Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Wheezy Child: Diagnostic and Therapeutic Approach Remziye Tanaç, M.D. Ege University Faculty of Medicine Department of Pediatric Pulmonology and Allergy, Izmir, Turkiye. 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. 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 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 Tucson Children’s Respiratory Study Taussig LM et al JACI 2003;111:661-75 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. 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. 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 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 14.4 % Parainfluenza 68 14.4 % Adenovirus, influenza, CMV, Chlamydia, rhinovirus, bacteria, mix infec. 129 27.3 % non-infective pathogen 68 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. 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 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. Allergic sensitivity and asthma Factors which alter asthma risc 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 Tucson Children’s Respiratory Study Transient wheezing Viral inf. wheezing Asthma Taussig LM et al JACI 2003;111:661-75 CLINICAL INDEX FOR ASTHMA RISC Major criteria Minor criteria Parental asthma Allergic rhinitis Eczema Wheezing without common cold Eosinophilia > 4 % Castro Rodriguez JA et al. AJRCCM 2000;162: 1403-6 CLINICAL INDEX FOR ASTHMA RISC Loose index Stringent index Early wheezing Early frequent wheezing ≥ 3 + + 1 major or two minor 1 major or two minor Castro Rodriguez JA et al. AJRCCM 2000;162: 1403-6 Performance of Indexes OR Sensitivity Specifity PPV NPV Loose index 4 42 % 85 % 59 % 87-94 % Stringent index 7 16 % 97 % 77 % 84-92 % Cystic Fibrosis • • • • • • • Recurrent RTI Prolonged jaundice Meconium ileus Rectal prolapse Extreme sweating Steatorrhea Growth retardness • Sweat test • Cl > 60 mEq/l • Mutation analysis Aspiration Syndromes • H type TEF • Swallowing malfunction Familial disautonomia Cleft palate Cerebral palsy Musculary dystrophia • GERH • Scintigraphy • pH monitorization Airway Compression • Airway wall insufficiency Laryngomalacia Tracheomalacia Subglottic hemangioma • Vasculary ring • Perihilar adenopathy • Bronchoscopy • HRCT • MRI Congenital Anomalies • • Congenital heart • disease • VSD, ASD, MS, hypoplastic • left heart • Tracheal bronchus • Diaphragmatic hernia ECG ECHO CT Bronchoscopy Immune Deficiencies • IgG and subgroup deficiencies • Selective IgA deficiency • X linked infantile agammaglobulinemia - Bruton • Common variable hypogammaglobulinemia IgA IgG IgG subgroup Nonspecific Airway Irritation • Child nursery centers • Tobacco smoke Active Passive • Air pollution SO2 NO NO2 Particles Infections • • • • RSV, Adenovirus.... Mycoplasma Chlamydia Tbc Agents in Respiratory Tract Infections with Wheezing 0-12 months 1-5 years 6-15 years RSV RSV Rhinovirus P.Influenza P.Influenza Influenza Adenovirus Influenza Mycoplasma RSV Complications • Acute Complications Apnea 0-6 ay 20 % SIDS • Long-term complications Airway hyperreactivity Wheezing-Asthma Long term prognosis of bronchial hyperreactivity seen in these patients Symptom 2 years % 82 % 0,9 0,8 0,82 0,69 0,7 0,6 3.5 years 4-5 years 6-8 years 69 % 55 % 31 % 0,55 0,5 0,4 0,31 0,3 0,2 0,1 0 2 3,5 4-5 6-8 years years years years RESULT RSV-LRTI Reactive airway 20-30 % EUTF Department Of Pediatric Pulmonology & Allergy 1994 - 1998 Acute Bronchiolitis 161 More than 3 attacks 14.1 % Family atopy history (+) 25 % EUTF Department Of Pediatric Pulmonology & Allergy Retrospective 314 patients 0-5 years old GERH 18 % CF .006% Tracheal Br .006% Asthma 32 % FBA 1% Bronchiolitis Ob. .025% Viral Inf.? 33 % If the diagnosis of patient is asthma with a high probability according to all criteria TREATMENT GINA 2006 Daytime symptoms CONTROLLED PARTLY CONTROLLED None More than twice /week (twice or less/ week) Nocturnal symtoms/ awakening None Limitation of activities None Any Need for releiver/rescue treatment None More than twice /week PEF or FEV1 Exacerbations (twice or less/ week) UNCONTROLLED Any Normal < 80% predicted or personal best None One or more /year Three or more features of partly controlled asthma present in any week One in any week GINA 2006 REDUCE Step 1 TREATMENT STEPS Step 2 Step 3 INCREASE Step 4 Step 5 Asthma Education Enviromental Control As needed rapid acting 2 agonists As needed rapid acting 2 agonists Select one Select one Add one or more Add one or both Low-dose ICS Low-dose ICS + LABA Medium or high dose ICS+ LABA Oral steroid LTRA Medium or high dose ICS LTRA Anti-IgE Low-dose ICS + LTRA Theophylline Controller options Low-dose ICS + Theophylline GINA 2006 • Antiinflammatory • LTRA • Bronchodilatators effective? Efficacy of Bronchodilatator Usage 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 Bronchodilatators 2 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 Bronchodilatators Metaanalysis– <2 years 2 