Effect of ipratropium bromide in bronchial asthma.
V Taskar, L Mirchandani, AA Mahashur, RR Sharma, VP Kolhatkar
Dept of Respiratory Medicine, KEM Hospital, Parel, Bombay, Maharashtra.
Dept of Respiratory Medicine, KEM Hospital, Parel, Bombay, Maharashtra.
The effect of inhalation of ipratropium bromide was evaluated in 20 patients with bronchial asthma. It was observed that there was no significant improvement in the forced vital capacity and the forced expired volume in one second, while there was significant improvement in the peak expiratory flow rate (PEFR) measured at 9 pm, after inhalation of 2 puffs of ipratropium bromide aerosol (0.02mg/puff) three to four times a day for 2 weeks. Since PEFR is a measure of large airway function and cholinergic mechanisms are primarily involved for airflow obstruction at large airways, improvement in PEFR by ipratropium bromide highlights its role as a useful bronchodilator in patients in whom vagal reflexes are responsible for the provocation of bronchoconstriction.
|How to cite this article:|
Taskar V, Mirchandani L, Mahashur A A, Sharma R R, Kolhatkar V P. Effect of ipratropium bromide in bronchial asthma. J Postgrad Med 1992;38:124-6
|How to cite this URL:|
Taskar V, Mirchandani L, Mahashur A A, Sharma R R, Kolhatkar V P. Effect of ipratropium bromide in bronchial asthma. J Postgrad Med [serial online] 1992 [cited 2019 Oct 19 ];38:124-6
Available from: http://www.jpgmonline.com/text.asp?1992/38/3/124/696
Bronchial asthma is a disease of the airways characterized by hyper-responsiveness of the tracheobronchial tree to a variety of stimuli and manifested by a widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy. Bronchodilators, especially the theophylline derivatives and B2 adrenergic drugs, are the mainstay of treatment in asthma. Anticholinergic drugs have a venerable history in the treatment of asthma and the role of ipratropium bromide, both in asthma and chronic bronchitis has been extensively studied . The aim of the present study was to assess objectively the effect of inhaled ipratropium bromide over a sufficient period of time in asthmatic patients.
Twenty patients (12 males and 8 females) above 12 years of age (mean age: 40 yr) with bronchial asthma of mild to moderate severity were selected for the study. Patients with chronic bronchitis, emphysema, cor pulmonale or cardiovascular disorders were excluded from the study. Pregnant and lactating women and severe steroid dependent asthmatics were also excluded.
After a detailed medical history and thorough physical examination, basal pulmonary function tests were performed including forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR). Patients were asked to keep a chart of the daily PEFR measurement at 6am and at 9am for a period of two weeks during which they inhaled 2 puffs of ipratropium bromide aerosol (0.02mg/puff) three to four times a day. Spirometry was repeated on the 7th and 14th day of this period. On each occasion, three measurements were taken and the best of the three was chosen.
Comparison of the lung function data was done using paired t-test.
Table-1 shows the average values of PEFR, FVC and FEV1 of twenty patients. As expected, there was a significant diurnal variation (p < 0.05) in PEFR values of these asthmatic patients. After institution of ipratropium bromide, there was no marked improvement in the early morning PEFR measurements over a period of 14 days. However, there was a significant improvement (p < 0.05) in the PEFR levels measured at 9 pm over 14 days. [Figure:1] shows the visual representation of the mean PEFR levels at 6am and 9pm over a period of 14 days.
There was no significant improvement in the FVC and FEV1 values at the end of 7 or 14 days of the treatment with ipratropium bromide. None of the patients reported any side effects following administration of the drug.
The bronchial hyperreactivity in asthma may be mediated by immunological mechanisms involving IgE or IgG, or non-immunological mechanisms, which include the cholinergic, adrenergic and the non-adrenergic non-cholinergic (NANC) control systems. Neural control of human airways is complex and the contribution of neurogenic mechanisms to the pathogenesis of asthma is still uncertain. The cholinergic nerves including the vagus are one of the dominant neural bronchoconstrictor pathways. Stimulation of the sensory receptors in the bronchial epithelium, initiates a reflex impulse along the vagus nerve, causing the release of acetylcholine and thus bronchoconstriction,. Anticholinergic drugs can reverse this process and hence are effective bronchodilators.
