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World Allergy Organization
WAO's mission: To be a global resource and advocate in the field of allergy, advancing excellence in clinical care through education, research and training as a world-wide alliance of allergy and clinical immunology societies.

Medical Journal Review

Posted: May 2008

Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief

1. House dust mite control (HDM) measures for asthma (review)
This is a review of 54 trials (3002 patients) which assessed whether or not mattress encasings, chemical treatment, and a combination of chemical and physical methods impact the exposure to HDM allergens in homes of people with mite sensitive asthma. With various dust prevention methods, there were no statistical differences in PEF, number of patients who improve, asthma symptom scores, or medication usage. The authors conclude that chemical and physical methods aimed at reducing exposure to HDM allergens do not work and that it is doubtful whether further studies similar to the ones reviewed would be worthwhile. Editor's comment: This Cochrane meta-analysis indicates that chemical and physical methods to reduce HDM allergen levels are not effective to treat mite sensitive asthma. Gøtzsche PC, Johansen HK, Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No: CD001187. DOI: 10.1002/14651858.CD001187.pub3.

2. Respiratory complications of obesity
This is a European Respiratory Society (ERS) designated CME review of the respiratory problems associated with obesity, which is associated with sleep apnea, obesity hypoventilation syndrome and asthma. Obesity is known to alter pulmonary function, respiratory mechanics, respiratory muscle strength and endurance, gas exchange, control of breathing, and exercise capacity. The authors also indicate that there is a relative risk of asthma in obese subjects of 1.4 - 2.2, a ratio which is stronger in women than men. There seems to be a dose-effect relationship as the prevalence of asthma increases in proportion to BMI, and while obesity may not cause asthma, it seems to be a complicating factor for this disease. Editor's comment: Obesity is associated with various medical problems, including asthma. Veale D, et al., Breathe 2008; 4:210.

3. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data
This is a meta-analysis of randomized trials based on individual patients' data assessing whether common signs and symptoms can be used to identify those patients who need and will benefit from antibiotics (Ab). Data from 2,547 adults in nine trials were checked and analyzed to assess the overall effect of antibiotic treatment and the prognostic value of common signs and symptoms by the number needed to treat (NNT) with Ab to cure one additional patient. 15 patients with rhinosinusitis-like complaints needed to be given Ab before an additional patient was cured (95% CI NNT[benefit] 7 to NNT[harm] 190). Patients with posterior pharyngeal discharge took longer to cure vs. those without the sign with an NNT of eight patients with this sign before one additional patient was cured (95% CI NNT[benefit] 4 to NNT[harm] 47). The authors conclude that signs and symptoms cannot identify patients with rhinosinusitis for whom Ab treatment is justified, even if their symptoms are present for longer than 7-10 days. Editor's comment: Acute rhinosinusitis almost always gets better, even without Ab treatment. Young J, et al., The Lancet 2008; 371:908.

4. Recent resurgence of mumps (M) in the United States
A total of 6,584 cases of M in 2006 were reported with 76% occurring between March and May. There were 85 hospitalizations, but no deaths. 85% of patients lived in eight contiguous Midwestern states. The incidence of M was 2.2 per 100,000, with the highest incidence among persons 18-24 years of age (an incidence 3.7 times that of other age groups combined). In a subgroup analysis, 83% reported current college attendance. Vaccination status revealed that 63% overall and 84% between the ages of 18 and 24 had received two doses of M vaccine. The authors conclude that despite a high coverage rate with two doses of mumps-containing vaccine, M occurred, indicating two-dose vaccine failure, particularly among Midwestern college-age adults. The paper calls for a more effective M vaccine or vaccine policy to avert future outbreaks. Editor's comment: National vaccine policies and enforcement are very important since vaccination remains the most effective method to prevent infectious diseases. Dayan GH, et al., N Engl J Med 2008; 358:1580.

5. Head and neck cancer (HNC): changing epidemiology, diagnosis, and treatment
HNC accounts for less than 5% of all cancers and for less than 3% of all cancer deaths in the United States. Those at greatest risk have a long-standing history of smoking and alcohol use. The incidence of oropharyngeal cancer in younger populations has increased associated with exposure to the human papillomavirus. This subset has a better overall prognosis and response to treatment. Squamous cell histology accounts for 90% of HNC, and the review calls for a multidisciplinary approach for diagnosis and treatment. The reviewer highlights treatment with surgery, chemotherapy, radiation therapy, and, in particular, the role of inhibitors of epidermal growth factor receptor. Worldwide, 644,000 new cases of head and neck cancers are diagnosed each year, with 2/3 of these in developing countries. Editor's comment: A thorough direct and indirect examination (via rhinoscopy) of the nasal, oral and laryngeal pharynx is of extreme importance, especially when cancer is suspected. Marur S, Forastiere AA, Mayo Clin Proc 2008; 83:489.

