Immunotherapy - top articles for August 2012

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Here are my suggestions for some of the top articles about immunotherapy for August 2012:

Immunotherapy prescribed for 5 years by 75% of US-Canadian allergists, for 3 years by the rest of the world http://goo.gl/K0Cr7

Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections - first human study ILIT with MAT–Fel d 1 http://goo.gl/jHAe9

Eosinophilic esophagitis induced by milk oral immunotherapy - 3 case reports http://goo.gl/NHljN

Allergen immunotherapy is a cost-effective treatment in modifying existing allergic respiratory diseases - Chest 2012 http://goo.gl/GdkbH

Therapies for allergic inflammation: refining strategies to induce tolerance - Nature Medicine 2012 review, full text http://goo.gl/te9XM

Fear needles? Looking away while you're getting an injection makes it hurt less (study) http://goo.gl/k7NSi

Allergen immunotherapy causes production of high-affinity allergen-specific blocking IgG(4) http://goo.gl/FvR0Z

Safety of Allergen Immunotherapy - 2012 Medscape review http://goo.gl/0ZsVx

Epinephrine in the treatment of anaphylaxis. Adult intramuscular dose is 0.3 to 0.5 ml of 1:1,000 concentration http://goo.gl/Qad6S

To expect clinical efficacy from SLIT for allergic rhinitis, sufficiently high doses have to be regularly administered for at least 3 consecutive years http://goo.gl/kl8Xx

Allergy shots: Do patients feel pain or fear? http://goo.gl/MlczE - Full text PDF: http://goo.gl/SVtLp

"Beat Allergies Drop by Drop" - WSJ - However, most insurers don't cover SLIT cost, typically $30-150/month http://goo.gl/71W2s

The articles were selected from my Twitter stream @Allergy and Google Reader RSS subscriptions. Some of the top allergy accounts on Twitter contributed links. I appreciate the curation provided by @JuanCIvancevich @AllergyNet @IgECPD4 @DrAnneEllis @AACMaven @AllergieVoeding @allergistmommy @mrathkopf @wheezemd.

Please feel free to send suggestions for articles to allergycases@gmail.com and you will receive acknowledgement in the next edition of this publication.

Image source: OpenClipArt.org, public domain.

Effect of childhood asthma and inhaled steroid on adult height: 1.2 cm lower height with budesonide vs. placebo

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The use of inhaled glucocorticoids (ICS) for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.

This study published in the NEJM measured adult height in 943 participants in the Childhood Asthma Management Program (CAMP) at age 25. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil (not available in the U.S. since 2010), or placebo daily for 4 to 6 years.

Mean adult height was 1.2 cm lower in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower in the nedocromil group than in the placebo group. A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (−0.1 cm for each microgram per kilogram of body weight) (P=0.007). The difference between ICS and placebo was noted only during the first two years of therapy and it was not progressive.

The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative.

Editor's note: This study shows that more severe asthma that requires treatment with ICS is associated with lower height as an adult. Many chronic diseases during childhood affect adult height and asthma is no exception. A longer time since asthma diagnosis and atopy (any positive skin test) were independent risk factors for shorter adult height. When asthma and atopy impair growth, the deficit may persist into adulthood. The conclusion is not to "stop" the use of ICS but to use the lowest effective ICS dose for symptom control, which is in agreement with the current asthma guidelines.

By the way, the findings of the 2012 study in the NEJM contradict a 2000 study published in the same journal that did not show an effect of ICS on growth (Effect of Long-Term Treatment with Inhaled Budesonide on Adult Height in Children with Asthma - NEJM http://goo.gl/qM3Nf).



Asthma Inhalers (click to enlarge the image).

Comments by other physicians:

This article is an attempts to address sensational headlines (http://bit.ly/RLkhSv) such as: "Everybody Panic: Asthma Inhalers May Stunt Growth Permanently", "Asthma Drug Stunts Kids' Height for Life", "Asthma drug may stunt growth permanently", "Study: Asthma medications make you short", etc.

The benefits of ICS in asthma far outweigh a slight decrease in height. However, when compared with placebo and nedocromil, the effect of budesonide is demonstrated as a cause of reduced stature, since all patients were also asthmatic and atopic.

In the paper all the patientes were mild-to-moderate asthma, although the authors didn't take into account the difference of severity of asthma between groups, patients were randomly assigned to the three treatment groups and the differences between the groups were significant.

Andrew S Nickels, MD:

Looking at the original Childhood Asthma Management Program (CAMP) cohort, the baseline characteristics that are reported seem matched, which would suggest adequate randomization. (1) One lacking aspect of initial enrollment demographics in the original trial cohort is the initial tanner staging being reported. This is pointed out by Mary Ellen Wohl and Joseph A Majzoub in their editorial response to the initial trial.(2) This seems a crucial baseline statistic when assessing growth velocity and final height.

