Tidal Breathing Method Research Articles

COMPARISON OF THE 2 BRONCHIAL PROVOCATION TESTS OF DIFFERENT DOSAGE CONCENTRATION GRADIENTS FOR INFANTS

INTRODUCTION: Bronchial provocation tests (BPTs) assist in diagnosing and evaluating the curative effect of asthma. OBJECTIVE: The objective of this study was to compare the sensitivity, reliability, and safety between 2 tidal breathing methods in BPT. METHODS: Sixty-five infants, including those with asthma and chronic cough, were divided into groups A and B at random. BPT by the improvement of tidal breathing method was performed in group A (35 infants), and the traditional tidal breathing method was performed in group B (30 infants). In 10 normal infants (control subjects), the traditional tidal breathing method was used. In addition, we observed arterial oxygen saturation, respiratory system resistance, %T-PF, percent of tidal volume of peak tidal expiratory flow, and lung symptoms and monitored the vital sign and adverse effects of the test. RESULTS: Results of the BPTs for all children with asthma were positive. The positive rates for children with chronic cough were 69.57% and 60.00% in groups A and B, respectively; the results of BPTs in control subjects were completely negative. There was no significant difference in positive rate, and both methods had a similar degree of airway hyperresponsiveness; however, in group A, the effect was of shorter duration and the test was more efficient. During the BPT, 6 infants in group A and 9 in group B had cough, but none exhibited an acute asthma episode. CONCLUSIONS: The improved tidal breathing method, used as a BPT, outweighs the traditional method in sensitivity, specificity, efficiency of detection, dosage of medicine, and safety.

Relationship between exhaled nitric oxide and pulmonary function test in children with asthma

Purpose : Asthma is characterized by reversible airway obstruction and bronchial hyperresponsiveness result from airway inflammation. Fraction of nitric oxide in expired air (FeNO) has recently been investigated as a noninvasive measure of airway inflammation. FeNO has been reported to correlate with induced sputum eosinophilia and methacholine challenge test that it is represent severity of asthma. The purpose of this study was to analyze the relationship of FeNO with pulmonary function tests in patients with intermittent asthma. Methods : Eighty children included in this study were diagnosed as asthma from April through August, 2005 in Department of Pediatrics, College of Medicine, Kyunghee University. They aged from 4 to 15 years who were able to conduct spirometry and FeNO monitoring. They did not have upper respiratory tract infection and did not use an asthma controller which contain corticosteroids within 4 weeks. Pulmonary function test was done and FeNO was measured with online tidal breathing method using a chemiluminescence NO analyzer (CLD 88 sp, Eco Medics, Duernten, Switzerland). The correlations between pulmonary function test and FeNO were analyzed using Spearman correlation coefficient method. Results : The mean of FeNO of subject was 16.88 parts per billion (ppb). The mean of forced expiratory volume in 1 second (FEV1) was 0.890±0.455 L and forced vital capacity (FVC) was 1.071± 0.630 L. The mean of predicted FEV1% (FEV1%pred) was 98.39±34.27% and FEV1/FVC was 88.53± 19.49. FeNO was significantly correlate with FEV1 (r=0.345, P<0.01) and FVC (r=0.244, P<0.05). FeNO did not correlate with FEV1%pred or FEV1/FVC. Conclusion : The measurement of FeNO could be a useful marker in the management of childhood asthma and it is evolving to provide a complementary role alongside existing pulmonary function test. We propose that measuring technique and establishment of normal reference range are important area for future research. (Korean J Pediatr 2008;51:181-187)

The analysis of the level of bronchial hyperresponsiveness in astmatic children(2 - 18 years) by dosimetric, oscilometric and tidal breathing methods to histamine and methacholine and analysis of polymorphisms genes ADAM33 and STAT6

The analysis of the level of bronchial hyperresponsiveness in astmatic children(2 - 18 years) by dosimetric, oscilometric and tidal breathing methods to histamine and methacholine and analysis of polymorphisms genes ADAM33 and STAT6

Bronchial responsiveness in bakery workers: relation to airway symptoms, IgE sensitization, nasal indices of inflammation, flour dust exposure and smoking

