Asthma/Food Allergy

From the 20th Annual Las Vegas Postgraduate Pediatric Conference, Advances in Pediatrics, presented by the American Academy of Pediatrics, California Chapter 2

Michael J. Welch, MD, Clinical Professor of Pediatrics, University of California, San Diego, School of Medicine,Co-Director, Allergy and Asthma Medical Group and Research Center, San Diego, CA

Educational Objectives

The goals of this program are to improve management of pediatric asthma and food allergies (FAs). After hearing and assimilating this program, the clinician will be better able to:

1.   Compare the 2007 National Heart, Lung, and Blood Institute (NHLBI) clinical  guidelines for management of pediatric asthma to earlier versions.

2.    Classify patients with asthma according to disease severity and level of control.

3.    Cite arguments for use of inhaled corticosteroids and leukotriene agonists in the management of mild persis­tent pediatric asthma.

4.    Explain the difference between FA and food intolerance, and identify the most common pediatric FAs.

5.    List the recommended steps for treating a significant allergic reaction in a child with a known FA.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Welch has received grant and/or research support from Alcon, Allux Medical, AstraZeneca, Boehringer Ingelheim, Capnia, Clay-Park Laboratories, Critical Therapeutics, Genentech, GlaxoSmithKline, Hoffmann-La Roche, Kos Pharmaceuticals, MediciNova, MedPointe,  Merck & Co., Novartis, Nycomed US, Pharmaxis, Rigel Pharmaceuticals, sanofi-aventis, Schering-Plough, Teva Pharmaceuticals USA, and Wyeth Pharmaceuticals. He has been a consultant and/or speaker for Abbott Laboratories, Adelphi, the American Academy of Pediatrics, AstraZen­eca, AtheroGenics, CyDex Pharmaceuticals, Genentech, GlaxoSmithKline, Merck & Co, Novartis, Pfizer, sanofi-aventis, Schering-Plough, Sepracor, and Teva Pharmaceuticals USA. The planning committee reported nothing to dis­close.

Acknowledgements

Dr. Welch spoke at 20th Annual Las Vegas Postgraduate Pediatric Conference, Advances in Pediatrics, held April 16-19, 2009, in Las Vegas, NV, and sponsored by the American Academy of Pediatrics, California Chapter 2. The Audio-Digest Foundation thanks Dr. Welch and the American Academy of Pediatrics, California Chapter 2 for their cooperation in the production of this program.

New NHLBI Guidelines for Asthma:Is Anything Really New?

Introductory remarks: new National Heart, Lung, and Blood Institute (NHLBI) guidelines for diagnosis and man­agement of asthma differ only slightly from previous version; written and published in 2007 (appeared in 2008); only available online

Guidelines unchanged in 2007: severity dictates therapy; must make distinction between intermittent and persistent; “rule of 2s” still embedded in guidelines; 4 levels of asthma severity (intermittent; 3 sublevels of persistent); in­haled corticosteroids (ICS) preferred for all levels of persistent asthma; use of Asthma Action Plans; spirometry still recommended

Rule of 2s: if symptoms present >2 days per week or >2 nights per month, asthma categorized as persistent; within this category, disease must be classified as mild, moderate, or severe; however, as severity of asthma not constant, must monitor patients for changes; as severity changes, therapy likely to change

Guidelines updated in 2007: category of “mild intermittent” disease eliminated (now just “intermittent”); concepts of “impairment”, “risk”, and “control” introduced (always included in guidelines, but now given new terminology); impairment  —refers to symptoms; risk  —  refers to likelihood that patient will eventually have exacerbation of asthma and present to emergency department (ED) or hospital, or need course of oral corticosteroids; control  —  refers to level of patient’s asthma control; emphasis now on monitoring control (considered more important than disease severity classification); must be done with validated tool (eg, spirometry); new guidelines conclude that ICS therapy probably does not make difference in prevention of airway remodeling; steps of therapy increased from 4 to 6; update on asthma medications available

