The relationship between airway responsiveness to histamine and pulmonary function level in a random population sample

The association of nonspecific bronchial responsiveness (BR) with pulmonary function level has been studied in a random population sample of 2,156 male and female subjects 15 to 64 yr of age participating in the Vlagtwedde-Vlaardingen field survey on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. About 25% of the subjects responded with a decrease in baseline FEV1 of 10% or more after challenge with histamine in a concentration of 16 mg/ml or less inhaled over 30 s (PC10). In a stratified analysis, pulmonary function level appeared to be associated with BR in a dose-response relationship. The mean %FEV1 was consistently lower in the more responsive subjects. This relationship was confirmed in linear regression analyses, adjusting for age, sex, area of residence, and smoking habits. Exclusion of subjects with %FEV1 less than 80% diminished but did not change the association between FEV1 and BR. The magnitude of the effect of responsiveness on level of pulmonary function was considerable and statistically significant. In the subjects older than 21 yr of age, male responders (PC10 at less than or equal to 16 mg/ml) on average had an adjusted FEV1 of 32.5 centiliters less than nonresponders, and female responders had an adjusted FEV1 of 30.5 centiliters less (p less than 0.001). BR appeared to be an independent predictor of pulmonary function level after adjustment for age, sex, area of residence, respiratory symptom prevalence, and cigarette smoking. The effect of cigarette smoking on pulmonary function level in this population sample was significant only in men older than 21 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Perception of airway obstruction in a random population sample. Relationship to airway hyperresponsiveness in the absence of respiratory symptoms.

Subjects with asymptomatic airway hyperresponsiveness in epidemiologic studies may have variable airway obstruction that is not perceived as dyspnea. We tested the hypothesis that such subjects are less likely to report an increase in dyspnea during histamine-induced bronchoconstriction than symptomatic hyperresponders. A random population sample of 412 middle-aged subjects was studied. Before and after a standardized histamine challenge test, subjects recorded Borg scores for dyspnea: any increase in Borg score was considered significant. More than 80% of hyperresponsive subjects (PC10 histamine < or = 16 mg/ml) had no symptoms. The presence of prechallenge dyspnea was related to increased airways responsiveness and current smoking. An increase in Borg score was associated with younger age, more severe airway responsiveness, atopy, and female sex. The level of and increase in the Borg score were not significantly related to level and change in airway caliber (FEV1). In hyperresponsive subjects (PC10 < or = 16 mg/ml), subjects who reported dyspnea, wheeze, or asthma were more likely to show an increase in Borg score during histamine provocation than asymptomatic subjects (adjusted odds ratio 4.01, 95% confidence interval 1.01 to 16.00, p = 0.049), after adjustment for age, sex, smoking habits, FEV1, and atopy. This suggests that asymptomatic hyperresponders may have variable airway obstruction that is not recognized as breathlessness.     

Prognosis of asthma from childhood to adulthood

The outcome of childhood asthma was studied in 101 adults who came from a group of 119 asthmatic children (85%) 6 to 14 yr of age who had originally been investigated between 1966 and 1969. Changes in respiratory symptoms, spirometry, and airway responsiveness to histamine in childhood and adult life were analyzed. It was found that 43 of the 101 adults (43%) had current symptoms; 29 of the 43 (67%) were receiving maintenance therapy. In the first study, 83 of the 101 children (82%) showed a response on inhalation of histamine (PC10-histamine less than or equal to 16 mg/ml). The number of subjects in the second study who still had a PC10-histamine less than or equal to 16 mg/ml fell to 29, suggesting that airway responsiveness decreases from childhood to adulthood. During the second survey (in adults), 25 of the 43 (59%) subjects with current symptoms and four of the 58 (7%) without respiratory symptoms responded to histamine. Adults with current symptoms had a significantly lower %FEV1 in both childhood and adulthood than did adults without current symptoms; %FEV1 was not different in females and males or in smokers and nonsmokers in either the first or the second survey. The outcome of childhood asthma is primarily predicted by the initial degree of bronchial obstruction (p = 0.041) and airway responsiveness to histamine (p = 0.050), and does not appear to be related to sex, smoking habits, or age of onset of respiratory symptoms.     

