Airway hyperresponsiveness,32 an exaggerated reduction in airway caliber after a stimulus, has been recognized as a hallmark of asthma from the time of Claudius Galen, a physician in about ad 150. Although not specific, airway hyperresponsiveness is a virtually universal finding in asthma, and is associated with airway inflammation. Airway hyperresponsiveness may be induced by allergens (eg, pollen, animal danders),36 chlorine,37 pollutants (eg, sulfur dioxide),38 diesel exhaust particulates,36 and viral upper respiratory tract Genetic variation accounts for some associations of environmental exposure and airway hyperresponsiveness,40 but specific genetic predispositions for airway hyperresponsiveness and other triggers remain poorly understood. Sympathetic control in the airway is mediated via β2-adrenoreceptors expressed on airway smooth muscle, which are responsible for the bronchodilator response to albuterol used in diagnosis and symptom relief and for longer-term bronchodilation facilitated by long-acting β2-agonist controller (Short- and long-acting β2-agonists are used for distinct purposes in asthma therapy.) Cholinergic pathways may further contribute to airway hyperresponsiveness43 and are the basis for the efficacy of anticholinergic therapy23,44 The methacholine challenge test uses inhaled methacholine, a direct cholinergic agonist, to evoke concentration-dependent airway smooth muscle Bronchoconstriction at low concentrations of methacholine (typically <4 mg/mL) suggest increased airway hyperresponsiveness .
During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every six hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenal cortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenal cortical suppression for 1¼ to 1½ days following a single dose) and thus are recommended for alternate day therapy.
When corticosteroids are taken as a medication, they can suppress the normal secretion of corticosteroids from the adrenal gland. If the corticosteroid medication is given over a very long time, it may cause the adrenal gland to no longer function effectively. It may take months to years for this gland to recover completely, long after use of a corticosteroid medication has been discontinued. The daily secretion of corticosteroids is essential to remaining healthy, particularly when the body is under physical stress (. severe illness or infection, surgery, acute asthmatic symptoms, or physical trauma). For example, if you become ill and your asthma worsens, the body normally responds to this physical stress by secreting up to 5 to 10 times the usual amount of natural corticosteroids. In addition, the adrenal gland's response to stress is also required for other important body functions.