Asthmatic responses to passive cigarette smoke: Persistence of reactivity and effect of medications

The present study assessed the persistence of cigarette-smoke reactivity and the effects of drug pretreatment on bronchial responsiveness to environmental tobacco smoke (ETS). Two groups of subjects were chosen for the study. Group I consisted of 15 atopic smoke-sensitive subjects with asthma, six of whom were defined “reactors” and nine “nonreactors” to ETS challenge. Group II consisted of 15 atopic subjects without asthma and with documented upper respiratory tract symptoms on exposure to ETS. All subjects were challenged for 2 to 6 hours with mechanically generated ETS in a static inhalation chamber. Five / six subjects in group I, who were previously demonstrated as reactors 24 months earlier, remained reactive within 1 to 2 hours of continuous ETS exposure. Pretreatment with albuterol, cromolyn, and a combination of albuterol and cromolyn 30 minutes before ETS exposure significantly diminished airway reactivity to ETS. All nine previous nonreactors in group I remained nonreactive despite rechallenge with ETS for up to 6 hours. Group II subjects challenged under identical conditions did not reveal a significant decline in FEV, on challenge with ETS. These studies demonstrate the persistence of ETS reactivity during a 2-year period. Although cromolyn sodium and/or albuterol can protect against reactivity, mechanisms of ETS-induced airway reactivity remain unknown.     

The effect of nedocromil sodium on the early and late reaction and allergen-induced bronchial hyperresponsiveness.

Bronchial hyperresponsiveness (BHR) to methacholine was studied in 14 patients with asthma and five healthy control subjects, with and without pretreatment with nedocromil sodium, 3 and 24 hours after allergen challenge. Eleven patients demonstrated a dual asthmatic response. A significant decrease in the provocative concentration causing a 20% fall in FEV1 was found from a geometric mean starting value of 1.18 mg/ml on the control day to 0.24 mg/ml (p less than 0.001) and to 0.17 mg/ml (p less than 0.001) 3 and 24 hours after allergen challenge. A significant correlation was observed between the increased BHR at 3 hours and the magnitude of the late response (r = -0.57; p less than 0.05). Nedocromil sodium (6 mg) significantly inhibited the increase in BHR, 1 mg/ml (p less than 0.001) at 3 hours and 0.50 mg/ml (p less than 0.001) at 24 hours. Nedocromil sodium shifted the severity of the early allergic reaction (EAR) from mean -34.8% to -6.9% and inhibited the later allergic reaction (LAR) from -30.5% to +0.4% (p less than 0.005). From the study can be concluded that nedocromil sodium inhibits the EAR and LAR and the allergen-induced increase in BHR. The inhibitory effect of nedocromil sodium on the LAR may be related to its ability to inhibit the increased BHR before the development of the LAR.     

Comparison of the intensity and duration of effects of inhaled bitolterol and albuterol on airway caliber and airway responsiveness to histamine

Inhaled beta-agonists can produce bronchodilatation and reduce airway hyperreactivity in patients with asthma. Using these two measures, we compared inhaled bitolterol (three puffs, 1110 micrograms), albuterol (two puffs, 180 micrograms), and placebo administered by metered-dose inhaler in a blinded, crossover study of 40 subjects with chronic asthma. On each study day, subjects underwent histamine challenges at 1 1/2 hours before, and 1/2, 2, 4, 6, and 8 hours after inhaling one of the three test-drug treatments. Both drugs produced significant bronchodilatation at 30 minutes through 4 hours and significant effects on airway reactivity at 30 minutes through 2 hours (p less than 0.05). Bitolterol also produced small but significant bronchodilator effects at 6 hours and effects on airway reactivity at 4 hours (p less than 0.05). Effects of bitolterol on airway reactivity diminished significantly more slowly than effects of albuterol in subjects with baseline provocative concentration causing a 20% fall in FEV1 greater than or equal to 1.0 mg/ml of histamine (half-life of biologic effect 1.37 versus 0.92 hours; p less than 0.05) but not in subjects with baseline provocative concentration causing a 20% fall in FEV1 less than or equal to 1.0 mg/ml (half-life of biologic effect of 1.01 versus 1.00 hours; p greater than 0.05).     

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.     

Protective effect and duration of action of inhaled formoterol and salbutamol on exercise-induced asthma in children.

