June 2006 World Medical Journal Review
Reviewed by Mark C. Glaum, M.D., Ph.D., WAO Guest Editor
1. ACID SUPPRESSION IMPROVES BREATHING FUNCTION IN PERSISTENT ASTHMATICS WITH GASTROESOPHAGEAL REFLUX (GERD) AND NOCTURNAL SYMPTOMS
Subjects with moderate to severe persistent asthma (n=770) were randomized to receive esomeprazole 40mg twice daily or placebo. Subjects were stratified into 3 groups: GERD with nocturnal symptoms; GERD without nocturnal symptoms; and nocturnal symptoms without GERD. In subjects with GERD and nocturnal symptoms, the esomeprazole-treated group showed improved morning (p = 0.03) and evening (p = 0.012) peak expiratory flows as compared to placebo. No improvement was observed in subjects without both GERD and nocturnal symptoms. Editor's comment: Treatment of gastroesophageal reflux is an important component of asthma management in certain patients. Kiljander TO, Harding SM, Field SK, et al. Am J Respir Crit Care Med 2006; 173: 1091-97
2. CONTACT HYPERSENSITIVITY IS MEDIATED BY NATURAL KILLER (NK) CELLS IN THE ABSENCE OF T AND B LYMPHOCYTES
Contact hypersensitivity is considered to be a T cell-mediated prototypical type IV Gel and Coombs reaction to haptens. Unexpectedly, in mice devoid of T and B lymphocytes, a model of contact dermatitis was found to be inducible with 2,4-dinitrofluorobenzene and oxazolone. If mice were depleted of all lymphocytes (including NK cells), contact hypersensitivity could not be induced. Specific contact hypersensitivity could be reconstituted in such mice after adoptive transfer of NK cells from NK-competent, sensitized donors. Editor's comment: NK cells are previously unrecognized mediators of hapten-specific immunity. Please also see excellent accompanying editorials. O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH. Nat Immunol 2006; 7(5): 507-16, Yokoyama WM; 437-9, Parham P. Nature 2006; 441(25): 415-16. No abstract is available.
3. NOVEL BETA-2 RECEPTOR (B2) POLYMORPHISM IS ASSOCIATED WITH ASTHMA SEVERITY IN AFRICAN AMERICANS
Of 2,032 subjects recruited for a multicenter randomized, placebo-controlled, crossover safety study evaluating an inactivated influenza vaccine in patients with asthma, 517 patients consented to participate in a genetic sub-study to evaluate the association of particular B2 polymorphisms with asthma exacerbation rates and symptoms. Forty percent of African American asthmatics homozygous for a C523 allele experienced an asthma exacerbation in a two-week period following placebo vaccine injection as compared to 29% in heterozygotes (p = 0.018). Editor's comment: Further studies are warranted to evaluate associations between B2 variants and asthma phenotypes, particularly in minority populations. Lima, JJ, Holbrook, JT, Wang J, et al. Asthma 2006; 43:185-9
4. SUBACUTE COUGH: IS IT A SEPARATE ENTITY?
One hundred eighty-four subjects diagnosed with subacute (lasting 3-8 weeks) cough were enrolled and treated prospectively using a clinical algorithm. Patients exhibiting clinical signs or symptoms of post-nasal drip or post-infectious cough were treated empirically with antihistamine/decongestant combination for 3 weeks. If no clinical improvement was noted, subjects were evaluated for airway hyperreactivity and, if sensitive, treated with inhaled corticosteroids. Of 184 subjects, 48% were found to have post-infectious cough, 33% had postnasal drip and only 16% had cough variant asthma that improved with inhaled corticosteroids. Editor's comment: Cough lasting 3-8 weeks is frequently post-infectious and self-limited. Kwon N, Oh M, Min T, et al. Chest 2006;129: 1142-7
5. DEFICIENCY OF IgA AND IgG2 CORRELATES WITH ASTHMA SYMPTOMS AND LUNG FUNCTION
Severe and mild asthmatic adults (n= 31, ages 23-50) and 15 adult control patients were recruited to evaluate any association of low immunoglobulins with asthma symptoms, lung function and cellular markers of inflammation by endoscopic bronchial biopsy. Levels of IgG (p = 0.02) and IgA (p=0.006) were lower in severe asthmatics as compared to control subjects. Only low levels of IgA correlated with asthma symptoms and lung function (p<0.009), while levels of IgA and IgG positively correlated with numbers of tissue mast cells. Editor's comment: Alteration in levels of antibody production may be a marker of severe asthma phenotypes. Balzar S, Strand M, Nakano T, Wenzel SE. Int Arch Allergy Immunol 2006; 140:96-102
