Sensitivity and maximal response to methacholine in perennial and seasonal allergic rhinitis

Background Airway hyperresponsiveness to pharmacological agonists is a common feature in subjects with allergic rhinitis.
Objective The aim of this study was to investigate differences in threshold value and shape of the concentration-response curves to methacholine between subjects with perennial allergic rhinitis and subjects with seasonal rhinitis.
Methods We studied a sample of 72 non-asthmatic patients with allergic rhinitis. They were subdivided into two groups: subjects with only seasonal symptoms and skin sensitization to grass and/or Parietaria pollen allergens (seasonal group, n = 38), and subjects with perennial symptoms and skin sensitization to house dust mite, alone or with other allergens (perennial group, n = 34). They were challenged with methacholine (up to 200mg/mL), and concentration-response curves were characterized by the threshold value (PC₂₀= provocative concentration of methacholine required to produce a 20% fall in FEV₁) and maximal response plateau, if possible. The measurements in the seasonal group were done within the pollen season.
Results The geometric mean methacholine PC₂₀ for subjects of the perennial group was 6.9mg/mL, compared with 23.4mg/mL in subjects of the seasonal group ( P 0.01). A plateau response was detected in 16 subjects of the perennial group and in 28 subjects of the seasonal group (p 0.05). Moreover, the level of plateau was higher in subjects of the perennial group when compared with subjects of the seasonal group (23.8 ±2.0% vs 19.2 ±1.6%, P 0.05).
Conclusion In subjects with allergic rhinitis, sensitization to perennial allergens is associated not only with lower methacholine threshold values, but also with lower prevalence and higher level of plateau than sensitization to pollen allergens.     

Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma.

Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.     

Influence of natural exposure to pollens and domestic animals on airway responsiveness and inflammation in sensitized non-asthmatic subjects

BACKGROUND: Atopy may be a risk factor in the development of asthma. Indoor allergens are considered to be more potent asthma inducers than outdoor ones such as pollens. Lower airway inflammation may be present in non-asthmatic subjects during natural exposure to relevant allergens and may eventually lead to the development of asthma. AIMS: To document seasonal variation in lower airway responsiveness and inflammation in sensitized non-asthmatic subjects, during natural exposure to allergens, and to determine whether it is more marked in those exposed to animals to which they are sensitized. METHODS: Twenty-two atopic subjects were seen during and out of the pollen season. All (but the controls) were sensitized to domestic animals, and to trees, grasses or ragweed. Eleven were not exposed to animals at home and 8 were exposed. They were compared with 3 normal controls. A respiratory questionnaire was administered, allergy skin prick tests, spirometry, methacholine challenge, blood and induced sputum with differential cell counts were obtained during the pollen season for all subjects. These tests were repeated out of the pollen season. RESULTS: Throughout the study, none of the subjects had asthma symptoms. Mean PC(20) was significantly lower in subjects exposed to animals compared with unexposed subjects or controls, both during and out of the pollen season. In season, subjects exposed to animals had significantly higher sputum eosinophil numbers than unexposed or normal control subjects. CONCLUSIONS: Non-asthmatic atopic subjects show variable degrees of airway responsiveness and inflammation. However, subjects exposed to animals show higher airway eosinophilia, which may suggest they are at increased risk of developing airway hyperresponsiveness and asthma.     

Monitoring of seasonal variability in bronchial hyper-responsiveness and sputum cell counts in non-asthmatic subjects with rhinitis and effect of specific immunotherapy

Bronchial hyper-responsiveness (BHR) is documented in a proportion of non-asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory events in the lower airways. Natural exposure to allergens is known to modulate BHR and the level of airway inflammation in asthma, but less consistently in NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR and airway inflammation. The influence of natural exposure to Parietaria pollen on BHR and sputum cell counts of NAAR was investigated and the effect of Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica, participated in a randomized, double-blind, placebo-controlled, parallel group study of the effects of a Parietaria pollen vaccine on symptoms/medication score, BHR to inhaled methacholine and adenosine 5'-monophosphate (AMP), and cell counts in the sputum collected out of and during the pollen seasons for 36 months. Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum cell counts were documented. Changes were consistent for AMP, but not methacholine, and invariably associated with modifications in sputum eosinophils and epithelial cells. The clinical efficacy of Parietaria SIT was associated with a decline in the seasonal deterioration of BHR to AMP, whereas no significant effect was observed on BHR to methacholine or sputum cell differentials. Between-groups comparison of the seasonal changes in PC15 methacholine values and sputum cell differentials calculated as the AUC were not statistically significant, whereas a significant difference in PC15 AMP was demonstrated throughout the study (P=0.029), the median (inter-quartile range) AUC values being 2478.5 (1153.3-3600.0) and 1545.5 (755.3-1797.9) for the SIT- and placebo-treated group, respectively. Bronchial airways of NAAR exhibit features of active inflammation that deteriorate during natural allergen exposure, particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT was exclusively associated with attenuation in seasonal worsening of PC15 AMP, suggesting that AMP may be useful in monitoring changes in allergic inflammation of the airways.     

