Changes in skin-test reactivity do not correlate with clinical efficacy of H1-blockers in seasonal allergic rhinitis

New-generation H-blockers may possess antiallergic properties, and their effect may differ, depending on the target organ. A double-blind, placebo-controlled, parallel-group study was carried out during the pollen season to compare the clinical effect on nasal and conjunctival symptoms of astemizole (10 mg o.d.) and loratadine (10 mg o.d.) with their effect on skin-test reactivity to allergen and histamine. Thirty-eight patients (12–56 years of age) were studied. Nasal and ocular symptoms were recorded daily from days 4 to 7. Skin prick tests with serial concentrations of allergens and one concentration of histamine were carried out before and at the end of the 7-day treatment period. Parallel-line bioassay, analysis of variance, and covariance were used to analyze skin test data. Loratadine and astemizole significantly decreased symptoms from baseline (P<0.004 and P<0.006), Skin-test reactivity to allergen and histamine was more profoundly decreased by astemizole than loratadine. The histamine covariant was more important in the allergen effect of astemizole than in that of loratadine. Two Hblockers having the same clinical effect on nasal and ocular symptoms during the pollen season have totally different effects on skin-test reactivity. Skin-test reactivity to allergen or histamine is not predictive of the clinical efficacy of H₁-blockers during seasonal allergic rhinitis.     

Amount of pollen has an effect on the systemic and local levels of soluble ICAM-1 in patients with seasonal allergic rhinitis

We investigated whether the amount of antigen has an effect on the systemic and local levels of soluble ICAM-1 (sICAM-1) in patients with pollinosis, and assessed its biologic significance. The levels of subjective symptoms and sICAM-1 in sera and nasal epithelial lining fluids (ELF) from 14 subjects with pollinosis (allergic group) and eight healthy subjects (control group) were measured from pre- to postseason in 1993 (total pollen count: 10854/cm²) and 1994 (total pollen count: 415/cm²), and the results were compared with each other among the four groups. The levels of subjective symptoms and sICAM-1 in ELF from the allergic group significantly increased during the season in both 1993 and 1994. However, there was a significant difference ( P < 0.01) between the levels of those in 1993 and those in 1994 during the season. The levels of sICAM-1 in sera from the allergic group were significantly upregulated during the seasons and postseasons only in 1993, and there was a significant difference ( P < 0.05) between the levels in 1993 and those in 1994 during the postseason. We conclude that amount of pollen has an influence on the local and systemic levels of sICAM-1, as well as the scores of subjective symptoms, in patients with seasonal allergic rhinitis.     

Adjunct effect of loratadine in the treatment of acute sinusitis in patients with allergic rhinitis

H₁-blockers are often added to the standard treatment of acute sinusitis, but this is not supported by a controlled study. A multicentric, randomized, double-blind, placebo-controlled, parallel-group study was done in 139 allergic patients (15–65 years) to assess the adjunct efficacy of loratadine in acute exacerbation of rhinosinusitis. Sinusitis was diagnosed by symptoms and confirmed by rhinoscopy and sinus radiograph. Allergy was characterized by skin tests, RAST, and history. Patients were treated with antibiotics (14 days), oral corticosteroids (10 days), and loratadine (10 mg OD) or placebo (28 days). Treatment efficacy was assessed over 28 days by symptom scores quoted daily by patients. Physicians also rated total symptom scores at entry and at day 28. At entry, both groups had similar symptoms. Placebo-treated patients improved significantly, but patients who received loratadine had a significantly greater improvement in sneezing ( P =0.003) after 14 days, and in nasal obstruction ( P =0.002) after 28 days. Physicians found that patients receiving loratadine were significantly improved compared to placebo patients ( P =0. 0125). Loratadine in addition to standard therapy was found to improve the control of some symptoms of sinusitis.     

