Medical Journal Review
Posted: October 2008
Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, and Guest Editor Mark Glaum, MD PhD
1. INHALED CORTICOSTEROID USE IS ASSOCIATED WITH DECREASED CARDIOVASCULAR AND ALL-CAUSE MORTALITY IN ASTHMATIC WOMEN
Inhaled corticosteroid (ICS) use decreases the risk of asthma exacerbations and may decrease all-cause mortality. In the 1970's the Nurses' Health Study (NHS) enrolled 121,700 registered nurses aged 33-55 years. In 1998, asthmatic participants from NHS were sent supplementary questionnaires on asthma diagnosis and ICS use. Mortality was assessed through 2003 and odds ratios (ORs) for death were adjusted for age, asthma severity, smoking, heart disease, cancer, stroke, aspirin and statin use. Of 2671 eligible women who responded to the 1998 survey, 2270 (85%) met criteria for persistent asthma and 1442 (54%) reported ICS use. Compared to asthmatic women who did not use ICS, those receiving ICS therapy had lower risk for all-cause mortality (OR, 0.58; 95% confidence interval [CI], 0.36-0.92) and cardiovascular death (OR, 0.35; 95% CI, 0.13-0.93) but not death from cancer (OR, 0.66; 95% CI, 0.32-1.38) or other causes (OR, 0.62; 95% CI, 0.30-1.27). Editor's comment: ICS may exert anti-inflammatory benefits beyond the airway. Camargo CA, Barr RG, Chen R, Speizer FE. Chest 2008; 134: 546-51.
2. SERIAL RHINOVIRUS INFECTIONS IN INFANTS WITH RECURRENT RESPIRATORY ILLNESSES
Acute viral infections are a major cause of respiratory morbidity and asthma exacerbations in infants and young children. This study examines the viral etiology of respiratory illnesses in a subgroup of infants from the Childhood Origins of ASThma (COAST) study, a prospective birth cohort of 300 newborns at increased risk of developing asthma based on family history. Attention was focused on infants who were frequently ill (27 infants out of 285), with five or more moderate-to-severe respiratory illnesses (MSIs) during the first year of life. In frequently ill infants, rhinoviruses were most commonly detected in nasal washes (detected in 61% of cases of moderate-to-severe respiratory illnesses and in 43% of mild illnesses). Rhinovirus infections occurred early in life, with the mean age of four months at first infection. Extended viral syndromes were usually caused by sequential infections with distinct rhinovirus strains, as opposed to a protracted infection with a single strain. Editor's comment: Human rhinovirus infection occurs early, pervasively and repetitively in infants with increased risk for asthma. Jartti J, Lee W-M, Pappas T, et al. Eur Respir J 2008; 32: 314-20.
3. BACTERIAL INFECTIONS IN HUMANS WITH MyD88 DEFECTS
MyD88 is an essential adapter molecule for many Toll-like receptors (TLR) that provides pivotal protection in innate immune defense. This report describes a series of nine children with autorecessive MyD88 deficiency who suffered from life-threatening recurrent pyogenic bacterial infections. While subjects were susceptible to infection with organisms such as Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa, they were otherwise healthy with normal resistance to most common bacteria, viruses, fungi and parasites. Susceptibility to bacterial infections tended to improve with age. Editor's comment: MyD88-dependent TLRs provide important but redundant protection against certain pyogenic bacteria. Von Bernuth H, Picard C, Jin Z, et al. Science 2008; 321: 691-6.
4. NONATOPIC CHILDREN WITH MULTITRIGGER WHEEZING HAVE AIRWAY PATHOLOGY COMPARABLE TO ATOPIC ASTHMA
Epidemiologic studies suggest that wheezing in children with infections is transient, while wheezing in atopic children persists into adolescence. This study examined differences in histopathology of airway biopsies from children with atopic and non-atopic asthma. Bronchial biopsies were obtained from 18 non-atopic asthmatic children, 20 atopic asthmatics and 17 non-asthmatic controls. There were no differences in biopsy specimens between atopic and non-atopic asthmatics in regard to epithelial cell loss, basement membrane thickening, angiogenesis, or number of IL-4 and IL-5 positive cells in the subepithelium. Editor's comment: When subjective symptoms of asthma occur in non-atopic children, the airway pathology is still typical of allergic asthma. Turato G, Barbato A, Barlado S, et al. Am J Respir Crit Care Med 2008; 178:476-82. Please see related editorial: Am J Respir Crit Care Med 2008; 178:437.
5. AVIAN IGY BINDS TO A MONOCYTE RECEPTOR WITH IGG-LIKE KINETICS DESPITE AN IGE-LIKE STRUCTURE
IgY is an immunoglobulin produced by birds, reptiles and amphibians that is structurally similar to IgE and is thought to protect against parasitic infections. This study finds that binding characteristics of IgY to its receptor are much weaker those of human IgE despite highly homologous structural motifs. Determining reasons for this discrepancy may provide new therapeutic strategies for blocking IgE binding. Editor's comment: Binding affinity of IgE to its receptor may be an attractive therapeutic target for allergic diseases. Taylor AI, Gould HJ, Calvert RA. J Biol Chem 2008; 24: 16384-90. Please see related editorial: Nature Medicine 2008; 14: 797.
6. DIFFERENTIATION OF HUMAN TH17 CELLS FROM NAÏVE T CELLS
TH17 cells are a subset of interleukin (IL)-17-producing T helper cells thought to contribute to the pathogenesis of a number of human autoimmune diseases. This study examines cytokines required for the production of IL-17A by memory and naive human CD4 T cells. The data demonstrate that transforming growth factor-beta (TGF-β) and IL-21, through the induction of the transcription factor RORC2, are critical for the differentiation of TH17 cells from highly purified naive (but not memory) CD4+ T cells. Editor's comment: This study helps further delineate human TH17 inflammatory responses associated with infection and autoimmune diseases. Yang L, Anderson D, Baecher-Allan C, et al. Nature 2008;454: 350-2.
7. HEREDITARY ANGIOEDEMA
Hereditary angioedema (HA) is an autosomal dominant condition caused by deficiency of functional C1 inhibitor. HA is characterized by recurrent episodes of nonpruritic, nonpitting, subcutaneous or submucosal edema involving the face, tongue, larynx, extremities, trunk, or viscera. This report is an excellent case presentation and review of clinical features, laboratory evaluation and treatment of this unusual but clinically challenging condition. Editor's comment: Outstanding updated review of hereditary angioedema. Zuraw BL. N Engl J Med 2008; 359: 1027-36.
8. ROLE OF BISPHOSPHONATES IN CLINICAL PRACTICE
This excellent review outlines the mechanism of action and appropriate clinical use of bisphosphonates in osteoporosis. Potential complications of bisphosphonate use and the roles of calcium and vitamin D supplementation are discussed. Editor's comment: Persistent asthmatics are at increased risk for side effects from high-dose inhalational and systemic corticosteroids. Asthma specialists should be familiar with appropriate use of bisphosphonates. Drake MT, Clark BL, Khosla S. Mayo Clin Proc 2008: 83:1032-45.
9. PRACTICE PARAMETER: DIAGNOSIS AND MANAGEMENT OF RHINITIS
This supplement to the Journal of Allergy and Clinical Immunology provides graded quality of evidence recommendations for the diagnosis and management of rhinitis. Editor's comment: A must-read for anyone who treats patients with chronic nasal symptoms. Wallace DV, Dykewicz MS, et al. J Allergy Clin Immunol 2008: 122 (suppl 1):1-84