Dissimilarity between seasonal changes in airway responsiveness to adenosine-5'-monophosphate and methacholine in patients with grass pollen allergic rhinitis: relation to induced sputum

BACKGROUND: In patients with allergic rhinitis, bronchial hyperresponsiveness (BHR) and airway inflammation may increase during pollen exposure. BHR can be assessed by adenosine-5'-monophosphate (AMP) or methacholine challenge. It has been suggested that BHR to AMP is more closely related to airway inflammation than BHR to methacholine. Seasonal allergic rhinitis offers a dynamic model to study changes in BHR and airway inflammation during natural allergen exposure. METHODS: We measured BHR [provocative concentration causing a 20% fall (PC(20)) in forced expiratory volume in 1 s (FEV(1))] to AMP and methacholine, and induced sputum cells in 16 rhinitis patients before and during the 2001 grass pollen season. RESULTS: There was a decrease in PC(20) methacholine during pollen exposure (geometric mean PC(20) from 3.22 to 1.73 mg/ml, p = 0.0023), whereas no reduction was observed for PC(20) AMP (p = 0.11). There was no increase in sputum eosinophils [pre: 0.69% (95% confidence interval 0.22-2.07); during: 1.85 (0.55- 5.6), p = 0.31]. Although the correlation of log PC(20) methacholine and log PC(20) AMP at baseline was good (r = 0.76, p = 0.001), individual seasonal changes (doubling concentrations) in PC(20) methacholine were not correlated with changes in PC(20) AMP (rho = 0.21, p = 0.44). There was no correlation between baseline log PC(20) methacholine or seasonal changes in PC(20) methacholine and sputum eosinophils (p > 0.12, all correlations). In contrast, there was a significant correlation between seasonal changes in PC(20) AMP and changes in sputum eosinophils (rho = -0.59, p = 0.025). CONCLUSIONS: These data show dissimilarity between seasonal changes in PC(20) AMP and methacholine in patients with seasonal allergic rhinitis. Moreover, PC(20) AMP seems to be more closely related to sputum eosinophils than PC(20) methacholine. The clinical significance of this discrepancy is unclear.     

Cytokine expression in the lower airways of nonasthmatic subjects with allergic rhinitis: influence of natural allergen exposure

BACKGROUND: Natural exposure to pollen provokes an increase in airway responsiveness in nonasthmatic subjects with seasonal allergic rhinitis. This natural exposure may induce inflammatory cell recruitment and cytokine release, leading to lower airway inflammation. OBJECTIVE: The aim of this study was to characterize lower airway inflammation in nonasthmatic pollen-sensitive subjects. METHODS: We performed immunohistochemical tests on bronchial biopsy specimens from subjects with rhinitis who had no past or current history of asthma to evaluate cytokine expression and inflammatory cell numbers and activation both in and out of the pollen season. RESULTS: The number of CD4(+), CD8(+), and CD45RO(+) lymphocyte subpopulations were significantly higher during the pollen season compared with the out-of-season period (P <.04). Furthermore, EG1(+) cells tended to increase after natural pollen exposure (P =.06). The number of IL-5(+) cells increased significantly after natural exposure to pollen compared with out-of-season numbers (P <.01). This increase in IL-5 expression was correlated with the numbers of CD3(+), CD4(+), CD45RO(+), and EG1(+) cells. The numbers of tryptase-positive, IFN-gamma(+), and IL-4(+) cells did not change after natural exposure. CONCLUSION: This study showed that natural pollen exposure was associated with an increase in lymphocyte numbers, eosinophil recruitment, and IL-5 expression in the bronchial mucosa of nonasthmatic subjects with allergic rhinitis.     

