Allergy Notes: 01/2008

Combination therapy with azelastine and fluticasone nasal sprays is better than each drug alone for seasonal allergic rhinitis

A 2-week, multicenter, double-blind trial was conducted during the Texas mountain cedar season -- 151 patients were randomized to treatment with:

1. azelastine nasal spray, 2 sprays per nostril twice daily
2. fluticasone nasal spray, 2 sprays per nostril once daily
3. azelastine nasal spray, 2 sprays per nostril twice daily, plus fluticasone nasal spray, 2 sprays per nostril once daily (the combination)

The efficacy was measured by the change in the total nasal symptom score (TNSS), consisting of sneezing, itchy nose, runny nose, and nasal congestion.

All 3 groups had improvements from their baseline TNSS, 27% with fluticasone, 25% with azelastine, and 38% with the 2 agents in combination, respectively.

The authors concluded that azelastine and fluticasone combination may provide a therapeutic benefit in seasonal allergic rhinitis compared with therapy with either agent alone.

This finding is in contrast with previously published studies that found no advantage from using the combination of an oral antihistamine and steroid spray. Two sprays seem to work better than a spray and a pill.

Patients should be instructed to angle the fluticasone spray towards the ear to direct it where the inflamed nasal mucosa is. Pumping it straight up will direct the medication to the nasal cartilage, leading to local side effects.

Azelastine-Fluticasone nose spray (Dymista) is effective for allergic rhinitis and is awaiting FDA approval (http://goo.gl/QbbDl and http://goo.gl/8DPwY).

A 2014 study showed that Dymista (FP and AZE) was twice as effective as AZE or FP for allergic rhinitis, 7 out of 10 patients became symptom-free after 1 month of therapy http://buff.ly/1dEajBO

References:

Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in the treatment of patients with seasonal allergic rhinitis. Annals of Allergy, Asthma and Immunology, 2008, vol. 100, no. 1, pp. 74 - 81.
Azelastine Plus Fluticasone Nasal Spray Effective for Seasonal Allergic Rhinitis. Medscape, 01/2008.
Image source: Azelastine, Wikipedia, public domain.

Related reading:

New tools help MDs treat allergies. National Review, 03/2008.

Positive study results for combined INS/INA spray for allergic rhinitis, Dymista, fluticasone/azelastine http://goo.gl/d6RZ7
Combination nose spray azelastine plus fluticasone works better than individual components in allergic rhinitis. JACI, 2012.

8 "Culprits" in Food Allergy

Some of the "culprits" in food allergy. Image source: Mcclatchy-Tribune.

Eight top allergens account for 90 percent of all food allergies. The 8 top allergens can be remembered by the mnemonic TEMPS WFS:

Tree nuts (almonds, cashews, walnuts)
Eggs
Milk
Peanuts
Shellfish (crab, lobster, shrimp)
Wheat
Fish (bass, cod, flounder)
Soy

Eight top allergens account for 90 percent of all food allergies. See more Allergy and Immunology mind maps here.

References:

Food Allergy: A Short Review. Allergy Cases.

Clinical review: ABC of allergies, Food allergy. BMJ 1998;316:1299, figure.

Related:
Everything you need to know about food allergies. Clifford W. Bassett, M.D. MSNBC, 01/2008.

02/02/2008

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).

"Asthma Capitals" Named by Asthma and Allergy Foundation of America

Top "asthma capitals" for 2008:

1. Knoxville, TN
2. Tulsa, OK
3. Milwaukee, WI
4. Atlanta, GA
5. Memphis, TN
6. Allentown, PA
7. Charlotte, NC
8. Greenville, SC
9. St. Louis, MO
10. Greensboro, NC
A full report of the rankings for 100 cities is available at AsthmaCapitals.com. The annual list is based on research sponsored by AstraZeneca.

Rankings are based on analysis of 12 factors grouped into three categories:

1. Prevalence factors such as the crude death rate (CDR) for asthma and estimated prevalence of adult and pediatric asthma.

2. Risk factors such as air pollution, pollen counts and public smoking bans

3. Medical factors such as the number of asthma medications used per patient and the number of asthma specialists in the area.

Click here for the PDF of the full report of 100 cities. For example, this is the list of the cities in Florida with the number of asthma specialists in the area:

- Pensacola, average
- Tampa, below average
- Jacksonville, below average
- Orlando, average
- Lakeland, below average
- Sarasota, below average
- West Palm Beach, below average
- Melbourne, below average
- Fort Myers, average
- Daytona Beach, below average

References:
Asthma Capitals Ranking Methodology. AAFA.org.
Image source: Wikipedia, public domain.

Related:
Asthma ranking's not news to doctors. Greensboro, NC.

Updated: 02/04/2008

Joint Task Force Report on Omalizumab-associated Anaphylaxis

The Joint Task Force concluded that 39,510 patients received Xolair (omalizumab) between 2003 and 2005. From this group, 35 patients had 41 episodes of anaphylaxis related to Xolair. Calculated anaphylaxis-reporting rate was 0.09% of patients, 61% of reactions occurred in the first 2 hours after one of the first 3 doses. Omalizumab binds to Cε3 region of IgE.

An observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions.

Click here for a case report of a delayed allergic reactions to omalizumab.

