Allergy Notes: 09/2011

Th17 cells as new players in asthma pathogenesis

CD4+ T effector lymphocytes are classified in different subsets on the basis of cytokine secretion:

- Th1 cells, thank to IFN-γ production, are responsible for cell-mediated immunity against intracellular pathogens

- Th2 cells, through the production of IL-4, provide protection against helminthes

- Th17 cells, via IL-17, promote neutrophils recruitment for the clearance of bacteria and fungi

T helper cells (click to enlarge the image).

However, beyond their protective role, T-helpers can also be involved in inflammatory diseases such as asthma.

Allergic asthma is the result of an inflammatory process driven by allergen-specific Th2 lymphocytes.

On the other hand, Th17 cells are mainly involved in those forms of asthma, where neutrophils more than eosinophils, contribute to the inflammation.

The identification of Th17/Th2 cells, able to produce both IL-4 and IL-17, fits the observation that different clinical phenotypes can coexist in the same patient.

References:

Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F. Th17 cells: new players in asthma pathogenesis. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02576.x.

Interleukin-17 (IL-17)

T Helper Cells

88% of moderate to severe asthmatics are not able to fully control their symptoms

Patients aged 18 to 64 years with moderate to severe asthma were asked to participate in a cross-sectional survey. Patients with chronic obstructive pulmonary disease (COPD) were excluded. The Asthma Therapy Assessment Questionnaire (ATAQ) was used as the measure of control. The ATAQ scores range from 0 to 4, with 0 indicating no asthma control problems.

1,200 patients (73% women) completed the survey. Only 12% of respondents scored 0 on the ATAQ, 77% scored 1 or 2, and 11% scored 3 or 4.

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

Severe asthma includes 3 groups:

(1) untreated severe asthma
(2) difficult-to-treat severe asthma
(3) treatment-resistant severe asthma

Decreasing levels of asthma control were associated with:

- sleep problems

- depression

- functional impairment

- effect on work and regular activities

Approximately 88% of patients with moderate to severe asthma were not fully controlled despite anti-inflammatory drug treatment. Lack of asthma control is associated with substantial patient burden.

References:

Impact of asthma control on sleep, attendance at work, normal activities, and disease burden. Wertz DA, Pollack M, Rodgers K, Bohn RL, Sacco P, Sullivan SD. Ann Allergy Asthma Immunol. 2010 Aug;105(2):118-23.

3 groups of severe asthma

How does interferon-gamma release assay (IGRA) (QuantiFERON) work?

How does interferon-γ release assay (IGRA) work? Does it show false positive resutls in patietns with baseline elevation of interferon-gamma, for example, in patients with chronic fungal infections, etc.?

Interferon-gamma release assays (IGRAs) are medical tests used in the diagnosis of tuberculosis. Interferon-gamma release assays rely on the fact that T-lymphocytes will release interferon-gamma when exposed to specific antigens.

Interferon gamma. Image source: Wikipedia.

The 3 types of interferons, remembered by the mnemonic ABG: alpha, beta, gamma (click to enlarge the image).

There are currently two interferon-γ release assays available for the diagnosis of tuberculosis:

- QuantiFERON-TB Gold (licensed in US, Europe and Japan)

- T-SPOT.TB, a form of ELISPOT (licensed in Europe)

QuantiFERON-TB Gold test quantitates the amount of gamma interferon produced in response to the ESAT-6 and CFP-10 antigens from Mycobacterium tuberculosis, which are distinguishable from those present in BCG and most other non-tuberculous mycobacteria.

T-SPOT.TB test determines the total number of individual effector T cells expressing gamma interferon.

Blood samples are mixed with one of the following:

- antigens that produce a reaction in the sensitized cells

- negative control (saline)

- positive control (phytohemagglutinin)

The antigens include mixtures of synthetic peptides representing two M. tuberculosis proteins, ESAT-6 and CFP-10. After incubation of the blood with antigens for 16 to 24 hours, the amount of interferon-gamma (IFN-gamma) is measured.

If the patient is infected with M. tuberculosis, their white blood cells will release IFN-gamma in response to contact with the TB antigens. The QFT-G results are based on the amount of IFN-gamma that is released in response to the antigens.

