Is normal bronchial responsiveness in asthmatics a reliable index for withdrawing inhaled corticosteroid treatment?

STUDY OBJECTIVE: Inhaled corticosteroid (ICS) treatment is first-line maintenance therapy in bronchial asthma. However, it is not clear whether and when ICS treatment can be withdrawn. The aim of this open study was to assess whether normalization of bronchial responsiveness could be used as a reliable index to assess the opportunity of ICS treatment withdrawal. DESIGN: Open study at two different points in time. SETTING: Outpatient pulmonary clinic. PATIENTS: Eighteen asthmatic subjects. MEASUREMENTS AND RESULTS: ICS therapy was withdrawn in subjects treated with beclomethasone dipropionate, at the maintenance dose of 889+/-246 microg/d for >3 months. Upon recruitment, all subjects were asymptomatic, had FEV1 >70% of predicted value, and were in treatment with beta2-agonists on an as-needed basis. Eight subjects (group 1) had normal bronchial responsiveness (methacholine provocative dose causing a 20% fall in FEV1 [PD20] >2,000 microg) and 10 subjects (group 2) had bronchial hyperresponsiveness (BHR) (PD20 < or = 2,000 microg). After withdrawal of ICS treatment, subjects were followed up for 3 weeks and were asked to record their asthma symptoms (cough, dyspnea, and wheezing) and their beta2-agonist use. At recruitment and at the end of follow-up, subjects underwent spirometry and a methacholine challenge test. Frequency of asthma exacerbation was similar in subjects with normal bronchial responsiveness (NBR) and in subjects with BHR (50% vs 60%), but subjects with NBR tended to remain asymptomatic for longer than those with BHR (mean+/-SD, 10.7+/-4.4 days vs 5.5+/-3.8 days) (p=0.08). None of the subjects reported any condition that could have triggered exacerbation. Asthma exacerbation was associated with a significant decrease in FEV1 (-105+/-107 mL; p<0.05) and in PD20 (-1,332+/-1,020 microg; p<0.001). CONCLUSIONS: Our study shows that the likelihood of asthma exacerbation is not reduced if ICS treatment is withdrawn when the subjects have NBR, but the exacerbation could be delayed. Further studies in larger populations of asthmatics are needed to confirm these findings.     

The inhibition of yohimbine injected intrathecally on electroacupuncture-induced analgesia and release of beta-endorphin from rat brain

No study has investigated the effects of ethanol on bronchial responsiveness in patients with alcohol-induced asthma, although acetaldehyde, which is a metabolite of ethanol and is thought to be a main factor in alcohol-induced asthma, causes both bronchoconstriction and bronchial hyperresponsiveness. The purpose of this study was to investigate the direct action of ethanol on the airway in patients with alcohol-induced asthma. First, we investigated the bronchial response to inhalation of ascending doses (5, 10, and 20%) of ethanol in nine patients with alcohol-induced asthma. Then, the bronchial responsiveness to methacholine was measured in 14 patients who were pretreated with saline or 20% ethanol in a double-blind, randomized, placebo-controlled, crossover fashion. Ascending doses of inhaled ethanol caused no significant changes in FEV1. The methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) after 20% ethanol (0.769 mg/ml, GSEM 1.514) were significantly (P = 0.0357) higher than those after saline (0.493 mg/ml, GSEM 1.368). This indicates that ethanol has a reducing effect on nonspecific bronchial responsiveness in patients with alcohol-induced asthma; this paper is the first report on the effects of ethanol on bronchial responsiveness.     

Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a pilot study

BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility of using a metered-dose inhaler (MDI) to administer methacholine in bronchial provocation tests, and the ability of such a device to diagnose bronchial hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover pilot study, we compared the provocative dose that induces a 20% fall in FEV1 (PD20 FEV1) obtained with the methacholine MDI with that obtained using a conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects. The MDI delivers 400 doses of 100 microg of methacholine, and was used via a spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000 microg with the conventional test using the nebulizer. The tests were performed in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20 FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and the two tests were highly concordant for the diagnosis of BHR (Pearson chi2, 36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of methacholine during bronchial provocation tests, if these results are confirmed in large samples.     