6. SPECIFIC SPUTUM INFLAMMATORY MARKERS CORRELATE WITH LUNG FUNCTION IN CYSTIC FIBROSIS BUT NOT CHRONIC BRONCHITIS
Expectorated sputum samples were obtained from 15 subjects with ATS-defined chronic bronchitis and 16 subjects with cystic fibrosis (CF) confirmed by sweat chloride test. Spirometry was performed at time of sputum collection and again at a later time point. Sputum samples were analyzed for presence of IL-8, myeloperoxidase (MPO) and DNA content. Cough transportability (CTR) of sputum (measure of adhesiveness) was also evaluated by in vitro methods. In subjects with CF, sputum concentrations of IL-8 and MPO were inversely correlated with FEV1 (p=0.003), while IL-8 and DNA concentrations were inversely correlated with CTR (p<0.05). No correlation was observed in subjects with chronic bronchitis. Editor's comment: Sputum concentrations of IL-8, MPO and DNA may serve as markers of airway obstruction in CF. Kim J, Okamoto K, Rubin BK. Chest 2006;129: 1148-54
7. POSITIVE ASSOCIATION BETWEEN AIR PARTICULATE LEVELS AND AIRWAY INFLAMMATION IN ASTHMATIC CHILDREN
Children with moderate to severe persistent asthma (n = 73) were followed prospectively over a two-year period. Daily concentrations of ambient fine particulates, daily use of bronchodilators, and levels of urinary leukotrienes were measured. Exposure to increased ambient particulates during the morning commute to school was associated with a 3.8% increase in bronchodilator use at school (p = 0.04). Stronger associations were noted in children with more severe asthma. Maximum morning particulate levels correlated with an average 6.2% increase in urinary leukotriene E 4 levels measured during school hours (p = 0.006) but not when levels were averaged over 24 hours. Editor's note: Exposure to ambient particulates may worsen airway inflammation and asthma symptoms in predisposed children. Also, see excellent accompanying editorial. Rabinovitch N, Strand M, Gelfand EW Am J Respir Crit Care Med 2006; 173:1098-1105, Delfino RJ, 173:1054-5
8. PINE DUST EXPOSURE MAY PREDISPOSE TO ATOPY AND DECREASED LUNG FUNCTION
New Zealand sawmill workers with (n = 59) and without (n = 167) asthma symptoms assessed by questionnaire were evaluated for personal inhaled dust exposure, percutaneous allergen skin test reactivity and pre/post work shift spirometry. High exposure to “green” pine dust (from fresh cut timbers) was associated with sensitization to >3 outdoor pollens (OR 3.1, p<0.05), while high exposure to "green" and "dry" (from kiln-dried timers) dust was associated with reductions in FEV1 and PEF. Editor's comment: Exposure to certain particulates may modulate allergen sensitization and airway function. Douwes J, McLean D, Slater T, et al. Eur Respir J 2006; May 17 (doi: 10.1183/09031936.06.00120305)
9. TASK FORCE REPORT ON SUBLINGUAL IMMUNOTHERAPY (SLIT)
This combined AAAAI/ACAAI task force report is a comprehensive review of the current evidence that supports the dosing, effectiveness and safety of sublingual immunotherapy. Other areas reviewed in this report include: the immunologic response to SLIT; changes in end organ inflammation; potential mechanisms and economics. Editor's comment: This report discusses the current literature regarding sublingual administration of immunotherapy and provides suggestions of where further studies are needed. Cox LS, Linnemann DL, Nolte H, et.al. J Allergy Clin Immunol 2006;117: 1021-35
10. Review of Testing and Treatment in Hereditary Angioedema
This review focuses on the current status of genetic testing for hereditary angioedema, however, it also provides a concise review of mechanisms, evaluation and treatment of the disease. There are several useful algorithms and charts that clearly summarize the classification of hereditary and acquired angioedema, as well as laboratory evaluation, treatment and surgical prophylaxis for patients with this problem. Editor's comment: This review summarizes evaluation and treatment of hereditary and acquired angioedema in a clear, accessible format. Weiler CR, Van Dellen RG. Mayo Clin Proc 2006; 81(7): 958-72
