Allergy Notes

30% of pet shop workers report airway symptoms at work and are sensitized to animal allergens

2012-01-26T09:07:00.000-05:00

Allergy to laboratory animals (mice, etc.) is a well-known occupational hazard. Less is known about allergic sensitization and respiratory symptoms among pet shop staff.

59 workers from 24 pet shops were included in this study from Sweden:

- 53% reported nasal symptoms
- 34% had eye symptoms
- 22% had experienced symptoms indicating asthma - only 7% were previously diagnosed with asthma
- 30% reported respiratory symptoms at work, mostly against rodents, birds, insects, and hay
- 29% were sensitized to work-related allergens, mainly rodents and fodder insects, e.g., Zophobas

Atopy and total IgE higher than 100 kU/l increased prevalence of pet shop sensitization.

A third of the pet shop workers reported airway symptoms at work or were sensitized, sometimes to unusual pet shop allergens, especially among atopics. Allergen avoidance among pet shop staff is important but may be difficult to achieve.

Mind map: Indoor allergens (click to enlarge the image).

Mind map: Animal Dander Avoidance (click to enlarge the image).

References:

Renström A, Olsson M, Hedrén M, Johansson SGO, van Hage M. Pet shop workers: exposure, sensitization, and work-related symptoms. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02591.x.

Image source: Wikipedia, GNU Free Documentation License.

Status of pediatric allergy and immunology in Spain

2012-01-26T08:04:00.002-05:00

The data of the ISAAC project in Spain show:

- prevalence of childhood asthma of 7-15%
- prevalence of 23-36% for rhinitis
- atopic dermatitis in 4-8% of children
- prevalence of food allergy is 3%

All children in Spain have the right to be evaluated in their National Health System. The medical care at the primary level is provided by pediatricians, who go through a 4-year medical residency training program.

There are currently 112 certified pediatric allergists in Spain, who have obtained the accreditation of the European Union of Medical Specialists. Future specialists in pediatric allergy will obtain their titles through a specific education program to be developed in one of the 4 accredited training units on pediatric allergy, after pediatric residency.

The Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) includes 350 pediatric allergists and pediatrician. SEICAP has yearly congresses and protocols. The official journal of SEICAP is Allergologia et Immunophatologia, published every 2months since 1972.

The web site of SEICAP, http://www.seicap.es, open since 2004, received 750 daily visits during 2011.

The pediatric allergy units perform immunotherapy and induction of oral "tolerance" in food allergy.

References:

Nieto A, Mazon A, Martin-Mateos MA, Plaza A-M, Garde J, Alonso E, Martorell A, Boquete M, Lorente F, Ibero M, Bone J, Pamies R, Garcia JM, Echeverria L, Nevot S, Martinez-Cañavate A, Fernandez-Benitez M, Garcia-Marcos L. Pediatric allergy and immunology in Spain. Pediatric Allergy Immunology 2011; 22: 742-750.

Image source: Openclipart.org, public domain.

Comments from Twitter:

Dr John Weiner @AllergyNet: Like in tennis, the Spanish punch above their weight in allergy/immunology

PPI lansoprazole doesn't help children with poorly controlled asthma if they don't have reflux symptoms (GERD)

2012-01-25T08:24:00.054-05:00

Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control. However, it it not clear if treating asymptomatic GERD with proton pump inhibitors (PPI) helps the asthma symptoms.

300 children with asthma with mean age of 11 years were enrolled at 19 US academic clinical centers and were followed up for 6 months.

There were no significant differences in:

- the Asthma Control Questionnaire (ACQ) score (primary outcome),
- FEV1, forced expiratory volume in the first second
- asthma-related quality of life
- asthma exacerbations

Watch the JAMA video report on the study:

Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no lansoprazole did not affect asthma outcomes.

There were slightly more respiratory infections in the PPI group (relative risk, 1.3).

In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, did not improve symptoms or lung function.

The key here may be whether the children with asthma have symptoms of GERD or not. A 2008 study, presented at the annual ACAAI meeting, showed that "in children with both asthma and gastroesophageal reflux disease (GERD), treating the latter can improve the former."

Severe asthma - differential diagnosis and management (click to enlarge the image). Related: Common Asthma-related Comorbidities. Medscape, 2011, (figure) http://j.mp/omHVc6

References:

Lansoprazole for Children With Poorly Controlled Asthma. JAMA. 2012;307(4):373-380. doi: 10.1001/jama.2011.2035

Costs and Perils of Therapeutic Creep: Children, Asthma, and Proton Pump Inhibitors - JAMA editorial.

