Section Of Allergy/Immunology American Academy of Pediatrics Session: 4819 Q & A Workshop Respiratory Allergies Chitra Dinakar, M.D., F.A.A.P. Professor of Pediatrics University of Missouri-Kansas City Faculty, Allergy, Asthma and Immunology Children's Mercy Hospitals and Clinics email address: cdinakar@cmh.edu
Disclosures Astra Zeneca: Speakers Bureau Aerocrine: Speakers Bureau Training
Learning Objectives To understand the most recent clinical research findings in pediatric asthma, eczema, food, drug and insect allergy To be able to apply recent advances in pediatric allergy/immunology to clinical practice
Course of Asthma Activity Ontario health data, 15-year follow-up study of 613,394 patients Primary outcome: active asthma (any physician claim ICD9 493; ICD 10 J 45, J 46) Secondary outcome: gap in asthma activity of 2 years or more Persistent asthma: 2 year gap between asthma claims not present Gershon A, Guan J, Victor C, et al: The course of asthma activity: a population study. J Allergy Clin Immunol 2012;129:679-686.
Course of Asthma Activity 82.3% had active asthma during follow-up, with a median of 4 asthma-related claims per person. 74.6% had at least a 2-year gap between claims. Factors associated with increased asthma activity: higher number of previous asthma claims; older and younger age, particularly 65 years or old presence of chronic obstructive pulmonary disease. Gershon A, Guan J, Victor C, et al: The course of asthma activity: a population study. J Allergy Clin Immunol 2012;129:679-686.
Asthma 'Remissions Are Common--But Most Patients Have Active Disease Study limitations: individuals may or may not use healthcare when disease is active (or inactive);asthma definition; potential misclassification) Most patients have active asthma; periods of "remission" occur and are prolonged 3/4 of patients had a gap of at least 2 years in their asthma activity The natural course of asthma is to wax and wane--but that it doesn't really resolve. Gershon A, Guan J, Victor C, et al: The course of asthma activity: a population study. J Allergy Clin Immunol 2012;129:679-686.
Should ucontrolled asthmatic children without overt GERD be treated? Lansoprazole for children with poorly controlled asthma; a randomized controlled trial. Writing Committee for the American Lung Association Asthma Clinical Research Centers. JAMA. 2012 Jan 25;307(4):373-81.
Lansoprazole in children with uncontrolled asthma Study of Acid Reflux in Children with Asthma (SARCA) Lansoprazole vs placebo with poorly controlled asthma Masked, PC RCT N=306, 19 USA academic centers f/u for 24 weeks
Lansoprazole in children with uncontrolled asthma Primary outcome: ACQ (asthma control questionnaire) Secondary outcome measures: FEV1, asthma related quality of life, or rate of episodes of poor asthma control) N=115 with esosphageal ph studies, GER =43% AE: resp infections in lansoprazole group (RR: 1.3)
No statistically significant difference in primary or secondary outcomes No Rx effect in positive ph probe sub-group Lansoprazole for children with poorly controlled asthma; a randomized controlled trial. JAMA. 2012 Jan 25;307(4):373-81.
Adverse events: No difference in activity related fractures URTI, sore throats and bronchitis? Non-acid reflux worsening asthma Does not evaluate GER and cough Lansoprazole for children with poorly controlled asthma; a randomized controlled trial. JAMA. 2012 Jan 25;307(4):373-81.