Eosinophils, secretory responsiveness and glucocorticoid-induced effects on the nasal mucosa during a weak pollen season

This study examined the seasonal effects on eosinophils and secretory responsiveness of the nasal mucosa in 22 patients with allergic rhinitis due to birch pollen (11 patients received placebo and 11 budesonide, 200 micrograms once daily in each nostril). The pollen counts during the study season were too low to produce a significant symptomatology. Hence, our findings demonstrate threshold alterations of the airway mucosa in allergic rhinitis and their inhibition by anti-inflammatory drug intervention. The patients were monitored for 8 weeks with daily recordings of pollen counts and symptom scores. Once every week a series of laboratory tests was carried out: the local eosinophil influx was determined using a Rhinobrush technique; the levels of eosinophil cationic protein (ECP) were analysed in nasal lavage fluids; and the secretory response to intranasal methacholine was measured. Treatments started after a 2-week run-in period. The proportion of eosinophils increased markedly in the placebo group and was elevated also during the last two study weeks when the pollen counts were practically nil. The secretory responsiveness to methacholine increased during the pollen season and returned to baseline towards the end of the study period. The topical glucocorticoid treatment reduced the proportion of eosinophils, the ECP levels, and the secretory response to methacholine compared to placebo. We conclude that the increased traffic and activity of eosinophils and less conspicuously the increased secretory responsiveness are expressions of the mucosal inflammation that precede the development of symptoms in seasonal allergic rhinitis.     

Non-specific airway hyperresponsiveness in mono-sensitive Sicilian patients with allergic rhinitis. Its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season

Background Initial attempts to evaluate the association between allergic rhinitis and nonspecific bronchial responsiveness has produced conflicting results. In fact, some studies showed a strong correlation and other failed to find an association. However, little is known about the effect of natural specific allergen exposure on the bronchial reactivity of mono-sensitive patients with rhinitis in the southern Mediterranean area, in relation to skin reactivity to allergens, total serum IgE levels and blood eosinophiis. Objectives The significance of the association between allergic rhinitis, and abnormal airway responsiveness with regard to the pathogenesis of asthma is unclear. For this reason, we have studied non-specific bronchiai hyperreactivity. in patients with seasonal allergic rhinitis, with reference to the responsible allergen. The aim of the study was to correlate the responsiveness to bronchoprovocation with methacholine in subjects a with allergic rhinitis during and out of the pollen season with total serum IgE and blood eosinophils. Methods Fourty-nine non-smoking patients with clinical diagnosis of allergic rhinitis and mono-sensitive skinprick tests to pollen allergens were enrolled in the study. Twenty patients suffered from seasonal rhinitis to Parietaria pollen. 15 patients to Gramineae pollen and 14 patients to Olea pollen. In all patients lung function measurements (assessed as response to methacholine). tolal serum IgE and blood eosinophii counts were measured during and out of the pollen season. Results During pollen season. 16 out of 49 rhinitis patients demonstrated values of bronchial responsiveness measured as response to inhaled metbacholine in the asthmatic range whereas out of the pollen season only eight patients were in the asthmatic range. By analysing the results with reference to the responsible allergen, during the pollen season 5 out of 16 patients were Parietaria -sensitive and out of the pollen season seven out of eight patients. Finally, in Parietaria -sensitive rhinitis bronchial responsiveness signifi-cantly correlated, during and out of the pollen season, with total serum IgE and with blood eosinophil counts. Conclusions Our results are consistent with the hypothesis that Parietaria is more important than Olea and Gramineae as a risk for developing non- specific bronchial hyperresponsiveness. On the whole, present observations provide further evidence that there is an interrelationship of allergen kind, total serum IgE. eosinophil and bronchial hyperressponsiveness suggesting that they may play a role in the development of bronchial asthma in rhinitis patients.     

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. RESULTS: Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS: These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.     

Effect of fluticasone propionate-salmeterol therapy on seasonal changes in airway responsiveness and exhaled nitric oxide levels in patients with pollen-induced asthma.

BACKGROUND: There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness. OBJECTIVE: To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids. METHODS: Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment. RESULTS: Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005). CONCLUSIONS: In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.     

