• In children with established bronchial asthma (eg. three attacks, or persistent long-standing dry cough), inhalational steroids are better started early.  (#4)
• Combinations of medicines continue to appear, the newest coming being Budesonide / Formoterol (inhalation steroid and long-acting bronchodilator).  (#8).  These may be convenient, but I prefer to use and titrate the individual components as needed.
• Minocycine (minocin) has been found to be steroid-sparing. (#10).  But the potential side-effects preclude, in my opinion, its use in all but the really difficult cases...which become much less difficult if they are treat comprehensively, including with Allergy Immunotherapy.
• Xolair (the anti-IgE agent) is useful for, and should be restricted for, only the severe cases.  Again remember allergy immunotherapy, often ignored...especially by Pulmonologists.
• "All that wheezes is not asthma".  And all asthmatics are not the same.  See Abstract #23 regarding asthma phenotypes.  Being able to categorize asthma patients genetically, with treatment implications, may become clinically very useful...but not yet.
• For example, Aspirin - sensitive asthmatics are generally more difficult to handle.
• Evidence is now developing th suggest that, besides being a serious co-morbid condition, Obesity may be primarily pro-inflamatory and may directly complicate bronchial asthma.  Yet another reason for all of us to work to reverse this rampaging epidemic.  (See www.medidietresourcers.com).
• Cystic Fibrosis is often accompanied by nasal polyps.  But nasal polyps are rarely accompanied by cystic fibrosis.  (#61)
• Bovine collagen injections in cosmetic surgery can produce allergic reactions, and might be associated with auto-immune disease.  (#66)
• Insulin antibodies, known to underly some insulin resistance, can also produce hypoglycemic reactions as the bound insulin is sporadically released.  (#71)
• Diesel fume exposure potentiates allergy - causing IgE and also worsens bronchial asthma.  (#92)
• Automobile air-bag deployment can precipitate an asthmatic attack and produce new-onset asthma, in addition to producing "corneal injury , burns, skin hyper-sensitivity reactions, pneumothorax, cardiac contusion and aortic rupture."  (#95)
• Lasik eye surgery can produce occupational rhinitis and asthma from allergic reaction to corneal antigens.  (#111).
• We read about lipstick allergic cheilitls (#125), swim cap latex allergy (#124), and allergy to Play-Doh and its wheat content. (#127).
• Persons allergic to soy should know that soy sauce retains its allergenicity despite the fermentation process. (#128).
• Penicillin and other beta lactam allergy often tends to reduce with time.  But the sensitivity can boosted by use of amoxycillin. (#129).  Thus in these cases it is wise to use other antibiotics.
• Acute allergic reaction to peanut can occur with "first exposure" because it probably was not the first exposure in the patient's environment.  (#136).
• Xolair has been used successfully to treat fire ant anaphylaxis, after standard allergy immunotherapy had for some reason failed.  (#151).  It should be remembered this use. like that for treatment of peanut allergy, are "off label" and for which the clinical justification should be quite strong.
• Anaphylaxis in the peri-operative period, usually related to muscle relaxants or to latex reactions, may also be due to starch-based plasma volume expanders. (#158)
• Regarding CPR for anaphylaxis, it was found that patients taking beta blockers were generally not greatly compromised.  (#160)
• The importance of availability of Epi-Pen, and familiarity with its indications and use for a given individual, is stressed.
• Persistent and severe allergic rhinitis may be a prelude to aspirin sensitivity, including aspirin - asthma.  (#188)
• The use of steroid nasal inhalation had no effect on exhaled nitric oxide / asthmatic inflamation.  (#201)
• After endoscopic nasal-sinus surgery, look out for Staph.aureus and P. aeruginosa superinfection.  (#229)
• The re-growth of adenoidal tissue after removal may be related to allergies and also to GERD.  (#231)
• Early environmental intervention significantly reduces the incidence of asthma at age 7 in high-risk children.  (#245)
• Post-IVIG treatment headache may be secondary to the sucrose content of the product. So, try other brands.  (#325)
• Sub-cutaneous Ig is a safe alternative to IVIG.  (#346)
• Glucosamine derived from shrimp shells is tolerated by shrimp-sensitive patients.  (#368)
• Sodium hypochlorite - containing disinfectants are useful in inhibiting the growth and allergenicity of mold in homes.  (#393)
• In the treatment of atopic dermatitis, prior treatment with steroid topicals...or staph. superinfection...reduces the effectiveness of tacrolimus.  (#410)
• Xolair use reportedly helped in the treatment of atopic dermatitis resistant to other (?) forms of treatment. (#417)  It should be noted that allergy immunotherapy in appropriate cases of atopic dermatitis can produce very good results.  But the treatment must be slowly and carefully advanced, since it is quite easy to cause a "flare"of the condition.
• A case of concurrent seminal fluid and latex allergy is reported. (#438)
• In a study of severe and difficult-to-treat asthma, skin tests correlated well with IgE level.  (#497).  This is really not news, but it should be remembered that about 10% of clearly atopic patients have negative skin tests and should be treated according to history - including with allergy immunotherapy.
• A case of interstitial cystitis (with pelvic pain and urinary urgency) accompanied by allergic rhinitis and asthma was successfully treated with allergy immunotherapy and anti-IgE therapy.  (#501) Although clearly a long shot, this connection should be considered in such cases.  The same is true in cases of "Chronic Fatigue Syndrome", which carry a two-fold incidence of concomitant allergic disorders than in the normal population.
• Here is a "dog bites man" story: the finding of relatively poor compliance between ER treatment of asthma and the relevant guidelines.  (#549) The same can be said for the non-specialty treatment of asthma in all venues.
• An important note relates to the existence of both acidic and non-acidic esophageal reflux in some infants and children,  the latter not responding to proton pump inhibitors.  In these cases, further studies and treatment are necessary.  (#606)
• A number of abstracts discussed "rush immunotherapy" as being "effective".  What was not clear was the long-term efficacy of this approach, and the fact that the high % of systemic reactions (about 15%) boost the same IgE whose reduction is the purpose of the treatment.  Furthermore, one abstract found a difference of only $300 between rush and standard treatments over the course of a year.  I do not use this approach, unless there is a special reaxon for the rush.  (#644,645)
• Clinical cat allergy can dissipate over about two years of non-exposure.  It can also return with restored exposure.  (#657)
• Stachybotrys chartarum, "toxic black mold",  produces potent mycotoxins with various and serious organic effects on exposure.  This contamination in water- damaged structures, and possibly even related to current new construction techniques, is creating havoc among affected persons and in the insurance industry.  Now a specific antigen has been developed as a marker to quatify exposure.  (#660)
• Oral desensitization to egg in egg-allergic children is reported to be successful, but with a 58% incidence of substantial gastrointestinal and respiratory reactions.  The indication for this should be uncommon.  And great care should be exercised.  (#668,669)
• Early life exposure to antibiotics for non-respiratory infections was found to increase the occurrence of asthma by age 7.  This is likely related to Hygiene Theory effects on the young immune system.  (#692)
• Another correlation regarding the increased incidence of asthma in recent decades was found in the reduced intake of anti-oxidants (including beta carotene and vitaminesC and E.  (#693)
• Chronic Urticaria is very commonly associated with thyroid auto-immunity (including antiperoxidase and anti-thyroglobulin antibodies).  These cases should be carefully worked up regarding thyroid function and regarding the presence of such antibodies.  And the use of thyroid therapy, in the form of levothyroxine 100 ugms daily for at least two months, is recommended in in a euthyroid state.  (#703,705)
• A connection between serum leptin levels and chronic urticaria is discussed in #704.
• Aspirin urticaria and angioedema can occur with as little as 81mg of aspirin.  In such patients, plavix should be substituted for adequate cardio-vascular indication.  (#708)
• The evaluation of chronic urticaria should includ consideration of a form fruste of Celiac Disease.  (#709)
• The use of dry powder inhalers has been found to be associated with persistent urticaria and eczema. (#713).
• The use of cephalosporins in patients with a history of penicillin allergy - and after a finding of negative pcn. skin testing, is reported.  (#716).
• Several abstracts discuss the DRESS Syndrome (severe drug rash with systemic signs including fever, adenopathy and organ failure).  #720 relates to Trimethaprim-Sulfa.
• Delayed-type hypersensitivity reaction can occur after injection of non-ionic radio-contrast media despite standard pre-medication.  (#723)
• Allergy to pork can produce allergic reaction to porcine-derived medications including heparin.  (#724).
• Aspirin sensitivity can produce substantial decrease in FEV1 even in non-asthmatic persons.  (#730).
• Possible sensitivity to amide-group local anesthetics like lidocaine and mepivacaine is better evaluated through controlled challenge testing with preservative-and-epinephrine free agent than with skin testing.  (#733).
• Trimethaprin-Sulfa hypersensitivity can be successfully treated with desensitization over two days.  This is important in cases of HIV - Pneumocystis infection and for peri-transplantation use.  (#734).
• Mast cells, the predominant leucocyte in middle ear mucosa, may reprersent another connection (in addition to eustacean tube blockage) between allergy and otitis media.  (#748).
• Eosinophilic Esophagitis seems to be a recurring topic.  (#767,768).
• A good marker of airway inflamation during inhaled steroid dose reduction is sputum eosinophile count. (#777).
• A high prevalence of migraine headaches in patients with allergic rhinitis has been found.  This may be related to histamine or other mediators.  (#786).  In any case, I have found that, when the combination is present, the migraine problem improves in many cases as the allergic rhinitis is effectively treated.
• The standard of care for treatment of chronic rhinosinusitis is medical / allergy treatment before considering surgery. (#788)
• In patients with nasal polyposis and persistent sinusitis, consider allergic fungal sinusitis, especially in an immuno-compromised patient.  (#791).  Think also about lymphoma(#796)
• Check out Kimura Disease, new to me.  (#797)
• An association between asthma and obesity is reported, possibly related to obesity as a pro-inflamatory condition.  (#812)
• Here is a treatment in search of a rationale: Xolaire and Rush Immunotherapy for ragweed hayfever.  (#827).  "Publish or perish" is still alive and well, I guess.
• Severe allergic reaction in the course of allergy immunotherapy is widely acknowledged to be extremely rare.  Such reactions almost always occur within 30 minutes of receipt of injections, and are generally worsened by delay in administering epinephrine.  (#829)
• Early childhood viral-induced wheezing, or its cough-variant, is a marker for later obstructive airway problems.  (#860)
• There seems to be an increased incidence of allergy in HIV positive patients.  (#891)
• HIV can be associated with sub-clinical adrenal insufficiency, which cah become suddenly clinically significant in the course of a routine short-course prednisone treatment and step-down for another condition.  (#897)
• "It says here" that cat Fel D antigen can be affected by their diet.  (#940)
• More on the Dress Syndrome.  (#959)
• Very low birth weight and very premature birth has been associated with a higher incidence of food allergy later.  (#963)
• The safety of open oral food challenge in an office setting is reported.  (#973).  I would be very careful before accepting that.
• Peanut oral immunotherapy/desensitization is discussed in Abstract #979.  This obviously has clinical utility, but should be further researched before trying it.
• In a patient with neck and facial "angioedema",  gradual or acute, think also of Superior Vena Cava Syndrome.  (#984).  In any case, time is critical.
• In patients with history of egg allergy, the ability to eat any amount of egg enables receipt of Flu vaccine.  Where the history is uneqivocal, a puncture-prick test probably precludes ise of Flu vaccine; a negative test allows it.  (#996)
• Acute angioedema from TPA intravenously (eg. for stroke) is more likely to occur in a patient taking an ACE inhibitor. (#997)
• The value of 2nd generation antihistamines in the treatment of bronchial asthma is reported in Abstract #1048.
• Check for staph superinfection in patients with nasal polyposis and chronic rhino-sinusitis.  (#1097)

