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Biomedical subjects

Beth E Davis

Publications and source records attributed to Beth E Davis.

At least 19 recordsLinked to original sources
PubMed2006

The bronchoprotective effect of inhaling methacholine by using total lung capacity inspirations has a marked influence on the interpretation of the test result.

Methacholine tests are widely used as a diagnostic aid for asthma. Their strength has been reputed to be the high sensitivity and very infrequent occurrence of false-negative test results (ie, high negative predictive value). There are 2 commonly used methods that have been outlined by the American Thoracic Society. These methods were thought to give equivalent results. However, in 3 investigations in which we have compared the 2 methods, we have demonstrated a marked lack of comparability. In subjects with borderline to mild airway responsiveness (tidal breathing, methacholine PC20 >2 mg/mL), the 5 deep inhalations required of the dosimeter method produce marked bronchoprotection in some subjects with asthma. The result of this bronchoprotection is that in 55 subjects with asthma, 50% of those whose tidal breathing PC20 value was greater than 2 mg/mL and 25% of the total had negative methacholine challenge results. This indicates that the standardized dosimeter method has an unacceptable loss of diagnostic sensitivity. We recommend that the dosimeter method not be performed as outlined by the American Thoracic Society and that methacholine should be administered by means of submaximal inhalations or tidal breathing.

Administration, Inhalation↗
PubMed2006

Mechanisms of airway hyperresponsiveness.

Airway hyperresponsiveness (AHR) to direct (histamine and methacholine) and indirect (exercise, cold air, hyperventilation, AMP) challenges is a universal and defining feature of asthma. One component of AHR is transient or inducible and occurs after allergen exposure, for example, and improves occasionally rapidly after inhaled corticosteroids or environmental control. This transient airway hyperresponsiveness is more marked to the indirect stimuli. There are convincing data linking this component of AHR to airway inflammation; however, the precise mechanisms linking airway inflammation and hyperresponsiveness of the airway smooth muscle are not clear. The other component of AHR is more persistent and is relatively refractory to environmental control and inhaled corticosteroids. This is likely secondary to structural airway changes, which are collectively referred to as airway remodeling, and which are a result of the chronic (rather than the acute) effects of airway inflammation. This persistent AHR is best reflected by airway hyperresponsiveness to direct stimuli such as methacholine. The mechanisms are also uncertain, but reduced airway caliber, increased airway wall thickness, increased airway smooth muscle mass, and perhaps contractility likely all play a role.

Asthma↗
PubMed2006

A comparison of 2 methods of continuous aerosol administration during methacholine challenge testing.

BACKGROUND: Exposure to the bronchoconstricting agent methacholine is a potential hazard to technical staff during methacholine challenge testing, which remains a useful and frequently performed test. There are several methods of performing the test. One of the 2 methods listed in the American Thoracic Society's guidelines is the 2-min tidal-breathing method. The methacholine can be inhaled using one of several methods. The loosely-fitting-mask method is likely to produce more contamination of the local environment than a filtered exhalation system. METHODS: We tested 2 variations of the tidal-breathing method of measuring the methacholine provocational concentration (PC(20), the dose that produces a 20% decrease in forced expiratory volume in the first second). One involved use of the open-mask technique and the other a T-piece-and-filter system that precluded the release of methacholine-containing droplets into the environment. We performed duplicate methacholine challenge tests with 10 subjects who had a wide range of PC(20). The tests were done in random order, and each subject performed one test using the mask and one using the T-piece/filter system. RESULTS: With the mask system the geometric mean PC(20) was 4.7 mg/mL, versus 5.1 mg/mL with the T-piece-filter system (p = 0.36). These values are very close and would not be substantially different clinically. CONCLUSION: The 2 methods are equivalent, and the low cost of the products used in the T-piece/filter method makes it suitable for reducing technician exposure to methacholine, using potentially completely disposable components.

Adult↗
PubMed2005

Effect of combined montelukast and desloratadine on the early asthmatic response to inhaled allergen.

