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Biomedical subjects

Mary Skowronski

Publications and source records attributed to Mary Skowronski.

3 recordsLinked to original sources

Bronchoprotective effects of single doses of salmeterol combined with montelukast in thermally induced bronchospasm.

STUDY OBJECTIVES: Salmeterol (S) and montelukast (M) individually inhibit the obstructive consequences of thermal stimuli such as exercise and hyperventilation (HV), but there is no information on whether these drugs can interact positively. DESIGN: Randomized trial. SETTING: University teaching hospital. PARTICIPANTS: Atopic asthmatic patients with sensitivity to thermal provocations. INTERVENTIONS: Eleven asthmatic patients generated stimulus-response curves to isocapnic HV while breathing frigid air without any interventions and then after pretreatment with 42 mug of S, 10 mg of M, and the combination. The order of testing was randomly determined. MEASUREMENTS AND RESULTS: Minute ventilation (Ve) was increased in 20-L increments until FEV(1) fell >or= 15%. Measurements were obtained before and 1 h after drug administration, and then again 5 min after each bout of HV. In the nonintervention trial, the provocation commenced after the patients presented to the laboratory. In the control challenge, the mean (+/- SEM) FEV(1) decreased 24.6 +/- 1.7% from baseline. S and M both increased the mean prechallenge FEV(1) significantly (S, 10.4 +/- 1.7% [p < 0.01]; M, 4.1 +/- 1.3% [p = 0.02]; S + M, p = 0.01). The combination of S + M produced greater bronchodilatation (mean improvement, 12.4 +/- 2.3%) than M alone (p = 0.004), but not greater than S alone (p = 0.80). Both drugs blunted the obstructive response similarly (protection: M, 34.6 +/- 15.1%; S, 60 +/- 8.7%; p = 0.13). The benefits added arithmetically with the combined regimen (protection with S + M, 84.9 +/- 5.5%; p = 0.01 vs S alone; p = 0.003 vs M alone). CONCLUSION: These data indicate that the concurrent administration of single standard doses of S and M appears to provide greater protection against thermal stimuli than does either drug alone. Further experimentation will be required to ascertain whether the combination will provide additional clinical benefits to patients over those of the single agents.

Acetates↗

The effects of hyperpnea on exhaled nitric oxide synthesis in normal subjects.

STUDY OBJECTIVES: To determine if the concentration of nitric oxide (NO) in the lungs increases with hyperpnea by contrasting calculated production (ie, the product of the fractional expired NO concentration [FeNO] and minute ventilation [Ve]) [Vno] with the amount of NO in equilibrium with the conducting airways (eNOair) and the amount of NO diffusing from the alveoli (eNOalv). DESIGN: Observational study. SETTING: University teaching hospital. PARTICIPANTS: Normal subjects. INTERVENTIONS: Measurements were made in 16 healthy people during and after 4 min of tidal breathing (10 L/min) and isocapnic hyperventilation of 60 L/min. MEASUREMENTS AND RESULTS: FeNO was measured by collecting the exhaled air during the last minute of each trial and passing it through a chemiluminescence analyzer. The expired NO levels in the plateau phases of slow (30 mL/s) and fast (200 mL/s) single-breath exhalations were also obtained before and after hyperventilation. The Vno (mean +/- SEM) increased from 89.8 +/- 12.3 to 329.1 +/- 36.2 nL/min as Ve rose (p < 0.001). However, neither the quantities of eNOair nor eNOalv changed with hyperventilation (eNOair range before to after, 34.9 +/- 7.7 to 30.9 +/- 6.4 parts per billion [ppb], p = 0.96; eNOalv range before to after, 7.3 +/- 1.5 to 6.5 +/- 1.1 ppb, p = 0.97). CONCLUSIONS: These data demonstrate that the amount of NO in equilibrium with the airway walls and alveoli are not altered by hyperpnea. Rather, the apparent augmentation in Vno in such circumstances appears to be an arithmetic artifact.

Adult↗

Morphometric changes after thermal and methacholine bronchoprovocations.

To determine whether there are distinctions in the location and pattern of response between different bronchoprovocations, we performed high-resolution computer-assisted tomography in 10 asthmatic subjects before and after isocapnic hyperventilation of frigid air (HV) and methacholine (Meth). The luminal areas of the trachea, main stem, lobar, and segmental bronchi were computed before and after each provocation and blindly compared. Both stimuli reduced the 1-s forced expiratory volume similarly (percent change in 1-s forced expiratory volume HV = 28.1 +/- 5.5%, Meth = 25.8 +/- 5.2%; P = 0.69) but did so in different fashions. Each provocation was associated with the development of both bronchial narrowing and dilation; however, more airways constricted with HV (67.7%) than with Meth (47.0%; P < 0.001). Furthermore, there was little concordance between either the magnitude or direction of change between stimuli in any region of the lung (r = 0.25). In general, the frequency of narrowing increased with branching. Constriction became more prominent in the lobar regions and increased further in the segmental branches, but a wide range of intensity existed. These data demonstrate that provocational stimuli evoke complex morphometric changes within the tracheobronchial tree and that different agonists produce different patterns. Thermal stimuli chiefly influence the segmental level, whereas the response to Meth develops more distally. Even within this distribution, the same airway does not respond in an identical fashion to different stimuli, so there does not appear to be a uniform trigger zone.

Adult↗