Microsoft word - best articles neas%202008

The Best Allergy and Asthma Articles of the Year

Rescue Use of Beclomethasone and Albuterol in a Single Inhaler for Mild Asthma.
Papi et al. NEJM 2007;356:2040-52.
Background: Treatment guidelines recommend the regular use of inhaled corticosteroids for
patients with mild persistent asthma. We investigated whether the symptom-driven use of a
combination of beclomethasone dipropionate and albuterol in a single inhaler would be as
effective as the regular use of inhaled beclomethasone and superior to as-needed use of inhaled
Methods: We conducted a 6-month, double-blind, double-dummy, randomized, parallel-group
trial. After a 4-week run-in, patients with mild asthma were randomly assigned to receive 1 or 4
inhaled treatments: placebo twice daily pluse 250mcg of bclomethasone and 100mcg of albuterol
in single inhaler as needed(as-needed combination therapy); placebo twice daily plus 100mcg of
albuterol as needed)as-needed albuterol); 250mcg of beclomethasone twice daily and 100mcg as
needed(regular beclomethasone therapy); or 250mcg of beclomethasone and 100mcg of albuterol
in a single inhaler twice daily plus 100mcg of albuterol as needed(regular combination therapy).
The primary outcome was the morning peak expiratory flow rate.
Results: In 455 patients with mild asthma who had an FEV1 of 2.96 liters(88% of predicted), the
morning peak flow rate during the last 2 weeks of the 6-month treatment was higher(p=.04) and
the number of exacerbations during the 6-month treatment was lower(p=.002) in the as-needed
combination therapy group than in the as-needed albuterol group, but the values in the as-needed
combination therapy group were not significantly different in the groups receiving regular
beclomethasone or regular combination therapy. The cumulative dose of inhaled beclomethasone
was lower in the as-needed combination therapy group than in the groups receiving regular
beclomethasone therapy or regular combination therapy(p<.001 for both comparisons).
Conclusions: In patients with mild asthma, the symptom-driven use of inhaled beclomethasone
and albuterol in a single inhaler is as effective as regular use of inhaled beclomethasone and is
associated with a lower 6-month cumulative dose of inhaled corticosteroid.
Overweight, Obesity, and Incident Asthma. Beuther and Sutherland. Am J Resp Crit Care
Med 2007;175:661-66.
Rationale: Although obesity has been implicated as an asthma risk factor, there is heterogeneity
in the published literature regarding its role in asthma incidence, particularly in men.
Objectives: To quantify the relationship between categories of body mass index(BMI) and
incident asthma in adults and to evaluate the impact of sex on this relationship.
Methods: Online bibliographic databases were searched for prospective studies evaluating BMI
and asthma in adults. Independent observers extracted data regarding annualized asthma
incidence from studies meeting predetermined criteria, within defined categories of normal
weight (BMI<25), overweight (BMI<25-29.9), and obesity (BMI>30). Data were analyzed by
inverse-variance-weighted, random-effects meta-analysis. Stratified analysis between BMI
categories and within sex was performed.
Results: Seven studies (n=333,102 subjects) met inclusion criteria. Compared with normal
weight subjects, overweight and obesity conferred increased odds of incident asthma, with an
odds ratio of 1.51. A dose-response effect of elevated BMI on asthma incidence was observed;
the OR for incident asthma for normal weight vs. overweight subjects was 1.38 and was further
elevated for normal weight vs. obesity (OR, 1.92; p<0.0001 for the trend). A similar increase in
the OR of incident asthma due to overweight and obesity was observed in men (OR, 1.46) and
women (OR, 1.68; p=0.232 for the comparison).
Conclusions: Overweight and obesity are associated with a dose-dependent increase in the odds
of incident asthma in men and women, suggesting asthma incidence could be reduced by
interventions targeting overweight and obesity.
Immediate and long term effects of weight reduction in obese people with asthma:
randomised controlled study. Stenius-Aarniala et al. BMJ 2000;320:27-32.
Objective: To investigate the influence of weight reduction on obese patients with asthma.
Design: Open study, two randomised parallel groups.
Setting: Private outpatient center, Helsinki, Finland.
Participants: Two groups of 19 obese patients with asthma (body mass index 30 to 42) recruited
through newspaper advertisements.
Intervention: Supervised weight reduction programme including 8-week very low energy diet.
Main outcome measures: Body weight, morning peak flow, FVC, FEV1; and also asthma
symptoms, number of acute episodes, courses of oral steroids, health status.
Results: At the end of the weight reducing programme, the participants in the treatment group
had lost a mean of 14.5% of their pretreatment weight, the controls 0.3%. The corresponding
figures after one year were 11.3% nd a weight gain of 2.2%. After the 8 week dieting period the
difference in changes in percentage of predicted FEV1 from baseline in the treatment and control
groups was 7.2%; p=0.0009). The corresponding difference in changes in FVC was 8.6% (p<
0.0001). After one year the differences in changes in the two groups was still significant: 7.6%
for FEV1 (p=0.02) NS 7.6% for FVC9p=0.001). By the end of the weight reduction program,
reduction in dyspnoea was 13 mm (on a visual analog scale 0mm to 100mm) in the treatment
group and 1mm in the control group (p=0.02). The reduction of rescue medication was 1.2 and
0.1 doses respectively (p=0.03). After one year the differences in the changes between the two
groups were –12 for symptom scores (p=0.04) and –10 for total scores (p=0.02). The median
number of exacerbations in the treatment group was 1 (0-4) and in the controls 4 (0-7); p=0.001.
Conclusion: Weight reduction in obese patients with asthma improves lung function, symptoms,
morbidity, and health status.
Acetominophen and the risk of asthma. Eneli et al. Chest 2005;127:604-12.
The prevalence of asthma has increased worldwide. The reasons for this rise remain unclear.
Various studies have reported an association between acetominophen, a widely used analgesic,
and diagnosed asthma. In a prospective cohort study, the rate of newly diagnosed asthma was
63% higher among frequent acetopminophen user than non-users in multivariate analyses.
Studies of patients with asthma suggest that acetominophen challenge can precipitate a decline in
FEV1 >15% among sensitive individuals. Plausible mechanisms to explain this association
include depletion of pulmonary glutathione and oxidative stress. This article reviews the existing
literature and evaluates the epidemiologic and pathophysiologic evidence underlying a possible
link between acetominophen and asthma.
Association of domestic exposure to volatile organic compounds with asthma in young
children. Rumchev at al. Thorax 2004;59:746-51.