Bronchial hyperresponsiveness (BHR) is common in bakery workers. The relation between bronchial responsiveness measured with a tidal breathing method and smoking, airway symptoms, IgE-sensitization, nasal indices of inflammation and flour dust exposure have been studied with bronchial responsiveness expressed as a continuous outcome. Bakery workers (n = 197) were subjected to interviews, questionnaires, allergy tests, workplace dust measurements and bronchial metacholine provocation. Eosinophil cationic protein (ECP) and alpha(2)-macroglobulin were measured in nasal lavage. Bronchial responsiveness was expressed as slope(conc), a measurement based on regressing the per cent reduction in FEV(1) at each provocation step. BHR expressed as slope(conc) was associated with smoking (P = 0.009), asthma symptoms at work (P = 0.001), and occupational IgE sensitization (P = 0.048). After adjusting for baseline lung function the association between BHR and IgE sensitization was no longer present. We demonstrated an association between nasal ECP and BHR (slope(conc) < 3: P = 0.012), but not to alpha(2)-macroglobulin in nasal lavage. No association was seen between BHR and current exposure level of flour dust, number of working years in a bakery or a history of dough-making. BHR is related to baseline lung function, work-related asthma symptoms, smoking and nasal eosinophil activity, but not to occupational IgE sensitization and current flour dust exposure when measured with metacholine provocation. The slope(conc) expression seems to be a useful continuous outcome in bronchial responsiveness testing.

The Effect of Challenge Method on Sensitivity and Reactivity to Adenosine 5′-Monophosphate in Subjects With Suspected Asthma

The following two methods of inhalation challenge have been used to determine the airway responsiveness: the tidal-breathing method; and the dosimeter method. The objective of the study was to determine the influence of the challenge method on the response to adenosine 5'-monophosphate (AMP). This study measured airway responsiveness to AMP by dosimeter and tidal-breathing methods in 25 subjects with suspected asthma. The two AMP challenges were conducted in random order, on separate days, at the same time of day, at intervals of 1 to 5 days. Concentration-response curves were characterized by the provocative concentration of a substance causing a 20% fall in FEV1 (PC20) and slope. The dosimeter PC20 values were significantly higher than the tidal-breathing PC20 values, with geometric mean (95% confidence interval [CI]) values of 50.35 mg/mL (95% CI, 19.50 to 129.72 mg/mL) and 28.97 mg/mL (95% CI, 11.99 to 69.98 mg/mL; p = 0.02), respectively. The mean difference in the PC20 values obtained with each method was 0.80 doubling concentrations (95% CI, 0.16 to 1.44 doubling concentrations). The mean values for the slope were 17.0%/log mg/mL (95% CI, 12.5 to 21.5 mg/mL) with the tidal breathing method and 13.8%/log mg/mL (95% CI, 9.0 to 18.7 mg/mL; p = 0.03) with the dosimeter. The tidal-breathing method produces AMP PC20 values that are significantly lower than the dosimeter method and slope values that are significantly higher than the dosimeter method. These data suggest that the results obtained with each method of testing may not be comparable.

Effect of challenge method on sensitivity, reactivity, and maximal response to methacholine

Recent data suggest that the tidal breathing method may produce methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) values significantly lower than the dosimeter method; however, the effect of the challenge method on the shape of the concentration-response curve has not been investigated. To determine the effect of the challenge method on sensitivity, reactivity, and maximal response to methacholine. We measured airway responsiveness to methacholine using dosimeter and tidal breathing methods in 30 individuals with suspected asthma. Concentration-response curves were characterized by their PC20 (sensitivity), slope (reactivity), and, if possible, level of plateau. Dosimeter PC20 values were significantly higher than tidal breathing values (geometric mean, 8.9 and 5.2 mg/mL, respectively); the mean difference in PC20 values obtained using each method was 0.78 doubling concentrations (P = .01). The mean slopes were 22.7%/log mg/mL using the tidal breathing method and 24.9%/log mg/mL using the dosimeter method; the mean difference in the slopes obtained using each method was -2.17%/log mg/mL (P = .18). In 10 individuals who showed a plateau with the 2 methacholine challenge tests, the mean level of plateau was 19.8% using the tidal breathing method and 19.5% using the dosimeter method; the mean difference in the plateau values obtained with each method was 0.3% (P = .87). Although the tidal breathing method produces methacholine PC20 values significantly lower than the dosimeter method, both methods provide similar values for slope and level of plateau. These results suggest that the technical factors that affect methacholine sensitivity and the shape of the curve are different.

