Disodium cromoglycate is effective in asthma and has been used clinically for the last 20 years in Japan. Children tend to respond better than adults and some Japanese pediatricians feel disodium cromoglycate is the first choice drug in childrens asthma. Perennial asthmatics without definable allergens may also respond. Exercise-induced asthma can often be prevented by therapy with disodium cromoglycate. Oral preparations of disodium eromoglycate-like drugs such as ketotifen (a Swiss product) and tranilast (from Japan) lead to a reduction in both the frequency and the intensity of asthma attacks. More money is spent on anti-allergic drugs than on any other preparation to treat asthma in Japan (Fig 2). Many similar drugs are coming into clinical use in Japan, including inhibitors of the lipoxygenase pathway and leukotriene antagonists.
Inhaled bronchodilators reduce airway resistance and increase maximum expiratory flow by relaxing bronchial smooth muscle. Two classes of inhaled bronchodilators are beta-adrenergic agents and anticholinergic agents. Barnes et al have recently shown that the density of cholinergic receptors is maximum in large airways and decreases in the more peripheral airways, while the opposite is true for beta-adrenergic receptors. The site of action of an inhaled broncho-dilator depends on where in the tracheobronchial tree it is deposited and on the density of receptors for that particular agent at the site of deposition. Previous studies using density dependence of maximal expiratory flow (Vmax) have produced conflicting results. Ingram et al found a decrease in density dependence after atropine and an increase after isoproterenol suggesting predominant large and small airway dilatation respectively. In another study, Hensley et al supported these observations with measurements of dead space and closing volume. On the other hand, MacNee et al found no preferential site of action following inhaled ipratropium-bromide and salbutamol employing changes in density dependence of Vmax as the method to determine site of action.
In the present study, we examined whether a selective beta-adrenergic agonist, fenoterol, or the newly developed anticholinergic agent, ipratropium bromide, would have a measurable difference in their site of action when administered in the usual manner by a metered dose inhaler. We measured the site of action of these bronchodilators by changes in the density dependence of Vmax as well as changes in the density dependence of pulmonary resistance (Rl). We took advantage of a computer averaging technique to measure Rl, which allowed more accurate and reproducible estimates by eliminating errors induced by cardiac artifacts.
As asthma increases in severity, more complex patterns of management are required. Figure 1 describes a suggested scheme for the management of asthma of different grades of severity, but within this framework many variations are possible. For ease of discussion, we have divided patients with asthma into three different groups according to disease severity.
Mild, Infrequent Asthma
This group includes the majority of patients with asthma. Mild asthma attacks occur every few months, and the patient is asymptomatic for extended periods between episodes. These acute episodes are best managed by the intermittent use of a selective beta, agonist, preferably delivered by ventolin inhalation.
Frequent Episodic Asthma
Patients in this group suffer acute episodes of asthma every four to six weeks, but have symptom-free intervals between attacks. Prophylactic treatment is usually indicated for this group of patients. Several different regimens have been advocated for the prophylactic treatment of asthma, the relative merits and disadvantages of which have recently been reviewed:1) longterm bronchodilator therapy either with a beta2 agonist or a sustained-release theophylline preparation; 2) cromolyn sodium; 3) inhaled steroids (beclomethasone diproprionate); 4) ipratropium bromide by metered aerosol.
It should be stressed that all patients on prophylactic regimens, particularly in the case of inhaled steroids or cromolyn, must have a bronchodilator drug available at home for treatment of acute exacerbations of asthma. These patients should also monitor PEFR on a daily or twice-daily basis to follow the response to treatment and identify fluctuations in the severity of airway obstruction. Visit onlineasthmainhalers.com and you will find ventolin inhalers to any taste and price.
Seventeen asthmatic subjects were challenged; all had a normal FEV, (ie, 80 percent of predicted) prior to challenge. The mean FEVj prior to challenge was 3.41 ± 0.2 L for the dual response groups (87 percent of predicted), and 4.26 ±0.1 L for the LAR response group (90 percent of predicted). Five subjects developed a LAR only and 12 had a dual (early and late phase) response (Table 1). None had an isolated EAR. Two of the 17 (11.8 percent) were density independent before aeroallergen challenge; the other 15 (88.2 percent) were density dependent. The two who were initially density independent (nonresponders) had dual responses but were excluded from further analysis (see discussion for clinical significance of initial responder status). Table 1 shows that the two groups, dual response and late response, were similar at baseline with respect to mean AVmax 50 percent and VisoV, but those with a dual asthmatic response had greater maximal changes in their FEVj after BPC.