A Bronchial Response Comparison of Exercise and Methacholine in Asthmatic Subjects

The authors compared the inhaled methacholine and exercise responses in 22 stable unmedicated asthmatic patients. The exercise and methacholine challenges were performed at one to three week intervals. Bronchial responsiveness to methacholine was measured in relation to the concentration of methacholine (PC₂₀M). The response to exercise was expressed as the percentage of fall in FEV₁, from the pre-exercise FEV₁ The findings showed that 21 of 22 subjects demonstrated a fall in FEV₁, of more than 20% after methacholine challenge, while only 9/22 subjects experienced a similar decrease in FEV₁. All 9 of these positive response exercise cases completed three consecutive exercise challenges prior to the methacholine challenge. Of these cases, five were refractory to the repeated exercise challenge, and the PD₂₀M at the nonexercise stage was significantly lower than the postexercise state. In fact, the methacholine challenge sensitivity actually decreased (PD₂₀ increased) after repeated exercise. The authors concluded that methacholine seems to be a more sensitive bronchial provocation test than exercise. Second, only 55.6% of the exercise test-positive subjects were refractory to the second exercise challenge. Therefore, other factors besides the release of mediators should be considered in exercise induced asthma. Third, methacholine sensitivity actually decreased (PD₂₀ increases) after repeat exercise challenge.     

Relation of Airway Reactivity and Sensitivity with Bronchial Pathology in Asthma

Airway hyperresponsiveness in asthmatics, which may result from inflammation or remodeling, is expressed as the concentration of methacholine that causes a 20% fall in FEV₁ in the concentration-response curve (PC₂₀). A decrease in PC₂₀ may be due to a steeper curve (hyperreactivity) and/or a curve shift to the left (hypersensitivity). Our purpose was to analyze the relation of airway sensitivity and reactivity to airway pathological changes. The PC₆, as sensitivity parameter, and the slope between PC₂₀ and PC₄₀ as reactivity parameter, were calculated. Total and differential cell counts in the bronchoalveolar lavage fluid, and percentage of epithelial shedding, basement membrane thickness, and submucosal thickness on bronchial biopsy, were measured. The PC₆ showed a correlation with the baseline FEV₁%. The slope was significantly correlated with the basement membrane thickness, and also demonstrated a strong association with submucosal thickness. The PC₂₀ showed a correlation with the baseline FEV₁% and the degree of epithelial shedding. These results suggest that the airway sensitivity and reactivity measurements reflect the degree of airway caliber and remodeling, respectively.     

The Effects of Ipratropium Bromide on Histamine-Induced Bronchoconstriction in Subjects with Cervical Spinal Cord Injury

Previously, we reported that a majority of subjects with chronic cervical spinal cord injury (SCI) demonstrated airway hyperreactivity in response to inhaled methacholine. To further investigate mechanisms of airway hyperreactivity, 15 male subjects with cervical SCI were challenged with aerosolized histamine, and on a separate day responders were rechallenged 30 min after the inhalation of 72 μg of ipratropium bromide. Twelve of 15 subjects demonstrated airway hyper-responsiveness to histamine (geometric mean PC₂₀ of 1.27 mg/ml), which was not blocked by pretreatment with ipratropium bromide (geometric mean PC₂₀ 1.50 mg/ml). Baseline forced vital capacity and forced expiratory volume in 1 sec were not significantly different between responders and nonresponders (2.8 ± 0.6 vs. 3.0 ± 0.4 L and 2.3 ± 0.6 vs. 2.4 ± 0.2 L, respectively). Findings that subjects with cervical SCI are hyperresponsive to methacholine and histamine, chemical agents with direct action through distinct receptor systems, suggest that bronchial hyperreactivity in these subjects represents a nonspecific process similar to that observed in patients with asthma.     

Short-Term Regular β2-Adrenergic Agonists Treatment Is Safe in Mild Asthmatics Taking Low Doses of Inhaled Steroids

Regular treatment with β₂ adrenergic agonists is controversial in bronchial asthma. To investigate whether β₂-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclometha-sone dipropionate (BDP 250 μg t.i.d.); after 1 week, 12 patients inhaled 400 μg of broxaterol and 12 patients received placebo t.i.d. FVC, FEV₁, PD₂₀-FEV₁ methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with (β₂-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.     

