Practical guide to skin prick tests in allergy to aeroallergens

I was alerted to this article by my partner Dr. Vitalpur. It comes from Allergy (European Journal of Allergy and Clinical Immunology) 2011 . The purpose of the article was to provide ‘pocket guidelines’ from a consensus report regarding the use of allergy skin prick tests for inhalant or aeroallergens.

The skin prick test (SPT) is a widely used, major diagnostic tool used for the diagnosis of allergy. The introduction of the article points out the many complexities in performing SPTs and recommends that they should be performed only by trained health professionals.

As for the methods used to create the guide; it was a combined effort from the Global Allergy and Asthma European Network (GA²LEN) and the Allergic Rhinitis and its Impact on Asthma (ARIA) task force. Once the document was created, it was reviewed by the membership of the networks. The authors point out that this is not an evidence-based guideline. It should be looked at as ‘…clear-cut answers to frequently asked questions by practitioners and patients.’ The evidence-based aspect follows the guide-in future reports.

The article is broken down into a series of 21 specific questions:

1. What are the indications for skin tests in clinical practice?
2. Which skin tests are recommended?
3. What role do intradermal tests play?
4. What is the recommended skin prick test technique?
5. Which treatments suppress skin tests?
6. Which diseases affect skin tests?
7. Which allergen extracts to choose?
8. Which allergen extracts should be tested?
9. What area of the body should be chosen and what is the ideal distance between tests?
10. Which negative and positive controls are recommended?
11. Which results are regarded as positive?
12. How do skin tests compare with serum-specific IgE?
13. How to interpret skin test results?
14. Which skin tests are recommended in adolescents and adults?
15. Which skin tests are recommended in the elderly?
16. Which skin tests are recommended in young children?
17. What is the role of skin tests in primary care?
18. How can skin tests be used in developing countries?
19. Are skin tests needed in allergen immunotherapy follow-up?
20. Can skin tests be used in research?
21. What are the future needs?

Each question has a short, concise answer. These are common concerns and questions. I would like to point out a few of them for this review. The link will direct the reader to questions not covered here.

1. What are the indications for skin tests in clinical practice?

Asthma and allergic rhinitis are the indications for aeroallergen testing. The SPTs can be used from infancy to old age. The repeating of SPTs is done to detect new sensitizations in children and when changes in symptoms have occurred. 

2.Which skin tests are recommended?

Prick skin tests have a high degree of correlation with symptoms. There is high specificity (a negative test when you do not have the disease) and sensitivity (when the test is positive when you have the condition) with the skin pricks used for inhalant allergy.

 Table 1 Performance of skin prick tests

1. Use standardized extracts when available (We have grass, house dust mites, and cat as standardized extracts.)
2. Include a positive and a negative control solution (histamine is the positive control)
3. Perform tests on normal skin (not on skin affected by severe eczema or urticaria)
4. Evaluate the patient for dermatographism (Means skin writing- pressure to the skin will cause a hive, this is a common reason for someone to allergic to everything including the negative control.)
5. Determine and record medications taken by the patient and the time of the last dose
6. Record the reactions after 15 minutes
7. Measure the longest wheal diameter

Skin prick testing may cause systemic reactions

The common errors in skin testing are listed in table 2

• Tests are placed too close together and overlapping reactions cannot be separated visually.
• Induction of bleeding, leading possibly to false-positive results.
• Insufficient penetration of the skin by the puncture instrument, leading to false-negative results. This occurs more with plastic devices.
• Spreading allergen solutions during the test or when the solution is wiped away.

 3. What role do intradermal tests play?

Intradermal skin tests (when a needle is used to inject the extract- almost like a TB test) are not useful for allergy diagnosis with inhalant allergens. The clinical value is unknown in patients who only have positive intradermal tests. They are less safe to perform. There are practices where this is the only type of test done or they are performed when the SPTs are negative. We use this type of test ONLY in the ‘Bee Clinic’- the protocol for pursuing stinging insect allergy utilizes the intradermal test.

4. Which treatments suppress skin tests?

Drugs can suppress skin tests.

 Antihistamines- have a significant impact on skin test results. They should be avoided for 7 days

Imipramine- anti-depressants, sometimes used for bed wetting- can affect skin test results for 21 days

Steroid ointments and creams- minimal if any effect on skin testing

UltraViolet light – used to treat skin condition, can effect skin test results for up to 4 weeks

Table 3 Inhibitory effect of various treatments on skin prick tests show other agents that may impact skin test results.

5. Which diseases affect skin tests?

Patients with widespread eczema or hives cannot be tested in areas of affected skin. Neurological disorders and infectious diseases (e.g. leprosy) can lead to false-negative results.

6. Which allergen extracts to choose?

The quality of the allergen extract is of key importance as variations in the quality and/or potency of commercially available extracts exists, in particular for animal mites, animal dander, and molds, but even pollens. Use standardized extracts if available.  

7. Which allergen extracts should be tested?

This varies per region. This answer was relevant to Europe. I comment on this at the end of the review.

 8. What area of the body should be chosen and what is the ideal distance between tests?

Usually, the skin tests are performed on the forearms depending on the age of the patient. The distance between tests should be 2 cm. We have used the child’s back for testing. There is a larger surface area to work with. If needed, more items could be evaluated using the larger space. It is also an area which would not be frequently treated with a topical steroid.

 9. Which results are regarded as positive?

The wheal and erythema have been used to assess the positivity of the skin test. However, only the wheal is needed. The largest size of the wheal is considered to be sufficient. Wheal diameters equal to or larger than 3 mm are considered positive in SPTs.  

Redness alone is not a significant response. There needs to be a wheal (swollen area) of proper size to be called significant. In our clinic, the physician who ordered the test reads them and decides on the significance. All too often, slight red marks are interpreted as positives.

