The following notes, chosen predominantly for clinical relevance, are taken from a highly detailed and informative text on the above subject; (Inhaled Glucocorticoids In Asthma, Edited by Schleimer,Busse, & O'Byrne, Marcel Dekker 1997) "Bronchial asthma has been identified as an inflammatory disease of the airways associated with epithelial injury and deposition of fibrous material in the sub-epithelial basement membrane. It is not known if damage in the airway epithelium occurs prior to the inflammatory reaction or as a result of the action of released mediators from different types of inflammatory cells and mast cells. The epithelium may have important functions in regulating the inflammatory processes".

Treatment reduces airway inflammation, but not even extended treatment reduces the thickening of the basement membrane or affects fibroblast distribution. This suggests that the inflammation, but not the fibrotic changes in the basement membrane is prevented by inhaled steroids treatment. "The normal epithelial structure is restored. However pathological changes which could cause asthma to become a more chronic disease have remained obscure. Recently many studies have been focused on the reversibility of collagen deposition in the airway epithelial basement membrane."

"Taken together, these studies indicate that treatment with inhaled steroids may result in a beneficial decrease in the inflammation seen in asthmatic tissue, but may not be beneficial and possibly be deleterious to restructured components of the airways".

The pathophysiology of both the inflammatory changes and the fibrotic changes is extremely complex and is undergoing very active research. However, it is certainly known that some individuals do not respond to steroid treatment, even at high dosage, orally or by inhalation. Such individuals are felt to fall into one of two categories of steroid resistance:

type 1 steroid-resistant asthma which is associated with an abnormally reduced glucocorticoid receptor binding affinity to T-cells; and the type 2, associated with normal binding affinity but with a markedly reduced number of glucocorticoid receptors per cell. It is noted, however, that steroid resistance appears to be localized to immune effector cells, particularly T-cells, in patients with steroid resistant asthma. Most patients with steroid resistant asthma can develop severe side effects (hypertension,osteoporosis, cataracts, skin stria). Thus, most other cells are quite sensitive to the biologic effects of steroids.

Regarding a comparison of oral and inhaled steroids, systemic steroids are essential for acute exacerbations of asthma and during superimposed respiratory tract infections. Inhalation steroids used in conjunction with oral steroids may often enable reduction of oral steroids use, but often cannot supplant the use of oral steroids in some cases. Only steroids, cromolin, and nedocromil have been found to produce anti-inflammatory effects. This does not include drugs like methytrexate, which carry side effects which preclude their recommended use. It is recommended that inhalation steroids, and where necessary oral steroids be initiated early in the treatment of established bronchial asthma in order to avoid the chronic effects of inflammation. However, as noted above, the long-term effects of steroids on such inflammation, and especially on fibrosis is still in question.

Nowhere in my readings in this text was allergy imunotherapy mentioned. Perhaps this was not part of the subject of the text; however, the findings of the reviewers definitely suggested that the use of steroids, although necessary, may not be sufficient and may be even deleterious long-term. Thus the even greater importance to be placed on the only form of therapy that deals with the causation of allergic asthma and of any allergic component of other chronic inflammatory airway disease (i.e. chronic bronchitis).

GS