Effects of H1-receptor antagonists on nasal obstruction in atopic patients

The aim of this study is to investigate whether H₁-receptor antagonists, besides their effect on nasal itching and sneezing, also have a measurable effect on nasal obstruction caused by allergen challenge. The antihistamine used was astemizole (10 mg) versus placebo, in a double-blind, cross-over, randomized study of two groups. Between the two sessions there was a wash-out period of at least 4 weeks. Seven patients of both sexes, with proven allergy to grass pollen, underwent a specific long-term provocation with grass pollen in the Vienna challenge chamber. Using a physiological method of challenge and a sensitive method for evaluating nasal function, we were able to prove H₁-receptor antagonist influence on nasal airway obstruction. The main parameters obtained arc nasal flow and nasal resistance at 75, 150 and 300 Pa, evaluated by active anterior rhinomanometry. We also investigated subjective symptom scores (0–3) of nasal, eye. and lung symptoms. It can be shown that the nasal flow under astemizole treatment is statistically significantly higher than the nasal flow under placebo treatment ( P = 0.034). This is in accordance with the findings in subjective nasal itching and sneezing.     

Loratadine treatment of rhinitis due to pollen allergy reduces epithelial ICAM-1 expression

Background Loratadine and cetirizine are new generation antihistamines, which are clinically effective in the treatment of allergic rhinitis. Objective The aim of the study was to evaluate antiallergic activity of loratadine compared with cetirizine, over a 2 week period under natural allergen exposure, in a double-blind parallel groups, randomized, controlled trial. Methods Twenty patients, sensitized to grass and/or Parietaria pollen, were subdivided into two groups, one receiving loratadine the other cetirizine respectively. Both were dosed at 10 mg/day. Evaluated parameters were: clinical symptoms, nasal inflammatory cell (such as neutrophil, eosinophil and metachromatic cells) counts, ICAM-1 expression on nasal epithelial cells, and nasal mediators (e.g. histamine, ECP, EPO and MPO). Results Loratadine and cetirizine significantly improved symptoms (P < 0.002), significantly reduced eosinophil (P < 0.016) and metachromatic cell (P < 0.01) infiltration, levels of ECP (F < 0.002), EPO (P < 0.006) and histamine (P < 0.01) and ICAM-1 expression on nasal epithelial cells (P < 0.02). No difference was demonstrated between the two drugs. Conclusion The antiallergic activity of loratadine and cetirizine is documented by their actions on the inflammatory and clinical parameters, especially ICAM-1 modulation.     

Localization and function of histamine H3 receptor in the nasal mucosa

Background Histamine is an important chemical mediator of allergic rhinitis (AR). Histamine H₃ receptors (H₃R) are located on cholinergic and NANC neurons of the myenteric plexus, and activation of H₃R regulates gastric acid secretion. However, little is known about the localization and function of H₃R in the upper airway.
Objective The objective of this study was to examine the localization and possible function of H₃R in the nasal mucosa.
Methods We extracted total RNA from the inferior turbinate mucosa of patients with AR. H₃R mRNA and β-actin mRNA were amplified by RT-PCR. We used immunohistochemistry to examine localization of H₃R protein in the inferior turbinate mucosa excised during clinically indicated surgery. We used alcian blue/periodic acid-shiff staining to examine the effects of the H₃R agonist (R)-α-methylhistamine and the H₃R antagonist thioperamide on secretion from rat submucosal glands.
Results H₃R protein was expressed around submucosal gland cells. Thioperamide induced degranulation in the submucosal gland in the nasal septum.
Conclusion The present results suggest that H₃R is localized mainly around submucosal glands, and that H₃R plays an important role in the secretion of submucosal glands in the nose.     

Onset of action in the nasal antihistaminic effect of cetirizine and loratadine in patients with allergic rhinitis

Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH₂O·1⁻¹·s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine ( P <0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine ( P <0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.     

Seasonal fluctuations of substance P and vasoactive intestinal peptide concentrations in nasal secretions of patients with nasal allergy to Japanese cedar pollen]

Substance P (SP) and vasoactive intestinal peptide (VIP) concentrations in nasal secretions and plasma from patients with nasal allergy to Japanese cedar pollen and healthy volunteers were measured from Jan to Dec, 1991 using EIA established by us. Simultaneously, the numbers of airborne pollens of Japanese cedar and cypress were counted, and the relation to the SP and VIP concentrations in nasal secretions from the patients with nasal allergy to Japanese cedar pollen was studied. The mean SP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 81.9 +/- 48.4 fmol/mg protein, which was significantly higher than that in the non-pollination season (30.4 +/- 14.7 fmol/mg protein) (p < 0.01). Likewise, the mean VIP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 14.2 +/- 10.4 fmol/ml protein, which was significantly higher than that in the non-pollination season (4.2 +/- 3.0 fmol/mg protein) (p < 0.01). The SP and VIP concentrations in nasal secretions from the healthy volunteers were not affected by the scattering of pollens. The SP and VIP concentrations in plasma from the patients and the healthy volunteers were not affected by the scattering of pollens.     

