September 2006 World Medical Journal Review
Reviewed by Richard F. Lockey, M.D., Editor-In-Chief
1. ANTI-INFLAMMATORY ACTIVITY OF IMMUNOGLOBULIN G (IgG) RESULTING FROM Fc SIALYLATION
IgG is both pro- and anti-inflammatory via engagement of its Fc fragment (Fc) with distinct Fcγ receptors (FcγRs). Some Fc-FcγR interactions generate pro-inflammatory effects of immune complexes and cytotoxic antibodies, however, in contrast, therapeutic IVIG and its Fc fragments are anti-inflammatory. These authors demonstrate that IgG acquires anti-inflammatory properties upon Fc sialylation, which is reduced upon the induction of an antigen-specific immune response. This differential sialylation may provide a switch from innate anti-inflammatory activity in the steady state to generating adaptive pro-inflammatory effects upon antigenic challenge. This study suggests that another type of difference between antibody molecules, determined by sequences of attached oligosaccharides, may be crucial for antibody function. Editor’s comment: The sugar moieties attached to the Fc fragment of IgG alter its activity. This knowledge may be useful in designing therapies for IVIG. This is exciting and innovative research and must reading for all allergists/immunologists. Kaneko Y, et al. Science 2006; 313: 670. Editorial by Burton DR, Dwek RA, p. 627.
2. MAST CELLS (MC's) CAN ENHANCE RESISTANCE TO SNAKE AND HONEYBEE VENOMS
It has been proposed that activation of MC's by snake or insect venoms can contribute to increased morbidity and mortality. However, the authors demonstrate that MC's can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which degrade venom components. MC's also significantly reduce the morbidity and mortality induced by honeybee venom. Editor’s comment: MC's mediators can be beneficial or detrimental to the host. Metz M, et al. Science 2006; 313: 526.
3. EFFECTS OF A LEUKOTRIENE RECEPTOR ANTAGONIST (LTRA) ON EXHALED LEUKOTRIENE E4 (LTE4) AND PROSTANOIDS IN CHILDREN WITH ASTHMA
This open-label study with oral montelukast (5 mg once d for 4 wk) in 17 atopic children with asthma and 16 atopic children without asthma was designed to study the effects of LTRA on exhaled LTE4 and prostanoids in children with asthma vs controls. Pretreatment exhaled LTE4 (P < .0001) and 8-isoprostane (P < .0001) values were higher in asthmatics than those without asthma. Montelukast reduced exhaled LTE4 by 33% (P < .001) in patients with asthma and the reduction was correlated with pretreatment LTE4 values (r = -0.90; P = .0001). Montelukast had no effect on exhaled LTE4 in atopic children without asthma or on exhaled 8-isoprostane and PGE2 in either group. Nitric oxide (NO) concentrations were reduced by 27% after montelukast in the asthma group. Editor’s comment: Is this a method to identify patients who are most responsive to LTRAs? Perhaps! Montuschi P, et al. J Allergy Clin Immunol 2006; 118: 347.
4. DURATION OF AIRBORNE FEL d 1 REDUCTION AFTER CAT WASHING
Twelve adult female American domestic short-hair and medium-hair cats were washed by the immersion technique (immersed in tap water to the level of their heads, pelts massaged for three minutes, followed by a three-minute immersion in fresh water and then towel dried) to determine duration of airborne Fel d 1 reduction after cat washing. These washings did result in a 4- to 5-fold decrease in Fel d 1 collection at three hours, with a return to baseline within one day after washing. The authors conclude that washings do result in significant Fel d 1 reduction, but the reductions are short lived. It is unlikely that the average cat owner will experience meaningful improvement in allergic symptoms with this environmental control method. Editor’s comment: Cat allergic individuals should eliminate cats from their homes. Nageotte C, et al. J Allergy Clin Immunol 2006; 118: 521.