 10. How do skin tests compare with serum-specific IgE?

Serum-specific IgE, SPTs and allergen challenge do not have the same biological and clinical relevance and are not interchangeable. Low levels of serum-specific IgE are less often associated with symptoms than higher levels, but they do not exclude allergic symptoms particularly in very young children.

Note- the paper did not use the term RAST. The proper term is serum-specific IgE- that blood test for allergy. I thought that the answer to this question was not as complete as it should have been.

 11. Are skin tests needed in allergen immunotherapy follow-up?

Skin test reactivity decreases with allergen-specific immunotherapy to inhalant allergens, but skin tests cannot be used to assess the efficacy of immunotherapy in practice. Moreover, skin tests cannot be used to decide the cessation of immunotherapy.

Reviewer’s Comments-From the original 21 questions, I chose 11 that tend to be more frequently brought up in our practice. Many of the questions that I omitted dealt with issues unique to Europe or to the adult population.

In a nutshell the skin prick tests for aeroallergens (inhalant allergens) are:

• Indicated for respiratory tract symptoms
• Can be done in very young children
• Should be done with the proper extracts and application technique
• Can be done if a few medications are out of the child’s system
• There may be a problem finding clear skin to do them on a child who has eczema or hives
• May be done on the arms,
• Are considered positive if the wheal (swollen area) is of proper size (redness alone does not qualify)
• Should not be used to monitor an allergy shot program.

This was a very neat, concise, and well done synopsis of how things are done in Europe. An additional tidbit was the answer to the question- Which allergens should be tested? The quick answer is that it depends on the allergen exposure for the area and that a common, standardized battery of tests should be recommended for Europe. The list was short;

• Pollens- Birch, Cypress, Grass (one species or a mix), Mugwort, Olive (or Ash), Parietaria, Plane, and Ragweed
• Mites- two species
• Animals- Cat and Dog
• Mold- Alternaria and Cladosporium (Aspergillus extract is not available in all countries).
• Insects- Cockroach

That panel for respiratory tract allergens would contain only 15 aeroallergens plus the two controls- 17 skin tests done to assess allergen sensitization.

A reference was also made to the National Health and Nutrition Examination Survey (NHANES) performed in the United States (2005) – 10 allergens were used.

FEL

11-30-2011

The document I am going to review is ‘2011 Burden of Asthma in Indiana’ from the Indiana State Department of Health (ISDH).

Writer’s note- as I reviewed this I got confused and I was not sure what year I was looking at. The same concerns may occur with your reading. The basis for the confusion is that this is the 2011 Asthma Burden Report. The first sentence in the Introduction says it is the 2010 Indiana Asthma Burden Report, yet all the data is 2009? Since it takes time to collect information and to run an analysis, my guess is that this is the Burden of Asthma in the State of Indiana in 2009 with some 2007 information included. Just watch the dates on the data.

A few facts regarding asthma in Indiana-in children;

• Asthma is the third leading cause of hospitalization for children under the age of 17 years.
• In 2009, an estimated 150,000 children (9.9%) reported currently having asthma.
• Nearly 15% of children reported having been diagnosed with asthma at some point during their lifetime.
• Nearly 24% of high school students reported having asthma at some time in their lives and 12.2% reported having current asthma in 2009.

The information in the report comes from a questionnaire, the Behavioral Risk Factor Surveillance System (BRFSS). This is a telephone survey. Using 2009 (the ISDH website as of 5-23-2011), there were 9,288 randomly selected individuals who were called and asked to participate. The response rate was just over 47%. What follows is asthma information for the state of Indiana regarding children (17 years of age or younger) from the BRFSS 2009 and a few interesting points regarding the entire sample.

            Since 2007 the lifetime and current rates of asthma have increased significantly. The prevalence of lifetime asthma is close to 15% and is above the national average for the year 2009. The prevalence of current asthma is also higher than the national average in 2009 (just under 10%). 

            The hospitalization rate for asthma (age-adjusted) has increased since 2007 and is 13.9 hospitalizations/10,000 residents in 2009.

            Age-adjusted emergency department visits for asthma have increased significantly since 2004; 30.4/10,000 residents to the 2009 rate of 49.7/10,000.

            Asthma mortality- death due to asthma is rare and are below national averages and continues to decline (end point was 2007).

            The highest rate of hospitalizations in Indiana was found among boy’s ages 0-4 years – 36.5/10,000 residents. Boys tended to have higher hospitalization rates until age 14 years at which time girls and women had significantly higher rates of hospitalization. Emergency department visits followed the same trend- more seen in boys less than 15 years of age then females more than males after age 15 years.

            Asthma can and does affect people of all races and ethnicities. This information was not broken down for children. The report is only on adults but does show which groups tend to be more or less affected. Hispanic adults had the lowest rate of asthma prevalence at 4.3% as well as the lowest rate of emergency department visits and hospitalizations. The white population had a prevalence of 9.2% and the black population had 12% asthma prevalence. Hospitalization occurred three times more often in the black population when compared to the white population.

            The report also looked at income, education, and geographic variation (county prevalence).

            There is a very interesting page on risk factors or behaviors associated with asthma. This however is not from 2009. This is information from the 2007 BRFSS. The following is a selection from that 2007 listing of behaviors reported by adults with asthma in Indiana.

• 40% were advised about changing the environment
• 10% had seen, smelled, or suspected mold in their environment
•   4% had seen cockroaches
•    5% had seen mice/rats in their homes
•  20% used a house dust mite cover on their bedding
•  80% had carpeting or rugs in their bedrooms
•  27% used a dehumidifier to reduce moisture
•  34% used an air purifier
•  57% had pets
•  28% had someone smoke in their home within the past week
•  29% were smokers

Writer’s note; look at all the allergy potential in this listing. Allergen triggers for asthma would include mold, roach, mice, dust mites, and pets.

