergen standardization involves a combination of RAST inhibition, isoelectrofocusing, and crossed immunoelectrophoresis techniques, and, if possible, quantitation of individual allergens.     

Trisetum paniceum (wild oats) pollen counts and aeroallergens in the ambient air of Madrid,Spain

BACKGROUND: Madrid has a short but intensive grass pollen season, in which 79% of the total grass pollen load is released from the middle of May to the middle of June. The main objectives of this study were to quantify Trisetum paniceum (wild oats) aeroallergen in the atmosphere in Madrid from February to December 1996 and to correlate the aeroallergen concentrations with grass pollen counts. METHODS: Two different samplers were used to assess allergen exposure; a Burkard spore trap was used to collect pollen grains and a high-volume air sampler to collect airborne particles. A total of 182 air filters were collected and extracted in 1 ml of PBS and analysed by ELISA inhibition, using pooled sera from highly allergic individuals. RESULTS: T. paniceum aeroallergens were detected not only during the grass pollen season, but also before and after. Wild oat allergens had two main peaks of 1 and 1.9 microg/m(3), occurring in late May and July, respectively. The time series analysis established the existence of lags between the two main variables pollen counts and aeroallergen activity. Analysis of the data by the Spearman rank test and linear regression showed a weak correlation between grass allergenic activity and grass pollen counts (Spearman's rho = 0.29). Data obtained from time series analysis demonstrated that grass allergenic activity correlated strongly with current and 5-week-old grass pollen grain counts (r(2) = 0.73). CONCLUSIONS: Wild oats allergenic activity was detected during the entire year and not only during the pollen season. This fact is an important aspect to be considered in the clinical follow-up and treatment of grass pollen-sensitised patients in Madrid.     

Inhalation challenge with ragweed pollen in ragweed-sensitive asthmatics

We reexamined the ability of inhaled ragweed pollen to induce bronchoconstriction in ragweed-sensitive asthmatic patients using a turbo-inhaler to administer pollen quantitatively. Adult subjects were selected for study on the basis of fall season asthmatic attacks, positive skin test, histamine release, RAST, and bronchial challenge responses to ragweed extract. Not one of 12 such subjects had any bronchial response to oral inhalation of whole pollen grains even when the dose was increased to 7640 pollen grains (more than the estimated maximum daily exposure in season), whereas nasal challenge by the same method produced brisk hay fever responses without bronchospasm. On the other hand, when the pollen was ground to fragments with a size range of 1 to 8 micrometers, oral inhalation produced a 35% fall in airways conductance in six of seven subjects in doses ranging from 59 to 20,000 pollen grain equivalents. Atropine pretreatment did not modify the response to pollen fragments, making an irritant response unlikely. These data, coupled with earlier observations that no more than a few pollen grains penetrate further than the larynx, raise further questions about the role of whole ragweed pollen in fall asthma in allergic patients. In addition, ragweed-allergic asthmatics appear not to have their symptoms at the time of maximum pollen load in the air. We believe that small-particle allergens other than ragweed pollen should be considered in most cases of fall seasonal asthma.     

Late summer and fall (March-May) pollen allergy and respiratory disease in Northern New South Wales, Australia.

BACKGROUND: Many people in the subtropical Northern Rivers area of New South Wales, Australia, blame the pollen of Tibouchina tree, which flowers at the same time as ragweed, Bahia grass and Bermuda grass, for hayfever and asthma exacerbations during fall between March and May. OBJECTIVES: To determine whether Tibouchina pollen is allergenic. To determine whether airborne ragweed pollen is present in this region for sufficient length of time and concentration to cause fall respiratory symptoms, and to determine if Bahia grass and Bermuda grass are associated with fall respiratory symptoms. METHODS: Pollen and Alternaria spores were monitored using a Burkard 7-day spore trap. Two hundred and six volunteers in the Northern Rivers area filled in questionnaires before skin prick tests (SPT) were performed with a panel of skin testing extracts. RESULTS: One hundred fifty-three (74.3%) subjects were atopic and reacted to one or more aeroallergens. Seventy were SPT positive to ragweed, OR 3.36 (CI 1.03 to 12.15) and 11 to Tibouchina (OR incalculable). Fifty of the 70 ragweed-positive subjects had fall hayfever or exacerbations of hayfever and/or asthma, OR 23.4 (CI 8.90 to 64.00). Eleven subjects were SPT positive to Tibouchina extract. There was a statistical association between Bermuda grass and hayfever, but not asthma OR 13.44 (CI 1.85 to 27.04). CONCLUSIONS: Ragweed pollen was present for a sufficient length of time and concentration to sensitize and provoke fall hayfever and asthma exacerbations. Tibouchina pollen is an aeroallergen causing mild-to-moderate allergic symptoms in a few people. There is an association between Bahia grass and asthma in children, and between Bermuda grass and allergic rhinitis in adults.     