The magnitude and duration of protection against exercise-induced asthma (EIA) afforded by salbutamol and the new, long-acting beta 2-agonist, formoterol, were compared in a double-blind, placebo-controlled crossover study. Twelve children with asthma and EIA (greater than 25% fall from baseline at a pretrial exercise test) were studied on 3 different days receiving, in random order, either formoterol, 12 micrograms, salbutamol, 200 micrograms, or placebo by inhalation. The effect on EIA was evaluated by standardized treadmill-exercise tests repeated at the following times after medication: 1/2 hour (test 1), 3 hours (test 2), and, if the trial drug still demonstrated an effect, 5 1/2 hours (test 3) and 8 hours (test 4). The mean (SD) maximum percent fall in FEV1 at the pretrial test was 45% (14%). Placebo treatment had no effect on EIA. The mean (SD) maximum percent fall in FEV1 was 44% (14%) (test 1) and 39% (13%) (test 2) (not significant). Salbutamol offered good protection against EIA after 1/2 hour (percent fall in FEV1, 18% [18%]; p less than 0.02) but was not significantly different from that of placebo after 3 hours, 39% (13%) fall in FEV1. Formoterol blocked EIA in all the children and demonstrated a significant effect in most children for at least 8 hours. The percent fall in FEV1 after the various tests were 8% (16%) (test 1), 10% (9%) (test 2), 18% (15%) (test 3), and 18% (7%) (test 4; N = 9) (all tests, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Repeatability of allergen-induced airway inflammation.

BACKGROUND: Allergen inhalation challenge is a useful clinical model to investigate the effects of asthma therapies on allergen-induced airway responses; however, the repeatability of allergen-induced airway inflammation is not known. OBJECTIVE: The purpose of this study was to investigate the repeatability of allergen-induced increases in sputum eosinophils. This information will allow the prediction of the number of subjects required in studies evaluating asthma therapies. METHODS: Seventeen subjects completed 2 allergen challenges using the same dose of allergen, at least 3 weeks apart. Allergen-induced airway responses were measured for 7 hours after challenge. Differential cell counts from induced sputum were determined the day before and 7 and 24 hours after challenge; methacholine PC20 was measured the day before and 24 hours after challenge. RESULTS: The intraclass correlation coefficient for maximum percent late fall in FEV1 was 0.32 and for the area of the late response was 0.61. The sample size predicted to be necessary to observe 50% attenuation of the maximum percent late fall in FEV1 and the late area under the curve with a power of 0.95 was 9 subjects. The intraclass correlation coefficient for percent of allergen-induced sputum eosinophils was 0.60 at 7 hours and 0.53 at 24 hours after challenge. With a randomized cross-over study design, the sample size predicted to be necessary to observe 50% attenuation of allergen-induced percent of eosinophils with a power of 0.95 was 5 subjects. CONCLUSION: Allergen inhalation challenge with measurements of sputum eosinophils is a noninvasive and reliable method for evaluating the anti-inflammatory effects of asthma therapies.     

Tachyphylaxis to inhaled histamine in asthma: its significance and relationship to basal airway responsiveness

Although some studies have clearly demonstrated tachyphylaxis to inhaled histamine in subjects with asthma, other studies have not. We speculated that histamine tachyphylaxis might be related to the degree of bronchial hyperreactivity (BHR) to histamine. We undertook three successive bronchial histamine challenges in two groups of 10 subjects with asthma chosen on the basis of their baseline BHR. In the group with mild asthma, the baseline provocative concentration of histamine causing a 20% fall in FEV1 (PC20) was greater than 2.5 mg/ml, and in the group with severe asthma, the baseline PC20 histamine was less than 1 mg/ml. The second and third histamine challenges in each subject were performed when FEV1 values had recovered to within 5% of the baseline FEV1 before the first challenge. There was no significant shift in reactivity to histamine from the first to the third challenge in either group. The geometric mean PC20 (+/- geometric SE) for the group with mild asthma was 4.27 (3.86 to 4.72) mg/ml for the first challenge and 5.42 (4.47 to 6.57) mg/ml for the third challenge. There was a mean increase of 0.34 doubling dilutions in PC20 for the group with mild asthma from the first to the third challenge, although this did not reach statistical significance. For the group with severe asthma, the geometric mean PC20 was 0.48 (0.39 to 0.59) mg/ml for the first challenge and 0.47 (0.38 to 0.59) mg/ml for the third challenge. There was no trend in this group toward any increase in PC20.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparative study in atopic subjects with asthma of the effects of salmeterol and salbutamol on allergen-induced bronchoconstriction, increase in airway reactivity, and increase in urinary leukotriene E4 excretion.