References:

Interferon-Gamma Release Assays (IGRAs) - Blood Tests for TB Infection. CDC.
Cellestis.com (PDF)
PedTB.gr
Interferons
Interferon-gamma

Experts: Oral immunotherapy (OIT) for food allergy is not ready for prime time

Analogy between oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT)

Office-based oral immunotherapy (OIT) for food allergy is safe and effective, according to an allergist group from Texas. The only death caused by OIT occurred during a formal trial at an academic center and was caused by a dosing error. Many more deaths have resulted from accidental exposure. The group experience represent the completed treatment of more than 175 patients.

Similar concerns have been raised in the treatment of allergic rhinitis by subcutaneous immunotherapy (SCIT), a treatment that was introduced more than a century ago and is one of the cornerstones of therapy for the specialty of allergy. In fact, the comparison of SCIT to OIT is quite revealing. Although the benefits of SCIT for airborne allergens are unquestionable, this treatment modality is not lifesaving but rather improves the quality of life.

Experts: Oral immunotherapy (OIT) is not ready for prime time

Oral immunotherapy (OIT) is not ready for prime time, say the leading experts in the field of food allergy.

In oral desensitization to peanut, adverse reactions requiring epinephrine occurred in 43% of patients. Overall, 32% of patients with food allergy were unable to continue.

Further investigation must address the less common but potentially more disabling consequences of OIT, such as eosinophilic esophagitis and other delayed-type reactions.

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

References

Office-based oral immunotherapy for food allergy is safe and effective. The Journal of Allergy and Clinical Immunology, Volume 127, Issue 1 , Pages 290-291, January 2011.

Oral immunotherapy: Ready for prime time? The Journal of Allergy and Clinical Immunology, Volume 127, Issue 1 , Pages 289-290, January 2011.

Reply. The Journal of Allergy and Clinical Immunology, Volume 127, Issue 1 , Pages 291-292, January 2011.

Sublingual and oral immunotherapy for milk allergy. Desensitization was lost in some cases within 1 week off therapy. JACI, 2011.

Image source: Roasted peanuts as snack food, Wikipedia, public domain.

Cancer, an ancient problem, may have an ancient solution: the role of Nuclear factor-kappa B

Cancer prevention may require avoidance of:

- tobacco
- alcohol
- high-fat diet
- polluted air and water
- sedentary lifestyle
- mechanical, physical, psychological, or chemical stress

How these factors listed above can cause cancer?

The mechanism is suggested by the transcription nuclear factor-kappa B (NF-kappa B), that is activated by:

- tobacco
- alcohol
- high-fat diet
- environment pollutants
- cancer-causing viruses (human papillomavirus, hepatitis B and C viruses, HIV) and bacteria (Helicobacter pylori)
- ultraviolet light
- ionizing radiation
- obesity
- stress

Suppression of NF-kappa B activation by the phytochemicals present in fruits and vegetables provides the molecular basis for their ability to prevent cancer.

Agents identified from spices and Ayurvedic and traditional Chinese medicines also suppress NF-kappa B activation and thus may have potential for cancer prevention.

Such agents are curcumin, resveratrol, silymarin, catechins and others. Thus, cancer, an ancient problem, may have an ancient solution.

References:

Nuclear factor-kappa B links carcinogenic and chemopreventive agents. Ralhan R, Pandey MK, Aggarwal BB. Front Biosci (Schol Ed). 2009 Jun 1;1:45-60.

High FENO distinguishes between allergic and non-allergic asthma in children

Fractional exhaled nitric oxide (FENO) has been proposed as a diagnostic test of asthma, recently reaffirmed by the ATS Guideline on Exhaled Nitric Oxide Levels (FENO) Use.

This 10-yr follow up of the Environment and Childhood Asthma Study in Oslo included 616 children of prospective birth cohort. Both FENO (single breath technique) and skin prick test (SPT) were measured in 331 children.

FENO was elevated in children with asthma (9.6 p.p.b.) compared with healthy children (5.8 p.p.b.).

FENO was highest among children with current allergic asthma (asthma and positive SPT) (14 p.p.b.). In contrast, children with non-allergic asthma (6 p.p.b) had comparable FENO levels to healthy children.

Allergic sensitization was most closely associated with FENO.

A FENO cut-off value of 20.4 p.p.b. had a high specificity (0.97), but a low sensitivity (0.41) for current allergic asthma.

High FENO levels were associated with current allergic asthma and not with current asthma without allergic sensitization.