Prednisolone Hastens Recovery from Histamine-Induced Bronchospasm in Asthmatics

Short-term treatment with oral steroids is very effective in controlling symptoms and improving lung function in asthma but has not been shown unequivocally to reduce bronchial hyperresponsiveness. Recently it has been shown to increase the activities of sodium-potassium and calcium adenosine triphosphatases, enzymes that regulate intracellular calcium levels. This action may be expected to promote recovery of cells from an excitatory stimulus. The present study was carried out to determine how prednisolone modulates airway response to histamine, including recovery from induced bronchospasm in asthmatics. Spirometry and measurement of bronchial responsiveness (forced expiratory volume in 1 sec [FEV₁] and concentration of histamine causing a 20% reduction FEV₁ [PD₂₀ FEV₁]) to inhaled histamine were carried out in 10 clinically stable asthmatics. Subsequently, all of the patients were prescribed oral prednisolone, 0.6-0.75 mg/kg body weight for 1 week. At the end of 1 week, spirometry was repeated and bronchial reactivity was measured again. Comparison of PD₂₀ FEV, values before and after treatment (geometric means 0.66 and 0.81 mg/mL, respectively) for the whole group did not show any significant change. The mean ± SD time for 95% recovery from histamine-induced bronchospasm was 33.00 ± 19.47 min before treatment and decreased significantly to 18.00 ± 7.88 min after treatment. It was concluded that short-term benefits from oral prednisolone do not result from changes in bronchial responsiveness. These benefits may be related to effects on mechanisms that lead to recovery from an excitatory stimulus.     

Determinants of the Severity of Exercise-Induced Bronchoconstriction in Patients with Asthma

Aim. In examining the mechanisms of exercise-induced bronchoconstriction (EIB), it is important to determine which factors most strongly affect the severity of EIB. We determined such factors in patients with asthma by stepwise multiple-regression analysis. Methods. Twenty-three patients with asthma underwent pulmonary function tests, methacholine provocation test, and sputum induction. Eosinophilic inflammatory indices and airway vascular permeability index (ratio of albumin concentrations in induced sputum and serum) were examined in sputum samples, and then an exercise test was performed by all asthmatics. Results. There was a significant correlation between the severity of EIB and degree of eosinophilic inflammation in induced sputum. Moreover, there was a significant correlation between the severity of EIB and airway vascular permeability index. Although we could not find a significant correlation between the severity of EIB and 1-sec forced expired volume, 20% provocation concentration of (PC₂₀) methacholine tended to be correlated with the severity of EIB. By stepwise multiple-regression analysis, we also found that airway vascular permeability index, eosinophil cationic protein levels in sputum, and PC₂₀ methacholine are independent predictors of the severity of EIB. Conclusion. We found that airway vascular hyperpermeability, eosinophilic inflammation, and bronchial hyperreactivity are independent factors predicting the severity of EIB.     

Potential Mechanisms of Improvement of Airway Hyperresponsiveness by Inhaled Corticosteroid Therapy in Asthmatic Patients

Objective. Recent clinical trials with administration of IL-5 antibodies to asthmatic patients have revealed reduction of eosinophilia but unaltered airway hyperresponsiveness (AHR). In contrast, inhaled corticosteroid (ICS) therapy eliminates both eosinophilia and AHR. This study was designed to examine the mechanisms by which ICS improves airway hyperresponsiveness in asthmatic patients.

Methods. Clinical variables of asthma involving vascular permeability and IL-5 levels were examined in 23 asthmatic patients and 11 normal control subjects. After the first sputum induction, inhaled beclomethasone dipropionate (BDP 800 μg/day) was administered to asthmatic patients for 8 weeks, and sputum induction was repeated.

