Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief and Guest Reviewer Gary Hellermann,
PhD, reviewed premier medical journal articles for practicing
実地医家のための今月の医学雑誌レビューはWAO web編集委員長Lockey教授とGary Hellermann先生が担当した。
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
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
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
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
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
Eur Resp J, 2008; 31:143-78.
あたらしい世界統一喘息ガイドラインGINA, the Global Initiative for
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.,
Editors: James N. Barabiuk & Dennis Shusterman
Series Editors: MA Kaliner & RF Lockey
Available from: Informa Healthcare, New York. Published 2007>
List Price: £140.00 (about $245.00 USD)
Ronald S. Walls MD, PhD
University of Sydney, Department of Immunology & Allergy, Concord Hospital, Sydney
Non-allergic rhinitis is the bane of many physicians' and surgeons' lives, not least because there is no readily accessible repository of information about it. This book is unique in drawing together many aspects of this problem in a comprehensive and accessible format. Discussions on the classification of non-allergic rhinitis help to put these poorly understood diseases into perspective. The pathogenesis of nasal disease including hyperreactivity, is addressed. There are helpful chapters on topics such as chronic rhinosinusitis, occupational rhinitis, rhinitis in the elderly, and a sobering discussion on midfacial pain, pointing out that many are incorrectly ascribed to chronic rhinosinusitis. Many other difficult subjects are addressed in an insightful manner -examples are the sensory irritation to environmental chemicals and irritants such as perfumes and car exhaust fumes seen in patients with rhinitis.
This book brings home to practicing clinicians the importance of this group of diseases - it points out that they account for up to 50% of cases of rhinitis, and that non-allergic rhinitis co-exists with allergic disease in many instances.
The book is easy to read, thought provoking and helpful, not only in the clinic, but for understanding of possible mechanisms for some of these difficult and distressing diseases. It can be warmly recommended.
Find more allergy book reviews on the WAO Website here.