References:

Diagnostic value of exhaled nitric oxide in childhood asthma and allergy. Sachs-Olsen C, Lødrup Carlsen KC, Mowinckel P, Håland G, Devulapalli CS, Munthe-Kaas MC, Carlsen KH. Pediatr Allergy Immunol. 2010 Feb;21(1-Part-II):e213-e221. doi: 10.1111/j.1399-3038.2009.00965.x.

ATS Guideline on Exhaled Nitric Oxide Levels (FENO) Use

Daily exhaled nitric oxide measurements ($17 each) could predict asthma exacerbations in children. Allergy, 2011.

Image source: NioxMino.

40% of Americans have ocular allergy, with peak symptoms in June and July

Allergies give rise to the fifth-leading group of chronic diseases.

The National Health And Nutrition Examination Survey III performed in the United States from 1988-1994 was the source for the data collected.

Classification of ocular allergy (click to enlarge the image).

The sample size was 20,000 patients:

- 6.4% reported ocular symptoms
- 16.5% reported nasal symptoms
- 30% reported both ocular and nasal symptoms
- 47% were asymptomatic

40% of the population reported at least 1 occurrence of ocular symptoms in the past 12 months.

Ocular symptoms are more frequent than nasal symptoms in relation to animals, household dust, and pollen.

This analysis provides the first representation of the epidemiology of ocular allergy in the United States. Up to 40% of the population, the highest reported to date, have experienced ocular symptoms at least once in their lifetime, with a peak of symptoms in the months of June and July.

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

References:

The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol. 2010 Oct;126(4):778-783.e6.
Image source: OpenClipArt.org.

Intestinal parasite infection may protect against allergic sensitization

The rate of increase in prevalence of allergic disease in some countries implies environmental exposures may be important etiological factors.

21 studies were included in this systematic review.

Current parasite infection was associated with a reduced risk of allergen skin sensitization (odds ratio [OR] 0.69). When analyses were restricted to current geohelminth infection, the size of effect remained similar, OR 0.68.

In species-specific analysis, a consistent protective effect was found for infection with:

- Ascaris lumbricoides

- Tricuris trichuria

- hookworm

- Schistosomiasis

Intestinal parasite infection appears to protect against allergic sensitization. Harnessing these in a safe way may reduce the global burden of allergic disease.

Colonoscopy Video Demonstrating a Moving Worm (NEJM).

References:

Feary J, Britton J, Leonardi-Bee J. Atopy and current intestinal parasite infection: a systematic review and meta-analysis. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02512.x00: 00–00.

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

Comments from Twitter:

@AllergyNet: My thoughts on where this may lead bit.ly/oS3F3S

@kfatweets: I think I will skip watching the video of the moving worm. :)

Refractory GERD can represent an initial stage of eosinophilic esophagitis

This study included patients with refractory gastroesophageal reflux disease (GERD) after using at least 40 mg of a proton pump inhibitor (PPI). They were placed on a restriction diet based on the results of skin prick testing and atopy patch testing with foods.

The prevalence of sensitization to foods was 28%. Asthmatic patients showed higher sensitization to foods.

Eosinophils were present in the esophageal mucosa in 16% of patients, and this correlated with greater sensitization to foods. One case of eosinophilic esophagitis was confirmed.

A diet excluding sensitizing foods led to clinical improvement regarding GERD symptoms.

The presence of eosinophils in esophageal mucosa associated with greater sensitization to foods and the response to a restriction diet in patients with positive test results suggest that refractory GERD can represent an initial stage of eosinophilic esophagitis.

References:

Sensitization to foods in gastroesophageal reflux disease and its relation to eosinophils in the esophagus: is it of clinical importance? Ann Allergy Asthma Immunol. 2010 Nov;105(5):359-63. Pomiecinski F, Yang AC, Navarro-Rodrigues T, Kalil J, Castro FF.
Image source: Eosinophilic esophagitis, Wikipedia, GNU Free Documentation License.

Asthma: an animation

From NHS Choices YouTube channel: Asthma is a chronic condition that can be managed but not cured. This animation explains asthma in detail.

Corneal disease is the primary cause of visual loss in allergic eye disease

Corneal disease is the primary cause of visual loss in allergic eye disease. It occurs almost exclusively in vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).

Classification of ocular allergy (click to enlarge the image).

