Step three employs the same steroids but a more powerful inhaler. Dry powder inhalers have cartridges which blast the powder when you breath in, and utilize more drug than the usual pressurized aerosol cartridges. Another possibility is the use of a spacer, which offers a "space" between the inhaler and the mouth to allow more time for the propellant chemical to evaporate before the drug reaches you. There are also nebulizers which produce a spray, slowly releasing the drug into the bronchial tubes.
If this still doesn't control your asthma or you have persistent symptoms at night despite all the other inhaled therapies, the BTS suggests that you move on to step four, increasing the daily dose of inhaled steroids and using an additional bronchodilator such as theophylline or aminophylline on top of the other medication. Theophylline belongs to a drug category called the xanthines, which includes caffeine. Theophylline works by relaxing the bronchial muscles and also breaking down a chemical that controls the muscles in the bronchial tubes. Another possibility is to take oral beta2-agonists, which release more drug into the body, or a non selective adrenoreceptor stimulant like ipratropium bromide, which affects your heart as well as your bronchial muscles.
If all else fails, you are put on a course of oral steroids, in addition to the other drugs in step four. You might even be given a trial of cyclosporin, originally developed to prevent the body's rejection of organ transplants and now medicine's drug of the month, investigated for everything from psoriasis to arthritis.
Beta2-agonists have been associated with an increased risk of death or near death. According to the Adverse Drug Reaction Bulletin (June 1992), which devoted an entire issue to asthma, the marked rise in asthma deaths during the 1960s in many countries "coincided with the introduction of high strength isoprenaline inhalers". When the inhalers were withdrawn, mortality fell to previous levels. But the problems haven't just been due to non selective beta2-agonists. In many countries, a renewed rise in asthma deaths occurred in the 1980s, particularly in New Zealand, which one study showed was linked to the popularity of fenoterol, but also theopylline and oral steroids.
Another study of beta2-agonists conducted by a variety of medical schools in America and Canada, including Montreal General Hospital and Yale University (New England Journal of Medicine, 20 February 1992) showed that the use of beta-agonists administered by a metered dose inhaler, specifically albuterol (salbutamol) and fenoterol, was associated with an increased risk of death or near death.
Several other studies have shown that regular inhalation of beta2-agonists cause "hyperresponsiveness" that is, excessive constriction of the bronchi (Journal of Allergy and Clinical Immunology 1985: 76).
The June issue of the Adverse Drug Reaction Bulletin postulated that beta2-agonists could be behind the increase in deaths by causing fatal abnormal heartbeats, spreading whatever the allergen is to more remote airways and thus increasing inflammation, or causing the bronchial muscles to constrict to a fatal degree.
Regular use of these drugs also causes the disease to worsen. Yet another study published in the Lancet in 1990 (336:1391:6) showed that patients receiving fenoterol regularly (that is four times a day) with additional inhalations as necessary had worse outcomes after six months than those given inhaled drugs only as needed. Regular use of certain beta2-agonists also causes a greater decline in lung function than does "on demand" use (The British Medical Journal, 7 December 1991). And some patients have been shown to have symptoms improve once doses of inhaled beta2-agonists are reduced.