Results. IL-5 levels in induced sputum and airway vascular permeability index were significantly higher in asthmatic patients. IL-5 was positively correlated with percentage of eosinophils in induced sputum, and negatively correlated with FEV1, but not correlated with PC₂₀ methacholine. After BDP therapy, eosinophils, ECP, and IL-5 levels were significantly decreased to the same levels as in normal subjects. Conversely, PC₂₀ methacholine and airway vascular permeability did not improve to the same levels as in normal subjects. Increase in PC₂₀ methacholine from before to after BDP therapy was significantly correlated with decrease in airway permeability index, but not with decrease in IL-5 level.

Conclusion. Our results suggest a clear dissociation between IL-5 and AHR. ICS therapy improves AHR at least in part through decrease in airway vascular permeability.     

Abstract

TITLE: Concomitant Chronic Sinusitis Treatment in Children with Mild Asthma. The Effect on Bronchial Hyperresponsiveness

AUTHORS: Tsao CH, Chen LC, Yeh KW.

JOURNAL: CHEST 2003; 123:750-764

Background. Bronchial hyperresponsiveness is an indicator of airways abnormalities and is central to pathophysiology of asthma. Frequent association of asthma and sinusitis has been noted with 80%-90% of children with asthma having concomitant nasal symptoms, and half of all individuals with asthma having radiographic evidence of sinusitis. Several investigators have noted an incidence of chronic sinusitis in the range of 40%-60% of children with bronchial asthma

Objective. The objective of the authors was to ascertain whether effective treatment of sinusitis could decrease bronchial hyperresponsiveness.

The clinical population included 61 children with a history of mild asthma with an age range of 7-10 years, and 10 age-matched health controls followed from 1999 to 2000. All children were mite sensitive in the asthmatic group. They also had occasional symptoms controlled only by betaagonists; 41 of the 61 children with mild asthma had allergic rhinitis.

The children with chronic sinusitis were placed in two groups; one group was treated with amoxicillin clavulanate for 6 weeks and then with nasal saline irrigation for 6 weeks. In the other group, the treatment order was reversed. The children without chronic sinusitis received nasal saline irrigation for 12 weeks.

Clinical Findings. The clinical findings were that there was a significant amelioration in clinical signs and symptoms of sinusitis, but not in FEV₁, after antibiotic treatment. Following aggressive therapy for sinusitis, it was discovered that the provocative concentration of methacholine causing a 20% decline in FEV₁ of children with mild asthma and sinusitis was significantly higher than before antibiotic treatment. PC₂₀s values of children with normal radiographic findings, who were only treated with intranasal salinc for 12 weeks, did not change significantly from baseline.

Conclusion. The result indicate that every asthmatic subject needs to be carefully assessed for concomitant sinusitis. Respiratory infections that meet the criteria for sinusitis even if they do not apparently trigger asthma should be aggressively treated. This study suggests that sinusitis should be kept in mind as a possible factor for producing increased bronchial hyperresponsiveness, and then aggressive therapy for chronic sinusitis is indicated when dealing with an asthmatic patient who has an unacceptable response to appropriate therapy.

Reviewer's Comment. In this study sign and symptoms of sinusitis disappeared after treatment. In a number of patients, nocturnal cough also markedly declined. In contrast with previous reports, however, there is no difference in FEV₁ before and after treatment for sinusitis and this maybe due to the fact that the subjects enrolled had only mild asthma, unlike subjects in previous reports. This study supports the relationship between sinusitis and asthma, the bronchial hyperresponsiveness, and the importance of aggresively treating chronic sinusitis to minimize symptoms of sinusitis, as well as to improve bronchial hyperresponsiveness.

Christopher Randolph, M.D.

Waterbury, CT     

Bronchoconstrictive Properties and Potentiating Effect on Bronchial Responsiveness of Inhaled Thromboxane A2 Analogue (STA2) in Guinea Pigs

Effect of subthreshold concentration of inhaled STA₂, a thromboxane A₂ (TXA₂) analogue, on bronchial responsiveness to histamine was investigated in anesthetized and artificially ventilated guinea pigs. Percent increase in pressure of the airway opening (Pao) by aerosol histamine (50, 100 /tg/ml) was significantly potentiated by subthreshold dose of aerosol STA₂ (0.10 μg/ml) which was determined by dose-response curve of % increase in Pao by inhaled STA₂ (0.033, 0.10, 0.33, 1.0 /xg/ml). These results demonstrated that thromboxane A₂ could contribute to bronchial hyperresponsiveness which is one of the major clinical features of bronchial asthma.     

