Exercise-induced respiratory symptoms turn into an "epidemic" among adolescents

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The diagnosis and treatment of exercise-induced asthma are well characterized.

However, other syndromes are relatively common but not well-established in the literature with high-quality evidence:

- exercise-induced vocal cord dysfunction
- exercise-induced paradoxical arytenoid motion
- exercise-induced hyperventilation

Laryngoscopic view of normal vocal folds. Image source: Wikipedia, Gray's Anatomy, public domain.

Controlled studies are necessary to define diagnostic and treatment algorithms for young patients experiencing respiratory symptoms during exercise who do not respond to asthma treatment.

References:
Exercise-induced respiratory symptoms: an epidemic among adolescents. Tilles SA. Ann Allergy Asthma Immunol. 2010 May;104(5):361-7; quiz 368-70, 412.

49-year-old man with childhood asthma who was told he would never be able to do exercise runs a marathon every day for a year. CNN, 2011.

Outdoor exercise is good for you, but if you have nasal allergies, take these 6 precautions. WebMD, 2011.
Exercise-induced bronchoconstriction - Am Fam Physician 2011 review.

Allergies and hyperreactive immune system might eliminate abnormal cells more effciently, thus lowering cancer risk

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Epidemiologic evidence regarding the association between allergic diseases and cancer has been inconsistent.

This Canadian study examined whether a history of asthma or eczema is associated with various cancers among men in a population based case-control study conducted in the 1980s. Questionnaire-based interviews were performed in 3,300 cancer cases and 512 population controls

A history of asthma was negatively associated with all cancer types combined (odds ratio (OR), 0.72) and similarly for a history of eczema (OR, 0.66).

Although ORs between asthma and eczema and most individual cancer types were below 1.0, only 2 ORs were significantly below 1.0: that between asthma and stomach cancer (OR, 0.27) and that between eczema and lung cancer (OR, 0.34).

Allergic conditions that result from a hyperreactive immune system might lead to a more efficient elimination of abnormal cells, thus lowering cancer risks.

References:
History of asthma or eczema and cancer risk among men: a population-based case-control study in Montreal, Quebec, Canada. El-Zein M, Parent ME, Kâ K, Siemiatycki J, St-Pierre Y, Rousseau MC. Ann Allergy Asthma Immunol. 2010 May;104(5):378-84.
Image source: Cancers are caused by a series of mutations. Wikipedia, public domain.

Comments from Twitter:

@lrlee: Guess I'll never get cancer then - Allergies may lower cancer risk http://goo.gl/JIv7

Vitamin D may play a role in anaphylaxis, especially food-induced anaphylaxis

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In a previous study by the same authors, latitude was positively associated with EpiPen prescription rates. This study sought to determine whether a similar geographic difference exists for emergency department (ED) visits for acute allergic reactions (including anaphylaxis).

The researchers combined National Hospital Ambulatory Medical Care Survey data for ED visits to noninstitutional hospitals from 1993 to 2005. Acute allergic reactions were identified by International Classification of Diseases - ICD codes.

Between 1993 and 2005, acute allergic reactions represented 1.3% of all ED visits. Per 1000 population, the Northeast had 5.5 visits and the South had 4.9 visits. The Northeast had a higher odds ratio (OR) than the South (1.13; P = .04). The association was stronger when restricting the analysis to visits for food-related allergic reactions (OR, 1.33; P lower than .001).

The ED visit rates for acute allergic reactions are higher in northeastern vs southern regions. These observational data are consistent with the hypothesis that vitamin D may play an etiologic role in anaphylaxis, especially food-induced anaphylaxis.

References:
North-south differences in US emergency department visits for acute allergic reactions. Rudders SA, Espinola JA, Camargo CA Jr. Ann Allergy Asthma Immunol. 2010 May;104(5):413-6.

Bacterial components plus vitamin D: The ultimate solution to the asthma (autoimmune disease) epidemic? JACI, 2011 (PDF).

Alvesco (ciclesonide) - review of marketing brochure

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Alvesco (ciclesonide) brochure uses green branding but the Alvesco MDI devices are brown (80 mcg) and red (160 mcg), respectively. There is risk for brand and patient confusion here.



Alvesco 80 mcg inhaler in brown and Alvesco 160 mcg inhaler in red. The marketing brochure itself however "promotes" the green brand color. For comparison, Symbicort inhalers are red and Advair Diskus devices are purple.