Specific bronchial provocation tests with flour in the diagnosis of occupational bronchial asthma

The gold standard in the diagnosis of occupational asthma is the specific bronchial provocation test (sBPT), but other diagnostic criteria have been proven to have a similar sensitivity, mainly in asthma due to high molecular weight compounds. In order to assess wether some clinical findings can predict the positive response to sBPT, we studied 37 subjects (14 millers and 23 bakers) with suspected occupational asthma who underwent sBPT with wheat flour dust (dust exposure in a small cabin: geometric mean 12.1 mg/m3 for up to 30 min). A positive response to sBPT (FEV1 > 20%) was elicited in 20 subjects (11 early, 4 late, and 5 dual responses). There was no significant difference between subjects with positive or negative sBPT as regards mean age, smoking, length of employment, duration of symptoms, atopy (skin positivity to one or more common allergens) and PD20FEV1 methacholine. The percentage of subjects with work-related symptoms was significantly higher in subjects with positive sBPT with respect to subjects with negative sBPT (81% versus 41.2%, p < 0.01 by chi 2 test); furthermore, FEV1 was significantly lower in subjects with positive sBPT. The percentage of positive skin response to wheat flour extract (mean wheal diameter > or = 3 mm) was mildly but not significantly higher in subjects with positive sBPT (68.4% versus 41.2%). None of the following clinical factors (age < 35 years, asthma symptoms pre-existing occupational exposure, non smokers, atopy and bronchial hyperresponsiveness to methacholine), alone or in combination, were associated with higher prevalence of positive sBPT. We conclude that the response to sBPT in subjects with suspected occupational asthma due to flour dust can not be adequately predicted by other clinical, allergologic and functional data. Therefore, sBPT with flour dust should always be performed in subjects with suspected occupational asthma.     

Is bronchial hyperresponsiveness more frequent in women than in men? A population-based study

To test the hypothesis that a greater proportion of women than men react to methacholine challenge and investigate the possible reasons for any differences observed, we recruited 495 subjects 20 to 44 yr of age (50.9% male) in Paris and 304 subjects (51.3% male) in Montpellier (France), as part of the European Community Respiratory Health Survey. The proportion of responders (PD20 < or = 4 mg methacholine) was 33.7% in women and 11.9% in men (odds ratio = 3.8; 95% confidence interval = 2.4-6.0) in Paris and 43.2% in women and 29.5% in men (odds ratio = 1.8; 95% confidence interval = 1.1-2.9) in Montpellier. These differences could not be explained by asthma, respiratory symptoms, atopy, or lung function parameters. In stepwise logistic regressions including sex, asthma, and asthma-like symptoms, nasal allergies, atopy, baseline FEV1, FEV1%pred, FVC, and FEV1%FVC, the odds-ratios for the effect of female sex on PD20 < or = 4 mg methacholine were 5.2 (3.0-9.0) in Paris and 2.2 (1.2-3.8) in Montpellier. Reacting to low doses of methacholine (PD20 < or = 0.5 mg) was associated with asthma and atopy in both men and women. In contrast, reacting to doses between 0.5 and 4 mg was associated with asthma and atopy only in men and with heavy tobacco consumption only in women. We conclude that the excess of hyperresponsiveness in women is not due to their having smaller lung size or airway caliber than men and may be related to a greater susceptibility to smoking.     

