Relationship between viral antibodies and bronchial hyperresponsiveness in 495 unselected children and adolescents

The purpose of this study was to investigate whether recent and previous subclinical viral respiratory infection can explain the presence of increased bronchial responsiveness to histamine. We studied a randomly selected population of 495 children and adolescents, aged 7–16 years, from Copenhagen. If the subjects had had symptoms of respiratory infection recently, the examination was postponed for at least 6 weeks. Bronchial hyperresponsiveness (BHR) to inhaled histamine was found in 79 (16%) of the subjects, of whom 28 had asthma. Forty-eight subjects (10%) had increased levels of serum IgM antibodies against either parainfluenza, influenza, adenovirus, or respiratory syncytial virus (RSV), reflecting a recently acquired infection. No association between BHR and antibodies against respiratory viruses was found, as 7 (8.9%) of the 79 subjects with BHR and 41 (9.9%) of the 416 subjects without BHR had viral antibodies. Furthermore, no association between degree of bronchial responsiveness and viral antibodies was found. Moreover, 251 individuals (51%) had signs of earlier RSV infection, i.e. IgG antibodies against RSV. No relationship was found between age of the subjects and the presence of antibodies against either respiratory viruses in general or IgG-RSV. No relationship was found between the presence of antibodies against RSV and BHR; furthermore, evidence of earlier RSV infection was unrelated to the level of lung function and degree of bronchial responsiveness. We conclude that increased bronchial responsiveness in asymptomatic, unselected schoolchildren and adolescents is not likely to be caused by recent or previous viral respiratory infections.     

Histamine hyperresponsiveness of the extrathoracic airway in patients with asthmatic symptoms

Functional abnormalities of the extrathoracic airway (EA) may produce symptoms mimicking bronchial asthma. We assessed the bronchial (B) and EA responsiveness to inhaled histamine in 40 patients with asthmatic symptoms and in nine asymptomatic controls. FEV1 and maximal mid-inspiratory flow (MIF50) were used as index of bronchial and EA narrowing. Hyperresponsiveness of the intra-(BHR) or extra-(EA-HR) thoracic airway was diagnosed when the provocative concentrations of histamine (PC20FEV1 or PC25MIF50) were less than 8 mg/ml. Fiberoptic laryngoscopy was performed in nine patients and three controls. The glottal region was measured at mid-volume of maximal inspiration (AgMI) and expiration (AgME) before and after histamine. Predominant EA-HR was found in 13 patients, predominant BHR in 12, equivalent BHR and EA-HR in another 12; no significant airway narrowing was observed in three patients and in the nine controls. EA-HR was significantly associated with female sex, sinusitis, post-nasal drip, dysphonia; BHR with atopy, wheezing and lower MEF50. The percent change in AgMI after histamine was closely related to the PC25MIF50 (r = 0.87, P less than 0.001), that of AgME to the PC20FEV1 (r = 0.78, P less than 0.01). These findings suggest that the assessment of EA responsiveness may be useful in the evaluation of asthmatic symptoms, especially in patients with no BHR.     

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. I. Relation to respiratory symptoms and diagnosed asthma

In order to explore the relationship between bronchial hyperresponsiveness (BHR) to inhaled histamine, respiratory symptoms and diagnosed asthma in children, we undertook a cross-sectional study of 2363 Australian schoolchildren aged 8–11 years. The methods used included a self-administered questionnaire to parents, which was shown to have a high degree of repeatability, and a histamine inhalation test to measure bronchial responsiveness (BR). The study showed that 17.9% of children had BHR, defined as a 20% fall in FEV₁ at a provoking dose of histamine (PD₂₀ FEV₁) of less than 7.8 μmol. The distribution of PD₂₀ FEV₁ appeared to be continuous. Most children with PD₂₀ FEV₁ values < 1.0μmol had symptoms of asthma. However, 6.7% of children had BHR without symptoms or a previous diagnosis of asthma and 5.6% had had a diagnosis of asthma but had no BHR. Although there was a good association between BHR and respiratory symptoms, questionnaire data of wheeze and diagnosed asthma do not reflect accurately the level of BHR in the community. We conclude that cross-sectional studies of BR to identify children with BHR probably do not reflect the prevalence of asthma in populations of children. However, the strong association between BHR and symptoms, particularly in children with severe and moderate BHR, suggests that measurements of BR in populations are useful for defining a group of children whose airways behave differently from those of the majority. Prospective studies are needed to define the level of BHR that is associated with important sequelae.     

