Role of the T cells in asthma is still to be defined

Cytokines derived from airway epithelium, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), might be important drivers of T(H)2-type inflammation in asthma.

The balance between effector T(H)2 cells and suppressive regulatory T cells is skewed toward a proinflammatory T(H)2 response in atopy and asthma.

Newly discovered T-cell subsets, including T(H)17, T(H)9, and T(H)22, may play a role in asthma.

Other T cells, including natural killer T cells, gamma/delta T cells, and CD8 T cells, have also been implicated in asthma, although their importance remains to be confirmed.



T and B Cells - Naive and Memory Cell Markers (click to enlarge the image).

Strategies directed specifically at the T cells are currently being evaluated, including new forms of allergen immunotherapy.

References:
The role of the T cell in asthma. Robinson DS. J Allergy Clin Immunol. 2010 Aug 14.
Redirecting T Cells - NEJM, 2011.


Patient needs are unmet in chronic spontaneous urticaria

Change in the name

Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought.

Prevalence - more common than previously thought

At any time, 0.5-1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age.

Can you predict duration?

The duration of the disease is generally 1-5 years. However, the duration is likely to be longer in:

- more severe cases
- cases with concurrent angioedema
- in combination with physical urticaria
- with a positive autologous serum skin test (autoreactivity).

Anti-FceRI antibodies test could be used instead of the autologous serum skin test (available trough Mayo Clinic/National Jewish).


Diagnosis of Chronic Urticaria (click to enlarge the image).



Anti-FceR1 autoantibodies in chronic autoimmune urticaria: IgG against FceRI (receptor for IgE) (click to enlarge the image).

Detrimental effects

Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life.

Causal and/or curative treatment is difficult

In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult.

Nonsedating H(1) -antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in less than 50% of patients.

Although guideline-recommended up-dosing up to 4-fold increases symptom control in many patients, a substantial number of patients have only little benefit from H(1) -antihistamines.

Consequently, there is a great need for new therapeutic strategies. Omalizumab showed a benefit in a short-term study reported at the 2010 ACAAI Annual Meeting.


Chronic Urticaria Treatment (click to enlarge the image).

References:

Unmet clinical needs in chronic spontaneous urticaria. A GA(2) LEN task force report(1).
Maurer M, Weller K, Bindslev-Jensen C, Giménez-Arnau A, Bousquet P, Bousquet J, Canonica GW, Church MK, Godse KV, Grattan CE, Greaves MW, Hide M, Kalogeromitros D, Kaplan AP, Saini SS, Zhu XJ, Zuberbier T. Allergy. 2010 Nov 17. doi: 10.1111/j.1398-9995.2010.02496.x.
Single-dose omalizumab (300mg) in patients with H1-antihistamine–refractory chronic idiopathic urticaria leads to improvement within 1-2 weeks. JACI, 2011.


Diagnosis of insect sting/venom allergy

History is essential for diagnosis

Venom-specific IgE antibodies are present in clinically non-reactive individuals, i.e. people without symptoms. The diagnosis of insect sting allergy relies on the history of allergic reaction.

The identity of the insect that caused the sting is a notoriously unreliable part of the history. However, the location and timing of the sting or the location of the nest may help to determine the type of insect.

Concurrent medications such as beta-blockers can contribute to anaphylactic reaction.


Figure 1. Mind map of insect venom allergy (click to enlarge the image).

Reaction to Wasp Reaction to Bee
More common Rarer
After a single sting After many stings
Typical narrow waist and little hair Hairy "fuzzy" bee
Table 1. Comparison of allergic reactions to wasp and bee venom.


Figure 2. A yellow jacket wasp with a typical narrow waist (left) and a honey bee with a fat hairy "fuzzy" body (right). Image source: Wikipedia 1, 2, GNU Free Documentation License.

Skin tests - intradermal

The standard method of skin testing is with the intradermal technique, using the 5 Hymenoptera venom protein extracts. Whole body extracts are not used, with the exception of fire ant.

For Hymenoptera venom testing, intradermal tests are performed with venom concentrations in the range of 0.001–1.0 μg/mL to find the minimum concentration giving a positive result. Epicutaneous tests at 1 μg/mL concentration is typically used initially, before the intradermal tests. 25% of patients are skin test positive only at the 1.0 μg/mL concentration (top dose).

