Allergy Notes: 03/2011

Parvalbumin content of fish species varies considerably - possibly contributing to variable allergenicity

95% of fish-allergic patients are sensitized to the major fish allergen parvalbumin. However, clinical reactions to different fish species vary considerably in symptoms, intensity and frequency in allergic subjects.

This study quantified the parvalbumin levels in salmon, trout, cod, carp, mackerel, herring, redfish and tuna.

Parvalbumin contents were (SDS-PAGE scanning):

- less than 0.5 mg per gram tissue for mackerel

- 0.5-2 mg for salmon and trout

- more than 2 mg for cod, carp, redfish and herring

Parvalbumin contents were (ELISA)

- less than 0.05 mg for tuna

- 0.3-0.7 mg for mackerel

- 1-2.5 mg for salmon, trout and cod

- more than 2.5 mg per gram raw muscle for carp, herring and redfish

The parvalbumin content of processed samples (cooked/commercial) was 20-60% lower.

The parvalbumin content of most commonly consumed fish species varies considerably. Differences range from severalfold to 100-fold. This has to be taken into account when designing food challenge tests and advising fish-allergic patients.

Fish-allergic patients should avoid all fish species until a species can be proven safe to eat by provocative challenge (Annals of Allergy and Imm, 1999).

References:

Important Variations in Parvalbumin Content in Common Fish Species: A Factor Possibly Contributing to Variable Allergenicity. Kuehn A, Scheuermann T, Hilger C, Hentges F. Int Arch Allergy Immunol. 2010 Jun 17;153(4):359-366.
Epitope Mapping of Atlantic Salmon Major Allergen by Peptide Microarray Immunoassay http://goo.gl/OGCnn
Image source: Gadus morhua, Atlantic cod. Wikipedia, public domain.

Immunotherapy-related tweets from 2011 AAAAI meeting

Here are some of the immunotherapy-related tweets from 2011 annual AAAAI meeting. They were labeled #AAAAI and based on real time updates by Sakina Bajowala, M.D @allergistmommy and Robert Silge, MD @DoctorMac and @utahallergy. The text was edited, modified, and added to by me.

Preventing systemic reactions

Premedication with antihistamines reduces risk of systemic reactions during immunotherapy, Antihistamine pretreatment in cluster and rush immunotherapy significantly decreases systemic reactions.

Systemic reactions are more frequent with rush immmunotherapy (as expected). Oral steroids in rush immunotherapy have benefit.

Omalizumab for preventing systemic reactions

Omalizumab has protective effect against systemic reactions during both rush and maintenance immunotherapy. There is no FDA-indication for it, but asthmatics on immunotherapy may benefit from omaluzumab.

Beta-blockers and immunotherapy

New practice parameters state that in life-threatening insect allergy, the use of beta blocker is not a contraindication. Venom mmunotherapy can be given during beta blocker therapy, based on risk-benefit analysis.

Oral allergy syndrome

Immunotherapy for oral allergy syndrome? Academic answer: no evidence. Practical answer: worth a try!

Image source: OpenClipArt.org, public domain.

4-year duration of SLIT with dust mite seems like the optimal choice

Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate.

In this prospective open controlled study, the patients with respiratory allergy who were monosensitized to mites (allergic to dust mites only) were followed for 15 years.

78 patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study.

In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years.

New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively).

It can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination.

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:

Long-lasting effects of sublingual immunotherapy according to its duration: A 15-year prospective study. Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. J Allergy Clin Immunol. 2010 Oct 7.

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

Drug allergy-related tweets from 2011 AAAAI meeting

Here are some of the drug allergy-related tweets from the 2011 annual AAAAI meeting. They were labeled #AAAAI and based on real time updates by Sakina Bajowala, M.D @allergistmommy and Robert Silge, MD @DoctorMac. The text was edited, modified, and added to by me.

Penicillin allergy

In syphilis infection, penicillin is the drug of choice. A history of penicillin allergy? Do skin testing.

Two minor determinants for penicillin allergy account for 10-20% of positive skin tests. These are not commercially available. The major determinant is available as Pre-Pen (costs $300),

However, the clinical relevance of these 2 minor determinants is unclear. Skin tests may be positive, but clinical reactions occur at a much lower frequency.

However, even without minor determinant, negative predictive value of testing with Pre-Pen & PCN G is very good.

10-20% of PCN-allergic patients may not react to Pre-Pen (major determinant) and PCN G (minor determinants substitute). Should you test with minor determinant? Yeah, if you have it! (minor determinants not commercially available as of 2011).