Terfenadine exerts antiallergic activity reducing ICAM-1 expression on nasal epithelial cells in patients with pollen allergy

Background: Rhinoconjunetivitis caused by pollen allergy is characterized by typical signs and symptoms and mucosal infiltration by inflammatory cells during the pollen season. It has recently been demonstrated that the adhesion molecule system is deeply involved in cell-to-cell interaction during the inflammatory response which follows allergic reactions. Objective: The aim of the present study (placebo-controlled, double-blind, randomized) was the evaluation of the antiallergic activity of Terfenadine in the model of the allergic rhinitis due to natural pollen exposure. Methods: Two groups of patients with pollen allergy were enrolled in this study. Ten patients were treated with Terfenadine (120mg/die) for 7 days and 10 with placebo. Evaluation criteria were: (a) clinical: signs and symptoms (recorded daily in a dian card by patients): (b) cytological: inflammatory cell count (neutrophils, eosinophils, metachromatic cells) from nasal lavage at T0 and T7; (c) immunocytochemical: ICAM-1/CD54 expression on nasal epithelial cells at T0 and T7; and (d) mediators dosage (ECP-MPO) on nasal lavage at T0 and T7. Results: As opposed to the placebo group, patients treated with Terfenadine showed a significant improvement of both symptoms (P< 0.022) and signs P< 0.001), a significant reduction of inflammatory cells infiltrate (P< 0.005), of ECP levels (P < 0.002) and ICAM-I expression on nasal epithelial cells (P < 0.005). Conlusions: In conclusion, these data demonstrate that Terfenadine exerts antiallergic activity since it is able to reduce inflammatory cell infiltrate and downregulates ICAM-1 expression.     

Inhibition of adhesion molecules by budesonide on a human epithelial cell line (lung carcinoma)

Inhaled corticosteroids in the treatment of asthma have been shown to produce marked reductions in the number of inflammatory cells (mainly mast cells and eosinophils) and their products at bronchial level (such as cytokines). Recently, it has been demonstrated that epithelial cells express ICAM-1/CD54 in allergic patients both during natural allergen exposure and after allergen challenge. We have previously demonstrated that deflazacort (a systemic steroid) reduces the expression of ICAM-1 on conjunctival epithelial cells. The present study aimed to evaluate the effects exerted by budesonide on adhesion molecule expression by a human epithelial cell line (lung carcinoma: DM) and on soluble ICAM-1. Budesonide was added at concentrations corresponding to 10⁻⁸, 10⁻⁷, and 10⁻⁶ mol/1 in cultured epithelial cells, either in the absence of any stimulus or in the presence of interferon-gamma (IFN-y) at 500 U/ml. After 24 h of incubation, cytofluorometric analysis was performed for ICAM-1 and CD29/VLAP1. The 24–h supernatants of the same cultures were collected and then evaluated for soluble ICAM-1 (sICAM-1). The results showed that budesonide inhibits ICAM-1 and CD29 basal expression on the cells studied (P<0.05): budesonide was effective in a dose-dependent manner. In addition, budesonide reduced surface ICAM-1 upregulation induced by IFN-γ at 500 U/ml (p<0.05). Finally, cell cultures with budesonide showed decreased levels of soluble ICAM-1 in basal condition, but not after IFN-γ stimulation.     