Nonspecific airway reactivity in cigarette smokers. Relationship to airway pathology and baseline lung function

To examine the relationship of cigarette smoking, starting airway caliber, and airway pathology to nonspecific airway reactivity, we performed inhalation dose-response curves in 40 patients prior to lung surgery. Airway reactivity was assessed by the provocative concentration of methacholine (n = 30) or histamine (n = 10) resulting in a 20% fall in FEV1 (PC20). All patients had measurements of maximal expiratory flow, diffusing capacity, and lung volumes preoperatively. After resection, the specimens were graded for small and large airways pathology and emphysema. The patients were divided into 4 groups: PC20 less than or equal to 1 mg/ml (n = 6), PC20 1 mg/ml to less than or equal to 4 mg/ml (n = 11), PC20 4 mg/ml to less than or equal to 16 mg/ml (n = 14), and PC20 greater than 16 mg/ml (n = 9). Subjects with PC20 less than or equal to 1 mg/ml had reduced measurements of maximal expiratory flow (FEV1, FEV1/FVC, Vmax50, and Vmax25). There were no differences in measurements of cartilaginous airway disease among the 4 reactivity groups. We found significant independent correlations of cigarette consumption, membranous bronchiole inflammation, and maximal expiratory flow rates (FEV1 and Vmax50) to PC20. The data suggest that cigarette smoking, starting airway caliber, and airway inflammation are associated with nonspecific airway reactivity and that each exerts an effect on airway reactivity that is not dependent on the contribution of the other 2 factors.     

Ventilatory function and chronic mucus hypersecretion as predictors of death from lung cancer

The relation of ventilatory function and chronic mucus hypersecretion to death from lung cancer has been studied in 13,946 subjects randomly selected from the general population of the city of Copenhagen, Denmark. During the 10-yr follow-up, 225 subjects died from lung cancer. Percent predicted FEV1 (%FEV1) and presence of chronic phlegm were used to characterize ventilatory function and chronic mucus hypersecretion, respectively. Mortality analysis employed the multiple regression model of Cox and included age, sex, pack-years of smoking, and inhalation as confounding factors. %FEV1 and chronic phlegm were found to be significant predictors of death from lung cancer. In both men and women with chronic phlegm, the risk of dying from lung cancer was 1.5 greater than in those without phlegm. Compared with subjects with %FEV1 greater than or equal to 80, the subjects with %FEV1 less than 40 and those with %FEV1 between 40 and 79 had a 3.9 and 2.1 higher risk of lung cancer death, respectively. A similar regression model in which %FEV1 was replaced with the ratio of FEV1 to FVC (FEV1/FVC) showed that lowered FEV1/FVC was also a significant predictor of lung cancer death, the subjects with FEV1/FVC less than 0.6 (0.6 to 0.7) having a 2.6 (1.5) higher risk for lung cancer death than those with FEV1/FVC greater than or equal to 0.7. It is concluded that lowered ventilatory function and chronic mucus hypersecretion are both significant predictors of death from lung cancer, even after standardization for smoking.     

Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population

The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.     