Bronchial hyperresponsiveness as a predictor of wheezing in a follow-up study of healthy men

We assessed the relationship between bronchial hyperresponsiveness (BHR) and the onset of wheezing 5 years later, by epidemiological analysis of 194 working men without asthma or wheezing at the first examination. In 1985/ 1986 and 1990/1991, subjects answered a British Medical Research Council questionnaire and performed lung function measurements and methacholine challenge tests (total dose 6 mg). BHR was measured in three ways: (1) FEV1 fall > or = 20% (PD20+); (2) the two-point response slope expressed as percentage decline of FEV1/dose, and (3) a four-parameter model: FEV1 at dose (d)/ prechallenge FEV1 = ONE-k(d-delta)+a, where 'k' is the slope of the relative variation of FEV1 with the dose, 'delta' the threshold dose, and 'alpha' a shape factor. In the 13 new wheezers, the mean values of the two-point slope and of k were significantly increased, and the proportion of reactors was almost threefold (the latter was not statistically significant). Among nonsmokers, delta was significantly lower in new wheezers than in the others, whereas the slope and k had similar mean values. Among smokers, new wheezers had increased mean values for the slope and k, and an increased proportion of reactors, whereas delta was not decreased. Thus, BHR was a significant predictor of wheezing, independent of the method of analysis. Moreover, the model distinguished between two components of bronchial response: wheezing was predicted by sensitivity (delta) in nonsmokers, and by reactivity (k) in smokers.     

Evaluation of the inhaled glucocorticosteroid effects on non specific bronchial reactivity with particular reference to the late inflammatory phase in atopic asthma patients. II. The effect of regular administration of budesonide R on specific and non-specific bronchial reactivity

The purpose of the study was to determine whether regular administration of budesonide R decreases inflammation, specific and non-specific bronchial hyperreactivity in allergic asthma patients. The studies were carried out on 16 patients suffering from mild to moderate allergic asthma, sensitive to D. pteronyssinus allergen. After performance of the specific and non-specific bronchial provocation tests, collection of blood samples for an ECP evaluation, the patients were regularly treated with budesonide R, 2 x 320 micrograms for a period of 8 weeks. At the end of the study the BPTs and blood collection were repeated. BPTs with methacholine and D. pteronyssinus were performed according to Ryan's method. After the allergen challenge, early (EAR) and late asthmatic reaction (LAR) were to be observed. After the therapy non-specific BHR to methacholine expressed as PC20FEV1 and specific BHR to allergen (PD20FEV1D. pteronyssinus) and serum ECP concentrations decreased significantly. Although after the treatment with budesonide R, the patients had to inhale much larger amounts of allergen, in order to induce EAR, the number of LAR did not change significantly. After treatment the LAR appeared about 1 hour later and the decrease in FEV1 was less than previously. We conclude that budesonide R decreases the intensity of the inflammation and BHR.     

Increase in non-specific bronchial hyperresponsiveness without specific response to isocyanate in isocyanate-induced asthma: a pilot study

Increased non-specific bronchial hyperresponsiveness (BHR) has been reported after positive reaction to isocyanates in patients with isocyanate-sensitive asthma. The increased responsiveness may, however, also precede the asthma attack. We therefore compared non-specific BHR to a cholinergic agent before and after exposure to toluene-diisocyanate (TDI) that induced no asthma symptoms in 11 workers with isocyanate-related asthma. Patients were exposed for 3 consecutive days to progressively increasing doses of TDI (5, 10, and 20 ppb min-1 for 20 min) in an exposure chamber with continuous TDI monitoring. No immediate nor late asthmatic bronchial reaction was observed in any patient after any dose of TDI during or after challenge. A significant increase in non-specific BHR was noted 24 h after the last dose of TDI challenge, however. This increase was at least one doubling dose for seven of 11 patients. In conclusion, our study shows that, in patients with isocyanate-induced asthma, exposure to TDI induces a slight but significant increase in non-specific BHR in the absence of any immediate or late bronchial response to isocyanate. This result, which requires further confirmation, may justify a proposal to measure non-specific BHR, even after a negative specific inhalation test to TDI, as an additional diagnostic element for TDI-induced occupational asthma, to help lower the percentage of the undetected occupational asthma cases.     