Finally, there is ample clinical and research evidence for the long-term benefit derived from a program of allergy immunotherapy of three to five years duration, on average.  Most patients remain symptom-free for over five years.  (#1057).  In my experience, about 85% of patients so treated do not need further AI.  10-15% of patients tend to relapse within 2-3 years and benefit long-term for a further 2 year course of AI.   A very small number of patients do not tolerate discontinuation of AI for more than 4-5 months and - if their condition is sufficiently troublesome, including all active asthma - require long-term AI.  Abstract #1055 describes IgG4 and IgE changes after discontinuing AI.

1. Heparin inhalation inhibits mast cell activation and may be useful as low molecular weight heparin as add-on treatment for bronchial asthma.
2. Astelin is clinically useful as a nasal spray, similar to intra-nasal steroids.
3. Effective inhalation drug delivery for children: blow-by with extension tube is cimilar to close-full mask, and is better tolerated by young children.
4. "Singular is better than theophyllin in asthma".  Maybe, but at least additive.
5. There are patients with irreversible asthma despite all treatment.  Efforts are being made to identify this cohort of patients early.
6. Cockroach allergy is very important, especially in urban communities.
7. Some children fail to respond immunologically to Pneumovax.   ??
8. IVIG preparations canbe given safely sub-cutaneously, with monitoring.  This is especially useful in patients who develop recurring troublesome reactions from the IV route.
9. Job's Syndrome often includes also skeletal abnormalities.
10. Mold contamination (especially toxic molds like stachybotyrum chartarum) is becoming ever-more important...not only in homes and in the work-place but also in autos.
11. Latex allergy substantially reduces in an individual with avoidance.  Also, cutaneous latex allergy can evolve...sometimes suddenly...into serious asthma.
12. Respiratory reactions have been detected from exposure to colophony and to the gasoline additive MBTS.
13. Allergic reactions are reported to many agents (eg. hops, beer, wheat....)  Just assume that anything, including cortisone, can be allergenic.
14. Allergy to the important drug methytrexate can be reduced with desensitization procedures.
15. There is cross-reactivity between beta-methasone and dexamethasone.  So that's why dexa-methasone is a fair substitute for celestone in patients who are otherwise steroid-resistant.
16. Alcohol-related eruptions from tacrolimus are reported.
17. In "penicillin-allergics", there is a low risk of allergy reaction to 2nd generation cephalosporins like cefuroxime.
18. Rapid desensitization is possible for allergy to TMP-SMX used for HIV infection.  "Easy and safe".
19. Regarding the question of stinging insect venom immunotherapy in response to large local reactions, the authors report a 10% incidence of progression to generalized reaction.  ??
20. The drug allergy history reported for hospitalized patients is often incomplete and innacurate.  Beware.
21. Interferon alpha is being used in treatment of systemic mastocytosis.
22. One interesting report suggests that the likelihood of later sensitivity to outdoor aero-allergens may be related to month of birth.  The observation suggests that contact with pollen allergens in the first six months of life may sensitize the infant.  In the Northeast, the tree pollen season extends from early April through May.  The grass season extends from later May through mid-July.  The ragweed season extends from later August through early October.  The mold season extends from March through November, with peaks between August and November.
23. Even in a soy allergic person, soybean oil is reported to be not allergenic.
24. Here's a peculiar one (abstract #388).  Researchers in San Francisco report a "Creative Syndrome": ..."artistically creative atopic individuals demonstrated more severe and more frequent Total IgE Deficiency (less than 21 IU/ml) compared to the control group of atopic non-creative patients".  From this they suggest extra-immunologic function for IgE.  ??
25. One abstract found no correlation between the findings of clinical history and skin testing, one the one hand, and total and specific IgE.  The authors suggest that using the former parameters is enough.  Of course, that is what most of us do most of the time.
26. Regarding peanut allergy: the sensitivity may not resolve; if it does resolve, it may recur; it is difficult to avoid completely exposure everywhere; Epi-pen should be carried at all times; roasting and boiling enhances the allergenic properties of peanuts.  Therefore, Beware!
27. In abstract #560 we learn that there may be a connection between alopecia areata and very high eosinophile count; that eosinophiles are activated by necrotic epithelial cells; and that eosinophiles can be activated directly by aero-allergens.
28. Sodium Hypochlorite solution (2.4%) is useful for cleaning moldy areas.
29. In abstract #619 we learn that patients sensitive to anti-microbial sulfonamides can generally tolerate non-antimicrobial solfonamides like sulfonureas, diazide and loop diuretics, carbonic anhydrase inhibitors, celebrex and dapsone.
30. NSAID sensitivity generally does not involve Cox-2 inhibitors like celebrex and vioxx.  However, there is cross-reactivity in 10% of cases.  Therefore, careful challenge testing is appropriate.
31. There was found to be a 56% incidence of exercise-induced bronchospasm in recreational road-runners.  This seems quite high, but may be explained by the fact that EIB can be overcome often by "running through it".  Of course, that could be risky.  Thus the need for awareness, possible pre-medication, and the availability of a rescue inhaler (albuterol) in such individuals.
32. The effect of paranasal sinus surgery on maxillary sinus mucosal function is slow and partial. Such surgery, including intra-nasal surgery, should generally follow - and often may be obviated by- proper allergy evaluation and comprehensive treatment.  This is true for children as well as for adults.
33. See abstract #714 for a discussion of "Hyper-IgD Syndrome".
34. Viteligo is an auto-immune process.
35. In Stevens-Johnson Syndrome, IVIG may be useful.
36. A new, potent, selective PDE4 inhibitor, Roflumilast, holds promise as another anti-inflamatory agent in the treatment of bronchial asthma (see abstracts #773,780,784,and 785).
37. As part of the "Hygiene Theory", early life exposure to sources of endotoxin may protect against allergic later in life.  As noted in abstract #812, this appears to be true also for eczema (atopic dermatitis).
38. There is ample evidence of under-utilization of Epi-Pen in appropriate circumstances by parents and teachers.  This is unfortunate and dangerous.
39. It is suggested that gender-based Epi-Pens may have to be marketed, in view of the finding that the generally greater depth of sub-cutaneous tissue in women makes the desired intra-muscular administration of the epinephrine more difficult.
40. IgE level tested shortly after an episode of anaphylaxis may be falsly deminished or negative.
41. Swimming in lakes has produced anaphylaxis secondary to allergy to algae.
42. Abstract #857 is an important report on "Idiopathic Anaphylaxis", a distressing and recurrent event for patient and physician alike.  One ray of hope: "Episodes decline over time in severity and frequency".
43. Pectin used during barium enema procedure may produce anaphylaxis.
44. Intra-operative anaphylaxis my rersult from latex sensitivity.
45. Specialty care is more effecive and cost-effective than that provided by family physicians and pediatricians.
46. Abstract #935 describes bi-phasic anaphylaxis, occurring in nearly 20% of cases, and within 10-38 hours.  In these patients, time to resolution of initial episode was significantly longer; and they generally received less epinephrine and corticosteroids. Thus, the issue of hospitalization should always be considered, as well as sufficient discharge instructions.
47. Abstract #936 emphasizes the importance of the intra-muscular route for epinephrine in the treatment of anaphylaxis.
48. "Promising" studies are underway of a sub-lingual epinephrine product.
49. The occurrence of RS virus infection early in life increases both the incidence of asthma and of Th2 mediated allergic disorders later in life.
50. A condition new to me is described in abstract #978:"Exercise Induced Laryngeal Prolapse in Elite Athletes - 'Curable Asthma'"
51. Beta blockers may be used judiciously for congestive heart failure in patients with bronchial asthma or COPD.
52. Beware sudden-onset near-fatal or fatal asthma.  Abstract #1048.  One circumstance where this can occur is in an aspirin-sensitive asthmatic.
53. Cancer Chemotherapy anaphylaxis (or anaphylactoid reaction) is being reported with some increased frequency. Abstract #1131 notes that this reaction may not be IgE mediated and is not prevented by conventional prophylaxis.
54. Abstract #1155 describes one approach to the vexing problem of "Multiple Drug Allergy Syndrome".
55. Abstract # 1215 discusses the possible role of IgA in allergic airway disease.
56. Abstract #1240 discusses the possible non-psychogenic, immunologic role of Lexapro in the treatment of atopic dermatitis.
57. Abstract #1241 discusses the use of Efalizumab (a humanized monoclonal IgG1 antibody in moderate to severe plaque psoriasis.