Effect of azelastine on the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. A randomized, double-blind placebo-controlled, crossover study

Azelastine, a phthalazinone derivative, is a new potent, long acting, orally active anti-allergic compound with particularly strong H1-histamine receptor antagonistic effects which has been proven to possess in vitro and in vivo a number of anti-inflammatory properties. The aim of the present study was to investigate whether azelastine would be able to prevent and/or reverse the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. Twelve atopic patients (5 males, mean age 31 years), skin positive exclusively to grass and/or Parietaria pollen extract, with rhinitis and mild asthma occurring in the spring for at least two years previously, were studied. After a 2 week run-in period, oral azelastine, 4 mg twice daily, or placebo, was given for 2 weeks from the start of the pollen season, according to a randomized, double-blind design. After 2 weeks, the treatments were crossed over. During both the run-in and study periods, patients recorded rhinitis and asthma symptoms, additional antihistamine and bronchodilator drugs taken and peak expiratory flow measurements. A methacholine inhalation test was carried out on four occasions in each patient: before the run-in period, before the start of the treatment, and at the end of the two 2 week treatment periods. Azelastine significantly reduced rhinitis symptoms and the need for antihistamine drugs, whereas asthmatic symptoms, use of bronchodilator drugs, peak flow recordings and bronchial responsiveness to methacholine were unaffected by the treatment. Compliance level and adverse side-effects were not significantly different between active treatment and placebo. In the final subjective evaluation of the two treatments, eight out of 12 patients preferred azelastine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis

BACKGROUND: Bronchial hyperresponsiveness (BHR) and airway inflammation are frequently associated with allergic rhinitis, and may be important risk factors for the development of asthma. Specific immunotherapy (SIT) reduces symptom in subjects with allergic rhinitis, but the mechanisms are not clear. AIMS OF THE STUDY: To assess the effect of Parietaria-SIT on asthma progression, rhinitic symptoms, BHR, and eosinophilic inflammation. METHODS: Nonasthmatic subjects with seasonal rhinitis were randomly assigned to receive Parietaria pollen vaccine (n = 15) or matched placebo (n = 15). Data on symptoms and medication score, BHR to methacholine, eosinophilia in sputum were collected throughout the 3-year study. RESULTS: By the end of the study, in the placebo group, symptoms and medication scores significantly increased by a median (interquartile range) of 121% (15-280) and 263% (0-4400) respectively (P < 0.01), whereas no significant difference was observed in the SIT group. We found no significant changes in sputum eosinophils and BHR to methacholine in both groups throughout the study. Nine of 29 participants developed asthma symptoms during the study; of these, only two subjects (14%) in the SIT-treated group (P = 0.056). CONCLUSIONS: Parietaria-SIT reduces symptom and rescue medication scores, but no changes in BHR to methacholine or sputum eosinophilia were observed. Moreover, Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma, suggesting that SIT should be considered earlier in the management of subjects with allergic rhinitis.     

Seasonal variation of airway function in allergic rhinitis

We set out to examine seasonal variation in airway bronchoconstriction in patients with seasonal allergic rhinitis. Airway conductance and response to methacholine challenge were measured during pollen season, as well as in winter when pollen exposure was not present. Airway conductance and spirometry were performed on 17 subjects during allergy season and in winter. In eight of these subjects the measurements were repeated in the successive allergy season. Methacholine bronchoprovocation was performed on 17 of the subjects in winter and in eight subjects in allergy season. We found airway constriction in both allergy seasons as evidenced by specific airway conductance (SGaw) of 0.188 +/- 0.06 and 0.203 +/- 0.03. In contrast, SGaw during winter was 0.27 +/- 0.11. When winter and summer seasons were compared, both summer SGaw values were significantly lower than winter SGaw, p less than 0.01 and p less than 0.05, respectively. Mean airway sensitivity to methacholine during allergy season was 16.1 breath units and not different than out of season 11.7 breath units; p = NS. The reactivity to methacholine (slope of the dose-response curve) and spirometry (FVC, FEV1, FEV1/FVC) in and out of allergy season were likewise not different. The data indicate that patients with allergic rhinitis have unique physiologic behavior separating them from patients with asthma or normal subjects. They develop seasonal bronchoconstriction unassociated with clinical bronchospasm, but this seasonal bronchoconstriction does not potentiate their sensitivity to methacholine. However, they have increased airway sensitivity to methacholine, and this feature distinguishes them from normal subjects.     

Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma

BACKGROUND: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma. METHODS: A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. RESULTS: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.     

Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic rhinitis sensitized to the same pollen allergen.

BACKGROUND: Some studies have reported that the levels of exhaled nitric oxide (ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and it has been postulated that atopic status might be the determinant of enhanced nitric oxide production in asthma. OBJECTIVES: The aim of this study was to determine differences in ENO levels between asthmatics and subjects with allergic rhinitis sensitized to the same allergen, and to correlate these levels with airway responsiveness. METHODS: Nineteen patients with asthma and 18 subjects with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the study. ENO values and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured during the pollen season. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV1 (PC20). ENO was measured with the single-exhalation method. RESULTS: The geometric mean (95% confidence interval) ENO values were significantly higher in asthmatics than in subjects with allergic rhinitis: 72.4p.p.b. (54.9-93.3p.p.b) vs. 44.7p.p.b. (30.9-64.6p.p.b., P = 0.03). In asthmatics, a significant correlation was found between ENO and PC20 AMP values (p = -0.57, P=0.02), whereas no correlation was detected between ENO and PC20 methacholine (p = -0.35, P = 0.14). CONCLUSIONS: Our results suggest that atopy is not the only determinant of increased ENO levels detected in subjects with asthma, and that responsiveness to AMP may be a more sensitive marker for assessing airway inflammation in asthma compared to methacholine.     

Modifications of PC20 and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients

We examined the effect of cessation of exposure to pollen on non-specific airway responsiveness in 10 grass and/or parietaria pollen sensitive asthmatics. Three methacholine inhalation challenges were performed, the first during pollen season (seasonal period), the second 2 months after the end of season (short lime after seasonal period), and the third 5 months after the end of season (long time after seasonal period). The dose response curves to methacholine were characterized by the PC20 (provocative concentration of methacholine required to produce a 20% fall in FEV|) and maximal response plateau, if possible. A maximal response plateau on the dose-response curve was considered to he present if three or more data points for FEV₁ fell within a 5% response range. The challenge was stopped when FFV₁ dropped more than 50% or the highest concentration of methacholine (200 mg/ml) was reached. The geometric mean (range) methacholine PC20 increased from 1.08 (0.18–37.22) in the seasonal period to 4.67 (0.71–200) mg/ml during the long time after seasonal period (P< 0.01). On the other hand, in six subjects in whom it was possible to obtain a plateau on at least one challenge, the level of the maximal response decreased from (mean ± s.e.m.) 44.1 ± 4.9 in the seasonal period to 30 ± 4.4 during the long lime after seasonal period (P < 0.05). These results suggest that in pollen sensitive asthmatic patients, the cessation of exposure to pollen is associated with a reduction of non-specific bronchial responsiveness (PC20 and maximal degree of airway narrowing to methacholine).     

Nasal physiology and inflammatory mediators during natural pollen exposure

Nasal allergen challenges in allergic rhinitis subjects provoke characteristic alterations in nasal and eustachian tube (ET) function. The purpose of this study was to examine the effect of natural pollen exposure on nasal physiology and inflammatory mediators. Grass pollen counts, ET function (sonotubometry), nasal resistance (rhinomanometry), symptoms, mediator levels (saline wash), and skin test reactivity in nine adults with grass allergy were monitored weekly before (week 1), during (weeks 2 to 9) and after (weeks 10 and 11) grass pollen season. Pollen counts peaked at week 3, and then decreased gradually. Mean nasal resistance (cm H2O/L/sec) increased from a baseline of 2.4 +/- 0.5 to 3.7 +/- 1.1 at week 3, peaked at week 4 (5.3 +/- 1.2), remained elevated (weeks 5-8), peaked again at week 9 (6.6 +/- 1.4), and then decreased, Bilateral ET obstruction was not present in any of the subjects at baseline, but was present in five of the nine subjects at week 4. Symptom severity paralleled grass pollen counts. Peak mediator levels were observed at weeks 2 and 9 for histamine and at weeks 3 and 10 for leukotriene C4. Seasonal increases in grass and histamine-induced wheal sizes were also observed. These data show that measurable changes in the function of the nose and ET and the levels of nasal mediators and dermal reactivity accompany and track pollen counts during seasonal exposure and suggest that therapy for seasonal allergic rhinitis should be (1) directed at reducing airway inflammation and (2) continued well beyond the time of peak pollen exposure.     