Salmeterol (SM) is a novel beta 2-adrenoceptor agonist with a duration of action in excess of 12 hours. Evidence from in vitro studies has also demonstrated that, unlike the short-acting beta 2-agonists, such as salbutamol (SB), it may have some anti-inflammatory properties. With a randomized, double-blind, crossover design, we have compared the inhibitory effects of SM (50 micrograms) and SB (200 micrograms) delivered by metered-dose inhaler on allergen-induced bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT) E4 excretion in 12 atopic subjects with mild asthma. The immediate bronchoconstriction to allergen was significantly reduced by both beta 2-agonists (p less than 0.005), when reduction was expressed either in terms of maximum fall in FEV1 at 15 minutes after allergen (percent fall in FEV1, mean +/- SEM: 6.2 +/- 4.9, SM; 5.7 +/- 2.5, SB; 40.4 +/- 6.3, placebo) or the area under the FEV1 time curve (AUC) for the first 120 minutes after allergen. Four hours after challenge, results in the SB-treated and placebo-treated groups were not significantly different and demonstrated a small persistent bronchoconstriction compared to bronchodilatation in the SM-treated group (percent fall in FEV1, respectively, 9.3 +/- 3.7, 14.3 +/- 7.1, and -6.3 +/- 2.7; p less than 0.005, SM versus SB; p less than 0.02, SM versus placebo). Expressed in terms of AUC, only SM significantly reduced bronchoconstriction in the period 120 to 240 minutes after allergen (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inflammatory cells and eicosanoid mediators in subjects with late asthmatic responses and increases in airway responsiveness

To determine the relationship of inflammatory cells and eicosanoid mediators to the pathogenesis of the late asthmatic response (LAR) and increases in nonspecific airway responsiveness, we studied bronchoalveolar lavage (BAL) cells and fluid in 27 subjects 12 hours after inhaled antigen challenge. Methacholine challenge was performed before antigen challenge and 24 hours later (12 hours after BAL). Eight subjects had no LAR (-LAR, less than or equal to 10% fall in FEV1), nine subjects had an equivocal LAR (+/- LAR, 11% 25% fall in FEV1), and 10 subjects had a definite LAR (+LAR, greater than 25% fall in FEV1). Subjects developing +LAR had increased airway responsiveness at baseline compared with that of subjects developing an +/- LAR, but not with subjects having -LAR. If airway responsiveness was markedly increased at baseline, further increases after antigen challenge were often not observed. We found that both percent neutrophils and eosinophils increased in BAL as the severity of the LAR increased, but significant differences between the groups with -LAR and +LAR were only observed when both cell types were considered together. In addition, there was a significant correlation between the combined cell percentages and the severity of the LAR as determined by fall in FEV1. Likewise, increases in airway responsiveness were associated with significant increases in both neutrophil and eosinophil numbers, but only neutrophils correlated with the change in airway responsiveness after antigen challenge. However, despite the significant physiologic and cellular differences that we found between our groups, no significant differences could be found in BAL eicosanoid-mediator concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of an oral leukotriene D4 antagonist L-649,923 on the response to inhaled antigen in asthma

We have compared the effects of the leukotriene (LT) D4 antagonist L-649,923 and placebo on the airway response to antigen challenge in eight men with mild asthma known to have both an early and late response to inhaled antigen. Subjects ingested 1000 mg of L-649,923 or placebo in a randomized, double-blind protocol and, two hours later, inhaled the dose of antigen known to induce a 20% fall in FEV1. Pulmonary function (specific conductance, FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity) was measured at intervals before and up to 9 hours after antigen. FEV1 fell in one subject after L-649,923 ingestion. L-649,923 in the other seven subjects caused no change in baseline pulmonary function, a small reduction in the early response to antigen for FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity but not for specific airway conductance (six subjects only) and no effect on the late response. The mean maximum fall in FEV1 in the early response was 1.35 L after L-649,923 ingestion and 1.78 after placebo ingestion. This relatively small degree of protection by L-649,923 suggests either that L-649,923 is not a sufficiently potent antagonist to diminish the effect of endogenous LTD4 in vivo or that LTD4 does not play a major role in the airway response to antigen challenge.     

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.     

Effects of albuterol and procaterol on exercise-induced asthma

Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.     