6. Impaired lung homeostasis in neonatal mice exposed to cigarette smoke (CS)
It is hypothesized that the perinatal lung in humans is particularly susceptible to the damaging effects of CS and that exposure may alter immune response genes and adversely affect lung growth. These authors expose neonatal mice to 14 days of CS. Immune response gene expression and impairment of alveolar growth were studied in exposed vs. controlled mice. Exposure to CS during the neonatal period inhibits expression of genes involved in innate immunity and impairs postnatal lung growth. The authors conclude that these findings may partly explain the increased incidence of respiratory symptoms in infants and children exposed to CS. Editor's comment: Exposure to tobacco smoke is a known risk factor for asthma; these findings in mice may be applicable to humans. McGrath-Morrow S, et al., Am J Resp Cell Mol Biology 2008; 38:393.

7. In the clinic - Chronic obstructive pulmonary disease
There has been a 100% worldwide increase in age-adjusted mortality between 1970 and 2002 secondary to COPD, the fourth leading cause of mortality. In 2000, the number of deaths in women was equal to that in men. 80% to 90% of COPD is secondary to tobacco smoke, whereas 10% to 20% is secondary to occupational or other exposures to chemical vapors, irritants, and fumes. COPD should be suspected with symptoms of chronic cough, sputum production, dyspnea, and decreased exercise tolerance. The spirometric criterion for the diagnosis of COPD is a postbronchodilator FEV1/FVC ratio less than 0.70. The FEV1 percentage predicted can be used to classify COPD as mild (>80%), moderate (50% - 80%), severe (30% - 50%), or very severe (<30%). Various treatments are also reviewed. Editor's comment: This is an extremely good review of COPD, its diagnosis and treatment. Littner MR, et al., Annals of Int Med 2008; 148: ITC3-1.

8. Atopic Dermatitis
Atopic dermatitis or eczema is a skin disorder that is becoming more common. This is a nice review that discusses the Th1 - Th2 paradigm and its role in allergy and the skin as the site of initiation for sensitization. Dendritic cells, Staphylococcus aureus, and the mechanism of pruritus are reviewed. The author proposes a unifying hypotheses for both IgE and non-IgE associated forms of atopic dermatitis. He concludes that genetic and immunologic mechanisms drive cutaneous inflammation in atopic dermatitis and highlights the critical role of the epidermal-barrier function and the immune system. Both contribute to IgE-mediated sensitization and should be considered as major targets for therapy. Editor's comment: A very nice review which summarizes the mechanism involved in atopic dermatitis. Bieber T, N Engl J Med 2008; 358:1483.

9. Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis
A 400-mg dose of inhaled mannitol improves mucus clearance; however, the effect of other doses remains unknown. In 14 patients aged 63.3 ± 5.7 yrs, mucus clearance at baseline and with mannitol, 160, 320 and 480 mg, were determined using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. Clearance over 45 min with 480 mg mannitol was greater vs. 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs was 36.1 ± 5.5, 40.9 ± 5.6 and 46.0 ± 5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline and control. In conclusion, mucus clearance increases with increasing doses of mannitol and is enhanced by cough in patients with bronchiectasis. Editor's comment: This paper supports the present and previous studies to indicate that doses > 400 mg of mannitol achieve optimal mucus clearance in patients with bronchiectasis. Daviskas E, et al., Eur Resp J 2008; 31:765.

10. Control of Treg and Th17 cell differentiation by the aryl hydrocarbon receptor (AHR)
Reviewed by Gary Hellermann, Ph.D.

The mechanism by which environmental pollutants, such as dioxin (D), affect the immune system is not understood. The AHR binds a variety of aromatic and polycyclic chemicals, such as D, and then acts as a transcription factor to promote expression of specific genes. Using a mouse model, the authors show that D treatment activates AHR which binds to the FoxP3 promoter to convert CD4+FoxP3- T cells to CD4+FoxP3+ Treg cells. These Treg cells suppress experimental autoimmune encephalitis (EAE) in mice. Binding of a different ligand to AHR interferes with Treg cell differentiation but enhances Th17 cell production and EAE. This supports other observations on the reciprocal relationship between Th17 and Treg cell differentiation. In another paper in this issue of Nature (Veldhoen M et al, Letters, Mar. 23, 2008; epub ahead of print), AHR expression in CD4+ T cells occurs predominantly in the Th17 subset. Binding of a ligand to the AHR induces Th17 cells to produce the pro-inflammatory cytokine IL-22 and to worsen the pathology of EAE. Editor's Comment: These new findings linking environmental factors with autoimmune disease suggest that closer scrutiny of specific pollutant levels may be necessary. Qintana FJ et al., Nature, 2008, Mar. 23, 2008; epub ahead of print.