Do children on ICS attain predicted adult height? NEJM 2012; 367; 904-12
ICS and Final Adult Height Transient decrease in height 1-4 yrs after initiation of ICS Rx in pre-pubertal children; not thought to decrease final adult height Continuation of the CAMP study; adult height of participants measured Subjects were given budesonide 400 mcg, nedocromil 16 mg or placebo daily starting at age 5-13 yrs 943/1041 (96%) had final adult ht. measured at ~ 25 yrs Adjusted for demographic variables, initial height and asthma features at trial entry
Mean adult ht was 1.2 cm lower in the budesonide group than placebo (p=0.001; CI -1.9 to -0.5) ) and not stat. sig. different in Nedocromil group NEJM 2012; 367; 904-12
A larger daily ICS does in first 2 yrs was associated with lower adult ht (p=0.007) The reduction in adult height in budesonide group was similar to placebo after first 2 yrs (-1.3 cm) During first 2 years decreased growth velocity occurred primarily in pre-pubertal children
ICS and Adult Height The initial decrease in height associated with ICS use in pre-pubertal children persisted as a reduction in attained adult height of approximately half an inch, though the decrease was not progressive nor cumulative NEJM 2012; 367; 904-12
Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%) Data from 67 phase I to IV clinical trials Prespecified primary analysis: incidence of primary malignancy in 32 RDBPC trials
Incidence rates per 1,000 patient-years were omalizumab (4.14; 95% CI, 2.26-6.94), placebo (4.45) (95% CI, 2.22-7.94) No association was observed between Omalizumab treatment and malignancy; the rate was below unity (0.93) JACI 2012; 129; 983-9
Hypertonic Saline and Viral-induced Wheezing Rhinovirus: main cause of acute wheezing episodes in preschool children; associated with decreased mucus clearance RCT evaluated inhaled hypertonic saline as a treatment option 41 children, mean age 32 months, seen in ED for wheezing X 1 albuterol, then 4 ml of inhaled hypertonic 5% saline, or normal saline Both Rx given with 0.5 ml albuterol: x2 q 20 minutes, then x 4 in the ED daily if the child was hospitalized. Ater D, Shai H, Bar B-E, et al: Hypertonic saline and acute wheezing in preschool children. Pediatrics. 2012;129:e1397-e1403.
Hypertonic Saline improves viral-induced Wheezing Primary Outcome: Length of stay (LOS) Secondary outcomes: admission rate and clinical severity score LOS: Median length of stay : 2 (HS group) vs 3 days (NS group) (p=0.027) Hospital admission rates were 62% versus 92%, respectively Improvements in clinical severity scores but not between the groups. Majority needed hospitalization (92%)- higher rate than before; greater disease severity; milder severity improved after prerandomization albuterol Groups were younger (less than 4 years) Inhaled hypertonic saline can improve outcomes in preschool-aged children with acute wheezing. Ater D, Shai H, Bar B-E, et al: Hypertonic saline and acute wheezing in preschool children. Pediatrics. 2012;129:e1397-e1403.
Hay Fever during Christmas? New onset of alder pollen allergies in 15-yr old children attending a school in Grabs, a village in n Switzerland They had symptoms during the winter, a time when runny noses are typically attributed to viral infections The genesis of this unusual occurrence was the serendipitous planting of 96 hybrid trees with winter resistance about 10 years ago along a commonly commuted boulevard This resulted in exposure to alder pollen in December (the geographical flowering season) and development of IgE antibodies causing symptoms Grassnner M et al. NEJM 368;4:393.