Bronchial Reactivity to Inhaled Methacholine in Infants with Asthma and Age-Matched Controls

To evaluate bronchial hyperresponsiveness (BHR) in infants with asthma and the influence of aging on BHR during the infantile period, bronchial reactivity to inhaled methacholine (BRm) in infants was monitored using the transcutaneous oxygen pressure (tcPO₂) method. One hundred thirty-seven infants with asthma (from 1 to 5 years, mean 3.4 years) and 97 age-matched children without chronic respiratory diseases (from 6 months to 5 years, mean 2.1 years) were enrolled in this study. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO₂ from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO₂ (D_min-PO₂) was considered to represent the reactivity of tcPO₂ to inhaled methacholine. D_min-PO₂ values in the asthma groups were lower than those in the control groups in each year-group from 1 to 5. There was no statistical difference in D_min-PO₂ among the 1-4-year-old asthma groups, but D_min-PO₂ in the 5-year-old asthma group was significantly lower than D_min-PO₂ in the 1 -4-year-old asthma groups. The same age-related change in D_min-Po₂ was also seen in the control groups. There was no difference in age-related D_min-PO₂ change between the female group and the male group. We concluded that BRm in asthmatic children increases during the infantile period, and that the age-related changes in BRm, observed in both asthmatic and control infants, may have an effect on the clinical symptoms of asthma during childhood.     

Effects of thoracoscopic upper dorsal sympathicolysis for essential hyperhidrosis on bronchial responsiveness to histamine: Implications on the autonomic imbalance theory of asthma

Abstract Autonomic nervous system abnormalities in airway control may contribute to the symptoms of asthma, and even to the pathogenesis of bronchial hyperresponsiveness (BHR). Partial pulmonary sympathetic denervation by means of bilateral upper dorsal thoracoscopic D₂–D₃ sympathicolysis (TS) is an accepted treatment in severe essential hyperhidrosis (EH). The effects of this intervention on BHR are unknown. The objective of this study was to evaluate whether partial pulmonary sympathetic denervation by means of TS has an effect on BHR. Bronchial challenge tests with histamine, enabling the calculation of the provocative dose causing a 20% reduction in FEV₁ (PD_{20 His}) were performed 1 day before, and 6 weeks and 6 months after TS in 35 patients with severe EH. In nine patients (including three patients with a previous history of asthma) with pre-operative BHR (defined as PD_{20 His} < 2 mg), mean PD_{20 His} did not change significantly at 6 weeks, nor at 6 months after TS (0.62 ± 0.33, 0.71 ± 0.42 and 0.93 ± 0.65 mg, respectively) although there was a non-significant trend towards an increase in PD_{20 His} at 6 months. Three of the 26 patients (12%) without pre-operative BHR became hyperresponsive after TS, whereas 1 of the 9 patients with pre-operative BHR lost hyperresponsiveness. No patient developed asthma symptoms after TS. Upper dorsal thoracoscopic D₂–D₃ sympathicolysis performed for the treatment of EH has no significant effects on mean PD_{20 His} and individual loss (11%) or development (12%) of BHR occurs only in a minority of patients.     

Different IL-5 and IFN-γ Production from Peripheral Blood T-Cell Subsets in Atopic and Nonatopic Asthmatic Children