Aim: To investigate the association between domestic exposure to volatile organic compounds
(VOCs) and asthma in young children.
Methods: A population based case-control study was conducted in Perth, Western Australia in
children aged between 6 months and 3 years. Cases (n=88) were children recruited at Princess
Margaret Hospital accident and emergency department and discharged with an asthma diagnosis
identified through the health department. Information regarding the health status of the study
children and characteristics of the home was collected using a standardized questionnaire.
Exposure to VOCs, average temperature and relative humidity were measure in winter and
summer in the living room of each participating household.
Result: Cases were exposed to significantly higher VOC levels than controls (p<0.01). ost of
the individual VOCs appeared to be significant risk factors for asthma with the highest odds
ratios for benzene followed by ehtylbenzene and toluene. For every 10 unit increase in the
concentration of toluene and benzene the risk of having asthma increased by almost two and
three times, respectively.
Conclusion: Domestic exposure to VOCs at levels below currently accepted recommendations
may increase the risk of childhood asthma. Measurement of total VOCs may underestimate the
risks associated with individual compounds.
Perennial allergen sensitization early in life and chronic asthma in children: a birth cohort
study. Illi et al. Lancet 2006;368:763-70.

Background: Reduced lung function is a feature of chronic asthma, which becomes apparent at
school age. Unknown factors between birth and school age determine the progressive loss of
pulmonary function in children with persistent asthma. We investigated the role of allergic
sensitization and allergen exposure early in life.
Methods: The German Multicentre Allergy Study followed 1314 children from birth to 13 years
of age. We regularly interviewed parents about their child’s asthma and measured IgE levels.
Allergen exposure was assessed at age 6 months,18 months, and at 3, 4, and 5 years; lung
function was assessed at 7,10, and 13 years; post-bronchodilator response at 10 and 13 years; and
a bronchial histamine challenge was done at 7 years.
Results: 90% of children with wheeze but no atopy lost their symptoms at school age and
retained normal lung function at puberty. By contrast, sensitization to perennial allergens (house
dust mite, cat and dog hair) developing in the first 3 years of life was associated with a loss of
lung function at school age. Concomitant exposure to high levels of perennial allergens early in
life aggravated this process: FEV1 to FVC ratio was 87.4 for those sensitized and with high
exposure compared with 92.6 for those not sensitized, p<0.0001; and MEF50 86.4 for sensitized
and with high exposure compared with 101.5 for those not sensitized (p=0.0031). Such exposure
also enhanced the development of airway hyper-responsiveness in sensitized children with
wheeze. Sensitization and exposure later in life had much weaker effects and sensitization to
seasonal allergens did not play a part.
Interpretation: The chronic course of asthma characterized by airway hyper-responsiveness and
impairment of lung function at school age is determined by continuing allergic airway
inflammation beginning in the first 3 years of life. However, children with a non-atopic
wheezing phenotype lose their symptoms over school age and retain normal lung function at
Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. Assa’ad et al. JACI
Background: Eosinophilic esophagitis (WEE) is a gastrointestinal disorder that is increasingly
diagnosed in pediatric patients.
Objective: We aimed to define, in pediatric patients with EE, their demographic and atopic
characteristics, the histopathlogy of all segments of the gastrointestinal tract, and the effect of
therapeutic interventions on the natural history.
Mehtods: We conducted a retrospective analysis of a database of pediatric patients with EE
followed over a period of 8 years.
Results: In 89 patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis
(6.2 +/-4.8 years), and atopy with sensitization to environmental and food allergens in 79 % and
75% respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and
77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the
stomach, duodenum, and colon. EE was chronic, with a duration of 0.91 +/- 0.84 years, until
first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed.
Concluion: Eosinophilic esophagitis in the pediatric population is a chronic and relapsing
condition, associated with atopy and sometimes with subsequent histopathology in other
segments of the esophagus.
Clinical implications: Physicians evaluating pediatric patients with chronic gastrointestinal
symptoms should consider the diagnosis of EE< particularly in young white male patints with