GS

The following are "pearls" extracted from the 2003 Year Book of Allergy, Asthma, And Clinical Immunology (Mosby), a yearly feature of this web site.  Please see also earlier year book offerings in this section.  These are the main themes for the last year.  Where appropriate, this information is augmented by the clinical experience of the undersigned, gleaned from over 46 years of medical practice...and counting.

• Always suspected and generally assumed, specific genetic bases for inheritance of both bronchial asthma and IgE / atopic allergies are being worked out, holding promise for the future of genetic therapy for these diseases.
• Dendritic cells are involved in the Th1-Th2 balance between immunocompetent cells, the Th2 cells being responsible for atopic diseases.  (See the Hygiene Theory).  Atopic dendritic cells produce less IL 10 and IL 12, this leading to more Th2 activity.  Th2 cytokines include IL4,5, and 13.
• Mycoplasma and Chlamydia pneumonia organisms are responsible for 58% of exascerbations of bronchial asthma.  The Macrolide Clarithromycin (Biaxin) is a good antibiotic for such infections.  Zithromax is generally ineffective as treatment for respiratory tract infections.  One mechanism of action by which these infections worsen asthma is through an increase in cytokine production.
• One important theme this year, amplifying on similar concerns expressed in recent years, is the increasing finding that some asthmatics do not respond to appropriate treatment with inhalational cortico-steroids (and the spectrum of other medications used for this condition).  The reason for this is unclear, but the result is a progressive decline in lung function over years despite such treatment.   However, once again no mention is made of the use of allergy immunotherapy, the only treatment that addresses causal agents instead of effects.   This treatment should be an integral part of the comprehensive treatment of all asthmatics in whom a historical and/or skin test basis for allergic basis is sought and detected.   In the experience of those of us who do this, progression of asthmatic debility is a rare occurrence.
• There is a striking amount of sensitivity to cockroach antigen in urban populations.   This is very likely a cause of the continued high prevalence and severity of asthma in such populations, especially in the children.  It must be sought out and can be treated with allergy immunotherapy.
• Nocturnal awakening in asthmatic children is a clear sign of worsening asthma and must be treated.
• Several studies have found that the proper use of MDI's is as effective as Inhalation Nebulizers.  The key is proper instruction and demonstrated use.
• Several studies found that, despite good instruction, environmental control in allergic households is usually poor.  This should be the basic mainstay of allergy treatment and must be required by the treating physician.
• Many studies show that parents, physicians, and sometimes even patients chronically under-estimate the severity of the patient's asthma.   This is serious...and can be fatal.
• Viral infections are responsible for over 80% of asthma exascerbations.   In chronic asthmatics and especially in patients with COPD, however, the bronchial tree may be chronically colonized with bacteria.  Thus, when an exascerbation becomes associated with purulent mucus discharge over 12-24 hours, appropriate antibiotics are indicated.
• There are several conditions that can mimic asthma, known as forms of "pseudoasthma": vocal cord dysfunction; rhinitis; GERD, chronic bronchitis, post-viral cough, hyperventilation, and obstructive sleep apnea.  These should be distinguishable by means of a thorough medical and allergy hostory; but pulmonary function testing - with or without methacholine challenge - may be necessary.  In addition, many patients have several of these conditions simultaneously.  One of the most common combinations include bronchial asthma, allergic rhinitis, GERD and obstructive sleep apnea.  This latter condition is very important and should not be missed.  Please see information and a questionaire on that subject in another section of this web-site.
• Exclusive breast feeding of an infant for the first four months of life has been found to reduce the later incidence of bronchial asthma in childhood.
• Inhalation cortico-steroids must always be a part of the treatment of anything but mild, sporadic asthma.  Thus, any asthma experienced on two or more days per week warrants this approach.  Furthermore, treatment with these agents must be constant and not "as needed" in order to be effective.
• Persistent, "refractory" asthma warrants re-evaluation for: missed allergies,  any exposure to cigarette smoke, occupational exposures...and evidence of persistent airway inflamation reflected in elevated induced sputum eosinophiles and/or in marked improvement in post-bronchodilator pulmonary function testing despite apparently good clinical control.  Non-responsiveness to prednisone and to methyl-prednisolone can often be overcome by use of celestone (betamethasone), when available, or possibly by use of dexamethasone.  Regarding cigarette smoking (or any smoking, for that matter), my long-standing rule is that an asthmatic smoker who simply wants to continue smoking and not to avail himself or herself of our effective help to stop smoking is discharged from my care.   Smoking and asthma is a sure prescription for advanced  chronic lung disease at an early age.
• Cardio-selective B blockers are generally tolerated in mild to miderate asthma.   Related eye drops may still be a problem, however.
• There is a rather high (20%?) incidence of persistent cough associated with the use of ACE inhibitors, much less so with ACE receptor inhibitors.
• Bronchial asthma can lead to COPD / chronic bronchitis.  It also often accompanies COPD (20-40%?) and may then be the only reversible part of the patient's condition.   Thus, it must always be looked for.
• "World Trade Center Cough" is an unfortunate new entity since 9/11/01.  It is characterized by chronic cough and bronchial hyper-reacivity.  It may be chronic.
• The incidence of atopic/allergic disease (asthma, allergic rhinitis, atopic dermatitis) has increased to 30% in developed countries, for various reasons.
• Allergic rhinitis has been found to lead to bronchial asthma, if not adequately treated,  in about 40% of cases.
• Children with asthma are as likely to "grow into" more asthma as "grow out" of asthma.  Therefore, delay in applying adequate treatment is a big mistake.
• One article gives a guide to the proper dose of Epi-Pen for children: up to 15 kg weight, use Epi-Pen Jr; over this weight, use the standard product.   Occasionally, the severity of an expected reaction my modify this upward.
• Fatal allergic food reactions are most commonly due to milk, and peanut, in that order.  This outcome is especially possible if asthma is part of the allergic reaction.   Great care must be taken for prevention.  For treatment, monoclonal anti-IgE (Xolair) is now available.
• One "old adage" that I just made up is: if you wish to do "original" research, read the medical literature of 40 years ago...and do it again.  That seems true of the recent and increasing interest in endotoxin lipo-polysaccharides as immunomodulators.  Stock bacterial vaccine, anyone?
• Benadryl, found in many OTC medications, is worse than alcohol in impairing reflexes and affecting driving ability.
• The treatment of atopic dermatitis (infantile eczema) now includes not only topical steroids but also tacrolimus and pimecrolimus (Elidel).  The latter may also be used, with fewer side effects, as chronic maintenance treatment.
• Bone marrow transplants (especially the allo-geneic variety) can produce IgE-mediated allergic reactions in the recipient.

This year's crop of Allergy Abstracts - and the forthcoming  research papers in the JACI - break some new ground and contain some clinically applicable advances to the treatment of allergies, bronchial asthma and related diseases.  The following are subject areas and brief pearls which will require a deeper dive to obtain real benefit regarding areas of personal interest.

