Effect of cetirizine on bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and asthma

Although H1 antihistamine compounds (H1) are highly effective in the treatment of allergic rhinitis (AR), their role in the treatment of asthma is still controversial. Because a strong association between AR and bronchial hyperresponsiveness (BHR) has been reported, this study was designed to assess the effect of a new H1 anti histamine, cetirizine (C), on nonspecific BHR in patients with AR. Twelve patients were included in a double-blind, crossover, placebo-controlled trial. All patients had positive skin tests for common allergens and showed BHR to inhaled methacholine after specific nasal allergenic challenge. After a washout period of 1 week to ensure the stability of the BHR, the patients received, by crossover randomization, C 10 mg daily or placebo (P) for 2 weeks. After each treatment period, BHR and nasal blocking index (NBI) were measured 1 and 6 h after nasal challenge. Bronchial responsiveness was expressed as methacholine PD20, the provocation dose of methacholine causing a 20% decrease in FEV1. Measurements were then performed after 2 weeks of C and after 2 weeks of P. Baseline values of PD20 (median) measured before challenge showed no difference after cetirizine or after placebo (1.36 mg). Results 1 h after allergen did not show significant differences between C (methacholine PD20=0.522 mg) and placebo (methacholine PD20=0.455 mg). By contrast, 6 h after challenge, methacholine PD20 was 0.918 mg for C and 0.483 mg for P (P=0.042). Similarly, NBI showed no change between C and P 1 h after challenge, whereas the difference was significant 6 h after challenge (P=0.011 ). These data demonstrate a protective nasal effect of C against BHR measured 6 h after nasal allergen challenge in patients with AR. They suggest that C may be useful in patients with asthma associated with AR.     

Effect of pranlukast on bronchial inflammation in patients with asthma

BACKGROUND: Pranlukast (8-[p-(4-phenylbutyloxy) benzol] amino-2-[tetrazol-5-yl]-4-oxo-4H-1-benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, has been reported to exhibit not only antileukotrine activity but also pharmacological activity including antieosinophilic effects. OBJECTIVE: This study was designed to investigate whether the antiasthmatic activity of pranlukast is associated with a reduction in eosinophilic inflammation. METHODS: A double-blind, randomized, crossover design was used. Subjects received 225 mg of pranlukast or placebo orally twice daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine in 32 adult patients with mild or moderate bronchial asthma; those who were in stable clinical condition were allocated to this study. Blood and sputum samples were taken the morning of the methacholine provocation test. Eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed. RESULTS: After the 4 weeks of treatment with pranlukast, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Furthermore, values of PC20-methacholine significantly improved in the treatment with pranlukast. CONCLUSION: Our results suggest that pranlukast has an anti-inflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of bronchial asthma.     

Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing

BACKGROUND: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. METHODS: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. RESULTS: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r= -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r= -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. CONCLUSIONS: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.     

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Sputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This study aimed to assess the distribution of sputum eosinophil count and its relationship with methacholine bronchial hyperresponsiveness in mild to moderate steroid-naive asthmatic people. METHODS: Sputum was induced by inhalation of hypertonic saline (NaCl 4.5%) in 118 mild to moderate steroid-naive asthmatic people consecutively recruited from our outpatient clinic, and in 44 healthy people. The asthma group was selected on the basis of an forced expiratory volume in 1 s (FEV(1)) of > or = 70% predicted, and a provocative methacholine concentration causing a fall of 20% in FEV(1) (PC20 methacholine; PC(20)M) < or = 16 mg/ml. RESULTS: In the asthma group, the median (range) of the percentage and the absolute values of sputum eosinophils were 4.8% (0-75) and 38 10(3)/g (0-14,191), respectively, vs 0% (0-2.3) (P < 0.001) and 0 10(3)/g (0-53) (P < 0.001) in healthy participants. Based on the 95% percentile for normal values calculated from our healthy group, 69% of the asthma group had significantly raised sputum eosinophil count (that is > 2%). In the asthma group, multiple regression analysis followed by a stepwise procedure revealed that sputum eosinophil count was significantly and inversely associated with PC(20)M accounting for 16% of its total variance (P < 0.001) while neutrophil counts positively related to PC(20)M accounting for 4% of total variance (P < 0.05). By contrast, no significant relationship was found between either eosinophil or neutrophil counts and the slope of forced vital capacity (FVC) vs FEV(1) from the methacholine challenge. CONCLUSIONS: We conclude that two-thirds of people in the mild to moderate asthma group had increased sputum eosinophilia, which plays a limited role in determining the degree of methacholine airway hyperresponsiveness.     