5. NO EFFECTS OF PROBIOTICS ON ATOPIC DERMATITIS (AD) IN INFANCY: A RANDOMIZED PLACEBO-CONTROLLED TRIAL
In this randomized, double-blind, placebo-controlled study, the clinical and immunological effects of two probiotics strains of bacteria on AD in infancy were assessed. After a 4-6 week baseline and double-blind, placebo-controlled challenge to diagnose cow’s milk allergy (CMA), and a 4-6 week baseline, infants less than five months old with AD received either a hydrolysed, whey-based formula as placebo (n = 17) or hydrolysed, whey-based formula supplemented either with Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for three months. Only four infants were diagnosed with CMA and no clinical or immunologic effects of probiotic bacteria were evident. Editor’s comment: The controversy continues about probiotics in the treatment of AD. Brouwer ML, et al. Clin Exp Allergy 2006; 36: 899.
6. RELATIVE CORTICOSTEROID INSENSITIVITY OF PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC's) IN SEVERE ASTHMA
PBMC's from patients with severe asthma (n = 16), as defined by the American Thoracic Society, were compared to nonsevere asthma (n = 19) and normal volunteers (n = 10) to determine the suppression of lipopolysaccharide (LPS)-induced cytokine release by dexamethasone (D). Baseline spontaneous or stimulated release of cytokines was similar among all groups, however, LPS-induced release of IL-1β (P < 0.03), IL-8 (P < 0.03), and macrophage inflammatory protein 1α (MIP-1α) (P < 0.003) was less suppressed by D in severe asthma. This phenomenon was associated with a reduction in nuclear histone deacetylase activity (P < 0.01), an important determinant of the inflammatory response and of corticosteroid responsiveness that parallels impaired corticosteroids sensitivity (CS). Editor’s comment: Diminished CS in severe asthma affects the PBMC's. Hew M, et al. Am J Respir Crit Care Med 2006; 174: 134.
7. SYSTEMIC CORTICOSTEROID (SC) THERAPY FOR ACUTE ASTHMA EXACERBATIONS
This is a nice summary of the management of acute asthma with systemic CS. The authors call for the early use of an IV, intramuscular or oral CS within one hour of arrival in the emergency department, shown to reduce admission rates by up to 60%. They state that there is no clear evidence to support any one route of SC administration over another and that the doses in a nine-study meta-analysis demonstrate that doses of >80mg/d methylprednisolone or its equivalent offer no therapeutic advantage in the initial management of acute severe asthma. Editor’s comment: A great review article on the use of SC for severe asthma exacerbations. Fiel SB, Vincken W. J of Asthma 2006; 43: 321.
8. CYTOKINES OR THEIR ANTAGONISTS FOR THE TREATAMENT OF ASTHMA
This review is about various cytokines or their antagonists as possible treatments for asthma. The use of human monoclonal antibodies against IL-5 and a recombinant human soluble IL-4 receptor have not proven successful in patients with persistent asthma. Neither has administration of the potential anti-inflammatory cytokines IL-12 and interferon-γ. Tumor necrosis factor (TNF)-α is important in the persistence of inflammation and in patients with severe oral steroid-dependent asthma. Soluble TNF-α receptor (anti-TNF-α) has demonstrated promising results. Editor’s comment: The magic cytokine or its antagonists are yet to be discovered, however, anti-TNF-α shows promise for severe asthma. O’Byrne PM. Chest 2006; 130: 244
9. OBESITY AND ASTHMA
Obesity leads to metabolic and cardiovascular diseases and may increase asthma risks. Animal experiments suggest that the airway inflammation response is enhanced by both endogenous and exogenous leptin, which is increased in obese humans and is also a central mediator of inflammation in obesity. Cross-sectional and prospective cohort studies in humans show a slight increased incidence and prevalence of asthma in obese subjects, however, body mass does not appear to be a significant modifier of severity. Editor’s comment: Obesity seems to increase the incidence and prevalence of asthma. Beuther DA et al. Am J Respir Crit Care Med 2006; 174: 112.
10. HERBAL MEDICINES FOR THE TREATMENT OF COPD: A SYSTEMATIC REVIEW
This is a review of 14 randomized clinical trials of 14 different herbal medicines.The conclusions are that the effectiveness of herbal medications to treat COPD is not established beyond reasonable doubt and that evidence from randomized clinical trials is scarce and often methodologically weak. Editor’s comment: The combination of long acting beta agonists and ipatropium bromide is a treatment of choice for COPD. Guo R, et al. Eur Respir J 2006; 28: 330.
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