In PCN skin testing, intradermals should be done in duplicate. Intradermal testing for penicillin seems very safe. Reaction rate was 0.12% in a Mayo clinic study of 1710 patients undergoing PCN skin testing. It is safe for outpatient use.

Cross reactivity of penicillin to cephalosporins

97% of patients with negative PCN skin test will also tolerate other beta-lactam antibiotic.

Cross reactivity of penicillin to cephalosporins is low, but the reported frequency varies “all over the place”. Probably less than 1% risk of cross-reactivity. If PCN skin test is negative, there is virtually no risk. Compare to PCN: 3% of patients with negative penicillin skin test will still have reaction to penicillin.

Use clinical history to decide whether to pursue full dose treatment or graded dose challenge after a negative PCN skin test.

If PCN skin test is positive, treatment can be pursued after drug desensitization. Can be done orally or IV.

Pencillin desensitization does not need to be repeated for weekly doses, IF the half life of the penicillin used is long enough.

Vancomycin

It can be difficult to differentiate anaphylaxis from "red-man syndrome" after administration of vancomycin.

“Red man syndrome” is volume dependent. If reaction happens within minutes, more likely to be vancomycin anaphylaxis. "Red-man syndrome" is generally related to infusion rate, and is primarily due to non-specific histamine release, not allergy.

Antihistamines and slow infusion rate should prevent “red man syndrome” with vancomycin.

Drug challenge and desensitization

Almost a quarter of the allergists in the AAAAI meeting room do neither drug challenges nor desensitization!

Most drug desensitizations occur in the inpatient setting - ICU preferred due to 1:1 nursing, rather than danger of procedure.

What is spirometry? A simple breathing test (video)

The Lung Association: Dr. Roger Goldstein explains what spirometry is (a simple breathing test), who should get tested and what spirometry tells health-care professionals. Visit www.lung.ca for more information.

Spirometry patient coaching: This 2 min video demonstrates how to prepare and properly coach a patient for spirometry testing using a Welch Allyn spirometer.

Food allergy-related tweets from 2011 AAAAI meeting

Here are some of the food allergy-related tweets from the 2011 annual AAAAI meeting. They were labeled #AAAAI and based on real time updates by Sakina Bajowala, M.D @allergistmommy and Robert Silge, MD @DrSilge. The text was edited, modified, and added to by me.

Diagnosis

The 2010 guidelines for diagnosis and management food allergy: tests should be based on medical history - do not order large panels of food testing. Sensitization alone is not sufficient for diagnosis of food allergy. Diagnosis is based on the combination of sensitization and clinical symptoms.

Delayed anaphylaxis to meat

Delayed anaphylaxis can occur due to alpha-1, 3 galactose in mammalian meats and milk. This is an example of carbohydrate (not protein) allergy. Alpha-gal sensitization may be triggered by tick or chigger bites. Alpha-gal sensitization may be associated with allergic reactions to cetuximab (food allegy link to drug allergy). Related reading: Delayed mammalian meat–induced anaphylaxis due to galactose-α-1,3-galactose in 5 European patients - JACI, 2011.

Advisory labels

Milk protein is found in significant concentrations in products labeled "may contain", "shared equipment", or "shared facility". Recommendation: do not use foods with advisory label. Use caution with unlabeled foods from small companies.

Pregnancy and diet

There is Insufficient evidence to recommend dietary modification during pregnancy. In high risk food allergy families, peanut may be a notable exception.

Oils

Soybean oil and soy lecithin are generally well-tolerated in IgE-mediated soy allergy. Soy oil gets a “free pass” for soy allergic patients. Soy lecithin is also not a concern.

There are some patient who can't tolerate the oil and lecithin from soy (if soy-allergic). However, they don't develop anaphylaxis.

Peanut and sesame oils may contain trace amounts of protein (depending on how they are processed), so they should be avoided.

Allergenicity of refined vegetable oils is extremely low http://goo.gl/EzUgp

Food Allergy Cases, Clinical Notes, Mind Maps and Mnemonics at AllergyCases.org

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

Fluticasone nasal spray relieves ocular symptoms of allergic rhinitis

Previous data suggest that intranasal fluticasone furoate (FF) improves ocular symptoms of allergic rhinitis (AR). This systematic review with meta-analysis confirmed the findings.

Primary outcomes were reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS), and reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS).

Secondary outcomes included the assessment of response to therapy, quality of life (QoL), and adverse effects.

