George A. Sprecace M.D., J.D., F.A.C.P. and Allergy Associates of New London, P.C.
www.asthma-drsprecace.com


INFLAMMATION AND REMODELING (SCARRING) IN
BRONCHIAL ASTHMA AND COPD

The role of Leukotriene-modifying drugs

Just as antihistamines and corticosteroids,  discovered around 1950, have made a major difference in the treatment of allergic disorders,  so too do we welcome the arrival  of leukotriene-modifying drugs (since 1996 in the U.S.A.).  Leukotrienes are chemicals released by blood inflammatory cells in tissues  responding to allergic reactions and to inflammatory stimulants.  The resulting  tissue injury  promotes tissue healing, part of which process is scarring or - as the term is applied to respiratory tissue - “remodeling”.

Leukotrienes may have 1000X the effect of histamine in bronchial asthma.  Since the processes of damage and repair in asthma and in  COPD are similar, and since as many as 40% of  COPD patients may have had or may still have an asthmatic component, what follows is applicable to both conditions, although especially to bronchial asthma.

The current standard of anti-inflammatory treatment for asthma, and to a lesser extent for  COPD,  is the use of adrenocorticosteroids - especially by the inhalation route in order to minimize the occurrence of serious side-effects.  Other non-steroid anti-inflammatory agents  include cromolyn (Intal) and nedocromil (Tilade).  Now leukotriene-modifying agents like Singulair and Accolate have been added.
Although these new agents are not as good as steroids in this effect,  persistently increased leukotriene levels have been found in tissues despite the use of steroids.
Furthermore, a recent published report  offers evidence that airway inflammation and disease severity persists despite steroid use. (Louis, Am.Jnl.Resp.Crit.Care Med., 2000;161:9-16).  Thus, steroids alone  cannot be depended upon to interrupt and reverse the inflammatory processes.  Even less likely are they to stop the consequent scarring of respiratory tissue that results in a progressive loss of lung function in patients with bronchial asthma and COPD treated less than comprehensively.  Indeed, there is evidence that steroid use might at least  theoretically enhance remodeling.  (Vignola et. al., JACI, June 2000).  (Also see my notes under “Inhaled Glucocorticoids in Asthma” within the category “Bronchial Asthma” on this web site).

Given the current state of medical research and clinical information,  the of treatment of bronchial asthma - and probably also of  COPD - should include  steroids and/or Intal/Tilade.  And treatment now should include also  the use of leukotriene-modifying agents.  These agents work differently from steroids, closer to the source of trouble, and should be considered complementary to steroid use.

Both Singulair and Accolate  have immediate bronchodilatory effects,  and more delayed anti-inflammatory effects.  Although they should Not be used as rescue medications for now, IV  Singulair and Accolate are currently being tested  for possible ER use.  If  the recommended dose does not work, the dose may be increased under the guidance of the physician, within narrow parameters.  If one of these agents does not work, the other should be tried, in each case for at least four to six weeks.  During this time, any reduction in concomitant steroid use should be gradual, again under the guidance of the physician.  In my experience, Singulair appears to be somewhat more  effective than Accolate - but I still use either one in selected  patients.

Side effects are minimal and mild - with the exception of a rare incidence of  acute vasculitis.  Even in the rare cases, it is unclear whether the drug caused the vasculitis, or whether the patient had the condition all the time, with appearance only when concomitant steroids were reduced or discontinued.  Nevertheless, I monitor my patients on either of these drugs with  a blood test ( ESR)  initially and every three months.

A Bonus:  these agents are now being used in clinical trials for a variety of  other conditions, including  allergic rhinitis, urticaria, arthritidies, inflammatory bowel disease, cystic fibrosis, and  RS virus disease.  Stay tuned.

The above information once again leads  logically to the importance of  avoiding these damaging processes entirely, through COMPLETE MEDICAL EVALUATION BY A QUALIFIED PHYSICIAN, ENVIRONMENTAL CONTROL, PROMPT  USE OF APPROPRIATE MEDICATIONS, PROMPT TREATMENT OF COMPLICATIONS, VACCINATION WITH  FLU AND PNEUMOVAX VACCINES,  AND  IMMUNOMODULATION  (ALLERGY IMMUNOTHERAPY) WHERE IMMUNE MECHANISMS HAVE BEEN SOUGHT AND IDENTIFIED.

This information, and all the other medical information on this web site, is provided  to help the patient participate actively  and  in his or her treatment decisions.   That sometimes may require bringing the information to the attention of the physician.  It has become impossible for physicians to keep up with everything.  that’s what specialists and sub-specialists are for.  What we all must always know, however, is what we don’t know!

 GS


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