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Archives: Medical Journal Reviews

Medical Journal Review

Posted: November 2007

Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief and Guest Reviewer Gary Hellermann, PhD, reviewed premier medical journal articles for practicing allergists.

1. Nothing to cough at
This is a case report article of a 73-year-old male with a 4-day history of a nonproductive cough that worsened at night. The differential cough is extensive and allergists/immunologists regularly see individuals who have a chronic cough of unknown etiology. In this particular case report, the cough is not secondary to upper respiratory tract infections, upper airway cough syndrome (post nasal drip), gastroesophageal reflux disease, asthma, cigarette smoking or the use of ACE inhibitors. It is caused by B. pertussis, a resurgent problem associated with the transmission of this organism in the face of waning vaccine-induced immunity among adults and adolescents. Erythromycin or another macrolide usually eliminates the organism within five days; without treatment the patient remains contagious for one month or more and the cough lasts for weeks. Childhood vaccination for B. pertussis wanes after five to ten years, accounting for the resurgence of this disease. Editor's Comment: Pertussis can account for up to 32% of cases of prolonged cough in adolescents and adults. Re-immunization with tetanus, diphtheria and pertussis (Tdap) vaccine is now recommended for adults 19 to 64 by the U.S. Communicable Disease Center. Cornia B et al., N Engl J Med 2007; 357:1432-7.

2.  Allergic airway responses in obese mice
A link between asthma and obesity has been demonstrated in epidemiological reports, but mechanistic studies are few. Here, an obese mouse (ob/ob) model is used to examine the effects of obesity on ovalbumin (OVA)-induced asthma. Pulmonary resistance is higher in ob/ob mice than wild type (WT) as is also the IgE level. There is no difference in the Th2 cytokine level and lung cell infiltration is actually lower in ob/ob mice compared to WT. Editor's Comment: The significant increase in airway hyperreactivity without concomitant increase in Th2 cytokines or cellular infiltration suggests additional mechanisms in obesity-associated asthma. Johnston RA et al., Am J Resp Crit Care Med 2007; 176: 650-658.

3.  Effectiveness of influenza vaccine in the community-dwelling elderly
This study of 713,872 person-season observations of pooled data from 18 cohorts of community-dwelling elderly members of various health maintenance organizations in the United States determined that during 10 seasons, influenza vaccine was associated with significant reductions in the risk for hospitalization for pneumonia or influenza and the risk of death among community-dwelling elderly persons. Vaccination was associated with 27% reduction in the hospitalization risk for pneumonia or influenza (OR, 0.73; 95% CI, 0.06 to 0.77) and a 48% reduction in risk of death (OR, 0.52; 95% CI, 0.50 to 00.55). Editor's comment: Influenza vaccine is indicated for high risks subjects. Nichol K et al., N Engl J Med 2007; 357:1373-81. Treanor J D, editorial, 357:1439-1441.

4.  Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immunotherapy with a house dust mite allergoid: a pilot study
Subcutaneous allergen-specific immunotherapy (SCIT) is effective in treating allergy and this study aims to determine if SCIT will benefit atopic dermatitis (AD) patients sensitive to house dust mite (HDM) allergens. 25 subjects, who had been diagnosed with AD for over two years, and had FEV1>70% and positive skin-prick test to Der p and/or Der f were enrolled. SCIT injections of HDM allergoid were given weekly for the first four weeks, then every four weeks up to 32 weeks. AD symptoms were quantified using the standardized SCORAD (scoring of atopic dermatitis) system. SCIT with HDM caused a significant reduction in objective and subjective SCORAD as well as reduction in HDM-specific IgE; the greatest improvement in eczema being seen in those with the severest disease. Editor's Comment: This small pilot study offers significant hope that allergen-specific SCIT may be helpful for AD. Bussmann C et al., Clin Expt Allergy 2007; 37: 1277-1285.

5.  Mast cell (MC)-derived interleukin-10 (IL10) limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B
The immune system possesses a natural anti-inflammatory activity that limits leukocyte infiltration and tissue damage. IL10 is a cytokine produced by macrophages, B cells, T helper type 2 cells, regulatory T cells and, as reported here, mast cells. Mice deficient in MC production were examined for inflammation in response to the urushiol (sensitizer) or chronic UVB irradiation. They that showed increased contact hypersensitivity (CHS) was reversed by injecting them with wild type MCs. MCs appear to be a major source of IL10 and exert an anti-inflammatory and immunosuppressive effect on CHS and the effects of chronic UVB irradiation. Editor's Comment: This finding in mice of a role for MCs in limiting CHS inflammation may be important for human CHS. Grimbaldeston MA et al., Nat Immunol 2007; 8: 1095-1104. (Abstract:

6.  Allergic rhinitis (AR) and onset of bronchial hyperresponsiveness (BHR)
There is an association between AR and increased BHR, but studies have not definitively linked AR to the onset of BHR. Data from the European Community Respiratory Health Survey (ECRHS) was used in this report to examine the factors associated with developing BHR (defined as a ?20% decrease in FEV1 in response to 1 mg methacholine). A cohort of 3719 subjects without BHR at baseline and, with or without, AR or atopy was examined at follow-up (about nine yrs later). The incidence of BHR is 9.7% in subjects with AR, 7.0% in subjects with atopy but not AR, and 5.0% in subjects with neither. When the AR is treated with ICS, the remission of BHR is enhanced. Editor's Comment: AR seems to be a risk factor for onset of BHR, but the exact mechanism is unknown. Shaaban R et al., Am J Resp Crit Care Med 2007; 176: 659-666. (Abstract:

7.  Phagocyte-derived catecholamines enhance acute inflammatory injury
There is a large body of evidence that the inflammatory response is intimately linked to autonomic signals through specific receptors on immune system cells. In this paper, not only do immune cells respond to neurohormones but they also produce them. Rat alveolar macrophages incubated with bacterial lipopolysaccharde produce high levels of adrenalin and noradrenalin and express the enzymes necessary for producing and degrading catecholamines. The secretion of macrophage catecholamine promotes lung inflammation and antagonist blockade of adrenoceptors prevents this. Similar experiments with neutrophils from peripheral blood (including human) show that these cells also produce inflammatory catecholamines. Editor's Comment: The multi-layered complexity of the immune response is further demonstrated by this finding of neurohormone production by phagocytic cells. Flierl MA et al., Nature 2007; 449: 721-725.

8.  Inhibition of allergen-induced airway remodeling by tiotropium and budesonide: a comparison
The neurotransmitter, acetylcholine, acts on muscarinic receptors to cause airway smooth muscle contraction, but chronic signaling can also lead to production of pro-inflammatory mediators and mitogenic proteins. This study looked at the effects of the anticholinergic, tiotropium bromide, in comparison with budesonide on airway remodeling, contractility and mucus production in ovalbumin-allergic guinea pigs. Both compounds were similarly effective in reducing tracheal hypercontractility and mucus cell hyperplasia. Editor's Comment: This report demonstrates that acetylcholine acting through muscarinic receptors may play an important role in the pathophysiology of airway remodeling. Bos IST et al., Eur Resp J 2007; 30: 653-661. (Abstract:

9.  Anti-inflammatory activity of human IgG4 antibodies by dynamic FAb arm exchange
IgG4 subtype antibodies differ from other IgGs in having anti-inflammatory activity, and this property has made them useful in immunotherapy. There have been reports that one monospecific IgG4 can switch a heavy/light chain with a different IgG4 to generate a bi-specific molecule. In this study, IgG4 in blood samples from subjects sensitive to cat and birch allergens was found to react with both antigens. Antibody arm exchange was also seen in mice injected with cat-specific and birch-specific IgG4s. Breakage of disulfide bonds between the arms by in vitro reaction with the reducing agent glutathione verified that this mechanism was involved in the exchange. Using a rhesus monkey model of immune myasthenia gravis, injection of IgG4 specific for the acetylcholine receptor (AChR) neutralized the pathological effects of AChR-specific IgG1. Editor's Comment: This unusual anti-inflammatory property of IgG4 antibodies may prove to be a promising avenue for developing more effective immunotherapy strategies. Kolfschoten M et al., Science 2007; 317: 1554-1557.

10.  A critical appraisal of "chronic Lyme disease"
Lyme disease, the most common tick borne infection in the Northern hemisphere, is caused exclusively by Borrelia burgdorferi, whereas in Europe it is caused by B. afzelii, B. garinii, B. burgdorferi and other species of Borrelia. This article is a very extensive and critical review of the subject of "chronic Lyme disease". The authors indicate that this disease is the latest in a series of syndromes postulated to attribute medically unexplained symptoms to particular infections. Earlier examples include "chronic candida syndrome" and "chronic Epstein-Barr virus". They go on to state that "chronic Lyme disease", which is equated to chronic B. burgdorferi, is a misnomer, and prolonged treatment with potentially dangerous and expensive antibodies is not warranted. Editor's comment: This is an excellent article for all to read about a "disease" for which there is no good scientific evidence. Feder H et al., N Engl J Med 2007; 357:1422-30.