More information is available at: http://www.alvesco.us//hcp/healthcare-professionals.html



Ciclesonide particles are exactly the same size as the beclomethasone particles (1.1 micrometers) but the clever use of perspective in the brochure makes them look smaller. The clinical significance of the particle size is unknown however. For example, the size of fluticasone particles (2.4 micrometer) is twice the size of beclomethasone particles (1.1 micrometers), which in theory should result in better lung deposition. Yet, fluticasone is twice as effective as beclomethasone. Budesonide has the largest particles in this graph at 5 micrometers - 4 times the size of a ciclesonide particles.

Switching the discussion to LABAs, formoterol has an advantage over salmeterol in terms of quicker action. One can make the case that the ideal ICS/LABA combination would be ciclesonide and formoterol (compared to Advair or Symbicort) because of:- smaller particle size (ciclesonide)- local activation (ciclesonide)- faster onset of action (salmeterol)Classically, dry powder inhalers (DPIs) have been the devices with the best lung deposition. However, if you look at the diagram above, the HFA solution achieve even greater deposition - 60% for HFA solutions vs. 28% for DPIs.



The diagram reflects differences in the area under the curve when evaluating the effect of ciclesonide and placebo on the adrenal function. Yet, the lower ciclesonide dose seems to be "better" than placebo while the higher dose is "worse." The absolute difference are small and this type of diagrams can be confusing.

Ciclesonide mnemonic

C

Ciclesonide

Converted to active form (des-CIC)

Carboxyl-esterases in bronchial epithelial cells

Clearance by liver

Chronic Urticaria with Elevated D-Dimer May Benefit from Therapy with Heparin and Tranexamic Acid

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Chronic urticaria (CU) patients often present activation of the coagulation cascade and fibrinolysis whose markers correlate with disease severity.

This study evaluated whether CU patients with elevated plasma D-dimer have a poor response to antihistamines, and anticoagulation and inhibition of fibrinolysis may be beneficial in these patients.

68 patients with CU were prescribed cetirizine 10 mg daily for 2 weeks; plasma D-dimer was measured. Patients with persistent uncontrolled CU and elevated D-dimer plasma levels were offered subcutaneous nadroparin 11,400 IU once a day and oral tranexamic acid 1 g three times a day for 2 weeks.

D-dimer levels were elevated in 20.6% patients and were associated with a more severe disease. All patients with elevated D-dimer levels did not respond to antihistamine treatment with cetirizine 10 mg daily and only 1 of these responded satisfactorily to cetirizine 30 mg daily.

8 patients with elevated D-dimer and whose disease was not satisfactorily controlled by prednisone received nadroparin and tranexamic acid. A marked improvement of symptoms was observed in 5/8 cases.

The authors concluded that CU patients with elevated D-dimer often present a more severe disease with reduced response to antihistamines. Based on this short pilot study, some of these patients may benefit from treatment with nadroparin and tranexamic acid.

Asthma is also associated with a procoagulant state in the bronchoalveolar space (Blood, 01/2012).

References:

Heparin and Tranexamic Acid Therapy May Be Effective in Treatment-Resistant Chronic Urticaria with Elevated D-Dimer: A Pilot Study. Int Arch Allergy Immunol. 2010 Mar 4;152(4):384-389. Authors: Asero R, Tedeschi A, Cugno M.
http://www.ncbi.nlm.nih.gov/pubmed/20203527?dopt=Abstract

Anti-FceR1 Autoantibodies in Chronic Urticaria

Untidy beds may "kill" dust mites

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The average bed could be home to up to 1.5 million house dust mites.

The bugs, which are less than a millimetre long, feed on scales of human skin and produce allergens which are easily inhaled during sleep.

Something as simple as leaving a bed unmade during the day can remove moisture from the sheets and mattress so the mites will dehydrate and eventually die.

Responses from Twitter:

@DoctorMac: Dust mites don't survive unmade beds. Good luck with your allergic kids now. They have science on their side.

@doc_rob: So there! Ya Ya Ya - I was right an Mom was wrong!

@candydye: Moms - Don't tell your kids! RT @Allergy: Untidy beds may "kill" dust mites - goo.gl/qsDW

Dust mite allergen avoidance. The main allergen is in the dust mite feces. Use 3 control measures for 3-6 months to see an effect on the allergy symptoms (click to enlarge the image).

Where are highest concentrations of dust mites found in home? Pillows, stuffed animals, mattress, bedding? http://goo.gl/l6KtR -- A: Mattress.