16 trials (5.348 patients) were selected.

Intranasal FF improved rTOSS and iTOSS scores compared with placebo in patients with seasonal and perennial AR.

Intranasal FF showed a consistent ocular and nasal efficacy along with improvement in QoL in AR patients.

Treatment with FF nasal spray at a dose of 110 mcg once daily is effective in relieving ocular and nasal symptoms in adolescents and adults with AR.

Medications for Allergic Conjunctivitis (click to enlarge the image).

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

References:
Efficacy of fluticasone furoate nasal spray vs. placebo for the treatment of ocular and nasal symptoms of allergic rhinitis: a systematic review. Clin Exp Allergy. 2010 Dec 1. doi: 10.1111/j.1365-2222.2010.03654.x. [Epub ahead of print]. Rodrigo GJ, Neffen H.

Image source: OpenClipArt.org.

Allergy Sufferers Try Acupuncture (video)

Allergy Sufferers Try Acupuncture, according to the Fox News report:

Allergy Sufferers Turn to Acupuncture: MyFoxPHOENIX.com

Allergy Sufferers Turn To Alternative Treatments - Acupuncture - WLKY Louisville.

However, this is what really helps (in addition to immunotherapy):

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

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

The frequency of adults reporting a history of asthma is rising. However, it is unclear whether this increased prevalence is due to a rising trend ("true asthma") or if it reflects an increase in asthma awareness (but no "real asthma").

Data from methacholine challenge, spirometry, and physician assessment were analysed from 304 adults who reported physician-diagnosed asthma.

27% of the patients had a negative methacholine test.

A negative test was associated with:

- an adult-onset of symptoms

- normal forced expiratory volume in 1 s (FEV1)

- no history of exacerbation requiring oral steroids

60% of those with a negative test reported weekly asthma-like symptoms (cough, dyspnea, chest tightness, or wheeze).

39% reported emergency department visits for asthma-like symptoms.

A sizeable percentage (27%) of subjects who report physician-diagnosed asthma have a negative methacholine challenge test. These subjects often have a diagnosis of asthma as an adult and normal or near normal spirometry.

Caution should be exercised in diagnosis of adults presenting with asthma-like symptoms, because they may not have asthma. Bronchoprovocation testing is warranted in this patient group, especially if their spirometry is normal.

If methacholine challenge is negative but FeNO is higher than 30 ppb, perform adenosine challenge to rule out asthma (Ann of Allergy and Imm, 2012).

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:

Negative methacholine challenge tests in subjects who report physician-diagnosed asthma. McGrath KW, Fahy JV. Clin Exp Allergy. 2010 Nov 24. doi: 10.1111/j.1365-2222.2010.03627.x.

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

Twitter comments:

@frozenwarning: Negative methacholine challenge on one day doesn't preclude asthma. Also, variation of 2 doubling doses. Not impressed with study.

"Family raising $15K for allergy assistance dog" (video)

"Family raising $15K for allergy assistance dog whose job is to find peanut protein on surfaces where you can't see it", according to the FOX Toledo News report:

Family raising $15K for allergy dog: Fox Toledo.com

I am not sure this will provide a complete solution. It is certainly a very expensive effort. The methods that are proven to work include:

- avoid allergens
- check labels
- carry "EpiPen 2-Pak" at all times
- learn when and how to use the EpiPen
- make people around you aware of your food allergies

Food Allergen Avoidance

Farm living may protect against childhood asthma and allergy - but how?

Many epidemiological studies have shown that children who grow up on traditional farms are protected from asthma, hay fever and allergic sensitization.

The most effective protective exposures include:

- early-life contact with livestock and their fodder

- consumption of unprocessed cow's milk

Studies of the immunobiology of farm living point to activation and modulation of innate and adaptive immune responses by intense microbial exposures and possibly xenogeneic signals delivered before or soon after birth.

References:

Farm living: effects on childhood asthma and allergy. Nature Reviews Immunology 10, 861-868 (December 2010) | doi:10.1038/nri2871

Farm exposure—a novel natural model of immunotherapy against allergic diseases? JACI, Apr 2009.
How to reduce your risk of asthma: spend your whole life on a farm

Children living on farms exposed to a wider range of microbes leading to lower asthma risk. NEJM, 2011.
Protective role of contact with livestock and farming lifestyle on asthma, in particular during childhood. ERJ January 1, 2012 vol. 39 no. 1 67-75.
Image source: OpenClipArt.org, public domain.

