March 2006 World Medical Journal Review
Reviewed by Richard F. Lockey, M.D., Editor-In-Chief
1. CD4+ INVARIANT T-CELL-RECEPTOR+ NATURAL KILLER T CELLS IN BRONCHIAL ASTHMA
Invariant natural killer T cells in humans are CD4+ with Va24-Ja18 receptors. They respond to glycolipid rather than peptide antigens. On activation they produce large quantities of interferon-? and IL-4. The authors found that 60% of pulmonary CD4+CD3+ cells in patients with moderate-to-severe persistent asthma were natural killer T cells, which expressed an invariant T-cell receptor and produced type 2 helper cytokines. Controls (normal and patients with sarcoidosis) had conventional CD4+CD3+ T cells, not natural killer T cells. Editor's comment: These findings call into question – is it the Th2 T cell or the natural killer T cell that is involved in the pathogenesis of asthma? Akbari O, et al. N Engl J Med 2006; 354: 1117. Kay AB, Editorial: 1186.
2. ß-ADRENERGIC RECEPTOR POLYMORPHISMS AND RESPONSE TO SALMETEROL
This study investigated whether genotype-specific effects occur when patients with asthma are treated with long-acting ß-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. In two separate cohorts, the subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy and in the second, randomized to regular therapy with salmeterol while continuing concomitant ICS. B16Arg/Arg compared to B16Gly/Gly subjects were found to have an impaired therapeutic response to salmeterol with or without concurrent ICS. Editor's comment: B16Arg/Arg subjects (approximately 1/6 of Caucasians and 1/5 of African Americans) may benefit from alternative asthma treatment strategies. Wechsler ME, et al. Am J Respir Crit Care Med 2006; 173: 519. Tattersfield AE, Harrison TW, Editorial: 473.
3. THEOPHYLLINE AND CETIRIZINE IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA (CIU)
This 6-month, double-blind, placebo-controlled parallel study of 134 (105 completed study) CIU subjects found that cetirizine plus theophylline (200 mg twice daily) was superior to cetirizine and placebo. Results, as measured by a visual analog scale and treatment effectiveness score, were statistically significant at certain points throughout the study. The authors conclude that theophylline was well tolerated and provided considerable additional benefit in the management of CIU. Editor's comment: We need all the help we can get with CIU. Theophylline for CIU? Kalogeromitros D, et al. Int Arch Allergy Immunol 2006; 139: 258.
4. EFFECT OF TIOTROPIUM ON EXACERBATIONS AND AIRFLOW IN COPD
This randomized, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 µg once daily (n = 500) and placebo (n = 510) on exacerbations, associated health resource use (HRU) and airflow limitation in COPD patients. Tiotropium reduced exacerbations and HRU and improved airflow over 1 year . Editor's comment: Tiotropium is a drug of choice for patients with COPD. Dusser D, et al. Eur Respir J 2006; 27: 547.
5. T CELL-MEDIATED HYPERSENSITIVITY TO QUINOLONES: MECHANISMS AND CROSS-REACTIVITY
Six patients with delayed hypersensitivity skin reactions to ciprofloxacin, norfloxacin or moxifloxacin underwent in vivo patch testing and in vitro lymphocyte proliferation testing to study delayed-type hypersensitivity reactions to quinolones. Three of the six patient patch tests were positive after 24 and 48 h, and all patients had positive lymphocyte proliferation tests. The authors conclude that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among different quinolones is frequent. Editor's comment: Quinolones are very important broad spectrum antibiotics which can cause delayed type hypersensitivity reactions. Schmid DA, et al. Clin Exp Allergy 2006; 36; 59.
6. SIDE-EFFECTS OF AQUEOUS SOLUTION WITH ALUMINUM HYDROXIDE ALLERGEN-SPECIFIC IMMUNOTHERAPY (SIT). A PROSPECTIVE MULTI-CENTRE STUDY
Four allergy centers in Denmark collected data from all patients initiating SIT in a three-year study to determine its safety. A total of 1,038 patients received treatment with 1,709 allergens (timothy, birch, mugwort, house dust mite, cat, and wasp and bee venoms), 23,047 injections in total. There were 582 systemic side-effects in 341 patients. Most were mild grade 2 reactions (78%) and grass vaccines were most likely to cause problems. The type of allergen, but not the patient or center, predicted side-effects. Gender or asthma did not influence the frequency of side-effects. Epinephrine was used for treatment in 2% of the side-effects. Editor's comment: This study indicates that aluminum hydroxide modified extracts are safe and that grass vaccines account for most side-effects. Asthma was not a risk factor. Winther L, et al. Clin Exp Allergy 2006; 36: 254. Frew AJ, Editorial: 251. No abstract is available for this article.
7. BUDESONIDE/FORMOTEROL IN A SINGLE INHALER
A six-month, randomized, double-blind, parallel-group study of 697 subjects, mean age 38 y, compared the effects of budesonide/formoterol (B/F) (80 µg/4.5 µg, two inhalations qd in the evening) plus B/F prn or budesonide (B) (160 µg, two inhalations qd in the evening) plus terbutaline (T) (0.4 mg) prn for maintenance or relief of mild-to-moderate asthma. Patients on B/F had higher morning PEF, less risk of severe exacerbation, and fewer hospitalizations/ED treatments. Increased efficacy with B/F was achieved with less ICS than in the B group (mean dose, 240 µg/d vs 320 µg/d, respectively) with 77% fewer oral steroid treatment days. The incidence and frequency of adverse events were similar. Editor's comment: Combination long-acting ß2-agonists and ICS are better than ICS alone and in this study are equally safe. Rabe KF, et al. Chest 2006; 129: 246.