References:

BBC NEWS | Health | Untidy beds may keep us healthy

Indoor Allergen Avoidance

Rhinitis and sleep - congestion decreases quality of life and productivity, increases daytime sleepiness http://goo.gl/Fym3B

House dust mite sensitization in toddlers predicts wheeze at age 12 years (JACI, 2011).

Millions suffer 'home fever' as allergy epidemic begins to bite - dust mites account for 58% of household allergies. The Independent, 2011.

Will U.S. Change Coin Composition to Cheaper Metals? Nickel Allergy Sufferers Will Not Miss Them

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Nickel, the most expensive and commonly used metal at the mint, is also the most allergy-producing metal in the world. For example, nickel allergy is the most common contact allergy in Europe.

People allergic to nickel who have sustained contact with the metal—used in nickels, quarters and dimes—develop an itchy, poison-ivy-type reaction that can last up to a month.

"My husband always has these weird rashes on his leg from the change in his pocket," a treasury official involved in the coinage plans says. "Maybe he would benefit from a plastic quarter."

References:

Feds Likely to Face Uproar if They Overhaul Pocket Change - WSJ.com.

Update on allergic contact dermatitis

Nickel allergy tracked to a single receptor - Toll-like receptor 4 (TLR4) http://goo.gl/PZic

Patch testing to metal implants. AAAAI - Ask the Expert, 2011.

"Nickel hidden in coins, bras and chocolate... the metal that triggers a life-wrecking allergy" http://goo.gl/dFtcm
Harry Potter star Daniel Radcliffe was allergic to wizard' glasses - the frames contained nickel http://goo.gl/FRRNd

Image source: US Nickel Reverse, Wikipedia, public domain.

Difference between HEPA and ULPA air filters

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There is a higher grade of air filtration than HEPA - it is called ULPA.

High Efficiency Particulate Air (HEPA) = 99.97% of particles 0.3 micrometers or greater are removed by the air filter.

Ultra Low Penetration Air (ULPA) = 99.999% of particles 0.12 micrometers or greater are removed by the air filter.

References:

What are HEPA and ULPA? Dr. Neil Kao Allergy and Asthma Website.
How HEPA Filters Work http://goo.gl/qOLF
Image source: Amazon, used for illustrative purposes only - NOT a suggestion to purchase any products.

HEPA Air Cleaners Not Very Effective For Decreasing Visits and Asthma Symptoms in Children Exposed to Tobacco Smoke http://goo.gl/fhAmh

Top Allergy Myths

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There are many allergy myths such as the one about short-haired pets being "allergy-free." "There is no such thing as a hypoallergenic dog or cat"

Some people actually believe chihuahuas can relieve or even cure asthma, or that eating local honey can help alleviate or prevent seasonal allergies. Neither is true.

Another myth is that subcutaneous immunotherapy ("allergy shots") always takes years to work. "You can change how long it takes for the allergy shots to kick in," Dr. Haden said. "Traditionally, It takes several months of doing shots kind of the traditional or old-fashioned way." But with rush immunotherapy, "you do an all-day jump start to the shot process, and then your shots can start kicking in in a matter of weeks."

References:
Top Allergy Myths. NBC Dallas-Fort Worth.

Image source: OpenClipArt.org, public domain.

Many pathways lead to asthma: the importance of natural killer T cells

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The pathogenesis of asthma is complex. It is associated with:

- a number of environmental factors, eg, allergens, infection, air pollution, exercise, and obesity
- multiple cell types
- several cellular and molecular pathways

These pathways include adaptive and innate immunity and involve T(H)2 cells, mast cells, basophils, eosinophils, neutrophils, airway epithelial cells, and natural killer T (NKT) cells.

Inflammation in asthma (click to enlarge the image).

NKT cells express NK cell and T lymphocytes markers. They recognize lipids in the context of CD-1.

NKT cells function in concert with T(H)2 cells or independently of adaptive immunity in causing airway hyperreactivity.

The clinical relevance of NKT cells in human asthma is supported by the observation that NKT cells are present in the lungs of some patients with asthma, particularly patients with severe, poorly controlled asthma.

NKT cells can explain some mechanisms that drive the development of asthma, particularly in the case of asthma associated with neutrophils, viral infection, and air pollution.

References:
Natural killer T cells are important in the pathogenesis of asthma: The many pathways to asthma. Umetsu DT, Dekruyff RH. J Allergy Clin Immunol. 2010 Mar 23.

