There are many tools that can help suggest the presence of
food allergies, but, in the end, the most reliable procedure to confirm or
exclude a diagnosis of food allergy remains the oral challenge. But how should allergists perform them? In this month’s issue of JACI, Drs.
Ballmer-Weber and Beyer provide their insights on how to effectively conduct a
food challenge (J Allergy Clin Immunol 2018; 141(1): 69-71). The majority of
children with food allergies require such challenges to diagnose their
condition, especially younger children with eczema who have skin prick or blood
tests suggesting that allergic sensitization may be a trigger for eczema
flares, or in whom a food allergy may no longer be present. However, not all patients should have
challenges. The risks of a severe, life-threatening
anaphylactic reaction have to be balanced with the benefits of more
definitively establishing a diagnosis.
In addition, the risks of an oral challenge may be too high in those who
are pregnant, have unstable asthma, or take medications that would interfere
with the treatment of challenge-induced allergic reactions, such as
Beta-blockers. The presence of other
conditions, like hives, uncontrolled eczema, allergic rhinitis, mast cell
disorders, or acute infection may make interpretation of results difficult and
therefore influence an allergist’s decision to pursue an oral challenge. Regardless, a very careful examination is
necessary beforehand. Once the decision
is made, increasing doses of a particular food are given, usually every 30
minutes, but there is considerable flexibility in the amount of food, number of
steps, and the time in between each step.
Throughout the challenge, patients have to be monitored. If there are any objective signs of food
allergy, the challenge should be stopped and treatment started. If the patient tolerates the challenge with
no reaction, then the food should be taken at least three times per week to
maintain tolerance. Although it is the
most accurate tool that the allergist has, false-positive results do occur, in
as many as 1 out of 25 challenges.
False-negative results can also occur, especially if the food allergy
tends to occur with an additional cofactor which was not accounted for in the
challenge, like alcohol use, exercise, or viral infection. In conclusion, oral challenges are a powerful
tool to identify food allergies, but safety always comes first and results have
to be placed in their right clinical contexts.
JACI Journal Club
Each month, the Editors of the Journal of Allergy and Clinical Immunology will select two JACI articles for discussion. Readers are invited to send in their questions and comments, which will be addressed by the authors. Articles highlighted on this blog are available free of charge from the links in each post.
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Tuesday, January 9, 2018
Food allergy: Update on prevention and tolerance
The
rate of food allergies in the United States keeps on rising, but nobody really
knows the exact reasons why. In this
month’s issue of the Journal of Allergy and Clinical Immunology, Du Toit and
colleagues review the literature and focus on the ‘dual allergen’
hypothesis (J Allergy Clin Immunol 2018; 141(1): 30-40). Briefly, they explain that
allergic sensitization may occur when there is low-level skin exposure to food
allergens, while tolerance is more likely to develop in children to have early
exposures to food proteins. The data are
mounting from both animal and human observational studies as well as randomized
control studies. The most notable has
been the LEAP study, which showed that infants aged 4 to 11 months who consumed
peanut products at least three times per week until age 60 months were far less
likely to develop peanut allergies than infants who had complete
avoidance. Only 3.2% in the
peanut-eating group developed peanut allergy, compared to 17.2% in the complete
avoidance group. The follow-up study,
LEAP-On, demonstrated persistence of this tolerance for at least 12 months,
even with strict avoidance in non-peanut allergic children. Similarly, the EAT study suggested that lower
rates of food allergies with early introduction of allergenic foods in
breastfed infants, although conclusions were less clear-cut than in the LEAP
study. The results of other studies have
been more variable. Regardless, the LEAP
and EAT studies show that early introduction of allergenic foods into infant
diet is achievable and safe, and does not affect breastfeeding rates as well as
later nutrition and growth. However,
there are a lot of challenges. Ensuring
adherence to dietary recommendations, determining the dosages of food proteins,
and powering studies sufficiently to show meaningful differences are challenges
that researchers and clinicians face.