Protecting them against asthma. This also comes from 2007 and deals with adults with asthma.

• 69% reported on getting instruction on how to recognize signs of an attack
• 77% were taught what to do during an asthma attack
• 33% received an asthma action plan
•   6% had taken a course on how to manage asthma

Health Interventions

            The document lists a number of endeavors out there to help with education including the ISDH Asthma Program and the Indiana Joint Asthma Coalition (InJAC).

 Reviewers Notes

These reports are notable. My tendency is to pick away at details and ask questions. There is a wealth of information within the report, however it can be confusing and sometimes it is not totally clear why something appears and for what year. A suggestion would be to make sure the reader knows the ‘when’ of the information- 2011, 2010, or 2009, or even 2007. You can see this report on the ISDH website. There are links to background information. However, the final document should be considered a ‘stand alone’ document and should mention the methodology and specifics of the population. I was also not clear about information that clearly was not from 2009. There were presentations of information from 2007. Was this new for a burden report? Was this a re-iteration from a past report? These reports follow a format; Introduction, Goals, Trends, Disparities, Risk & Protective Factors, Conclusion, Resources, References, and Appendices. Was all the information available from the 2009 BRFSS? Will we see 2009 data later? There should have been some explanation as to why the timeline skipped around so much. That would have been very helpful for this reader.

This is the state of asthma within our state. Clearly more needs to be done. There is clearly more ‘asthma’ out there. We are higher than the national average for children. There are more emergency department visits for asthma. There are a number of possible allergy issues involved.

The ISDH has a state asthma plan and a partner organization InJAC that is looking for interested partners to help make a difference. Checkout the InJAC website and join us.

FEL

I was intrigued to see a recent article in the American Journal of Respiratory and Critical Care Medicine (Volume 183. pages 582-588, 2011) that dealt with asthma and swimming pools. The title of the article was ‘Swimming Pool Attendance, Asthma, Allergies, and Lung Function in the Avon Longitudinal Study of Parents and Children Cohort’ written by Font-Ribera and others. What follows are a number of interesting points about swimming pools and asthma that appear in the article.

Background

There is the suggestion that swimming in chlorinated swimming pools is a risk factor for developing asthma. The theory was that cleaning products had an effect on the airway which could lead to the development of asthma. Studies were references showing increased asthma in lifeguards and a higher prevalence of asthma in elite swimmers.

These observations were also thought to be due to ‘reverse causation (where the effect preceded the cause)’- swimming is recommended for those with asthma.

There have been many epidemiologic studies done in Europe regarding swimming as a risk factor for asthma, however the results are conflicting. Of note is the statement “….there is agreement on the complexity of the potential role of swimming asthma etiology and the important public health implications.

Asthma is one of the most common chronic conditions in childhood and swimming is one of the most popular sports/activities. So, a study was done to address some of these issues

The purpose of the study

To examine whether swimming at different periods during early childhood is associated with the prevalence of asthma and allergy symptoms.

How they did it

This was part of a large cohort study. In such a study a group of children are recruited and watched over time for events to occur. This was done as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) and comes from the United Kingdom. More than 5,700 children were evaluated. Asthma symptoms were reported using a standardized tool (the International Study of Asthma and Allergies in Children- ISAAC). Lung function was measured and a methacholine challenge was performed (measures airway hyper-reactivity)

Swimming frequency was asked at various times of the child’s life. There were a variety of possible confounding variables looked at as well; sex, birth weight, number of siblings, atopy, maternal education, maternal and paternal social class, maternal age at delivery, maternal asthma, allergy and hay fever, contact with pets, hours of TV watching, exposure to environmental smoke, and body mass.

What they found

The total number of children in the study was 5,738. Only 12% of the mothers had asthma. Positive allergy skin tests were seen in 21.4%. Asthma was present in 20%.

The crude and an adjusted model looked at using a variety of variables and both gave similar results. When all the confounders were accounted for, swimming was not associated with ever having asthma. Interestingly, swimming was associated with a lower prevalence of currently having asthma and currently using asthma medication at age 7 years. There was also no significant association seen between swimming and current wheezing, eczema, nasal symptoms, or eye symptoms at age 7 or at age 10 years.

The data was looked at from the perspective of the effect of swimming when there were previous respiratory tract symptoms at different ages. The protective effect of swimming was only seen among children who wheezed prior to age 3.5 years.

Of note, there was no significant association between swimming and bronchial hyper-reactivity.

Swimming also did not increase the risk of any respiratory tract symptom in children who were atopic.

Conclusions

This large prospective birth cohort study did not find that swimming increased the risk for asthma, atopy, or any respiratory/allergic symptom in British children. Swimming was associated with better lung function and decrease asthma prevalence in children who had previous respiratory tract symptoms.

The authors do point out a few problems with the study. The questionnaire asked about swimming and not swimming pool attendance. It was assumed that since this was done in the United Kingdom and the weather being what it is, the assumption was that the affirmative answer did refer to pools. Chlorine is the most commonly used disinfectant. However, no information was collected regarding the amount of chlorine exposure.

Reviewers Note

This was a large study and a prospective study that looked into a very practical question. The more children the study, the stronger the conclusions.
Swimming did not make things worse and in fact lung function was better and the risk of asthma symptoms and medication used was lower in those children who were known to have wheezing when they were younger.

Swimming is a good thing!

FEL

Does improvement management of atopic dermatitis influence the appearance of respiratory allergic diseases? A follow-up study. Clinical and Molecular Allergy 2010 8:8 Published June 30, 2010. Authors- G Ricci, A Patrizi, A Giannetti, A Dondi, B Bendandi, and M Masi.