Classification of asthma severity: impairment domain  —  in addition to usual questions about daytime and nighttime symptoms, physicians now instructed to ask how often patient uses short-acting b-agonist (SABA; eg, albuterol) and about interference with normal activities; risk domain  —  guidelines now require physicians to count number of exacerbations per year (if >2, patient candidate for daily controller medication, particularly if 1 of 2 major risk fac­tors for asthma [parental history of asthma or history of eczema] present)

Classification of control: new guidelines also require physicians to classify patient’s asthma as “well-controlled,” “not well-controlled” or “very poorly controlled”; concept of symptom control important (goal of therapy), but speaker considers classification unnecessary

Office spirometry in pediatrics: study comparing spirometry done in office by pediatricians and in pulmonary func­tion test laboratory found office procedures not done well; error rate too high (22% of tests unacceptable; 21% in­terpreted incorrectly) to suggest spirometry should be done routinely in pediatric office, unless physician highly trained, certified, and experienced

Childhood Asthma Control Test (ACT): validated down to age 4 yr; adult questionnaire for teenagers; 4-question form completed by patient, 3-question form completed by parent; total score can determine whether patient’s asthma under good control; benefits  —  simple and short; assesses control; encourages child-parent dialogue; easy to implement in office; online and easily downloaded

Airway remodeling and ICS therapy: airway remodeling and its important determinants not yet understood; ICS therapy does not uniformly prevent remodeling, but remains best means of controlling symptoms

Treatment steps: last guidelines had 4; step 1  —  SABA as needed; step 2  —  low-dose ICS monotherapy; step 3  —  low-to-medium dose ICS plus long-acting b-agonist (LABA); step 4  —  high-dose ICS therapy plus LABA and (if needed) systemic corticosteroids

New guidelines: step 4 (for patients with severe persistent disease) split into 2 steps because of availability of omal­izumab (Xolair; anti-IgE agent); now prescribed before placing patient on daily oral corticosteroids; step 3 (for moderate persistent disease) also split into 2 steps because of concerns about safety of LABAs; Food and Drug Administration (FDA) advises physicians to increase dose of ICS before moving on to combination therapy; however, combination therapy still offered as alternative as early as step 3; therefore, in speaker’s opinion, this split unnecessary

Treatment of patients <5 yr of age with persistent asthma: much of recommendations inferred from knowledge about adult population; guidelines continue to recommend use of ICS monotherapy primarily (little data about combination therapy in this age group; more difficult to deliver)

Treatment of mild persistent disease: new guidelines recommend low-dose ICS or, alternatively, leukotriene recep­tor antagonist (LTA); review of comparison studies of LTAs vs ICS in management of asthma found ICS therapy more effective, but arguments in favor of each persist; speaker’s recommendations  —  LTAs reasonable alternative for treatment of mild disease; monitor patients carefully with ACT

Choice of ICS: many available; 2 most critical determinants  —1) delivery system best for patient’s developmental stage; 2) optimal lung deposition; other factors  —  eg, potency, systemic effects, growth studies; can be controlled by dosage or do not occur at low doses; “trump card” whether drug on patient’s formulary; all ICS excellent medi­cations, but “sabotaged” by poor inhaler technique and “steroid phobia”; if no questions from parents, ask about their concerns and provide reassurance about safety of ICS therapy

Particle size and lung deposition of ICS: 2 newer hydro-fluoroalkane (HFA)-propelled aerosol drugs (beclometha­sone [Qvar] and ciclesonide [Alvesco]) have smaller particle size that results in good lung deposition; recom­mended for children (due to small airways); as particle size of ICS increases, lung deposition tends to decrease

Comments: incorrect inhaler technique rampant, and spacers do not solve problem; do not consider increasing medi­cation dose until patient’s compliance and inhaler technique assessed

Conclusions: ICS/LABA combination therapy effective and widely used in adults; be cautious and use guidelines to determine which children should be placed on combination therapy; in many cases, ICS monotherapy just as effec­tive

Practical Management of Food Allergies

Introductory remarks: adverse food reaction  —  defined as any untoward reaction to food or food additive; food al­lergy (FA)  —  reaction that has immunologic mechanism (IgE-mediated or non-IgE-mediated); food intolerance or sensitivity  —reaction that has nonimmunologic mechanism; patients can have both intolerance and allergy to same food (eg, milk)

