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Wheezy Child: Diagnostic and Therapeutic Approach

Wheezy Child: Diagnostic and Therapeutic Approach. Remziye Tanaç, M.D. Ege University Faculty of Medicine Department of Pediatric Pulmonology and Allergy, Izmir, Turkiye.

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Wheezy Child: Diagnostic and Therapeutic Approach

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  1. Wheezy Child: Diagnostic and Therapeutic Approach Remziye Tanaç, M.D. Ege University Faculty of Medicine Department of Pediatric Pulmonology and Allergy, Izmir, Turkiye.

  2. Wheezing; Generally a pathological sound ( sometimes can be heard normally during forced expiratory maneuver) which shows pathological obstruction of lower respiratory tracts. Wheezy Child; A child whose wheezing persists more than one month and/or has had 3 or more wheezing attacks.

  3. Typical Wheezing Transient wheezing Nonatopic (viral) Atopic (persistent) Severe intermittent (PRACTALL) Atypical Wheezing GERH Cystic fibrosis Primary ciliary dyskinesia Immune deficiencies BPD Heart diseases FBA Tbc Congenital anomalies

  4. Tucson Children’s Respiratory Study n= 1246 Beginning in 1980, birth-cohort-11 years 49 % wheezing in 0-6 years. Martinez FD. et all. N. Eng. J. Med. 1995, 332: 133-138

  5. Tucson Children’s Respiratory Study Taussig LM et al JACI2003;111:661-75

  6. Transient Early Wheezing • Exists in 0-3 years. • Disappears in third year. Responsible for 80 % in first year 60 % in second year 40 % in third year of all. • Similar frequency history in family. • No asthma or atopy history in family. • No atopy, eosinophilia or inflammation in infant. • Wheezing after viral infections.

  7. Transient Early Wheezing (Lung Function Tests) • Lung functions are decreased at birth. • Improves as the infant gets older. • Can’t exactly catch his/her coequals. • PEF variability in 11 years old and response to metacholine are similar to normal children. • Becomes COPD if smokes in adulthood.

  8. Transient Early Wheezing Risc Factors • Prematurity, low birth weight • Maternal smoking during pregnancy or in postnatal period • Going to day-care center early • Siblings at home • Lower maternal age

  9. Non-atopic Wheezing • 40 % of persistent wheezy infants • They are non atopic. • Change in control of airway tonus Congenital, infection relation? • Attacks are related with viral infections (most commonly RSV) • RSV increases the risk until 10th year, ineffective after 13rd year. • Tucson Children’s Respiratory Study • 472 LRTI; 207 43.9% RSV 6814.4% Parainfluenza 68 14.4% Adenovirus, influenza, CMV, Chlamydia, rhinovirus, bacteria, mix infec. 129 27.3% non-infective pathogen

  10. Non-Atopic Wheezing (Lung function tests) • 0-3 years, RSV (+) Lung function test < RSV(-) • Bronchodilatator response RSV (+) Lung fxn test > RSV (-) The difference persists during 11st year.

  11. Atopic Wheezing (Asthma) • 60 % of persistent wheezers. • 50 % : before 3rd year, 80 % : before 6th year • Family asthma history • Allergic rhinitis or atopic dermatitis in patient • Eosinophilia, high serum IgE level, BHR(+) • Early aeroallergen sensitization

  12. Early and Late Atopic Wheezing Early atopic wheezing If atopic wheezing of children has been detected before 3 years old and if it persists during 6th year Have worse lung function tests, more severe bronchial reactivity, higher serum IgE levels. Late atopic wheezing If atopic wheezing of children has been detected after 3rd year and if it persists during 6th year Have better lung function tests, milder bronchial reactivity, less high serum IgE levels.

  13. Increases Early allergic sensitization Sensitization with some aeoroallergens (perennial) Eosinophilia Decreases In young ages Contact with other children Contact with cats Contact with some farm animals Allergic sensitivity and asthmaFactors which alter asthma risc

  14. Tucson Children’s Respiratory Study Transient wheezing Asthma Viral inf. wheezing Taussig LM et al JACI2003;111:661-75

  15. CLINICAL INDEX FOR ASTHMA RISC Castro Rodriguez JA et al. AJRCCM 2000;162: 1403-6

  16. CLINICAL INDEX FOR ASTHMA RISC Castro Rodriguez JA et al. AJRCCM 2000;162: 1403-6

  17. Performance of Indexes

  18. Recurrent RTI Prolonged jaundice Meconium ileus Rectal prolapse Extreme sweating Steatorrhea Growth retardness Sweat test Cl > 60 mEq/l Mutation analysis Cystic Fibrosis

  19. H type TEF Swallowing malfunction Familial disautonomia Cleft palate Cerebral palsy Musculary dystrophia GERH Scintigraphy pH monitorization Aspiration Syndromes

  20. Airway wall insufficiency Laryngomalacia Tracheomalacia Subglottic hemangioma Vasculary ring Perihilar adenopathy Bronchoscopy HRCT MRI Airway Compression

