Asthma desensitization

In general, treatment of the asthma underlying NSAlDs sensitivity should follow standard asthma guidelines. This type of asthma is often severe and frequently high doses of inhaled corticosteroids and daily doses of oral corticosteroids are necessary. A special treatment option is a chronic desensitization to aspirin [8]. Desensitization and aspirin maintenance is routinely used in some centers for treatment of chronic rhinusinusitis with nasal polyposis. It is the only available procedure which allows AIA patients with ischemic heart disease to use aspirin. During the state of desensitization to aspirin, not only aspirin but almost all strong NSAIDs are tolerated, so desensitization and NSAID maintenance could be used for treatment of rheumatic disease or chronic pain syndromes. 

Since elucidation of the sequences of the genes encoding the alr a2, and subtypes of adrenoceptors, it has become clear that there are relatively common genetic polymorphisms for many of these receptor subtypes in humans. Some of these may lead to changes in critical amino acid sequences that have pharmacologic importance. Often, distinct polymorphisms occur in specific combination termed haplotypes. Some of these polymorphisms have been consistently shown to alter the susceptibility to diseases such as heart failure, to alter the propensity of a receptor to desensitize, and to alter therapeutic responses to drugs in diseases such as asthma. This remains an area of active research because studies have reported inconsistent results as to the pathophysiologic importance of some polymorphisms. 

Eapen SS, Connor EL, Gern JE. Insulin desensitization with insulin lispro and an insulin pump in a 5-year-old child. Ann Allergy Asthma Immunol 2000 85(5) 395-7. 

Sublingual immunotherapy House dust mite Desensitization Asthma Rhinitis... 

This double-blind, placebo-controlled study included 58 children aged between 5 and 12 years 30 received sublingual desensitization and 28 a placebo for 18 months. The criteria for inclusion were rhinitis and asthma having progressed for at least 3 years. The criteria used to assess efficacy were based on the results of skin tests, symptom and medication scores, nasal inspiratory peak flow, nasal challenge test, nonspecific methacholine bronchial challenge test, assay of IgG (G1 and G4) specific to mites and the levels of T cells CD4 and CD8. 

A beneficial effect was observed with desensitization to mites via the sublingual route in rhinitis and asthma, with six out of eight studies producing... 

Only one study considered this very important question, namely that conducted by Mungan et al. [8], Despite its small population, it appeared that in terms of rhinitis, the two types of allergen administration were equally effective, although this did not apply in the case of asthma, where classic subcutaneous desensitization proved to be superior. However, the authors raised questions as to the doses employed, which differed considerably and may have explained... 

Half life of PAF in blood ranges seconds to a few minutes (Pickard et. al. 1979) and it is inactivated by plasma acetyl hydrolase (Farr et. al. 1980 Cabot et.al., 1984). Endogenous levels of PAF rise in a variety of pathological state e.g. allergy, asthma, sepsis, ischemia (Braquet et. al. 1987). It is therefore logical to expect that ia vivo, imder elevated blood PAF levels, desensitization of platelets to PAF may occur. 

Asthma induced by aspirin is often severe and resistant to treatment. Avoidance of aspirin and substances to which there is cross-sensitivity is the only satisfactory solution. Desensitization is not usually successful and repeated treatments are needed to maintain any effect (84,85). 

Shahar E, Krivoy N, Pollack S. Effective acute desensitization for immediate-type hypersensitivity to human granulocyte-monocyte colony stimulating factor. Ann Allergy Asthma Immunol 1999 83(6 Pt l) 543-6. 

It has been estimated that 60 million patients receive this treatment annually (2). Bearing in mind that about 40% of the population have atopy and that about half of these develop clinical disease ranging from rhinitis to life-threatening asthma, the scope for an effective and safe programme of desensitization is very large. However, there is no consensus on which extracts should be used, how often therapy should be given, and how long it should be continued if there is clinical improvement. 

The benefit to harm balance in desensitization treatment was examined in a meta-analysis published in 1995, covering 20 randomized, placebo-controlled, doubleblind trials of allergen immunotherapy for asthma. Systemic reactions occurred in a mean of 32% (20-44%) of patients, but anaphylaxis was reported on only four occasions. It was concluded that immunotherapy was a treatment option in highly selected patients with extrinsic allergic asthma where a clinically relevant and unavoidable allergen is identified (7). 

Ortega N, Castillo R, Blanco C, Alvarez M, Carrillo T. Oral iron cutaneous adverse reaction and successful desensitization. Ann Allergy Asthma Immunol 2000 84(l) 43-5. 

Yoshizawa S, Yasuoka A, Kikuchi Y, Honda M, Gatanaga H, Tachikawa N, Hirabayashi Y, Oka S. A 5-day course of oral desensitization to trimethoprim/sulfa-methoxazole (T/S) in patients with human immunodeficiency virus type-1 infection who were previously intolerant to T/S. Ann Allergy Asthma Immunol 2000 85(3) 241. ... 

Chopra N, Oppenheimer J, Derimanov GS, Fine PL. Vancomycin anaphylaxis and snccessfnl desensitization in a patient with end stage renal disease on hemodialysis by maintaining steady antibiotic levels. Ann Allergy Asthma Immunol 2000 84(6) 633-5. 

Patients with aspirin sensitivity can be desensitized. The ease of desensitization correlates with the sensitivity of the patient. Highly sensitive patients who react initially to less than 100 mg aspirin require multiple rechallenges to produce desensitization. Desensitization usually persists for 2 to 5 days following discontinuance, with full sensitivity reestablished within 7 days. Cross-desensitization has been established between aspirin and aU NSAIDs tested to date. Because patients may experience life-threatening reactions, desensitization should be attempted only in a controlled environment by personnel with expertise in handling these patients. In addition, there have been reports of patients who have failed to maintain a desensitized state despite continued aspirin administration. The chronic asthma symptoms have improved markedly in a number of aspirin-sensitive asthmatics who have undergone desensitization. ... 

Continued stimulation of cells with agonists generally results in a state of desensitization (also referred to as adaptation, refractoriness, or down-regulation) such that the effect that follows continued or subsequent exposure to the same concentration of drug is diminished. This phenomenon, called tachyphylaxis, occurs rapidly and is important therapeutically an example is attenuated response to the repeated use of receptor agonists as bronchodUators for the treatment of asthma (see Chapters 10 and 27). 

Chronic treatment with a receptor agonist often leads to receptor desensitization and diminished effect (see Chapter 1). The receptors on human bronchial smooth muscle are relatively resistant to desensitization, whereas receptors on mast cells and lymphocytes are desensitized rapidly following agonist exposure. This may help to explain why there is little evidence that these drugs are effective in inhibiting airway inflammation associated with asthma. 

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