IgE-mediated allergic reaction: IgE antibody on surface membrane of mast cells; contact with food allergen causes perforation of cells, resulting in release of histamine and other nonhistamine mediators (some cause immediate symptoms; others cause late-phase reaction)

Eight most common food allergies: any food can cause reaction, but >90% due to egg, milk, peanuts, tree nuts (4 most common in pediatrics), soy, wheat, fish, and shellfish; latter 4 tend to occur later in life

Symptoms of FA: cutaneous (hives associated with »80% of significant allergic reactions); gastrointestinal (GI; cramping, diarrhea, or repeated vomiting); respiratory; cardiovascular; some children exhibit only central nervous system symptoms

Oral allergy syndrome (OAS): local reaction to fresh fruits and vegetables (usually when raw); due to cross reactiv­ity between pollen and food; patients who have OAS not at serious risk for anaphylactic episode

Anaphylaxis: no agreement on diagnostic criteria; systemic allergic reaction; multiple organ systems may be in­volved; rapid onset; clinical manifestations vary from mild to fatal (cutaneous, respiratory, and GI symptoms most frequent); can be biphasic (initial phase of symptoms followed 6-8 hr later by second phase; not common, but war­rants keeping patient who presents with initial anaphylactic reaction under observation for few hr)

Basic treatment of anaphylaxis: immediate epinephrine imperative; in »99% of children, almost no contraindica­tions (most fatalities due to administration of drug too late or not at all); auto-injector (eg, EpiPen, Twinject) must be available at all times and locations child frequents; after administration of epinephrine, call should be placed to 911 for transport to ED; can add antihistamine; if no response to epinephrine within 5 to 10 min, repeat dose

Medications for front-line therapy: antihistamine; epinephrine auto-injector; albuterol useful in asthmatic patients when epinephrine not available; some data on use of activated charcoal for, eg, management of allergic reaction to peanuts (not standard recommendation for children due to potential for aspiration)

When to give epinephrine: general rule  —  epinephrine must be given if patient has more than cutaneous symptoms; however, not applicable in all cases; must make judgment based on patient’s clinical history

“Eighty percent rule”: recent study of fatalities due to FA found that in »80% of cases, patients knew about allergy, had asthma, and/or in age range of 10 to 29 yr; peanuts and tree nuts responsible; foods obtained or eaten outside of home; epinephrine not administered in timely manner; compliance with carrying auto-injector not as good in young adult population as in children and adults

Role of antihistamine: diphenhydramine (eg, Benadryl) standard; liquid form recommended; round dose up, rather than down; indicated when accidental ingestion of allergen suspected or for mild symptoms; do not give antihista­mine in place of epinephrine if signs or symptoms of anaphylaxis present

Auto-injectable epinephrine: fairly easy to use; generally administered between knee and hip; data from several studies suggest 15% to 35% of patients having anaphylactic episode require second dose (data possibly skewed); EpiPen auto-injector available in “2-Pak”, while Twinject contains 2 doses (second dose “hidden” inside device and must be administered by another individual with needle and plunger); speaker shows parents both options, advises about pros and cons of each, and involves them in choice of device; school officials often uncomfortable with Twin­ject (due to need to train health aides to administer second dose) and prefer that students carry 2 EpiPens

After giving epinephrine: symptoms should subside within 1 to 2 min (if not, or if they worsen, give second dose); return auto-injector to carrying case (bend needle back) and call 911; recommended that family bring used device to hospital for inspection to confirm dose administered correctly

Comments: in most cases, family will not use auto-injector device before expiration date; family members should be encouraged to use expired device to practice auto-injection technique on grapefruit; use of medical identification alert jewelry (eg, MedicAlert bracelet) also recommended; speaker finds MedicAlert products most durable

Food allergy action plan (FAAP): Food Allergy & Anaphylaxis Network (FAAN) recommends every patient with serious FA have FAAP; can download form from FAAN website; when completed, provides clear directions on when to administer epinephrine or antihistamine, and gives instructions on use of auto-injector