20% of food allergy reactions occur in schools and 70% of schools have at least one child at risk of anaphylaxis

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Allergy affects at least 25% of European schoolchildren. It reduces quality of life and impairs school performance. There is a risk of severe reactions with food allergy and, in rare cases, death.

Allergy is a multi-system disorder, and children often have several co-existing diseases, i.e. allergic rhinitis, asthma, eczema and food allergy.


Eight top allergens account for 90 percent of all food allergies.

Severe food allergy reactions may occur for the first time at school, and overall 20% of food allergy reactions occur in schools. Up to two-thirds of schools have at least one child at risk of anaphylaxis but many are poorly prepared.

Schools should ensure that all staff can prevent, recognize and initiate basic treatment of allergic reactions.

References:

The management of the allergic child at school: EAACI/GA2LEN Task Force on the allergic child at school. Muraro A, Clark A, Beyer K, Borrego LM, Borres M, Lødrup Carlsen KC, Carrer P, Mazon A, Rancè F, Valovirta E, Wickman M, Zanchetti M. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02343.x

Management of Food Allergy in the School Setting - Pediatrics, 2010 http://goo.gl/J7qsI

Amid Protest, Florida School Stands Behind Tough New Peanut Allergy Regulations http://goo.gl/joUsS - Little evidence to back this approach: http://goo.gl/59VKU

Helping Families Manage Food Allergy in Schools - Medscape http://goo.gl/kCsTs

Management of food allergy in schools - AAAAI Ask the Expert, 2011.

Overhyped Panics - WSJ, 2011.

Allergy to steroids is rare but should be investigated

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Allergic reactions to systemically administered corticosteroids (PO or IV) are infrequent, especially considering their extensive use. The aim of this Spanish study was to evaluate the IgE response in 4 patients with immediate allergic reactions to methylprednisolone (MP).

4 patients who developed immediate reactions after MP administration and 10 controls with good tolerance to MP administration were evaluated.

Skin prick and intradermal testing were done using MP, hydrocortisone (HC), and dexamethasone (DX). If negative, a drug provocation test (DPT) was done to confirm the diagnosis and assess cross-reactivity. The in vitro IgE response was evaluated by the basophil activation test (BAT) and ImmunoCAP.

3 patients were diagnosed by the presence of a positive skin test in the immediate reading with MP, two by prick and one by intradermal testing, and one patient was skin test negative and diagnosed by DPT.

All 4 patients had good tolerance to HC and DX. The BAT was positive for just MP in those patients with positive skin tests. Two patients were ImmunoCAP positive to MP.

The study confirms the existence of immediate allergic reactions to MP and that some are mediated by specific IgE antibodies.

Skin testing, ImmunoCAP and the BAT are useful to confirm the diagnosis.

References:
Aranda A, Mayorga C, Ariza A, Doña I, Blanca-Lopez N, Canto G, Blanca M, Torres MJ. IgE-mediated hypersensitivity reactions to methylprednisolone. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02386.x
http://www3.interscience.wiley.com/journal/123429129/abstract

Image source: Methylprednisolone (MP), Wikipedia, public domain.

Some patients prefer subcutaneous administration of IgG several times per week instead of weekly

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If the time, number of sites, or volume per site in the planned regimen seems excessive, splitting the dose into two or more infusions per week should be considered.

In many cases, the patient's tolerance of local site reactions increases with repeated infusions, and the time for each infusion can be shortened or the volume of IgG infused per site can be increased.


Hizentra is 20% immunoglobulin for subcutaneous therapy (SCIG) of immunodeficiency.

Each of the parameters in table 1 (shown below) may be considered independently, and varied to reach a regimen that fits easily into each patient's preferences.

Some investigators have explored options at the extremes of the above regimens.

For example, Shapiro in Minnesota and Ochs in Seattle have reported anecdotally that many patients prefer to increase the parameter of the number of infusions per month out to 20 to 30, by giving “daily pushes” of 10 mL each, which is done conveniently by repeatedly pushing 1 to 2 mL from a 10-mL syringe without any mechanical pump at all. Daily doses of 10 mL (1.6 g, if a 16% IgG solution is used) are easily given over 5 to 10 minutes in this way, and are well tolerated by many patients. Infusing 1.6 g every weekday gives a monthly dose of 35.2 g, and the patient does not have to take infusions on the weekends. In contrast, if the patient takes a 1.6-g infusion every day, the total monthly dose will be 48.8 g per month.

