June 2005 Medical Journal Review
Reviewed by Richard F. Lockey, M.D., Editor-In-Chief
1. ENDOGENOUS BRONCHODILATOR PROTECTS AGAINST EXPERIMENTAL ASTHMA.
S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthma airways, suggesting a protective role. In this experiment, wild-type mice, which exhibit airway hyperresponsivity following allergen challenge, have increased airway levels of the enzyme GSNO reductase and are thereby depleted of lung S-nitrosothiols (SNOS), endogenous bronchodilators. In contrast, mice with a genetic deletion of GSNO reductase exhibit increases in lung SNOS and are protected from airway hyperresponsivity indicating that endogenous SNOS, governed by GSNO reductase, are critical regulators of airway responsiveness. Editor's comment: SNO homeostasis may contribute to the asthma phenotype and provide for novel therapeutic strategies to alleviate airway obstruction. Que LG et al. Sciencexpress/www.sciencexpress.org/26 May 2005/Page 1/10.1126/science.1108228
2. DIAGNOSIS OF PEANUT ALLERGY WITH SKIN PRICK AND SPECIFIC IgE TESTING.
Food allergy occurs commonly in children, with 8% of infants being allergic to common foods. A clinical history of food allergy is accurate about 50% of the time, and the only way to reliably diagnose food allergy is by an oral double-blind food challenge. These authors examined 157 children with a history suggestive of peanut allergy. All children underwent skin prick as well as ELISA tests for specific IgE, and an oral food challenge to peanut. A wheal measurement of 8mm or greater had a 95% predictive value whereas in vitro specific IgE had a 92% predictive value (when specific IgE was 15 kUA/L or greater) for a positive (usually open and not double-blind) oral challenge. Editor's comment: This paper demonstrates that a skin prick test and/or specific IgE can accurately predict true peanut allergy. Roberts G, et al. J Allergy Clin Immunol 2005; 115: 1291.
3. HIGH DOSE INHALED FLUTICASONE MORE EFFECTIVE THAN INTRAVENOUS HYDROCORTISONE TO TREAT ACUTE ASTHMA IN ADULTS.
The efficacy of fluticasone (3,000 µg per hour) administered through a metered-dose inhaler and spacer at 10-minute intervals for 3 hours or 500 mg of intravenous hydrocortisone were compared for efficacy in 106 patients in a double-blind randomized manner (mean age, 33.5 +/- 8.8 years) as a standard treatment for adult patients with severe acute asthma. Fluticasone showed 30.5% and 46.4% greater improvements in PEF and FEV1, respectively, compared with hydrocortisone. Fluticasone worked earlier and resulted in a more rapid discharge from the emergency department. The therapeutic benefit was primarily seen in those with the most severe obstruction. Editor's comment: This paper demonstrates that high dose inhaled fluticasone is an effective treatment for acute severe asthma. Rodrigo GJ, Am J Respir Crit Care Med 2005: 171: 1231.
4. NITRIC OXIDE MAY BE BENEFICIAL TO GUIDE ASTHMA TREATMENT.
Ninety-seven patients with asthma, regularly receiving inhaled glucocorticosteroids (IC), had their dose adjusted in a stepwise fashion either on the basis of exhaled nitric oxide (FENO) measurements or an algorithm based on conventional guidelines. The final mean dose of fluticasone was statistically lower in the FENO group than in the control group. A similar study in 40 children reported that exhaled nitric oxide (eNO) and sputum eosinophilia both were predictive of success or failure to reduce IC. Editor's comment: Inhaled nitric oxide measurements (as well as sputum eosinophilia, which is more difficult to obtain) may permit and predict effective reductions in IC. Smith AD, et al. N Engl J Med and Zacharasiewicz A, et at. Am J Respir Crit Care Med 2005; 171: 1077.
5. HYPERSENSITIVITY REACTIONS TO GENERAL ANESTHESIA IN 68 CHILDREN ARE PRIMARILY SECONDARY TO NEUROMUSCULAR BLOCKING AGENTS (NMBA).
