Medical Journal Review

Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief and Guest Reviewer Mark C. Glaum, MD, PhD

1. Risk Factors Associated with Utilization of Acute Asthma Care
The aim of this study is to identify modifiable risk factors that predispose asthma patients' use of acute care. Adult asthmatics (n = 554) were recruited from a large HMO network. At their initial visit, subjects underwent skin prick allergy testing, spirometry and completed a questionnaire related to modifiable asthma risk factors. Acute care utilization data was recorded for the following 30 months. The most significant risk factors for seeking acute asthma care use were low FEV1 (RR, 4.33), current cigarette smoke exposure (RR, 1.6), and skin prick reactivity and ownership of a cat or dog (RR, 1.5). Editor's comment: Decreased FEV1 is a strong predictor of increased asthma morbidity. Osborne ML et al. Chest 2007; 132 (4): 1151-68

2. Leukotriene Modifiers Prevent Viral URI Symptoms in Asthmatics
Viral upper respiratory tract infections (URI) are common causes of asthma exacerbations. Reports suggest that leukotriene antagonists (LTRA) may decrease rates of rhinovirus infection through down-regulation of receptors expressed on nasal epithelial cells. Adult asthmatics (n = 279) who presented to an emergency department were retrospectively categorized into LTRA treated and untreated groups. Outcomes examined included frequency of exacerbations, emergency room visits and hospitalizations over the prior 12 months. In the LTRA treated group, number of infections (p < 0.05), exacerbations, emergency room visits and hospitalizations (p < 0.01) were all lower than the untreated group. Editor's comment: Leukotriene receptor antagonists may provide protection against viral-induced asthma exacerbations. Horiguchi T et al. Allergol Int 2007; 56: 263-7

3. The Importance of Vaccines in Disease Prevention
Vaccines are among the greatest success stories in U.S. public health over the past century. National recommendations provide guidelines for use of vaccines to prevent or eliminate 17 vaccine-preventable diseases. This study compares morbidity and mortality before and after widespread implementation of national vaccine recommendations in place up to 2005. Primary outcomes include numbers of cases, hospitalizations and deaths for 13 vaccine-preventable diseases. A 92% decline in cases and 99% decline in deaths were shown for diphtheria, mumps, pertussis and tetanus, while an overall 80% or greater reduction in cases and deaths were observed for most other vaccine-preventable diseases. Editor's comment: Appropriate influenza, pneumonia, and pertussis vaccinations make sense in all patients with asthma and other chronic respiratory diseases. Roush SW et al. JAMA 2007; 18: 2155-63

4. Early Thimerosal (T) Exposure and Neuropsychological Outcomes at 7 to 10 Years.
Mercury exposure of 1047 children (aged 7-10 years) was determined from medical immunization records and patient interviews to access neuropsychological performance and exposure to mercury during the prenatal and neonatal periods (birth to 28 days) and the first 7 months of life. The results of the analysis do not support a causal association between early exposure to mercury from T-containing vaccines and immune globulins and deficits in neuropsychological functioning at age 7 to 10 years. Editor's comment: This paper confirms many others showing that T does not cause neuropsychological problems. Thompson W et al. N Engl J Med. 2007; 357:1281-92

5. IFN-γ Production in Infancy Predicts Childhood Wheeze
Blunted IFN-γ responses during infancy are associated with an increased risk for allergen sensitization. The aim of this study is to assess the effect of low peripheral blood cytokine levels in the first year of life on the development of wheeze in childhood. At age 9 months, peripheral blood samples of healthy infants were assayed for levels of IFN-γ and IL-2 following mitogen-stimulation of mononuclear cells. Cytokine levels were correlated with occurrence of wheeze at ages 2, 3, 6, 8, 11 and 13 years. Risk of wheezing is significantly higher for subjects with low IFN-γ levels at age 9 months (relative risk, 2.29; 96% CI, 1.35-3.89) compared to high IFN-γ producers. Editor's comment: This study suggests that immune susceptibility to asthma is established in the early postnatal period. Stern DA et al. J Allergy Clin Immunol 2007;120 (4): 835-41