"Childhood Asthma - JAMA Patient Page" mistakenly skips allergy tests in asthma evaluation but includes CXR (PDF). All children with asthma should undergo allergy testing in order to identify potential allergic triggers (http://goo.gl/tosfJ).

T reg cells may offer a key for treatment of autoimmune diseases

2012-01-24T08:15:00.001-05:00

T regulatory cells (Treg) are distinguished by CD4+, CD25+, GITR+, CTLA-4+. Some of T regs also express the transcription factor Foxp3 (nTreg).

Treg subsets include:

- Natural Tregs (nTreg). nTregs develop in the thymus and constitutively express Foxp3 and CD25. They depend upon IL-2 for their survival.

- Induced Tregs (iTreg). iTregs are induced from naïve CD4 in the periphery. They express Foxp3 only after development by TGF-b.

- T Regulatory 1 (Tr1). Tr1 do not express CD25 or Foxp3. They depend on IL-10 from DCs for development. Tr1 produce high levels of IL-10.

Regulatory T cells - 6 groups have been described (click to enlarge the image).

A lack of regulatory T (TReg) cells that express CD4, CD25 and forkhead box P3 (FOXP3) results in severe autoimmunity in humans (IPEX).

There has been intense investigation aimed at determining how they protect an organism from autoimmunity and whether defects in their number or function contribute to the development of autoimmunity.

The next phase of investigation — focused on defining the role that defects in TReg cells have in human autoimmunity — is now underway. This knowledge might have a significant impact on the diagnosis and treatment of autoimmune diseases.

References:

Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases. Nature Reviews Immunology 10, 849-859 (December 2010) | doi:10.1038/nri2889

Regulatory T cells

Image source: A scanning electron microscope (SEM) image of a single human lymphocyte.Wikipedia, public domain.

Needles/lancets are tools of choice for skin prick testing - according to a study comparing 5 techniques in Europe

2012-01-23T08:28:00.020-05:00

Skin prick tests (SPT) represent indispensable tools in allergy, even more than 30 years after their introduction in clinical practice (note: skin prick testing has been used in the U.S. for a lot longer than 30 years).

A wheal with multiple pseudopods and a satellite lesion in the upper left. Image source: Modified from Sakurako Kitsa's photostream, Flickr (used with the author's permission).

Four instruments were investigated in this European study:

- 23G intravenous (IV) needle
- ALK Lancet - SoluPrick SQ (TM)
- Stallergenes (STG) Prick Lancet
- Stallerpoint (using two different methods)

In terms of sensitivity, the IV needle (100%) and metal lancets (96% for the ALK Lancet and 98% for the STG Prick Lancet) were superior to the two Stallerpoint® methods (20% and 57%).

The instruments that were best tolerated by the patients were the IV needle and the two metal lancets.

The authors concluded that metal needles and/or lancets are the tools of choice for skin prick testing. The study did not include some of the most popular devices for SPT in the U.S. such as:

- ComforTen (PDF)
- Multi-Test II (instructions)

Quintest device

Comparison of diagnostic methods for peanut, egg, and milk allergy - skin prick test (SPT) vs. specific IgE (sIgE) (click to see the spreadsheet). Sensitivity of blood allergy testing is 25-30% lower than that of skin testing, based on comparative studies (CCJM 2011).

Skin prick test vs. serum IgE

Skin testing correlates better with nasal allergen challenge (the gold standard) than blood testing for the diagnosis of inhalant allergy. According to current guidelines, skin tests are the preferred method for diagnosing IgE-mediated sensitivity to inhalants (CCJM 2011).

References:

Comparison of five techniques of skin prick tests used routinely in Europe. Masse MS, Granger Vallée A, Chiriac A, Dhivert-Donnadieu H, Bousquet-Rouanet L, Bousquet P-J, Demoly P. Comparison of five techniques of skin prick tests used routinely in Europe. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02679.x.

Comparison of the Multi-Test II and ComforTen allergy skin test devices. Dykewicz MS, Dooms KT, Chassaing DL. Allergy Asthma Proc. 2011 May;32(3):198-202.

Skin prick tests (SPT)

Bullying, teasing, and harassment of children with food allergy is common, frequent, and repetitive

2012-01-18T08:43:00.018-05:00

This U.S.based study from Mount Sinai Hospital in New York City included 350 questionnaires. Most surveys were completed by parents of food-allergic children.

24% of respondents reported that the food-allergic individual had been bullied, teased, or harassed because of food allergy.

Of those who were bullied, teased, or harassed, 86% reported multiple episodes. 82% of episodes occurred at school, and 80% were perpetrated by classmates.

21% of those who were bullied, teased, or harassed reported the perpetrators to be teachers or school staff.