However, while the cohorts may have been similar at baseline, there were significant differences between the inhaled Budesonide and Placebo groups in regards to several outcomes. These include the following: course of oral Prednisone (70/100 person-years vs 122/100 person-years, P below 0.0001), Urgent care visits due to asthma (12/100 person-years vs 22/100 person-years, P below 0.0001), and Hospitalizations due to asthma (2.5/100 person-years vs 4.4100 person-years, p = 0.04). (1) Intuitively, one would expect the higher burden of asthma morbidity felt by the placebo group would negatively effect height,
but that conclusion is outside of the scope of these investigations. As pointed out by Wohl and Majzoub, growth is a complex and poorly understood process. (2) This study outlines a loose association at best between two groups whose developmental years are dissimilar. A larger cohort would be needed with tighter subgroup analysis to tease out this finding. This will be limited by the unethical nature of enrolling known asthmatic children in placebo control trials. (3)

1. The Childhood Asthma Management Program Research Group. Long Term Effects of Budesonide or Nedocromil in Children with Asthma. N Engl J Med 2000; 343:1054-1063.

2. Wohl M, Majzoub J. Asthma, Steroids, and Growth. N Engl J Med 2000; 343:1113-1114.

3. Coffey MJ, Wilfond B, Ross LF. Ethical assessment of clinical asthma trials including children subjects. Pediatrics. 2004; 113: 87-94

References:

Effect of Inhaled Glucocorticoids in Childhood on Adult Height. H. William Kelly, Pharm.D., Alice L. Sternberg, Sc.M., Rachel Lescher, M.D., Anne L. Fuhlbrigge, M.D., Paul Williams, M.D., Robert S. Zeiger, M.D., Ph.D., Hengameh H. Raissy, Pharm.D., Mark L. Van Natta, M.H.S., James Tonascia, Ph.D., and Robert C. Strunk, M.D. for the CAMP Research Group, September 3, 2012 (10.1056/NEJMoa1203229) (free full text).

Inhaling steroids stunts growth, but not much. "This is mostly good news. Now we know what it is. It is a half an inch" | Reuters  http://goo.gl/zkTpc

Image source: Image source: FDA and Wikipedia, public domain.

10 principles for clean air - what to do to achieve the goal?

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A recent analysis from the USA attributed 18,000,000 lost work days annually to PM2.5 exposure, and 11,000,000 school absence days to ozone exposure. Mortality increases by 6–8% for every 10 μg·m−3 increase in long-term PM2.5 concentrations in the community.

Here are the proposed 10 principles for clean air from the official journal of the European Respiratory Society:

1) Citizens are entitled to clean air, just like clean water and safe food.

2) Outdoor air pollution is one of the biggest environmental health threats today, leading to significant reductions of life expectancy and productivity.

3) Fine particles and ozone are the most serious pollutants. There is an urgent need to reduce their concentrations significantly.

4) Roadside pollution poses serious health threats that cannot be adequately addressed by regulating fine particle mass or ozone. Other metrics such as ultrafine particles and black carbon need to be considered in future research and so inform further regulation.

5) Non-tailpipe emissions (from brakes, tyres and road surfaces, etc.) pose a health threat for road users and subjects living close to busy roads.

6) Real-world emissions of nitrogen dioxide from modern diesel engines are much higher than anticipated. This may expose many road users, and subjects living on busy roads, to short-term peak concentrations during rush hours and periods of stagnating weather that may impact on health.

7) Global warming will lead to more heatwaves, during which air pollution concentrations are also elevated and during which hot temperatures and air pollutants act in synergy to produce more serious health effects than expected from heat or pollution alone.

8) Combustion of biomass fuel produces toxic pollutants. This is true for controlled fires, such as in fireplaces, woodstoves and agricultural burning, as well as for uncontrolled wildfires.

9) Compliance with current limit values for major air pollutants confers no protection for public health. In fact, very serious health effects occur at concentrations well below current limit values, especially those for fine particles.

10) Policies to reduce air pollution are needed that ultimately lead to air that is clean and no longer associated with significant adverse effects on the health. The benefits of such policies outweigh the costs by a large amount.

References:

Ten principles for clean air. B. Brunekreef et al. ERJ March 1, 2012 vol. 39 no. 3 525-528.


Image source: OpenClipArt, public domain.