Defective Th1 and enhanced Th2-type cytokine responses have been implicated in the development of atopic disease. However, the immunopathology of nonatopic asthma, especially in children, remains unclear, and there have been few studies to compare the cytokine profile in peripheral blood T-cell subsets between atopic and nonatopic asthmatic children. To document whether atopic asthmatic children have a cytokine imbalance and to compare the cytokine profile between atopic and nonatopic asthmatic children, we investigated the interleukin (IL)-5-producing and interferon (IFN)-γ-producing T-cell subsets from peripheral blood mononuclear cells (PBMC). The percentages of IFN-γ-producing CD4⁺ and CD8⁺ T cells from atopic asthmatic children were decreased, but those in nonatopic asthmatic children were not decreased. In both groups of asthmatic children, the percentages of IFN-γ-producing CD4⁺ T cells were inversely correlated with the peripheral blood eosinophils and had a significant correlation with airway responsiveness (PC₂₀). Thus, we found that the mechanism underlying allergic inflammation of nonatopic asthma is not simple a Th1/Th2 cytokine imbalance. Considering the inverse relationship between IFN-γ-producing CD4⁺ T cells and eosinophilia or airway hyperresponsiveness, IFN-γ from CD4⁺ T cells may play an important role in allergic inflammation and airway hyperresponsiveness in asthmatic children.     

Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma

It is unclear whether angiotensin II receptors are involved in bronchial hyperresponsiveness in asthmatic patients. We examined the effect of losartan, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in eight patients with stable asthma. Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV(1) (PC(20)-FEV(1)) and a 35% fall in standardized partial expiratory flow at 40% of FVC (PC(35)-PEF(40)), was measured on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally administered for 1 wk before methacholine provocation test in a double-blind, randomized, crossover fashion. Although the PC(20)-FEV(1) values after placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC(35)-PEF(40) values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml with placebo to 0.456 (GSEM, 0.186) mg/ml with losartan. We conclude that AT1 receptors are involved in bronchial hyperresponsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.     

Effect of Ibudilast: A Novel Antiasthmatic Agent, on Airway Hypersensitivity in Bronchial Asthma

Ibudilast, a unique agent with vasodilating and antiallergic actions, was studied in 13 asthmatics for its effect on airway hypersensitivity to histamine inhalation. The PC₂₀ values improved significantly from 355.6 to 620.5 μg/ml at 3 months and further to 731.4 μg/ml at 6 months following the initial treatment with ibudilast (20 mg twice daily orally). In addition, the severity of the attacks decreased significantly. Improvements in the PC₂₀ and asthmatic symptoms also were observed in the disodium chromoglycate group, but these were equal to or lesser than those in the ibudilast group. No improvement was observed in the untreated control group. These results suggest that ibudilast would be an effective agent for improving nonspecific airway hypersensitivity in asthmatics.     

Development of Lung Function in Relation to Increased Degree of Bronchial Responsiveness

To study the relationship between development of lung function and bronchial responsiveness, we examined 106 subjects recruited from a random sample of 527 subjects, aged 8-18 years, from Copenhagen. Lung function and bronchial responsiveness to inhaled histamine were measured at two occasions, in 1986 and 1988. The participating subjects (n = 106) were divided into three groups: (a) 20 asthmatics with bronchial hyperresponsiveness (BHR), (b) 42 nonasthmatic subjects with BHR in 1986, and (c) 44 controls without BHR. In 1986, FEV₁ expressed as percentage of predicted value, was found to be similar in the three groups (91%, 94%, and 99%, respectively). The increase in height during the observation period was found to be 5, 6, and 6 cm, respectively, in the three groups. However, at the second examination, in 1988, FEV₁ was found to be significantly reduced in both asthmatics (87%) and nonasthmatic subjects (85%) compared with the controls (103%). In 1988, 16 asthmatics (80%) and 24 (57%) nonasthmatic subjects were found to have BHR, whereas none of the controls were found to have BHR. A multiple regression analysis was used to determine the correlation between change in FEV₁ and potential factors of importance. The change in FEV₁ was highly correlated with the presence of BHR in 1986, however, no correlation was found between change in FEV₁ and change in bronchial responsiveness. In conclusion, nonasthmatic subjects with former BHR showed signs of airflow obstruction and less increase in lung function during growth irrespective of the change in level of bronchial responsiveness, which may suggest a risk for subsequent development of obstructive lung disease.     

Longitudinal changes of pulmonary function and bronchial responsiveness in cough-variant asthma treated with bronchodilators alone.