Background and purpose of the study

Atopic dermatitis (AD) is one of the most common skin conditions that affect children. AD is characterized by dry, itchy, rough, and flaky skin. Between 70-80% of children who have AD have an elevation of the antibody associated with allergy- IgE and antibodies to foods/inhalants.  Many children outgrow this condition and in some it persists into their adulthood. In some children AD is the first step along the allergic march; going on to have asthma and allergic rhinitis. Depending upon who you ask or quote, 25-80% go on to have asthma. That is a huge range. The authors of this study published a 10 year follow-up study in 2006 looking at this issue. They showed that the AD disappeared in 60%, 34% developed asthma, and 58% developed nasal allergy. So some, not all finish the allergic march with a better chance of having nasal allergy and about a 1/3 chance of developing asthma. This begs the question as to whether or not anything can be done about it.

This current study looked at the effect of clinical management on the subsequent development of other allergic conditions and they used more standardized and contemporary measures of the conditions in asking what are the risk factors in children who have AD that may predict the development of other allergic conditions.

This is a study from Italy. It was a retrospective analysis; children who had AD between 9-16 months of age were contacted for participation. They had to have been seen in the clinic between 1993-2002.

Methodology

The assessment included;

1. Diagnosis of AD based on Hanifin and Rajka criteria (well established for this condition)

2. AD was evaluated by the SCORAD index at the first visit ( a measure of disease severity)

The clinical management program involved;

1. Environmental management- house dust mite avoidance, high-filtration vacuum cleaning,

2. Skin care- emollients, topical corticosteroids, calcineurin inhibitors, oral steroids, immunosuppressants, biologicals, antibiotics, antihistamines, and leukotriene inhibitors

Allergy Assessment;

1. Skin prick tests (SPT), total IgE  and specific IgE tests- milk, egg, soybean, wheat, peanut, nut, codfish, apple, grass pollen, house dust mite, cat dander, and dog dander. A positive was any value >0.35 for the blood test and a wheal response on the SPT.

Telephone interviews

Results

Telephone interviews were conducted with the families of 176 children. Their ages ranged from 6-12 years. The average age at the time of the first evaluation was about 1 year.

One hundred of the 176 (57%) showed a sensitization by SPT to at least one of the foods/inhalants.

One hundred and three of the 176 (58.5%) had an elevation at least one specific IgE blood test.

After an average of 7.5 years 84 (48%) still had AD- it disappeared in 52%. In the group of children who still had AD, 44% had a single site involved (mostly on a limb) and 18% had multiple locations of AD.

When AD disappeared on the average, the child was 3.25 years old.

In this group of children, respiratory allergy conditions appeared in 66/176 (37.5%).The specific respiratory ailments were; 36 (20.5%) developed only nasal allergy, 18 (10%) developed only asthma, and 12 (7%) developed both.

The nasal allergy appeared at 4.8 years of age. The mean age of appearance of asthma was 3.33 years. Asthma tended to precede the development of the nasal allergy.

A mathematical model, logistic regression, was used to predict the occurrence of asthma. A child who developed nasal allergy or was positive to at least one inhalant (serum specific IgE >0.35) at the time of the first evaluation had a greater risk to develop asthma (odds ratio was 4.219).

Conclusions (authors’)

The results of this study were compared to their earlier study in which disease-specific management was not evaluated. In the current study, the use of integrated management of AD did not seem to influence the natural course of AD. However, the early diagnosis and improved management at specialty centers decreased the percentage of children who went on to develop respiratory allergic disease. The presence of early allergic sensitization at age 1 year may predict the development of respiratory allergy.

                                Percentage of Children with Allergic Conditions – Comparing the two studies

                                1981-1989 study                                                                               1993-2002 study

Resolved AD             60.5%                                                                                                  52%^*

Asthma                     34.1%                                                                                                  17%

Nasal Allergy            57.6%                                                                                                  27%

* not significantly different

In the present study at age 8 years (mean age of the children) 15% already had asthma. In the previous study, 29% had asthma by age 8 years. The management program accounted for a reduction in the appearance of asthma in this group. Similarly, the percentage with nasal allergy fell from about 35% to 17%. This could be due to better management of the AD.

This study used quantitative evaluations with determinations of specific IgE sensitivities and the use of improved clinical tools for assessing AD (SCORAD index, environmental prevention, integrated management) that helped with the early diagnosis, appropriate therapy, and monitoring of children with AD. This may have been  helpful in decreasing the numbers who go on to have respiratory allergy.

Reviewer’s comments

I was surprised at the wide range of children who go on from Atopic Dermatitis to Asthma to Allergic Rhinitis. More definitive epidemiologic work is needed to have a more precise estimate. I hear all too often from other allergists that it is an absolute fact; if the child has AD they will have…..This group of investigators had previously  looked at this evolution to other allergic conditions in the 1980s. This earlier study served as a nice comparison group for the current study.

Back in the80′s the tools and criteria differed. The current study tries to standardize the diagnosis of the allergic conditions. The entire group of children were evaluated with the same tools for AD severity and for respiratory allergy.

This study looks at the impact of early evaluation and the impact of management programs on the occurrence of detouring children who may have been on that allergic march. The first detour was asthma and the second change of course was allergic rhinitis.

Evaluation and management seems to re-direct some of these children away from respiratory allergy. it is not known if these conditions appear later in life. That will be a paper for review perhaps 10 years from now.

 The foods that were important were eggs and milk. A specific IgE level was >2.0KU/L to milk or egg was found to be predictive of sensitization to inhalants in late infancy.

Other considerations are that this is a group of children from Italy- the genetics may differ and certainly the environment differs. Such a study needs to done on our population of children to see if the results can be replicated.

As noted by the authors, demographic information was lacking making it a bit more difficult to describe and characterize the population.