Treatment of recurrent corneal erosion using phototherapeutic keratectomy with the excimer laser

Tachyphylaxis to methacholine has been reported in nonasthmatic subjects. In a recent study on the prevalence of airway hyperresponsiveness (AHR) and atopy, we performed duplicate methacholine inhalation tests at a 60-min interval, in subjects with symptomatic asthma (n = 33), asymptomatic AHR (AAHR) (n = 72) and in a group of normal subjects (n = 130); 135/235 subjects were atopic. All subjects had a respiratory questionnaire, allergy skin prick tests, blood eosinophil counts and determination of total serum IgE level. In asthmatic subjects, PC20 just failed to be significantly higher on a second methacholine challenge (p = 0.09); when they were stratified according to severity of AHR and use of inhaled corticosteroids, we observed a significant increase in PC20 on the second test in asthmatic subjects with mild AHR not using corticosteroids (p < 0.01). In normal controls, PC20 methacholine was slightly increased on rechallenge (p < 0.01) as it was in those with AAHR (p < 0.01). There was no relationship between the magnitude of the change in PC20 and age, sex, baseline airway responsiveness, percent fall in FEV1 on the first challenge, atopic score, blood eosinophil counts and serum IgE levels. In conclusion, tachyphylaxis to methacholine is observed in normal or mild asthmatic subjects not using inhaled corticosteroids and in subjects with AAHR; however, in most subjects this change is of a small magnitude.     

Bronchial hyperresponsiveness after cervical spinal cord injury

Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20] = 1.42 +/- 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 > 25 mg/ml [p < 0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.     

Citric acid-induced cough thresholds in normal subjects, patients with bronchial asthma, and smokers

Several challenge procedures have been developed to characterize the cough reflex in patients with airway diseases. This study was performed to compare the interindividual range of cough sensitivity in asthmatic and normal subjects as well as smokers using an identical method. Sixteen normal subjects, 20 patients with mild bronchial asthma, 6 patients with moderate to severe bronchial asthma, 9 current smokers, and 7 occasional smokers were included. In all subjects, methacholine challenges and standardized citric acid challenges were performed. Sensitivity of the cough reflex was expressed as cough threshold, i.e., as concentration at which coughing occurred. Reproducibility was assessed in 23 subjects. Within a concentration range of 0.625-320.0 mg/ml, inhaled citric acid caused cough in all subjects. Geometric mean (range) cough threshold was 13 (2.5-160) in normal subjects, 14 (5-40) in patients with mild, and 32 (20-40) mg/ml in patients with moderate to severe asthma, 40 (20-80) in current smokers, and 119 (80-160) in occasional smokers. Cough thresholds were reproducible within one doubling concentration. In normal subjects and patients with mild bronchial asthma, thresholds were not significantly different from each other but lower than those of the other groups (p<0.05 each). Cough thresholds in smokers and patients with moderate to severe asthma did also not differ significantly and were lower than in occasional smokers (p<0.05). There was no significant correlation between cough threshold, baseline FEV subset1 , and methacholine responsiveness. Our data indicate that (1) subjects with mild asthma showed on average similar cough thresholds as normal subjects, (2) there was a large variation in cough thresholds within groups, (3) the reproducibility of cough thresholds was within one doubling concentration, (4) cough thresholds did not correlate with methacholine responsiveness or baseline airway tone. In view of the prevalence of cough as a symptom of bronchial asthma, it appears that the determination of citric acid-induced cough thresholds does not yield additional diagnostic information in these subjects.     

Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI)