Vernal keratoconjunctivitis is a relatively rare ocular allergic disease affecting children and young adults living in warm climates. In 50% of cases, it is associated with other allergic diseases. Cyclosporine eye drops prevent seasonal recurrences of vernal keratoconjunctivitis in a 2-year study (JACI, 2011).

By contrast, AKC typically presents later in life, occurring in 20–40% of patients with atopic dermatitis.

Corneal disease currently requires aggressive treatment with topical steroids.

Clinicians should also be aware of steroid resistance and dependency. In these cases, new, off-label treatments can be considered.

Topical cyclosporin (CsA) has the longest history of clinically proved efficacy in controlling the signs and symptoms of severe allergy.

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

References:

Mechanisms of Corneal Allergic Reaction: New Options for Treatment. Medscape.
Ocular Allergy: Allergic Conjunctivitis and Related Conditions, Brief Review
Cyclosporine eye drops work as steroid sparing therapy in vernal keratoconjunctivitis http://goo.gl/GTNyS and http://goo.gl/Vi82k

Food-specific IgE tests aren't sufficient evidence for eliminating foods from a child’s diet

In a study of more than 100 children on food elimination diets based on positive serum IgE immunoassay results, oral food challenges (OFCs) demonstrated that most of the foods were being unnecessarily eliminated from the diet.

OFCs were not performed in children with:

- a history of a life-threatening reaction
- a convincing history of a reaction within the previous 6 to 12 months
- an immunoassay test result (level) that exceeded 95% predictive value for milk, egg, peanut, or fish
- an associated large prick skin test (PST)

For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, are:

- egg, 6 kilounits of allergen-specific IgE per liter kU
- milk, 32 kU (or 15 in newer studies)
- peanut, 15 kU
- fish, 20 kU

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).

89% of oral food challenges (OFCs) performed with foods being actively avoided at baseline were negative.

All reactions during the OFCs occurred within the 2-hour observation period. There were no documented cases of atopic dermatitis flares on the day after an OFC.

84-93% of the foods being avoided were returned to the diet after an OFC, indicating that the vast majority of foods that had been restricted could be tolerated.

Many of the children were unnecessarily on "overly restrictive" diets that excluded foods that they had never eaten or foods that they once tolerated based primarily on sIgE test results (ImmunoCAP).

The erroneous practice of ordering a large panel of serum IgE tests and eliminating a large number of foods without the expertise of an allergist to interpret these tests must be changed.

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).

Oral Food Challenges (click to enlarge the diagram).

References:

Study Warns of Over-Reliance on Blood Tests for Food Allergy. Medscape and Reuters, J Pediatr. Published online October 29, 2010.
Levels of specific IgE that predict food allergy reaction
Outpatient open oral food challenges should be considered if the likelihood of success is greater than 50%

Sublingual Immunotherapy (SLIT) Works for House Dust-Mite Allergic Rhinitis in Children

House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis. This double blind, placebo-controlled trial evaluated the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in 31 pediatric patients with HDM allergic rhinitis.

Extract or placebo (1 ml) was administered at 10-fold dilution once weekly for 40 weeks.

The symptom scores in the active group began to decrease 24 weeks (6 months) after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks.

The symptom scores for the last 4 weeks of the study were significantly lower than those for the first 4 weeks in the active group.

The only local adverse effect was a bitter taste reported by 1 patient. There were no other local or systemic adverse effects associated with SLIT.

SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children.

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).

References:

Sublingual Immunotherapy with House Dust Extract for House Dust-Mite Allergic Rhinitis in Children. Allergology International. 2010;59.

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

Sublingual immunotherapy (SLIT) not effective in house dust mite-allergic children in primary care http://goo.gl/EdFHJ

Cannabis (marijuana) may be an important allergen in young people

Cannabis, also known as marijuana, is the illicit drug most widely used by young people in higher-income countries. Allergy symptoms have only occasionally been reported as one of the adverse health effects of cannabis use.

This Spanish study included 340 patients who were cannabis users, with mean age 27 years.

The participants were selected from a database of 21,582 individuals with asthma, sensitized to pollen; and others sensitized to tobacco, tomato and latex, considered as cross-reacting allergens.

Among the marijuana users, 61% of males were sensitized to cannabis.

72% of the patients allergic to tomato were sensitized to cannabis, but a positive specific challenge to cannabis was highest in patients sensitized to tobacco (62%).

Pollen allergy was not a risk factor for cannabis sensitisation.