Methacholine responsiveness, respiratory symptoms and pulmonary function in aluminum potroom workers

The relationship between nonspecific bronchial reactivity and work-related asthmatic symptoms was examined in a cross-sectional study of 337 aluminium potroom workers by a shortened method of continuous methacholine nebulization. The provocative concentration producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) was less than or equal to 8 mg.ml-1 (hyperresponsiveness) in 17 workers (5%), whilst minor responsiveness (8 mg.ml-1 less than PC20 less than 32 mg.ml-1) was present in 24 subjects (7%). The prevalence of work-related asthmatic symptoms was 9%. Female sex, ex-smoker and airflow limitation were significant predictors of methacholine responsiveness (p less than 0.05). In a multiple logistic regression analysis the odds ratios (OR) for work-related asthmatic symptoms was 10.8 (95% confidence interval: 2.9-40.6) for hyperresponsiveness and 4.4 (95% confidence interval: 1.2-16.4) for minor responsiveness. The sensitivity, specificity and predictivity of PC20 less than 32 mg.ml-1 for work-related asthmatic symptoms were 35, 92 and 35%, respectively, whilst the agreement, when adjusted for the by chance expectation, was 0.27 (95% confidence interval: 0.10-0.54). Although a significant association was found between bronchial reactivity and work-related asthmatic symptoms, the usefulness of the methacholine test as a tool for detection of work-related asthmatic symptoms appears to be of limited value due to its low sensitivity.     

Nonspecific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in subjects with respiratory symptoms of uncertain etiology

Fifty adult subjects referred to a respiratory function laboratory of a tertiary care hospital for respiratory symptoms of uncertain etiology were investigated prospectively by means of a questionnaire, isocapnic inhalation of dry cold air (-20 degrees C), histamine inhalation tests, monitoring of peak expiratory flow rates, total eosinophil counts, and total IgE. Wheezing, tightness in the chest, dyspnea, and cough were reported by 35, 23, 41, and 30 subjects, respectively. FEV1 values less than 80% pred were found in only 2 subjects. Twenty-nine subjects had a PC20 histamine less than or equal to 16 mg/ml. Twenty, 15, and 10% falls in FEV1 were found in 10, 18, and 26 subjects, respectively, using hyperventilation of cold air. Significant eosinophilia and increased total IgE levels were seen in 5 and 18 subjects, respectively. Eight subjects had daily changes in PEFR greater than 20% on at least 1 day of monitoring. There was no significant association between specific responses to the respiratory questionnaire or the presence of rhinitis on the one hand and bronchial responsiveness to histamine and cold air on the other hand. The 10 subjects who demonstrated a greater than 20% change in FEV1 after cold air inhalation also had a PC20 less than 16 mg/ml, and 5 of them reacted at a concentration less than or equal to 2 mg/ml. Two subjects who had a PC20 less than or equal to 2 mg/ml demonstrated a less than 20% change in FEV1 after inhaling cold air. There was no association between the increase in total eosinophils or IgE and bronchial hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased airways responsiveness in swine farmers

A respiratory questionnaire, pulmonary function tests, and an examination of airways responsiveness were conducted on 20 swine farmers and 20 control subjects. The swine farmers represented almost the complete work force from 13 Hutterite colonies and had worked in confinement buildings with more than 2,000 swine (3,270 +/- 1,221 swine) for at least four hours (6.6 +/- 1.8 hours) per day for more than two years (10.5 +/- 7.5 years). The control subjects were randomly selected from outdoor city workers from the city of Saskatoon and were matched for gender, age (+/- 2 years), and smoking status. Eleven swine farmers (55 percent) had chronic cough, compared with three (15 percent) of the control subjects (p less than 0.01). Eight (40 percent) of the swine farmers had symptoms of wheezing, compared with three (15 percent) of the control subjects (p less than 0.05). The FEV1 was significantly lower in swine farmers (97.2 +/- 11.5 percent predicted) than in control subjects (106.0 +/- 12.0 percent of predicted) (p less than 0.05). Airways responsiveness was measured by methacholine challenge with doubling concentrations ranging from 0.25 to 256 mg/ml. The provocation concentrations resulting in a reduction of 10 percent (PC10) and 20 percent (PC20) in FEV1 were lower in swine farmers than in control subjects (PC10, 77.2 +/- 78.8 mg/ml vs 180.8 +/- 96.5 mg/ml; p less than 0.01; and PC20, 154.5 +/- 99.9 mg/ml vs 229.6 +/- 66.8 mg/ml; p less than 0.05). Twelve swine farmers (60 percent) had PC20 of less than 256 mg/ml, compared with three (15 percent) of the control workers (p less than 0.01). Fewer swine farmers demonstrated atopy as measured by skin prick tests than did control workers (21 percent vs 56 percent; p less than 0.05). These findings suggested that occupational exposure in swine confinement buildings is associated with mild increases of nonspecific, nonatopic airways responsiveness in swine farmers.     