Deep inhalation bronchoprotection in asthma: Correlation with airway responsiveness

Deep inhalation bronchoprotection in asthma: Correlation with airway responsiveness

Dalhousie dyspnea scales: Pictorial scales to measure dyspnea during induced bronchoconstriction

The aim of this study was to validate our Dalhousie Dyspnea Scales in children referred for histamine bronchoprovocation challenge. Seventy-four children rated their dyspnea after each FEV(1) measurement following inhalation of doubling histamine concentrations from 0.125 to 8.0 mg/ml by the standard tidal breathing method. Serial FEV(1) and dyspnea rating using the Dalhousie Dyspnea Scales were recorded and Kendall's tau was computed for dyspnea rating versus fall in FEV(1). Subjects were split into those with positive (DeltaFEV(1) >or= 20% with PC(20) <or= 8 mg/ml) or negative histamine challenge test. During histamine inhalation, dyspnea ratings on each of the subscales rose as FEV(1) fell across subjects, whether or not they were histamine-responsive (main effect), and then fell dramatically following relief of induced obstruction by bronchodilator.The Dalhousie Dyspnea Scales are useful and accurate tools to measure dyspnea due to bronchoconstriction in children.

Feasibility of Shortened Methacholine Challenge in Preschool Children

The aim of our study was to assess the feasibility and safety of a recently suggested tripling-dose methacholine (Mch) challenge in preschool children. Fifty-seven children aged 3-6 years were studied. Mch challenge was carried out using a tidal breathing method, with concentrations of 0.22, 0.66, 2.0, 6.0, and 18.0 mg/ml, at 5-min intervals, given by a Pari Turbo Boy compressor and Pari LC Plus nebulizer, for 1 min only. Oxygen saturation (SaO(2)) was monitored during the challenge. The challenge was terminated if there was wheeze, SaO(2) below 91%, or persistent cough. This final Mch dose was considered the provocative concentration inducing audible wheeze (PCW). Nine healthy children, 17 with cough and 25 with wheeze, completed the study. Mean output from nebulizers (SD) in these 51 children was 0.30 (0.05) ml/min. Geometric means for PCW in these groups were 2.88, 2.58, and 1.28 mg/ml Mch, respectively. The wheezing children were significantly more hyperresponsive than the coughing children (P < 0.05). A tripling-dose Mch protocol is safe and practicable in children over 3 years of age. A further reduction in nebulized dose may be needed for a more discriminatory test.

Difference Between Dosimeter and Tidal Breathing Methacholine Challenge: Contributions of Dose and Deep Inspiration Bronchoprotection

Two bronchoprovocation methods are widely used. Compared to the tidal breathing method, the dosimeter method delivers approximately half the dose and involves five deep inhalations. Both the lower dose and the bronchoprotective deep inhalations contribute to the lesser airway response of the dosimeter.To determine the relative role of dose and deep inspiration in the difference between the two methods.Subjects with asthma (n = 24) underwent three methacholine challenges: a dosimeter challenge, a 2-min tidal breathing challenge (twice the dose), and a modified 2-min tidal breathing challenge (twice the dose plus five deep inhalations).The dosimeter method produced a nonsignificantly lower response than the modified tidal breathing method (p = 0.14). Both deep inhalation methods produced significantly less response than did the standard tidal breathing method (p = 0.011). In the 12 subjects with the most mild airway hyperresponsiveness (AHR), the differences between the deep inhalation method and the tidal breathing method were greater (p = 0.007). By contrast, deep inhalations produced no effect in the 12 subjects with greater AHR; the two tidal breathing methods produced identical results, while the dosimeter produced less response than either (p = 0.033). Six current asthmatics with mild airway responsiveness (tidal breathing method) had negative dosimeter methacholine challenge results.In subjects with moderate airway responsiveness, the difference between the methods is due to the difference in dose, whereas in subjects with mild AHR, deep inhalations had a large effect overwhelming the dose effect and producing false-negative methacholine challenge results in 25% of the subjects.