Prick tests and IgE for cannabis had a good sensitivity (92 and 88%, respectively) and specificity (87 and 96%) for cannabis sensitisation.

Cannabis may be an important allergen in young people. Patients previously sensitised to tobacco or tomato are at risk. Cannabis prick tests and IgE were useful in detecting sensitisation.

References:

Allergic hypersensitivity to cannabis in patients with allergy and illicit drug users. Armentia A, Castrodeza J, Ruiz-Muñoz P, Martínez-Quesada J, Postigo I, Herrero M, Gonzalez-Sagrado M, de Luis D, Martín-Armentia B, Guisantes JA. Allergol Immunopathol (Madr). 2011 Jan 25.

Low-dose Marijuana Exposure Improves Pulmonary Function Over 20 Years, claims JAMA, 2012. Were data reliable?

Image source: Cannabis, common hemp. Wikipedia, public domain.

Comments from Facebook:

Matthew Bowdish: "We have seen several patients with cannabis allergy who are involved in the medical marijuana industry. No great tests but their histories are quite suggestive. Insert MJ-IT joke here."

Is Johnny wheezing? Parents underestimate burden of asthma experienced by their children

A telephone-based survey was conducted in 2004 among a sample of 280 children (aged 10-15) with current asthma and their parents in the United States.

Parents underestimated the burden of asthma experienced by their children, especially the effects on physical activity:

- More than half (58%) of children replied that exercise was a trigger for their asthma compared to only 35% of parents.

- Children were more likely than parents to mention activity limitations, specifically avoiding physical exertion (63% vs. 49%).

- Prevalence of symptoms was also underreported by parents relative to children, particularly breathing problems (41% vs. 67%) and cough (45% vs. 64%).

- Maintenance therapy use in the past 4 weeks was reported by 35% of children, whereas 44% of parents believed their children had used maintenance therapy).

Parents underestimated avoidance tactics used by their children with asthma, including exercise and physical activity self-limitation to prevent the onset or worsening of asthma symptoms. Parents also underreported asthma symptoms of their children.

References:

Davis KJ, DiSantostefano R, Peden DB. Is Johnny wheezing? Parent-child agreement in the childhood asthma in America survey. Pediatric Allergy Immunology 2011: 22: 31-35.

Complete asthma control is uncommon in children worldwide. Parents underestimate asthma severity, overestimate control. ERJ January 1, 2012 vol. 39 no. 1 90-96.

Intranasal steroids help allergic conjunctivitis too

Intranasal corticosteroids (INSs) are a mainstay of treatment of allergic rhinitis (AR) nasal symptoms. The INS mometasone furoate nasal spray (MFNS) has well-documented efficacy and safety for the treatment and prophylaxis of nasal symptoms of seasonal AR (SAR) and for the treatment of nasal symptoms of perennial AR (PAR).

Increasing interest has focused on whether INSs may have beneficial effects on the ocular symptoms frequently associated with AR.

Treatment Options for Allergic Rhinitis (click to enlarge the image).

This meta-analysis included 10 randomized, placebo-controlled trials (3,000 patients) of the efficacy of MFNS 200 mcg daily in relieving ocular allergy symptoms, including itching/burning, redness, and tearing/watering in both SAR and PAR.

Treatment effect was significant for all three individual ocular symptoms in the SAR studies and in the PAR studies.

There is a growing body of literature supporting the positive class effect of INSs on ocular symptoms associated with SAR and PAR.

References:
Bielory L, Chun Y, Bielory BP, Canonica GW. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis. Allergy 2011; DOI: 10.1111/j.1398-9995.2010.02543.x.

Polymorphous Light Eruption

Polymorphous Light Eruption - Mayo Clinic video: "Imagine this: Every time you go out into the sunlight to walk the dog or get the mail your skin gets red, itchy and inflamed. That's what happens to people with a condition called polymorphous light eruption."

Outpatient open oral food challenges should be considered if the likelihood of success is greater than 50%

Screening tests, such as skin tests (SPT) and serum IgE levels can predict food allergic reactions but ultimately, feeding patients the suspected allergic food is the only way of confirming or ruling out a food allergy (oral food challenge).

Oral Food Challenges (click to enlarge the diagram).

The double-blind oral food challenge (OFC) is the best method from from research perspective but the procedure can take upwards of 8 hours and is often impractical in most real-life settings.