• There are many articles regarding the proven effectiveness of Allergy Immunotherapy ("shots, desensitization") for a variety of allergic problems, notably allergic rhinitis and bronchial asthma (#1,4,5,6,7,9,425,531,677,699).
• The uses of leukotriene receptor inhibitors like Singulair has expanded to include allergic rhinitis and chronic sinusitis in addition to bronchial asthma, in children as well as in adults (#10,313).
• The safety of orally inhaled steroids in children continues to be documented, especially regarding those agents least absorbable systemically (Flovent, Nasonex); (#12,607,800).  See below for more reasons to consider their use much earlier in affected children.
• Zyrtec continues to lose the debate regarding  somnolence/reflex impairment side-effects of second generation anti-histamines,  as compared with  Allegra, Claritin and Clarinex.(#14).  It still is best for allergic rashes and itching.  And all are much better than Benadryl for effectiveness and for side-effect profile.
• Simple saline  irrigation of the nasal passages (Nasal, Ocean Spray) is effective in reducing nasal congestion, not only in dry winter conditions but throughout the year. (#23).  "Try it.  You'll like it".
• Chronic Rhinitis and Sinusitis in children is increasingly being recognized as a significant problem, both in its own right and as related to accompanying or later bronchial asthma.  But it must be thought of  to be diagnosed, by procedures including allergy evaluation, testing for immune deficiency and for ciliary dysfunction, and ENT evaluation.  (#28,33,223).
•  Anti-Ig E, in the form of Omalizumab and Xolair, has left the research labs and is entering the clinical realm, despite practical shortcomings.  Stay tuned. (#54,295,299,534).
• The central importance of mold sensitization (in addition to mites and cockroach emanations in urban settings) is clear - even without discussing the toxic molds (Stachybotyrum) that are beginning to create havoc in some homes and businesses throughout the country.  (60,92,287).
• Toxic mold infestation can be insidious and pervasive, requirng only water damage and darkness added to the building practices of the last 25 years, and leading to generalized, vague but very troublesome symptoms and impairment, including cognitive impairment.   It is difficult to diagnose and to treat.  But prompt and thorough mold remediation  in an affected structure can be very effective.  (#92,548,549,712).
• A large variety of allergic reactions to medications, vitamins and other agents are reported.  (#75,108,110,119,135,137,342,343,345,404,737,968).  Bottom line: anything can cause an allergic reaction in a susceptible individual...even anti-histamines and cortisone.
• An article regarding Latex allergy points out that the use of powder-free gloves can go a long way to mitigating this problem in the workplace (#94)
• In some patients with exercise-induced anaphylaxis, often involving the post-prandial setting, wheat - containing foods have been eskpecially implicated (#116).
• Abstract #126 documents the compliance problem with the recommended immediate availability of Epi-Pen for patients susceptible to acute generalized allergic reactions.  It is of no use to you if it is not with you at the time.
• As GERD has been diagnosed more frequently in infants, the possibly associated condition called eosinophilic esophagitis has been reported to be associated with food allergies in children (#131).
• A large number of abstracts discuss the treatment of Bronchial Asthma, still probably the most poorly diagnosed and poorly treated serious disease in America today - with no excuse for that state of affairs (#162,231,358,367,580,586,587,608,753).
• Tacrolimus and related agents (Protopic, Eladil) are proving to be a great addition to the treatment of atopic dermatitis and also other dermatoses; long-term safety appears to exist also (#244, 352).
• More uses for the "black box" called IVIg (an immunomodulator with many uses) are reported (#289,668).
• It has now become evident that, although ACE inhibitors are the main culprits associated with angioedema, ACE Receptor Inhibitors also can occasionally have this adverse effect (#394).
• Aspirin desensitization, around since the mid-1980's, is experiencing a resurgence of interest for some patients with Aspirin sensitivity because of its very useful anti-inflamatory effects.  But it must be performed under a specific and carefully-controlled protocol - because aspirin sensitivity can kill! (#410).
• The special case of pruritis in the course of hemodialysis is discussed in Abstract #435).
• Of course, chronic urticaria, the bane of patient and physician alike, is represented (#453,674).
• Peanut allergy, very dangerous, was discussed under anti-IgE (above) and is also found in Abstract #502 et al).
• Flushing, rashes and other symptoms that may be confused with allergies are the serious problems of systemic mastocytosis and carcinoid syndrome (#552).
• The possible relationship between the histamine content of some foods and food-associated reactions is discussed in Abstract #750.
• Abstract #895 discusses newer approaches to the diagnosis of Cystic Fibrosis and its "forms fruste".
• The Hygiene Theory is alive and well, with more and more being reported regarding a central role for endotoxin (#903,1111).  We may yet see an FDA -approved form of Stock Bacterial Vaccine.
• The possible utility of Vitamine C as a beneficial immune modulator is noted in Abstract #1004.
• The perennial and serious problem of Hereditary Angioneurotic Edema and C1 esterase inhibitor (quantitative and/or functional) deficiency is discussed in Abstracts #1018 and 1019.
• Abstract #1042 reviews the established relationship between tobacco use (both before and after delivery) and illnesses in children, including atopic diseases.  That is why I consider tobacco use in these contexts to be forms of child abuse.
• There are several Abstracts which discuss the feasibility of skin testing and also of desensitization for antibiotic sensitivities.  (#1070...).

1. The tablet forms of plain Robitussin - type mucolytics, such as Duratuss G (1,200 mg. twice a day) and Humibid LA (twice a day) are useful in the ancillary treatment of bronchitis, asthma and URI - sinusitis.
2. Added to the many useful effects of Theophyllin agents (bronchodilator, mucolytic, cardiotonic, ciliary stimulant, diaphgramatic musculotonic) can now be added anti-inflamatory agent,  through now well-defined immunologic mechanisms.
3. Eye drop use such as Ketotifen may now improve also nasal allergic symptoms, through the lachyrmal duct connection.
4. Allergic Rhinitis and large-tonsil-associated Obstructive Sleep Apnea in children can be confused with ADHD, a very unhelpful error on several levels.
5. Substantial chronic airway inflamation in the young (ie. chronic sinusitis even in the first few years of life) is now being increasingly recognized.
6. Mast cell-derived chemicals like histamine are associated with late as well as early-phase inflamatory-allergic reactions.  Thus the importance of reducing and even eliminating the release of these chemicals in the first place by means of properly applied allergy immunotherapy.
Serum Tryptase levels can be auseful marker for suspected allergic reactions.  In fact, elevated serum tryptase levels have been detected in infant deaths diagnosed as SIDS.