Effect of seasonal exposure to pollen on specific bronchial sensitivity in allergic patients

Bronchial provocation tests with aerosol of birch extract were performed before and after pollen season in 11 sensitized subjects. Changes of metacholine bronchial responsiveness and serum-specific IgE level were also assessed. In five patients who did not take steroids to control their symptoms, both early and late asthmatic responses to inhaled allergen were enhanced after season, whereas IgE serum level, but not methacholine sensitivity, was significantly increased. In six patients who needed steroids, neither responses to allergen nor IgE serum level and methacholine sensitivity were significantly changed after season. For the whole group, the increase in immediate bronchial sensitivity to allergen was positively correlated with the increase in specific IgE antibodies. We conclude that seasonal exposure to pollen has, in sensitized patients, a priming effect on bronchial mucosa that may be blunted by steroid treatment. The increased production of specific IgE antibodies appears to be an important mechanism for this priming effect.     

Influence of natural antigenic exposure on bronchoalveolar lavage in subjects with pollen-induced rhinitis

To determine if atopic subjects without asthma naturally exposed to antigens to which they are sensitized demonstrate evidence of lower airway inflammation, we studied 10 subjects with recurrent seasonal allergic rhinitis to pollens. Each subject had a monthly methacholine challenge and two bronchoalveolar lavages (BAL), one during symptoms of allergic rhinitis and one out of season. The percentage of macrophages, lymphocytes, neutrophils, eosinophils, and mast cells in the lavage fluid were determined on Diff-Quik, nonspecific esterase, or toluidine blue-stained cytocentrifuge preparations. The total number of cells recovered on BAL was 23.2 +/- 3.5 X 10(6) (mean +/- SEM) (13.3 +/- 2.3 X 10(4) cells per milliliter) in season, during symptoms of allergic rhinitis, and 33.8 +/- 7.4 X 10(6) (15.2 +/- 3.1 X 10(4) cells per milliliter) out of season (p greater than 0.05). BAL cell-differential counts (percent) in/out season were similar for macrophages (89.0/84.6), lymphocytes (9.1/12.8), neutrophils (1.3/2.1), eosinophils (0.5/0.5), epithelial cells (0.37/0.46), and mast cells (0.0008/0.0013). Blood eosinophil counts, taken, respectively, in and out of season, were 135.5 +/- 26.8 X 10(6)/L and 102.8 +/- 20.6 X 10(6)/L (p greater than 0.05). Although overall airway responsiveness increased slightly during the pollen season, it did not reach statistical significance (geometric mean of provocative concentration causing a 20% fall in FEV1 [milligrams per milliliter], 98.8 during antigenic exposure compared to 121.4 out of season) (p greater than 0.05. These observations suggest that in subjects without asthma, no changes in cell differential are detected on BAL at the time of maximal symptoms of allergic rhinitis.     

Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is an effective therapy for symptoms of seasonal allergic rhinitis, a disease governed by patients' individual sensitivity and exposure to relevant allergens. OBJECTIVE: To evaluate the relationship of montelukast treatment effect vs pollen exposure in studies conducted during 3 consecutive fall allergy seasons. METHOD: A combined analysis of these multicenter, randomized, double-blind, parallel-group studies was performed; 1 of the 3 studies is presented for the first time in this article. After a placebo run-in period, 1,862 symptomatic patients were randomly assigned to receive either a 10-mg montelukast tablet (n = 929) or placebo (n = 933) once daily for 2 weeks. Pollen exposure was summarized by mean daily weed pollen count. The interaction between treatment effect and pollen exposure was evaluated on the primary efficacy endpoint and daytime nasal symptom score, as rated by patients; also evaluated was the influence of the timing of the 2-week treatment period relative to the peak of the weed pollen season. RESULTS: Montelukast significantly improved daytime nasal symptoms score and individual scores of congestion, rhinorrhea, itching, and sneezing compared with placebo. There was a significant interaction (P < .043) between treatment effect and weed pollen exposure; a larger treatment effect was noted in patients exposed to higher pollen counts. An interaction between treatment effect and timing of treatment in relation to peak pollen season was suggested. CONCLUSIONS: Montelukast significantly improved daytime nasal symptoms score in patients with seasonal allergic rhinitis, and the effect was greater in patients exposed to higher pollen levels.