  21. Congenital heart disease VSD, ASD, MS, hypoplastic left heart Tracheal bronchus Diaphragmatic hernia ECG ECHO CT Bronchoscopy Congenital Anomalies

  22. Immune Deficiencies • IgG and subgroup deficiencies • Selective IgA deficiency • X linked infantile agammaglobulinemia - Bruton • Common variable hypogammaglobulinemia IgA IgG IgG subgroup

  23. Nonspecific Airway Irritation • Child nursery centers • Tobacco smoke Active Passive • Air pollution SO2 NO NO2 Particles

  24. Infections • RSV, Adenovirus.... • Mycoplasma • Chlamydia • Tbc

  25. Agents in Respiratory Tract Infections with Wheezing

  26. RSV Complications • Acute Complications Apnea 0-6 ay 20 % SIDS • Long-term complications Airway hyperreactivity Wheezing-Asthma

  27. Long term prognosis of bronchial hyperreactivity seen in these patients

  28. RESULT RSV-LRTI Reactive airway 20-30 %

  29. EUTF Department Of Pediatric Pulmonology & Allergy1994 - 1998 Acute Bronchiolitis 161 More than 3 attacks 14.1 % Family atopy history (+) 25 %

  30. EUTF Department Of Pediatric Pulmonology & AllergyRetrospective

  31. If the diagnosis of patient is asthma with a high probability according to all criteria TREATMENT

  32. GINA 2006

  33. GINA 2006 TREATMENT STEPS INCREASE REDUCE Step 1 Step 2 Step 3 Step 4 Step 5

  34. GINA 2006 • Antiinflammatory • LTRA effective? • Bronchodilatators

  35. Efficacy of Bronchodilatator Usage

  36. Bronchodilatators • Double-blind, randomized, placebo, cross over Atopic, n=48, 3 months - 1 year 2 months 3x200 mg Salbutamol Clinical symptoms, Lung fxn tests Result; Partial recovery. No statistical difference. Chavasse R.:Arch.Dis.child. 2000, 2-5, 370-75

  37. Bronchodilatators b2 agonists (short acting) Atopic n=43 < 2 years Clinical Score +SD 3.75+1.25-2.80+1.65 p<0.01 02 saturation 94.8 + 2.84 %– 95.2+ 2.54 Effective(in acute period) Bentur L.:Pediatrics 1992:89,133-37 ICS + Bronchodilatator effective Teper A.M.: Am.J.Crit.Car.Med., 2005:171, 587

  38. Bronchodilatators Metaanalysis– <2 years b2 agonist (short acting) • Randomized placebo controlled 8 study 3 at home 2 in hospital 3 in Lung Function Test lab. • Symptom scores No obvious benefit under 2 years Bronchomotor tonus? Chavasse R.:Cochrane Database Sys.Rev. 2002: (3) CD 002873

  39. Result: The studies are not sufficient to make a certain comment (bronchomotor tonus?). But it can be used according to guidelines in patients who are thought to be asthma with a high probability.

  40. Efficacy of LTRA Usage

  41. LTRA (Asthma) • Double-blind, placebo controlled • n=689 n=228(placebo) n=461(LTRA) • 2-5 Years intermittent asthma • Duration 12 weeks • Symptom score • Drug usage Knorr B.:Pediatrics 2001: 108:3, 1-3 Phase I PreparationMono-blind Phase II Active Treatment(12 weeks)Double-blind Montelukast 4 mg*(n=461) Placebo Placebo (n=228) 0 2 14 Weeks

  42. 0.05 0.00 –0.10 –0.20 –0.30 –0.40 –0.50 –0.60 Placebo (n=227) Montelukast 4 mg* (n=458) Marked relief in symptoms. Change in Score (Mean ± SE) 0 2 4 6 8 10 12 Weeks in study (postrandomization) Knorr B et al. Pediatrics 2001;108:e48.

  43. LTRA (Asthma) • Placebo controlled study • n = 30 atopic asthma 2-5 years • Duration 4 weeks (montelukast 4 mg) • eNO, airway resistance (Rint) • Statistically significant difference in antiinflammatory effect and resistanceStraub D.A.:Chest 2005 ; 127:509-14

  44. Viral Infection – WheezingLTRA

  45. RSV RSV Inflammation IFNg Th1 T-cell activation IL-4, IL-5 Th2 Macrophages NK cells Neutrophils BasophilsMast cellsEosinophils TNFa,bRANTES IL-1 IL-6 Cysteinyl Leukotrienes (CysLTs) Inflammatorymediators Wheezing 48 van Schaik SM et al. Pediatr Pulmonol 2000;30:131-138

  46. p=0.006 p=0.009 500 cysLT concentration in secretion (log pg/ml) 50 Acute URI (n=17) Bronchiolitis (n=35) Recurrent wheeze (n=10) van Schaik SM et al. J Allergy Clin Immunol 1999;103:630-636

  47. Montelukast - RSV Post-Bronchiolitis • Randomized, double-blind, parallel • Hospitalized bronchiolitis • Proved RSV • 130 children • 3-36 months (mean 9 months) • Beginning of treatment: In 7 days • Duration of treatment: 28 days • Symptom score Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383

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