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Archives: Medical Journal Reviews

Medical Journal Review

Posted: February 2008

Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief and Guest Reviewer Gary Hellermann, PhD

1. Mast cell (MC) derived TNF is essential for allergic airway disease.
Mast cell-deficient (MCD) mice were examined to determine their role in producing inflammatory mediators that contribute to airway disease pathology. MCD mice exhibit reduced airway hyperresponsiveness, less goblet cell hyperplasia and lower inflammatory cytokine levels, and this effect is reversed by injecting wild type MCs into the MCD mice. Injection of MCs from mice lacking TNF, however, gives similar results to MCD mice suggesting that TNF is necessary for the inflammation associated with airway disease. Editor's comment: MCs are key players in airway disease and offer potentially effective therapeutic targets. Reuter S et al., Eur Resp J, 19 Dec 07 [Epub ahead of print].

2. Antibiotics and topical nasal steroid (NS) for treatment of acute maxillary sinusitis (AMS).
Amoxicillin (A) and budesonide (B), either separate or in combination, were tested in a DBPC randomized trial of 240 adults with acute nonrecurrent sinusitis. Patients with fewer than two Berg-Carenfelt criteria or those with two or more acute attacks of sinusitis in the previous year were excluded. Subjects were randomized to either: A + NS; placebo A + NS; A + placebo NS; or placebo A + placebo NS. They were given A 500 mg three times daily for seven days with or without B 200 µg per nostril once per day for 10 days. Study participants kept a symptom diary, filled out questionnaires and returned the drugs for compliance testing. No improvement in symptom scores was seen with A or B alone or in combination versus placebo. Editor's comment: AMS resolves with or without A or B or their combination. Williamson IG et al., JAMA, 2007; 298:2487-96. [Editorial: Lindback M, pp. 2543-4.]

3. The prevention of COPD exacerbations by salmeterol/fluticasone propionate (S/FP) or tiotropium bromide (T).
This study is a two year double-blind, double-dummy multicenter comparison of the combination of S 50 µg plus FP 500 µg (SFC) twice a day to T 18 µg once per day in preventing COPD exacerbations in 1323 subjects with severe to very severe COPD (FEV1 < 50% of predicted). Two treatment groups (SFC, n = 658; T, n = 665) were randomized and pre- and post-dose FEV1s obtained. Symptom diaries, medication use (short-acting beta-agonists and oral steroid), healthcare utilization, and filled out respiratory questionnaires were accessed. While there were no significant differences between the two groups in the number of exacerbations, those in the SFC group were less likely to withdraw, had better overall health and lower mortality than those given T. Editor's comment: SFC treatment versus T resulted in fewer deaths and less morbidity, although the primary outcome, COPD exacerbations, was no different. Wedzicha JA et al., Am J Resp Crit Care Med, 2008; 177:19-26.

4. Augmented epithelial endothelin-1 (EDN1) expression in refractory asthma.
Ten healthy controls, ten steroid-naïve patients with mild asthma, and 18 severe asthmatic patients on glucocorticosteroid treatment were recruited for this study. Bronchoscopy specimens were obtained and laser-capture microdissection used to obtain bronchial epithelial cell samples for quantitative real-time PCR analysis of 17 transcripts for a panel of growth factors, cytokines and chemokines. PCR data were verified by immunohistochemistry on bronchial biopsy specimens. The levels of IL-8, CXCL8 and EDN1 were elevated in patients with severe asthma. EDN1 is involved in airway remodeling, and the presence of large numbers of epithelial cells producing EDN1 may account for the increased airway smooth muscle mass and fibrosis seen in these patients. Editor's comment: Therapeutic intervention targeting the endothelin receptor may be effective in treating refractory asthma. Pégorier S et al., J Allergy Clin Immunol, 2007; 120:1301-1307.

5. Factors associated with 5-year risk of hip fractures in postmenopausal women.
This report utilized a multiethnic cohort of 93,676 USA postmenopausal women, aged 50-79 years, enrolled in the Women's Health Initiative to examine a number of clinical risk factors and to develop an algorithm for predicting the 5-year likelihood of hip fracture. The model obtained from this observational study was validated by examining data from women in the clinical trial arm and tested in a subset of women from the clinical trial who underwent dual-energy x-ray absorptiometry (DXA) scans. Eleven factors predicted hip fracture within 5-years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Editor's comment: This large 5-year study should prove helpful in counseling individuals as to their risk of hip fracture. Robbins J et al., JAMA, 2007; 298:2389-98.

6. Safety and efficacy of bronchial thermoplasty (BT) in symptomatic, severe asthma.
To test the efficacy of BT as a method of reducing airway smooth muscle mass and improving patency by vasorelaxation, a group of patients whose asthma symptoms persisted in spite of treatment with high dose ICS, LABA, and oral glucocorticosteroids (OCS) were randomized into control or BT groups. Thirty-two subjects (15 in BT and 17 in controls) with severe refractory asthma, according to the GINA criteria, were included. About half of each group were taking OCS as well as using ICS-LABA. Outcomes were diary symptoms scores, questionnaires and interviews, and PEF, FEV1 and PC20. BT caused an initial increase in asthma exacerbations followed by statistically significant improvement in airway function, rescue medication use, and symptoms. Editor's comment: Treatments such as BT are welcome additions to the therapeutic arsenal for severe asthma. Pavord ID et al., Am J Resp Crit Care Med, 2007; 176:1185-91.