References:
American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV. J Allergy Clin Immunol. 2007 Dec;120(6):1373-7. Epub 2007 Nov 9.
Delayed allergic reactions to omalizumab: Are patients reporting all cases? JACI, 03/2008.
Image source: Wikipedia, public domain.
Images: Mechanisms of action of omalizumab. JACI, 02/2008.

Updated: 03/08/2008

Optimal Dose of Sublingual Immunotherapy (SLIT) for Allergic Rhinitis

Grass pollen tablets with an index of reactivity (IR) of 300 provided the best risk-benefit ratio for sublingual immunotherapy (SLIT) of seasonal allergic rhinitis in a recent study.

The study included 628 adults with grass pollen allergic rhinoconjunctivitis who were randomized to receive standardized 5-grass pollen extract as SLIT daily. Treatment began 4 months prior to the expected pollen season and continued during the season. Both the 300-IR and 500-IR doses of SLIT improved symptoms compared to placebo.

Adverse events led to discontinuation of treatment in 5.2%, and 6.9% of patients in the 100-IR, 300-IR and 500-IR groups, respectively. No serious side effects were seen.

References:
Optimal Dose of Sublingual Immunotherapy for Allergic Rhinitis Identified. Medscape, 01/2008.
J Allergy Clin Immunol 2007;120:1338-1345.
Talking Points on Sublingual Immunotherapy (SLIT) for Physicians Practicing in the United States. ACAAI.

Sublingual immunotherapy is an extremely complex issue in the U.S. - AAAAI http://goo.gl/wVOKr

Timothy grass allergy immunotherapy tablets safe and effective in American children with allergic rhinitis http://goo.gl/tsKL4

Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults - it works. http://goo.gl/ePOFG
Image source: Wikipedia, GNU Free Documentation License.

Video: How to Use Asthma Devices -- Inhalers, Spacers, Peak Flow Meters

How To Use A Peak Flow Meter

More videos:

Inhaler Technique

Spacer Devices part 1

Spacer Devices part 2

Source:
Builth & Llanwrtyd Medical Practice is a Doctors Surgery in rural Mid Wales, UK. Thye produce information videos for their patients on YouTube.

Related:
YouTube as a Source of Health Misinformation. Highlight HEALTH 2.0, 02/2008.
YouTube as a source of information on immunization: a content analysis. Keelan et al. JAMA. 2007 Dec 5;298(21):2482-4.
Spacers should not be regarded as interchangeable: each pMDI–spacer combination should be treated as a unique system (ERJ, 2012).
Inhaler Technique Videos. Asthma Foundation http://goo.gl/5H5i

Medications reference chart. Asthma Foundation http://goo.gl/ourq

Proper techniques for the administration of inhaled medications to treat asthma - AAAAI - Ask the Expert, 2011.

Video: How to use an asthma inhaler spacer

Spacers should not be regarded as interchangeable: each pMDI–spacer combination should be treated as a unique system (ERJ, 2012).

How to use an asthma inhaler spacer. Kellen Glinder, a PAMF Pediatrician.

Asthma Inhalers and Spacers. Dr Mdk.

Related:
YouTube as a Source of Health Misinformation. Highlight HEALTH 2.0, 02/2008.
YouTube as a source of information on immunization: a content analysis. Keelan et al. JAMA. 2007 Dec 5;298(21):2482-4.
Inhaler Technique Videos. Asthma Foundation http://goo.gl/5H5i
Medications reference chart. Asthma Foundation http://goo.gl/ourq

Proper techniques for the administration of inhaled medications to treat asthma - AAAAI - Ask the Expert, 2011.

Cold Urticaria on Flickr

A Flickr user has uploaded photos of what it looks and sounds (from the description) like cold urticaria.

Testing procedures for diagnosis of physical urticarias depend on the cause (stimulus):

- Dermographism: Stroking with narrow object, e.g. a tongue depressor

- Cold urticaria: ice cube test

- Heat urticaria: test tube water at 44°C (111°F)

- Pressure urticaria: Sandbag test or a bag with heavy books (Middleton's Allergy textbook, 2 volumes)

- Vibratory urticaria: vibration with laboratory vortex for four minutes

- Cholinergic urticaria: exercise for 15-20 minutes or leg immersion in 44°C (111°F) bath

- Aquagenic urticaria: challenge with tap water at various temperatures

Podcasts in Allergy and Immunology

A podcast is a downloadable audio or video file that you can subscribe to and get regular updates when a new episode is released (weekly or monthly). Almost all podcasts are free and the best way to use them is via Apple's iTunes/iPod.

ACAAI Podcast Library

The American College of Allergy, Asthma & Immunology (ACAAI) has started publishing free podcasts/videocasts since the 2006 Annual Meeting:

2007 Annual Meeting Podcasts

2006 Annual Meeting Podcasts

Published: 12/10/2008

Updated: 01/11/2011

What is laryngopharyngeal reflux (LPR) and should we treat it?

Laryngopharyngeal Reflux Disease (LPR or LPRD) is a common condition described as reflux disease similar to Gastroesophageal reflux disease (GERD).

What is the difference between GERD and LPRD?

If the reflux makes it all the way up through the upper sphincter of the esophagus and into the back of the throat, it is called LPRD.

There is no consensus on the diagnosis and treatment of LPRD and the disease concept is still somewhat controversial.