The distribution of bronchial responsiveness to histamine and exercise in 527 children and adolescents

The aim of the study was to describe the bronchial responsiveness to inhaled histamine and exercise in a randomly selected group of 527 children and adolescents from Copenhagen, aged between 7 to 16 years. The distribution of the bronchial responsiveness was described as (1) the provoking concentration that causes a 20% reduction in FEV1 (2) the dose-response slope (DRS), that is, the linear slope of the dose-response curve, and (3) reduction in FEV1 after 6 minutes of exercise on a treadmill. The distribution of the concentration that causes a 20% reduction in FEV1 in the responsive range was not significantly different from a unimodal distribution, although the findings were skewed toward the less responsive end of the range (p greater than 0.05). The subjects with asthma represented a subgroup within the responsive distribution tail rather than a separate distribution peak. In asymptomatic individuals, the values of DRS were distributed symmetrically on a logarithmic scale. The deviation from normal was such that the standard deviation only slightly underestimated the "normal" range. The distribution of the bronchial response to exercise was found to be significantly different from a normal distribution. However, a significant relationship was found between the bronchial response to inhaled histamine and exercise (p less than 0.0001). We conclude that there is a log-normal distribution of the bronchial response to inhaled histamine in a random sample of children and adolescents.     

Relationship Between Atopy and Bronchial Hyperresponsiveness

Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.     

Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma

Ulrik CS, Backer V, Bach-Mortensen N. Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma. The purpose of this study was to compare the bronchodilating effect of ipratropium bromide (IB) administered by a conventional Ingelheim powder device system (IPI) and by a metered dose inhaler (MDI) in children and adolescents with stable bronchial asthma. Seventy patients, aged 7 to 16 years, with stable bronchial asthma from our outpatient clinic were tested for bronchial responsiveness to inhaled IB. Fifteen (21%) of the 70 subjects were found to have a substantial bronchial response to inhalation of 40 γg IB, i.e. at least 15% increase in FEV₁ 30 min after inhalation; the remaining 55 subjects had <15% increase in FEV₁. No relationship between severity of asthma, age or sex and bronchial responsiveness to inhaled IB was found. Among the 15 subjects who had substantial bronchial response to IB, the increase in FEV₁ after inhalation of fenoterol tended to be greater than the response to inhaled IB, although this did not reach statistical significance. Responders, i.e. subjects who had at least 15% increase in FEV₁ after inhalation of IB, took part in a double-blind, cross-over study of the bronchodilating effect of 40 γg IB delivered by IPI and MDI. We found no significant differences in the bronchodilating effect during a 6-h follow-up. Maximum bronchodilating effect of IB was reached after 30 min and the maximum response lasted for 90 min. No side or adverse effects were observed following inhalation of IB. We conclude that before starting treatment with ipratropium bromide for bronchial asthma in children and adolescents, the patients should be tested for bronchial responsiveness to inhaled IB to find out whether they are responders or nonresponders; and further that, among responders, inhalation of powder is as effective as inhalation from a dosis-aerosol.     

Bronchial responsiveness to exercise in a random sample of 494 children and adolescents from Copenhagen

To investigate the bronchial response to exercise, we studied a random sample of 494 children and adolescents, aged 7-16 years, from Copenhagen. Exercise challenge consisted of steady running on a 10% sloping treadmill for 6 min in a climate chamber. Furthermore, in 464 subjects a histamine challenge test was also performed. Of the 494 subjects studied, 81 (16%) had at least 10% and 30 (6%) at least 15% reduction in FEV1 within 15 min after exercise. Twenty-nine (6%) subjects had bronchial hyperresponsiveness to both histamine and exercise, 48 (10%) subjects had bronchial hyperresponsiveness to exercise, but histamine responsiveness within the normal range, whereas 340 (73%) subjects had neither bronchial hyperresponsiveness to exercise nor inhaled histamine. With regard to the presence of asthma defined as substantial exercise induced bronchoconstriction (delta-FEV1 greater than or equal to 10%), exercise testing may not be appropriate for identifying clinical asthma in a random sample, because the highest predictive value of a positive test was 25%. On the other hand, a history of clinical asthma was frequently associated with increased bronchial responsiveness to exercise (77%). In conclusion, 16% of a random sample of children and adolescents had abnormal bronchial responsiveness to exercise (delta FEV1 greater than or equal to 10%), 6% of the subjects had a delta FEV1 greater than or equal to 15%. Furthermore, because of a low predictive value of a positive test, the exercise challenge test has only a supplementary role in the detection of clinical asthma in population samples.     

