Prof. Richard F. Lockey, MD, WAO Web
Editor-in-Chief, reviewed premier medical journal articles
for practicing allergists.
1. Oral or IV prednisolone (P) in the
treatment of COPD exacerbations - A randomized,
controlled, D-B study.
435 patients were referred for a COPD exacerbation
warranting hospitalization. 107 received P, 60 mg IV and
130, 60 mg orally. Rx failure, the primary outcome, was
defined as death, admission to ICU, readmission to ICU
because of COPD, or intensification of pharmacologic Rx
during a 90-day follow-up period. Overall Rx failure
within 90 days was similar in both groups. The authors
conclude that oral P is equally effective as is IV Rx for
up to 90 days after starting Rx. Editor's comment: Oral
vs. IV P Rx for COPD is easier and probably more cost
effective; findings are similar for Rx of asthma
exacerbations. de Jong YP, et al.,
Chest 2007; 132(6):1741-47. (editorial: Tashkin,
2. Budesonide/formoterol (B/F)
maintenance and reliever Rx: impact on airway inflammation
After two weeks of usual therapy, 1538 patients were
randomized for six months to open-label B/F maintenance
and reliever Rx 160/4.5µg 2X/day and as needed or
guideline-based conventional best practice. Severe asthma
exacerbations, reliever medication use and total inhaled
glucocorticosteroid (IC) dose were analyzed in all
patients. No differences were seen in time to severe
exacerbation and severe asthma exacerbation rate. However,
there were numerically fewer ED visits/hospitalizations
with B/F maintenance and reliever Rx (4.4 vs. 7.5/100
patients/year; 41% reduction; p=0.09). Mean total IC dose,
reliever use, asthma medication costs and total annual
costs per patient were all significantly lower with B/F
maintenance and reliever Rx (all p<0.01). The authors
conclude that B/F maintenance and reliever Rx is superior
compared to conventional best practice in patients with
persistent asthma. Side-effects were similar in the 2
groups. Editor's comment: B/F 160/4.5µg 1 spray
2X/daily plus additional doses as needed up to 12
inhalations daily is effective asthma therapy. Sears
MR, et al.,
ERJ Express 2008; doi: 10.1183/09031936.00104007.
3. Clarithromycin (CL) targets
neutrophilic (N) airway inflammation in refractory asthma.
45 patients with severe refractory asthma were randomized
to receive CL 500 mg 2X/daily or placebo for eight weeks.
The primary outcome was sputum IL-8 concentration. Other
inflammatory outcomes included sputum N numbers and
concentrations of N elastase and matrix metalloproteinase
(MMP)-9. Clinical outcomes included lung function, airway
hyperresponsiveness to hypertonic saline, asthma control,
QOL and symptoms. CL significantly reduced airway
concentrations of IL-8, N numbers, and improved QOL scores
vs. placebo. Non-significant reductions in N elastase and
MMP-9 concentrations were also observed. The authors
conclude that CL can modulate IL-8 levels and N
accumulation and activation in the airways of refractory
asthma and could reduce noneosinophilic, particularly N
inflammation, in asthma. Editor's comment: CL could be
helpful in individuals with N airway inflammation and
refractory asthma. Simpson JL, et al., Am J Res
Crit Care Med 2008; 177:148-55. (Abstract: http://ajrccm.atsjournals.org/cgi/content/abstract/177/2/148)
4. Platelet-activating factor (PAF),
PAF acetylhydrolase (PAFA), and severe anaphylaxis (A).
PAFA activity was measured in 41 patients with A and 23
controls. PAFA was also measured in nine patients who had
fatal A to peanuts and compared to 26 nonallergic
pediatric controls (C), 49 nonallergic adult C, 63
patients with mild peanut allergy, 24 patients with
nonfatal A, 10 people who died of nonanaphylactic causes,
15 with life-threatening asthma, and 19 with non-life
threatening asthma. PAF levels were significantly higher
in the A (805±595 pg per ml) than in C (127±104 pg per ml,
P<0.001 after log transformation) and were correlated with
the severity of A. There was an inverse correlation
between PAF and PAFA activity (P<0.001). The authors
postulate that failure of PAFA to inactivate PAF may
contribute to the severity of A. Editor's comment: The
lack of adequate amounts of PAFA may contribute to
increased severity of A. Vadas P, et al.,
N Engl J Med 2008; 358: 28-35. (editorial:
Burks, pp. 79-81).
5. Allergology International.
The December issue of Allergology International
contains 3 reviews on airway remodeling and asthma. The
first, by Yamauchi K, et al., is entitled "Airway
Remodeling in Asthma and Irreversible Airflow Limitation -
ECM Deposition in Airway and Possible Therapy for
Remodeling"; the second, by Tagaya E, et al., is entitled
"Mechanisms of Airway Remodeling in Asthma"; and the
third, by Sumi Y, et al., is entitled "Airway Remodeling
in Asthma". Editor's comment: This is a nice update on
the subject of airway remodeling and asthma. Yamauchi
K, et al.,
Allergology International 2007; 56: 321-29.