A proton pump inhibitor twice daily for 2 months is currently recommended for patients with laryngeal signs and symptoms. If the condition responds to therapy, tapering to once-daily therapy and then to minimal acid-suppression to control symptoms is prudent.

Patients whose symptoms do not respond to a proton pump inhibitor are unlikely to benefit from surgery. Other diagnoses should be entertained, while the drug is tapered to prevent rebound acid reflux.

The current practice of empirical treatment with proton-pump inhibitors (PPI) is based on weak evidence.

In patients with asthma and chronic productive cough, polymorphonuclear (PMN) neutrophil leukocytes in sputum suggest:

(A) infection

(B) GERD

(D) exercise-induced asthma

(E) extrinsic asthma

Correct answers: A, B, C

References:

Laryngopharyngeal reflux: diagnosis and treatment of a controversial disease. Current Opinion in Allergy & Clinical Immunology. 8(1):28-33, February 2008. Ali, Mahmoud El-Sayed.
Laryngopharyngeal Reflux Disease and Recommendations to Prevent Acid Reflux. Columbia University.
Laryngopharyngeal Reflux Disease: A Case Presentation. Baylor College of Medicine.

Laryngopharyngeal reflux: More questions than answers. Cleveland Clinic Journal of Medicine May 2010 vol. 77 5 327-334.

Image source: Wikipedia, public domain.

Related reading:
Vocal cord dysfunction. WebMD.

What is Considered a Normal Number of Reflux Episodes? ENT blog, 2011.

Role of laryngoscopy in children with respiratory complaints and suspected reflux (LPR). Allergol Immunopathol (Madr). 2011 Oct 4.
Rapid Saliva Test for Laryngopharyngeal Reflux (LPR) http://goo.gl/LEsMO and http://goo.gl/GCean

Mnemonic for different causes of cough: GREAT BAD CAT TOM

This is a mnemonic for differential diagnosis of cough:

Bronchitis or pneumonia
Asthma
Drugs, e.g. ACEi

Cardiogenic, e.g. mitral stenosis
Aspiration, e.g foreign body in children, achalasia in adults
TB

Thyroid enlargement, e.g. goiter
Other, e.g. GERD, PE
Malignancy, e.g. lung cancer

Differential diagnosis of cough, a simple mnemonic is GREAT BAD CAT TOM. Click here to enlarge the image: (GERD (reflux), Laryngopharyngeal Reflux (LPR), Rhinitis (both allergic and non-allergic) with post-nasal drip (upper airway cough syndrome), Embolism, e.g. PE in adults, Asthma, TB (tuberculosis), Bronchitis, pneumonia, pertussis, Aspiration, e.g foreign body in children, Drugs, e.g. ACE inhibitor, CF in children, Cardiogenic, e.g. mitral stenosis in adults, Achalasia in adults, Thyroid enlargement, e.g. goiter, "Thoughts" (psychogenic), Other causes, Malignancy, e.g. lung cancer in adults).

References:

One hundred coughs. Can Fam Physician, Vol. 54, No. 2, February 2008, pp.236 - 237.
The Lancet Seminar: Prevalence, pathogenesis, and causes of chronic cough and Management of chronic cough. The Lancet 2008; 371:1375-1384.
Image source: Wikipedia, the free encyclopedia, fair use.

Related:

Diagnosis of chronic cough in children
Green or yellow phlegm likely to be bacterial - confirming beliefs by doctors & patients http://goo.gl/zff8X and http://goo.gl/cwKGs

CNN: Mystery cough? 8 possible culprits http://bit.ly/nHMQo
ACCP cough guidelines http://bit.ly/wLvuO
Long-term low-dose erythromycin in patients with unexplained chronic cough: no effect http://goo.gl/8eOUS

How should one investigate a chronic cough? Cleveland Clinic Journal of Medicine, 2011.
Diagnostic algorithm for the approach to children with chronic cough. ER, 2011.
Diagnostic Checklist (mobile version) - UToronto and standard web version

Chronic Cough - COLA video lecture http://bit.ly/URcUQa:

Clinical approach from the concept of cough hypersensitivity - figure: http://buff.ly/1Jej9Cq

Survey: How Patients with Allergic Rhinitis Feel about Their Condition

The Patient Voice Allergy Survey included 3562 patients with allergic rhinitis (16 years and older):

- 50% of the responders reported symptoms lasting more than one season
- Preventive household adjustments were perceived as expensive with little benefit
- Sleep and emotional life were affected by allergic rhinitis
- 25% reported dissatisfaction with current allergic rhinitis medications.

References:
The voice of the patients: allergic rhinitis is not a trivial disease. Current Opinion in Allergy & Clinical Immunology. 8(1):1-9, February 2008. Valovirta, Erkka et al.

Video: What to do in case of allergic reaction?

If I Had - An Allergic Reaction - Dr. Robert Wood, MD

If I Had An Allergic Reaction - Dr. Robert Wood, MD

From Insidermedicine:

"Dr. Robert Wood, MD is a pediatric allergist and professor of pediatrics at the Johns Hopkins Children’s Center, and director of the Division of Pediatric Allergy and Immunology at Johns Hopkins University. A world-renowned expert in the treatment of peanut allergy, Dr. Wood is also the author of the book, "Food Allergies For Dummies." We asked Dr. Wood for his thoughts on the detection and treatment of severe allergic reactions."