Selective subsensitization of beta-adrenergic receptors in central airways of asthmatics and normal subjects during long-term therapy with inhaled salbutamol

In five subjects with mild asthma and in five normal subjects, we determined the effect of a 4 wk course of inhaled salbutamol (albuterol), 200 μg q.i.d., on (I) acute bronchodilator responsiveness, (2) bronchial sensitivity to inhaled histamine, (3) beta-adrenergic protection against histamine-induced bronchospasm, and (4) beta-receptor density of peripheral blood lymphocytes. We observed a diminution in central airway bronchodilator responsiveness (as measured by airway conductance responses) to acutely inhaled salbutamol and to subcutaneous terbutaline in both groups of subjects, although only the response to subcutaneous terbutaline was statistically significant (p < 0.02). On the other hand, no impairment of small airway bronchodilator responsiveness was noted in either group of subjects when responses were measured as partial expiratory flow rates at 60% below total lung capacity. These findings suggest the development of selective subsensitization of beta-receptors in the larger central airways, where a proportionately greater amount of the inhaled beta-agonist aerosol would necessarily be deposited. A greater loss of protection against histamine-induced bronchospasm was seen in asthmatics than in normals (approximately twofold), although the difference was not significant. A modest but not significant reduction in peripheral blood lymphocyte beta-receptor density was observed by the end of the 4 wk treatment period. The possibility that the observed changes in bronchodilator responsiveness might influence the morbidity and mortality associated with bronchial asthma is discussed.     

Bronchial responsiveness increases after seasonal antigen exposure in non-asthmatic subjects with pollen-induced rhinitis

This study looked at the effects of natural antigenic exposure on non-specific airway responsiveness (NSAR) in pollen-sensitized non-asthmatic subjects with seasonal rhinitis. Eight subjects had daily recordings of their respiratory symptoms and peak flow rates during and out of the pollen season. Airway response to methacholine was measured at 1-week to 2-week intervals. Pre-season spirometry and NSAR were normal in all subjects. Their PC20 methacholine ranged from 64 to greater than 256 mg/mL. During natural pollen exposure, all subjects had symptoms of rhinoconjunctivitis. The only chest symptom observed was coughing. No significant change in peak flow rates was observed throughout the study. A significant increase in bronchial responsiveness to methacholine occurred in five subjects although it did not reach the asthmatic range (less than 16 mg/mL). This change in NSAR was reproduced after antigen (tree pollen) challenge in the laboratory in one of the subjects. A significant increase in blood eosinophils was observed during seasonal pollen exposure. This study shows that following natural antigenic exposure, NSAR can increase in non-asthmatic subjects with allergic rhinitis, although it may not reach the "hyperresponsive range," and is associated with the development of a cough. These data suggest that natural exposure in non-asthmatic atopics may induce an inflammatory reaction in the airways to a degree that may increase NSAR.     

Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis and allergic sensitization at the age of 7 years

BACKGROUND: Bronchial responsiveness (BR) to histamine or methacholin is a common finding in adult non-asthmatic patients with allergic rhinitis. OBJECTIVE: We tested whether BR is also present in children with a comparatively short history of allergic rhinitis in a paediatric cohort. METHODS: We performed pulmonary function tests and histamine challenges in a total of 654 children (age 7 years, participants of the German Multicenter Allergy Study) and compared PC20 FEV1 values in children with asthma, allergic rhinitis, asymptomatic allergic sensitization and non-atopic controls. RESULTS: Most pronounced BR to histamine was observed in allergic asthmatics (n = 28), irrespective of the presence or absence of allergic rhinitis. Furthermore, PC(20)FEV(1) values in non-asthmatic children with allergic rhinitis (n = 24) were not significantly different from those seen in asymptomatic atopic (n = 54) or non-atopic controls (n = 92). CONCLUSIONS: In contrast to adult study populations, 7-year-old non-asthmatic children with allergic rhinitis do not show a higher degree of BR than asymptomatic atopic or non-atopic controls. Therefore, secondary preventive measures in non-asthmatic children with allergic rhinitis (such as regular local anti-inflammatory therapy or specific immunotherapy) should be studied and applied more intensely to prevent bronchial hyper-responsiveness (BHR) and asthma in this high-risk group.     