CX3C - a breathtaking chemokine in asthma and allergy

Allergic asthma is a chronic inflammatory lung disease that is thought to be driven by T helper 2 (TH2) cells. The understanding of the mechanisms responsible for T cell recruitment and activation in the allergic lung remains limited.

A new study now shows that CX3C-chemokine receptor 1 (CX3CR1) and its ligand, CX3C-chemokine ligand 1 (CX3CL1), exacerbate allergic airway disease by promoting the survival of effector T cells in the inflamed lung.

52 chemokines from 4 families have been described. They interact with 20 receptors (click here for a larger image).

References:
Asthma and allergy: A breathtaking chemokine. Nature Reviews Immunology 10, 810-811 (December 2010) | doi:10.1038/nri2897

Chemokines

Anti-acid medications may be a risk factor for food allergy

An important feature for oral allergens is their digestion-resistance during gastrointestinal (GI) transit.

Gastric acid levels determine the activation of gastric enzyme pepsin and also the release of pancreatic enzymes.

Some effect of the anti-acid medications related to food allergy include the following:

- When anti-ulcer drugs neutralize gastric acid, they allow persistence of intact food allergens (and protein-bound drugs) to elicit allergic reactions

- Anti-ulcer drugs containing aluminum compounds act as Th2 adjuvants

- Proton pump inhibitors (PPI) act on expression of the morphogen "Sonic hedgehog", which has been related to the development of atrophic gastritis. Atrophic gastritis and hypoacidity are correlated with enhanced sensitization food allergens in elderly patients

Impairment of gastric function is a documented risk factor for sensitization against oral proteins in food allergy and drugs.

References:
Pali-Schöll I, Jensen-Jarolim E. Anti-acid medication as a risk factor for food allergy. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02511.x.

Anti-acid drug sucralfate may increase risk for food allergy

Image source: Omeprazole (brand names include Losec, Prilosec, Zegerid), Wikipedia, public domain.

Statins enhance anti-inflammatory effects of inhaled corticosteroids in asthma

In this study, 50 asthmatic patients were treated with 200 μg of budesonide and randomly assigned to either 10 mg of simvastatin (low dose) or placebo for 8 weeks.

Sputum eosinophils were reduced by the combined therapy with budesonide and simvastatin compared with budesonide alone.

Inhaled corticosteroids work in part by activating indoleamine 2, 3-dioxygenase (IDO) through increased IL-10 secretion. Corticosteroids activate glucocorticoid-induced TNF receptor ligand, which induces activation of p52 through the nuclear factor κB pathway (NFkB). This leads to increased transcription and activation of IDO.

Simvastatin enhanced corticosteroid-activated NFkB-induction of IDO by activating type I interferons. It also enhanced the effect of corticosteroid on IL-10 release.

A statin enhances the anti-inflammatory effect of an inhaled corticosteroid in asthma, and this was mediated through the alteration of IDO activity in macrophages.

Statins May Worsen Asthma - New Findings Contradict Earlier Studies (ACAAI, 2011).

References:

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase. J Allergy Clin Immunol. 2010 Oct;126(4):754-762.e1.

Simvastatin provides little help for reducing steroid use in asthma. JACI Blog, 2010. http://goo.gl/7xllp

Statins for treatment of asthma?

Statins associated with reduced hospitalization for asthma - Taipei Veterans Hospital, 2011.

Adding clarithromycin to inhaled steroid in uncontrolled asthma was ineffective

PCR studies have shown Mycoplasma pneumoniae and Chlamydophila pneumoniae in the lower airways of patients with asthma.

92 adults with an Asthma Control Questionnaire score greater than 1.5 after a 4-week period of treatment with fluticasone propionate were enrolled in this study from National Jewish Health in Denver, Colorado.

13% demonstrated PCR evidence of M pneumoniae or C pneumoniae in endobronchial biopsies.

Clarithromycin did not improve lung function or airway inflammation. There was some improvement in airway hyperresponsiveness with clarithromycin.

Adding clarithromycin to fluticasone in adults with mild-to-moderate persistent asthma that was suboptimally controlled by low-dose inhaled corticosteroids alone did not further improve asthma control.

A 2012 retrospective study, suggested that neomacrolides may be useful as an add-on therapy in patients with severe asthma (Medscape, 2012).

References:

A trial of clarithromycin for the treatment of suboptimally controlled asthma. J Allergy Clin Immunol. 2010 Oct;126(4):747-53.

Image source: Clarithromycin structure, Wikipedia, public domain.