• IL 4 and IL 5 both contribute to airway inflammation in bronchial asthma by promoting airway eosinophylia through a mechanism of suppressing IFNy.
• IL 18 may be an important non-invasive inflamatory marker of asthma activity, being higher with active disease.
• Exhaled nitric oxide (NO) is such a marker, although it is not known whether NO plays a harmful or beneficial functional role.
• Lung function is not a good predictor of “health related quality of life - HRQL”; this reflects the substantial variability from patient to patient regarding tolerance to bronchospasm, shortness of breath and consequent hypoxia.  Particularly dangerous to themselves and to their physicians are those patients with a high tolerance.  They must be identified promptly and watched closely, both clinically and with frequent peak expiratory flow testing. See also Abstract 2-36.
• Both local and systemic responses to inhaled lipopolysacchride (LPS, purified endotoxin), ubiquitous contaminants of our environment, were found to correlate inversely with atopic status.  These chemicals are now considered immune modulators that may be the explanation behind the paradox called the “Hygiene Theory”.  “...some, but not all, the effects in LPS may want to be examined and used for treatment of atopic disease in asthma.” Abstract 2-13, p36.  Of course, this is what many of us allergists trained in the use of “stock bacterial vaccine” were achieving for decades - until the FDA took the product off the market as being “without proof of efficacy”.  Too bad.  But maybe....
• One article supports the use of the telephone for evaluating breath sounds in our asthmatic patients.  We have recognized and used this for decades.
• Several articles reflect the often poor treatment asthmatic children - and often adults - get in emergency rooms.
• Abstract 2-23 points out that the presence of pets in the house of atopic children is associated with an increased incidence of childhood asthma.  Thus, having pets is not the way to get the benefits of the “Hygiene Theory”, in our opinion.
• Abstract 2-27 is entitled “Reasons for Pediatrician Nonadherence to Asthma Guidelines”.  Really!  These physicians as a group, generalists in the care of children, frequently “don’t know what they don’t know”.  They certainly do not make proper use of specialists and of specialty guidelines for the care of their patients.  It pains me to say this.  But I, and my patients who were referred  finally by their mothers, have experienced it all too often...and have had to pick up the pieces.  See also Abstract 2-46, and the note below.
• Now there is some evidence that pre-born children with atopic family histories may benefit - not only from maternal pre-natal diet manipulation - but also from maternal pre-natal environmental control.  Abstract 2-29.
• The benefits of inhaled levalbuterol (Xopenex) over  racemic albuterol are outlined in Abstract 2-34.   My patients and I can clinically attest to that.  It is to be hoped that an appropriate oral inhaler may be developed soon.  See also Abstracts 6-14,15.
• Abstract 2-39 addresses the long and increasingly common experience of non-allergic, non-asthmaticchildren and adults developing a viral respiratory tract infection that produces wheezing and related dry cough.  If not treated early and aggressively, sometimes requiring not only inhalational but also oral steroids and other medications, it can be the beginnning of years of asthma.  These conditions are called “acute asthmatic bronchitis” and “post-viral hyper-reactive airways syndrome”.   Some of the incriminated viruses include RS virus, rhinovirus and coronavirus.  Some specific bacterial infections, including Mycoplasma and Chlamydia pneumonia, may be especially associated with asthmatic responses and with chronic bronchial asthma.  Abstract 2-42.
• Non-invasive predictors of asthma control, both generally and during backtitration of inhaled steroids, include sputum eosinophilia and exhaled NO.
• Dexamethasone may be a better steroid for short-term asthma control than prednisone, with fewer side effects and shorter dose schedule.  Abstract 2-44.
• “Airway Responsiveness in Early Infancy Predicts Asthma, Lung Function, and Respiratory Symptoms by School Age”.  Abstract 2-46.  No, you don’t wait until “the kid outgrows it”.  You evaluate, follow and treat it appropriately from the beginning.
• The relationship between bronchodilator overuse (and anti-inflamatory medication underuse) and mortality from asthma is addressed in Abstract 2-47.  This is a very big problem, and physicians are generally not dealing with it.
• Abstract 2-51 deals with those serious asthmatics who, despite respectable treatment,  progress on a down-hill course through the years, as demonstrated by deterioration on serial pulmonary function studies.    This is undoubtedly a heterogeneous group of patients.  But the common denominators to dealing with this issue include: complete and accurate initial diagnoses, including a search for underlying atopic disease even where inapparent, and including a search for serious upper airway disease;  comprehensive medicinal treatment, clearly understood by the patient;  insistence upon adherence to treatment and follow-up, including total and permanent discontinuation of tobacco use; regular monitoring of pulmonary function tests to detect those patients who - although clinically controlled - demonstrate high-grade airway reversibility...and therefore continuing active airway inflammation;  and comprehensive treatment of any underlying atopic activity with allergy immunotherapy, the only form of modulation which deals with causes and not only consequences.  With this approach, it is the very rare patient with bronchial asthma in whom I cannot demonstrate improved or at least stable lung function over decades of follow-up.
• Once again it is demonstrated that leukotriene receptor antagonists (eg. singulair) are not adequate substitutes for inhaled steroids;  but they enhance the benefit to be derived from inhaled steroids when used with them.
• Similarly, adding a long-acting inhaled B-agonist (Serevent or Foradil)  to a regimen including an inhaled steroid produces better results than even doubling the steroid dose.  This combination is also more anti-inflamatory than is either chemical alone.  This relates directly to mitigation and possibly to reversal of “airway remodeling”, as reflected in thickness of the basement membrane with types 3 and 5 collagen and related fibroblast activity, hyperplasia and hypertrophy of smooth muscle, goblet cell hyperplasia, and angiogenesis.
• There are two types of croup in children: one associated with wheeze (usually related to RS virus infection); and the other not associated with wheeze (usually related the parainfluenza infection).  Only the one associated with wheezing is very often followed by persistent wheezing for years to come.  Abstract 2-56.
• Aspirin, besides being a potential cause of serious allergic reactions, is also a potent immunomodulator in achieving its anti-inflamatory effects.  It has been found to significantly inhibit IL-4, a cytokine that increases bronchial hyperreactivity.  Thus, it should be part of our weaponry, although it should be used carefully and selectively, in view of its ability at times to “blow up in our hands”.
• In addition to the well-known activities of eosinophiles, IL-4 and IL-5 in the inflamatory processes affecting Asthma, studies are now identifying PMI’s, through the action of IL-8 and IL-8 as involved in similar fashion.  These findings are important in providing more targets for possible therapeutic intervention.
• Several mechanisms are proposed for the established efficacy of allergy immunotherapy in modulating - desensitizing - allergic sensitivities: production  of blocking IgG antibodies; reducing CD-4 cell helper activity or  stimulating  CD-8 cell suppresser activity to effect the demonstrable reduction in specific IgE levels.  To these must now be added the promotion of rapid apoptosis (cell death) of Th2 lymphocytes when stimulated - after immunotherapy - with specific antigens.  Abstract 3-6.
• The Hygiene Theory has produced a debate regarding whether the presence of pets in the house (specifically cats) is beneficial or detrimental to atopic infants and children.  (See Abstract 3-14).  I, for one, believe that  the probable beneficial effects of early exposure to pollution, infection and other sources of endotoxin can be attained in ways other than by introducing such sources of strong allergens into the household of allergic individuals. See Abstract 3-25.  In fact, I have for some time suspected that Cats are the first Aliens to reach Earth, and that they are about to take over!
• Several articles offer evidence that premature birth reduces the incidence of later atopic sensitization.  This appears to depend on the fact that the more immature immune system, when first encountering the outside environment, may be more able to develop tolerance to antigens.  Abstract 3-15.  Indeed, the risk of atopic sensitization was found to increase progressively with gestations of 35 weeks or more. Abstract 3-16.
• The bacterial colonization of infants born by the vaginal route differs from that resulting from caesarean section birth. And it has been found in at least one study that children born by caesarean  section have a much higher incidence of asthma later in life.  Abstract 3-18.
• The use of “probiotic milk”,  containing cultures of lactobacillus, by the pregnant woman and also by infants and children has been shown to substantially decrease the incidence of allergy and of respiratory infections in these children.  This is another offshoot of the Hygiene Theory.  Abstracts 3-20,21,
• Childhood exposure to second-hand smoke is well-known to produce several bad results: increase in middle ear infections, bronchitis, pneumonia, and stunting of the ultimate size of the developing lung.  To all this is now added the finding that such exposure may promote allergic sensitization.  Abstract 3-22.  I fact, I advise parents of children referred to me that, after receiving such information, their continued smoking in their child’s household will be considered by me a form of child abuse.
• There are many articles describing the benefits of tacrolimus ointment (protopic, elidel) in the treatment of atopic dermatitis.  Indeed, this is probably the greatest advance in this area sinde the advent of topical steroids.  And another article describes its effectiveness in the treatment of the skin manifestations of chronic Graft-vs-Host Disease, a common complication of allogeneic bone marrow transplntation, used for a variety of cancers.  Abstract 4-5.
• The utility of leukotriene receptor inhibitors (eg. montelukast - singulair) for treatment of atopic dermatitis is also described.  Abstract 6-8.
• The benefits of higher - dose IVIG  in the treatment of primary immunodeficiency states is described.  Abstract 5-3.
• Omalizumab, a recombinant humanized anti-IgE monoclonal antibody that can block the interaction of IgE with mast cells and basophiles in allergic reactions, has been found to be both safe and effective in the treatment of serious bronchial asthma patients in a Phase 3 trial, as required by the FDA before approval.  Its availability must be that much closer to reality - but not yet.
• Once again, over and over again in the last four decades, theophylline is found to be useful in the treatment of bronchial asthma (and COPD).  It is a remarkable medicine that has many therapeutic effects.  Abstract 6-22.  In fact, if you want to do “original research”, read the literature of 40 years ago - and do it again.

GS

The following represent my “take” on the Year 2002 research and clinical offerings previewed for the March,  2002 annual meeting of the American Academy of Allergy, Asthma and Immunology  held in New York City.  These notes are derived from over 1,100 abstracts recently published in the Journal of Allergy amd Clinical Immunology, January 2002.

This seems to be a year of building upon previous break-throughs, with a few developments new to me.  The disease of the decade continues to be Bronchial Asthma, still the most underestimated and undertreated serious disease in America, except perhaps for high blood pressure.  This is a real shame, for there is no lack of scientific insights or of therapeutic modalities for both of these potential killers.  There is still an embarrassing and risky lack of implementation on the part of many physicians, and a devil-may-care attitude on the part of many people.

The numbers which accompany each personal commentary refer to the related abstract(s).  Many if not most of the abstracts will be published as complete articles during  the coming months in the Journal of Allergy and Clinical Immunology.

1)  Aspirin / NSAID-Induced Asthma (#50,220):

Contrary to decades - old clinical impressions, aspirin - induced asthma commonly is associated with underlying allergic (atopic) tendencies.  Such patients should thus be fully evaluated.  Potential reactions fall into two categories, although not totally separate: urticarial / angioedema reactions; and severe (or suddenly lethal) asthmatic reactions.  Aspirin desensitization under controlled circumstances is not only possible, but is also useful in achieving better control (through subsequent constant aspirin dosage) of both asthma and rhino-sinusitis.

Heparin is an agent generally used as an anti-coagulant.  It has several other pharmacologic properties which may find clinical utility.  One of these is its anti-inflamatory property which, when applied by inhalation has been reported to reduce both early and late phase asthmatic reactions.  On the other hand, heparin is highly antigenic.  This, in addition to the well-known side-effect of thrombocytopenia,  it may produce acute allergic reactions.  Immediate and delayed-type skin testing may be useful in evaluating this problem.

It has been known for years that, in addition to being generally noxious, diesel fumes contain chemicals which increase the level of IgE (the allergic antibody) in humans.  Such exposure also favors the development of Th2 - type immune responses.  Both actions provide the conditions necessary to produce allergic reactions and may be an important reason for the epidemic of asthma in the western world during the last two decades.  In fact, the particular preponderance of bronchial asthma in children of inner cities may well be related to the inordinate amount of time school - age children spend on school buses with diesel engines running, estimated to be about 180 hours per year.  Local and state agencies are beginning to address the issue of school bus engine practices.