Detection of Parietaria judaica airborne allergenic activity: comparison between immunochemical and morphological methods including clinical evaluation

Abstract. Airborne pollen grains und small plant particles of respirable size are the main causes of rhinitis and asthma in pollinosis patients. Consequently, it could be useful to quantify atmospheric variations in these biological aerosols and their allergenic activity as a basis for establishing correlations with the clinical symptoms in these allergic subjects. Our study was conducted in Naples from May to August 1992 and from May to August 1993 and concentrated on Perietaria judaica (Par j ) the most important hay fever-provoking plant in southern Italy. The aim of this study was lo evaluate the day-to-day variation in counts of Par j. pollen, the day-to-day variation in allergenic activity specific for this plant, and to relate these two variables to symptom scores in patients with respiratory allergy to Par j. The airborne pollen grains were collected by a Hirst-like volumetric trap and examined through an optical microscope, while the allergenic activity of particles trapped on glass fibre filters in a high volume air-sampler was determined by immunochemical assay. The two devices were placed on the flat roof of the "A. Cardarelli" Hospital. The results of this preliminary study suggest that both methods could have useful clinical relevance, since these two biological parameters were significantly correlated with the symptom scores of allergic patients. However, pollen count with morphological quantification of grains/m³ of air is a more simple technique.     

Reactivity of ragweed allergens with IgE antibodies. Analyses by leukocyte histamine release and the radioallergosorbent test and determination of cross-reactivity.

Five distinct proteins with allergenic activity have been isolated from short ragweed pollen. We initially tested three of these, AgE, AgK, and Ra3, for reactivity with IgE antibodies by leukocyte histamine release and by the radioallergosorbent test (RAST). We found highly significant correlations between the reactivities of these allergens by leukocyte histamine release and by the RAST, consistent with the view that both procedures detected comparable allergenic activity. We next tested the allergenic cross-reactivity of all five ragweed allergens. AgE, AgK, Ra3, Ra4, and Ra5, by RAST inhibition. With solid-phase AgE the only nonhomologous inhibitor was AgK, which cross-reacted weakly and required a 140-fold mass excess of AgK compared to AgE. With solid-phase AgK both AgK and AgE produced significant inhibition; AgE was slightly more potent than the homologous AgK, Ra3 and Ra5 were allergenically unique, because only the homologous allergen produced 50% inhibition. Ra4 was weakly inhibited by AgE, Ra3, and Ra5 when these allergens were added in 300- to 5---fold mass excesses; this weak inhibition may represent either cross-reaction or cross-contamination. We found that RAST inhibition could be used as an assay for the individual ragweed allergens and we demonstrated the presence of all of the allergens in a whole ragweed extract. The sensitivity of the RAST inhibition assay ranged from 10 ng to 100 ng for 50% inhibition. Finally, the solid-phase ragweed allergens were used to determine the frequency of elevated IgE antibody levels in 65 patients with ragweed hay fever. Virtually all of the patients reacted with AgE (97%), while 88% reacted with AgK, 51% reacted with Ra3, 28% reacted with Ra4, and 17% reacted with Ra5. These results highlight the usefulness of the RAST as a specific and sensitive tool for immunochemical studies of allergens.     

Immunochemical and physicochemical characterization of commercial Altemaria extracts: a model for standardization of mold allergen extracts

To develop a model for mold allergen extract standardization, we studied eight commercial Alternaria extracts from various suppliers by a variety of immunochemical and physicochemical techniques, including measurement of Alt-I, a purified allergenic fraction of Alternaria. Wide variations were noted in the allergenic and antigenic potencies of these extracts. Estimates of Alt-I content measured by Alt-I RAST inhibition and by radioimmunoassay correlated significantly (p < 0.05), but Alt-I activity by either method could not be correlated with allergenic potency as measured by RAST inhibition using solid-phase Alternaria. Each test extract produced unique and differing patterns of Coomassie blue-stained bands in isoelectrofocusing gels and in crossed immunoelectrophoresis gels using rabbit antibodies to Alternaria. The optimal method for mold allergen standardization involves a combination of RAST inhibition, isoelectrofocusing, and crossed immunoelectrophoresis techniques, and, if possible, quantitation of individual allergens.     