In a recent JACI article, data was reviewed from 700 oral challenges performed at a university-based pediatric allergy outpatient clinic (Mount Sinai School of Medicine, New York) during 2 years.

Patients were rarely challenged if the risk of reaction was deemed to be greater than 50%.

19% of the challenges were positive, i.e. elicited a reaction. Milk, peanut, wheat, and soy most commonly elicited a reaction.

Factors associated with positive challenges included:

- larger positive reaction on skin tests
- higher food-specific serum IgE levels
- history of past reaction to the food (as compared to those patients who were avoiding a food due to previous test results and had never eaten the food)

The majority (88%) of reactions were treated with an antihistamine alone. Only 1.7% of all challenges required epinephrine.

Open OFC can be very effective in adding foods back to the diets of the majority of patients, if selected when the testing and history are favorable (estimated less than 50% chance of reaction).

OCF is a relatively safe procedure with systemic reactions occurring at a rate that is equivalent to systemic reactions to "allergy shots."

There has been no reported death from oral food challenge done by a board-certified allergist in a supervised clinical setting. Please do not attempt an oral food challenge at home because of the risk of fatal reaction.

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).

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).

References:

Outpatient open oral food challenges – feasible and “feed-able”. AAAAI.
Food Challenges for Diagnosis of Food Allergy
When to Attempt a Food Challenge in Tree Nut Allergy?

Comments from Twitter:

@allergistmommy: I've been doing more peanut OFC's lately, esp in concert with component resolved diagnostics.

New Recruitment Cycle for Allergy/Immunology Fellowship

Allergy/immunology subspecialty programs will change their recruitment cycle from second to third year (from PGY-2 to PGY-3) starting with ERAS 2013 (Electronic Residency Application Service).

The residents will now apply to A/I fellowships in their third year, not their second. It gives both pediatric and internal medicine residents a little extra time to get experience and do research during their 2nd year.

Attention Fellowship Applicants: Many allergy/immunology subspecialty programs will not participate in ERAS 2012; please contact programs to confirm their participation status before applying.

References:
ERAS for Fellowship Applicants (scroll to the bottom of the page for the A/I announcement).
Image source: Wikipedia

ATS Guideline on Exhaled Nitric Oxide Levels (FENO) Use

Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FENO) is a quantitative and noninvasive method of measuring airway inflammation.

The American Thoracic Society (ATS) aimed to develop evidence-based guidelines for the interpretation of FENO measurements. According to them, in the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV1 reversibility or provocation tests are only indirectly associated with airway inflammation.

FENO offers added advantages for patient care including:

- detecting of eosinophilic airway inflammation
- determining the likelihood of corticosteroid responsiveness
- monitoring of airway inflammation to determine the potential need for corticosteroid
- unmasking of otherwise unsuspected nonadherence to corticosteroid therapy

FENO levels above 50 parts per billion (ppb) suggest the presence of eosinophilic airway inflammation and likely responsiveness to inhaled corticosteroids. FENO levels below 25 ppb suggest that eosinophilic airway inflammation is unlikely and that the individual is not likely to respond to treatment with (or increasing the dose of) inhaled corticosteroids depending on the clinical context.

FENO cut-points

The guidelines propose a series of cut-points to help make clinical decisions:

- FENO lower than 25 ppb (lower than 20 ppb in children) indicates that eosinophilic inflammation and responsiveness to inhaled corticosteroids are less likely.

- FENO higher than 50 ppb (higher than35 ppb in children) indicates that eosinophilic inflammation and, in symptomatic patients, responsiveness to inhaled corticosteroids are likely.

- FENO values between 25 ppb and 50 ppb (20-35 ppb in children) should be interpreted cautiously with reference to clinical context.

What is a significant change in FENO?

FENO increases of 20% or more for values over 50 ppb (or 10 ppb more for values less than 50 ppb) are significant, from one visit to the next. Conversely, reductions of 20% or 10 ppb indicate significant response to anti-inflammatory therapy.

Videos by the manufacturer of the FENO measurement device Niox Mino, Aerocrine:

References:

An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine Vol 184. pp. 602-615, (2011). Full text PDF.
ATS Publishes Clinical Practice Guidelines on Interpretation of FENO Levels
Practical points on using NIOX MINO fractional exhaled nitric oxide (FENO) measuring device
Image source: NioxMino.