The patient may be sensitized to multiple venoms even when there has only been a reaction to only a single insect. Therefore, skin testing should be performed with:

- complete set of the 5 Hymenoptera venoms
- negative diluent (human serum albumin-saline) control
- positive histamine control

Some patients have negative skin tests for 6 weeks after a sting reaction attributed to a refractory period of ‘anergy’.

Negative skin tests in a history-positive patient may represent the loss of sensitivity, especially if the sting was in the remote past.

ImmunoCAP is positive in 10% of patients with negative skin tests. Patients with negative skin tests and a convincing history of anaphylaxis should be further investigated with serologic testing, and if still negative, the skin tests should be repeated after 3–6 months.

In vitro tests, specific IgE

High levels of venom-specific IgE are typically diagnostic. The problem lies with the low levels that are more difficult to detect.

There is no exact correlation between venom skin tests (intradermal) and venom-specific IgE assays (ImmunoCAP).

Specific IgEs are negative in up to 20% of skin-test positive subjects. Venom skin tests are negative in 10% of persons with elevated IgE antibodies.

Neither test alone can detect all cases of insect sting allergy. Each test is useful as a supplement to the other - if the other test is negative.

References:

Chapter 57 – Insect Allergy, David B.K. Golden, Adkinson: Middleton's Allergy: Principles and Practice, 7th ed., 2008.
Insect Venom Allergy: Brief Review
Bee Aware Allergy - Insect allergy educational website by Hollister-Stier Laboratories.


Asthma, type 2 diabetes and increased BMI are associated

This Danish study examined the relationship between asthma, type 2 diabetes and increased body mass index (BMI) in adult twins.

The risk of asthma was increased in subjects with type 2 diabetes relative to nondiabetic subjects both in men (13.5% vs. 7.5%) and in women (16.6% vs. 9.6%), p value was quite significant at 0.001.

BMI remained a highly significant predictor for asthma independently of diabetes status in women, but not in men.

Asthma, type 2 diabetes and increased BMI are strongly associated in adults, particularly in women. These results may suggest a common aetiology for asthma and metabolic syndrome.

References:
Risk of asthma in adult twins with type 2 diabetes and increased body mass index. Thomsen SF, Duffy DL, Kyvik KO, Skytthe A, Backer V. Allergy. 2010 Nov 17. doi: 10.1111/j.1398-9995.2010.02504.x.

Image source: Wikipedia, public domain.


Sinusitis - Mayo Clinic video



William E. Bolger, M.D., an otolaryngologist at Mayo Clinic's campus in Florida, talks about sinusitis. Sinusitis is one of the most-reported chronic diseases in the United States. Learn more about this issue as well as ways to relieve the condition. For patients with complex challenges, medical and endoscopic sinus surgery options are available.


Potential role of S. aureus superantigens in allergic respiratory diseases

An association between bacterial products and allergic airway diseases has been suggested, especially between Staphylococcus aureus enterotoxins and atopic diseases.

This systematic review included 10 of studies in adults and/or children affected by asthma/early wheeze and/or allergic rhinitis.

Patients with asthma or allergic rhinitis showed an increased prevalence of S. aureus.

Patients with asthma were more likely than controls to have serum-specific IgE to Staphylococcus aureus enterotoxins (OR = 3.3).


Similarly, patients with allergic rhinitis were more likely than controls to test positive for local or systemic exposure to Staphylococcus aureus and/or or its enterotoxins (OR = 2.4).

A potential role of S. aureus superantigens in allergic respiratory diseases is supported by results of this meta-analysis of clinical studies.

References:
Pastacaldi C, Lewis P, Howarth P. Staphylococci and staphylococcal superantigens in asthma and rhinitis: a systematic review and meta-analysis. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02502.x.
Loss-of-function mutations in filaggrin gene are associated with atopic dermatitis, and now with peanut allergy too. JACI, 2011.
Colonization of S. aureus in early childhood eczema (72.7%) originates from childrens' own noses, not from mothers http://goo.gl/0fptY


Spirometry changes assessment of asthma control in children

Lung function testing changed the assessment in 11% of pediatric patients with asthma - the disease status was worse than expected. However, spirometry should not be seen as the "gold standard" for assessing asthma control. Instead, a combination of objective and subjective measures provides the best approach.