Ipratropium bromide, which is a quaternary ammonium derivative of atropine has been found to have significant bronchodilator action in patients with chronic bronchitis as well as in asthmatics. Improvements in PEFR, FVC and FEV1 have been noted,,. However, it is not associated with any modification of volume or apparent viscosity of secretions or of their clearance from the lungs.  Inhalation of anticholinergic drugs produces a slower onset and lesser peak of bronchodilator effect than that seen following B2 adrenergic agonists. Ipratropium bromide is therefore not a first choice bronchodilator in the treatment of asthma. However, since the site of anticholinergically mediated bronchodilation is the large, central airways while that of beta-adrenergic agents is mainly the small airways, inhalation of the adrenergic and cholinergic agents together could be more effective than either alone. Improvements with anticholinergic drugs alone are small, so that some workers report benefit due to ipratropium bromide, whereas others report 'trends' in the drug effect, that fail to reach any statistical significance.
In this study, there was no significant improvement in the forced vital capacity and forced expired volume in one second in asthmatics who had inhaled 2 puffs of ipratropium bromide aerosol (0.02mg/puff) three to four times a day, for two weeks. However, a significant improvement in the peak expiratory flow rate (PEFR) was noted at 9 pm. PEFR is a measure of large airway function and it is known that cholinergic mechanisms are most relevant in those patients in whom the main site of airflow obstruction is the large airways. Besides acetylcholine, many other mediators are responsible for bronchial hyper reactivity causing bronchoconstriction. Therefore, the effect of ipratropium bromide in improving ventilatory capacity in asthmatics still remains controversial, though it will be helpful in patients in whom vagal reflexes are responsible rather than local release of cellular mediators. This is probably the reason why ipratropium bromide has been found to be very effective in chronic bronchitis,.
Systemic absorption of atropine produces tachycardia, blurring of vision, urinary retention, drying of mucous secretion and central effects including mental confusion. However, since ipratropium bromide is relatively lipid insoluble, most of these side effects are avoided. An unpleasant taste and dryness of mouth has been noticed with this drug. Paradoxical bronchoconstriction has also been reported to bromide radical. However, in this study, no significant side effects were noted after its administration,
American Thoracic society. Chronic bronchitis, asthma and pulmonary emphysema. Rev Resp Dis 1962; 85:762-768.|
|2||Chick TW, Jenne JW. Comparative bronchodilator responses to atropine and terbutaline in asthma and chronic bronchitis. Chest 1977; 72:719-721.|
|3||Roberts AM, Kaufman MP, Baker DG. Reflex tracheal contraction induced by stimulation of bronchial-C fibres in dogs. J Appl Physiol 1981; 51:485-490|
|4||Nadel JA. Adoration of the vagi? N Engl J Med 1984; 311:463.|
|5||Alien W, Campbell AH. Dose-response of ipratropium bromide assessed by two methods. Thorax 1980; 35:137-139.|
|6||Behera D, Malik SK. A Comparative study of feneterol and ipratropium bromide aerosols in Indian bronchial asthmatics. Lung India 1988; 6:9-11.|
|7||Premanand R, Sreenivasa Reddy C, Sundaramma M. Ipratropium bromide and salbutamol inhalations in asthma and chronic bronchitis. Lung India 1989; 7:26-30.|
|8||Taylor RG, Paria D, Agrew JE. Effect of four weeks high dose ipratropium bromide treatment in lung mucociliary clearance. Thorax 1986; 41:295-300.|
|9||Seaton A, Seaton D, Leitch AG. Crofton and Douglas', Respiratory Diseases, 4th ed. Oxford: Blackwell Sci Publ; 1989, pp 192-269|
|10||Gross NJ, Skorodin MS. Anticholinergic, antimuscarinic bronchodilators. State of the art. Am Rev Resp Dis 1984; 129:856-870.|
|11||Mann JS, George CF. Anticholinergic drugs in the treatment of airways disease. Br J Dis Chest 1985; 29:209-211.|
|12||Empey DW, Latinan LA, Jacobs L, Gold WM, Nadel JA. Mechanism of bronchial hyperactivity in normal subjects after upper respiratory tract infections, Am Rev Resp Dis 1976; 113:131-139.|
|13||Leitch AG, Hopkin JM, Elis DA, Merchant S, McHardy GJR. The effect of aerosol ipratropiurn bromide arrd salbutamol on exercise tolerance in chronic bronchitis. Thorax 1978; 33:711-713.|
|14||Patel KR, Tullett WM. Bronchoconstriction in response to ipratropium bromide. Br Med J 1983; 1286: 1318-1320.