Evaluation of cytokine mRNA in induced sputum from patients with allergic rhinitis: relationship to airway hyperresponsiveness

Background:  Although airway hyperresponsiveness (AHR) is a characteristic feature of asthma, it is also frequently present in allergic rhinitis (AR). However, the pathogenesis of AHR is unclear and the roles of cytokines in the airway have not been well established in AR. We sought to compare cytokine mRNA levels in the sputum of AR patients with or without AHR and those of asthma patients, and to evaluate whether differences in cytokine levels are associated with the development of an abnormal airway response and the absence of respiratory symptoms in AR patients with AHR.
Methods:  Airway cells were obtained by sputum induction from 18 AR patients with AHR, 58 AR patients without AHR, and 27 asthma patients. Airway cell cytokine levels, interleukin (IL) -4, IL-5, IL-13, vascular endothelial growth factor (VEGF), and interferon-γ (IFN-γ), were studied at the mRNA level by RT-PCR.
Results:  Vascular endothelial growth factor and IL-5 mRNA levels were significantly higher in AR patients with AHR than in AR patients without AHR, but these were lower than those of asthmatic patients. Eosinophils were significantly higher in AR patients with AHR and in asthmatic patients than in AR patients without AHR. Interleukin-4, IL-13, and IFN-γ levels were not elevated in AR patients with or without AHR vs asthma patients.
Conclusions:  These findings suggest that VEGF and IL-5 can be important determinants of the development of AHR in AR patients and that lower levels of other cytokines may be associated with the absence of asthmatic symptoms in AR patients with AHR.     

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.     

Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients

Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A-BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge-induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short-evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A-BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]-5) were analyzed, before and 24 h after A-BPT. Methacholine BHR, assessed before and 32 h after the A-BPT, was defined by M-PD20 values and, when possible, by maximal response plateau (MRP). The A-BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late-phase responses (LPR). M-PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P = 0.025). The A-BPT induced no change in sputum albumin, tryptase, or IL-5 values. We conclude as follows: 1) In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA. 2) MRP levels increased in both AA and AR patients after allergen challenge; however, M-PD20 values significantly changed only in the AA group, suggesting that the components of the airway response to methacholine were controlled by different mechanisms. 3) It is possible that the differences between AR and AA lie only in the quantitative bronchial response to allergen inhalation.     

Allergen-induced bronchial inflammation in house dust mite-allergic patients with or without asthma