Tagaya E, et al.,
331-40. Sumi Y, et al.,
update on the subject of airway remodeling and
6. Atopic features of cough variant
asthma (CVA) and classic asthma (CA) with wheezing.
These authors examine specific IgE levels to seven common
aeroallergens in 74 CVA patients (subjects who had a cough
in absence of wheezing or dyspnea, the presence of airway
hyperresponsiveness to methacholine, and a symptomatic
response of coughing to bronchodilators) vs 115 CA
patients of varying severity. Patients with CA had higher
total IgE levels (P<0.0001), more sensitization to
allergens (P = 0.03), and higher rates of
sensitization to dog dander (24% vs 3%, P<0.0001),
HDM (46% vs. 28%, P = 0.02), and moulds (17% vs.
7%, P = 0.047) vs. CVA. Wheezing developed in 6
(15%) patients with CVA, who were sensitized to a larger
number of allergens (P = 0.02) and had higher rates
of sensitization to HDM (P = 0.01) and dog dander (P =
0.02) than the 34 patients in whom wheezing did not
develop. The authors conclude that atopy is related to the
development of wheezing in CVA and that to prevent
progression from CVA to CA, avoidance of relevant
allergens may be helpful. Editor's comment: This is a
nice study on CVA, a disease which is rarely studied and
with which all physicians who care for patients with CA
are familiar. Takemura M, et al.,
Clin Exp Allergy 2007; 37:1833-39.
7a. British Society for Allergy and
Clinical Immunology (BSACI) guidelines for the management
of allergic and non-allergic rhinitis
7b. BSACI guidelines for the management of
rhinosinusitis and nasal polyposis
These two clinical guideline articles are on the subject
of allergic and non-allergic rhinitis and rhinosinusitis
and nasal polyposis. They summarize the medical science
behind these diseases and how they should be treated.
Editor's comment: Nice articles and must reading for all
those interested in these subjects. Scadding GK, et
Clin Exp Allergy 2008; 38:19-42. Scadding GK,
Clin Exp Allergy 2008; 38:260-75.
8. HLA-B*5701 screening for
hypersensitivity to Abacavir (A)
The presence of the HLA-B*5701 allele is associated with
hypersensitivity reactions to A. 1956 patients infected
with HIV type 1 who had not previously received A were
studied in this D-B prospective randomized study to
establish the effectiveness of prospective HLA-B*5701
screening to prevent hypersensitivity reactions to A.
Screening eliminated immunologically confirmed
hypersensitivity reactions (0% in the
prospective-screening group vs. 2.7% in the control group,
P<0.001), with a negative predictive value of 100% and a
positive predictive value of 47.9%. The authors conclude
that HLA-B*5701 screening can prevent a specific toxic
effect of A. An editorial entitled "Pharmacogenomic
Biomarkers for Prediction of Severe Adverse Drug
Reactions" accompanies this article. There are now at
least seven biomarkers which predict reactions to:
6-mercaptopurines, irinotecan, warfarin, tricyclic
anti-depressants, abacavir, carbamazepine, and
ximilagatran. Editor's comment: Some pharmacogenomic
biomarkers can predict severe adverse drug reactions.
Mallal S, et al.,
N Engl J Med 2008; 358:568-79. (editorial:
Ingelman-Sundberg, pp. 637-38).
9. Seafood allergy (SA) and
radiocontrast media (RCM): Are physicians propagating a
This is an anonymous survey of 231 faculty radiologists
and interventional cardiologists at six Midwest academic
medical centers to question whether SA is related to RCM
reactions. 69% of the responders indicated that they
inquire about a history of SA before RCM administration
and 37.2% replied that they withhold it or recommend
premedication on the basis of this history. The authors
conclude that the myth that SA is a risk factor for RCM
reactions is common among physicians. Editor's comment:
SA is not a risk factor for RCM reactions. Beaty AD,
Am J Med 2008; 121:158.e1-158.e4.
10. Proceedings of the American
This entire journal is devoted to adult and pediatric
sleep-disordered breathing. It covers the epidemiology,
pathophysiology, diagnosis, medical and surgical
treatment, as well as potential sequelae from this
disease. Editor's comment: A wonderful symposium on a
very common problem in patients seen by
allergists/immunologists. Mokhlesi B, Gozal D (guest
Proc of the Am Thoracic Society 2008; 5:135-284.
11. Supplement to the Journal of
Allergy and Clinical Immunology entitled "Mini-Primer on
Allergic & Immunologic Diseases."
This issue contains CME review articles on "Lymphocytes,"
"Dendritic Cells as Regulators of Immunity and Tolerance,"
"Adhesion Molecules and Receptors," "Gastrointestinal
Mucosal Immunity," "Genetics of Allergic Disease,"
"Secondary Immunodeficiencies, Including HIV Infection,"
"Immunologic Lung Disease," " Hereditary Angioedema,"
"Anaphylaxis," and "Occupational Asthma." Editor's
comment: Drs. Ed Shearer and Don Leung (eds) and the
authors are to be congratulated for this wonderful JACI
JACI (Suppl) 2008; 121: S363-S411.
12. Effect of glucosamine sulfate (GS) on hip
This is a 222 patient randomized, controlled trial study
of hip O to determine whether or not GS affects symptoms
and structural progression of hip O during 2 years of Rx.