This theory is based upon numerous observations  noting  an inverse relationship between exposure to air pollutants and/or number of respiratory tract infections on the one hand, and the incidence of allergies.  The immunologic effect associated with this connection is the tendency for infections to stimulate the immune system from Th2 reactions (favoring allergic disorders) to Th1 activity.  Although the connection is very likely valid, a few reports have tended to confound the lessons to be learned from these experiments of Nature.  One study, referenced here, suggests that allergic tendencies might protect against respiratory tract infections.  Other studies suggest that having a pet in the house might be of benefit to allergic individuals.  Both of these suggestions fly in the face of broad clinical experience that relates allergies to increased frequency and severity of infections, and that associates prolonged exposure to dogs and cats in the home environment with almost inevitable sensitization and worsening of the allergic manifestations.  (If chronic urticaria is the bane of allergists’ existence, CATS especially are their cross.  Might CATS  really be the first aliens to arrive on this planet, preparing to take over the world??)  Indeed, the preponderance of evidence for the Hygiene Theory and related research seem to support the decades-long  use by some allergists - myself included - of  “stock bacterial vaccine”  especially in children as a useful adjunct to reducing asthmatic responses to respiratory tract infections.  It has always been suspected that its effectiveness was probably due to the endotoxin content of the vaccine (#96,104,580,611).  This product is no longer available because of “lack of proof of efficacy”.  Too bad...but that may change as this question is necessarily revisited by researchers and by the FDA.

Severe bronchial asthma, often steroid-resistant, is the subject of many studies.  The “Tenor Study”, as established, is positioned to provide much epidemiologic and longitudinal information, perhaps similar to the Framingham Study.  The Denver Study describes troublesome evidence that - despite all the therapeutic modalities in use - loss of lung function and often loss of steroid responsiveness continue, especially in asthma dating from childhood.  In my opinion, this unfortunate situation is due to at least three factors: a) the lack of compliance by most physicians - who should know better - with the numerous treatment protocols clearly established for the proper treatment of bronchial asthma; b) although controversial, developing evidence that prolonged use of inhaled steroids may actually contribute to “re-modeling” - scarring of lung tissue; c) the tendency of many people to underestimate the severity of their asthma; d) the continuing failure of most physicians, pulmonologists and even some timid allergists to implement the clear theoretical and abundant evidence-based knowledge supporting the use of immunomodulation - in the form of specific high-dose allergy immunotherapy - to eliminate the causes of the asthmatic disease process, rather than pursuing its effects.  The proper approach to bronchial asthma is a complete medical and allergy evaluation by a certified allergist (since no one else seems able or willing to do it right).  The proper treatment is comprehensive, including environmental control, absolute cessation of smoking, expert use of the multiple medications readily available and - where unavoidable allergenic agents are detected - allergy immunotherapy to reduce or eliminate the patient’s reactivity to such agents.  Using this approach, the vast majority of asthmatics (85%+)  can achieve at least stabilization and very often reversal of their disease process, with the ability to discontinue the immunotherapy after a few years.   This has been my experience over the last 40 years, dealing with a practice predominating in bronchial asthma, adult and pediatric.  The message here for patients is clear:
“Caveat emptor...Let the Buyer Beware!”

Nothing like adding an enigma to a puzzle.  But the author is probably right.  Both conditions exist and may be interrelated, despite our inability to clearly define their mechanisms.  That’s why we call this the “Practice of Medicine”...we never get it quite right!

This appears to be a victory for HEPA - type air cleaners of adequate air-handling size over fancy vacuum cleaners, if one or the other must be chosen.

Although by no means as great a break-through as were the antihistamines which came on the scene around 1950, the anti-leukotrienes (Accolate, Singulair) are important.  They are agents which block the pro-inflamatory actions of leukotrienes, products of white blood cells involved in the defenses and immune mechanisms of the body.  Clinically, the best of the three appears to be singulair (montelukast); and it has found wide application in the comprehensive treatment of bronchial asthma.  Since this chemical also has bronchodilator properties, it is also under study as an intravenous medication for emergency use in acute asthma.
The above references describe other uses being studied for this class of medications:

1. Reduction of pain and itching from local reactions to allergy limmunotherapy.  Rarely, a patient may experience recurrent delayed (12-24 hour) indurated local reactions which interfere with compliance and with progression of treatment.  Singulair, 10 mg., taken two hours before injections may be useful here.
2. Treatment of nasal polyposis, an inflamatory condition often associated with, but distinct from,  nasal allergy.
3. Treatment of “Samter Syndrome”: asthma, nasal polyposis and aspirin/NSAID intolerance.
4. Pre-treatment for aspirin/NSAID intolerance manifesting as hives and angioedema.  This, however, is not to be tried (other than possibly in association with aspirin desensitization)  when the sensitivity has manifested as acute asthma.  Such a reaction can be quickly fatal.  (See item 1, above).
5. Possible utility, not yet established, for atopic dermatitis (“infantile eczema”).
6. Reduction of exercise-induced asthma.

Copper, Hepatitis -B Vaccine, heparin, beta-methasone (celestone), omeprazole (prilosec), parabens (widely used preservatives), sesame and pistachio (often hidden in sauces), nicklel (possibly also in foods;eg. vegetables),  pine nut (often added to sauces and vegetables), gummi-bears, menthol - peppermint oil - mint (included in toothpastes).  So...an Epi-Pen should be part of the daily attire of any person (without high blood pressure) who has or strongly suspects food and/or medicine allergies.

This is a condition characterized by an excess number of mast cells in the body (in skin and/or in mast cell tumors), the major source of histamine and other chemicals that can produce allergic reactions or allergic-looking reactions.  It can be an occult cause of anaphylactic reaction.  It can be detected fairly easily with a blood and/or urine test, and occasionally with a biopsy.

Numerous studies have shown that allergic rhinitis (hay fever with or without ”sinus trouble”) is often a precursor to the development of bronchial asthma, a sequence which can be avoided by treating the allergic rhinitis with specific allergy immunotherapy.

Many more people carry a history of “allergy to penicillin” than are actually allergic to penicillin.  This is not to minimize in any way the central role of the medical history in making treatment decisions about the use of penicillin and related antibiotics.  However, where circumstances warrant  a more definitive diagnosis with direct effect on the choice among limited antibiotics, skin testing is very useful and dependable.  It can reduce the use of more high-tech antibiotics and thus reduce the development of resistance to these important agents, for which there are sometimes no substitutes.

Dyspepsia may be just another manifestation, reflecting similar tissue changes, of allergic reactions in some patients.  Certainly, the frequency of such symptoms is increased over normal levels in patients with asthma as well as in those with allergic rhinitis and atopic dermatitis.  In any case, such symptoms should be treated aggressively, primarily with proton pump inhibitors (prilosec, prevacid, nexium, aciphex),  because lower esophageal acidity can produce reflex bronchospasm; and actual regurgitation can substantially complicate both upper and lower respiratory tract disease.

Budesonide (Pulmocort) has emerged as a prerferred agent.  Meanwhile, the side effects in children appear to be overestimated, leading to the under-use of budesonide and other inhaled steroids.  And the potential steroid side-effects in adults (such as osteoporosis and adrenal insufficiency) appear to be underestimated.
Prudent use is the message here.

Here is another area where we constantly “practice” Medicine: we never get it right!
These articles again point out the frequent association between  “chronic” hives (6 or more months duration) and auto-immune diseases and auto-antibodies (expecially anti-thyroid and ANA antibodies).  Other associations discussed include insulin (definite) land H. pylori (uncertain).  The prolonged use of sulfadiazine (6 weeks) is also suggested  (#365) as a treatment for chronic urticaria of unknown cause.  This would be in line with the fact that “hives” can be the body’s response to allergens (eg. foods), infections (eg. urinary tract or dental infections, hepatitis, etc.), or to a malignancy.

17) Acquired C1 Esterase Inhibitor Deficiency and  Underlying Lymphoma (Ref.#374)

18) Facial Edema can represent subcutaneous emphysema resulting from micro-perforation of the bowel during Colonoscopy!  (Ref. #375)

19) Tylenol Cross-Reactivity With Aspirin / NSAID Sensitivity.  (Ref.#412, 413, 416):

This is real, but the greater dangers  from tylenol  are overuse, leading liver toxicity, and deliberate overdosage - with likely fatal consequences if not treated promply.

This agent, still in clinical trials, will very likely be an effective addition to our  treatment modalities.  But, is this another “anti-”drug  rather than an effort to reverse  the underlying immunologic mechanism through specific immunotherapy?  I think so.

This is the newest non-steroidal topical agent for moderate to severe eczema, and appears to be a real addition to available therapies.  If this doesn’t work,  the authors suggest a really big gun: cyclosporine.

Intravenous gammaglobulin is used as replacement therapy in immunoglobulin deficiency states.  It has also been used in recent years to treat an increasing number of pathologic conditions of ill-defined cause through an ill-defined mechanism generally assumed to be immunomodulation.  And it works many times!
The treatment is, however, somewhat laborious to administer; and it carries a small risk of side effects, including the possibility of anaphylactic - type reaction.  The above reference describes the sub-cutaneous administration of Ig, avoiding the inconvenience and  the side-effects with reportedly better trough levels.  This is worth checking out if you are in that arena.

A little more information.

We may soon have a sub-lingual epinephrine for use in acute allergic reactions, instead of the Epi-pen self injectors.  Stay tuned.
25) Gluten Intolerance (Celiac Syndrome) and Wheat Intolerance (Ref.#932,933):
Avoiding gluten in foods is more difficult than might be expected for patients so afflicted.  It is, of course, the entire basis for their treatment and is thus highly important.