Comparison of histamine and acetylcholine for use in bronchial challenge testing in atopic and nonatopic subjects with chronic airways obstruction: a review of 180 cases.

A retrospective study was performed to evaluate the diagnostic yield for bronchial hyperresponsiveness from histamine and acetylcholine challenge tests. The records of 180 cases from the last 10 years were analysed. They were selected because their hyperresponsiveness to inhaled histamine or acetylcholine was equal or less than 32 mg.ml-1. Increasing doses of histamine and acetylcholine were given up to a maximum of 32 mg.ml-1 according to the method of de Vries et al. [3]. The challenges were accomplished on two separate days. The provocative dose of agonist causing a 20% fall in FEV1 (PC20) was noted. The interrelationships between smoking history, objective markers of allergy, patient's complaints, histamine and acetylcholine responsiveness were examined. Separate statistical analyses are presented for atopic and nonatopic subjects with chronic airways obstruction. More subjects had a measurable PC20 with acetylcholine than with histamine (43 vs. 16 subjects, p < 0.0001). Using the chi 2 test, the relationship between PC20 histamine and PC20 acetylcholine was similar in smokers and nonsmokers, and in atopics and nonatopics. It is concluded that for an equal molar basis, acetylcholine evokes a higher frequency of bronchus obstruction than histamine in patients.     

Indices of nonspecific bronchial responsiveness in a pediatric population

A cross-sectional survey of the prevalence of asthma and bronchial hyperreactivity among schoolchildren (7 to 11 years old) was carried out in three areas of the Latium region (Central Italy). Out of 1,777 children tested with methacholine challenge (MCT), 15.1 percent had a 20 percent fall in FEV1 after a provocative concentration (PC20FEV1) of 4 mg/ml of methacholine or less; 69.7 percent had a PC20FEV1 less than 64.0 mg/ml, whereas 50.3 percent were nonresponders. Two continuous measures of bronchial responsiveness, the slope (percentage of change in FEV1 per mg/ml of methacholine) and the area under the dose response curve, were calculated in order to avoid the loss of information in nonresponders. Applying a receiver operating characteristic (ROC) curve analysis, the three estimators did not show any statistically significant difference in their overall performance in detecting asthma (ROC areas: PC20FEV1 = 0.683, slope = 0.681, area = 0.702 or asthma-like symptoms. The log transformation of slope, having a unimodal and slightly skewed shape, is an appealing continuous measure of bronchial responsiveness useful for epidemiologic studies. The final choice of an appropriate estimator of the concentration-response curve to methacholine, however, depends upon both the statistical tests or the modelling procedures to be used and clarification of the prognostic value of different indices of bronchial responsiveness.     

Patterns of improvement in spirometry, bronchial hyperresponsiveness, and specific IgE antibody levels after cessation of exposure in occupational asthma caused by snow-crab processing