Review: Dietary prevention of allergic diseases in infants and small children

Breastfeeding is highly recommended for all infants irrespective of atopic heredity.

Recommendations for prevention of allergic diseases in high-risk infants:

1. The most effective dietary regimen is exclusively breastfeeding for at least 4–6 months. Shorter duration and nonexclusivity of breastfeeding are associated with increased risk of asthma symptoms in children. ERJ January 1, 2012 vol. 39 no. 1 81-89.

2. In absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months.

3. Avoidance of solid food and cow's milk for the first 4 months.

Eight top allergens account for 90 percent of all food allergies. See more Allergy and Immunology mind maps here.

Fatty acids in breast milk, n-3 long-chain polyunsaturated fatty acids (LCPs), may have a protective role in the development of atopic disease.

References:

Review Up-date: Dietary prevention of allergic diseases in infants and small children. EAACI. Pediatr Allergy Immunol 2008: 19: 1–4.

Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. http://goo.gl/YBf6
Food Allergy: Brief Review. Allergy Cases, 01/2008.

Infants with family history of allergies less likely to develop peanut allergy if they start solid foods before age 4 months. Reuters, 2011.

Food introduced before age 4 months reduces risk of peanut sensitization by age 2-3 years, but only if FMH is positive for asthma or allergy, JACI, 2011.
Shorter duration and nonexclusivity of breastfeeding are associated with increased risk of asthma symptoms in children. ERJ January 1, 2012 vol. 39 no. 1 81-89.

New therapies for hereditary angioedema (HAE)

Hereditary angioedema (HAE) is an autosomal dominant condition associated with episodic attacks of nonpitting edema. Patients with HAE have low levels of C1 inhibitor (a serine protease inhibitor). Edema is caused by unregulated generation of bradykinin.

C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia.

Classical and alternative complement pathways. Image source: Wikipedia.

Angioedema (AE) Classification (click to enlarge the image):

Angioedema (AE) can be allergic or non-allergic.

There are 5 types of non-allergic angioedema (AE):

- acquired AE
- hereditary AE (HAE)
- ACE-inhibitor induced AE
- idiopathic AE, can occur with chronic urticaria
- pseudoallergic AE, e.g. reaction to NSAIDs

There are 3 types of HAE that are differentiated by C4 and C1-INH levels

- type I HAE - low C4, low C1-INH function, low C1-INH antigen level
- type II HAE - low C4, low C1-INH function, normal C1-INH antigen level
- type III HAE - all normal

Effective chronic therapy for HAE has been available for decades -- androgens or plasmin inhibitors. Until recently, there was no therapy for acute attacks available in the U.S.

Treatment of acute HAE attacks

- C1-INH, 20 units/kg, IV infusion
- Icatibant, 30 mg SC, bradykinin B2 receptor antagonist
- Ecallantide, 30 mg SC, kallikrein receptor antagonist

Prophylaxis of HAE attacks

- C1-INH, 1,000 units, IV infusion every 3-4 days
- attenuated androgen, e.g. danocrine 200 mg PO TID

References

New Directions in the Treatment of Angioedema. Medscape, 2012.
http://www.medscape.org/viewarticle/759075

In recent years, 5 pharmaceutical companies have developed drugs which stop acute attacks of HAE or can be used for prophylaxis.

There are 2 preparations of C1 inhibitor purified from plasma which have been used in Europe for decades (Cinryze and Berinert P). There is also a recombinant C1 inhibitor (not obtained from plasma). A kallikrein inhibitor (Ecallantide) and a bradykinin type 2 receptor antagonist (Icatibant) are in testing phases. It is likely that HAE treatment will change dramatically in near future.

New therapies for hereditary angioedema (HAE) (click to enlarge the image).

In summary, the new products for acute treatment and prophylaxis of hereditary angioedema (HAE) are:

- C1 inhibitor purified from plasma (Cinryze and Berinert P)
- recombinant C1 inhibitor. Recombinant C1 inhibitor is in phase III studies and should be available for HAE attacks in the near future http://goo.gl/Nxf8k
- kallikrein inhibitor (Ecallantide)
- bradykinin type 2 receptor antagonist (Icatibant)

References:

New therapies for hereditary angioedema: Disease outlook changes dramatically. Frank et al. JACI, Volume 121, Issue 1, Pages 272-280 (January 2008).
New Directions in the Treatment of Angioedema. Medscape, 2012.

Hereditary angioedema, Supplement of Annals of Allergy, Asthma and Immunology, 01/2008.

Further reading:

Angioedema Due to Angiotensin Converting Enzyme Inhibitors. Allergy Cases, 01/2008.
Audio: New Therapies on Horizon for Angioedema Attacks. AAAAI, 03/2008.
HAE: annual drug cost alone for prophylactic C1 esterase inhibitor is $450k - nearly $5 mln for every decade of life http://goo.gl/BCVtu
Recombinant C1 inhibitor is in phase III studies and should be available for HAE attacks in the near future http://goo.gl/Nxf8k
HAE patients can self-administer Berinert C1-INH by IV infusion - FDA, 2012.

New Articles about Allergic Rhinitis

Herbal medicines for the treatment of allergic rhinitis: a systematic review.
Ruoling Guo et al. Annals of Allergy, Asthma and Immunology, 01/2008.