Primary outcomes include pain and function subscales over
24 months and joint space narrowing after 24 months.
Secondary outcomes include pain, function, and stiffness
after 3, 12 and 24 months. There are no statistical
differences between the Rx vs. the placebo groups.
Editor's comment: GS is not effective treatment for hip O.
Rozendaal RM, et al.,
Annals of Int Med 2008; 148:268-77.
13. Snoring (S) in preschool
children: prevalence, severity and risk factors.
6,811 children aged 1-4 yrs were evaluated for the
prevalence, severity and risk factors for S, especially
habitual S. In 59.7% of the children, parents reported S
in the previous 12 months, including 7.9% with habitual S
and 0.9% with habitual S and sleep disturbance. Prevalence
increased with age from 6.6% in 1-yr-olds to 13.0% in
4-yr-olds. Habitual S was associated with: one and both
parents smoking (adjusted odds ratio (OR) 1.46 and 2.09,
respectively); road traffic (OR 1.23); single parent (OR
1.60); and in White but not South Asian children,
socioeconomic deprivation (OR 1.25 and 2.03 for middle and
upper thirds of Townsend score, respectively). There was a
strong association with atopic disorders, viral infections
and environmental exposures suggesting a complex etiology.
Editor's comment: S occurs in children and adults.
Physicians should be aware that children develop sleep
disorders leading to educational and behavioral problems.
Kuehni CE, et al., Eur Respir J 2008;
14. Systemic responses after
bronchial aspirin challenge in sensitive patients with
19 patients with a history of aspirin-induced asthma
underwent placebo (P)-controlled bronchial challenges with
lysine-aspirin (LA). Peripheral blood was collected before
and then 1 and 20 hours after challenge with P or LA and
numbers of leukocyte and eosinophil progenitors
determined. The challenge was positive in 13 with six
having an isolated local bronchial reaction and seven
systemic (bronchial and extrabronchial symptoms).
Leukocyte progenitors increased significantly at 1 and 20
hours (P<0.05). Eosinophil progenitors increased
significantly from mean 0.017% before challenge to 0.04% (P<0.05)
at 20 hours after the challenge. At the 20 hour challenge,
the increase in leukocyte and eosinophil progenitors was
observed only in patients with systemic reactions. Eotaxin
was also increased with positive challenges in two
subjects. Bronchial challenge with LA causes a systemic
reaction associated with mobilization of leukocyte and
eosinophil progenitor cells from the bone marrow.
Editor's comment: Aspirin sensitive asthmatics have a
systemic disease, not just asthma. Makowska JS, et
JACI 2008; 121:348-54.
Lippincott's Illustrated Reviews:
Authors: Thao Doan, Roger Melvold, Susan Viselli,
and Carl Waltenbaugh
Editors: Richard A. Harvey, Pamela C. Champe
Wolters Kluwer/Lippincott Williams & Wilkins
List Price: 46.95 USD
Josh Phillips, MD
Division of Allergy & Immunology, University of South
Florida College of Medicine
Lippincott's Illustrated Reviews is a
highly-regarded series designed to provide a review of
essential topics for undergraduate, graduate, and medical
students. The series is recognized for their full-color
illustrations, chapter summaries, study questions, and
case studies. Such learning tools synthesize clinical and
scientific concepts, giving students a more complete
review. This latest addition to the series lives up to
their high standards.
The authors have divided the text into
four units, representing larger immunological concepts:
Self/Non-self, Innate Immune System, Adaptive Immune
System, and Clinical Aspects of Immunity. These broad
topics are subdivided into chapters, with emphasis on
molecular aspects, MHC recognition, lymphocyte development
and activation. Later chapters focus on specific topics
such as immunodeficiency, transplantation, and laboratory
techniques to evaluate immunity.
This series is well-known for its
figures, and an early figure stands out in its depiction
of infection as a monopoly-style board game. A roll of the
dice may land a microbe on a natural killer cell (depicted
as a rabid dog) or an immune defect, in which the microbe
advances to the end (sepsis). Another figure depicts the
neutrophil as a restaurant patron selecting from a limited
menu, while the lymphocyte can mix-and-match from dozens
of palatable options. This effectively illustrates the
contrast of the relatively limited innate response vs. the
adaptive response in which clonally-derived lymphocytes
can respond to 10
10 different receptors.
At the conclusion of each chapter there
are five-to-ten USMLE-style questions to solidify core
concepts, accompanied by answers and explanations on the
same page. This is preferred over other texts, which may
refer back to a page number for the explanation, but some
may be tempted to merely read the explanations rather than
answer the questions. Also, the clinical applications and
case presentations are short, too few in number, and not
followed by questions.
The preliminary chapters oversimplify
some concepts, but later chapters are quite thorough,
using molecular cell biology to explain complex ideas. As
such, this text may be too advanced for undergraduate
study and overly broad for PhD candidates in immunology.
However, medical students looking for more detail than the
typical "high-yield" review may find the balance ideal.
While this review is by no means all-inclusive, it
provides a thorough review of important topics and
concepts in immunology.
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