Do we need to be more aggressive with our AD children? When should all these evaluations be performed. In this study many of the children had progressed and were very severe at the time they presented to the specialty clinic. The study did not look at how long treatment should be tried before embarking on a more Allergy/Dermatology Specialty oriented evaluation.

I like the selection of allergy tests here. Nut and apple were a surprise for a first evaluation for specific IgE to food at age 1 year. We did not see shrimp or scallops as a choice here.  Also, the evaluation for the inhalants was looking at sensitization- has the child begun to make antibodies towards these items? The study used these as associations and not necessarily as cause/effect items.

I think we need to re-think about the number of children who march from AD to other allergic conditions. It never was 100% – here is it about a third of children who do this. A take home message here is to consider being more aggressive with our evaluations, monitor more frequently, and carefully in hopes of halting that march from AD to Asthma to Allergic Rininits.

FEL

During a career you hear many words of wisdom from your mentors who are with you seeing children in the office and from meetings, curbside conversations/consultations, and from the literature. The adage that allergic children get sick easier, more frequently, and have more severe illnesses has been out there for many years. There are a number of theories for this contention. Children with allergy tend to remedy their itchy nose with internal manipulation, otherwise known as nose-picking. The finger serves as the vector for direct inoculation of viral particles onto the respiratory tract. Also, a number of years ago a publication reported that allergic noses actually had more receptors for the cold virus than non-allergic noses.

The May issue of the  Journal of Allergy, Asthma, and Immunology (Volume 125 No 5.) has an article by Jaime Olenec, ‘Weekly monitoring of children with asthma for infections and illness during common cold seasons’ concluded that atopic (showing IgE antibodies) children with asthma do have more frequent and more severe asthma exacerbations due to the common cold. The bottom line for me is the impact that the specialty of allergy and the determination of sensitization to allergens can make on children with asthma. The study did not address allergen control measure effects on frequency/severity of asthma symptoms.

My review of the study-

The group who did this is excellent and has a long established research track record and publication record regarding the role of viruses and allergy in pediatric asthma.

The journal in which this was published is peer-reviewed and a top-notch allergy journal. Also of note is that the manuscript was submitted in September, 2010 and was accepted for publication four months later.

The support for the work was from the National Institutes of Health.

The purpose of the study was to look at the impact of viral infections and allergic sensitization on the loss of asthma control during the peak ‘cold’ season.

The study involved 58 children between the ages of 6-8 years who were known to have asthma. These children were followed for three years. Skin testing and specific IgE testing was performed on all. Nasal samples were collected and analyzed for human rhinovirus infection. Diary cards were kept for symptoms. Cold and asthma symptom scores were collected along with peak flow value recordings and notations of the frequency albuterol (rescue inhaler) usage.

There were 42 children who had at least one season of complete data. The average age was 6.5 years and there were 30 boys and 12 girls. In this group 50% had one or more positive skin prick test for an allergen. Of note is that 69% had one or more positive blood tests for an allergen. Additional baseline information included; daily asthma controller medications used by 88%, and oral corticosteroids were used by 57% in the past year. Fifty five percent of the mothers and 40% of the fathers had allergy.

The number of viral illnesses per season was higher in the allergen sensitized group; 47% more virus-associated illness per season. During documented viral infections (viral cultures were frequently performed), the non-atopic children commonly reported no or mild cold symptoms. In the sensitized (atopic) children symptoms tended to be more moderate or severe. Also, almost half of the viral infections in the sensitized children caused moderate or severe asthma symptoms.

The author’s conclusions were that respiratory tract illnesses (asthma symptoms) due to viruses were more severe and were more frequent in children who are atopic.

These were children with asthma who had a positive allergy test. The terms sensitized and atopy were used to describe the group. Asthma frequency and asthma severity was increased in those who have made at least one IgE antibody to something.

This was a small study which was done in only one site. Larger studies in a variety of populations need to be done to confirm these observations.

This work re-affirms my practice of being aggressive with my allergic asthmatic children when the first signs of a cold occur. I advocate stepping-up the treatment program and continuing it for up to 14 days. One of the charts shows that the average duration of cold symptoms was 8.1 +/- 5.6 days and the average duration of asthma symptoms was 7.2 +/- 7.8 days in those who had a documented rhinovirus infection. For me this fits nicely with what I advise- on the average cold symptoms may begin the day prior to asthma symptoms and at the extremes of the range, asthma symptoms may last 14 days in some children.

FEL

A message was forwarded to me about a news broadcast from Chicago that highlighted a tool that can be used to help with asthma diagnosis and management. The FDA has recently approved this according to the message. This tool is the measurement of exhaled nitric oxide (eNO). In allergic asthma  airway inflammation involves numerous inflammatory cells especially eosinophils. These inflammatory cells have a marker for their involvement and activation called nitric oxide. We are able to measure this by-product of airway inflammation in the breath. I also received another link on this measure of airway inflammation. In this second newsbroadcast Dr. Wolfe, an allergist, does a nice job in explaining this test, this measure, and allergic asthma.

This is not a new procedure. At Riley Hospital our group has been using this measurement in the care of children with asthma. It is nice to see that the concept of eNO is catching on and its value is appreciated.

I feel that a measure of eNO offers a significant amount of information regarding the role of allergy and the level of control patients with asthma have. I use eNO measures frequently in my Allergy/Asthma practice.

FEL

Saints celebrate a Super Bowl win

I just returned from New Orleans where I attended the American Academy of Allergy, Asthma, and Immunology (AAAAI) annual meeting. It was very hard for an Indianapolis Colts fan to venture into the city that beat my team in the most recent Super Bowl. They still celebrate that victory – deservedly so. It’s just that everywhere you go you see ‘Who dat’ Saints stuff. 