Cough due to cough-variant asthma (CVA) responds well to bronchodilators such as beta 2 adrenergic agonists. The aim of this study was to assess longitudinal changes of pulmonary function and bronchial responsiveness in CVA, which was treated with bronchodilators alone. Seventeen CVA patients recorded intensity and frequency of cough every day. Spirometry and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20) were measured in the run-in period and after cough almost completely relieved on therapy. Cough score had improved within 2 weeks after the initiation of bronchodilator therapy. Forced expiratory volume in one second (FEV1) was significantly increased from 2.7 +/-0.7 L in the run-in period to 2.8+/-0.7 L after improvement of cough. However, the geometric mean (GSEM) PC20 value did not change from the run-in period [1542 (GSEM 1.29) microg/mL] to the time of improvement [2600 (GSEM 1.43) microg/mL]. Mildly increased bronchial responsiveness in CVA does not improve when only bronchodilator therapy is carried out. Because bronchial hyperresponsiveness has been shown to be a risk factor for typical asthma onset from CVA, the effect of inhaled corticosteroids on the longitudinal changes in bronchial responsiveness should be examined.     

Bronchial Asthma Showing Reduction in FEV1 after Inhalation of Qvar™

The administration of Qvar (a hydrofluoroalkane-134a beclomethasone dipropionate; HFA-BDP) is highly useful for the treatment of patients with asthma. However, we found in a case of bronchial asthma that replacing the prior inhaled corticosteroids with Qvar resulted in temporary dyspnea and reduction in forced expiratory volume in 1 second (FEV₁). Qvar contains beclomethasone dipropionate combined with absolute ethanol and an alternative to fluorocarbon. The patient had complicated alcohol-induced asthma. FEV₁ decreased markedly and immediately after Qvar inhalation. The Qvar placebo is free of beclomethasone but contains other ingredients (ethanol and fluorocarbon). FEV₁ did not decrease after the Qvar placebo, Aldecin inhalation, and Qvar inhalation orally treated with atropine before inhalation of Qvar™. It seems unlikely that the components of Qvar (except beclomethasone) are responsible for the reduction in FEV₁ observed immediately after inhalation of Qvar. These findings would be noteworthy when using Qvar for Japanese patients with asthma known to have a relatively high frequency of the complication of alcohol-induced asthma.     

Expression of Transforming Growth Factor β1 in Bronchial Biopsies in Asthma and COPD

The role of transforming growth factor β₁ (TGF β₁) in airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) has not been fully described. To evaluate the possible pathogenetic role of TGF β₁ in asthma and COPD, immunohistochemical expression of TGF β₁ was described in bronchial biopsies from patients with asthma and COPD compared with healthy individuals. Twelve subjects with asthma, 13 subjects with COPD, and 10 healthy individuals enrolled in the study. Bronchial biopsies were stained with hematoxylin and eosin and anti-TGF β₁ antibody. As a result, immunoreactive TGF β₁ was mainly localized in association with connective tissue in all groups. The staining intensity was not statistically different among the groups in bronchial epithelium, whereas it was significantly higher in the group of asthma in the submucosa. Because there is evidence showing a significant increase of staining intensity in the submucosa from asthmatics but not from subjects with COPD, we may conclude that TGF β₁ may play a significant role in pathogenesis of asthma but not in COPD.     

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.     

Airway responses to salbutamol after exposure to chemical warfare

Background and objectives:   Increased airway responsiveness to β-agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to β-agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare.
Methods:   The threshold concentrations of inhaled salbutamol required for a 20% change in FEV₁ as PC₂₀, or a 35% change in specific airway conductance (sGaw) as PC₃₅ were measured in 22 persons exposed to chemical warfare and 15 normal control subjects.
Results:   In 11 of the 22 subjects PC₂₀ salbutamol could be measured and in 15 of the 22 subjects PC₃₅ salbutamol could be measured. This group of patients was the responder group (PC₂₀ = 10.79 and PC₃₅ = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC₂₀ = 237.68 and PC₃₅ = 88.72 mg/L, P  < 0.001). There was a significant correlation between FEV₁ and PC₂₀ salbutamol ( r  = 0.815, P  < 0.001).
Conclusions:   These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.