Small airways response to naturalistic cat allergen exposure in subjects with asthma

BACKGROUND: It is currently unclear whether the small airways (diameter <2 microm) contribute significantly to late asthmatic reactions to inhaled allergen. OBJECTIVES: We sought to determine whether naturalistic exposure to cat allergen induced late responses in the small airways as measured by pulmonary function testing and high-resolution computed tomography (HRCT) of the chest performed at end-expiration. METHODS: In a group of 10 subjects with cat-induced asthma, physiologic studies (spirometry and lung volumes, including closing volume) and HRCT were performed before and 6 and 23 hours after a cat room challenge that caused a 20% or greater acute fall in FEV(1). RESULTS: There was no significant decline in FEV(1) at 6 or 23 hours after cat exposure. Forced expiratory flow at 25% to 75% of forced vital capacity was significantly decreased at 6 hours after the challenge and returned to normal by 23 hours. HRCT image analysis as well as closing volume demonstrated increased air trapping from baseline at both 6 and 23 hours after the challenge. In addition, image analysis demonstrated a significant increase in small airways hyperresponsiveness to methacholine at 23 hours after the challenge. No significant mean changes were noted in lung volumes at either 6 or 23 hours or in PC(20) FEV(1) at 23 hours postchallenge. CONCLUSION: These findings demonstrate that naturalistic exposure to cat allergen results in significant small airways obstruction and hyperresponsiveness persisting for at least 23 hours, at which time these changes cannot be detected by conventional physiologic measures. CLINICAL IMPLICATIONS: Physiologically silent distal lung inflammation persists after an antigenic challenge.     

Occupational challenge studies with laboratory workers allergic to rats

To relate airborne Rat N I concentrations to airway responses in allergic laboratory workers, we collected allergen on personal monitors while workers and control subjects were exposed in a rat vivarium for 1 hour. Allergen concentrations ranged from less than 1.5 to 310 ng/m3 and were significantly (p less than 0.001) higher during cage cleaning (19 to 310 ng/m3) than during quiet activity (less than 1.5 to 9.7 ng/m3). Among 12 rat-allergic volunteers, all had a nasal response during the exposure with an increase in nasal lavage histamine concentrations or TAME-esterase activity, but only five volunteers had a lower respiratory tract response (fall in FEV1 greater than 10%). Two of five allergic control subjects had a small change in nasal TAME-esterase activity, and none had a 10% fall in FEV1. A dose response was demonstrated between the allergen concentrations and the intensity of the nasal allergic response. This occupational challenge procedure thus was able to measure the nasal and lower respiratory tract response to airborne allergen exposure in a work environment. It can be used to define further the determinants of this response.     

Bronchial responsiveness to adenosine-5''-monophosphate and methacholine as predictors for nasal symptoms due to newly introduced allergens. A follow-up study among laboratory animal workers and bakery apprentices

BACKGROUND: In asthma patients, bronchial hyper-responsiveness (BHR) to adenosine-5'-monophosphate (AMP) reflects bronchial inflammation more closely than BHR to methacholine. In this follow-up study we studied bronchial responsiveness to both stimuli as predictors of new-onset airway symptoms. METHODS: We included 118 laboratory animal workers and bakery apprentices with a work experience of maximally 1 year. The baseline survey comprised a questionnaire, skin prick tests (SPTs) to common and work allergens, blood eosinophil counting, and bronchial challenge with methacholine and AMP. At follow-up, questionnaire and SPTs to work allergens were repeated. Airway symptoms to common allergens and work allergens were defined as nasal symptoms, chest tightness or asthma attack during or after contact with either common or work allergen. Bronchial challenge tests were analysed by BHR at a 15% fall in forced expiratory volume of 1 s (FEV1), and by dose-response-slope (DRS). RESULTS: Fourteen subjects (12%) developed airway symptoms to work allergens, of whom 12 had nasal symptoms. A positive SPT to work allergens occurred in 64%, and was the strongest predictor of airway symptoms [relative risk (RR) 7.5, 95% confidence interval (CI) 2.0-28.6]. Other predictors were airway symptoms to common allergens (RR 4.3, 95% CI 1.4-12.8), blood hypereosinophilia (RR 4.4, 95% CI 1.2-15.4) and BHR, with a slightly higher risk estimate for AMP than for methacholine (RRAMP 3.7, 95% CI 1.1-12.5 and RRmeth 2.8, 95% CI 1.0-8.5). The difference was more distinct analysing airway responsiveness by DRS, for which AMP predicted symptoms better than methacholine (P < 0.05). CONCLUSIONS: Pre-existent bronchial inflammation or a preinflammatory state marked by AMP (hyper)responsiveness increases the vulnerability to develop nasal symptoms.     