BACKGROUND: It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite-allergic individuals. The level of allergen-specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem to differ significantly between asthmatic and non-asthmatics individuals. AIM: It was hypothesized that the presence or absence of asthmatic symptoms in house dust mite-allergic patients is associated with quantitative or qualitative differences in the cellular bronchial inflammatory response during the late phase of the allergic reaction. This hypothesis was tested in the bronchial allergen challenge model. MATERIAL AND METHODS: Whole lung challenges with house dust mite extract were performed in 52 house dust mite-allergic subjects, of whom 26 had asthma and 26 had perennial rhinitis without asthmatic symptoms. Primary outcomes were parameters for bronchial inflammation in serial samples of induced sputum (cell differentials, eosinophil cationic protein (ECP), interleukin-8 (IL-8), myeloperoxydase (MPO)). In addition, lung function, non-specific bronchial hyper-responsiveness and serial blood samples (eosinophils and IL-5) were analysed. RESULTS: At baseline sputum eosinophils and ECP were similar in both groups but neutrophils and IL-8 were higher in asthmatics. The early bronchoconstriction after allergen challenge was similar in asthma and non-asthmatic rhinitis (median decrease in FEV1: asthma -31.7% vs. non-asthmatics -29.1%, P > 0.1). The late phase bronchoconstriction was significantly greater in asthma (median decrease in FEV1: asthma -27.6% vs. non-asthmatics -18.9%, P = 0.02). Induction of bronchial hyper-responsiveness was similar in both groups. Bronchial allergen challenge elicited significant increases in sputum eosinophils and ECP, which were indistinguishable for both groups (P > 0.1 and P = 0.07, respectively). In contrast, higher numbers of neutrophils persisted in asthma 24h after challenge and were accompanied by significant increases in IL-8 and MPO, which were absent in non-asthmatics (difference between groups P = 0.007 and P = 0.05, respectively). CONCLUSION: Allergen challenge inducedvery similar increases in eosinophils and ECP in induced sputum in allergic asthmatics and in allergic non-asthmatic patients. The difference in bronchial inflammation between asthma and non-asthmatic rhinitis appeared to be more closely related to indices for neutrophilic inflammation.     

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.     

Comparison of the effects on bronchial hyperresponsiveness of antiallergic agents and beclomethasone dipropionate in long-term bronchial asthma

The effect of antiallergic agents (DSCG (disodium cromoglycate), ketotifen, and ibudilast) and beclomethasone dipropionate inhaler (BDI) on bronchial hyperresponsiveness to histamine inhalation was retrospectively assessed in 72 asthmatic patients with more than a year's duration of the disease. Decrease in bronchial hyperresponsiveness to histamine was observed in 10 out of the 33 (30%) antiallergic-agents-treated patients (group A, mean duration = 7.8 months), in 12 of 19 (63.2%) BDI-treated patients (group B, 6.2 months), but only 2 of the 20 (10%) control patients (group C, 7.8 months). Improvement of histamine PC₂₀ was from 310 to 597 μg/ml ( P <0.01) in group A, from 308 to 1622 μg/ml ( P <0.0005) in group B, and from 575 to 525 μg/ml (NS) in group C. A significant decrease in the peripheral eosinophil count was observed only in group B. The improvement in bronchial hyperresponsiveness was parallel with that of asthmatic symptoms; the percentage of patients becoming symptom-free rose from 12 to 42%, 5 to 89%, and 5 to 20% in groups A, B, and C, respectively. Out of 11 unimproved patients in group A, 7 showed a significant improvement in their histamine PC₂₀ by BDI treatment (mean PC₂₀: 311 → 1828 μg/ml). These results suggest that BDI might be more effective than antiallergic agents in the treatment of patients with long-standing bronchial asthma.     

Airway angiogenesis in patients with rhinitis and controlled asthma

Background Airway angiogenesis may be an important part of structural remodelling in the pathogenesis of asthma. The development of asthma is frequently preceded by rhinitis.
Objective We sought to determine whether the levels of angiogenesis-related factors are elevated in airways of patients with rhinitis or controlled asthma.
Methods We analysed the induced sputum of 18 rhinitis patients, 16 asthmatic patients, and 15 healthy controls. The concentrations of angiogenin, vascular endothelial growth factor (VEGF), IL-8, fibroblast growth factor (bFGF), and TNF-α were measured by cytometric bead arrays.
Results We found significantly increased angiogenin and VEGF concentrations in the induced sputum supernatant of both rhinitis and asthma patients compared with that of the healthy control group ( P 0.0005). With the exception of TNF-α, there was no difference in the other angiogenic factors; TNF-α levels were higher in the rhinitis group than in the control group ( P =0.02).
Conclusion These in vivo results suggest increased airway angiogenesis in patients with rhinitis without asthma as well as in corticosteroid-treated and well-controlled asthma patients.     

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.     

