August 2005 World Medical Journal Review
Reviewed by Richard F. Lockey, M.D., Editor-In-Chief
1. HOUSE DUST MITE FACILITATES OVALBUMIN-SPECIFIC ALLERGIC SENSITIZATION AND AIRWAY INFLAMMATION.
This mouse study demonstrates that house dust mite extract augments ovalbumin-specific (OVA) allergic sensitization. Balb/c mice were exposed to daily house dust mite extract (HDM) intranasally followed immediately by exposure to aerosolized OVA for five weeks. Eight weeks later, they were re-challenged with OVA for three consecutive days. A robust eosinophilic inflammatory response in the lung was associated with an increase in bronchial hyperreactivity. Significant elevated serum levels of OVA-specific IgE and IgG and increased production of Th2 cytokines (IL-4, IL-5, IL-13) by splenocytes stimulated in vitro with OVA were observed. House dust mite extract induces a lung mico-environment that fosters development of allergic sensitization. Editor's comment: House dust mite debris may facilitate the sensitization process to different aero-allergens. Fattouh R, et al. Am J Respir Crit care Med 2005; 172: 314.
2. REACTIVE OXYGEN SPECIES (ROS) GENERATED BY POLLEN AUGMENT ANTIGEN-INDUCED ALLERGIC AIRWAY INFLAMMATION.
These investigators demonstrated in mice that pollen grains and their extracts contain intrinsic NADPH oxidases. The pollen NADPH oxidases rapidly increase the levels of ROS in lung epithelium as well as the amount of oxidized glutathione (GSSG) and 4-hydroxynonenal (4-HNE) in airway-lining fluid. These oxidases, and products of oxidative stress, induce neutrophil recruitment to the airways. Removal of pollen NADPH oxidase activity from the challenge material reduces antigen-induced allergic airway inflammation, the number of mucin-containing cells in airway epithelium, and antigen-specific IgE levels in sensitized mice. Amb a 1, which does not posses NADPH oxidase activity, induces low-grade inflammation. The addition of GSSG or 4-HNE to Amb a 1 challenge material boosts allergic airway inflammation. The authors propose that oxidative stress generated by pollen NADPH oxidases (single 1) augments allergic airway inflammation induced by pollen antigen (single 2). Editor's comment: Pollen and house dust mites both may augment the adaptive immune responses (increase specific IgE) to both intrinsic as well as extrinsic allergens. Boldogh I, et al. J Clin Invest 2005; 115: 2169.
3. STOP AND GO TRAFFIC WORSEN CHILDHOOD ASTHMA.
Infants living near stop and go bus and truck traffic had significantly higher rates of wheezing as demonstrated in the Cincinnati childhood allergy and air pollution study. Factors that increase the risk suggest that the type of traffic and the distance from it, not just the volume, are associated with wheezing. Those within 100 m of “stop and go traffic” wheeze twice as often as those within 400 m and more than three times as often than infants living in unexposed areas. African Americans experience the highest rates at 25%. Editor's comment: Both man made and naturally occurring pollutants are important factors causing asthma. Ryan PH, et al. J Allergy Clin Immunol 2005; 116: 279.
4. PREVALENCES OF POSITIVE SKIN TEST RESPONSES TO 10 COMMON ALLERGENS IN THE US POPULATION.
The 3rd National Health and Nutrition Examination Survey (NHANES III) was conducted from 1988 to 1994 and demonstrates that 54% of the USA population, aged 6 to 59 years, had a positive prick-puncture skin test to at least one of ten common allergens. Individuals who have a positive skin test reacted to an average of 3 to 5 allergens, most commonly to dust mites, perennial rye grass, short ragweed and German cockroach, and least commonly to peanut. The prevalence of a positive skin test response was higher in NHANES III than in the NHANES II study, the latter conducted from 1976-1980. Editor's comment: Is the prevalence of allergy increasing in the United States? Most probably. Arbes SJ, et al. J Allergy Clin Immunol 2005; 116: 377.
5. DEVELOPMENTAL OUTCOMES AFTER EARLY OR DELAYED INSERTION OF TYMPANOSTOMY TUBES
Four-hundred and twenty-nine children with persistent middle-ear effusion were randomly assigned to have tympanostomy tubes inserted either promptly or up to nine months later if effusion persisted. A developmental outcome in 395 of these children was assessed at six years of age. There were no significant differences in mean scores in any of the 30 assessed measures. In these otherwise healthy young children, less than three years of age with persistent middle-ear effusion, prompt insertion of tympanostomy tubes does not improve developmental outcomes at six years of age. Editor's comment: Middle-ear effusions in children less than 3 years of age should be managed conservatively. Paradise JL, et al. N Engl J Med 2005; 353: 576.
6. ALENDRONATE & PARATHYROID HORMONE THERAPY FOR OSTEOPOROSIS
One-hundred and twenty-six women with osteoporosis who had been taking alendronate for at least one year were randomly reassigned to continue: (a) alendronate by mouth plus parathyroid hormone (1-34) SC daily, (b) alendronate plus parathyroid hormone (1-34) SC for three 3-months cycles alternating with 3-month periods without parathyroid hormone, or (c) alendronate alone for 15 months. In both parathyroid hormone groups, bone formation indexes rose swiftly. In another study, the question was posed as to whether antiresorptive therapy is required to maintain gains in bone mineral density after one year of therapy with parathyroid hormone (1-84). Of the 119 subjects, densitometer gains are maintained or increased with alendronate but lost if parathyroid hormone is not followed by antiresorptive therapy. Editor's comment: Advances in understanding osteoporosis and its treatment are welcome. 1) Cosman F, et al. N Engl J Med 2005; 353: 566. 2) Black DM, et al. N Engl J Med 2005; 353: 555. 3) Editorial by Heaney RP, Recker RR, accompanies these two reports. N Engl J Med 2005; 353: 624.