Ability of polymorphonuclear leukocytes to generate active oxygen species in children with bronchial asthma. Use of chemiluminescence probes with a Cypridina luciferin analog and luminol.

Airway inflammation with polymorphonuclear leukocytes (PMN) may play an important role in bronchial hyperresponsiveness (BHR). PMN generate superoxide anion (O2-) and other oxygen radicals that can damage lung tissue. We investigated the ability of peripheral PMN of children with bronchial asthma and control subjects to generate O2- and other active oxygen species using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one, a highly sensitive and specific chemiluminescence (CL) probe for O2-, and luminol-dependent CL. The ability of PMN of subjects with asthma to generate O2- and other active oxygen species was significantly greater than that of PMN of control subjects when stimulated with opsonized zymosan (OZ), phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine. Furthermore, in the same asthmatic children, the generation of O2- and other active oxygen species was significantly higher with attacks than without attacks when PMN were stimulated with OZ. We also demonstrated that O2- generation correlated with the degree of BHR to inhaled histamine. These results suggest that PMN of asthmatic children, especially those with attacks, generate more active oxygen species than that of control subjects and that airway inflammation caused by O2- may be closely related to BHR in subjects with bronchial asthma.     

Distribution of serum IgE in children and adolescents aged 7 to 16 years in Copenhagen, in relation to factors of importance

The distribution of total serum-IgE and factors of importance for the level of IgE was studied in a random sample of 508 children and adolescents, aged 7-16 years, from Copenhagen. A detailed history about asthma, rhinitis, dermatitis and urticaria was obtained, and a physical examination, skin prick test with 9 common allergens, lung function test, bronchial challenge with inhaled histamine and exercise, and measurement of IgE (kU/l) were performed. The distribution of IgE among children and adolescents was found to exhibit a log normal distribution and a positive skin prick test, allergic symptoms, a family history of allergic diseases, age and smoking were found to be significantly related to an increased level of IgE. No relationship was found between increased bronchial responsiveness and IgE. The geometric mean of "normal" values of IgE (*1 SD and *2 SD) of the Danish children and adolescents was 18 kU/l (*4.7, *18.2), suggesting that normal IgE values were within 330 kU/l. Measurement of IgE as the only screening for allergic disease is unreliable, as the predictive value of an elevated IgE in population samples was found to be 50%, whereas misclassification (1-specificity) of asymptomatic subjects as allergic because of an increased IgE was low (4%). In conclusion, total IgE is highly influenced by allergen skin reactivity. Further, this study suggests that normal IgE values were within 330 kU/l, although the range was wide.     

The type of sensitizing allergen can affect the evolution of respiratory allergy

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.     

Atopy in infancy predicts the severity of bronchial hyperresponsiveness in later childhood

We have prospectively followed 52 children of atopic parents from birth to age 7 years, documenting clinical atopic disease and allergen skin test reactions. We found bronchial hyperresponsiveness (BHR) to histamine in 13 (25%) of the children at 7 years of age with 25 (48%) being atopic on skin testing and 15 (29%) having current wheeze, whereas 30 children (58%) had wheezed at some time during this period. BHR was significantly associated with wheeze and atopy at 5 and 7 years of age, but not during infancy. The six children with moderate to severe BHR (provocative dose causing a 20% fall in FEV1 less than 0.8 mumol) formed a distinct subgroup with significantly more wheeze and atopy both during infancy and at 5 years of age when these children were compared to children with milder degrees of BHR. The group with moderate to severe BHR also differed significantly from the nonhistamine-reactive group, whereas children with milder degrees of BHR were not significantly different. We conclude that subjects most likely to develop the more severe degrees of BHR during later childhood are children who manifest atopy in infancy.     

Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up

BACKGROUND: A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7-year follow-up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development. METHODS: Twenty-eight children (6-15 years) with AR were studied. At enrollment (T(0)), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)(1) fall (PD(20)FEV(1)) and as dose-response slope (D(RS)). Subjects were reassessed after 7 years (T(1)) using the same criteria. RESULTS: At T(0), 13 children (46%), showing a PD(20)FEV(1) <1526 microg of Mch, had BHR (Mch+), although PEF variability (PEFv) was within normal limits. None of the children with negative methacholine test developed bronchial asthma after 7 years. Of the 13 Mch+, only two reported asthma symptoms after 7 years. No significant change was seen in the other parameters of atopy considered. CONCLUSION: Children with allergic rhinitis present a high prevalence of BHR. Nevertheless, their PEFv is normal and the rate of asthma development low.     