Effect of glucocorticosteroids on tumour necrosis factor-α-induced intercellular adhesion molecule-1 expression in cultured primary human nasal epithelial cells

OBJECTIVE: In order to confirm the direct effect of glucocorticosteroids on epithelial intercellular adhesion molecule-1 (ICAM-1) expression, we examined ICAM-1 expression on primary cultured human nasal epithelial cells (HNECs) at both protein and mRNA levels. MATERIAL AND METHODS: HNECs were stimulated with recombinant human TNF-alpha (20 pg/mL-20 ng/mL) for specified time periods (0, 12, 24, and 48 h) and ICAM-1 mRNA and the soluble ICAM-1 (sICAM-1) concentrations were measured by quantitative RT-PCR and ELISA, respectively. We also evaluated surface expression of ICAM-1 by flow cytometry 48 h after stimulation and determined the effect of dexamethasone (DEX) on TNF-alpha-induced ICAM-1 expression. RESULTS: Significant increases in ICAM-1 gene expression in HNECs were initially detected at 24 h, peaking at 48 h after the stimulation. The TNF-mediated-ICAM-1 mRNA and ICAM-1 surface expression at 48 h was significantly inhibited by co-incubation with human recombinant soluble TNF receptor I. Similarly, TNF-alpha-induced release sICAM-1 occurred in a time- and concentration-dependent manner. DEX 10(-6) M attenuated the TNF-alpha-induced ICAM-1 expression at mRNA and protein levels. CONCLUSIONS: Our finding suggests a potential role for topical steroids in allergic rhinitis in suppressing inflammatory reactions in the nasal mucosa by regulating ICAM-1 expression on nasal epithelium.     

Inhibition of mediator and cytokine release from dispersed nasal polyp cells by terfenadine

The mechanism of action of H₁-blockers requires elucidation because they may possess properties unrelated to the blockage of histamine at its receptor level. A study was performed with enzymatically dispersed cells obtained from nasal polyps to examine the effect of terfenadine (0.1–10 μmol) on the release of leukotrienes (LT) (LTC₄/D₄ and LTB₄) after stimulation by anti-IgE, and on the spontaneous release of cytokines (granulocyte/macrophage-colony stimulating factor [GM-CSF] and tumor necrosis factor-alpha [TNF-α]) released from cells cultured for 6 h. Terfenadine inhibited significantly, and in a dose-dependent manner, the release of LTC₄/D₄, LTB₄, TNF-α, and GM-CSF. IC₅₀ values were determined for LTC₄/D₄ (8 μmol), LTB₄ (9.9 μmol), TNF-α (6.1 μmol), and GM-CSF (4 μmol). Terfenadine was found to possess new antiallergic properties with a novel in vitro model which mimics more closely inflammatory cells of allergic rhinitis or asthma.     

In vivo and ex vivo inhibitory effects of loratadine on histamine release in patients with allergic rhinitis

Background The aim of this study was to evaluate the in vivo and ex vivo effects of the H.-antagonist loratadine on histamine release.
Methods The study was designed as a double-blind, crossover trial. Ten patients with allergic rhinitis due to Dermatophagoides pteronyssinus were treated with loratadine (10 mg daily p.o.) and with placebo for 1 week, with a 2-week interval between the two treatments. Nasal lavages with saline solution were done before and after challenge with the relevant allergen at the end of treatments with loratadine and placebo. Venous blood was taken after treatments, and basophil histamine release induced by anti-IgE (10 μg/ml), N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 μM). and Ca²⁺ ionophore A23187 (1 μM) was evaluated by ati automated fluorometric method.
Results Treatment with loratadine attenuated early antigen-tnduced nasal obstruction, rhinorrhea. and itching. Nasal symptoms were accompanied by a significant histamine release in the nasal lavages collected 5 min after stimulation when the patients received placebo (median 4 ng/ml, range 1-28; P<0.05). After treatment with loratadine, histamine release in the 5-min postchallenge lavages was almost abrogated (median 0.5 ng/ml, range 0-3; P<0.01 vs placebo). Median anti-IgE-induced histamine release from basophils was 41.9% (range 27.8-79.2) after placebo and 30.0% (range 1.7-73.3, P < 0.05) after loratadine. Active treatment exerted an inhibitory effect also on basophil histamine release induced by fMLP and Ca²⁺ ionophore A23187.
Conclusions Treatment for 1 week with loratadine reduces allergen-mduced nasal symptoms and inhibits in vivo and ex vivo histamine release in patients with allergic rhinitis.     

Preliminary evidence for 'aberrant' expression of the leukocyte integrin LFA-1 (CD11a/CD18) on conjunctival epithelial cells of patients with mite allergy.

