August 2006 World Medical Journal Review
Reviewed by Richard F. Lockey, M.D., Editor-In-Chief
1. DIRECT DETECTION OF BACTERIAL BIOFILMS ON THE MIDDLE-EAR MUCOSA (MEM) OF CHILDREN WITH CHRONIC OTITIS MEDIA (OM)
This study tested the hypothesis that chronic OM in humans is bacterial biofilm-related. MEM biopsy specimens were obtained from 26 children (mean age, 2.5 [range, 0.5-14] yrs) undergoing tympanostomy tube placement for OM with effusion (OME) and recurrent OM. Control biopsies were obtained from 8 subjects undergoing cochlear implantation. Samples were analyzed using microbiological culture, polymerase chain reaction (PCR) – based diagnostics, direct microscopic examination, fluorescence in situ hybridization and immunostaining. Mucosal biofilms were visualized by confocal laser scanning microscopic images using generic and pathogen-specific probes on 46 (92%) of 50 MEM specimens (vs none from controls) from children with OME and recurrent OM. Editor’s comment: The finding of biofilms on biopsy specimens from children with OME and recurrent OM supports the hypothesis of a cause and effect in the pathophysiology of chronic OM. Hall-Stoodley L, et al. JAMA 2006; 296: 202.
2. ULTRA-RUSH VENOM IMMUNOTHERAPY (VIT) INDUCES DIFFERENTIAL T CELL ACTIVATION AND REGULATORY PATTERNS ACCORDING TO THE SEVERITY OF ALLERGY
The objectives of this study were to assess the early effects of ultra-rush VIT on T lymphocyte activation and regulatory profile induction in 30 vespid-allergic patients according to the four severity grades of the Mueller classification. The authors found that a T helper type 2 (Th2)-to-Th1 switch occurs during ultra-rush VIT, in parallel with a natural and acquired regulatory T cell increase. These immunologic events occur earlier and at a higher level in less severe subjects, suggesting that VIT tolerance induction is easier to achieve in patients with less severe reactions. Editor’s comment: The immunologic changes induced during ultra-rush venom immunotherapy are impressive and easier to achieve in patients with milder vs more severe reactions. Mamessir E, et al. Clin and Exp Allergy 2006; 36: 704.
3. CONTROL OF AIRWAY INFLAMMATION MAINTAINED AT A LOWER STEROID DOSE WITH 100/50 μg OF FLUTICASONE PROPIONATE (FP)/SALMETEROL
Eighty-eight subjects, age > 18 yr, who demonstrated improved asthma control after an increase of FP from 100 μg twice daily to 250 μg twice daily were randomized to receive 100/50 μg of FP/salmeterol twice daily or continued FP 250 μg twice daily both through a Diskus inhaler for 24 weeks. Clinical outcomes, bronchial biopsy results, and bronchoalveolar fluid analysis results were similar. The authors conclude that a lower dose of FP with salmeterol versus a higher dose of FP is equally effective in controlling inflammation and asthma symptoms. Editor’s comment: Salmeterol augments the clinical benefits of FP. Jarjour NN et al. J Allergy Clin Immunol 2006; 118: 44.
4. SHORT COURSE OF SYSTEMIC CORTICOSTEROIDS (SC) IN SINONASAL POLYPOSIS (SP): A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL WITH EVALUATION OF OUTCOME MEASURES
Subjects with symptomatic endoscopically diagnosed SP received prednisolone (P) 50 mg daily for 14 days or placebo in a double-blind, randomized, placebo-controlled trial. The P-treated group showed significant improvement in nasal symptoms (P<.001); Rhinosinusitis Outcome Measure score (P<.001); and reduction in polyp size, as noted with nasendoscopy (P <.001) and MRI (P <.001). Fourteen days of prednisolone 50 mg daily was both safe and effective therapy for SP. Editor’s comment: Medical treatment for SP is effective. Hissaria P, et al. J Allergy Clin Immunol 2006; 118: 128.
5. ANTI-APOPTOTIC FUNCTION OF A microRNA ENCODED BY THE HSV-1 LATENCY-ASSOCIATED TRANSCRIPT
The herpes simplex virus-1 (HSV-1) lies dormant in the peripheral nervous system until reactivated causing cold sores. Just one viral gene is expressed during the latency phase when no virus is produced. The virus produces a microRNA that protects infected neurons from apoptosis or cell death, so that the infection persists until reactivated. Editor’s comment: MiRNAs are not only major regulators of gene expression in mammalian cells but also in HSV-1, providing a hiding place in neurons for this virus. Gupta A, et al. Nature 2006; 442: 82. Editorial by Sugden B, p 33.