Of those bullied, 57% described physical events, such as being touched by an allergen and having an allergen thrown or waved at them, and several reported intentional contamination of their food with allergen.

Bullying, teasing, and harassment of children with food allergy seems to be common, frequent, and repetitive. These actions pose emotional and physical risks that should be addressed in food allergy management.

References:

Bullying among pediatric patients with food allergy. Lieberman JA, Weiss C, Furlong TJ, Sicherer M, Sicherer SH. Ann Allergy Asthma Immunol. 2010 Oct;105(4):282-286.

Food allergy bullies - ABC video

Image source: Wikipedia, public domain.

Lung function decreases and AHR increases with greater sgE levels or SPT wheal diameter to inhalant allergens

2012-01-17T08:06:00.008-05:00

Studies in children show specific serum IgE (sIgE) and size of skin test wheal to inhalant allergens predict wheezing and reduced lung function. Few studies in adults have investigated that link.

FEV1 and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 1,000 UK adults (controls and 183 patients with asthma).

Atopic status was assessed by skin prick tests (SPT) and sIgE to common inhalant allergens. Sensitization was defined using standard definitions for sIgE>0.35kUa/l and SPT 3mm>negative control.

16% of subjects showed evidence of airway hyperresponsiveness (AHR).

Increasing levels of sIgE to dust mite, cat and dog were associated with lower FEV1.

Similar findings were observed when using the size of wheal on skin testing, with decreasing lung function with increasing skin test size (dust mite, cat, dog, grass).

Lung function decreased and AHR increased with increasing sgE levels or SPT wheal diameter to inhalant allergens. Atopy influences lung function and AHR.

References:

Quantification of atopy, lung function and airway hypersensitivity in adults. Susana Marinho, Angela Simpson, Paul Marsden, Jacky A Smith and Adnan Custovic. Clinical and Translational Allergy 2011, 1:16.

Image source: Spirometry, from Wikipedia, the free encyclopedia, GNU Free Documentation License.

Related:

IL-10-producing B cells (regulatory B-cells) induction by helminths may open a new avenue in asthma treatment

2012-01-16T08:58:00.008-05:00

Chronic helminth infections are often associated with a reduced prevalence of inflammatory disorders, including allergic diseases.

Helminths influence the immune system by downregulating T-cell responses and IL-10 appears to play a central role in this process.

Over the last decade, evidence has emerged for a new regulatory cell type, in addition to the well-known T regs: IL-10-producing B cells (regulatory B cells).

Initially, regulatory B cells were described in autoimmunity models where they decrease inflammation. Patients suffering from autoimmunity have an impaired regulatory B-cell function. They were also found in several helminth infection models.

Helminth-induced regulatory B cells suppress allergic inflammation and may open a new avenue for the treatment of inflammatory diseases, such as allergic asthma.

Regulatory T cells - 6 groups have been described (click to enlarge the image).

References:

Regulatory B-cell induction by helminths: Implications for allergic disease. Hussaarts L, van der Vlugt LE, Yazdanbakhsh M, Smits HH. J Allergy Clin Immunol. 2011 Jun 17.

Interleukin-10 (IL-10)

Image source: Trichuris egg in stool sample (40x). Wikipedia, GNU Free Documentation License, Version 1.2.

What are the risk factors and protective factors for allergic rhinitis at age 4?

2012-01-13T08:39:00.000-05:00

Allergic heredity plays a significant role in the development of allergic rhinitis. The introduction of solid foods may also influence the risk of allergic disease.

Allergic (atopic) march (click here to enlarge the image).

This Swedish study analysed early risk factors and protective factors for allergic rhinitis at preschool age (4 years) via questionnaires.

At 4½ yr of age, 5.5% of children had reported symptoms of allergic rhinitis.

Risk factors for allergic rhinitis were:

- allergic sensitisation to food allergens at 4½ yr (OR 10.21)
- recurrent wheeze at 4½ yr (3.33)
- doctor-diagnosed eczema at 4½ yr (2.72)
- parental rhinitis (2.21)
- eczema first year (1.97)
- male gender (1.82)

The risk was reduced with fish introduction before 9 months of age (0.49).

References:

Alm B, Goksör E, Thengilsdottir H, Pettersson R, Möllborg P, Norvenius G, Erdes L, Åberg N, Wennergren G. Early protective and risk factors for allergic rhinitis at age 4½ yr. Pediatr Allergy Immunol 2011: Doi: 10.1111/j.1399-3038.2011.01153.x

Allergen-specific immunotherapy was performed by the ancient king Mithridates (132-63 B.C.)