At this meeting I had two major agendas; to update my understanding of the conditions I see and care for in my profession and to begin the process of recruiting our third full-time allergist for Riley Hospital. When I got to Riley in 1994, I was the first staff allergist there in 22 years. The allergy service has been up and running. We (Dr. Vitalpur and I) are looking to expand and we need to expand.  We interviewed a few current fellows in training and we look forward to their visits with us. It is exciting to interact with physicians currently in their training programs. These are young people eager and ready to embark on their career choice of patient care, teaching, and research in the field of allergy/clinical immunology. This is an exciting time for the allergy program at Riley. 

In a later posting I plan to include more material on food allergy. I have been invited to give an update from the meeting (food allergy topics only) at a food allergy support group this Tuesday (March 16) in Greenwood, In.  My thought is to have the group hear my presentation first then publish it on the web. The early preview of the update is for the support group. 

Food Allergy 

More on this later however, the meeting had many talks on the concept of ‘tolerance’. The is the condition by which despite a specific IgE (blood test/skin test) to a food that food has been ingested and continues to be ingested without any clinical symptoms. 

Now here is the clinical scenario that we need to think carefully about. Trail mix (made of peanut and tree nuts and other stuff) is ingested and an allergic reaction occurs. The child is treated in the office and the advice is to not eat peanuts or tree nuts. Blood is drawn and the specific IgE is positive to a number of tree nuts and to peanut. The history of food exposure before the reaction indicated that roasted peanut products are eaten every day by this child. Tree nut exposure has occurred in the past but very irregularly. So which food caused the reaction? Peanut which was a daily part of the child’s diet (you have exposure, constant ingestion, and an positive allergy test) or a tree nut (you have exposure, rare re-exposure, and a positive allergy test).  In this case, despite a positive IgE to peanut, the child was ‘tolerant’ to peanut. The history indicated that there was frequent exposure to peanut. The problem is that by avoiding peanut, tolerance may be lost and re-introduction of peanut may cause clinical symptoms. 

Food sensitization in children may be due to environmental exposures to the food (vs. ingestion). 

The Future of Inhalant Immunotherapy 

Currently we have subcutaneous (SQ) allergen immunotherapy (IT)- allergy shots, injections. This form of therapy has been well established for 100 years. It is somewhat crude/unrefined and reactions can occur. The advances in this field include; 

1.  Sublingual immunotherapy (SLIT)- not approved in this country 

2.  Peptide immunotherapy (PIT) 

3.  Allergen fusion proteins 

4.  Allergens attached to viruses 

Anaphylaxis 

Fatal allergic reactions may not always have skin manifestations. Low blood pressure was seen in 80% and 60% had respiratory effects. Skin reactions occurred in 60%. All too often there is a delay in recognizing anaphylaxis when skin reactions are absent. Not everyone experiencing an anaphylactic reaction will have a skin reaction. 

Asthma 

I was involved as a principle investigator in the first phase of the National Cooperative Inner-City Asthma Study (NCICAS). I attended a session on inner-city asthma given by Herman Mitchell. Dr. Mitchell has been involved with this issue for many years. He shared a number of observations that spanned almost two decades of investigation. 

            Asthma is not just one disease. It is many diseases. It is complex and multi-causal. There are many factors that interact that determine its development and its exacerbations. This would be true for all populations with asthma. 

            The inner-city asthma studies emphasized the importance of sensitization (having a positive allergy test) and exposure (measuring the allergen in the environment). 

            House dust mites were found more often and in greater amounts in detached, low-rise housing and less in high rise apartments. In evaluating a child with asthma, we need to know what type of building they live in. 

            High humidity in the home is a factor. 

            Air pollution poses a conundrum. Overall air pollution levels have decreased, yet asthma prevalence has increased. Could this be a protective effect? Approximately 25% of children currently live in environments that exceed the standards for safe air. Things to consider in the child’s environment include how far away they live from a main road. 

            Asthma is a weighty problem. Inner-city asthma studies have shown 29% of the children with asthma are obese and 56% are over the 85%tile for weight. Between 85-90% of the child’s time is spent indoors where it would be difficult for active play/exercise. Safety concerns of the inner-city environment contributes to this problem. 

Human Genome Studies 

            This is a very hot topic. Most of it is research based however one of the anticipated outcomes would be to look at someone’s genetic profile and be able to predict susceptibility, expression, and severity of asthma and allergic diseases. We may be able to predict the kind of asthma someone will have and design very specific programs to prevent/treat. 

Asthma Treatment- Inhaled Corticosteroids 

            Not everyone responds to inhaled corticosteroids (ICS) given for asthma. Up to 50% of those on ICS may not respond. There are no biomarkers that we can use to determine in which patients a ICS will work; we depend on a clinical response. 

            The question is how long do you wait until it is determined that the ICS has made no difference? 

            This presentation posed many probing asthma management questions. It is important to set goals/outcomes when starting a program and to bring the patient back in a reasonable period of time to see if those goals/outcomes have been achieved. We also have to make sure that there was adherence to the therapeutic program (it is hard to tell if something was a failure/success if it was not used). In this situations it may be of benefit to start at a higher than anticipated dose looking for any response. 

Allergy Blood Testing 

            There are three companies that offer the blood tests for IgE and the results they provide are not equal. You cannot compare one with the other. 

            The future microarray technology will help us sort out relevant allergens. Skin testing and blood tests for allergy use very crude protein extracts that may have different and numerous proteins. The results obtained may be due to cross-reactivity with other substances or even binding to proteins that cause no clinical reactivity. 

            Of importance- the blood test result, the concentration of IgE antibody (kU/L) provides predictive power for a reaction it does not tell us anything about the severity of a reaction. 

            Do not use the term RAST- it is outdated, it refers to a technology no longer used. 