8. EMERGENCY DEPARTMENT (ED) INTERVENTIONS TO IMPROVE CARE OF PATIENTS WITH ACUTE ASTHMA
Three–hundred and eighty-four patients (age 2 to 54 y) participated in a randomized, control trial to compare the effects of two interventions on primary care (PC) follow-up after ED treatment for asthma exacerbations. Baseline demographics, chronic asthma severity and access to care were similar in both groups. Intervention, including free medicine, transportation vouchers and appointment assistance significantly increased the likelihood that discharged asthma patients obtained PC follow-up but did not impact long-term outcomes. Editor's comment: Strategies to impact long-term asthma morbidity are needed for patients who utilized the ED for acute asthma. Baren JM, et al. Chest 2006; 129: 257.
9. INFLUENCE OF BODY MASS INDEX ON THE RESPONSE TO ASTHMA CONTROLLER AGENTS
A post hoc analysis pooled data from four, double-blind, placebo-controlled studies randomizing 3,073 moderate asthmatic adults to montelukast, beclomethasone, or placebo. End points included asthma control days, FEV1, ß-agonist use and nocturnal awakening. Body mass index (BMI) classifications included normal, overweight, obese and continuous variables. Results indicate that the placebo response for all end points was generally lower with increasing BMI. Similarly, the response to the inhaled corticosteroid (ICS) decreased whereas the response to leukotriene antagonist remained stable. Editor's comment: Obesity may not only be a risk factor for asthma, particularly in women, but may also decrease response to ICS. Peters-Golden M, et al. Eur Respir J 2006; 27: 495.
10. PREVENTION OF OSTEOPOROSIS ASSOCIATED WITH CHRONIC GLUCOCORTICOID THERAPY
An article from the Archives of Dermatology is reviewed in the Journal of the American Medical Association. It outlines treatment options and current recommendations for dermatologists treating patients with systemic glucocorticosteroids. Editor's comment: What is good for the dermatologist is good for the allergist. Summey BT, Yosipovitch G. Arch Dermatol 2006; 142: 82. Commentary by: Heffernan MP, et al. JAMA 2006; 295: 1300.
11. ANAPHYLAXIS AND THE AMERICAN ACADEMY OF ALLERGY, ASTHMA, AND IMMUNOLOGY (AAAAI)
This wonderful review of the pioneers and milestones of anaphylaxis and remarkable accounting of the contributions that allergists/immunologists, throughout the world, have made to the understanding of the pathogenesis and treatment of anaphylaxis appears in JACI. Editor's comment: Allergists should be proud of their contributions to the understanding and treatment of this disease. Lieberman, PL, et al. J Allergy Clin Immunol 2006; 117: 478. No abstract is available for this article.
12. CONTINUING MEDICAL EDUCATION (CME) MINI-PRIMER ON ALLERGIC AND IMMUNOLOGIC DISEASES
This mini-primer contains chapters on: Overview of the Human Immune Response; Update on Primary Immunodeficiency Disease; Cytokines and Chemokines; Autoimmunity, Vasculitis, and Autoantibodies; IgE, Mast Cells, Basophils, and Eosinophils; Asthma: Factors Underlying Inception, Exacerbation, and Disease Progression; Control of Allergic Airway Inflammation Through Immunomodulation; Drug Allergy; Food Allergy; and Atopic Dermatitis. Credit can be obtained for 10 CME hours. Editor's comment: Must reading for CME and for physicians in training. Shearer WT, Leung D (eds). J Allergy Clin Immunol 2006; 117: S429. No abstract is available for this article.
13. ALLERGEN CHALLENGE CHAMBERS
A supplement on "The Role of Allergen Challenge Chambers in the Evaluation of Anti-Allergic Medication: An International Consensus Paper." It provides an in-depth review of the role of allergen challenge chambers as a means to evaluate treatments for rhinitis. Editor's comment: Interesting reading on a complicated but very scientific subject. Day JH, et al. Clin and Exp Allergy Rev 2006; 6: 31.
14. CONSULTATION AND REFERRAL GUIDELINES CITING THE EVIDENCE: HOW THE ALLERGIST/IMMUNOLOGIST CAN HELP
This is a 28 page document on how the allergist/immunologist can help in the diagnosis and treatment of ABPA; Anaphylaxis; Asthma Diagnosis; Asthma: Environmental Diagnosis and Management; Asthma Treatment: Immunotherapy; Asthma Treatment: Prevention of Morbidity; Asthma Treatment: Prevention of Mortality; Asthma Treatment: Adherence; Occupational Asthma; Conjunctivitis; Cough; Atopic Dermatitis; Contact Dermatitis; Drug Allergy; Food Allergy; Hypersensitivity Pneumonitis; Insect Hypersensitivity; Occupational Allergic Diseases; Rhinitis; Sinusitis; Urticaria and Angioedema. Editor's comment: Allergy is a small specialty. This supplement defines how the allergist/immunologist should be involved in the diagnosis and treatment of these diseases. Leung D, Schatz M (eds). J Allergy Clin Immunol 2006; 117: S495. No abstract is available for this article.