Hypersensitivity reactions during general anesthesia were assessed in 68 children between 1989 and 2001. IgE-mediated anaphylaxis was diagnosed in most children, 31 from NMBA, 14 from latex, 7 from colloids, 5 from opioids, and 6 from hypnotics. Vecuronium was the NMBA causing the largest number of reactions. All were confirmed by IgE skin testing. Editor's comment: Anaphylaxis during anesthesia in children is primarily IgE-mediated and most commonly secondary to neuromuscular blocking agents. Karila C, et al. Allergy 2005; 60: 828.
6. ACCELERATED INTESTINAL EPITHELIAL CELL TURNOVER: A NEW MECHANISM OF PARASITE EXPULSION.
These researchers show that the intestinal epithelial barrier forms a major defense against invading pathogens, including gastrointestinal-dwelling nematodes. They show an increased rate of epithelial cell turnover in this TH-2 mediated disease. The epithelial cell turnover in the large intestine acts like an "epithelial escalator" to expel Trichuris and is controlled by the cytokine, interleukin 13, and the chemokine, CXCL 10. The TH-2 helper immune response expels parasites; conversely, mice that generate a TH1 immune response are highly susceptible and maintain infection to chronicity. Editor's comment: Perhaps the epithelial shedding that occurs in asthma is a "normal" immunologic response whereby the host mistakes allergens (e.g., mites and cockroaches) for parasites. Cliffe LJ, et al. Science 2005; 308: 1463
7. INTRALESIONAL IMMUNOTHERAPY WITH MUMPS, CANDIDA, AND TRICHOPHYTON SKIN TEST ANTIGENS IS EFFECTIVE THERAPY FOR WARTS.
Two-hundred and thirty-three patients clinically diagnosed with having one or more warts were treated in a randomized single-blind, controlled trial with intralesional immunotherapy using Mumps, Candida, and Trichophyton skin test antigens. The results were statistically significant (p<.001) with treatment vs. control. Resolution of distant untreated warts was observed. Editor's comment: Intralesional immunotherapy with Candida, Mumps or Trichophyton skin test antigens stimulates a cell mediated immune response causing wart resolution. Perhaps these same non-specific alterations in cell-immunity are an important reason why allergen immunotherapy is an effective treatment for allergic diseases and allergic asthma. Horn TD, et al. Arch Dermatol. 2005; 141: 589
8. PANDEMIC OF AVIAN FLU? ARE WE READY?
A review on potential world-wide dangers of a human pandemic caused by avian flu. There are several steps that countries can take to decrease the likelihood of this pandemic. The question is, are they being done? This article outlines the necessary steps to prevent this potential disaster. Editor's comment: "A stitch in time saves nine" is certainly applicable for this potentially very dangerous virus. Nature 2005; May 26, pp: 399-409, 415-424.
9. REVIEW OF THE SCIENCE OF AUTOIMMUNITY.
NatureInsight has a review section on autoimmunity. Subjects include: "Paths to understanding the genetic basis of autoimmune disease; Cellular and genetic mechanisms of self tolerance and autoimmunity; Regulation of immunity by self-reactive T cells; An array of possibilities for the study of autoimmunity; Design of effective immunotherapy for human autoimmunity; and Treatment of severe autoimmune disease by stem-cell transplantation". Editor's comment: Physicians with interest in autoimmunity should review this manuscript. www.nature.com/Nature 2005; 435: issue #7042/2 June.
10. SUMMARY OF THE ASTHMA PREVENTION MANAGEMENT GUIDELINES FROM JAPAN.
International Archives of Allergy and Immunology has published the "Asthma Prevention and Management Guidelines 2003, Japan (JGL 2003): English Summary". The guidelines cover: definitions, epidemiology, and pharmacologic therapy to control asthma. Editor's comment: A very informative outline, in particular, of asthma management. Makino S, et al (eds). Int Arch Allergy Immunol 2005; 136: (suppl 1), pp 1-49.
11. EXCELLENT REVIEW OF EOSINOPHILS AND THEIR ROLE IN ALLERGY AND RELATED DISEASES.
An excellent review appears in the International Archives of Allergy and Immunology entitled, "Eosinophils in Allergy and Related Diseases". Presentations are from Japan and Korea. Editor's comment: Excellent summary of primary research about eosinophils and their role in the pathogenesis of allergic diseases. Makino S et al (eds), Int Arch Allergy Immunol 2005; 137(suppl 1):1-82.
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