7. A population-based study of the incidence and complication rates of Herpes zoster (HZ) before zoster vaccine introduction.
This retrospective study involves 1669 adults with confirmed HZ between 1 Jan 1996 and 31 Dec 2001, prior to the use of HZ vaccine. The adjusted incidence of HZ was 3.6 per 1000 person-years, and 68% of cases occurred in persons 50 years of age or older. Most (92%) were immunocompetent and 60% female. The most common complication was post-herpetic neuralgia (18% of the HZ patients) and 25% had at least some HZ-related sequelae. Editor's comment: This is the first large, population-based study to provide baseline data (before Zostavax®, Merck & Co., Inc, New Jersey) on HZ by age, gender and immunocompetence. Yawn BP et al., Mayo Clin Proc, 2007; 82:1341-1349.

8. Virtual Symposium on Airway Smooth Muscle (ASM).
This symposium begins with an introduction emphasizing the role of ASM changes in the pathology of asthma, COPD and cystic fibrosis, and the realization that ASM is an active player in secreting molecules involved in inflammation and airway remodeling. There are 18 articles covering topics ranging from the mechanics of smooth muscle contraction and interactions of smooth muscle cells with their matrix to ASM growth in asthma, genetic differences in ASM function and the ASM cell as an inflammatory cell. Editor's comment: This is essentially a book in journal form-- an up-to-date review of ASM by experts in the field. Panettieri RA, Jr., and Solway J, editors, Proc Am Thoracic Soc, 2008; 5:3-132.

9. Randomized trial of nasal surgery for fixed nasal obstruction in obstructive sleep apnea (OSA).
This study tests the efficacy of surgical treatment (septoplasty) in 49 OSA patients to improve nasal as opposed to oral breathing. Subjects were randomized into surgery (27) or sham surgery (22) groups. Baseline measurements were similar in the two groups. The average apnea / hypopnea index (AHI) was similar in the two groups, but the surgery group included four treatment successes (significant increases in nasal breathing epochs and decrease in AHI) while there were none in the sham group. Editor's comment: Only four patients improved with nasal surgery, 23 did not. Treatments other than nasal surgery are needed for OSA. Koutsourelakis I et al., Eur Resp J, 2008; 31:110-117.

10. Flu myths: dispelling the myths associated with live attenuated influenza vaccine (LAIV).
This timely review compares LAIV to conventional trivalent inactivated influenza vaccine and dispels the misperceptions associated with the former. Live virus shedding is one fear, but data demonstrate that viral titers from LAIV are well below the dose needed to cause infection. Also, there is no evidence that the attenuated virus can revert to the wild type and cause disease. Side effects from LAIV can include rhinorrhea and low-grade fever; serious adverse reactions have not been reported. Although LAIV is not recommended for asthmatics, one trial of children with moderate to severe asthma showed that LAIV was well-tolerated and effective. Editor's comment: Increase use of LAIV could reduce the worldwide incidence of this disease. Tosh PK et al., Mayo Clin Proc, 2008; 83:77-84.

11. Global strategy for asthma management and prevention: GINA executive summary.
GINA, the Global Initiative for Asthma, is dedicated to providing accurate and useful information on asthma management. The current emphasis is on optimizing "asthma control"; the GINA recommendations are adapted for regional differences in treatment availability, resources and services. Editor's comment: This is a comprehensive document about asthma management and prevention with 409 references. Bateman ED et al., Eur Resp J, 2008; 31:143-78.

12. Sinusitis in children.
Sinusitis in children may manifest with cough, nasal congestion and other symptoms of an URI. Recurrent sinusitis can be associated with GERD, anatomic defects or immunodeficiency. This comprehensive review explains the clinical symptoms of sinusitis in children and the current best methods to diagnose, prevent, and treat this disease. Editor's comment: This review is excellent reading for all physicians who care for children. Virant FS, Ped Asthma Allergy & Immunol, 2007; 20:157-67.

13. Morbidity and mortality for vaccine-preventable diseases in the U.S.
This review compared morbidity and mortality before and after wide spread implementation of national vaccine recommendation for 13 vaccine-preventable diseases for which recommendations were in place prior to 2005. A greater than 92% decline in cases and a 99% or greater decline in deaths due to diseases prevented by vaccines recommended before 1980 were shown for diphtheria, mumps, pertussis, and tetanus. Epidemic transmission of polio virus, measles, and rubella viruses was eliminated. Smallpox was eradicated worldwide. Declines were 80% or greater for cases and deaths of vaccine-preventable diseases targeted since 1980 including hepatitis A, acute hepatitis B, HiB, and varicella. Declines in cases and deaths of invasive S pneumoniae were 34% and 25%, respectively. Editor's comment: Vaccines work! Every physician should make sure their patients are up-to-date on all vaccinations. Roush, SW et al., JAMA, 2007;298:2155-63.

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