Recent changes in food labeling: manufacturers must now clearly indicate on label if product contains protein de­rived from one of 8 major food allergens; in addition, manufacturers increasingly labeling products with warning statements (eg, product “may contain” or “is manufactured on the same equipment that processes” food allergen); difficult for parents and physicians to know whether to heed or ignore these statements; FAAN study of warning labels  —  looked at 179 packages with advisory statements about peanuts; 13 products (»7%) had detectable levels of peanut protein; authors found no correlation between likelihood of detectable levels of protein and terminology of advisory statement; 9 of 13 products contained enough protein (>5 ppm) to cause anaphylactic reaction if full serving consumed

Peanut allergy (PNA) study: double-blind placebo-controlled study exposed 32 children with significant PNA to contact and inhalation challenges with peanut butter; results  —  no systemic reactions; 10 cases of minor local reac­tion; suggests casual exposure unlikely to elicit significant allergic reaction

Testing for FA: scratch test helpful when negative (has high negative predictive value); problematic when positive, as false-positive findings can occur (also true with radioallergosorbent [RAST] test); do not use intradermal skin tests (associated with high false-positive rate); benefits  —  helpful in monitoring patients to determine whether FA out­grown (commonly occurs with milk, egg, soy, and wheat allergies, but not as often with peanuts or tree nuts); can relieve significant burden placed on family by food avoidance

Prevention of FA (American Academy of Pediatrics [AAP] Position Statement): recent data suggest mother’s diet during pregnancy or breastfeeding not important in prevention of FA; in high-risk infants, breastfeeding decreases chance of developing eczema, milk allergy, and wheezing during first 2 yr of life; in bottle-fed high-risk infants, use of hydrolyzed formula may also help delay or prevent allergic disease (soy formula not recommended)

Early exposure to peanuts and prevalence of PNA: study compared prevalence of PNA in children of primary school age in Israel (where infants often given peanut-flavored teething biscuits) to those in United Kingdom (UK), where exposure of infants to peanut largely avoided; relative risk of developing PNA »17 times higher in UK; re­sults suggest possible prevention protocol (ie, introducing consumption of peanut earlier in life to induce tolerance)

Oral immunotherapy: early data suggest that patients with PNA can be desensitized by giving peanut in small incre­mentally increasing doses until maintenance dose reached (and continuing that dose on daily basis thereafter)

Suggested Reading

Bock SA et al: Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 119:1016, 2007; Du Toit G et al: Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Al­lergy Clin Immunol 122:984, 2008; Gibson PG et al: Long-acting beta2-agonists as an inhaled corticosteroid-sparing agent for chronic asthma in adults and children. Cochrane Database Syst Rev (4):CD005076, 2005; Hefle SL et al: Consumer at­titudes and risks associated with packaged foods having advisory labeling regarding the presence of peanuts. J Allergy Clin Immunol 120:171, 2007; Jones SM et al: Clinical efficacy and immune regulation with peanut oral immunotherapy. J Al­lergy Clin Immunol 124:292, 2009; Kelso JM: A second dose of epinephrine for anaphylaxis: how often needed and how to carry. J Allergy Clin Immunol 117:464, 2006; Kim JS: Food allergy: diagnosis, treatment, prognosis, and prevention. Pedi­atr Ann 37:546, 2008; Lack G: Clinical practice. Food allergy. N Engl J Med 359:1252, 2008; Leach CL: The CFC to HFA transition and its impact on pulmonary drug development. Respir Care 50:1201, 2005; National Asthma Education and Pre­vention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Re­port 2007. J Allergy Clin Immunol 120(5 Suppl):S94, 2007; Ng D et al: Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev (2):CD002314, 2004; Scarfone RJ et al: Demonstrated use of metered-dose inhalers and peak flow meters by children and adolescents with acute asthma exacerbations. Arch Pediatr Adolesc Med 156:378, 2002; Simonte SJ et al: Relevance of ca­sual contact with peanut butter in children with peanut allergy. J Allergy Clin Immunol 112:180, 2003; Spahn JD, Szefler SJ: Steroid therapy for asthma in children. Curr Opin Pediatr 19:300, 2007; Zanconato S et al: Office spirometry in pri­mary care pediatrics: a pilot study. Pediatrics 116:e792, 2005.