7. COMPARISON OF TIOTROPIUM ONCE DAILY, FORMOTEROL TWICE DAILY OR BOTH IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Seventy-one COPD patients were randomized in a double-blind, three-way, crossover study to receive tiotropium 18 µg q.d., formoterol 12 µg b.i.d or both for three 6-week periods. Tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs was most effective and provided an additive effect throughout the 24-h dosing interval. Editor's comment: Patients with COPD benefit from combined tiotropium bromide and formoterol. van Noord JA, et al. Eur Respir J 2005; 26: 214.
8. ECHINACEA FOR THE COMMON COLD.
Four hundred and thirty seven volunteers were randomly assigned to receive one of three preparations of Echinacea angustifolia extract or placebo either seven days before challenge or beginning at the time of rhinovirus type 39 challenge. Of these, 399 were challenged with the virus and observed in a sequestered setting for five days. None of the extracts or placebo had clinically significant effects on the infection or the illness that resulted. Editor's comment: The burden of proof for any treatment lies with those who advocate it. Turner RB, et al. N Engl J Med 2005; 353: (4) 341. 341.
9. INTERLEUKIN-10 GENE EXPRESSION IN ACUTE VIRUS-INDUCED ASTHMA.
Virus-induced asthma is characterized by marked neutrophil influx and eosinophil degranulation, an immunopathogenesis different from that of allergen-induced asthma. Induced sputum cytokine responses were evaluated in severe acute asthma exacerbation associated with URIs, patients with stable asthma, healthy controls, and virus-infected nonasthmatic subjects. Viruses detected in the subject with acute asthma include rhinovirus (83%), influenza virus (15%), enterovirus (4%) and respiratory syncytial virus (2%). Acute asthma exacerbation from a respiratory viral infection is characterized by increased IL-10 gene expression; this could explain the suppressed eosinophil influx. Airway neutrophilia due to respiratory virus in acute asthma or no asthma is associated with chemokine gene expression involving RANTES and macrophage inflammatory protein-1 a. Editor's comment: The pathogenesis of viral-induced asthma is different than allergen-induced asthma. Grissell TV et al. Am J Respir Crit Care Med 2005; 172: 433.
10. HISTAMINE RELEASING FACTORS ARE PRESENT IN SERA OF NON-ALLERGIC ASTHMATICS.
Twenty-four subjects with non-allergic asthma had in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assays with autologous basophils and basophils from normal donors. ASST was positive in 14/24 non-allergic asthmatics (58%) and negative in all control subjects. The serum of one of twelve of these ASST-positive asthmatics induced in vitro histamine release from autologous basophils. Serum from another induced histamine release from membrane IgE-stripped autologous basophils. No sera from either study or control subjects provoked significant histamine release from basophils from three normal donors. Circulating histamine-releasing factors could contribute to the initiation/maintenance of inflammation in airways of non-allergic asthmatics. However, functional in vitro antibodies (anti-FceRI and anti-IgE) are difficult to demonstrate. Editor's comment: Perhaps non-allergic asthma is triggered and maintained by an autoimmune response. Tedeschi A, et al. Clin Exp Allergy 2005; 35: 849.
11. OCCUPATIONAL ASTHMA
Occupational agents have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes: (1) immunologic occupational asthma (OA), (2) nonimmunologic OA, and (3) work–aggravated asthma. Removal of the worker and treatment with inhaled glucocorticoids is the treatment of choice. Editor's comment: This is an excellent review article on a subject of importance for all patients with asthma. Mapp CE, et al. Am J Respir Crit Care Med 2005; 172: 280.
12. ADHERENCE TO OR COMPLIANCE WITH MEDICATION REGIMEN
This review in the New England Journal of Medicine outlines the reasons why individuals are not compliant in adhering to a medication regimen. Adherence is directly related to frequency of doses. Compliance decreases from 80% for once daily administration to 50% for a qid regimen. There are major predictors for poor compliance, barriers to adherence, and strategies to improve adherence to medication regimens included in the article. Editor's comment: This is a wonderful review article and a major reason why patients fail therapy. Osterberg L, et al. N Engl J Med 2005; 353: 487.
13. REVIEW ARTICLE ON ACUTE SERIOUS AND FATAL REACTIONS TO CONTRAST MEDIA.
This article reviews the serious or fatal reactions to contrast medium (CM). They are unpredictable and rare. A history of a serious reaction to CM, bronchial asthma or multiple allergies appears to increase the incidence of a serious reaction by a factor of 5. The exact ideology of these reactions remains unknown. Editor's comment: An excellent review article. Morcos SK, Br J Radiol 2005; 78: 686.
14. A TREATISE ON "ALLERGIC RHINITIS, ARIA GUIDELINES AND ANTIHISTAMINES: STATE OF THE ART".
This treatise reviews the pharmacotherapy of antihistamines; the association between atopy and the clinical expression of allergic disease: one airway one disease; the anti-inflammatory properties of antihistamines; pharmacological interventions and outcomes; quality of life questions; epidemiology and economics of allergy treatment; and the role of antihistamines to treat allergic diseases. Editor's comment: This is very worth-while reading. van Cauwenberge P (ed), Clin Exp All Rev 2005; 5: 1.