2012-01-12T08:57:00.003-05:00

A hundred years ago, Leonhard Noon and John Freeman published their pioneering works on allergen-specific immunotherapy (ASIT) using grass pollen extracts.

ASIT is the only causal treatment of IgE-mediated allergies. The history of ASIT started with the anecdotal descriptions of ASIT performed by the ancient king Mithridates (132–63 B.C.) and Jenner’s development of a cowpox vaccine.

Some of the products used for ASIT include:

- aqueous pollen extracts
- whole bee extracts
- chemically modified allergens (allergoids)
- various recombinant allergens

In addition to allergen-specific immunotherapy, non-specific immune response modifiers have been used in the past, or are in the developmental stage.

Mechanisms of allergen-specific immunotherapy (click to enlarge the image).

References:

Ring J, Gutermuth J. 100 years of hyposensitization: history of allergen-specific immunotherapy (ASIT). Allergy 2011; DOI: 10.1111/j.1398-9995.2010.02541.x.

Image source: OpenClipArt.org, public domain.

Girl's death highlights allergy safety in schools - CNN video

2012-01-11T19:03:00.001-05:00

Key points:

- There is no cure for food allergies

- About 8% of U.S. children under 18 have at least one food allergy

- Epinephrine is the first line life-saving medication in severe food allergic reaction. Always carry an EpiPen with you, and remember these simple memory rules in severe food allergic reaction:

- "No Epi, no eat-y" (always carry an EpiPen with you, don't sit down to eat if you don't have an EpiPen available)

- "If it's more than the skin, the Epi goes in" (only mild hives may respond to antihistamine, for anything else you may need an EpiPen)

References:

Girl's death highlights allergy safety in schools. CNN, 2012.

Are Profilins Mimickers of Allergy or Mighty Pan-Allergens?

2012-01-11T09:10:00.003-05:00

Profilins are ubiquitous proteins, present in all eukaryotic cells and identified as allergens in pollen, latex and plant foods.

Profilins have a highly conserved structure that may be the reason for cross-reactivity. IgE antibodies against plant profilins react to wide varity of allergens, hence the designation of prolifins as pan-allergens.

Primary sensitization to profilin arises from pollen sensitization with later development of cross-reactive IgE antibodies against plant food (and possibly latex) profilins.

Cross-reactivity in Pollen-Food Allergy Syndrome (PFAS) or Oral Allergy Syndrome (OAS) (click to enlarge the image).

IgE cross-reactivity among profilins is associated with multiple pollen sensitization and with various pollen-food syndromes (oral allergy syndrome).

In respiratory allergy, sensitization to pollen to which the patient has virtually no environmental exposure has been identified as a manifestation of profilin sensitization.

As a food allergen, profilin usually elicits mild reactions, such as oral allergy syndrome. However, 1-10% of patients with oral allergy syndrome may develop anaphylactic reactions, and many allergists started prescribing EpiPens to the patients with this condition.

Prolifins are especially important in allergy to some fruits, such as melon, watermelon, banana, tomato, citrus fruit and persimmon.

Natural and recombinant profilins are available for in vitro and in vivo allergy tests in some countries.

Although the role of profilins in triggering allergic symptoms is still controversial, they are relevant allergens. As a pan-allergen, profilin is associated with multiple pollen sensitization and pollen-food-latex syndromes that allergists, and other physicians, must to be aware of.

References:

Profilins: Mimickers of Allergy or Relevant Allergens? Santos A, Van Ree R. Int Arch Allergy Immunol. 2011 Feb 2;155(3):191-204.

Single dose of dexamethasone as effective as a 5-day course of oral steroids for asthma exacerbations in children

2012-01-10T08:57:00.016-05:00

Traditionally, mild-to-moderate pediatric asthma exacerbations have been treated with a short course of oral steroids - often 5 days of prednisone or prednisolone. According to a recent review from the journal Canadian Family Physician, a similar outcome can be acheived with a single dose of dexamethasone, which has a longer half-life and powerful anti-inflammatory effects, along with easier administration and compliance.

Oral administration of dexamethasone is the preferred route, especially considering the 80% bioavailability.

One study followed 110 children at 5 days after randomization to either a single dose of oral dexamethasone (0.6 mg/kg, maximum 18 mg) or oral prednisolone (1 mg/kg per dose, maximum 30 mg) twice daily for 5 days. Overall hospital admission rates at 5 days did not differ significantly between dexamethasone and prednisolone. Self-assessment scores returned to baseline in 5 days in both groups.

References:

Single-dose dexamethasone for mild-to-moderate asthma exacerbations: Effective, easy, and acceptable. Cross KP, Paul RI, Goldman RD. Can Fam Physician. 2011 Oct;57(10):1134-6.