Index to volume 66

Eighty ragweed-sensitive patients in four cities were recruited to study the safety and efficacy of partially purified, polymerized whole ragweed (PRW) as an improved form of immunotherapy. Groups of 20 patients in Chicago, Boston, Memphis, and St. Louis had blood drawn for immunologic studies before and after the 1978 and 1979 ragweed seasons and completed detailed daily symptom score sheets each day of the 1978 and 1979 ragweed pollen seasons. Beginning in March, 1979, all patients except one received 15 weekly injections of PRW totaling 50,000 protein nitrogen units (PNU) and containing about 500 μg ragweed AgE. One patient received 25,000 PNU. Symptom score indices of the posttreatment 1979 season were compared with those from the pretreatment 1978 season and also with the scores of similar groups of ragweed-sensitive patients in each city treated only with medication for symptomatic relief during the 1979 season. Local reactions to polymerized ragweed immunotherapy were minimal. No abnormalities in complete blood count, erythrocyte sedimentation rate, chest x-ray film, urinalysis, or rheumatoid factor occurred in the immunotherapy-treated groups. Total serum antibody binding of ragweed AgE increased 12-fold following immunotherapy. When compared either with their 1978 untreated group scores or when compared with scores from the untreated group in each city in 1979 (control group), the symptom score indices of the immunotherapy-treated groups in 1979 were significantly improved. PRW is efficacious in the treatment of ragweed hay fever and can be administered more safely and in higher doses with fewer injections than conventional extracts. It represents an improved form of immunotherapy.     

A multi-institutional trial of polymerized whole ragweed for immunotherapy of ragweed allergy

Eighty ragweed-sensitive patients in four cities were recruited to study the safety and efficacy of partially purified, polymerized whole ragweed (PRW) as an improved form of immunotherapy. Groups of 20 patients in Chicago, Boston, Memphis, and St. Louis had blood drawn for immunologic studies before and after the 1978 and 1979 ragweed seasons and completed detailed daily symptom score sheets each day of the 1978 and 1979 ragweed pollen seasons. Beginning in March, 1979, all patients except one received 15 weekly injections of PRW totaling 50,000 protein nitrogen units (PNU) and containing about 500 μg ragweed AgE. One patient received 25,000 PNU. Symptom score indices of the posttreatment 1979 season were compared with those from the pretreatment 1978 season and also with the scores of similar groups of ragweed-sensitive patients in each city treated only with medication for symptomatic relief during the 1979 season. Local reactions to polymerized ragweed immunotherapy were minimal. No abnormalities in complete blood count, erythrocyte sedimentation rate, chest x-ray film, urinalysis, or rheumatoid factor occurred in the immunotherapy-treated groups. Total serum antibody binding of ragweed AgE increased 12-fold following immunotherapy. When compared either with their 1978 untreated group scores or when compared with scores from the untreated group in each city in 1979 (control group), the symptom score indices of the immunotherapy-treated groups in 1979 were significantly improved. PRW is efficacious in the treatment of ragweed hay fever and can be administered more safely and in higher doses with fewer injections than conventional extracts. It represents an improved form of immunotherapy.     

Antigenic activity of nonpollen parts (leaves and stems) of allergenic plants (Parietaria judaica and Dactylis glomerata)

In patients with respiratory allergy to pollen it is common to correlate the onset, duration and intensity of clinical symptoms with the count of atmospheric allergenic pollen grains. Pollen counts, however, may not reflect the total airborne allergen exposure since previous data suggest that pollen allergens may also be carried in microaerosol suspensions. These microdroplets may penetrate deeply into the airways, where pollen grains are too large to penetrate, eventually inducing asthma. The origin of these allergenic aerosols is still uncertain. We investigated whether antigenic activity is present in vegetative parts of allergenic plants. We have used extracts from leaves and stems of Parietaria judaica and Dactylis glomerata to evaluate patients with allergic sensitization to pollen allergens of these plants (19 grass-sensitive patients and 23 Parietaria sensitive). By using skin prick testing and RAST to stem and leaf extracts other than pollen extracts we observed that most patients sensitive to grass or Parietaria pollen had small responses to extracts of stem or leaf. We conclude that allergenic components are present throughout most of Parietaria judaica and Dactylis glomerata plants, most highly concentrated in the pollen but present in the leaves with a trace in the stems.     