Example of cross-reactivity: allergy to kiwi in patients with baker's asthma

Baker's asthma is a frequent IgE-mediated occupational disorder provoked by inhalation of cereal flour. Allergy to kiwi has being increasingly reported in the past few years but no association between both baker's asthma and kiwi allergy has been described so far.

This Spanish study evaluated 20 patients with occupational asthma caused by wheat flour inhalation (baker's asthma). Kiwi ingestion elicited oral allergy syndrome in 35% patients with baker's asthma.

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

Profilin is an actin-binding protein involved in the restructuring of the actin cytoskeleton. It is found in all eukaryotic organisms in most cells. Profilin may be a pan-allergen among plants that crossreacts between pollen, fruits, vegetables and latex.

References:
Allergy to kiwi in patients with baker's asthma: identification of potential cross-reactive allergens. Palacin A, Quirce S, Sánchez-Monge R, Fernández-Nieto M, Varela J, Sastre J, Salcedo G. Ann Allergy Asthma Immunol. 2008 Aug;101(2):200-5.

Cross Reactions Among Foods (PDF).

Rapid desensitization for drug hypersensitivity - EAACI consensus statement

Drug hypersensitivity reactions can occur with most drugs. They are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis.

SOAP III mnemonic for classification of adverse reactions to drugs (click to enlarge the image).

In most cases, the suspected drug is simply avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed.

Drug desensitization is defined as the induction of a temporary state of tolerance of a drug responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated.

Drug desensitization is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a risk/benefit analysis.

Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs.

Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated.

Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication.

Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course.

References:
General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, Campi P, Sanz ML, Castells M, Demoly P, Pichler WJ; for the European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. Allergy. 2010 Aug 17.

Adverse Reactions to Drugs: Brief Review
Mind Maps: Drug Allergy
Mnemonics: Drug Allergy

Spirometry use in primary care settings for asthmatic children does not conform to guidelines

A 4-page survey was mailed to a national, random sample of office-based family physicians and pediatricians.

Among the 360 respondents who provided care to children with asthma:

- 52% used spirometry in clinical practice

- 80% used peak flow meters

- 10% used no lung function tests

Only 21% routinely used spirometry for all guideline-recommended clinical situations.

More family physicians than pediatricians reported using spirometry (75% vs 35%).

Family physicians were more comfortable in interpreting spirometric results (50% vs 25%).

Only 50% of respondents interpreted correctly the spirometric results in a standardized clinical vignette. Frequency of underrating asthma severity increased with the inclusion of spirometric results.

The most common barriers to the use of spirometry were time and training.

The use of spirometry in primary care settings for children with asthma does not conform to national guidelines.

References:

Spirometry Use Among Pediatric Primary Care Physicians. PEDIATRICS Vol. 126 No. 4 October 2010, pp. 682-687 (doi:10.1542/peds.2010-0362).
Daily home spirometry does not reduce exacerbations in children with severe asthma. ERJ, 2012.

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

Twice-daily budesonide/formoterol for asthma works better than once-daily dosing or budesonide alone

This 12-week multicenter, double-blind randomized controlled study included 521 patients aged 6 to 15 years with mild/moderate persistent asthma.

Patients stabilized during a 4-week run-in with twice-daily budesonide/formoterol pMDI 40/4.5 µg x 2 inhalations (160/18 µg daily) received:

- twice-daily budesonide/formoterol pMDI 40/4.5 µg x 2 inhalations (160/18 µg daily)

- once-daily budesonide/formoterol pMDI 80/4.5 µg x 2 inhalations (160/9 µg daily; evening)

- once-daily budesonide pMDI 80 µg x 2 inhalations (160 µg daily; evening).

Once-daily budesonide/formoterol demonstrated better efficacy than once-daily budesonide for most pulmonary-function variables.

Twice-daily budesonide/formoterol (160/18 µg daily) maintenance therapy was more effective than stepping down to once-daily dosing (160/9 µg daily).

References:
Once- vs Twice-Daily Budesonide/Formoterol in 6- to 15-Year-Old Patients With Stable Asthma. PEDIATRICS Vol. 126 No. 3 September 2010, pp. e565-e575 (doi:10.1542/peds.2009-2970).

Image source: Please note that the photo used to illustrate this blog post shows a dry powder inhaler (DPI) rather than a MDI. Combination formulation containing budesonide and formoterol - unopened Symbicort Turbuhaler (left) and opened (middle and right), Wikipedia, public domain.

Allergy Notes