Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed premier
medical journal articles for practicing allergists.
1. House dust mite (HDM) control measures for asthma
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
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
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
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
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
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,
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.
Litt's Drug Eruption Reference Manual, 13th Edition; Including Drug
Author: Jerome Z. Litt, MD
Available from: Informa Healthcare, 2007
List Price: 309.95
James Young Joon Choi, MB BS, FRACP
Immunologist and Allergist
Dermatology Registrar, Westmead Hospital,
This thirteenth edition is a timely update to an invaluable clinical
tool. Its main purpose is to help find the cause for a possible drug
induced rash. Using the two main chapters within the book, you can
approach this clinical problem from two separate paths - starting with the
generic name of any drug, you can very quickly find a list of associated
cutaneous eruptions for which it has been responsible, or alternatively,
especially useful if the patient is taking many medications, you can look
up the cutaneous eruption type itself, and then scan through a
comprehensive list of all the drugs which have been responsible for that
The book is structured to minimize page flipping - drug names (generic)
and types of drug reactions are each arranged alphabetically in two
separate chapters, eliminating the need for a separate index. The
information under each drug (over 1000, including substances such as
caffeine, red clover, and even myrrh) is split into two main sections.
There is a brief list of its common trade names, clinical indications,
pharmacologic category (e.g. inhalation anesthetic), half life, and
important drug interactions. Following this, there is a comprehensive list
of all the different types of reported reactions (predominantly
cutaneous), each reaction type accompanied by relevant and up to date
references (predominantly from journal articles, but also from books and
The target audience for this book is mainly for dermatologists and
allergists. Although there is a small chapter at the end of the book
describing the features of some of the different types of cutaneous
reactions, it is not an atlas. There is not a single photo or diagram.
This is not the book that will help a medical student make a diagnosis of
a lichenoid eruption. However, once the dermatologic diagnosis is made,
the book will quickly help even a student identify the likely causal drug.
And because of this, and because it is now up to date, it is a most useful
tool for the busy clinician to keep under the prescription pad.
Find more allergy book reviews on the WAO Website here.