Image source: Dexamethasone, Wikipedia.

Epinephrine injection is the first line treatment of food allergy-related anaphylaxis - a tragic case reminder

2012-01-05T08:18:00.012-05:00

Here is the Twitter timeline of Dr. Silge, an allergist/immunologist, with comments on a recent news report:

Tragic death in VA school w/ peanut allergic patient bit.ly/yWxgXI. This is why schools need access to epi. bit.ly/wyJrFP
— Robert Silge, MD (@DrSilge) January 4, 2012

While I have no info beyond a news story, also tragic it seems she had an action plan, without epi as part of it. bit.ly/yWxgXI
— Robert Silge, MD (@DrSilge) January 4, 2012

Very unclear to me why such a limited plan was in place. Article implies that the school wouldn't accept the family's Epipen.
— Robert Silge, MD (@DrSilge) January 4, 2012

Text summary (edited):

Robert Silge, MD @DrSilge: "Tragic death in VA school with a peanut allergic patient bit.ly/yWxgXI. This is why schools need access to EpiPen (bit.ly/wyJrFP). While I have no info beyond a news story, also tragic it seems she had an action plan, without epi as part of it ( bit.ly/yWxgXI). It's very unclear to me why such a limited plan was in place. The article implies that the school wouldn't accept the family's EpiPen.

Always remember: Epinephrine injection (EpiPen) is the first line treatment of food allergy-related anaphylaxis

Tips for managing food allergy (MJA, 2004):

- Always carry an EpiPen 2-Pak
- Always read food labels
- Ask questions about food preparation (be aware of the risk of cross-contamination)
- No label/no eat
- No EpiPen/no eat
- Tell friends about a serious food allergy
- Tell friends if feeling unwell, especially after eating

Eleanor Garrow, Vice President of Education and Outreach for FAAN, talks about living with food allergies, 2010.

This is a good summary from USA Today:

Pediatric allergy specialist Robert Wood of the Johns Hopkins Children's Center in Baltimore: "We reassure parents that kids will have a reaction. Somebody is going to make a mistake. But we reassure parents that kids are not going to die. These are preventable deaths. Kids who die from food allergies tend to have three things in common: asthma; nut allergies, which are usually more serious; and a delay in getting injectable epinephrine, which can stop fatal allergic reactions."

References:

Food Allergy Basics (video)

How To Use An Epipen (Epinephrine Autoinjector)

Related reading:

Pupil, 7, who 'loved school' dies after suffering allergic reaction to peanuts during recess break. Mail Online.

Methacholine not as sensitive to diagnose asthma as previously thought

2012-01-04T09:12:00.005-05:00

A negative methacholine test should not be relied upon to rule out asthma

Methacholine is not as sensitive to identify bronchial hyper-responsiveness (BHR) as previously thought, according to a recent review. A negative methacholine test should not be relied upon to rule out asthma.

Further, a positive methacholine test alone should be interpreted with caution as it may reflect airway injury or remodelling, rather than currently active asthma or exercise-induced bronchoconstriction (EIB).

What is 'direct' and 'indirect' bronchial provocation test (BPT)?

The terms 'direct' or 'indirect' refer to the mechanism by which a BPT causes bronchoconstriction.

For example, methacholine acts directly on bronchial smooth muscle (BSM) receptors causing it to contract and the airways to narrow.

In contrasr, the indirect stimuli (e.g. exercise or mannitol) cause the release of mediators (prostaglandins, leukotrienes and histamine) locally in the airways and these mediators act on BSM receptors to cause contraction.

However, the laboratory protocols currently used for exercise testing have a high failure rate to identify EIB that occurs in the field ("real life").

The other indirect stimulus mannitol is not ideal either. It identified a similar prevalence of BHR to methacholine and identified more patients than a single exercise test in 3 studies. However, neither mannitol nor methacholine identified all patients with EIB. Mannitol has a higher specificity for a physician diagnosis of asthma than methacholine.

Indirect stimuli are now being used to assess athletes, fire fighters, defence force personnel, smokers, children, to evaluate cough, to confirm asthma, and to assess drugs.

Both 'direct' AND 'indirect' tests may be needed for correct diagnosis

Bronchial provocation using both a direct test (methacholine) and an indirect test may be required in some patients to confirm or exclude a diagnosis of asthma with certainty.

References:

Bronchial provocation testing: the future. Anderson SD, Brannan JD. Curr Opin Allergy Clin Immunol. 2011 Feb;11(1):46-52. Review.

Bronchial Provocation Testing: The Future: Stimuli Used for Bronchial Provocation Test Act Either Directly or Indirectly. Curr Opin Allergy Clin Immunol. 2011;11(1):46-52, Medscape, 2011.