BACKGROUND: The early asthmatic response (EAR) to inhaled allergen results from IgE-mediated release of multiple mast-cell mediators, including leukotrienes and histamine, both of which cause bronchoconstriction. Combination therapy directed at blocking the effects of both mediators might protect against the EAR better than either therapy alone. OBJECTIVE: We sought to evaluate the effect of desloratadine and montelukast, administered alone and in combination, on the EAR to inhaled allergen. METHODS: Ten adults with mild-to-moderate atopic asthma participated in a randomized, 4-way crossover study design comparing placebo, 5 mg of desloratadine, 10 mg of montelukast, and the combination administered at 26 hours and 2 hours before each allergen challenge conducted at least 7 days apart. The primary end point was the concentration of allergen that resulted in a 20% decrease in FEV1 (PC20). RESULTS: The geometric mean allergen PC20 (mean log +/- SEM) for combination therapy, montelukast, desloratadine, and placebo was 697 U/mL (2.8433 +/- 0.3253), 338 U/mL (2.5295 +/- 0.2979), 123 U/mL (2.0883 +/- 0.2102), and 104 U/mL (2.0166 +/- 0.2553), respectively (n = 9; P < .00001, ANOVA). Montelukast increased the allergen PC20 4.8-fold, and combination therapy increased the allergen PC20 8.9-fold. The effect of the combination was greater than that with montelukast alone (P < .02). Desloratadine treatment was no different than placebo. CONCLUSIONS: The early response to inhaled allergen was unchanged after desloratadine therapy and partially inhibited with montelukast therapy. The combination of desloratadine and montelukast provided superior efficacy to either blocker administered alone. Investigations into the possible mechanisms of the enhanced inhibition are necessary.

Acetates↗
PubMed2005

Importance of dosimeter calibration method on nebulizer output.

BACKGROUND: We have observed that dosimeter-run nebulizers have a much smaller output when manually activated than when breath activated; however, this has not been adequately investigated. OBJECTIVE: To evaluate the effect of different calibration methods on nebulizer output. METHODS: Six healthy subjects performed all calibrations. The nebulizers were operated by 2 different dosimeters and were calibrated to produce 9 microL per actuation by breath activation followed by exhalation to the room. The nebulizers were then operated at these identical settings, and the output determined in 3 ways: (1) breath activation followed by exhalation to the room, (2) breath activation with exhalation into the nebulizer, and (3) manual activation (with no subject using the nebulizer). These 3 methods were termed regular, rebreathe, and manual, respectively. RESULTS: There was a large and statistically significant difference in nebulizer output among the 3 methods. The measured rebreathe outputs (5.6 and 5.7 microL per actuation) were approximately two thirds and the manual outputs (3.2 and 3.9 microL per actuation) were approximately one third of the regular calibration outputs (8.6 and 8.9 microL per actuation); the 2 values are for the 2 dosimeters. The results were highly statistically significant (P < .001). CONCLUSIONS: The method by which a nebulizer-dosimeter system is calibrated results in different nebulizer outputs. This has a high likelihood of influencing the concentration of methacholine causing a 20% decrease in volume in the first second of forced expiration.

Adult↗
PubMed2005

Deep inspiration avoidance and methacholine response in normal subjects and patients with asthma.

BACKGROUND: Deep inspiration (DI) avoidance and time intervals between inhalation and measurement of FEV1 may influence methacholine challenges. OBJECTIVES: (1) To compare the degree of airway response to methacholine when the initial FEV1 measurements are obtained either 30 s or 3 min after inhalation, (2) to evaluate a simplified method to study the influence of DI avoidance before inhalation on the fall in FEV1, and (3) to determine if methacholine has a cumulative effect. PARTICIPANTS/METHODS: Twenty-five patients with asthma and 21 normal subjects without asthma. Four methacholine inhalation tests (MITs) were performed: two standard tidal-breathing MITs, with the first FEV1 measured 30 s (test A) and 3 min (test B) after the end of inhalation; a single-dose MIT, using the last concentration from test B, with no control of DI and the first FEV1 obtained 3 min after inhalation (test C); and an identical single-dose MIT preceded by 20-min of DI avoidance (test D). We compared the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from tests A and B (aim 1), the percentage fall in FEV1 from tests C and D (aim 2), and the percentage fall in FEV1 from tests B and C (aim 3). RESULTS: Mean PC20 values from tests A and B were 1.5 mg/mL and 1.0 mg/mL (p = 0.002) in patients with asthma, and 69.8 mg/mL and 29.9 mg/mL (p < 0.0001) in control subjects, respectively. The mean falls in FEV1 for tests C and D were 22.0% and 24.5% (p > 0.05) in patients with asthma, and 22.1% and 38.9% (p = 0.0005) in control subjects, respectively. The mean falls in FEV2 for tests B and C were 30.2% and 22.0% (p = 0.01) in patients with asthma, and 27.5% and 22.1% (p > 0.05) in control subjects, respectively. CONCLUSIONS: In both groups, the longer the time interval between the end of inhalation and the first FEV2 measurement, the greater the fall in FEV2 (lower PC20). DI avoidance before inhalation does not enhance the fall in FEV2 in subjects with asthma, while it does in control subjects. Methacholine has a slight cumulative effect that is significant in patients with asthma (p = 0.007).