atopy. Once diagnosed and treated, the physicians should follow the patients over a period of
several years because the course of the disease is protracted , other gastrointestinal segments may
be affected, and relapses are common.
Obtaining concomitant control of allergic rhinitis and asthma with a nasally inhaled
Camargos et al. Allergy 2007;2:310-16.
Allergic rhinitis and asthma coexist frequently and a dual treatment is recommended by
prescribing topical nasal plus oral inhaled corticosteroids. The purpose of this study was to
assess the efficacy of a nasally inhaled corticosteroid aiming at concomitant control of AR and
asthma. A controlled trial was conducted among 60 patients with AR and asthma, aged 6-18
years, who were randomized into 2 groups. During 8 weeks, the experimental group received
exclusively Flovent-HFA inhaled through the nose (mouth closed) using a large volume spacer
attached to a facemask. The comparison group received a nasal spray of isotonic saline plus oral
inhalation of Flovent-HFA through a mouthpiece attached to the same spacer. Clinical scores for
AR and asthma, nasal inspiratory peak flow, and spirometry were assessed by blinded observers.
There was a significant improvement in AR scores and NIPF in the experimental group (p< 0.01)
up to week 8, when a worsening was observed after the intervention was interrupted. Asthma
symptom scores, FEV1, and FEF 25-75, were not statistically different between groups at the
baseline visit or along follow-up visits. Pre-bronchodilator FEV1 improved by 10% in both
groups, comparing values at inclusion with those obtained at the end of follow-up. Our results
suggest that nasally inhaled Flovent-HFA through a spacer may control AR and asthma in
children and adolescents. This approach is likely to result in higher compliance, lower costs, and
fewer side effects.
Wait and see prescription for the treatment of acute otitis media. Spiro et al. JAMA
Context: Acute otitis media is the most common diagnosis for which antibiotics are prescribed
for children. Previous trials that have evaluated a “wait-and-see prescription” (WASP) for
antibiotics, with which parents are asked not to fill the prescription unless the child is either not
better or is worse in 48 hours, have excluded children with severe AOM. None of these trials
were conducted in an emergency department.
Objectives: To determine whether treatment with a WASP significantly reduces use of
antibiotics compared with a “standard protocol” and to evaluate the effects of this intervention on
clinical symptoms and adverse outcomes related to antibiotic use.
Design, setting and patients: A randomized controlled trial conducted between July 2004 and
July 2005. Children with AOM aged 6 months to 12 years seen in an ememrgency department
were randomly assigned to receive either WASP or an SP. All patients received ibuprofen and
otic analgesic drops for use at home. A research assistant, blinded to group assinment,
conducted structured phone interviews 4 to 6, 11 to 14, and 30 to 40 dys after enrollment to
determine outcomes.
Main Outcome Measures: Filling of the antibiotic prescription and clinical course.
Results: Overall, 283 patients were randomized either to WASP group (n=138) or the SP group
(n=145). Substantially more patients in the WASP group did not fill the antibiotic prescription
(62%vs 13%; p<0.001). There was no statistically significant difference between the groups in
the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within th e
WASP group, both fever (RR 2.95; p<0.001) and otalgia (RR 1.62; p,0.001) were associated
with filling the prescription.
Conclusion: The WASP approach substantially reduced necessary use of antibiotics in children
with AOM seen in an emergency department and may be an alternative to routine use of
antimicrobials for treatment of such children.
Inhaled steroids are associated with reduced lung function decline in subjects with asthma
with elevated total IgE. DeMarco et al. JACI 2007;119:611611-17.
Background: Few studies have invertigated the association between ICSs and lung function
decline in asthma.
Objective: To evaluate whether prolonged treatment with ICSs is associated with FEV1 decline
in adults with asthma.
Methods: an international cohort of 667 subjects with asthma (20-44) years old) was identified
in the European Community Respiratory Health Survey (1991-93) and followed up from 1999-
2002. Spirometry was performed on both occasions. FEV1 decline was analyzed according to
age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for
potential cofounders.
Results: As ICS use increased, the decline in FEV1 was lower (p trend=0.025); on average,
decline passed from 34 mL/y in nonusers to 20mL’y in subjects treated for 48 months or more
(18%). When adjusting for all covariates, there was an interaction (p=0.02) between ICS use and