27% of patients with "physician-diagnosed asthma" had a negative methacholine test - misdiagnosis?

Image source: Spirometry, from Wikipedia, the free encyclopedia, GNU Free Documentation License.

What is NNT for omalizumab to prevent one hospitalization for asthma exacerbation? 33

2012-01-03T08:19:00.003-05:00

What is the number of patients that need to be treated (NNT) with omalizumab to prevent one hospitalization for asthma exacerbation?

The number needed to treat (benefit) (NNTB) is 33.

In a recent meta-analysis, during the stable-steroid phase, the asthma exacerbation rate was lower in the omalizumab group (RR, 0.57, NNTB, 10). There were significantly fewer hospitalizations from asthma exacerbation in the omalizumab group (RR, 0.44; NNTB, 33).

Patients treated with omalizumab were more likely to withdraw from corticosteroid treatment completely vs the placebo group (RR, 1.80; NNTB, 5). A higher proportion in the omalizumab group was able to reduce corticosteroid dosage by 50% or more (RR, 1.34; NNTB, 5).

Severe asthma - differential diagnosis and management (click to enlarge the image). Related: Common Asthma-related Comorbidities. Medscape, 2011, (figure) http://j.mp/omHVc6

References:

Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Chest. 2011 Jan;139(1):28-35.

Humanized Monoclonal Antibody May Be Effective, Safe in Asthma Patients. Medscape, 2011.

"Super-omalizumab" new monoclonal XmAb7195 has 5-fold higher affinity for IgE, 400-fold higher affinity for FcγRIIb. JACI, 2012.

Image source: Wikipedia, public domain.

"Cedar Fever" hits Central Texas again: allergic rhinitis/conjunctivitis in December-February

2011-12-30T09:30:00.006-05:00

From the local ABC TV station:

Just the sight of cedar is enough to make Millie Stefonsky start itching: "Itchy eyes, very watery eyes, scratchy throat, not having that energy we all need."

After years of fighting cedar fever, Stefonsky tried allergy shots and says they've made a world of difference. "I swear by it. I think that's the best way to go," she says.

Here are the Treatment Options for Allergic Rhinitis and Non-Allergic Rhinitis (click to enlarge the image):

Ocular antihistamines (eye drops) (click to enlarge the image):

References:

"Cedar Fever" hits Central Texas

Treating rhinitis improves asthma symptoms

2011-12-28T08:20:00.001-05:00

Allergic rhinitis, especially when persistent (PER) and associated with asthma heavily impairs patients' quality of life (QoL). This Italian study assessed the effect of mometasone furoate nasal spray (MFNS) on the QoL of patients with PER and asthma.

52 adults patients used momethasone 200 μg/day or placebo for 28 days.

The total 5-symptom score (T5SS) for rhinitis, the asthma symptom score and the sum of the two [global symptoms score (GSS)] were recorded daily. The primary outcome was the change in the Rhinasthma global summary (GS) at the end of treatment.

Momethasone produced a significant change in the Rhinasthma GS and improved symptoms.

The authors concluded that in in patients with PER rhinitis and intermittent asthma, momethasone nose spray improves the QoL and the burden of respiratory symptoms. Treating rhinitis may affect the asthma-related QoL.

Limitations of the study: The study relied only on subjective criteria such as patient symptoms, and no objective criteria such as FEV1 were included in the assessment of respiratory function.

Severe asthma (click to enlarge the image).

References:

Effects of mometasone furoate on the quality of life: a randomized placebo-controlled trial in persistent allergic rhinitis and intermittent asthma using the Rhinasthma questionnaire. Clin Exp Allergy. 2010 Dec 1. doi: 10.1111/j.1365-2222.2010.03660.x. Baiardini I, Villa E, Rogkakou A, Pellegrini S, Bacic M, Compalati E, Braido F, Le Grazie C, Canonica GW, Passalacqua G.

Image source: Illustration for "Aquiline or Roman Nose", Wikipedia, GNU Free Documentation License.

Children with allergic and nonallergic rhinitis have a similar risk of asthma: 20%

2011-12-26T09:44:00.002-05:00

This study included 38 seven-year-old children with allergic rhinitis, 67 with nonallergic rhinitis, and 185 without rhinitis from the Copenhagen Prospective Study on Asthma in Childhood birth cohort. They were compared for prevalence of asthma, eczema, food sensitization, filaggrin null-mutations, total IgE, blood eosinophil count, fractional exhaled nitric oxide (FeNO), lung function, and bronchial responsiveness.