Lack of Tachyphylaxis to Methacholine at 24 h

To examine for tachyphylaxis to methacholine at 24 h and to use these data to assess the repeatability of the provocative concentration of a substance causing a 20% fall in FEV1 (PC20) for methacholine and to obtain statistical power calculations. Retrospective review of four double-blind, placebo-controlled studies with two methacholine PC20 values measured at 24-h intervals. Tertiary university hospital bronchoprovocation laboratory. Thirty-two subjects with mild-to-moderate well-controlled asthma. The placebo arms of the four studies were examined. Methacholine PC20 (using 2-min tidal breathing method) initial determination and repeat testing at 24 h. The geometric mean PC20 values were 1.57 mg/mL (95% confidence interval [CI], 1.0 to 2.4 mg/mL) and 1.62 mg/mL (95% CI, 1.0 to 2.6 mg/mL NSD; p = 0.64). The mean absolute difference between the two measurements was < 0.4 doubling concentrations, and 31 of 32 measurements had both values within one doubling concentration. These data provide a statistical power of 92% for 10 subjects to show a one-half concentration deltaPC20 and a mean power of 99 +/- 1% to show a one-concentration deltaPC20. There is no evidence for methacholine tachyphylaxis at 24 h in subjects with asthma. At 24 h, the average repeatability was well within a one-half concentration change, and individually 31 of 32 measurements (97%) were within one doubling concentration.

Inhalation method determines outcome of capsaicin inhalation in patients with chronic cough due to sensory hyperreactivity

Background For patients with idiopathic chronic cough, a subgroup is recognised with respiratory symptoms induced by scents and chemicals. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a capsaicin inhalation test. The aim of the present study was to compare the results of inhaling capsaicin by tidal breathing with those obtained by the dosimeter method regarding repeatability, agreement, and ability to distinguish patients with SHR from healthy controls. Methods A total of 15 patients with chronic cough due to SHR and 15 healthy control subjects underwent a randomised cross-over protocol and were provoked in a double-blind, randomised fashion with vehicle and two concentrations of inhaled capsaicin, using either the tidal breathing or dosimeter method, in a total of four challenges opportunities, two with each method. Results Patients coughed more and showed more respiratory symptoms than healthy controls with each dose of capsaicin. Compared with tidal breathing, inhalation of capsaicin with the dosimeter method caused a significantly greater number of coughs and respiratory symptoms in both patients and controls. Among the patients, the mean number of coughs after inhalation of 1 mL of capsaicin 0.4 μmol/L from the first provocation with tidal breathing was 12 (95% CI: 7; 17) and after inhalation from the first provocation with the dosimeter method 32 (95% CI: 19; 46) ( P<0.05). Both methods showed good repeatability and similar ability to distinguish patients with SHR from healthy control subjects. Conclusions For patients with SHR, capsaicin cough sensitivity is increased and repeatable. The dosimeter method caused more coughs and other respiratory symptoms than the tidal breathing method, indicating that the methods cannot be used interchangeably. Knowledge of the type of inhalation device used, the particle size, the airflow rate and the inspiratory flow rate are essential when comparing different studies of capsaicin-induced cough.

Socioeconomic Risk Factors for Asthma in Chilean Young Adults

We studied the association between socioeconomic status (SES) and asthma symptoms, severity of asthma, atopy, and bronchial hyperresponsiveness (BHR) to methacholine. We studied 1232 men and women born between 1974 and 1978 in a semirural area of Chile. We assessed asthma symptoms with a standardized questionnaire, atopy with a skin-prick test to 8 allergens, and BHR to methacholine with the tidal breathing method. SES was derived from several indicators: education, occupation, completion of a welfare form, belongings, housing, number of siblings, and overcrowding. Those with fewer belongings had more asthma symptoms. Those who had higher education and those who owned cars had fewer asthma symptoms and BHR. Overcrowding was negatively related to atopy, atopy with asthma symptoms, and BHR. Higher education and noncompletion of a welfare form were risk factors for atopy. The strength and direction of the association between asthma and SES depended on what definition of asthma was analyzed. Asthma symptoms were more common among poor people. There was some support for the hygiene hypothesis, as overcrowding was associated with less wheezing with atopy, less atopy, and less BHR.