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Table 1:

Establishing an optimal subcutaneous immunoglobulin regimen for any individual patient

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1. Predetermination: dose of IgG in mg/kg/mo. Start with estimated dose of 500 mg/kg/mo, use current monthly IV dose, or use current monthly IV dose × correction for bioavailability if desired.

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2. Parameters that should be selected in accordance with patients preferences:

Number of infusions per week or month
Volume per infusion
Number of sites per infusion
Volume per site
Total time for each infusion
Decision to use multiple sites simultaneously or sequentially
Number of pumps

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References:
Subcutaneous administration of IgG. Berger M. Immunol Allergy Clin North Am. 2008 Nov;28(4):779-802, viii.

Bonus offer: 15% off NFL scrubs with coupon code "nfl_savings"

Menstruation increases bronchial hyperreactivity in women with asthma

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Day of menstruation cycle at the time of methacholine challenge was calculated in 571 menstruating women, aged 28 to 58 years. A window of risk was defined 3 days before and after the first day of menstruation.

The prevalence of BHR was 13% (fall of or greater than 20% in FEV(1) up to a maximal cumulative dose of 2 mg), and 6% had asthma.

There was an increase in BHR within the window of risk (odds ratio [OR], 2.3). The OR lower than 1 in women using oral contraceptives (OCs).

There is variation in BHR during the menstruation cycle, supporting the hypothesis of a hormonal influence. Oral contraceptives (OCs) appear to have a protective effect.

References:
Perimenstrual increase in bronchial hyperreactivity in premenopausal women: Results from the population-based SAPALDIA 2 cohort. Dratva J, Schindler C, Curjuric I, Stolz D, Macsali F, Gomez FR, Zemp E; on the behalf of the SAPALDIA Team. J Allergy Clin Immunol. 2010 Mar 12.

Women are more likely to be diagnosed with asthma and suffer greater morbidity than men. Medscape, 2011.

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

Why Asthma Patients Need Frequent Follow-Up

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From AllergistMommy blog:

"There have been a few disgruntled phone calls after a patient learns that only 3 months worth of refills have been submitted to the pharmacy, instead of the standard 6-12 month supply.

Inhaled corticosteroids, when taken regularly as prescribed, generally take around 2 weeks to begin exerting their beneficial effects, but take around 6 weeks to reach maximal efficacy. So, after changing a patient's asthma controller medicine dose or regimen, I will wait at least 6 weeks before deciding if the new dose is working adequately. If it is working well, I will continue the dose for at least 3 months before attempting to decrease the dose. I always attempt to decrease, as long as the patient has done well for the past 3 months."

Asthma classification and treatment for each stage (click to enlarge the image).

References:

The Doctor Will See You... Sooner Than You Thought? Why Asthma Patients Need Frequent Follow-Up. Achoo!- Adventures of an Allergist Mommy, 2010.

Diagnosis of Asthma

Treatment of Asthma
Exercise-induced asthma and bronchospasm
Mind Maps: Asthma
Mnemonics: Asthma

Stedivaze (apadenoson) - A2A receptor agonist in trials as stress agent for patients with asthma and COPD

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Stedivaze (Apadenoson) Demonstrated Safety and Tolerability in Patients with Asthma and COPD in Phase I Trial.

Stedivaze is a potent and highly selective agonist of the adenosine A2A receptor subtype in development as a pharmacologic stress agent for myocardial perfusion imaging (MPI). Currently available adenosine agonists must be used with caution or are contraindicated in patients with asthma and COPD.

Adenosine and dipyridamole are the currently available vasodilators for myocardial perfusion imaging and they produce hyperemic coronary flow by stimulating A(2A) adenosine receptors on arteriolar vascular smooth muscle cells. However, both vasodilators are nonselective activators of the adenosine receptors A(1), A(2B), and A(3), which contributes to common undesirable effects.

Regadenoson is a new highly selective, low-affinity A(2A) adenosine agonist that is a coronary vasodilator. It was approved by the United States Food and Drug Administration on April 10, 2008 and is marketed under the tradename Lexiscan.

References:

Clinical Data, Inc. Reports Results of Phase I Studies of Stedivaze(TM) Demonstrating Safety and Tolerability in Patients with Asthma and COPD. MarketWatch.

The future of pharmacologic stress testing: selective A2A adenosine receptor agonist regadenoson (Lexiscan)?

Image source: Heart, Gray's Anatomy, 1918, public domain.