Grassnner M et al. NEJM 368;393
High-dose SLIT with single-dose grass pollen extract in children RCPCT: efficacy and safety of high-dose SLIT in children allergic to grass pollen in 34 centers in Germany and Polans After a baseline seasonal observation, 207 children aged 4 to 12 years with grass pollen-allergic rhinitis/ rhinoconjunctivitis with/without bronchial asthma (Global Initiative for Asthma I/II) received either high-dose grass pollen SLIT or placebo daily for 1 pre-/co-seasonal period. High-dose sublingual immunotherapy with single-dose aqueous grass pollen extract in children is effective and safe: A double-blind, placebo-controlled study. Ulrich Wahn et al, SLIT Study Group. The Journal of Allergy and Clinical Immunology - October 2012 (Vol. 130, Issue 4, Pages 886-893.e5,
High-dose SLIT with single-dose grass pollen extract in children The primary end point: change of the area under the curve of the symptom-medication score (SMS) from the baseline season to the first season after start of treatment. Secondary outcomes were well days, responders, immunologic changes, and safety. High-dose sublingual immunotherapy with single-dose aqueous grass pollen extract in children is effective and safe: A double-blind, placebo-controlled study. Ulrich Wahn et al, SLIT Study Group. The Journal of Allergy and Clinical Immunology - October 2012 (Vol. 130, Issue 4, Pages 886-893.e5,
Mean changes in area under the curve of the SMS were - 212.5 (active group) and -97.8 (placebo group (P =0.0040). Rhinoconjunctivitis SMS (p=0.002), separated symptom (p=0.012) and medication scores (p=0.022) were statistically different The number of well days and the percentage of responders were greater in the active group. High-dose sublingual immunotherapy with single-dose aqueous grass pollen extract in children is effective and safe: A double-blind, placebo-controlled study. Ulrich Wahn et al, SLIT Study Group. The Journal of Allergy and Clinical Immunology - October 2012 (Vol. 130, Issue 4, Pages 886-893.e5,
Changes in allergen-specific IgE and IgG levels indicated a significant immunologic effect (increase in IgG1 and IgG4). The treatment was well tolerated, and no serious treatmentrelated events were reported. Significant improvement on symptoms, well tolerated, and viable option in children with grass-pollen rhinoconjunctivitis Responder analysis: patients with 40 decrease in SMS from baseline at end of 1 treatment period: 50% responders in active group versus 33% in placebo group High dose SLIT in children allergic to grass pollen aged 4-12 years is safe and efficacious High-dose sublingual immunotherapy with single-dose aqueous grass pollen extract in children is effective and safe: A double-blind, placebo-controlled study. Ulrich Wahn et al, SLIT Study Group. The Journal of Allergy and Clinical Immunology - October 2012 (Vol. 130, Issue 4, Pages 886-893.e5,
Summary: Suggested Practice Counsel families: Changes that while some patients with asthma have periods of clinical remission, the majority continue to have active disease there is an initial decrease in height of about ½ inch associated with ICS use in pre-pubertal children, though not progressive or cumulative There is no increased risk of malignancy with use of Xolair
Suggested Practice Changes Consider administration of inhaled hypertonic saline, along with albuterol, in preschool-aged children with acute wheezing Be aware of out of season seasonal allergic rhinitis due to geographical and climate changes Consider SLIT as an option in children with uncontrolled grass pollen rhinitis/rhinoconjunctivitis
Thank You For Your Attention!
Asthma Medications during Pregnancy and Risk of Birth Defects Association between maternal asthma medication use and the risk of birth defects in offspring; a population-based, case control study of 2,853 infants using data from the National Birth Defects Prevention Study Periconceptional use (from 1 month before pregnancy through the third month of gestation) of asthma medications (bronchodilators or anti-inflammatory drugs) Most birth defects were unrelated to use of asthma medications. However, significant positive associations: isolated esophageal atresia and bronchodilators, adjusted odds ratio (OR) 2.39; isolated anorectal atresia and anti-inflammatory drugs, OR 2.12; and omphalocele and either type of asthma medication, OR 4.13. Further studies are needed to clarify whether the associations are attributable to asthma medications or the severity of asthma itself. Lin S, Munsie JPW, Herdt-Losavio ML, et al: Maternal asthma medication use and the risk of selected birth defects. Pediatrics. 2012;129:e317-e324.
Are Inhaled Glucocorticoids Safe during Pregnancy? Data from a Danish national birth cohort study to assess the association between ICS during pregnancy and disease risk 4,083 live singleton offspring born to pregnant women with asthma Of 1,231 pregnant mothers receiving ICS, 79.9% used budesonide. Offspring were followed up to a median age of 6.1 years. Most categories of disease not significantly increased in offspring. Exception: increased risk of endocrine, metabolic, and nutritional disorders: hazard ratio 1.84 (similar for mothers using budesonide). The possible association with endocrine, metabolic, and nutritional disorders warrants further study. Currently only budesonide has a class B indication for pregnancy; approximately 80% of this study cohort was treated with budesonide Tegethoff M, Greene N, Olsen J, et al: Inhaled glucocorticoids during pregnancy and offspring pediatric diseases: a national cohort study. Eur Respir J. 2012;185:557-563.