Adolescent↗
PubMed2005

Methacholine challenge: comparison of two methods.

BACKGROUND: 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. OBJECTIVE: To compare the 2-min tidal-breathing and the five-breath dosimeter methacholine challenges. SETTING: Tertiary care university-based bronchoprovocation laboratory. PATIENTS: Forty subjects with currently symptomatic asthma. INTERVENTIONS: The two methacholine tests were done in random order on separate days at the same time of day at 1- to 7-day intervals. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed2005

The effect of ipratropium nasal spray on bronchial methacholine challenge.

PURPOSES: To determine the effect ipratropium bromide nasal spray has on methacholine challenge testing for airway hyperresponsiveness. MATERIALS AND METHODS: Ten subjects with known airway hyperresponsiveness to methacholine who had been clinically stable in the preceding 2 months participated in a randomized, double-blind, placebo-controlled, crossover study. Methacholine challenge testing was conducted on successive days: day 1 after pretreatment with aqueous 0.03% nasal ipratropium, and day 2 with normal saline solution placebo. RESULTS: The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was higher after nasal ipratropium than after saline solution placebo (2.1 mg/mL vs 1.6 mg/mL, p = 0.02). This difference is equal to approximately one-half concentration difference, probably within the limits of reproducibility of the test. CONCLUSIONS: Pretreatment with nasal ipratropium results in a small increase in PC20. Although this difference achieves statistical significance, it is probably not clinically significant.

Adult↗
PubMed2005

Lack of tachyphylaxis to methacholine at 24 h.

OBJECTIVE: 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. DESIGN: Retrospective review of four double-blind, placebo-controlled studies with two methacholine PC20 values measured at 24-h intervals. SETTING: Tertiary university hospital bronchoprovocation laboratory. PATIENTS: Thirty-two subjects with mild-to-moderate well-controlled asthma. INTERVENTIONS: The placebo arms of the four studies were examined. MEASUREMENTS: Methacholine PC20 (using 2-min tidal breathing method) initial determination and repeat testing at 24 h. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2005

Difference between dosimeter and tidal breathing methacholine challenge: contributions of dose and deep inspiration bronchoprotection.

BACKGROUND: 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. OBJECTIVE: To determine the relative role of dose and deep inspiration in the difference between the two methods. 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). RESULTS: 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. CONCLUSIONS: 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.

Administration, Inhalation↗
PubMed2004

Dosimeter methacholine challenge: comparison of maximal versus submaximal inhalations.

BACKGROUND: Deep inhalation has bronchodilating and bronchoprotective effects, particularly in subjects who are normal or have mild airway hyperresponsiveness (AHR). We have anecdotally observed that the 5 breath to total lung capacity (TLC) dosimeter method reduced the response to methacholine in some subjects with mild AHR. OBJECTIVE: To compare prospectively submaximal inhalations with TLC inhalations during the dosimeter methacholine challenge. METHODS: Sixteen subjects with asthma and a methacholine PC 20 <8 mg/mL performed 2 methacholine challenges in random order; the standard dosimeter method was compared with a modified dosimeter challenge in which methacholine inhalations were performed to approximately 50% to 60% below TLC. RESULTS: The standard methacholine challenge PC 20 was almost twice that obtained with the modified submaximal inhalation method (geometric mean PC 20, 5.2 mg/mL vs 2.8 mg/mL, respectively; P = 0.0216). In the 5 subjects with the mildest AHR, there was a 2.5-fold to 14-fold difference in PC 20 between methods. The standard (full TLC) PC 20 s were falsely negative (>16 mg/mL) in these 5 subjects with current asthma, 4 of whom required inhaled corticosteroids. CONCLUSION: A submaximal inhalation dosimeter methacholine challenge results in a significantly lower PC 20 compared with the standard 5-breath dosimeter method. This effect is limited to the mildly responsive group, probably because of the bronchoprotective effect of the deep inhalation during the standard method, and results in false-negative tests in some subjects.