6. SAFETY AND EFFICACY OF SELF-ADMINISTERED SUBCUTANEOUS IMMUNOGLOBULIN (SCIg) IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES (PIDD)
This open-label study investigated the efficacy and safety of SCIg (16% IgG) in patients with PIDD. Sixty-five patients entered a three-month, wash-in/wash-out phase, designed to bring patients to a steady-state with SCIg. This was followed by 12 months of weekly SCIg infusions resulting in a mean weekly dose of 158 mg/kg. Mean trough serum IgG levels increased from 786 to 1,040 mg/dL during the study, a mean increase of 39%. The most frequent treatment-related adverse event was an infusion-site reaction, reported by 91% of patients and tolerated by most. Editor’s comment: SCIg is safe, effective and an alternative to IVIg. It should be more cost effective. Ochs HD, et al. J Clin Immunol 2006; 26: 265
7. THE UNDERRECOGNIZED BURDEN OF INFLUENZA (INF) IN YOUNG CHILDREN (CH)
This population-based surveillance of medical visits associated with laboratory-confirmed INF demonstrated that the average annual rate of hospitalization associated with INF was 0.9 per 1,000 CH (0-6 yr). The estimated burden was 50 clinic visits (CV) and 6 emergency department (ED) visits per 1000 CH during the 2002-2003 season and 95 CV and 27 ED visits per 1,000 CH during the 2003-2004 season. Few CH who had laboratory-confirmed INF were given a diagnosis of INF in the inpatient (28%) or outpatient (17%) settings. Outpatient INF was 10 to 250 times more common than hospitalized INF. Editor’s comment: INF commonly causes respiratory illness in children < 6 yrs. Perhaps all children < 6 yrs should be vaccinated for INF. Poehling KA, et al. N Engl J Med 2006; 355: 31.
8. APHTHOUS ULCERATION
The author outlines an extensive differential diagnosis for recurring mouth ulcers. The etiology for aphthous ulcers remains unknown, but this condition can be quite bothersome and painful. Recommended treatment based on data available from randomized controlled trails includes topical corticosteroids in a paste, 5% amlexanox paste, or treatment with a mouth rinse such as chlorhexidine gluconate. Editor’s comment: Often times patients believe that aphthous ulcers and other mouth lesions are caused by allergy; therefore, it behooves allergists to understand the differential diagnosis and how to treat this common disorder. Scully C. N Engl J Med 2006; 355: 165.
9. TREATMENT OF CHRONIC RHINOSINUSITIS (CRS) AND ITS EFFECTS ON ASTHMA
This paper reports on the results of 43 patients with CRS with and without nasal polyps and concomitant asthma. Both medical and surgical treatment were associated with subjective and objective improvements in asthma. However, it was better maintained following medical therapy, where improvement could also be demonstrated in the subgroup of patients with nasal polyps. Medical vs. surgical therapy was also superior with respect to a decrease in exhaled nitric oxide and increase in FEV1 in polyp patients. Editor’s comment: This study demonstrates that medical or surgical treatment of CRS improves asthma. Medical treatment seems to be better. Ragab S, et al. Eur Respir J 2006; 28: 68.
10. TOWARDS SUBTLETY: UNDERSTANDING THE ROLE OF TOLL-LIKE RECEPTOR (TLR) SIGNALING IN SUSCEPTIBILITY TO HUMAN INFECTIONS.
There has been a dramatic improvement in understanding the role of innate immunity, in particular, TLR signaling in human host defense. In six pages, these authors brilliantly outline defects in human TLR signaling which enhance susceptibility to infection. The review highlights the mechanisms of infectious susceptibility that result from complex interactions between the genetically variable host and microbe and explores how this knowledge ultimately will translate into better care for patients. Editor’s comment: Abnormalities of the innate immune system, in this case, TLR signaling, are important in clinical medicine. Turvey SE, Hawn TR. Clin Immunol 2006; 120: 1.
11. REVIEWS ON ATOPIC DERMATITIS (AD)
The July JACI has a variety of papers on AD. Subjects discussed include: Epidermal barrier dysfunction in AD and gene-environment interaction, genetics of AD, clinical pearls about this subject, a consensus report on AD from the European and American Academies, the vasculature in AD, sleep disturbance associated with AD and its management, innate immune defects in AD, a Rostrum article challenging three prevailing concepts, an original article about "“Loss of function variations within the filaggrin gene predispose for AD", and patient perspectives about AD. Editor’s comment: Progress is being made in understanding and treating this complex vexing medical problem.
J Allergy Clin Immunol, July 2006; 118(1)
12. UPDATE IN GENERAL INTERNAL MEDICINE (IM)
This paper summarizes the major advancements in IM published in 2005 of interest to general practitioners. For example, the herpes zoster virus vaccine is recommended for all immunocompetent patients > to 60 yrs of age. In addition, vitamin D, 800 IU/d, plus calcium supplements are recommended for women at high risk for fracture. Another recommendation to consider is tiotripium bromide therapy for patients with COPD. Physicians also should stop prescribing high dose vitamin E supplements (no benefit) and bisphosphonate therapy (not cost-effective) to prevent fractures in women with osteopenia (T-score between -1.5 and -2.4). Editor’s comment: A wonderful easily understood review of major innovations in medicine for all physicians. Knight CL, Fihn SD. Ann Intern Med 2006; 145: 52.