BACKGROUND: TDI-induced asthma exhibits clinical, functional and morphological similarities with allergen-induced asthma, suggesting that an immunological mechanism is involved in the sensitization to TDI. In vitro studies using the technique of cloning lymphocytes demonstrated that a great proportion of T-cell clones derived from bronchial mucosa of subjects with TDI-induced asthma produced IL-5 and interferon-gamma, but not IL-4, upon in vitro stimulation. OBJECTIVES: To investigate in vivo the role of IL-4 and IL-5 on the inflammatory response of the bronchial mucosa to TDI in sensitized subjects, we performed a quantitative analysis of bronchial biopsies. METHODS: We obtained bronchial biopsies from six subjects with TDI asthma 48 h after an asthmatic reaction induced by TDI challenge (challenged group), in six subjects with TDI asthma 1-4 weeks after the last exposure to TDI (chronic group), and in six non-asthmatic controls. The number of eosinophils, mast cells, T-lymphocytes, and IL-4 and IL-5 protein positive cells was determined by immunohistochemistry in the area 100 microm beneath the epithelial basement membrane. RESULTS: The characteristic increase of submucosal eosinophils, but not of mast cells and T-lymphocytes, was observed in the subjects with TDI-induced asthma when compared with controls. No differences were detected between the two groups of asthmatics. In the subjects with TDI-induced asthma, cell immunoreactivity for IL-5 was increased when compared with normal controls. There was no difference in the expression of IL-5 protein between challenged and chronic asthmatics. In contrast, the expression of IL-4 protein was increased only in the asthmatic subjects tested after recent exposure to TDI. CONCLUSIONS: We demonstrated that TDI asthma 48 h after specific bronchial challenge was associated with increased numbers of cells expressing IL-4 and IL-5, whereas chronic TDI asthma was associated with increased expression of IL-5, but not of IL-4. The results suggest that subjects who developed TDI asthma exhibit increased production of IL-5 even in the absence of a recent trigger by the exogenous sensitizer and that production of TH2-like cytokines in TDI-induced asthma may not always be co-ordinately regulated in vivo.     

Vladimir Vladimirovich Sakharov--an outstanding disciple of N. K. Kol''tsov

OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) in the atmosphere of indoor swimming pools and to examine how they relate to irritant and chronic respiratory symptoms, indices of pulmonary function, and bronchial hyperresponsiveness to methacholine in lifeguards working in the pools. METHOD: 334 lifeguards (256 men; 78 women) recruited from 46 public swimming pools (n = 228) and 17 leisure centre swimming pools (n = 106) were examined. Concentrations of NCl3 were measured with area samplers. Symptoms were assessed by questionnaire and methacholine bronchial challenge (MBC) test by an abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose-response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: 1262 samples were taken in the 63 pools. Mean NCl3 concentrations were greater in leisure than in public pools. A significant concentration-response relation was found between irritant eye, nasal, and throat symptoms-but not chronic respiratory symptoms-and exposure concentrations. Among women, the prevalence of MBC+ was twice as great as in men. Overall, no relation was found between bronchial hyperresponsiveness and exposure. CONCLUSIONS: The data show that lifeguards exposed to NCl3 in indoor swimming pools are at risk of developing irritant eye, nasal, and throat symptoms. Exposure to NCl3 does not seem to carry the risk of developing permanent bronchial hyperresponsiveness, but this association might have been influenced by self selection. The possibility that subjects exposed to NCl3 are at risk of developing transient bronchial hyperresponsiveness cannot be confidently ruled out.     

Potentiating effect of inhaled acetaldehyde on bronchial responsiveness to methacholine in asthmatic subjects

BACKGROUND: It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS: Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS: Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS: Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.     

Changes in neurokinin A airway responsiveness with inhaled lysine-acetylsalicylate in asthma

Endogenously released cyclooxygenase products modulate the bronchoconstrictor response to various stimuli in asthma. Little is known of the change in airway responsiveness to neurokinin A (NKA) after cyclooxygenase blockade. In this randomized, double-blind, placebo-controlled study, we have investigated the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on the bronchoconstrictor response both to neurokinin A (NKA) and methacholine in nine asthmatic subjects. Subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg.mL-1) or matched placebo (glycine, solution of 30 mg.mL-1) 15 min prior to bronchial challenge with NKA or methacholine, in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness, expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). L-ASA elicited a significant fall in FEV1 from baseline. When compared with placebo, inhaled L-ASA reduced the airway responsiveness to NKA in 8 of the 9 subjects studied, the geometric mean (range) values for PC20 NKA increasing significantly from 153.2 (52.0-258.9) to 303.1 (83.4-668.5) micrograms.mL-1 after placebo and L-ASA, respectively. However, no significant change in airway responsiveness to methacholine was recorded after L-ASA, their geometric mean (range) PC20 values being 1.60 (0.17-9.59) and 1.53 (0.09-14.01) mg.mL-1 after placebo and L-ASA, respectively. The small decrease in airway responsiveness to neurokinin A after administration of lysine acetylsalicylate by inhalation suggests that endogenous prostaglandins may play a contributory protective role in the airway response to neurokinin A in human asthma.     

Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.     

Comparison of bronchial reactivity to ultrasonically nebulized distilled water, exercise and methacholine challenge test in asthmatic children

We studied the responses to ultrasonically nebulized distilled water (UNDW) challenge, exercise challenge and methacholine challenge in asthmatic children. Fifty-four asthmatic and fourteen nonasthmatic control children participated in this study. The UNDW inhalation test was by the methodology described by Anderson. The average output of water was approximately 3.0 mL/min (SD = .1) and inhalation times were 30 seconds, one minute, two minutes and four minutes. Some subjects performed exercise challenge on a bicycle ergometer and methacholine challenge by an Astrograph technique. Twenty-three of 54 asthmatic patients (42.6%) and none of the controls showed a fall in FEV1 greater than 20% with UNDW challenge. The fall in FEV1 with UNDW correlated with that induced by exercise challenge (r = .89) and Log Dmin, which may reflect bronchial sensitivity (r = .70). Our method is not sensitive enough for detecting bronchial hyperresponsiveness in all asthmatic children. Bronchoconstriction induced by UNDW has a similar mechanism of action as exercise and methacholine.     

Discrepancies between diagnosed asthma, asthma-like symptoms and a test for abnormal lung function

For the diagnosis of asthma, it is neither clear to which degree various tests and symptoms identify the same subjects nor how these characteristics are best combined. We assessed the interrelationship between physician-diagnosed asthma, asthma-like symptoms and abnormal airway function in a population based sample of 495 12-15 year old schoolchildren. Participants filled in a questionnaire and underwent baseline spirometry (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. Most symptomatic subjects with any test positive were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). Although interest agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, between PEF and EXE and between FEV1% and PD15. However, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology, and the combined use of the two tests may be helpful as an epidemiological screening tool for asthma.     

A review of the effectiveness of Cimicifuga racemosa (black cohosh) for the symptoms of menopause

1. Environmental contact with cold air is a common cause of respiratory distress in obstructive lung disease, and direct and reflex changes in bronchial calibre are well documented with this stimulus when it is inhaled or contacts the exposed skin respectively. It is now known that skin chilling does not amplify the effects of breathing cold air, but it is not established if this lack of interaction is unique, or applies to other forms of airway constrictors. 2. To provide data on this issue, 10 subjects with atopic asthma underwent methacholine bronchoprovocations with and without chilling of the integument of their heads and thoraces for 30 min. Chilling was accomplished with a specially designed thermal garment. Spirometry as well as core and skin temperatures were serially monitored during all experiments. 3. In the control phase (no cooling), integumental temperatures rose slightly, the forced expiratory volume in 1.0 s (FEV1.0) did not change, and the mean provocative concentration of methacholine required to reduce the FEV1.0 by 20% (PC20 meth) was 0.47 +/- 0.17 mg/ml (2.4 +/- 0.87 mmol/l). In the cold trial, the temperature of the back fell 5.1 +/- 1.7 degrees C to 28.7 +/- 1.8 degrees C (P < 0.01), core temperatures did not change, and airway obstruction developed (delta FEV1.0 = -6.7 +/- 2.1%; P < 0.05). The PC20 meth, however, was unaltered [PC20 meth = 0.45 +/- 0.13 mg/ml (2.3 +/- 0.66 mmol/l); P = 0.85]. 4. These results demonstrate that although skin cooling produces mild airway obstruction in subjects with asthma, it does not change the response to non-specific bronchoconstrictors such as methacholine.