In study presented at the 2010 ACAAI Annual Meeting, the initial analysis, excluding spirometry, showed that participants had well-controlled asthma 67% of visits. However, when spirometry was included, 11% of the patients were reclassified to have uncontrolled asthma.

William Dolen, MD comments: "All people who do the subjective assessment and also do spirometry have patients who give you an excellent control score and yet when you do the spirometry, it's terrible. It can also work the other way -- patients complain about symptoms, but have excellent lung function on spirometry. Monitoring lung function by spirometry is key to the successful control of asthma in more severe patients. But lung function testing is not done as often as it should be because many asthma patients are treated by their family doctor. They don't have spirometers and they're not trained in how to interpret the results, so the testing is not done."



Most board-certified allergists have spirometers in their clinics and can provide an accurate assessment of your asthma control within minutes. The youngest age to perform spirometry with reproducible results varies between 5 and 7 years, depending on the patient.

References:
Impulse oscillometry for evaluation pediatric asthma - noninvasive rapid technique requiring only passive cooperation http://goo.gl/znFYg
Daily home spirometry does not reduce exacerbations in children with severe asthma. ERJ, 2012.
Image source: Spirometry, from Wikipedia, the free encyclopedia, GNU Free Documentation License.


People with nut allergy not able to visually identify the nuts they are allergic to

What is the nut shown on the right? (the answer is in the references section).

Only 50% of people with a nut allergy can visually identify all the nuts they are allergic to, according to a study presented during the 2010 ACAAI meeting and published in December 2011.

Adults were able to identify 58.4% of the nuts, while those under 18 were able to name just 24%.

More than half of adults were able to identify a range of common nuts, with peanuts leading the way at 95% for unshelled nuts.

Less than 50% could pick out such nuts as hazelnuts or pecans.

Of parents with an allergic child, 73% were able to name all those that affected the child.
Allergic children could only name 34% of the nuts.

Over a five-year period, 55% of people with peanut allergy had reactions after accidentally eating the wrong nut.

The only safe way to avoid one kind of nut is to avoid them all. "I tend to tell my patients with a true peanut allergy to just stay away from all nuts. You never know when there's going to be some peanut, especially in mixed nuts."

Treatment for nut allergy should include education on how to recognize different nuts.

References:

The ability of adults and children to visually identify peanuts and tree nuts is unreliable (study). Annals of Allergy, Asthma and Immunology, 2011.
Image source: Unshelled Brazil Nut, Wikipedia, GNU Free Documentation License.


Omalizumab (Xolair) effective against chronic idiopathic urticaria

The monoclonal antibody omalizumab (anti-IgE), given at doses higher than those used in asthma, rapidly reduced urticaria activity scores.

The study followed up an unexpected observation that, in asthma patients with urticaria, the skin condition often responded quickly when they were treated with omalizumab (trade name Xolair). This was an "unanticipated benefit" because "a lot of urticaria is not necessarily allergic-oriented."

The primary endpoint was the change from baseline in the 7-day urticaria activity score (UAS7), which is a diary-based combined score of severity of itch and number of hives. The maximum score is 42.

Patients who received 300 mg of omalizumab had a UAS7 decline of 19.93 points, down from a baseline average of 27.72.

The effect was rapid, patients in the 300-mg group had an average 13-point drop in the UAS7 one week after the single dose.

Omalizumab is expensive, but for urticaria the benefit appears with only a single dose.

References:
Single-dose omalizumab (300mg) in patients with H1-antihistamine–refractory chronic idiopathic urticaria leads to improvement within 1-2 weeks. JACI, 2011.
Single dose of omalizumab (one 300 mg injection) relieves chronic idiopathic urticaria refractory to H1-antihistamines. Medscape, 2011.
Images: Mechanisms of action of omalizumab. JACI, 02/2008.
Image source: Wikipedia, public domain.


Cold Urticaria - 9-year-old "Allergic" to Temperatures Under 70F - Today Show Video

Visit msnbc.com for breaking news, world news, and news about the economy


School-based asthma education improves knowledge and self-management of the disease

Asthma self-management education is critical for high-quality asthma care for children.