Prevalence and severity of allergic rhinitis in house dust mite-allergic patients with bronchial asthma or atopic dermatitis

BACKGROUND: Allergic rhinitis, asthma and atopic dermatitis are closely associated. Although population-based studies report a high prevalence of rhinitis among asthma patients, less is known of the association between rhinitis and atopic dermatitis and the severity of concomitant rhinitis. OBJECTIVES: We aimed to determine the prevalence and severity of allergic rhinitis among asthmatics and patients with atopic dermatitis and assessed whether age and comorbidity influence the severity of rhinitis signs and symptoms. METHODS: Three hundred and twenty-five patients recruited for a multicentre trial to study the effect of encasings of mattresses, pillows and duvets on signs and symptoms of allergic rhinitis and/or asthma and/or atopic dermatitis recorded visual analogue scores (VAS) and daily symptom scores and underwent nasal challenge tests with house dust mite (HDM). RESULTS: Based on history and clinical symptoms 92% of the 164 asthmatic patients and 85% of the 86 patients with atopic dermatitis could be diagnosed as having rhinitis. Inclusion of a positive provocation to HDM did not result in a substantial lower prevalence of rhinitis. Subjects reported moderate symptoms, with mean rhinitis VAS scores ranging from 40.0 to 55.0. Presence of atopic dermatitis was associated with lower rhinitis VAS and symptoms scores, whereas in multivariate analysis the presence of asthma was positively associated with nasal responsiveness to HDM. CONCLUSION: The prevalence of nasal symptoms in patients with bronchial asthma or atopic dermatitis and sensitized to house dust mites is high. Although the majority of patients experience mild to moderate symptoms, the presence of nasal disease needs to be examined in all patients with atopic disorders.     

Genome screen for asthma and bronchial hyperresponsiveness: interactions with passive smoke exposure

BACKGROUND: Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma. OBJECTIVE: We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions. METHODS: A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families. RESULTS: For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q ( P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families. CONCLUSION: The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.     

Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum

BACKGROUND: Eosinophilic inflammation is a crucial aspect of allergic diseases such as bronchial asthma. An eosinophil-active chemokine, eotaxin, may play a role in the pathogenesis of the tissue eosinophilia accompanying asthma. METHODS: Induced sputa were obtained from 53 patients with atopic asthma and six healthy subjects, and the concentration of eotaxin in the sputum was measured by ELISA. We investigated whether the sputum content of eotaxin is related to 1) asthma status or corticosteroid therapy, and 2) other sputum indices, including percentage of eosinophils and concentration of eosinophil cationic protein (ECP). RESULTS: The patients with stable or unstable asthma showed significantly higher concentrations of sputum eotaxin than the normal controls. The level of sputum eotaxin demonstrated a positive correlation with the percentage of eosinophils in stable asthmatics not receiving corticosteroid therapy, but not in stable patients treated with corticosteroids, or in unstable patients. Sputum eotaxin demonstrated a positive correlation with ECP in asthmatic patients who were either in a stable state or not receiving steroid therapy. CONCLUSIONS: The elevated level of eotaxin detected in association with increased eosinophils and ECP in the sputum of asthmatics suggests that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation. The relationship of eotaxin to airway eosinophilia may be modified by the stability status of asthma and corticosteroid therapy.     

Allergic rhinitis with or without concomitant asthma: difference in perception of dyspnoea and levels of fractional exhaled nitric oxide