Administration, Inhalation↗
PubMed2004

Seasonal fluctuations in airway responsiveness in elite endurance athletes.

BACKGROUND: It has been suggested that exposure to winter training conditions (irritants in indoor facilities and/or cold, dry air in the outdoors) can increase airway responsiveness in elite endurance athletes. OBJECTIVES: It has yet to be elucidated whether elite endurance athletes experience seasonal fluctuations in their airway responsiveness. METHODS: Eighteen members of a varsity cross-country running team underwent screening procedures and five members were enrolled in the study. Each athlete completed a respiratory and training questionnaire, and underwent allergy skin prick testing. Airway responsiveness was evaluated using a methacholine challenge on four occasions. RESULTS: The participants demonstrated a significant (more than twofold) increase in airway responsiveness (P=0.0496) during the first winter evaluation compared with the autumn baseline. The second winter evaluation still showed an increase but it was not statistically significant. Airway responsiveness had returned to baseline (autumn) values at spring testing. CONCLUSION: Elite endurance athletes experience seasonal fluctuations in airway responsiveness. The specific stimuli that cause this are unknown, but it is speculated to be due to exposure to cold, dry air and/or inhaled irritants that may be present in indoor training facilities.

Adult↗
PubMed2003

Development of a methacholine challenge method to minimize methacholine waste.

BACKGROUND: The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine being discarded. OBJECTIVE: To develop a method with reduced methacholine waste and to compare it to the standard method. METHODS: Twelve subjects with mild, well-controlled asthma volunteered for this investigation. They underwent three methacholine challenges in random order. The first challenge was the conventional 2-min tidal breathing method using 3 mL of doubling concentrations inhaled for 2 min at 5-min intervals. The first modification utilized 1.5 mL of quadrupling concentrations inhaled for 1 min and then 2 min, keeping the time interval constant at 3 min between completion of one inhalation and commencement of the next inhalation. The second modification utilized 1.5 mL of eightfold concentration step-ups inhaled for 30 s, 60 s, and 120 s with a time interval of 3 min between completion of one inhalation and commencement of the next inhalation. For each method, the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was calculated based on a 2-min equivalent-dose inhalation. RESULTS: There was no significant difference in the geometric mean PC(20) (1.5 mg/mL, 1.6 mg/mL, and 1.6 mg/mL for the three methods, respectively; p = 0.47). The quadrupling concentration method was preferred because it was less subject to error than the other modification. CONCLUSION: The amount of methacholine discarded during a methacholine challenge can be reduced by two thirds by decreasing the volume from 3 to 1.5 mL, and by using quadrupling concentrations inhaled either with quadrupling-dose step-ups, or with doubling-dose step-ups by using sequential 1-min and 2-min inhalations.

Adult↗
PubMedDate not supplied

Formoterol thrice weekly does not result in the development of tolerance to bronchoprotection.

BACKGROUND: Loss of bronchoprotection routinely follows regular treatment with beta2-agonists. There are no data on the effects on bronchoprotection for thrice weekly use of a beta2-agonist. METHODS: A double-blind, randomized, placebo controlled crossover trial was conducted to investigate the effects of thrice weekly administration of 12 microg of formoterol versus placebo on bronchoprotection against methacholine. As an expected positive control, formoterol 12 microg once daily was also evaluated. RESULTS: There was no significant difference versus placebo in the bronchoprotective effects of 12 microg of formoterol administered on day 8, following daily treatment for seven days or treatment every other day (analysis of variance P=0.34). However, a nonsignificant trend towards lower concentration of methacholine that caused a 20% fall in forced expiratory volume in 1 s developed only following the daily formoterol dosing. CONCLUSIONS: Thrice weekly dosing does not result in the development of tolerance to bronchoprotection against the direct acting stimulus methacholine.

Administration, Oral↗