Tiotropium (LAMA) step-up therapy for asthma uncontrolled with ICS works as well as adding LABA

Tiotropium bromide (Spiriva) is a long-acting anticholinergic agent (LAMA) approved for the treatment of chronic obstructive pulmonary disease (COPD) but not asthma.

210 patients with asthma were included in a trial with the addition of tiotropium to an inhaled glucocorticoid (ICS), as compared with a doubling of the dose of the inhaled glucocorticoid or the addition of the LABA salmeterol (a component of Advair).

The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by:

- measuring the morning peak expiratory flow (PEF), with a mean difference of 26 liters per minute.
- the proportion of asthma-control days
- the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (a small difference)
- daily symptom scores

The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters.

When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol.

It looks like we will have to add Spiriva to the list of the asthma inhalers below:

Asthma Inhalers, including the cost of each inhaler (click to enlarge the image).

References:

Tiotropium Bromide Step-Up Therapy for Adults with Uncontrolled Asthma. N Engl J Med 2010; 363:1715-1726, October 28, 2010.
Wind of Change? The TALC Trial Blows into Town
Tiotropium has a profound effect on methacholine challenge - it has to be stopped 1 week prior to challenge http://goo.gl/DiCb2

Anatomical Tutorial During Trans-Nasal Endoscopy (video)

The ENT specialist Dr. Christopher Chang describes the various anatomy objects he encounters during a trans-nasal endoscopy: " This procedure is also called rhinoscopy. These exams are performed without any sedation and are easily tolerated by patients as young as 5 years of age with their full cooperation. Prior to examination, the nose is decongested and anesthetized with a nasal spray."

Interestingly, this strictly professional video has received close to 40,000 million views on YouTube.

References:

Fiberoptic Endoscopy and Its Variations (Nasal Endoscopy, Nasopharyngoscopy, & Laryngoscopy).

How Primary Care Physicians Can Help Patients To Improve Asthma Control

Many adolescents and adults with asthma continue to have poorly controlled disease, often attributable to poor adherence to asthma therapy.

Failure to adhere to recommended treatment may result from:

- desire to avoid regular reliance on medications
- inappropriate high tolerance of asthma symptoms
- failure to perceive the chronic nature of asthma
- poor inhaler technique

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

If asthma treatment is not working, check DAT:

Diagnosis - not asthma at all (VCD, CF, FBA), asthma plus AR, GERD

Adherence - compliance with medication

Technique - NEB, HFA with spacer, DPI, etc.

3 C's of care - communication, continuity, concordance (finding common ground) are critical for asthma management (http://goo.gl/8gJM6).

Few adolescents or adults with asthma currently have asthma “checkup” visits, usually seeking medical care only with an exacerbation. Therefore, nonrespiratory-related office visits represent an important opportunity to assess baseline asthma control and the factors that most commonly lead to poor control.

Tools such as the Asthma Control Test, the Asthma Therapy Assessment Questionnaire, the Asthma Control Questionnaire, and the Asthma APGAR provide standardized, patient-friendly ways to capture necessary asthma information.

For uncontrolled asthma, physicians can refer to the stepwise approach in the 2007 National Asthma Education and Prevention Program guidelines to adjust medication use.

However, doctors must consider step-up decisions in the context of:

- quality of the patient's inhaler technique
- adherence - 24% of asthma exacerbations are attributable to ICS medication nonadherence http://goo.gl/1i8ET
- ability to recognize and avoid or eliminate triggers

Dr. Barbara Yawn, Family Physician and Director of Research at the Olmsted Medical Center in Rochester, MN, discusses her article appearing in the September 2011 issue of Mayo Clinic Proceedings on ways physicians can enhance patient education for asthma control by not missing opportunities.

References

The Role of the Primary Care Physician in Helping Adolescent and Adult Patients Improve Asthma Control. Barbara P. Yawn. Mayo Clinic Proceedings September 2011 vol. 86 no. 9 894-902.

24% of asthma exacerbations are attributable to ICS medication nonadherencehttp://goo.gl/1i8ET

"How Asthma Makes Me Feel" video

"How Asthma Makes Me Feel" video. The Allergy & Asthma Network Mothers of Asthmatics (AANMA) asked children to tell us—in pictures and in their own words—how they felt during an asthma attack, and how they felt when they could breathe again. What they told us was enlightening—and heart-rending.

Allergy Notes