total IgE: in subjects with high (>100) IgE, use for 4 years or more was associated with a lower
FEV! Decline (23mL/y) compared with nonusers. This association was not seen in those with
lower IgE.
Conclusion: Although confirming a beneficial long-term association between ICSs and lung
functinon in asthma, our study suggests that subjects with high IgE cold maximally benefit from
a prolonged ICS treatment.
Clinical implications: This study adds further evidence to the beneficial effect of inhaled
steroids on lung function in asthma; future studies will clarify whether calibrating the
corticosteroid dose according to the level of total IgE is a feasible approach to asthma
Socioeconomic status and inflammatory processes in childhood asthma: the role of
psychological stress. Chen et al. JACI 2006;117:1014-20.
Background: Although social environment variables such as socioeconomic status (SES) have
been linked to childhood asthma, little is known about the psychobiological mechanisms
underlying this relationship.
Objectives: The goal of this study was to investigate relationships among SES, psychological
stress, and immune processes implicated in asthma. METHODS: Thirty-seven children ages 9 to
18 years, physician-diagnosed with asthma, and 39 healthy children participated. Families were
interviewed about chronic life stress, perceptions of threat, and SES. Blood samples were drawn
from children to assess stimulated production of cytokines implicated in asthma (IL-4, IL-5, IL-
13) and eosinophil counts.
Results: In children with asthma, lower SES was associated with heightened production of IL-5
and IL-13 and higher eosinophil counts (P values < .05). Lower SES also was associated with
higher chronic stress and perceived threat (both groups: P values < .05). Higher levels of stress
and threat perception were associated with heightened production of IL-5 and IL-13, and higher
eosinophil counts in children with asthma (P values < .05). Statistical mediation tests revealed
that chronic stress and threat perception represented statistically significant pathways between
SES and immune processes in children with asthma (P values < .05). In healthy children,
associations were in the opposite direction from the asthma group, though generally not
Conclusion: This is one of the first studies to document empirically a psychobiological
explanation for the epidemiologic relationship between low SES and poor asthma outcomes.
Conclusions: Associations among SES, psychological stress, and immune pathways suggest that
the experience of stress, particularly among lower SES children, has implications for childhood
asthma morbidity.
Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a
randomized, double-blind, placebo-controlled study. Pajno et al. JACI
Background: Atopic dermatitis often has an allergic component, and immunotherapy may
therefore prove beneficial.
Objective: To assess the effect of sublingual immunotherapy (SLIT) in children with atopic
Methods: Children age 5 to 16 years with atopic dermatitis (Scoring Atopic Dermatitis
[SCORAD] > 7) and sensitization to dust mites alone, without food allergy or chronic asthma,
were enrolled in a randomized, double-blind, placebo-controlled study and stratified according to
disease severity. SLIT or placebo was given for 18 months in addition to standard therapy.
SCORAD, visual analog scale, and rescue medication consumption were recorded at 3-month intervals. Results: Fifty-six children were enrolled, and 28 were allocated to SLIT. Forty-eight completed the study, with 2 dropouts in the active and 6 in the placebo group. The difference from baseline in the SCORAD was significant (P = .025) between the 2 groups starting from month 9. Similarly, there was a significant reduction in the use of medications only in the active group. A trend toward significance was seen for the visual analog score only in the active group versus baseline (P = .07). A significant difference in the considered parameters was found only in patients with a mild-moderate disease, whereas severe patients had only a marginal benefit. SLIT had to be discontinued in 2 patients because of exacerbation of dermatitis. Conclusion: Sublingual immunotherapy to dust mite improves mild-moderate atopic dermatitis. Clinical implications: Sublingual immunotherapy may represent an additional therapeutic tool for the treatment of extrinsic atopic dermatitis in properly selected children.


Microsoft word - september 12 2006 usac summary.doc

September 12, 2006 USAC Meeting Summary Submitted by Terri Weaver, 2006-2007 USAC Chair Thanks to all who have submitted suggestions/questions/concerns to the University Staff Advisory Committee. Please join us in our discussions by continuing to post messages through the staff advisory council website: ( Members in Attendance: Eri



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