Skin testing, (particularly intradermal skin testing, acknowledged as the gold standard), is very important, second only to a carefully taken medical and allergy history in the diagnosis of allergic, IgE mediated diseases.  The intake of anti-histamines suppresses and may negate the results, which depend on the release of histamine in the skin resulting from the antigen-antibody reaction being sought.  1st generation anti-histamines (Chlortrimeton, Benadryl) should no longer be used, except in an emergency, because of the sedative effects and also because of their reflex -  impairing activity (eg. in driving).  2nd generation anti-histamines generally lack these side effects.  But their effect on skin tests is of much longer duration.  This is true of claritin, allegra, zyrtec, and astelin; and it is especially true of clarinex, the newest arrival on the scene.  Based upon the latest reported evidence, none of these anti-histamines should be taken by a patient scheduled for skin testing for one week before the procedure.  Of course, the patient’s symptoms must be otherwise controlled during that period.   This can ordinarily be accomplished with inhalational or nasal steroid sprays - or in more complicated cases with a short course of oral steroids.

GS

A)  Prevention:

Diesel fumes, toxic and  carcinogenic in many ways, also stimulate IgE, the allergy - producing antibody in everyone.  This problem is considered one important reason for the near - doubling of allergies in the general population in recent decades.  (#480)

Pregnancy and infancy are the times to put preventive measures into effect, including mother’s smoking, secondary smoke, pet avoidance and other environmental control measures, and also mother’s diet during  breast - feeding.  (#985, 766)

Skin tests, puncture - prick and especially intradermal, are the gold standard of allergy diagnosis and are far more useful and reliable than the “RAST” tests.  (#54)

Penicillin is the most common cause of medicinal allergic reactions.  Penicillin skin testing ( with both major and minor determinant agents) is only 70% effective in detecting penicillin sensitivity.  Thus, history is the most important diagnostic tool.  In the rare cases where there is no substitute for penicillin in a penicillin - allergic patient,  careful desensitization is available in expert hands.

Local anesthetic reaction is not uncommon, but true allergic reaction is rare.  A form of testing/rapid desensitization  is available, again in expert hands...since such approaches can carry a risk.

“Multiple Antibiotic Drug Allergy” (MADA) is a vexing syndrome of unclear causation -- but it is real.  (#40)

Eosinophilic Gastroenteritis is a particular ailment which can mimic GERD and other GI conditions.  After a positive diagnosis, Singulair may be helpful.  (#641, 99,643)

Anxiety/depression is reported to be more common in patients with allergic disorders.

Urticaria ( hives, acute and especially chronic)  continues to be a challenge for both physician and patient.  But much can be done.  (#178,180)

Latex allergy is a problem of increasing frequency, especially in health care workers.  It can be mild or severe and life-threatening; it can be obvious or obscure.  It is diagnosed by history, blood tests, and possibly skin tests.  Treatment ultimately consists of avoidance, since the sensitivity tends not to disappear.    There is also cross-reaction with a group of foods.  (#384,794)

Occupational diseases  include chronic beryllium poisoning.  In addition to pulmonary and skin involvement, there is reported an allergic contact reaction the gums from beryllium-containing dental implants.  (#420)

Soy protein sensitivity is not ruled out by tolerance to soy sauce.  Also, soy oil may cause problems.   (#464,623)

Chronic sinus disease, complicating fungus infection, the relation to bronchial asthma, and the potential utility of leukotriene inhibitors (eg. singulair) are  discussed.   (#536,537, 549,551)

Cat protein sensitivity, as manifested in skin testing, is the most common  allergen: fluffy, sticky, easily and persistently airborne, nearly impossible to get rid of, and easy to be exposed to on others’ clothing, is a bad actor.  (#564)

Oral Allergy Syndrome, involving allergic mouth symptoms on ingestion of certain foods (particularly certain fruits), may progress to generalized symptoms.  Thus, patients so afflicted should carry  an epi-pen or ana-kit for self-administration.  (#656)

Bumble Bee venom allergy can be yet another occupational illness, affecting workers in vegitable crop greenhouses that use bumble bees for pollenation.  In such cases, bumble bee venom and not honey bee venom should be used for immunotherapy.  (#727)

MSG (monosodium glutamate)  is well known for causing “Asian food syndrome”; but it is not considered to cause asthmatic reactions.

“Food-Dependent Exercise-Induced Anaphylaxis” can exist despite negative food skin tests and negative RAST tests.  (#877)  Thus, the history is all-important.

Grape allergy is rare but exists.  (#887)

Myasthenia Gravis is an immunologic disease which may at times benefit from treatment with IVIG, an important immunomodulator for many diseases with an immunologic base.

 “Graft-vs-Host Disease is another immunologic disease which can complicate treatment efforts which are associated with host immunodeficiency, either natural or acquired (eg. secondary to some treatments for cancers).  (#975)

Stachybotyris fungus toxicity/allergy  is an emerging causal agent in a variety of clinical syndromes occurring in the context of exposure to homes or buildings which have been water-damaged. This goes well beyond  well-known mold allergy found in similar circumstances.  (#1034)

Bupropion (Welbutrin, Zyban), a psychotropic agent widely used and effective for smoking cessation, may rarely produce a serum sickness-like reaction (fever, rash, arthralgias) even days after beginning its use.  (#30)

Steroids, used topically, orally or by injection, may rarely produce allergic reactions, the precise problems for which they are ordinarily given.  This is true also for H1 (claritin, allegra, zyrtec, etc.) and H2 (zantac, pepcid, etc.) antihistamines.  (#31)   The moral of this story is that any medications or chemicals used for medical purposes can produce  allergic or ideocyncratic, as well as toxic, reactions.

Insulin, even human-derived (Humulin) can produce anaphylactic reactions, in addition to local and cutaneous allergy.  (#35)

NSAID’s (and aspirin) are well known to react allergically with sulfonamides (like bactrim, septra, gantricin, etc).  Cox-2 agents (vioxx, celebrex) may react in the same way, although to a lesser extent.  (#442,443)  The worst of the possible reactions is sudden, severe, sometimes fatal asthma.  This, like penicillin allergy, can kill you!

Singulair, a leukotriene-receptor inhibitor increasingly prescribed for lower and also upper respiratory allergic disorders, as well as for some other inflamatory disorders, may rarely cause a serious systemic condition called a “vasculitis”.  Although some reported “reactions” may really represent the unmasking of “Churg-Strauss Syndrome”,  patients should be given the benefit of the doubt by discontinuing Singulair.  (#866)

“Natural or Alternative” products  may themselves produce hypersensitivity and toxic reactions.  (#886)  This is really a “black box” which should be avoided until the FDA finds the political courage to subject that industry to its thorough oversight.  One exception may be the combination of Glucosamine and Chondroitin sulfate, which may have some place in the treatment of degenerative joint diseases.

1) The unresolved controversy regarding whether to use “beta adrenergic” drugs only “as needed”, or on a maintenance basis (eg. proventil-albuterol, serevent-salmeterol).  (#338,339,365)   I try to avoid ahe maintenance use of these drugs, for both theoretical and practical reasons.
2) Steroid  burst treatment (#448),  steroid withdrawal (#473), steroid resistance (#771)  and  the side effects of inhaled steroids (more prominent with fluticasone).
3) Monoclonal anti-IgE antibody  under investigation for the treatment of allergic disorders.

The concomitant use of “beta-blockers” and/or ACE inhibitors may complicate the treatment of rare systemic reactions to allergy injection treatment; but they are not contraindicated.  The physician should have glucagon and ipatropium, in addition to adrenalin, benadryl, etc. available to use if needed.  (#236)

“Stock bacterial vaccine” is  a product used for the last fifty years by many, but not all, allergists and initially introduced by the pioneer Dr. Robert Cooke.   It has always been  suspected,  in the absence of confirmatory research but based upon decades of clinical experience,  to be effective in the reduction of “allergic” reactions to infectious agents, particularly in children (eg. recurrent acute asthmatic bronchitis). The mechanism has been thought to be its endotoxin content.  Now comes increasing evidence to support this,  including the “hygiene hypothesis”  and related studies of TH2/Th1 cell changes, and  “design-allergen for DNA -based desensitization.  (#310,313,747,749,1057)

Notes Taken from Articles Abstracted in the Yearbook of
Allergy, Asthma, and Clinical Immunology 2000