Hiperreactividade brônquica na sarcoidose

The purpose of this study was to measure airway responsiveness in patients with sarcoidosis using bronchoprovocation test with methacholine (BPT) in comparison to roentgenographic findings, respiratory symptoms, activity and duration of the disease. There were 17 patients with Sarcoidosis, 20 asthmatics and 21 assymptomatics. We used the tidal breathing method with standardizes output for the nebulizers. We administered increasing and successively concentrations of methacholine beginning with 0.125 to 16mg/ml. The responses were measured by changes in FEV1 or the final concentration was reached. The results were expressed as the concentration of methacholine causing 20% fall in FEV1 (PC20). Aerosolized bronchodilator was given at the completion of all tests. There were 4 patients with sarcoidosis who had positive BPT, 3 of them with PC20<8mg/ml associated with respiratory symptoms, bilateral hilar adenopathy, more than twoyear duration and active disease. All the asthmatic subjects had positive BPT with CP20<8mg/ml. The entire assymptomatic group had negative BPT. Positive bronchodilator response was reached in 6 patients with sarcoidosis, 20 asthmatics and 8 assymptomatic subjects. We concluded that: (a) airway responsiveness can be reached in 17.6% patients with sarcoidosis related to bilateral hilar adenopathy, chronic and active disease; (b) 50% of sarcoidosis patients with cough and/or wheeze had positive BPT, (c) the BPT was able to discriminate asthmatic from assymptomatic subjects.Rev Port Pneumol 2005; XI (2): 97-110

Methacholine Challenge: Comparison of Two Methods

Guidelines for the 2-min tidal-breathing and the five-breath dosimeter methods for methacholine challenge have recently been published by the American Thoracic Society (ATS). Although subjects are exposed to twice as much aerosol at any given concentration during the tidal-breathing method compared to the dosimeter method, they were thought to give equivalent results. To compare the 2-min tidal-breathing and the five-breath dosimeter methacholine challenges. Tertiary care university-based bronchoprovocation laboratory. Forty subjects with currently symptomatic asthma. The two methacholine tests were done in random order on separate days at the same time of day at 1- to 7-day intervals. The dosimeter provocation concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was almost twice that of the tidal-breathing PC(20): 2.4 mg/mL vs 1.3 mg/mL (paired t test, p < 0.00005). The difference was greater in those with mild airway hyperresponsiveness (AHR) [PC(20) > 1.0 mg/mL; 3.2-fold] compared to those with moderate AHR (PC(20) < 1.0 mg/mL; 1.6-fold) [p = 0.04]. Three subjects with mild asthma and mild AHR (tidal-breathing PC(20), 1.9 to 4.3 mg/mL) had a nonmeasurable PC(20) (> 32 mg/mL) with the dosimeter. The tidal-breathing method, which exposes the subject to twice as much aerosol at each concentration, produced approximately twice the response. The total lung capacity maneuvers with breathhold during the dosimeter method may inhibit the response in some patients with asthma.

Hypertonicity of the challenge solution may increase the diagnostic accuracy of histamine challenge

There is significant overlap in the responsiveness to direct airway challenges, such as the histamine challenge, between asthmatic and non-asthmatic subjects, which decreases their accuracy in the diagnosis of asthma. To minimise this overlap, a new test, hypertonic histamine challenge, was developed. Fifteen healthy subjects, 16 subjects with steroid-naive asthma, and 16 asthmatic subjects undergoing inhaled corticosteroid treatment underwent inhalation challenges with hypertonic saline, isotonic histamine, and hypertonic histamine, using an ultrasonic nebuliser and 2-min tidal breathing method. The increase in histamine solution tonicity decreased the histamine PC20 values only in the steroid-naive asthmatic subjects (1.1 (0.5-2.7) vs. 0.5 (0.2-1.2) mg/ml, P = 0.047). Using 1mg/ml as the cut-off value, the sensitivity, specificity, and accuracy of the hypertonic histamine challenge to detect steroid-naive asthma was 81%, 100%, and 90%. The respective values for the isotonic histamine challenge were 56%, 100%, and 77%. Furthermore, there was a statistically significant difference in the hypertonic histamine PC20 between steroid-naive and steroid-treated asthmatic subjects, which could not be detected in the isotonic histamine PC20. The hypertonic histamine PC20 was highly repeatable, with a single determination 95% range of +/-1.35 doubling concentrations. The hypertonic histamine challenge was safe but provoked more cough and throat irritation than the other two challenges. In conclusion, compared with a conventional, isotonic histamine challenge, hypertonic histamine challenge may be more accurate in the diagnosis of asthma and also, more capable to detect the effects of inhaled corticosteroid treatment.