Thirty-one workers with occupational asthma caused by snow-crab processing were assessed by a long-term follow-up on three occasions at mean +/- SD intervals of 12.8 +/- 5.4, 31.4 +/- 6.3, and 64.4 +/- 6.3 months after leaving work. The diagnosis of work-related asthma was initially confirmed in all of them by specific inhalation challenges at the workplace or by laboratory inhalation of snow-crab boiling water (n = 24) or by serial monitoring of airway caliber and bronchial responsiveness to histamine at work and off work (n = 7). Total duration of work-related exposure was 12.8 +/- 5.6 months (range, 3 to 21 months), and the duration of symptoms after onset was 6.8 +/- 4.2 months (range, 1 to 18 months). At the time of diagnosis, all 31 subjects required medication for asthma, 11 had a FEV1 less than or equal to 85% predicted, and all subjects had a PC20 less than or equal to 16 mg/ml. Twelve of 25 serum samples assessed showed high levels of specific immunoglobulin E (IgE) antibodies to crab meat and/or boiling water. At the time of the first follow-up, there was a reduction in the number of subjects still requiring medication, with a significant reduction in FEV1, and a PC20 less than or equal to 16 mg/ml. However, no further change was observed afterwards. Similarly, the mean FEV1 and FEV1/FVC improved significantly from the time of diagnosis to the first follow-up (p less than 0.01), with a plateau thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway responsiveness to inhaled histamine in chronic obstructive airways disease. Chronic bronchitis vs emphysema

Airway responsiveness to inhaled histamine was examined in two groups of carefully selected patients with nonasthmatic chronic obstructive airways disease (COAD). Twelve patients with chronic bronchitis and airflow obstruction but little emphysema and 13 with predominantly emphysema and airflow obstruction but little bronchitis were selected based on history, chest roentgenogram, and diffusing capacity for carbon monoxide (Dsb). Emphysema patients had less cough, less sputum, less chronic bronchitis, lower Dsb, and more radiographic evidence of vascular deficiency. There was no difference in anthropometric features, smoking history, atopic skin sensitivity, hemoglobin, blood eosinophilia, PaO2, PaCO2, ECG, lung volumes, or expiratory flow rates. The two groups had similar airway responsiveness to inhaled histamine; the geometric mean provocation concentrations producing a 20 percent FEV1 fall (PC20) was 0.56 mg/ml for the bronchitis patients and 0.28 mg/ml for the emphysema patients (p greater than 0.20). Regression of log histamine PC20 vs percent predicted FEV1 showed a high correlation in both groups (r = 0.73, p less than 0.01 in bronchitis and r = 0.79, p less than 0.001 in emphysema). The regression lines were almost identical. These data suggest that in COAD bronchial responsiveness to inhaled histamine is mainly due to the altered airway geometry, and that there is no difference in histamine responsiveness between patients with emphysematous COAD and nonemphysematous COAD with chronic bronchitis.     

Relationship of skin test reactivity and eosinophilia to level of pulmonary function in a community-based population study.

We studied the relationship of skin test reactivity (sumscore greater than or equal to 3) and eosinophilia (greater than or equal to 275 cells/mm3 blood), separately and combined, to the level of FEV1 in a community cohort. We used the regression analysis technique, adjusting for age and area of residence, and stratifying by gender and cigarette smoking. Eosinophilia, among men, was associated with lower levels of FEV1 in skin test negative subjects with moderate cigarette smoking (greater than or equal to 10 pack-yr: beta = -250 ml, p = 0.02; greater than or equal to 10 pack-yr: beta = -234 ml, p less than 0.01) and in skin test positive subjects who either never smoked (beta = -228 ml, p = 0.06) or had only a brief history of smoking (beta = -428 ml, p less than 0.01). Eosinophilia, among women, was significantly associated with lower levels of FEV1 in never smokers (beta = -95 ml, p less than 0.01), especially if subjects were skin test positive as well (beta = -289 ml, p less than 0.01). Moderate cigarette smoking was uncommon in women. These data suggest an association of indices of inflammation (eosinophilia alone) and allergic inflammation (eosinophilia combined with skin test reactivity) with lower levels of FEV1, independent of the effect of cigarette smoking.     