Role of FEF25%-75% as a predictor of bronchial hyperreactivity in allergic patients.

BACKGROUND: The small airways may play an important role in the clinical manifestations of asthma. Forced expiratory flow between 25% and 75% (FEF25%-75%) has been proposed as an approximate measure of the caliber of distal airways. Bronchial hyperreactivity (BHR) is a feature of asthma. OBJECTIVE: To evaluate the possible role of FEF25%-75% as a predictor of BHR in allergic patients with asthma and rhinitis. METHODS: A total of 726 patients (mean +/- SD age, 24.7 +/- 6.3 years) were evaluated. Spirometry and methacholine bronchial challenge were evaluated in all the participants. RESULTS: A difference between forced expiratory volume in 1 second and FEF25%-75% greater than 20 or a ratio between these variables greater than 1.24 discriminates between patients with no response to a mild response to methacholine vs patients with a moderate-to-severe response with high sensitivity (P < .001). CONCLUSION: This study highlights the possible role of FEF25%-75% in predicting BHR in allergic individuals with airway disorders.     

Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo

Background Interleukin-8 (IL-8) hus been shown to be a chemotactic factor for netitrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which arc released trotn C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness. Methods IL-8 at a dose of 5μg/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness. Result The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness. Conclusion We conclude that repeated intranasal administratioti of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.     

Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats.

Bronchial responsiveness to inhaled acetylcholine (ACh) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred Brown-Norway rats actively sensitized to, and later exposed to, ovalbumin (OA). We examined animals 21 days after initial sensitization at 18 to 24 hours, or 5 days after a single challenge, or after the last of seven repeated exposures administered every 3 days. BALF was examined as an index of inflammatory changes within the lung. Animals repeatedly exposed to OA aerosols had an increased baseline lung resistance and a significant increase in bronchial responsiveness to inhaled ACh compared to control animals at both 18 to 24 hours and 5 days after the last OA exposure. Sensitized animals receiving a single OA aerosol also demonstrated bronchial hyperresponsiveness (BHR) to inhaled ACh (p less than 0.01) at 18 to 24 hours of a similar order as the multiple-exposed group. There was a significant increase in eosinophils, lymphocytes, and neutrophils in BALF at 18 to 24 hours but not at 5 days after single or multiple exposure to OA aerosol in the sensitized groups. Control animals demonstrated no changes in bronchial responsiveness, although a small but significant increase in inflammatory cells was observed compared to saline-only treated animals. There was a significant correlation between bronchial responsiveness and eosinophil counts in the BALF in the single allergen-exposed group (Rs = 0.68; p less than 0.05). We conclude that (1) BHR after allergen exposure in sensitized rats is associated with the presence of pulmonary inflammation but persists despite the regression of inflammatory cells in BALF after multiple OA exposures, and (2) this rat model has many characteristics of human allergen-induced BHR.     

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.     

Bronchial hyperreactivity and spirometric impairment in patients with perennial allergic rhinitis

BACKGROUND: Allergic disorders are characterized by a systemic involvement of the immune response. There is a clear link between allergic rhinitis and asthma. Bronchial hyperreactivity (BHR) may be present in rhinitics. Smaller airways may also be impaired in mild asthma. This study aimed at evaluating a group of subjects suffering from perennial allergic rhinitis alone to investigate the presence of BHR and spirometric impairment. METHODS: One hundred rhinitics sensitized only to perennial allergens were evaluated. Spirometry and methacholine bronchial challenge were performed. RESULTS: Five rhinitics showed reduced values of forced expiratory volume/1 s (FEV(1)) without symptoms of asthma. Forty-eight rhinitics had reduced forced expiratory flow at 25 and 75% of pulmonary volume (FEF(25-75)) values. Seventy-two patients showed a positive methacholine challenge. In this group, reduced values of FVC (p < 0.05), FEV(1) (p < 0.05), and FEF(25-75) (p < 0.01) were demonstrated in comparison with BHR-negative rhinitics. There was a relationship between the degree of BHR and FEV(1) values (p < 0.05) and FEF(25-75) values (p < 0.01). CONCLUSIONS: This study evidences that an impairment of spirometric parameters may be observed in patients with perennial allergic rhinitis alone. A high percentage of these patients have BHR. Thus, new management strategies should be employed in rhinitics.