Most studies in this meta-analysis that compared asthma education to usual care found that school-based asthma education improved:


- knowledge of asthma
- self-efficacy
- self-management behaviors

Fewer studies reported favorable effects on quality of life (4 of 8 studies), days of symptoms (5 of 11 studies), nights with symptoms (2 of 4 studies), and school absences (5 of 17 studies).

References:
Do School-Based Asthma Education Programs Improve Self-Management and Health Outcomes? PEDIATRICS Vol. 124 No. 2 August 2009, pp. 729-742 (doi:10.1542/peds.2008-2085).
Asthma educations of urban adults with moderate or severe asthma: FEV1 and quality of life improved by 6%. JACI, 2011.
Image source: Wikipedia, public domain.

Twitter comments:

@harriet75: Yup, I created on in NYC that used Drama to teach kids about asthma.


Parent Mentors Improve Asthma Outcomes in Minority Children

Asthma disproportionately affects minorities. This study evaluated the effects of parent mentors (PMs) on asthma outcomes in minority children.

This randomized, controlled trial allocated minority asthmatic children to the PM intervention or traditional asthma care. Intervention families were assigned PMs (experienced parents of asthmatic children who received specialized training). PMs met monthly with children and families at community sites, phoned parents monthly, and made home visits.

The average monthly cost per patient for the PM program was $60.42, and net savings of $46.16 for high participants.

For asthmatic minority children, PMs can reduce wheezing, asthma exacerbations, ED visits, and missed parental work days while improving parental self-efficacy. These outcomes are achieved at a reasonable cost and with net cost savings for high participants. PMs may be a promising, cost-effective means for reducing childhood asthma disparities.

References:
Improving Asthma Outcomes in Minority Children: A Randomized, Controlled Trial of Parent Mentors. PEDIATRICS Vol. 124 No. 6 December 2009, pp. 1522-1532 (doi:10.1542/peds.2009-0230)


How Accurate Is Penicillin Skin Testing?

The immunogenic components of PCN include:

1. major determinant is benzylpenicilloyl
2. minor determinants are penicillin G (benzylpenicillin), penicilloate, and penilloate

The major determinant, conjugated to a polylysine carrier molecule, has been available as a commercial product (Pre-Pen®) since 2009.

Minor determinants, other than PCN G, are not commercially available. Some allergists synthesize their own minor determinates. AllerQuest, LLC plans to develop a minor determinant mixture.

The predictive value of a negative skin test has been reported to be 97-99%.

Testing with benzylpenicilloyl polylysine (Pre-Pen®) alone identifies up to 90% of patients likely to have IgE-mediated reactions to PCN. The addition of PCN G to the testing regimen raises the predictive value to 97%.

However, some studies have suggested that 3-30% of patients with IgE-mediated allergy to PCN may be missed by routine skin testing.

A positive PCN skin test result should rule out the use of PCN agents and other beta-lactams.

However, a negative PCN skin test does not definitively rule out the risk for an IgE-mediated reaction upon administration of the offending agent.

All patients should receive a graded challenge of the drug in settings with emergency medical support.



Manifestations of beta-lactams hypersensitivity: MAUS (click to enlarge the image).

Mnemonic for diagnosis of drug allergy: HASTA la vista (Spanish, See you later)

History
Assemble a list of drugs and rank them
Stop all drug candidates
Test
Administer - dose escalation or desensitization

References:

How Effective Is Penicillin Skin Testing? Medscape, 2010.
How Prepen Made it Back to Market: Another Twist in the Storied History of Penicillin. Gary Stadtmauer, MD.
The role of penicillin in benign skin rashes in childhood: A prospective study based on drug rechallenge. Caubet JC, Kaiser L, Lemaître B, Fellay B, Gervaix A, Eigenmann PA. J Allergy Clin Immunol. 2010 Oct 27.
Image source: Penicillin nucleus, Wikipedia, GNU Free Documentation License.


Oral immunotherapy for cow's milk allergy is effective in 30% of patients

Cow's milk allergy (CMA) in children is an important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach but the studies are still ongoing. The first U.S. Food Allergy Clinical Practice Guidelines were published on December 6, 2010 and according to them the current evidence supporting oral immunotherapy for food allergy is inconclusive.

This Italian study included 30 children with IgE-mediated cow's milk allergy confirmed by double-blind placebo-controlled food challenge.