1. Many articles address the various functions of different interleukens in the pathogenesis of allergies.
2. An article on page 17 demonstrates that Staphylococcal toxin, a type of super antigen, augments specific IgE responses by atopic patients exposed simultaneously to allergen.  The mechanism of this augmentation is defined.  This supports the long-known observation that developing certain respiratory tract infections in pollen seasons in an otherwise non-allergic individual may initiate the allergic response to those seasonal antigens.
3. An article on page 23 describes the hyper-IgE (Job’s) syndrome characterized by very high levels of serum IgE together with chronic dermatitis and often severe infections of skin, paranasal sinuses, and lungs.
4. The article on page 24 reviews further evidence that atopy and asthma have been on the rise in developed countries, while remaining uncommon in less developed countries, especially in rural areas.  The increase is most marked in urban groups.  Inverse relationships are reported between atopy and number of siblings and atopy and early entry into communal daycare.
5. Another article on page 29 discusses this finding further, noting that infectious diseases produce TH1 type responses resulting in environments rich in interferon gamma which participates in the suppression of TH2 responses.
6. An article on page 43 discusses the fact that polyaeromatic hydrocarbons associated with diesel exhaust particles favor IgE production, bronchial hyper-responsiveness, and airway inflammation.
7. In two articles beginning on page 49, the observation is reported that there is substantial expression of Cox-2 in airway, epithelial, and inflammatory cell in the absence of evident airway inflammation.  This, in addition to the known importance of Cox inhibition precipitating asthma attacks in aspirin-sensitive individuals suggests the possibility that specific Cox-2 inhibition, with or without other leukotriene antagonists may have a role in treatment of this condition.
8. An article on page 57 reports the contribution of IL4 in the development of allergy inflammation and asthma.  Conversely, it discusses the utility of soluble human IL4 receptor (Nevance) in reducing asthmatic inflammation.
9. An article on page 60 describes the utility of anti-IgE in inhibiting mast cell activation, although without interfering with eosinophilic infiltration.  Thus treatment with anti-IgE is limited in its effectiveness to early phase response.  It was also found that concurrent treatment with anti-IL5 suppresses eosinophilic infiltration and interferes with the inflammatory response.
10. An article on page 63 defines the pathophysiology of allergic asthma as involving TH2 cytokines including interleuken 4 and interleuken 5.
11. An article on page 68 supports the evidence of discordance between suppression of inflammatory interleukens such as IL4 and IL5 and continued changes of remodeling in asthma.  Once again this increases the importance of avoiding the entire reaction in the first place with comprehensive treatment including allergy immunotherapy and environmental control.
12. An article on page 72 points out that aerobic exercise, in this case swimming, raises exercise tolerance resulting in increased oxygen uptake and reduced ventilation requirement, thus allowing an individual with exercise-induced bronchospasm to exercise for a longer period before triggering EIB.  It is emphasized, however, that “working through” EIB is to be discouraged because it can produce severe reaction.
13. An article on page 74 also addresses EIB noting that numerous medications are effective including Cromalin, Tilade, and Singulair.  One suggests the use of Salmeterol powder by Discus for 12-hour protection.
14. An article on page 86 emphasizes that importance of introducing inhalational steroids early in the treatment of childhood asthma in order to avoid reduced responsiveness later, probably associated with airway remodeling.
15. An article on page 90 describes the central role of eosinophils and eosinophilic cationic protein and major basic protein in the development and worsening of airway inflammation.  This appears to be true regardless of whether the underlying mechanism is allergic or otherwise.
16. An article on page 93 reiterates the central role of RSV virus as a common respiratory tract infection in early childhood stimulating both asthmatic reactions and bronchiolitis.  It discusses the value of a safe and effective RSV vaccine when available.  In addition, the article on page 97 describes treatments other than the usual supportive care which may be appropriate in patients with serious underlying disorders.  Such treatments might include antiviral therapy, such as Ribavirin and RSV immunoglobulin.  It is generally thought, though not completely proven, that patients who have had acute bronchiolitis are much more likely to develop asthma subsequently.
17. An article on page 101 notes a significant correlation between exhaled nitric oxide and sputum eosinophils as markers of airway inflammation in children with mild to moderate asthma.
18. An article on page 102 once again suggests that some degree of airway inflammation persists despite inhaled leukocorticoid therapy and in the absence of symptoms.
19. An article on page 105 notes that treatment with Singulair results in reduced levels of exhaled nitric oxide.
20. An article on page 107 demonstrates that allergen avoidance is associated with fall exhaled nitric oxide supporting the importance of environmental control.
21. Two articles on page 113 and 115 discuss vocal cord dysfunction in child as well as adults.  This problem is identified as a paradoxical adduction of the vocal cords during the respiratory cycle, usually on inspiration but also possibly on expiration.  This can imitate asthma and will not respond to anti-asthmatic treatment.  Once identified, it is best treated with respiratory phonation exercises, and perhaps psychotherapy.
22. An article on page 125 discusses the occupational asthma involving red cedar and notes that the reactions to this antigen manifest late or biphasic asthmatic reactions to the plicatic antigen.
23. An article on page 129 describes glucocorticoid insensitive asthma as being a problem which changes over time, so that individuals may vary between steroid-sensitive and steroid-insensitive situation.
24. An article on page 136 describes airway hyper-responsiveness in the absence of asthma, noting that the development of asthma symptoms apparently involves both atopy and hereditary factors.  In addition, the presence of airway inflammation and remodeling in patients with asymptomatic AHR is confirmed.  It also notes that some of these asymptomatic patients go on to develop clinical asthma, those being uniformly atopic with positive family histories.  There is also a suggestion that a critical threshold in airway inflammation/remodeling must occur in asymptomatic AHR before the development of asthma.  This increases the importance of identifying patients with AHR even without asthma as in the case of patients with upper respiratory allergies without the development as yet of overt asthma.
25. An article on page 138 describes IVIG as a glucocorticoid-sparing agent in patients with chronic severe asthma.  The mechanism is probably immunomodulation, so far not elucidated.
26. An article on page 140, addressing recognition of early asthma, noted that at least 40 percent of all children with wheezing, lower respiratory illness during their first three years will still have wheezing episodes at six years of age when more specifically several major and minor criteria were identified in predicting persistent asthma.  Major criteria are hospitalization for bronchiolitis/wheezing, at least three wheezing lower respiratory illnesses during previous six months, parental history of asthma, and atopic dermatitis.  The minor criteria are rhinorrhea separate from colds, wheezing separate from colds, eosinophilia, and male sex.
27. Further information from the University of Arizona group emphasizes the difficulty in identifying those wheezing infants who will or will not proceed to persistent asthma and also emphasizing the importance of initiating anti-inflammatory treatment in present and future asthmatics as early as possible; thus the need to give these infants the benefit of the doubt with anti-inflammatory treatment.
28. On page 150, there is further evidence of the importance of the eosinophilic process in the pathophysiology of severe asthma.  The paper notes two distinct pathologic subtypes of severe asthma:  (1) the classic eosinophilic process with inflammation, (2) the other, eosinophil negative, with little evidence of classic asthmatic inflammation. The eosinophil-positive type was associated with greater inflammatory cell infiltrate and higher incidence of respiratory failure.
29. On page 156, we find once again the importance of endotoxin, in this case inhaled endotoxin highly concentrated in organic dust.  This is a potent inflammatory agent likely to have a significant role in airway inflammation in patients with asthma.  This relates to our premise over many decades that the stock bacterial vaccine effectiveness is related at least in part to its endotoxin content.
30. On page 161, we find a new name for exercise-induced bronchospasm, namely “thermally-induced asthma” by E. R. McFadden.  He holds that the severity of exercise-induced asthma depends largely on the rate of airway rewarming after the cessation of exercise.
31. The article on page 163 addresses the issue of remissions of asthma.  It is noted that in adults, remissions are relatively rare and restricted to mild cases and elimination of cigarette smoke.  In children, however, variability is the defining characteristic.  The prognosis is largely unpredictable, although children will retain increase airway responsiveness and will remain at risk as they reach middle age.
32. An important observation is noted on page 169, namely severe exacerbation of asthma occurring with the use of interferon A for the treatment of chronic hepatitis C.  The problem diminished with cessation of interferon therapy.  Reinstitution of interferon therapy produced severe asthma once again.
33. The next article on page 170 finds that there is no evidence that long term asthma leads to the development of emphysema in non-smoking patients.  However, it is noted that non-reversible airflow obstruction is more likely to occur with highly variable airflow obstruction at baseline.  Thus, some patients with apparently stable asthma who have high bronchodilate reversibility may need more intense anti-asthma therapy to improve airway function and control inflammation.  However, in this ten-year longitudinal study, it was once again noted that individuals with moderate to severe asthma remain at risk for development of non-reversible airway obstruction despite treatment with inhaled leukocorticoids.  Thus, we should be more aggressive with anti-inflammatory treatment in patients with marked reversibility and we should treat them comprehensively including the use of allergy immunotherapy in appropriate cases to avoid the entire cascade toward chronic inflammation and airway remodeling.
34. Articles on page 175 and 176 discuss the delayed-type relations to amino- penicillins, exploring diagnostic approaches.  These include patch testing and intradermal skin testing looking for delayed intradermal test results.  These latter tests were found to be a more sensitive diagnostic tool.
35. The article on page 181 casts doubt on previously reported suggestions that MSG ingestion causes asthma.
36. On page 188 an article reviews breast-feeding in allergic infants and emphasizes the desirability of initiating breast-feeding on atopic infants.
37. The article on page 192 discusses the “latex-fruit syndrome” reflecting the now recognized cross-sensitization between latex and the growing list of fruits including chestnut, avocado, and banana.  Latex sensitivity may also exist without the concurrent fruit sensitivity.
38. Another article on page 197 notes that the prevalence of occupational allergy to natural rubber latex is reported to be between 8 and 17 percent.  The incidents of latex-induced occupational asthma are between 2 and 6 percent.
39. On page 199, the article addresses skin test safety and notes that in one large experience, there were only six systemic reactions and no deaths in more than 18,000 patients undergoing allergy skin tests.
40. On page 207, we notice once again reference