Children with allergic rhinitis compared with asymptomatic controls had increased prevalence of:

- asthma (21% vs 5%),
- food sensitization (47% vs 13%)
- eczema (66% vs 43%)
- increased total IgE (155 kU/L vs 41 kU/L)
- blood eosinophil count (0.46 x 10(9)/L vs 0.30 x 10(9)/L)
- FeNO (15.9 ppb vs 6.6 ppb)
- bronchial hyperresponsiveness (23% vs 9%)

Children with nonallergic rhinitis also had increased asthma prevalence (20% vs 5%) but showed no association with eczema, food sensitization, total IgE, blood eosinophil count, FeNO, or bronchial responsiveness.

The study authors concluded that asthma is similarly associated with allergic and nonallergic rhinitis, suggesting a link between upper and lower airways beyond allergy-associated inflammation.

Modified Asthma Predictive Index (API) (click to enlarge the image).

References:

Children with allergic and nonallergic rhinitis have a similar risk of asthma. Chawes BL, Bønnelykke K, Kreiner-Møller E, Bisgaard H. J Allergy Clin Immunol. 2010 Sep;126(3):567-573.e8.

SPT < 7mm and sIgE < 2kU/L identify children likely to tolerate peanut (only 5% likelihood of failing oral challenge)

2011-12-22T08:28:00.000-05:00

A growing number of preschool children are identified as peanut sensitized in the course of investigation of other allergic conditions. But are they "truly allergic"? Although many have never ingested peanuts and their clinical reactivity is not known, it has been common practice to place these children on avoidance diets for many years.

This Australian study aimed to determine the utility of skin prick tests (SPT) and fluorescent-enzyme immunoassays (FEIA) for identifying either peanut allergy or tolerance in preschoolchildren with peanut sensitization.

49 preschool children (younger than 5 years of age) with peanut sensitization (defined as SPT larger than 2 mm or peanut-specific IgE greater than 0.35 kU/L) but unknown clinical reactivity had graded open peanut challenges reaching a total of 11 grams. A positive challenge was defined as an IgE-mediated reaction during challenge or the 2-h observation.

49% of children had positive challenges. An SPT greater than 7 mm on the day of challenge predicted a positive challenge with a sensitivity of 83% and a negative predictive value (NPV) of 84%.

sIgE greater than 2.0 kU/L showed a sensitivity of 79% and an NPV of 80%.

The tests worked much better when combined. Predicting challenge outcome from a combination of SPT and FEIA (SPT greater than 7 mm and/or FEIA greater than 2) increased sensitivity to 96% and NPV to 95%.

At least half of preschool children with peanut sensitization and no history of peanut ingestion can tolerate peanuts.

A SPT less than 7 mm and FEIA less than 2 kU/L identify children most likely to tolerate peanut, with only a 5% likelihood of failing an oral challenge. This study would definitely help allergists when considering oral challenges in peanut-sensitized children.

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).

References:

Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschoolchildren with peanut sensitization. Johannsen H, Nolan R, Pascoe EM, Cuthbert P, Noble V, Corderoy T, Franzmann A, Loh R, Prescott SL. Clin Exp Allergy. 2011 Mar 24. doi: 10.1111/j.1365-2222.2011.03717.x.
Food Allergen Avoidance
Food Challenges
Mind Maps: Food Allergy
Image source: Roasted peanuts as snack food, Wikipedia, public domain.

Asthmatics who slept beneath the stream of cool air device for one year had improved quality of life and decreased airway inflammation

2011-12-21T08:03:00.002-05:00

A randomized, double-blind, placebo-controlled trial evaluated whether environmental control with nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of 300 patients aged 7–70 with inadequately controlled persistent atopic asthma in 19 European asthma clinics. TLA devices were installed in the bedrooms of patients to provide a stream of cool air above their heads (see the video embedded below).

The manufacturer advertises the device, called Protexo, as "treatment for patients with atopic asthma without side-effects" (video).

There was a statistically significant difference in treatment response rate between active (76%) and placebo (61%) groups (p=0.02). There was also a difference between groups in fractional exhaled nitric oxide (FeNO) change of −7.1 ppb (p=0.03). Interestingly, the nocturnal temperature controlled laminar airflow (TLA) was associated with less increase in cat-specific IgE than placebo.

The study authors concluded that TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. Even if the benefits of TLA are confirmed in future trials, the expected relatively high cost of the device (Protexo) may be problematic. A similar device (Opragon) by the same Swedish company (Airsonett) is used to reduce surgical site infections. Neither device is available in the U.S.

References:

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial. Thorax doi:10.1136/thoraxjnl-2011-200665

Comments from Twitter:

Jennifer Gunter @DrJenGunter: re: cool air device, is that like heading for "sea air" as docs of yore recommended?