Causes of Astigmatism

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Astigmatism is an eye problem or condition in which a person has blurred vision because of an eye problem. In this situation, the front exterior of the eye does not have the accurate curve in the cornea of the eye. The curve is irregular with one-half of the cornea being flatter or steeper than the other half. The distorted image results because the rays of light entering the eye do not focus correctly on the retina.
Astigmatism occurs in both children and adults. In addition, it happens frequently, but it is not contagious. It usually is present at birth but can result following eye surgery or after an eye injury. These eye problems are part of classifications of eye conditions known as refractive errors: hypermetropia or far-sightedness, myopia or shortsightedness and presbyopia or aging of the eye's lens.
Astigmatism takes two common forms. Corneal astigmatism occurs when the cornea is unevenly shaped and lenticular astigmatism when the lens is irregularly shaped.
In corneal astigmatism, the cornea is irregularly shaped. The cornea, which is a clear coating of tissue that covers the front of the eye, transmits and focuses light in the eye as well as protecting the eye from becoming infected and from damage. The cornea has to be perfectly curved to refract or bend light correctly as it enters the eye.
When the cornea does not have a perfect curve, the light is not refracted correctly and results in the retina receiving a distorted image. Consequently, the result will be imprecise vision or astigmatism in that eye.
People who have astigmatism often have a cornea, which is oval instead of a perfect circle. When the cornea’s arc is oblong, the light rays concentrate on two points within the retina.
Specialists are uncertain as to why some people have a cornea that is not curved correctly at birth. Some reports reveal that babies have a greater chance of astigmatism if the parents also have the condition. A higher proportion of babies who are born prematurely or with a lower body weight have astigmatism as compared with other babies.
Lenticular astigmatism is similar to corneal astigmatism but occurs in the lens instead of the cornea. The lens’ curvature varies instead of being perfect. The images at the back of the eye at the retina are distorted. Many of the patients who have lenticular astigmatism have a cornea with a normal shape. The imperfection is in the curve of the lens.
People who are diabetic develop lenticular astigmatism when higher levels of blood sugar produce a change in the shape of the lens. The change occurs slowly. It is identified at the time the patient begins the diabetic treatment. As the treatment controls the diabetes near normal levels, the shape of the lens returns to the regular level but may result in hypermetropia or far sightedness. It is often advised that those receiving diabetic treatments should wait for the lens to return to normal before receiving testing for new glasses.
Astigmatism also arises when the shape of the cornea is more oblong than it is round. The oval shape results in the rays of light focusing on two points in the back of the eye.
Sometimes astigmatism is caused by pressure of the eyelids on the cornea. It also can result from incorrect posture or use the eyes for detailed work. Some people inherit the problem.
Infrequently, astigmatism is caused by chalazia when the eye's lids swell or because of scars on the cornea. The scars may be caused by eye injury and the direction of light of the eye changes. It also may be owing to keratoconus, which is an uncommon condition in which a cornea changes from its normal round shape. Sometimes after eye surgery, a patient will develop astigmatism when the sutures are placed firmly produce the cornea to wrinkle, resulting in astigmatism until the injury is healed.

Eye Floaters Treatment

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If you have eye floaters, you know how irritating they can be. Fortunately, eye floaters are usually a harmless sign of aging. They can, however, be a sign of more serious eye problems, so it is always good to have your eyes examined to know for certain. The good news is that there are several options when it comes to eye floaters treatment, so you can consult with your ophthalmologist to decide which one is best for you.

Eye floaters are tiny specks or thin stands that you sometimes see roaming around your vision. They are caused by very tiny fragments in the vitreous of the eye becoming detached from within the eye's interior. Floaters are usually more noticeable if you are staring at a mono-colored clear surface such as the sky or a piece of blank paper. They can occur at any time.

Eye floaters are a normal occurrence as you age; however, there are times when they signal a serious eye problem. The biggest eye problems associated with floaters are torn or detached retinas. If you suddenly see a lot of floaters accompanied by flashes of light that resemble lightning strikes, one of your retinas may be torn or detached from the rest of the eye. Seek medical help immediately if this happens, as a torn or detached retina could cause permanent loss of eyesight.

One method of eye floaters treatment is through laser therapy. In this procedure, an ophthalmologist directs a special laser on the floaters. The laser breaks the floaters into smaller ones which can make them less noticeable and irritating. Results are mixed for this procedure, with some people reporting improvement and others noticing little, if any, difference. Laser treatment for floaters is still considered to be experimental and is not currently widely used.

Another treatment for eye floaters is by surgery. Because most floaters fade over time, doctors usually only advise surgical treatment if there is a significant visual impairment. Vitreoretinal eye surgery is the medical term for this procedure. After general or local anesthesia is administered, the eye surgeon makes several miniscule slits in the eye to insert surgical instruments. The vitreous in the eye is removed and replaced with liquid saline, and over time the body makes more fluid on its own to maintain the shape of the eye.