Urticaria- Hives 

            This is one of the most frustrating clinical conditions that we see. Parents, patients, and healthcare providers want the answer for the hives. I think the frustration of not knowing will continue. Idiopathic is the medical term used to describe something for which no cause has been determined. In some contexts it means the healthcare provider is the ‘idiot’ because they were unable to figure it out. 

            More than 80% of the time, chronic (more than 2 months) hives is idiopathic. The evaluation needs to consider the role of aspirin and other non-steroidal anti-inflammatory medications. Physical reasons for hives also need to be considered (light, pressure, water, heat, cold, or vibration). 

            The list of agents used to treat hives was described as ‘weird’. Frequently, a typical (H1) antihistamine has added to it an H2 antihistamine (commonly used to treat excess stomach acid). There are a variety of combinations used, however the definitive study that showed a positive effect was the used of hydroxyzine and cimetidine. The mechanism of action was the impact of the cimetidine on the liver metabolism of the hydroxyzine- cimetidine allowed the hydroxyzine to be around longer. 

            A somewhat new therapy for hives was the immunosuppressive agent cyclosporine. Adding a second H1 antihistamine may help. 

These are some of the highlights from the meeting. More specifically these comments come from the notes taken that I could read. 

Check-in next week – I plan to post my notes on the majority of food allergy topics after my presentation on March 16, 2010. 

FEL 

 The article did contain something that I strongly feel needs to be critiqued and clarified. The content expert for the quote was an associate professor of family practice at Michigan State University. Dr. Reinhardt is quoted as saying that the National Heart, Lung, and Blood Institutes (NHLBI) Guidelines for the Diagnosis and Management of Asthma 2007 advocates the use of the Phadia test to determine whether a person has allergies to common indoor allergens. He also states that too few clinicians are using this test.

 The first comment is out of context with other considerations that need to be addressed prior to ordering an expensive and perhaps unreliable laboratory test. The comment supports one commercially available product (fair balance). It assumes that this commercial product is the one the Guidelines recommend. As to the last comment regarding the use of the Phadia test for inhalant allergens, this is most probably because clinicians may be aware of the problems with this approach to allergy.

 The 2007 asthma guidelines do not specific the Phadia test for determining allergy. On page 168 of the NHLBI Asthma Guidelines Key Points clearly indicate that there are more steps involved- a relevant history, skin testing or in vitro testing, and an assessment of the significance of the test results. The guidelines do not mention specifically the Phadia test in the Key Points. This test has value, but only in the context of a patient’s history. The Phadia test for inhalant allergens is frequently falsely positive. In a recent national survey (JACI 2009;123:1163-9) 20% had symptoms of allergic disease. The Phadia test for inhalants demonstrated that 50% of the population had a positive test (for more on this article see ‘Incidence of Allergy in Children: Using Allergy Testing Panels (Pharmacia ImmunoCap) or Symptoms?’ one of my earlier posts on this topic). It is very important to point out that any test used in allergy only tells us that antibodies are produced. It is the history of symptoms plus the results of the test together that fulfill the criteria for allergy. A test result alone makes no one allergic and is only as useful as the history that supports it.

 In my opinion the reason why the Phadia test is not being used is because clinicians are aware of the need of taking a history, they dislike the obligatory panel of analysis offered by the Phadia panel, there is worry about the cost, and the test declares many more positive than actually have symptoms.

 Do we let the laboratory test dictate the diagnosis/treatment or the patient’s history matched to relevant laboratory studies to decide how to manage asthma?

I am old school- I make sure that I understand the history of the condition and the environmental exposures. From this I decide what tests for allergy are relevant and use testing to verify my clinical impression. Sometimes we don’t need to test. Sometimes we have to take the test results and re-evaluate the history and exposures to make sense of it all. Health care is expensive, laboratory tests for specific IgE is expensive. The consequences of questionable results taken out of context can have a cost as well. Allergen-environmental control is a big business. Consider the hidden costs of extra work, alteration of living environments, and the status of pets. Seek out consultation of experts who can sort through both a medical and environmental history and make sense of what to test for. You also need to consider what the gold standard is for the assessment of allergic sensitization and that is the allergen skin prick test. Look also to the credentials of the providers that you are working with.

Fred Leickly

Your Indiana Joint Asthma Coalition (InJAC)  just put online a Continuing Medical Education (CME) offering on the most recent national asthma guidelines. As the chair of the Health Care Committee of InJAC it was my job to oversee the project. This gave me the opportunity to go over that 400+ document known as the “Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma”. The CME program can be viewed by anyone without registering for the credit. The online program is a slide set on the various sections of the guidelines. Each reviewer summarized the essential points and provided notes for each slide in the presentation. A shorter Summary report of the Asthma Guidelines (EPR-3) is also available.  This is the 3rd such report. The first came in 1991. Number two was 1997. There was a publication that dealt with 5 specific hot topics from the guidelines in 2002. In 2007 the most recent EPR was published.

As I reviewed the EPR-3 I noted how often allergy/atopy appears in the document. Consider a few of the following statements;

1. Atopy, the genetic predisposition for the development of immunoglobulin E (IgE)-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma (Key Point- page 11).
2. The onset of asthma for most patients begins early in life with the pattern of disease persistence determined by early, recognizable risk factors including atopic disease, recurrent wheezing, and a parental history of asthma (Key Point- page 12).
3. This working definition (of asthma) and its recognition of key features of asthma have been derived from studying how airway changes in asthma relate to the various factors associated with the development of airway inflammation (e.g. allergens, respiratory viruses, and some occupational exposures) and recognition of genetic regulation of these processes (page 14).
4. Sensitization and exposure to house-dust mites and Alternaria (mold) are important factors in the development of asthma in children (page 22).
5. The asthma predictive index…..identifies the following risk factors for developing persistent asthma among children younger than 3 years of age who had four or more episodes of wheezing during the previous year: either (1) one of the following: parental history of asthma, a physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens, or (2) two of the following: evidence of sensitization to foods, > 4 percent peripheral blood eosinophilia, or wheezing apart from colds (page 25).
6. Tests to consider in the differential diagnosis of asthma- allergy testing (page 45).
7. Key Points in the Initial Assessment of Asthma- identify precipitating factors (inhalant allergens…) and identify co-morbid conditions that may aggravate asthma (rhinitis –nasal allergy…) page 47.
8. Referral to an Asthma Specialist for Consultation and Co-management- ….for allergy skin testing (authors note- not RAST or blood specific IgE)…..for consideration of allergen immunotherapy (page 68).