6. A Once Yearly Bisphosphonate Reduces Clinical Fracture Rates
Hip fractures are related to increased morbidity, mortality and functional decline in older adults. Patients (n = 2127) admitted to the hospital for surgical repair of a hip fracture were randomized to receive yearly intravenous zoledronic acid or placebo along with supplemental vitamin D plus calcium. The primary clinical endpoint was diagnosis of a new clinical fracture. Rates of new clinical fracture were 8.6% in the zoledronic acid group vs. 13.9% in the placebo group resulting in a 35% risk reduction (p = 0.001). A 28% reduction in mortality rate from any cause was observed in the zoledronic acid group (p = 0.01). Editor's comment: Osteoporosis occurs in COPD and steroid dependant asthma. Annual administration of zoledronic acid may reduce fracture rates and mortality in high-risk individuals. Lyles KW et al. New Engl J Med 2007; 357: 1799-809

7. Review of Leukotrienes in Inflammation
Leukotrienes are important mediators of allergic airway inflammation. This concise article provides an overview of leukotriene biology. Concepts discussed include leukotriene synthesis and effects of receptor activation and blockade. The correlation of leukotriene-associated inflammation in various diseases is discussed. Editor's comment: The leukotriene pathway is an important target in allergic inflammation. Peters-Golden M et al. N Engl J Med 2007;357: 1841-54

8. Invasive Methcillin-Resistant Staphylococcus Aureus (MRSA) Infections
This report describes the incidence and distribution of invasive MRSA disease in 9 US communities to estimate the burden of invasive MRSA infections in the United States in 2005. Main outcome measures include incidence rates, estimated number of invasive MRSA infections and related in-hospital deaths. In 2005 the standard incidence rate of invasive MRSA was 31.8 per 100,000. Highest incidence rates were seen among individuals > 65 years (127.7 per 100,000), blacks (66.5 per 100,000) and males (37.5 per 100,000). With 1589 in-hospital deaths among patients with MRSA, the standardized mortality rate was 6.3 per 100,000. Of the 8987 reported cases of invasive MRSA infections in 2005, 58.4% were community-onset infections, 26.6% were hospital-onset and 13.7% were community-associated. Editor's comment: Invasive MRSA infection is a major public health problem no longer confined to the hospital environment. Klevens RM et al. JAMA 2007; 298 (15):1763-71

9. Hepatitis a Postexposure Prophylaxis: Vaccine vs Immune Globulin
Following hepatitis A exposure, immune globulin is known to provide effective protection from fulminant infection. This study compares the protective benefit of hepatitis A vaccine vs. immune globulin following exposure to an infected individual. Contacts (n = 1090) of hepatitis A-infected individuals were randomized to receive a single dose of hepatitis A vaccine or immune globulin within 14 days following exposure. Evidence of symptomatic hepatitis A infection was monitored from 15 to 56 days following exposure. Of the 568 subjects who received the vaccine, infection was confirmed in 25 (4.4%) vs. 17 (3.3%) who received immune globulin. Editor's comment: Hepatitis A vaccine provides comparable postexposure protection to immune globulin and confers the benefit of long-lasting protection. Victor JC et al. N Engl J Med 2007; 357 (17):1685-94

10. Review of Dendritic Cells in Allergy
This review is one of several in this issue devoted to dendritic cell biology. In particular, this article outlines the importance of dendritic cells in the pathogenesis of atopic diseases including contact dermatitis, asthma and atopic dermatitis. Particular attention is focused on the role of haptens as maturation factors for dendrtic cells in the skin. Editor's comment: Dendritic cells play a critical role in the pathogenesis of allergic disease. Aiba S. Allergol Int 2007: 56:201-8

11. Early Treatment with Prednisolone (P) or Acyclovir (A) in Bell's Palsy.
This is a DBPC, randomized, factorial trial of patients with Bell's palsy recruited within 72 hours following the onset of symptoms. Patients were assigned to receive 10 days of treatment with P, A, both agents, or placebo. The primary outcome was facial function. Secondary outcomes included QOL, appearance, and pain. 496 of 551 patients underwent randomization and at three months, the proportions of patients who had recovered facial function were 83.0% in the P group as compared to 63.6% who did not receive P (P<0.001) and 71.2% in the A group as compared to 75.7% of those who did not receive A (adjusted P=0.50). After nine months, the proportions were 94.4% of P versus 81.6% for no P (P<0.001) and 85.4% for A and 90.8% for no A (adjusted P=0.10). In patients treated with both drugs the proportions were 79.7% at three months (P<0.001) and 92.7% at nine months (P<0.001). There were no differences in secondary outcomes or serious adverse events. P improves the chance for complete recovery at three to nine months whereas A does not add any benefit for Bell's palsy. Editor's comment: P given as early as possible is the treatment of choice for Bell's palsy. Sullivan F et. al. N Engl J Med 2007; 357:1598-607

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