BACKGROUND: We have previously shown aberrant expression of the 'leukocyte' integrin LFA-1 on epithelial cells in chronic autoimmune thyroiditis. In the present study we investigated whether conjunctival epithelial cells, which bear the adhesion molecule ICAM-1 on their surface during allergic inflammation, may also aberrantly express its natural ligand, the 'leukocyte' integrin LFA-1. METHODS: We studied 13 patients with rhinoconjunctivitis allergic to mites, chronically exposed to the allergen, 11 patients allergic to pollen tested out of the pollen season and 8 normal volunteers. Single and double immunocytochemical staining of conjunctival smears was employed. RESULTS: LFA-1 staining on epithelial cells was demonstrated in 12/13 patients allergic to mites and not in normal controls or in patients allergic to pollen tested out of the pollen season. The epithelial localization of LFA-1 was confirmed by double staining with anti-LFA-1 and anti-cytokeratin antibodies (both immunocytochemical and immunofluorescence). CONCLUSIONS: Coexpression of LFA-1 and ICAM-1 during persistent allergen stimulation may be relevant for interaction between epithelial cells and activated effector cells, such as eosinophils, which bear on their surface both ICAM-1 and its beta2 integrin ligands.     

Molecular properties and signalling pathways of the histamine H1 receptor

With cloning of the gene encoding the histamine H₁ receptor, a new area of histamine research has become reality. Finally, it seems feasible to study the target of the thera-peutically important clans of antihistamine. Expression of the genes in mammalian cells allows detailed investigations of the various signal transduction routes of the histamine H₁ receptor. Moreover, using molecular biological techniques, it is now possible to investigate ligand receptor interaction at the molecular level. Studies with mutant H₁ receptors have shown that H₁ antagonists bind to a specific amino acid residues in TM3 and 5. It is expected that these new developments will provide much fundamental knowledge on the ligand interaction with the H₁ receptor.     

H1 receptor-mediated vasodilatation contributes to postexercise hypotension

In normally active individuals, postexercise hypotension after a single bout of aerobic exercise is due to an unexplained peripheral vasodilatation. Histamine has been shown to be released during exercise and could contribute to postexercise vasodilatation via H₁ receptors in the peripheral vasculature. The purpose of this study was to determine the potential contribution of an H₁ receptor-mediated vasodilatation to postexercise hypotension. We studied 14 healthy normotensive men and women (ages 21.9 ± 2.1 years) before and through to 90 min after a 60 min bout of cycling at 60%     on randomized control and H₁ receptor antagonist days (540 mg oral fexofenadine hydrochloride; Allegra). Arterial blood pressure (automated auscultation) and femoral blood flow (Doppler ultrasound) were measured in the supine position. Femoral vascular conductance was calculated as flow/pressure. Fexofenadine had no effect on pre-exercise femoral vascular conductance or mean arterial pressure ( P > 0.5). At 30 min postexercise on the control day, femoral vascular conductance was increased (Δ+33.7 ± 7.8%; P < 0.05 versus pre-exercise) while mean arterial pressure was reduced (Δ−6.5 ± 1.6 mmHg; P < 0.05 versus pre-exercise). In contrast, at 30 min postexercise on the fexofenadine day, femoral vascular conductance was not elevated (Δ+10.7 ± 9.8%; P = 0.7 versus pre-exercise) and mean arterial pressure was not reduced (Δ−1.7 ± 1.2 mmHg; P = 0.2 versus pre-exercise). Thus, ingestion of an H₁ receptor antagonist markedly reduces vasodilatation after exercise and blunts postexercise hypotension. These data suggest H₁ receptor-mediated vasodilatation contributes to postexercise hypotension.     

Intrathoracic pressure changes and cardiovascular effects induced by nCPAP and nBiPAP in sleep apnoea patients