A Simple Method of Bronchoprovocation Using a Valved Holding Chamber

This study was undertaken to ascertain whether the use of a valved holding chamber (VHC) during bronchial provocation testing might increase lung deposition and repeatability of the test relative to the tidal breathing method. The 2-min tidal breathing results were compared to five inhalations from a VHC device in patients using the Pari-provoII nebulizer (MMD = 2.1mkm). Lung and mouth deposition, losses though the exhaled air and losses before aerosol delivery to the patient's mouth were measured in patients using a radiolabeled 99Tc-DTPA solution and gamma camera. The study revealed that lung deposition was 67% with the VHC method, and losses with exhaled air were 29% of the inhaled amount. The tidal breathing method resulted in lung deposition of 20.9 ± 3.4%, and losses with exhaled air were 77.5 ± 3.5%. Mouth deposition did not differ significantly between methods. Variability in lung deposition was 15.3% for the VHC and 32.0% for the tidal breathing method. In addition to greater lung deposition and reproducibility, the VHC method allows easier calculation of the inhaled dose.

A Simple Method of Bronchoprovocation Using a Valved Holding Chamber

This study was undertaken to ascertain whether the use of a valved holding chamber (VHC) during bronchial provocation testing might increase lung deposition and repeatability of the test relative to the tidal breathing method. The 2-min tidal breathing results were compared to five inhalations from a VHC device in patients using the Pari-provoII nebulizer (MMD = 2.1mkm). Lung and mouth deposition, losses though the exhaled air and losses before aerosol delivery to the patient's mouth were measured in patients using a radiolabeled 99Tc-DTPA solution and gamma camera. The study revealed that lung deposition was 67% with the VHC method, and losses with exhaled air were 29% of the inhaled amount. The tidal breathing method resulted in lung deposition of 20.9 +/- 3.4%, and losses with exhaled air were 77.5 +/-3.5%. Mouth deposition did not differ significantly between methods. Variability in lung deposition was 15.3% for the VHC and 32.0% for the tidal breathing method. In addition to greater lung deposition and reproducibility, the VHC method allows easier calculation of the inhaled dose.

Comparison of single-breath and tidal breathing exhaled nitric oxide levels in infants

The aim of this study was to compare two different methods, tidal breathing (TB) and single-breath (SB), for measuring fractional exhaled nitric oxide (FENO) in infants. FENO was measured in 71 infants with either recurrent wheeze (n=32), recurrent cough (n=16) or no symptoms (healthy, n=23) using both methods. For TB measurements five breaths were collected into a gas sampling bag (off-line reservoir sampling). The SB method was modified from the raised volume rapid thoraco-abdominal technique. Agreement between the two methods was investigated and both methods were used to compare FENO in infants with and without symptoms. Flow dependence of SB FENO was demonstrated using two expiratory flows (11 and 40 mL x s(-1)). There was a moderate correlation (r=0.60) but poor agreement between levels using the TB and SB methods. A significant difference in FENO between healthy children and children with wheeze was found using the SB but not the TB method. Due to lower expiratory flow and reduced nasal nitric oxide contamination the single-breath technique may be more sensitive than the tidal breathing method for detecting differences in exhaled nitric oxide between infants with and without respiratory symptoms.

Methacholine Challenge Testing*: Comparison of the Two American Thoracic Society-Recommended Methods

Recent American Thoracic Society guidelines recommend two different methods of methacholine challenge testing: the 2-min tidal breathing method with twofold increases in concentration, and the five-breath dosimeter method with fourfold increases. Since the tidal breathing method delivers more methacholine to the mouthpiece, we hypothesized that the provocative concentration of methacholine required to decrease FEV(1) by 20% (PC(20)) would be lower than with the dosimeter method. Twelve subjects 18 to 45 years old with stable asthma were selected on the basis of a screening PC(20) (by tidal breathing) of < 1 mg/mL, 1 to 4 mg/mL, or 4 to 16 mg/mL (4 subjects in each concentration range). On subsequent visits within a 7-day period, methacholine challenge testing with tidal breathing or dosimeter were performed on separate days, in a randomized crossover manner. The geometric mean PC(20) was 1.8 mg/mL (95% confidence interval [CI], 0.7 to 4.3) after tidal breathing and 1.6 mg/mL (95% CI, 0.7 to 3.7) after dosimeter (p = 0.2). There was no significant difference between the screening PC(20) and the PC(20) obtained by either method on randomized study days. The maximum decrease in FEV(1) from diluent baseline after the last concentration was 27.8% (range, 20 to 50%) during tidal breathing and 27.9% (range, 16 to 47%) during the dosimeter method (p = 0.35). Both methods give similar results. Fourfold increases in methacholine concentration with the dosimeter method are as safe as twofold increases with the tidal breathing method.