Lymphocyte responses to purified ragweed allergens in vitro: I. Proliferative responses in normal,newborn, agammaglobulinemic,and atopic subjects

To evaluate cell-mediated immune responsiveness to pollen allergens in atopic subjects, we studied the deoxyribonucleic acid (DNA) synthetic responses of their cultured lymphocytes to purified ragweed antigens E, K, and Ra-3. Since lymphocytes from some highly ragweed-sensitive subjects gave poor proliferative responses when harvested on day 6, we undertook a series of dose-response and time-course studies in atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed-sensitive atopic adults (8 immunotherapy treated, 11 untreated); 13 nonatopic controls; 4 newborns, and 9 agammaglobulinemic patients. The geometric mean of peak response counts per minute in all 45 subjects was 21,163 and in unstimulated cultures was 2,416 (p = < 0.0001). The mean day on which the maximal responses occurred was 8.7, and the mean dose eliciting the maximum responses was 59 μ/ml. Statistical comparisons of the stimulated culture data revealed no significant intergroup differences. The finding of vigorous responsiveness to these purified pollen allergens by lymphocytes from nonatopic normal, newborn, and agammaglobulinemic subjects suggests that ragweed pollen antigens are either ubiquitous and lead to cell-mediated responsiveness in all subjects with intact cell-mediated inmunity, or that they may have mitogenic properties in addition to their known antigenic properties.     

Diagnostic tests in ragweed hay fever. A comparison of direct skin tests, IgE antibody measurements, and basophil histamine release

In 87 patients with both spring and fall hay fever symptoms the radioallergosorbent test (RAST) technique for specific IgE antibodies to ragweed was compared with basophil histamine release and direct intradermal skin testing by the threshold dilution technique. The three techniques gave good agreement except with the leastsensitive patients, some of whom had a positive skin test but undetectable histamine release or IgE antibodies. Twenty-one patients who were highly sensitive to ragweed as measured by all three techniques were followed without specific immunotherapy. There was significant agreement between the level of positivity of all three tests and the symptom index obtained during the ragweed season. In 14 of the 21 patients there was a significant correlation between daily ragweed pollen counts and daily symptom indexes during the season. On the other hand, among the 16 least-sensitive patients (as judged by histamine release) the correlation between daily ragweed pollen counts and symptom indexes was significant in only 3 patients. Other significant allergens could not be identified in the latter group, and the cause of their symptoms is not clearly identified but appears not to be ragweed. The RAST is a quantitative technique that gives diagnostically useful information in ragweed hay fever, although not significantly different from basophil histamine release or carefully performed skin testing. The convenience to the patient may, however, offer a noticeable advantage.     

Immunochemical quantitation, size distribution, and cross-reactivity of lepidoptera (moth) aeroallergens in southeastern Minnesota

With an immunochemical method, we analyzed outdoor air samples during a 3-year period for concentrations of the predominant local species of moth, Pseudaletia unipuncta (Haworth). Airborne particulates were collected on fiberglass filter sheets with an Accu-Vol sampler located 1.5 m above ground on the southeastern Minnesota prairie. Filter eluates analyzed by RIA inhibition contained concentrations of moth protein peaking in June and August to September of each year, with levels comparable to reported immunochemically measured levels of pollen and mold allergens. These peaks also corresponded with total numbers of moths captured in light traps. Moth-allergen activity was distributed in particle sizes ranging from 0.8 to greater than 4.1 micron when sized samples were obtained by use of an Andersen cascade impaction head. By RIA inhibition, there was cross-reactivity between P. unipuncta and insects of different genera, families, and orders, but not with pollens or molds. Forty-five percent of 257 patients with immediate positive skin tests to common aeroallergens had positive skin tests to one or more commercially available whole body insect extracts. Of 120 patients with allergic rhinitis believed to be primarily caused by ragweed sensitivity, 5% also had elevated specific IgE to moths. We conclude that airborne concentrations of Lepidoptera can be measured immunochemically and that moths may be a seasonal allergen in the United States.     

