Chest
Volume 103, Issue 2, February 1993, Pages 488-495
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The Acute Effect of Ipratropium Bromide Bronchodilator Therapy on Cough Clearance in COPD

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Using radiolabeled, monodispersed aerosols (99mTo-iron oxide) and gamma camera analysis, we measured the efficacy of cough for clearing mucus from the airways of the lung following inhalation of the bronchodilator ipratropium bromide (IB) (Atrovent, Boehringer Ingelheim, Inc), a drug that has been shown to have no effect on mucociliary clearance in COPD. Clearance of radiolabeled aerosol was studied over a 2.5-h period on three separate days, a control day with no coughing, and two study days during which the patient performed controlled cough maneuvers over the course of clearance measurements following IB or placebo therapy (double blind, crossover). Fifteen patients, age >45 years, with stable moderate-to-severe airway obstruction (mean FEV1/FVC=0.45) were studied. IB diminished the effectiveness of cough for clearing the radiolabeled particles from the airways. This effect of IB on cough clearance may be due to (1) changes in the airflow dynamics induced by bronchodilation or (2) altered rheology or depth of airway secretions.

Section snippets

METHODS

Fifteen patients (nine men and six women), ranging in age from 49 to 78 years (mean, 63 years), were studied. Table 1 provides data on each subject's age, pulmonary function, smoking history, and medications. Patients had relatively stable moderate-to-severe air-way obstruction with an FEV1/FVC ratio of <0.70 (mean = 0.46). Subjects had a smoking history of at least 10 pack-years (subjects were instructed to refrain from smoking on the days of the study) and were free of respiratory infections

RESULTS

Figure 2 is a plot of retention versus time for one of the subjects who met the criterion for sufficient particle retention at 60 min. In this patient, the clearance of particles from the lung was similar through 60 min for all three study days but during the cough period (60 to 120 min) the rate of clearance was much greater for the placebo + cough versus IB + cough day. Three of the 15 patients did not meet the criterion of R60 ≥0.50 for all three study days (subjects 4, 6, and 12). An

DISCUSSION

We chose IB to test the effect of bronchodilation on cough clearance because others had shown that similar doses of the drug had caused no change in baseline mucociliary clearance in normal, asthmatic, or chronic bronchitis subjects.6, 7, 8 Consequently, we decided that it was not necessary to repeat these studies by adding an additional two study days to determine IB and placebo effects on mucociliary clearance. Consistent with these previous studies, we found no difference in IB versus

CONCLUSION

We have found that the effectiveness of voluntary cough for clearing mucus from the airways is diminished following IB therapy. Cough clearance of radiolabeled particles deposited in the airways was faster following placebo than IB therapy despite a tendency for higher peak flow rates for coughing following the bronchodilator. It is not clear whether this inhibition of cough clearance is due to (1) flow and airway mechanics effects induced by bronchodilation or (2) an effect on the rheology of

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  • Cited by (0)

    Supported by contract from Boehringer Ingelheim Pharmaceuticals, Inc, NHLBI FIRST Award HL39411, and US EPA Cooperative Agreement CR812738.

    This study was performed in laboratories of the US Environmental Protection Agency; thus, this manuscript has been reviewed by the Health Effects Research Laboratory, US EPA, and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

    Manuscript received April 14; revision accepted June 30.

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