The 30 participants were equally randomized to desensitization with:

- cow's milk
- soy milk as control (please have in mind that 40-50% of patients with cow's milk allergy are also allergic to soy)

The weekly up-dosing lasted 18 weeks.

Two patients in the cow's milk group discontinued the desensitization after experiencing severe reactions.


Full tolerance to cow's milk (200 mL) was achieved in 10 active patients and partial tolerance in one (1). A significant increase in specific IgG4 levels was found in the active group.

This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective in approximately 30% of patients and induced immunologic changes.


8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).


Different types of oral food challenges for diagnosis of food allergy, mind map diagram (click to enlarge the image).

3 Types of oral food challenges: DOS:

Double-blind placebo-controlled food challenge (DBPCFC)
Open food challenge (OFC)
Single-blind placebo-controlled food challenge (SBPCFC)

References:

Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Pajno GB, Caminiti L, Ruggeri P, De Luca R, Vita D, La Rosa M, Passalacqua G. Ann Allergy Asthma Immunol. 2010 Nov;105(5):376-81. Epub 2010 Jul 31.
Sublingual and oral immunotherapy for milk allergy. Desensitization was lost in some cases within 1 week off therapy. JACI, 2011.
Eosinophilic esophagitis after specific oral tolerance induction for egg protein http://goo.gl/fzmip
In children, casein-specific IgE linked to cow's milk allergy while IgG4 antibodies possibly linked to tolerance. Clinical and Molecular Allergy 2012, 10:1.
Image source: Wikipedia, GNU Free Documentation License.


Only 6.8% of children with "rash due to penicillin" have penicillin allergy

Delayed-onset urticarial or maculopapular rashes are frequently observed in children treated with beta-lactams. Many are labeled "allergic" without testing for penicillin allergy. The etiology of these rashes may be infectious rather than allergic.

This study population included 88 children presenting to the emergency department with delayed-onset urticarial or maculopapular rashes.

The tests included:

- acute and convalescent sera for viral screening
- throat swab
- intradermal and patch skin testing for β-lactams 2 months after presentation
- anti-β-lactam blood allergy tests (specific IgE)

All subjects underwent an oral challenge test (OCT) with the culprit antibiotic.

Results:

- 12.5% of children had positive intradermal and no positive patch tests
- 2.3% had positive blood allergy tests
- 6.8% had a positive OCT - a total of 6 children - 2 were intradermal-negative, and 4 were intradermal-positive
- most subjects had at least one positive viral study, 65.9% in the oral challenge test negative group

Beta-lactam allergy is clearly overdiagnosed because the skin rash is only rarely reproducible (6.8%) by a subsequent challenge. Viral infections may be an important factor in many of these rashes.

The oral challenge test was positive in a minority of intradermal skin test-positive subjects. Patch testing and blood testing provided no useful information.

Oral challenge tests should be considered in all children who develop a delayed-onset urticarial or maculopapular rash during treatment with a β-lactam.


Manifestations of beta-lactams hypersensitivity: MAUS (click to enlarge the image).

Mnemonic for diagnosis of drug allergy: HASTA la vista (Spanish, See you later)

History
Assemble a list of drugs and rank them
Stop all drug candidates
Test
Administer - dose escalation or desensitization

Mnemonics for penicillin allergy skin testing

Major penicillin determinant test detects
Majority of patients with penicillin allergy

Minor determinant test
Minorizes the risk

References:

The role of penicillin in benign skin rashes in childhood: A prospective study based on drug rechallenge. Caubet JC, Kaiser L, Lemaître B, Fellay B, Gervaix A, Eigenmann PA. J Allergy Clin Immunol. 2010 Oct 27.
Non IgE-mediated reaction to penicillin - AAAAI - Ask the Expert, 2011.
Diagnosis of Immediate Hypersensitivity to β-Lactam Antibiotics Can Be Made Safely with Current Approaches. Int Arch Allergy Immunol. 2011 Nov 1;157(3):311-317.
Testing for penicillin allergy can be done at any age. Consider testing with PrePen, Penicillin G and ampicillin. AAAAI Ask the Expert, 2012.
Image source: Penicillin nucleus, Wikipedia, GNU Free Documentation License.


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