According to the authors, there is encouraging evidence suggesting that P hybridus (Butterbur) may be an effective herbal treatment for seasonal (intermittent) AR. There are also promising results generated for other herbal products, particularly Aller-7, Tinospora cordifolia, Perilla frutescens, and several Chinese herbal medicines. Confirmation in larger and rigorously designed clinical trials is warranted.

Safety and tolerability of fexofenadine hydrochloride, 15 and 30 mg, twice daily in children aged 6 months to 2 years with allergic rhinitis.
Frank C. Hampel et al. Annals of Allergy, Asthma and Immunology, 01/2008.

Which antihistamine to use in young children? Antihistamines are first-line treatment for allergic rhinitis and are widely prescribed in infants for allergic symptoms but their safety profile in very young children is not well-established. Fexofenadine (Allegra) given for a mean duration of 8 days was well tolerated, with a good safety profile, in the study population of children aged 6 months to 2 years.

Pathophysiology and progression of nasal septal perforation.
Bobby Lanier et al. Annals of Allergy, Asthma and Immunology, 01/2008.

What are the causes of nasal septal perforation? The article lists different causes of nasal septal perforation (NSP): piercings, exposure to industrial chemicals, illicit drug use, intranasal steroid use, surgical trauma, bilateral cautery, and possibly improper use of nasal applicators.

Image source: Wikipedia, a Creative Commons license.

How many respiratory infections in children are "normal" per year?

Respiratory infections are the most frequent illness in childhood.

How many respiratory infection episodes can be expected in a normal child?

According to a German study of 760 children followed for 12 years, the mean cumulative number of respiratory infections up to age 12 yr was 22. In infancy, the mean annual number was 3.4 episodes; at pre-school age, 2.3 episodes; and at school, age 1.1 episodes.

Based on a two-fold standard deviation of the mean, the number of "normal" respiratory infections was up to:

- 11 respiratory infection episodes per year in infancy
- 8 episodes per year at pre-school age
- 4 episodes per year at school age

Episodes within these reference values should not cause unwarranted concerns of suspected immunodeficiency.

References:

History of respiratory infections in the first 12 yr among children from a birth cohort. Christoph Grüber et al. Pediatric Allergy and Immunology (OnlineEarly Articles).
doi:10.1111/j.1399-3038.2007.00688.x
Why children with asthma get sick in September?
Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. http://goo.gl/PghX
Most Helpful Warning Signs to Identify Primary Immunodeficiency Diseases - Medscape, 2011.
Rhinoviruses: markers of, or causative for, recurrent wheeze and asthma? ERJ 2012.
Image source: Molecular surface of a rhinovirus, Wikipedia, GNU Free Documentation License.

Comments from Twitter:

Nazım Coşkun @nazimcoskun: I am not sure if 11 respiratory infection episodes per year in infancy should not cause concerns of immunodeficiency.

@Allergy: agree, that's why I've embedded the PDF with "10 warning signs for PIDD" at the end: http://goo.gl/LMZ7

Interview with John Routes: Newborn Screening for “Bubble Boy Disease”

Berci Mesko of ScienceRoll.com interviewed John Routes from the Children’s Hospital of Wisconsin about the screening for Severe Combined Immune Deficiency (SCID), sometimes called “Bubble Boy Disease.”

SCID is a heterogeneous group of genetic disorders characterized by an arrest in T lymphocyte development which leads to an abnormal differentiation of B and NK cells.

References:

Severe combined immunodeficiency: A cohort of 40 patients in Iran. Mehdi Yeganeh et al. Pediatric Allergy and Immunology (OnlineEarly Articles). doi:10.1111/j.1399-3038.2007.00647.x

The state of Wisconsin approach to newborn screening for SCID: 5 infants with SCID detected in 3 years. JACI, 2012.

How to read labels in peanut allergy? Which foods are "safe"?

Eight top allergens account for 90 percent of all food allergies. The 8 top allergens can be remembered by the mnemonic TEMPS WFS:

Tree nuts (almonds, cashews, walnuts)
Eggs
Milk
Peanuts
Shellfish (crab, lobster, shrimp)
Wheat
Fish (bass, cod, flounder)
Soy

Eight top allergens account for 90 percent of all food allergies. See more Allergy and Immunology mind maps here.

Peanut allergy

Peanut allergy is usually lifelong, often severe, and potentially fatal. It is not uncommon. In North America and the UK, prevalence among school children is more than 1%.

Remission of peanut allergy can be predicted by low levels of IgE to peanut in the first 2 years of life or decreasing levels of IgE sensitization by the age of 3 years.

How to read labels in peanut allergy?

Medical Websites (by Hospitals or Universities)

Decoding Food Labels: Tools for People with Food Allergies. University of Florida.
Peanut Allergy Diet. University of Michigan.
Peanut allergy. Children's Hospital at Westmead, Sydney Children's Hospital.

Which foods may be "safe"?
(shown for illustration only, information is not verified, use at your own risk, please see this website disclaimer)

Patient-support Websites (non-professional)

10 Peanut Allergy Safe Candy Canes for 2007. AllergyMoms Blog.
Safe Foods. Peanut Aware Inc.
Reading Food Labels. Allergic Child Publishing Group.