This has led to the National Institutes of Health’s recommendation for
early peanut introduction to prevent peanut allergy. Other countries have also recommended
inclusion of potential common food allergens in complementary feeding regimens
at around 6 months. With more research,
it is possible that we may find more effective ways to help prevent food
allergies.
Thursday, October 26, 2017
Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index
Asthma
affects about 1 in 11 American children, making it one of the most common
diseases of childhood. It carries a huge burden on families, especially
during exacerbations when disease activity suddenly flares, leading to
breathlessness and even death. In this month’s issue of JACI, Hoch and
colleagues discuss their research in validating the Seasonal Asthma
Exacerbation Predictive Index, the saEPI (J Allergy Clin Immunol 2017; 140(4): 1130-1137). The saEPI is a score ranging from 0 to 16 that can
help predict how likely a child is to have an asthma flare. Using data
from the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations
(PROSE) study, they looked at 348 children randomized to two groups: one with
omalizumab, and another with guideline-based therapy alone. They then
calculated and validated the saEPI, moreover the authors looked at other
factors that were associated with exacerbations. In short, they found
that children who required more aggressive treatment (high doses of inhaled corticosteroids),
had higher blood eosinophils, and were younger were more likely to have a
flare. The saEPI, on the other hand, was better at determining which
children were unlikely to have an asthma exacerbation. The authors
encourage providers to use data such as this to personalize their care of
children at risk for asthma exacerbations. Because the children that were part
of the PROSE study were largely from inner-city and minority populations and
the study inclusion criteria limited some children from particpating, a similar
analysis should also be performed in a more general population of children, as
well as adults. Regardless, the researchers conclude by noting the
importance of such an index in managing children with asthma until even better
methods are identified to classify children with asthma at risk for an asthma
exacerbation.
Wednesday, October 25, 2017
Role of viral infections in the development and exacerbation of asthma in children
Wheezing is a common complaint among parents of
infants. About 1 in 5 children have
acute wheezing illnesses in their first two years of life. This is important because an overwhelming
majority of these wheezing illnesses are related to viruses, and are linked to
asthma development. In this month’s
issue of JACI, Jartti and Gern review the role of viral infections in the
development of asthma in children (J Allergy Clin Immunol 2017; 140(4): 895-906).
They survey the viruses -rhinoviruses, respiratory syncytial
viruses, and others – and how they impact the developing set of lungs. Genetic variation and low interferon
responses are two factors that increase the risk of these types of
infections. In addition, increased
eosinophil counts in blood and nasal mucus and atopic eczema all increase the
risk of later asthma.
Additionally, viral infections can lead to exacerbations in
children who already have asthma. This
may explain why the rates of asthma exacerbations are higher during the fall
and winter, and why omalizumab, a potent medication for asthma control, may
help to prevent exacerbations due to viruses like rhinovirus. The authors conclude that these insights may
allow for new strategies to help prevent and manage viral wheezing illnesses so
that they don’t lead to and worsen later asthma.
Tuesday, October 24, 2017
Promising approaches for the treatment and prevention of viral respiratory illnesses
There are hundreds of viruses that cause respiratory tract
infections. While most of us think about
them as nuisances causing cough and wheezing, they bear a huge toll on health,
especially in people who have lung diseases like asthma and COPD, as well as an
economic toll in lost workdays and inappropriate use of medical resources. In this month’s issue of JACI, Papadopoulos
and colleagues look at the treatment and prevention of these diseases (J Allergy Clin Immunol 2017; 140(4): 921-932).
They look at new medications that target the specific viruses
in their reproductive phases. In
addition, they review how natural products like echinacea can prevent recurrent
respiratory tract infections. On the
other side, there are promising insights about the use of immunostimulators in
order to boost the body’s own responses to these viruses. Vitamin D, probiotic supplements, exercise
and meditation are all helpful in resolving these infections. But perhaps the
most promising strategies are in prevention, where vaccines are being developed
to prime the immune system to fight against viruses. Currently, vaccines are available only against
influenza virus. There are other
developments on the horizon and may have a tremendous effect on addressing
these diseases. The authors conclude that multiple strategies are necessary and
that there may be tremendous benefits in such research, especially when it
comes to dealing with more severe diseases that can cause epidemics and
pandemics.
