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Biomedical subjects

David C Todd

Publications and source records attributed to David C Todd.

7 recordsLinked to original sources
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

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↗
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↗
PubMedDate not supplied

Altered respiratory physiology in obesity.

The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.

Adiposity↗