AAAAI: Gradual Exposure Reduces Kids' Peanut Allergy. MedPage Today, 03/2008.

References:
Peanut allergy: Emerging concepts and approaches for an apparent epidemic. Sicherer SH, Sampson HA. J Allergy Clin Immunol. 2007 Aug 7.
Early clinical predictors of remission of peanut allergy in children. JACI, 03/2008.
Food Allergy: A Short Review. Allergy Cases.
Image source: Wikipedia, public domain.

Related:
Guest Columnist Allegra Cullen, Age 12, on Peanut Allergy. Achoo! Allergy.

New Articles about Asthma

Tolerability of indacaterol, a novel once-daily beta 2-agonist, in patients with asthma: a randomized, placebo-controlled, 28-day safety study.
William H. Yang et all. Annals of Allergy, Asthma and Immunology, 01/2008.

Indacaterol, a new once-daily beta 2-agonist for asthma treatment, was tolerated well in one-month study.

Long-term safety study of levalbuterol administered via metered-dose inhaler in patients with asthma. Annals of Allergy, Asthma and Immunology, 01/2008.
Daniel L. Hamilos et al.

Few studies have explored the safety of long term use of racemic albuterol, and none have examined long-term dosing of levalbuterol. In this trial, regular use of levalbuterol HFA MDI or racemic albuterol HFA MDI was well tolerated, and no deterioration of lung function was detected during the study period of 52 weeks (1 year).

Image source: Wikipedia, public domain.

Mediterranean diet can protect children from asthma

According to some recent studies, Mediterranean diet seems to be the "miracle cure" which can decrease the cardiovascular risk and even prolong life.

This research study published in Thorax was done in rural Crete and included a survey of 690 children between the ages of 7 and 18 years. Parents completed questionnaires on their children's respiratory and allergic symptoms and diets. According to researchers, intake of grapes, oranges, apples, and fresh tomatoes protected against wheeze and nasal allergies. High consumption of nuts was inversely associated with wheezing, whereas margarine increased the risk of both wheeze and allergic rhinitis.

A 2012 review did not show a Significant Influence of Mediterranean Diet on Asthma Symptoms http://buff.ly/YcVEq0

References:
Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete. Thorax. 5 April 2007. doi:10.1136/thx.2006.069419.
Mediterranean Diet Linked to Lower Pediatric Atopy. MedPageToday.com.
Mediterranean Diet May Protect Against Childhood Asthma-Like Symptoms and Rhinitis. Medscape.com.
Mediterranean Diet Seems to Improve Cardiovascular Risk Factors After Just 3 Months
Mediterranean Diet Protects Against Allergies & Asthma. achoo! Blog.
Mediterranean diet wards off asthma, allergy: study. Reuters, 01/2008.
Why to Eat Like a Greek http://goo.gl/Chpwf - Mediterranean diet improves heart risk factors http://goo.gl/DkPhF

A high-fat meal augments neutrophilic airway inflammation, suppresses bronchodilator recovery in asthma http://goo.gl/ZNGpL

Allergic rhinitis is associated with more severe and difficult to control asthma

Allergic rhinitis (AR) and asthma often occur concomitantly. According to a study conducted by French GPs, the frequency of AR in asthmatic patients was 55.2%. The frequency and severity of AR increased with the severity of asthma and AR was associated with worse asthma control.

In conclusion, AR was associated with more severe asthma, more difficulty to control asthma and substantial impairment of quality of life.

It makes sense to use immunotherapy to control symptoms of AR and hopefully have a positive impact on asthma symptoms as well.

The new asthma guidelines by the National Heart, Lung, and Blood Institute (NHLBI) recommend immunotherapy for treatment of asthma for the first time since their inception (quote from page 195):
“The Expert Panel recommends that allergen immunotherapy be considered for patients who have persistent asthma if evidence is clear of a relationship between symptoms and exposure to an allergen to which the patient is sensitive (Evidence B).”

Severe asthma - differential diagnosis and management (click to enlarge the image).

References:

Frequency and impact of allergic rhinitis in asthma patients in everyday general medical practice: a French observational cross-sectional study. Magnan A, Meunier JP, Saugnac C, Gasteau J, Neukirch F. Allergy. 2007 Nov 20.
Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute (NHLBI).
Links between allergic rhinitis and asthma still reinforced. P. Demoly, P. J. Bousquet (2008). Allergy 63 (3), 251–254.
Poor asthma control? – then look up the nose. The importance of co-morbid rhinitis in patients with asthma http://goo.gl/0nNZg
Image source: Wikipedia, a Creative Commons license.

Egg Allergy: Brief Review

Eight top allergens account for 90 percent of all food allergies. The 8 top allergens can be remembered by the mnemonic TEMPS WFS:

Tree nuts (almonds, cashews, walnuts)
Egg white (not egg yolk)
Milk
Peanuts
Shellfish (crab, lobster, shrimp)
Wheat
Fish (bass, cod, flounder)
Soy

Eight top allergens account for 90 percent of all food allergies. See more Allergy and Immunology mind maps here.

Egg allergy is one of the most common food allergies in young children.

The diagnostic algorithm for food allergy is remembered by the mnemonic SAD F:

1. Symptoms: close relation between specific food intake and symptoms, often affect 2 or more organs.
2. Allergy testing: skin testing, ImmunoCAP.
3. Diagnostic diet: restricted diet leads to symptoms disappearance or significant reduction
4. Food challenge: original symptoms reappear during challenge.