Determinants of bronchial responsiveness in the European Community Respiratory Health Survey in Italy: evidence of an independent role of atopy, total serum IgE levels, and asthma symptoms

The aim of the analysis was to test whether total serum IgE levels, specific serum IgE levels, and asthma symptoms are independent predictors of bronchial hyperresponsiveness (BHR), after controlling for known risk factors or potential confounders. The study was carried out on a sample of 875 young adults, 20–44 years old, who took part in the European Community Respiratory Health Survey in Italy The subjects underwent a dose-response methacholine challenge test. We also measured airway caliber as the baseline FEV, in absolute terms and as percentage of forced vital capacity (FVC); skin wheal response to 11 common environmental allergens; and total and specific serum IgE levels to mites, molds, pets, and respiratory symptoms by means of a standardized questionnaire. Atopy (positive skin prick test and/or positive specific IgE assay), total IgE, asthma symptoms, airway caliher, and age appeared to be independent predictors of BHR. When all the other risk factors were taken into account, atopy and total IgE were associated with a threefold increase in BHR risk and thus emerged as the main determinants of BHR. The importance of symptom status as a determinant of BHR decreased remarkably after controlling for atopy and IgE: the odds ratio of current asthmatics to asymptomatic subjects decreased from 15.3 to 8.8. When controlling for symptoms and atopy, a family history of allergic diseases and early respiratory infections was not found to be associated with BHR. Both FEVi and FEV/FVC were strongly and inversely associated with BHR. When airway caliher was taken into account, older age was associated with decreased responsiveness, and the level of responsiveness did not differ significantly between males and females and between smokers and nonsmokers. The results from this analysis indicate that at any given age, irrespective of sex and smoking habits, total serum IgE, specific IgE, airway caliber, and asthma symptoms are the main independent factors influencing the occurrence of BHR in a young adult sample.     

Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in patients with allergic rhinitis

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59 mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.     

Increased responsiveness to histamine after propranolol in subjects with asthma nonresponsive to the bronchoconstrictive effect of propranolol

Eight nonsmoking subjects with asthma, nonresponsive to the bronchoconstrictive effect of oral propranolol, were studied. The airway response to increasing concentrations of histamine aerosol was assessed by measuring FEV1. The threshold provocative dose of histamine needed to cause a 20% fall in starting FEV1 (PD20) was measured by log dose-response curve. Histamine challenge was performed in duplicate after premedication with placebo or 40 mg of propranolol on separate days. The mean starting FEV1 did not change significantly after placebo and after propranolol administration. The mean PD20 values after propranolol (0.37 mg/ml and 0.32 mg/ml, respectively, for the first and the second challenge) were significantly lower (p less than 0.01) than mean control PD20 values (1.36 mg/ml and 1.48 mg/ml, respectively, for the first and the second challenge). These results indicate that propranolol increases airway responsiveness to histamine, even in those subjects with asthma in whom propranolol has little bronchoconstrictive effect.     

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.     

Exposure to a sensitizing occupational agent can cause a long-lasting increase in bronchial responsiveness to histamine in the absence of significant changes in airway caliber

A 58-year-old subject with a history of occupational asthma to red-cedar sawdust underwent specific inhalation challenges with this product. Significant increases in airway responsiveness to histamine (tenfold fall in PC20 FEV1) were documented 7 hours after exposure for 5 minutes to red cedar while baseline spirometry remained unchanged. A dual asthmatic reaction was induced during the following days by exposing the subject to red-cedar sawdust for 30 minutes and plicatic acid for 7 minutes. After recovery of PC20, the subject was reexposed to plicatic acid for 15 and 30 seconds on 2 consecutive days. No significant changes in FEV1, forced vital capacity, and residual volume were demonstrated in the following 8 hours, although minimal changes in forced expiratory flow rate between 25% and 75% of FVC were observed. PC20 dropped significantly and required 2 weeks to recover. This example illustrates that bronchial hyperresponsiveness to histamine can precede the changes in airway caliber after an antigen challenge. It also demonstrates that such changes can persist for up to 2 weeks after the challenge, even when no significant changes in FEV1 are induced.