Effect of terfenadine on the response to exercise and cold air in asthma

To assess the role of histamine as a mediator in the response to exercise and isocapnic hyperventilation of cold air (IHCA) in asthma, we studied nine asthmatic subjects, age 13 to 25 years. All had exercise induced asthma (EIA) and positive responses to IHCA. Baseline lung function was measured before standardized challenges with histamine, exercise and IHCA. On separate days, these tests were repeated 3 h after a single oral dose of 120 mg terfenadine (TF). Histamine responsiveness decreased significantly, with a provocative concentration, producing a greater than or equal to 20% fall in FEV1 (PC20), of 1.1 +/- 0.8 mg/ml (mean +/- SEM) before and 12.0 +/- 4.9 mg/ml after the antihistamine. EIA was significantly less after TF, with 53 +/- 5% mean maximal falls in FEV1 from baseline before, and 29 +/- 9% after treatment (P less than 0.01, paired t-test). In contrast, the effect of TF on the response to IHCA was insignificant, with mean maximal falls of 45 +/- 7% in FEV1 before, and 41 +/- 7% after treatment. There was a correlation between PC20 and lowest FEV1 (% predicted) for EIA (r = 0.56, P less than 0.05), but not for IHCA (r = 0.34, NS). This study indicates a role of histamine as a mediator in EIA but not in IHCA, supporting different mechanisms for both stimuli.     

Bronchial hyperresponsiveness in subjects with gastroesophageal reflux

BACKGROUND: The relationship between gastroesophageal reflux (GER) and asthma has been widely studied in the last years. GER may interfere with airway reactivity and aggravate or even induce asthma. OBJECTIVE: To assess the prevalence of bronchial hyperresponsiveness (BHR) in patients with GER disease with a view to judging the potential influence of GER on BHR. METHODS: 30 patients with GER disease and no clinical evidence of asthma and 30 normal subjects underwent a methacholine bronchial challenge. The methacholine concentration that caused a 20% fall in the FEV(1) (PC20) was used to assess bronchial responsiveness. RESULTS: In the GER group 11 subjects of the 30 studied showed a PC20 methacholine equal to or less than 8 mg/ml while in the control group only 2 subjects had a PC20 methacholine equal to or less than 8 mg/ml (p < 0.01; ANOVA test). CONCLUSIONS: Subjects with GER had a greater increase in airway reactivity when inhaling methacholine compared to disease-free normal subjects.     

The relationship of nonspecific bronchial responsiveness to respiratory symptoms in a random population sample

The relationship of airway responsiveness to respiratory symptom prevalence has been studied in a cross-sectional analysis of a random subpopulation from a large-scale population study on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. In 1,905 subjects with complete data on age, sex, area of residence, smoking habits, and respiratory symptom prevalence, airway responsiveness was assessed by a histamine challenge test. Subjects with a decrease in FEV1 of greater than or equal to 10% at a histamine concentration of less than or equal to 16 mg/ml were considered to be responders. Bronchial hyperresponsiveness appeared to be age dependent, with the proportion of responders increasing from 13% in those 14 to 24 yr of age to 40% in those 55 to 64 yr of age (p less than 0.001). Respiratory symptom outcomes included chronic cough, chronic phlegm, dyspnea, bronchitic episodes, persistent wheeze, and asthmatic attacks. Respiratory symptom prevalence rates were significantly higher in responders (p less than 0.001 for all symptoms). Cigarette smoking is known to be related to respiratory symptom prevalence and possibly to bronchial responsiveness. Because of these associations, we examined the relationship of bronchial responsiveness to respiratory symptoms within cigarette smoking categories. For all respiratory symptoms, it was found that, regardless of smoking category, responders were more likely to be symptomatic than were nonresponders. Odds ratios ranged from 1.7 for chronic cough to 4.4 for asthmatic attacks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ascorbic acid on increased bronchial responsiveness during upper airway infection