There are also all-natural, holistic treatments available for eye floaters. These include herbs, such as billberry, that improve blood vessel circulation and assist with the delivery of oxygen and nutrients. Vitamin C improves capillary strength, which helps transport the necessary amount of blood to the retina. Aspalathus linearis and sutherlandia frutescens have anti-oxidant and restorative effects and are considered good natural treatments.

Eye floaters are usually more of an annoyance than a danger. In time they fade and the eye adapts to them, making them less aggravating. Surgical treatment is very effective but should only be done in cases of severe visual impairment. If you are concerned about your floaters, consult an ophthalmologist.

Epinephrine autoinjectors are expensive, allergists suggest low-cost alternative: a prefilled syringe

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The wholesale price of 1 epinephrine autoinjector increased annually from $35.59 in 1986 to $87.92 in 2011 (147%). Among patients prescribed autoinjectors, only 40% of teens/adults and 60% of children less than 12 years of age had them refilled over a 6-year period. The retail price of the new "EpiPen 2-pak" that the patients often quote is more than $250 for each "pak". In August 2012, the FDA approved Auvi-Q - the first-and-only epinephrine autoinjector with audio and visual cues that guide patients and caregivers step-by-step through the injection process. No information about the price of Auvi-Q is available at this time but it is not expected to cost significantly less than EpiPen.

There are lower-cost alternatives to epinephrine autoinjectors. Recently, three allergists from the University of South Florida suggested in JACI thar prefilled epinephrine syringes made in a clinic can be safely provided to patients who cannot afford prescription autoinjectors.

Prefilled syringes are stable and sterile for 2 months in dry climates and 3 months in humid climates.

Materials needed to prepare a prefilled syringe are simple:

1. ampule containing 1 mg/mL epinephrine plus a preservative
2. disposable plastic 1-mL syringe
3. 23-gauge, 2.5-cm needle

Parents take 140 seconds to withdraw epinephrine from an ampule into a syringe, therefore a prefilled syringe is recommended.

Epinephrine is light sensitive, and the ampule and prefilled syringes should be protected from light by:

- wrapping them in aluminum foil
- keeping them in a light-free container, such as an eyeglasses case

This 2-minute video shows the Sanofi's new voice guided Auvi-Q epinephrine injector in action:



References:

Increasing cost of epinephrine autoinjectors. The Journal of Allergy and Clinical Immunology
Volume 130, Issue 3 , Pages 822-823, September 2012.

Image source: OpenClipArt.org, public domain.

Comments from Twitter:

Allergic Living @AllergicLiving: Would anyone prescribe epi syringe? + short shelf life. Should allergists press for a 1-pak too, as 1 better than 0? #foodallergy

‏@Allergy: As you know, EpiPen Single Packages were Discontinued 1 year ago. Only "2-paks" are available now: http://bit.ly/P7J0Ch

Allergic Living @AllergicLiving: That's my point, should they be "encouraged' to return as an additional option, perhaps by AAAAI?

Craig, CEN, CCRN @CraigCCRNCEN: My ANA kit with Benadryl also is cheaper and less painful to administer.

Tiffany @iknowtiffany: Yah, right. That's *perfect* for schools, parents in midst of crisis, carrying around at all times. #not

Neutrophilic inflammation as a possible explanation for a reduced treatment response in obese patients with asthma

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Increased number of neutrophils are present in the airways during the late-phase reaction after allergen challenge, in fatal or nocturnal asthma, and in severe asthma.

The incidence of asthma and obesity is increasing worldwide, and reports suggest that obese patients may have more severe asthma or reduced response to therapy. This study from the Netherlands included data from four asthma cohorts.

At baseline, FEV(1)  and bronchial hyperresponsiveness were comparable in 63 obese (BMI equal or more than 30 kg/m(2) ) and 213 lean patients (BMI  lower than 25 kg/m(2) ).

After a two-week treatment with corticosteroids, there was less corticosteroid-induced improvement in FEV(1) in obese patients (median 1.7% vs 6.3% respectively, P = 0.04). The percentage of sputum eosinophils improved significantly less with higher BMI.

The smaller improvement in FEV(1) and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics.

Editor’s note: Previous studies of anti-IL-5 agents showed benefit only in some asthmatic patients with predominantly eosinophilic inflammation. As a future research avenue, it would be interesting to see if localized anti-neutrophilic therapies can bring improvement in obese patients with asthma.

Question & Answer

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

(A) infection
(B) GERD
(C) presence of a foreign body
(D) exercise-induced asthma
(E) extrinsic asthma

Correct answers: A, B, C

References:

Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response. Telenga ED, Tideman SW, Kerstjens HA, Hacken NH, Timens W, Postma DS, van den Berge M. Allergy. 2012 Aug;67(8):1060-8. doi: 10.1111/j.1398-9995.2012.02855.x. Epub 2012 Jun 12.

Image source: Wikipedia, free GNU license.