SUMMARY  The effect of nasal continuous positive airway pressure (nCPAP) and nasal bi-level positive airway pressure (nBiPAP) on intrathoracic pressure and haemodynamics during wakefulness was studied in a group of nine patients with severe sleep apnoea. No patient took cardiovascular medication.
Patients were studied with a Swan Ganz catheter, an arterial line and an oesophageal balloon. nCPAP and nBiPAP were applied in the following pressure sequence: 5, 10 and 15 cm H₂O of CPAP and 10/5 and 15/10 cm H₂O of nBiPAP. Measurements were made at the end of a 5-min period at each pressure level. Intrathoracic pressure was noted to increase to a level of approximately 50% of the pressure delivered at the mask. At a CPAP of 10 cm H₂O and above, as well as at BiPAP of 10/5 or higher, there was a decrease in cardiac output (CO) and cardiac index (CI). CI fell below the normal value in two of the patients. Transmural pulmonary artery pressure (PPA_tm) decreased at a CPAP of 15 cm H₂O and at both BiPAP levels. Transmural right atrial pressure (PRA_tm) decreased at both BiPAP levels. There were no differences in CO, CI, PPA_tm and PRA_tm between nCPAP and nBiPAP at equal inspiratory pressures. SaO₂ increased during BiPAP 15/10 cm H₂O, whereas heart rate and arterial blood pressure did not change significantly. The data presented here are consistent with the literature on positive end-expiratory pressure (PEEP) applied via intratracheal tube and are likely to be due to a reduced venous return. It is concluded that nasally applied positive pressure may have acute negative effects on cardiac function in patients with sleep apnoea.     

Clinical advantages of dual activity in allergic rhinitis

Symptoms of allergic rhinitis include sneezing; itching of the eyes, nose, and throat; nasal obstruction; and rhinorrhoea; they may be seasonal or perennial, depending on the causative allergen. The major symptom of perennial allergic rhinitis is nasal obstruction. Sneezing and rhinorrhoea are often present, but are less troublesome than in seasonal allergic rhinitis. Symptom relief is a priority in allergic rhinitis because patients have a severely impaired quality of life. The nasal vascular system is complex. Histamine acts on postcapillary venules during both the immediate and late phase of reactivity and causes plasma extravasation. Other inflammatory mediators can also induce this reaction. Thus, histamine antagonists that also have some additional antiallergic properties have advantages in the treatment of allergic rhinitis. Mizolastine is a second-generation antihistamine that has been shown, in experimental studies, to possess 5-lipoxygenase inhibitory properties in addition to its H₁-receptor antagonistic activity. In the treatment of seasonal allergic rhinitis, mizolastine 10 mg/day has been shown to be effective in reducing nasal and ocular symptoms. It has been shown to be significantly more effective than placebo with a greater percentage of responders. Another study has shown that symptoms of seasonal allergic rhinitis in mizolastine-treated patients were reduced more significantly than in cetirizine-treated patients on the second and third days of treatment. In perennial allergic rhinitis, mizolastine significantly improved symptoms of nasal obstruction compared with placebo and also significantly reduced nasal membrane colour, nasal secretions, and mucosal swelling as shown by rhinoscopy. These effects were maintained over a 5-month treatment period. Mizolastine has also been shown to be at least as effective as loratadine, and in one trial even superior in the treatment of perennial allergic rhinitis.     

Effect of terfenadine and budesonide on nasal symptoms, olfaction, and nasal airway patency following allergen challenge

The study investigated the effect of the oral H₁-blocker terfenadine on allergen challenge in subjects with nasal allergy in comparison with the topical steroid, budesonide. A randomized, placebo-controlled, double-blind, crossover study with 3 experimental days was performed outside the pollen season. Seventeen nonsmokers with hay fever 'symptoms, positive skin prick test, and RAST against timothy) were treated for 14 days before each experimental day, where the response to nasal challenge with four different concentrations of timothy was measured every 15 min for 6 h. The nasal cavity dimensions were measured by acoustic rhianometry and the olfactory function as the threshold for the sense of smell of butanol. Nasal symptoms were determined by questionnaires. Both terfenadine and budesonide dry powder had an effect on the hay fever symptoms during nasal pollen challenge. Terfenadine was more efficient than budesonide against histamine-mediated symptoms such as sneezing and itching. Budesonide increased nasal airway dimensions better than terfenadine ' P < 0.01). A marked effect of budesonide was seen 1-2 h after challenge, suggesting an effect on 'early late phase' reaction in the nose. In 7/17 subjects, a significant ' P < 0.05) improvement of olfactory function after budesonide treatment was seen. In conclusion, topical steroid 'budesonide) is superior to antihistamine 'terfenadine) in treatment of nasal congestion in hay fever, especially for the postchallenge reaction, and may, in some cases, relieve the decreased sense of smell during pollen challenge.