@Allergy: Protexo is a bit different - it probably changes the exposure to indoor rather than outdoor allergens

RNA interference (RNAi) - by Nature Video

2011-12-20T19:47:00.000-05:00

RNA interference (RNAi)is used by many different organisms to regulate the activity of genes. This animation explains how RNAi works and introduces the two main players:

- small interfering RNAs (siRNAs)
- microRNAs (miRNAs)

The Nature video takes you on an audio-visual journey, diving into a cell to show how genes are transcribed to make messenger RNA (mRNA) and how RNAi can silence specific mRNAs to stop them from making proteins.

Chronic Rhinosinusitis (CRS)

2011-12-19T08:47:00.000-05:00

Chronic rhinosinusitis (CRS) affects 12.5% of the US population.

Risk factors for CRS

The following associations are found between CRS prevalence and:

- air pollution
- active cigarette smoking
- secondhand smoke exposure
- perennial allergic rhinitis
- gastroesophageal reflux (GERD)

The majority of pediatric and adult patients with CRS are immune competent (editor note: this has been challenged recently by a study that showed that more than 70% of adult patients with chronic sinusitis may have a poor response to pneumococcal immunization).

Nose and nasal cavities. Image source: Wikipedia, public domain.

Classification of CRS

- CRS without nasal polyposis (CRSsNP)
- CRS with nasal polyposis (CRSwNP)
- allergic fungal rhinosinusitis (AFRS)

Treatment of CRS

The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics.

The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations.

Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP.

Sinus surgery followed by use of systemic steroids is recommended for AFRS.

Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled trials.

References:

Chronic rhinosinusitis: Epidemiology and medical management. Hamilos DL. J Allergy Clin Immunol. 2011 Sep 2.

Daily vs. Intermittent Budesonide in Preschool Children with Recurrent Wheezing: No Difference

2011-12-16T08:02:00.001-05:00

Daily inhaled corticosteroids are recommended for young children at risk for asthma exacerbations and an exacerbation in the preceding year. However, concerns remain about effects on growth. This study published in the NEJM compared daily therapy with intermittent therapy with nebulized budesonide in 278 children aged 12 to 53 months. All of them had positive modified asthma predictive index (API), recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment.

Modified Asthma Predictive Index (API) (click to enlarge the image).

They were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during respiratory tract illness) or a daily regimen (0.5 mg nightly).

The daily regimen of budesonide 0.5 mg did not differ significantly from the intermittent regimen with in terms of exacerbations or adverse events.

The authors concluded that a daily low-dose regimen of budesonide 0.5 mg was not superior to an intermittent high-dose regimen (1 mg twice a day) in reducing asthma exacerbations. This is an important development especially considering that the mean exposure to budesonide was 104 mg less with the intermittent regimen.

Asthma Inhalers (click to enlarge the image).

References:

Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing. N Engl J Med 2011; 365:1990-2001, November 24, 2011.

No dose-response relationship for fluticasone furoate in moderate/severe asthma: 200 mcg once daily worked as well as 800 mcg

2011-12-15T08:53:00.000-05:00

Fluticasone furoate (FF) is a new inhaled corticosteroid with 24-hour activity. GlaxoSmithKline is developing FF as a once-daily asthma treatment in combination with the long-acting β2 agonist vilanterol.

This 8-week multicentre, randomized, double-blind study included 600 adult patients with persistent moderate-to-severe asthma, who were symptomatic on medium-dose inhaled corticosteroid therapy. The study was sponsored by GlaxoSmithKline and company employees were among the co-authors.

The patients were randomized to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a new dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus or Accuhaler).

Fluticasone furoate, Veramyst (US) and Avamys (EU and Canada), is different in structure from fluticasone propionate (see below). Image source: Wikipedia, public domain.

Fluticasone propionate, Flonase (US and Canada) Flixonase (EU and Brazil). Fluticasone propionate is also part of the ICS/LABA combination product Advair. Image source: Wikipedia, public domain.

Each inhaled steroid dose was superior to placebo for the primary endpoint which was pre-dose evening forced expiratory volume in one second (FEV1). There was no dose–response relationship across the FF doses studied. Peak expiratory flow improved in all groups. The incidence of oral candidiasis was higher with FF 800 μg than placebo; there was also a higher systemic exposure of FF at this highest dose level.

The study authors concluded that FF doses below 800 μg have a favorable therapeutic index, and 200 μg is an appropriate dose in patients with moderate persistent asthma.

References:

Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax 2012;67:35-41 doi:10.1136/thoraxjnl-2011-200308