What is the prognosis of egg allergy?

Majority of children outgrow the allergy by school age.

90% of infants allergic to milk and 50 % those allergic to eggs outgrow their clinical reactivity by the age of 3 but most patients allergic to peanuts do not. Therefore, diagnosis should therefore be re-evaluated yearly. There is some evidence that milk and egg allergies are becoming harder to outgrow.

There is a correlation between IgE titres and the severity of clinical reaction to egg after the diagnosis has been established. A cut-off level of 8.20 kU/l had a 90% probability of clinical reactivity. IgE titres may help determine which patients are at risk of a reaction to eggs.

Who will "outgrow" food allergy? It depends on the epitope

Each food is composed of many proteins and these proteins have multiple areas, termed epitopes, to which the immune system can respond. Epitopes that are dependent upon the folding of the proteins are called conformational epitopes. Epitopes that are not dependent upon folding are called linear epitopes.

A linear epitope oftens means a more prolonged allergy which is “stable” and persistent. A conformational epitope (egg, milk) often means a mild, transient allergy.

What is the treatment of egg allergy?

Management of egg allergy involves exclusion of egg from the diet.

There is no current active treatment for food allergy. Traditional injection immunotherapy (SCIT) has been proved unsafe, and therefore there is a need for other forms of immunotherapy. Occasional studies of egg oral immunotherapy (OIT) are currently at the stage of proof of concept.

Potentially life-threatening reactions may arise from immunization with vaccines prepared in eggs.

EpiPen Jr. is life saving in cases of anaphylaxis.

When is diet elimination no longer required in egg allergy?

This decision may be helped by:

- demonstrating loss of sensitivity by skin prick or specific IgE testing
- supervised food challenge

Is it true that egg allergy is no longer considered a contraindication to MMR vaccine?

Several studies have documented the safety of measles and mumps vaccine (which are grown in chick embryo tissue culture) in children with severe egg allergy. Neither the AAP's "Red Book" Committee nor ACIP consider egg allergy as a contraindication to MMR vaccine. ACIP recommends routine vaccination of egg-allergic children without the use of special protocols or desensitization procedures. The MMR vaccine is grown on fibroblasts and is generally free of egg protein. MMR can be administered safely to all egg-allergic children.

Source: National Center for Immunization and Respiratory Diseases (Grant No. 5U38IP000290) at the Centers for Disease Control and Prevention (CDC), http://www.immunize.org/askexperts/experts_mmr.asp

Influenza vaccine

In 2008, the Advisory Committee on Immunization Practices recommended that all children get flu shots except infants younger than 6 months and those with serious egg allergies.

Egg-allergic patients without anaphylaxis to egg may safely receive the influenza vaccine in a 2-dose, graded fashion without a vaccine skin test. Safety of Influenza Vaccine Administration in Egg-Allergic Patients. Pediatrics, Vol. 125 No. 5 May 2010, pp. e1024-e1030.

References:

Egg allergy. Kemp AS. Pediatr Allergy Immunol 2007: 18: 696–702.
Food Allergy: A Short Review. Allergy Cases.
Clinical review: ABC of allergies, Food allergy. BMJ 1998;316:1299, figure.
RCP: New recommendations for MMR vaccine in egg-allergic children. BSACI Paediatric Allergy Group, Politics.co.uk.
Egg oral immunotherapy in nonanaphylactic children with egg allergy. JACI, Volume 119, Issue 1, Pages 199-205 (January 2007).
Milk and Egg Allergies Harder To Outgrow, Hopkins Study Shows. Johns Hopkins Children's Center, 01/2008.
Correlation between specific immunoglobulin E levels and the severity of reactions in egg allergic patients. Avigael H. Benhamou, Samuel A. Zamora, Philippe A. Eigenmann. Pediatric Allergy and Immunology 19 (2), 173–179, 2008.

Tolerance to egg-containing baked foods (cake, bread) does not exclude the possibility of egg allergy (AAAAI Ask The Expert).
Image source: Wikipedia, public domain.

Diagnosis and treatment of asthma in childhood: a consensus report by AAAAI and EAACI

Review article:
Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report
L. B. Bacharier et al. AAAAI and EAACI.
Allergy 63 (1), 5–34. doi:10.1111/j.1398-9995.2007.01586.x

This is a guideline for clinical practice in Europe as well as in North America. The consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The included figures in the sidebar are also very useful.

Allergy Topics in the News

Do antihistamines make allergies worse?
11 January 2008 | Nature | doi:10.1038/news.2008.436

'Going green' means gasping for air: Cost of inhalers doubles
The Detroit News

A room -- with nothing to sneeze about
The Chicago Tribune

Breastfeeding May Lower Allergy Risk
WebMD Medical News

You can use text-to-speech to listen to articles you do not have time to read.

References:
Text-to-Speech Programs and Continuous Medical Education. Clinical Cases and Images - Blog.
Image source: OpenClipArt, public domain.

Video Lectures in Immunology

Immunology
University of South Carolina

Video Lectures in Immunology
LearnersTV.com. These are the same videos from the University of South Carolina but hosted on a different website.