Tuesday, September 19, 2017
Diagnostic accuracy of fractional exhaled nitric oxide in predicting cough variant asthma and eosinophilic bronchitis in adult patients with chronic cough: A systematic review and meta-analysis
Cough is an important reflex we
need to remove irritants from the airways, but for many people, a
hypersensitive cough reflex can negatively affect quality of life. A major trigger of chronic cough is airway
inflammation from immune cells including type
2 helper T-cells (TH2), but conventional tests required for
diagnosis are technically challenging and often require specialist
expertise. Fortunately, measurement of
the fractional exhaled nitric oxide
(FENO), a potential marker of TH2 airway inflammation, has become
much more common in allergy and pulmonary practices. In this month’s issue of JACI, Song and
colleagues review the literature on the use of FENO to diagnose Cough-Variant
Asthma (CVA) and Eosinophilic Bronchitis (EB), two major causes of TH2-mediated
chronic cough (J Allergy Clin Immunol 2017; 140(3): 701-709).
They looked at thousands of
articles from multiple databases in order to answer the question “What is the
diagnostic accuracy of FENO for CVA and/or EB in patients with chronic cough?” After an exhaustive search, they found 15
studies with 2187 adult patients. The
authors then collected and compared the data to determine the accuracy. Overall, when looking at either CVA or EB,
the pooled sensitivity and specificity were 0.73 and 0.89. For diagnosing CVA, they found moderate
diagnostic accuracy, suggesting that the FENO test alone is not sufficient to
diagnose CVA. However, its high
specificity means that it may be more useful as a rule-in test than as a
rule-out test. In contrast, results for
EB suggested that FENO testing may not be precise enough for prediction.
This article provides guidance on
how to further research on how best to use FENO testing in patients with
chronic cough. However, there remain many unanswered questions because of
limitations of the review, including the limited number of studies,
generalizability of studies which were mostly conducted in Asia, and the
imprecision of current diagnostic criteria for CVA.
Tuesday, September 12, 2017
Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients
Asthma is a complex disease of the
airways characterized by inflammation and dynamic airway obstruction. Despite the single, more recent evidence
suggests that asthma is mediated by a set of distinct immune abnormalities. In this month’s issue of JACI, Silkoff and
colleagues report the results of the ADEPT (Airways Disease Endotyping for
Personal Therapeutics) study, in which 83 patients with mild, moderate, and
severe asthma as well as 25 healthy non-asthmatic subjects were examined for
biomarkers of asthma (J Allergy Clin Immunol 2017; 140(3): 710-719). They underwent
bronchoscopy to obtain tissue samples, and then had the biomarkers measured in
the lab to characterize them as having either high or low levels of type 2
inflammatory mediators. These were then
correlated with clinical variables.
They determined the presence of
type 2 inflammation based on airway expression of CCL26, periostin, and IL-13
in vitro signature (IVS). They then
looked at the clinical variables, including fraction of exhaled nitric oxide
(FENO) levels, blood eosinophil counts, serum CCL26 expression and serum CCL17
expression. What they found was that the
combination of Fractional Excretion of Nitric Oxide (FENO), blood eosinophil
counts, serum CCL17 and serum CCL26 had a positive predictive value of 100% for
patients determined to be in the asthma group driven by type 2
inflammation. This is important because
individual clinical characteristics alone could not predict the pattern of type
2 inflammatory markers, and eosinophilic inflammation was associated with , but
not limited to, gene expression for type 2 inflammation in airways.
By describing a set of relatively
easily obtainable clinical markers consistent with type 2 inflammation, the
authors report information that can help researchers and practitioners tailor
the most appropriate therapy for those with asthma mediated by type 2
inflammation.
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