Rapidly released allergens from short ragweed pollen: II. Identification and partial purification

We have identified several basic allergens in 16-min extracts of short ragweed (Ambrosia elatior) pollen and obtained a partially purified fraction (G50 II) using a combination of ion-exchange (CM-Sephadex C25) and gel-filtration (Biogel P30 and Sephadex G50) procedures. G50 II was allergenically and antigenically distinct from known allergens antigen E, Ra3, and Ra5. It gave a highly symmetrical peak on Sephadex G50 (fine), corresponding to a molecular weight of 11,500 daltons, and a single band on SDS polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. However, two cathodic antigens were detectable by both agarose electrophoresis and crossed immunoelectrophoresis. Allergenic activity of G50 II, assessed by puncture testing in ragweed-sensitive subjects, showed a characteristic pattern of response independent of patient response to AgE, Ra3, and Ra5. The major antigenic and allergenic component of G50 II is designated Ra6.     

Allergen carriage by atmospheric aerosol: II. Ragweed-pollen determinants in submicronic atmospheric fractions

Outdoor air was drawn by a vacuum system through a 0.8 μm molecular membrane filter and a back-up, refrigerated condenser from 8 A.M. to 5 P.M. daily during the 1982 ragweed-pollen season. Sample sets from each day were collected and stored separately. Condensate was collected in a freezing jacket, thawed, refiltered through a 0.45 μm filter, and lyophilized. Reconstituted condensates evoked wheal-and-flare skin reactions in a ragweed-sensitive individual and produced significant inhibition in an IgG-ELISA system by use of ragweed-pollen protein or ragweed antigen E conjugated to polystyrene microtiter plates, pooled serum of patients on ragweed immunotherapy, and alkaline phosphatase-labeled anti-human IgG. Earlier, in 1983 in this Journal, we reported the presence of airborne ragweed-pollen antigen in aerosol fractions below 5 μm. The present data demonstrate similar activity in filtrates well below the micronic range. Furthermore, these antigenic properties are substantially associated with atmospheric water vapor-either naturally or as a readily-induced result of the collection procedure. These results suggest that naturally occurring mists, although free of native particulates, may yet carry allergens of clinical significance.     

Birch and ragweed pollinosis north of Milan: a model to investigate the effects of exposure to "new" airborne allergens

BACKGROUND: The effects of sudden and massive exposure of the general population to novel airborne allergens are not known. This study aimed to investigate the clinical effects of two "new" allergens, ragweed and birch, in an area north of Milan during the last 15 years. METHODS: We reviewed the records of 2571 monosensitized patients seen during the last 10 years in two allergy units north of Milan. Data included age at onset of allergic symptoms, and family history of allergic diseases. In this sample, 500 were allergic to grass, mite, birch, and ragweed; 293 to pellitory; 167 to mugwort; 100 to Alternaria; and 11 to plantain. RESULTS: Birch pollen-allergic patients and ragweed pollen-allergic patients showed a similar mean age at onset (35.3 years vs. 35.1 years; P = NS), but were significantly older than all other groups of patients (P < 0.001). Patients allergic to ragweed and birch pollen, 304 and 323 respectively, were >30 years at the onset of allergic symptoms. A family history of allergic disorders among first degree relatives was far less frequent among patients allergic to birch pollen (29%) or ragweed pollen (27%) than among patients sensitive to all other airborne allergens, except those allergic to mugwort pollen (P < 0.001). In both ragweed and birch groups, a positive family history was significantly more common among subjects < 30 years than in those > 30 years at onset of respiratory allergy (81/196 (41%) vs. 54/304 (18%), P < 0.001 for the ragweed group; 80/177 [45%]vs. 65/323 (20%), P < 0.001 for the birch group). CONCLUSION: Exposure of the general population of this area to two new airborne allergens resulted in the onset of respiratory allergy in many older people who lacked any relevant predisposing factor. Although we cannot exclude the possibility that those who became allergic had been exposed to birch or ragweed pollen elsewhere, a more likely explanation is a specific susceptibility that remains viable until the subject encounters the "right" allergen.