BACKGROUND/AIM: Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover, AR is often associated with bronchial hyper-responsiveness (BHR). The aim of the present study was to investigate whether patients with AR and asthma differed from AR with or without BHR in degree of perception of dyspnoea and airway inflammation, measured as fractionated exhaled nitric oxide (NO). MATERIALS: Twenty-nine patients with seasonal AR (timothy) were investigated with metacholine challenge test. Fourteen healthy non-reactive subjects served as controls. METHODS: (1) Metacholine challenge test, cut-off value forced expiratory volume in 1 s (FEV(1)) PD20 2,000 microg. Slope value for metacholine was calculated as %fall in FEV(1)/mol metacholine. Dyspnoea during challenge was measured with a 10-graded modified Borg score. (2) Measurement of fractional-exhaled nitric oxide (FENO) at flow rate 50 mL/s. RESULTS: Eighteen patients reported AR only, without asthma symptoms, and 12 (67%) were BHR. Eleven subjects had both rhinitis and asthma symptoms. Patients with rhinitis and asthma reported significantly more dyspnoea per percent fall in FEV(1) compared with those with rhinitis and BHR. Moreover, those with rhinitis and asthma had significantly higher NO values compared with those with rhinitis and BHR. CONCLUSION: The difference between rhinitis patients with or without asthma symptoms seems to be mainly a question of perception of dyspnoea. However, FENO measurement indicates that dyspnoea may also be associated with increased inflammatory activity in the peripheral airways.     

Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma

BACKGROUND: Albeit its exact pathogenesis is still ambiguous; aspirin-intolerant asthma is one of several types of asthma for which antileukotriene therapy is useful, because it is widely accepted that bronchial over-production of leukotrienes may be involved in its pathogenesis. Pranlukast (8-[p-(4-phenylbutyloxy) benzol] amino-2-(tetrazol-5-yl)-4-oxo-4H-1-benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, is now widely used in the treatment of asthma. OBJECTIVE: This study was designed to investigate the protective effect of pranlukast on airway sensitivity to sulpyrine provocation testing, bronchial responsiveness to methacholine provocation testing, and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary LTE4 (uLTE4), a marker of the cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma. METHODS: We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to sulpyrine provocation testing were allocated to this study. A double-blind, randomized, crossover design was used. uLTE4 was measured using combined reverse-phase high-performance liquid chromatography (rp-HPLC)/enzyme immunoassay. RESULTS: Pranlukast protected against analgesic-induced bronchoconstriction through mechanisms that were not related to the bronchodilator property, but were related to the improvement both of bronchial hyperresponsiveness and hypersensitivity to analgesic (P < 0.005 and P < 0.0001). Pranlukast showed little effect on excretion of uLTE4. CONCLUSION: These results support the hypothesis that cysteinyl leukotriene is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Pranlukast improves not only hypersensitivity to analgesic, but also bronchial hyperresponsiveness in aspirin-intolerant asthma. It is also possible that pranlukast has another anti-asthmatic effect besides that of a leukotriene receptor antagonist.     

Changes in bronchial hyperresponsiveness following high- and low-sulphite wine challenges in wine-sensitive asthmatic patients

BACKGROUND: Previous studies suggest that challenge of most wine-sensitive asthmatic patients may not result in a reduction in forced expiratory volume in 1 s (FEV(1)). OBJECTIVE: The aim of this study was to assess whether changes in bronchial hyperresponsiveness (BHR) occur following wine challenge of asthmatic patients who report sensitivity to wine, and whether such changes could help clarify the role of sulphite additives in wine-induced asthmatic responses. METHODS: Eight self-reporting wine-sensitive asthmatic patients completed double-blind challenges with high- and low-sulphite wines on separate days. FEV(1) and histamine PC(20) were measured before and after consumption of 150 mL of wine. RESULTS: None of the eight subjects demonstrated a clinically significant >or=15%) reduction in FEV(1) following challenge with either high- or low-sulphite wine. In contrast, one patient demonstrated clinically significant increase in BHR following challenge with both high- and low-sulphite wines, and a smaller increase in BHR following placebo challenge. A second patient showed a significant increase, while another showed a significant decrease in BHR following challenge with low-sulphite wine. A fourth patient showed borderline increases in BHR following challenge with both high- and low-sulphite wines. CONCLUSIONS: Although changes in BHR, in the absence of reductions in FEV(1), were observed in some asthmatic patients following wine challenge, these changes were not consistent with a single aetiology. Consequently, this study did not support a major role for the sulphite additives in wine-induced asthmatic responses in the patients studied. The aetiology of wine-induced asthma is likely to be complex and appears to vary among individuals who are sensitive to these drinks.