Immunology
University of Cambridge

Immunology I & II
MIT OpenCourseWare

Immunology: Lecture Series
Howard Hughes Medical Institute

Allergy and Immunology Lectures at the University of South Florida. USF (University of South Florida, USA) Allergy & Immunology Lecture Series. The 55-minute lectures are recorded in wma format and are best viewed by using Windows Media Player software.

Related:

Sites of Medical/Scientific Videos: The List. ScienceRoll, 08/2007.

Clinical Cases in Allergy and Immunology

Allergy Cases
A Case-Based Curriculum of Allergy and Immunology

Practical Approaches to Asthma Using Case Studies
American Academy of Allergy Asthma & Immunology

Allergic Disorders
American Academy of Allergy Asthma & Immunology

Compass: New Directions in the Treatment of Allergic Conjunctivitis and Related Disorders
American Academy of Allergy Asthma & Immunology

Budesonide vs. montelukast in children with mild persistent asthma: budesonide worked better

Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation over montelukast (Singulair).

The percentage of patients requiring oral corticosteroids over 1 year was lower with budesonide vs. montelukast (25.5% vs. 32.0%.) Peak flow and Caregiver and Physician Global Assessments also favored budesonide.

Other studies in older children have also shown better outcomes with inhaled corticosteroids versus montelukast.

A mnemonic:

S
Singulair
Single daily dose
Suicude risk (potential)

Leukotriene Receptor Antagonists (LTRA)

Antagonists of the CysLT1 receptor (LTRA) are efficacious as controller therapy in asthma and montelukast is FDA-approved for treatment of seasonal allergic rhinitis.

Mast cells quickly generate different mediators from the metabolism of arachidonic acid: leukotrienes and prostglandins (LTC4, LTB4, PGD2). These substances are produced within minutes of IgE-receptor crosslinking on the surface of mast cells.

Eicosanoids are signaling molecules made by oxygenation of 20-carbon essential fatty acids. There are 4 families of eicosanoids (PP-LT): prostaglandins (PG), prostacyclins (PGI), leukotrienes (LT) and thromboxanes (TX).

Mast cell mediators including PP-LT): prostaglandins (PG), prostacyclins (PGI), leukotrienes (LT) and thromboxanes (TX). See more Allergy and Immunology mind maps here.

References:
Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. J Allergy Clin Immunol. 2007 Nov;120(5):1043-50. Szefler SJ, Baker JW, Uryniak T, Goldman M, Silkoff PE.

Urinary leukotriene E(4)/exhaled nitric oxide ratio predicts montelukast response in childhood asthma http://goo.gl/i5cG
Suicide and a common allergy medication. NewsChannel 13, WNYT.com.
Mast Cells and Basophils. Allergy Cases.
Pathogenesis of Asthma. Allergy Cases.

Image source: Montelukast, from Wikipedia, the free encyclopedia, public domain.

Updated: 02/27/2008

Will Platelet-Activating Factor (PAF) be the "BNP" of Anaphylaxis?

Brain Natriuretic Peptide (BNP) was a new test when I started my internship and the NEJM had just published a study showing that it might help physicians diagnose CHF exacerbation. I remember my seniors arguing during journal club that the new BNP test had a limited value and CHF exacerbation would always be a clinical diagnosis. I begged to disagree by pointing out that clinical examination would have its place but nobody should ignore such a simple (and cheap) diagnostic helper as BNP which would be a first-line diagnostic test in near future.

Several short years later, and now most patients with SOB (shortness of breath) get a bedside BNP in the ER soon after the chief complaint is written by the triage nurse. BNP has become as important in rapid diagnosis of CHF exacerbation as troponin is in diagnosis of chest pain and acute coronary syndrome.

The push for biochemical markers will always be there because physical diagnosis is time-consuming and there is variability between different providers. For example, Dr. B's "rales" may sound like "crackles" to Dr. C. I cannot emphasize enough the importance of physical examination but on the other hand, no sensible physician will ignore a rapid and useful lab test.

Platelet-Activating Factor (PAF). Image source: Wikipedia, GNU Free Documentation License.

Platelet-Activating Factor (PAF) may become the "BNP" of anaphylaxis in the future -- a laboratory test which greatly helps in diagnosis. The analogy between PAF and BNP also comes from the fact that both tests help stratify the severity of the disease. The higher then BNP, the more severe the CHF exacerbation is. The same rule applies to PAF.

According to a study published in the NEJM, serum PAF levels were directly correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P less than 0.001).

PAF acetylhydrolase is the enzyme that inactivates PAF. Not surprisingly, PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis.

The NEJM study is the first one to report on the roles of PAF and PAF acetylhydrolase in anaphylaxis in humans. It included only 41 patients with anaphylaxis and 23 controls, and its findings need independent confirmation but it looks like PAF and PAF acetylhydrolase will play an important role in diagnosis of anaphylaxis in the future. New medications which block PAF may prevent fatal anaphylaxis.

References:
Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis. Peter Vadas et al. NEJM, 01/2008.
Rapid Measurement of B-Type Natriuretic Peptide in the Emergency Diagnosis of Heart Failure. Alan S. Maisel et al. NEJM, 2002.
Anaphylaxis Study Offers Clues to Better Diagnosis and Treatment. MedPage Today. Listen to an interview with Peter Vadas, M.D., Ph.D., one of the authors of the NEJM study.