The above excerpts came from section 2 (asthma definition, pathophysiology, pathogenesis, and natural history of asthma) and section 3 part one- Asthma Management- measures of asthma assessment and monitoring. These remaining sections comprise over 300 pages of material. 

The remaining sections of the EPR-3 cover education, environmental control, medications, long-term management, and managing exacerbations of asthma. These sections also include information on the significant role of allergy in asthma. These sections go over specifics on how to manage the allergens.

 Through the allergist’s eyes- Asthma is significantly intertwined with allergy. We should look at it as a manifestation of the allergic condition. It is not allergy and asthma anymore, in many children it is allergy showing itself as asthma! Asthma can be a manifestation of allergy.

FEL

Animals and Asthma- to have or to have not?

  Photo by Bethany King

Recent research has challenged our previous recommendations regarding the role of a pet in the development of asthma and in the development of allergy. The hot topic today is a review of a publication by M. Kerkhof and colleagues titled ‘ Effects of pets on asthma development up to 8 years of age: the PIAMA study’ (Allergy 2009; 64: 1202-1208).

Background: four papers written between 1999-2003 found that a pet in the home during the early years of a child’s life prevented the development of allergy. Six reports between 1999-2004 gave mixed results as to whether or not a pet prevented the development of asthma. A meta-analysis (where the findings of a number of studies are combined) found a small (20%) increase in asthma with early pet exposure up to age 6 years. There have been no studies published regarding the relationship of pet exposure after the first few years of life and the development of asthma. This study fills that void.

Purpose: the study looked at the effect of the presence of cats and dogs in the home at any age during childhood and the incidence of asthma up to age 8 years.

Methods (how they studied this): This was a major survey performed in the Netherlands. There were 2951 children involved. Questionnaires were completed every year for 8 years.

Results (what they found): at age 3 months, 34 % of the children had a cat and 16% had a dog in the home.

1. When a dog was in the home, there was less allergy to house dust mites and to pollen at age 8 years.

2. The presence of a dog or cat in the home at 3 months of age was not associated with the presence of asthma or asthma symptoms when the child was 8 years old.

3. The occurrence of wheeze and a dry cough at night after age 2 years was higher in the children who had a dog in the home at the beginning of the study. The wheeze was more in boys and the dry nighttime cough favored the girls.

4. Removing a dog from the home was associated a higher incidence of wheezing (Odds Ratio = 2.59) and having a prescription for an inhaled steroid (Odds Ratio = 3.03). This was observed in the year after the removal of the animal. Note: a simple way of interpreting the Odds Ratio is that wheezing occurred 159% more and prescriptions for inhaled corticosteroids were 203% more in children where the dog was removed.

  Kita one of our Siberian Huskys- a real snow dog

Conclusions:

1. Pet exposure early in life may prevent the development of allergic sensitization to pollen and house dust mites at age 8 years.

2. Exposure to pets at any age in childhood did not affect the development of asthma up to age 8 years.

3. Exposure to dogs after the first two years of life increased the transient symptoms of wheeze and dry cough.

4. Dog removal increases the risk of wheeze and the need for an inhaled steroid.

Comments: the authors point out weaknesses in their study. One weakness is the problem with having a clear definition of asthma. This is a problem for many studies like this. The authors were able to examine 1132 of the 2951 children and validated the presence of asthma with specialized tests. This becomes an issue when trying to understand the transient wheeze and dry cough. Was this truly asthma or symptoms due to a viral illness? In the discussion it was thought that this was a response to the endotoxin in the environment from the dog that stimulates immune processes away from allergy.

Another potential weakness identified by the authors is that the measurement for allergy was done in only 1248 of the children.

Studies like this start us thinking about what advice to give to families on this subject. It is important to note that this work was done in the Netherlands and not done  in this country. This concept needs to be proven in the United States.  The differences in the populations  may limit our ability to extend the findings to current clinical practices here.

When evaluating a child for asthma, I think we have to be sure of the relationship of the symptoms to the skin test findings. All too often a family is told to get rid of the pets based on the results of an initial set of allergy tests. I am not sure this is an immediate way to proceed and we need to think of other family dynamics that are involved. I have frequently taken advantage of a more sophisticated measure used in asthma care/diagnosis to help figure out the relationship between triggering events and the clinical relevance of an allergy test result. At Riley we can measure exhaled nitric oxide. eNO is a by-product of allergic airway inflammation. When it is elevated there is most probably an allergic trigger causing the symptoms. I may not consider that a positive allergy test to dog relevant when there is significant exposure and the eNO is normal during an event. The asthma episode may be triggered by something else that requires investigation.

No, I am not ready to tell all my families to obtain an array of pets in anticipation of having children. I wonder what to do for those families who do not want the expense of feeding/picking up after pets. Ccould they purchase a ‘Bag o Pet’. This would contain all those things that are responsible for preventing sensitization and the development of asthma and not the live creature. Just a quick thought.

  Loki- (Brandon and Amanda’s cat- name for the Norse god of mischief)

Fred Leickly