We investigated the acute effect of ascorbic acid on histamine bronchial responsiveness (PC 20: concentration causing a 20% fall in FEV1) in 9 hospital staff members with upper respiratory tract infection (URI) and cough. Subjects were examined within 5 days from the start of illness and 6 weeks after. On day 1, the reproducibility of PC20 was assessed by 2 consecutive inhalation challenges 1 h apart; the two values were closely related (r = 0.96, p less than 0.001). Five subjects had bronchial hyperresponsiveness (PC20 less than 8 mg/ml histamine). On the following day, PC20 was measured before and 1 h after oral intake of 2 g ascorbic acid. Vitamin C produced a significant increase in average PC20 (p less than 0.01) from 7.8 +/- (SE) 1.2 to 25.1 +/- (SE) 1.2 mg/ml. None had airway hyperresponsiveness after treatment. Six weeks after the onset of URI, bronchial responsiveness was normal in all the subjects but one. The mean PC20 was 15.5 +/- (SE) 1.25 mg/ml, significantly higher than during URI (p less than 0.05); after ascorbic acid it increased nonsignificantly to 25.7 +/- (SE) 1.35 mg/ml. Our results indicate that vitamin C inhibits the transient increase in bronchial responsiveness occurring in otherwise normal subjects during URI.     

The role of cyclooxygenase products on bronchial responsiveness to methacholine in patients with sino-bronchial syndrome

The role of cyclooxygenase products on bronchial responsiveness to methacholine was studies in 9 patients with sino-bronchial syndrome. Provocative concentrations of methacholine, producing a 20% fall in forced expiratory volume in one second (FEV1)(PC20-FEV1) and a 35% fall in inverse respiratory resistance (Grs) (PC35-Grs), were measured before and after oral administration of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin). Baseline values of FEV1 and respiratory resistance (Rrs) were not altered by OKY-046 or indomethacin. Geometric mean values of PC20-FEV1 and PC35-Grs were significantly (p less than 0.005 and p less than 0.05) increased from 2.19 mg/ml (GSEM, 1.58) and 0.79 mg/ml (GSEM, 1.70) to 8.13 mg/ml (GSEM, 1.92) and 1.55 mg/ml (GSEM, 1.38) by indomethacin, whereas these values were not significantly increased by OKY-046. These findings indicate that not thromboxane A2 but bronchoconstricting prostaglandins may play a role in bronchial hyperresponsiveness in sino-bronchial syndrome.     

Predictors of late asthmatic response. Logistic regression and classification tree analyses

To identify predictors of the late asthmatic response (LAR), we reviewed data from 60 asthmatic subjects who had undergone allergen challenge over the past 5 yr (33 females, age 31.4 +/- 6.7 yr [mean +/- SD], FEV(1) 90% +/- 14% predicted). Variables considered likely predictors of LAR included baseline FEV(1), PC(20) methacholine (PC(20)), sputum eosinophil percent, and the decrease in FEV(1) within 20 min of allergen challenge. A LAR (FEV(1) >/= 15% fall between 3 and 7 h after challenge) was documented in 57% of subjects. A variety of logistic regression methods revealed a significant inverse association between LAR and PC(20) (odds ratio [OR] = 0.14 [95% CI = 0.03-0.66]) and a positive association between LAR and the decrease in FEV(1) at 20 min (OR = 1.18 [1.04 -1.33]). Classification tree analysis revealed that a threshold of 0.25 mg/ml for PC(20) was most predictive of LAR; LAR developed in 87% of those with PC(20) 0.25 mg/ml (n = 37). Notably, in subjects with PC(20) > 0.25 mg/ml, the incidence of LAR increased from 38% to 57% if the allergen-induced decline in FEV(1) at 20 min was >/= 27%. Surprisingly, baseline FEV(1) and percent eosinophils in induced sputum were not significantly associated with LAR. We conclude that a threshold value of 0.25 mg/ml for PC(20) methacholine is a good predictor of LAR. Measuring the PC(20) methacholine may be useful as a screening method to improve the efficiency of identifying asthmatic subjects with a LAR.