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 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. Efficacy of LTRA Usage LTRA (Asthma) • • • • • • Double-blind, placebo controlled n=689 n=228(placebo) n=461(LTRA) Phase I Phase II 2-5 Years intermittent asthmaPreparation Active Treatment Mono-blind Double-blind Duration 12 weeks Symptom score Drug usage (12 weeks) Montelukast 4 mg* (n=461) Placebo Placebo (n=228) 0 2 Knorr B.:Pediatrics 2001: 108:3, 1-3 14 Weeks Change in Score (Mean ± SE) 0.05 0.00 Placebo (n=227) Montelukast 4 mg* (n=458) –0.10 –0.20 –0.30 –0.40 –0.50 –0.60 0 2 4 6 8 10 12 Weeks in study (postrandomization) Marked relief in symptoms. Knorr B et al. Pediatrics 2001;108:e48. • • • • • 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 resistance Straub D.A.:Chest 2005 ; 127:509-14 Viral Infection – Wheezing LTRA RSV Inflammation RSV Th1 T-cell Th2 activation Macrophages NK cells Neutrophils TNFa, RANTES IL-1 IL-6 Inflammatory mediators 48 IFNg IL-4, IL-5 Basophils Mast cells Eosinophils Cysteinyl Leukotrienes (CysLTs) Wheezing van Schaik SM et al. Pediatr Pulmonol 2000;30:131-138 p=0.006 p=0.009 cysLT concentration in secretion (log pg/ml) 500 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 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 30 Montelukast (n=61) mean number %22 Placebo (n=55) mean number % 4 Symptom-free 20 day and nights (%) 10 p=0.015 0 0 7 14 Days 21 28 Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383 Age: 2-5 years (mean 44 months) Mild asthma ≥3 attacks in 12 months after URTIs Placebo Placebo run-in Montelukast 4 or 5 mg Weeks -3 -2 0 8 16 24 36 48 Visits 1 2 3 4 5 6 7 8 Bisgaard H et al. PREVIA Am J of Resp Crit Care Med 2005; 171, 315-22 Exacerbations / years 3 p0.001 2.34 32% 2 1.60 1 0 Montelukast 4 mg (n=265) Placebo (n=257) Bisgaard H et al. Am J of Resp Crit Care Med 2005; 171, 315-22 As a result; in patients who has asthma with a high probability, LTRA can be used due to the guidelines. But in patients whose asthma diagnosis is uncertain, good evaluation of the patient and more studies on this issue are needed for definite indication. According to GINA 2006, LTRA is effective in postinfectious asthma exacerbations. Usage and Efficacy of Inhaled Steroids Antiinflammatory Treatment Effectiveness ICS School Child, Adolescent, Adult • Reduction in symptoms • Improvement in lung functions • Improvement in airway reactivity • Reduction in admissions to emergency room and hospitalization Rytila P.:Allrgy 2004;59:839-41 Merkus PJFM.:Eur.resp.J. 2004;23:861-68 Boehmer ALM.:Carr.Op.IPL Pulm.Med. 2006;12:34-41 ICS Placebo controlled recurrent wheezing n = 30 age mean 16 (7-24) months Treatment: FP. 100-250 micrograms/day, duration 6 months Symptom score – 2 agonist usage Side effect (development, bone density) Result: effective, no side effects Teper A.M.:Ped.Pulmonol.2004;37:111-15 ICS Placebo controlled recurrent wheezing n = 26 age: (0-2) Treatment: FP 250 micrograms/day, duration 6 months Vmax – FRC Result: Effective Teper A.M.:Am.J.Crit.Care.Med. 2005;171: 584-89 ICS Placebo controlled wheezy child n = 62 Age: 11.3 (7-20) months Treatment: FP 200 micrograms/day, duration 3 months Symptom score, VmaxFRC Result: Ineffective, duration is short Hofius W.:Am.J.Crit.Care.Med. 2005;171:328-33 ICS Boehmer ALM: Cur.Op.Pulm.Med. 2006;12:34-41 ICS – Viral Wheezing Placebo controlled study n = 104 Age: 100 (84-119) months Treatment: BDP 400 mg/gün duration 6 months Number of attacks, score , FEV1 No difference from placebo Doul I.J.:BMJ. 1997;315:858-62 Beclomethasone 400 μg/gün Placebo Days with RTI sypmtoms % 16 ± 26 26 ± 29 Frequency (day/year) 5.6 ± 4.2 7.0 ± 6.1 Attack max score 3.2 ± 1.7 3.7 ± 1.8 Mean duration (day) 6.8 ± 6.0 6.3 ± 3.6 ICS – Viral Wheezing FEV1 Effective Doul I.J.:BMJ 1997;315:858-62 ICS – Viral Wheezing Placebo controlled study n = 40 Age:1.9 (0.8-6.0) years Treatment: 4 months Score, admission to E.R. Budesonide Placebo Daily score (med) 0.6 0.6 Symptom-free days (med) 73 78 30 31 Nocturnal / daytime cough 7.8/4.0 7.3/4.0 Nocturnal / daytime whe. 7.5/5.1 7.6/5.0 2.6 2.4 8.0 8.6 Total duration Acute episode No difference from placebo. Willson N.:Arch Dis.Child. 1995;72:317-20 Total score (mean) Number of episode Episode duration (d) Result: Although ICSs are less effective in young ages when compared to school children and adults, it’s still more effective than the other medications in these ages. Should be used in treatment. Treatment in 0-2 Years (asthma) • >3 exacerbations in last 6 months, responsive to bronchodilatators •In acute attack (intermittent), first choice is β2 agonists. •LTRA in viral wheezy child for controller effect •In patients with persistent asthma, first choice is inhaled steroids (100-200 µgr /day) •In frequently repetitive acute attacks, oral corticosteroids 3-5 days PRACTA L.L.Allergy 2008; 63;5-34 Treatment in 3-5 Years (asthma) • ICS first choice BDS 100-200 µgrx2 days or Flutic 50-125 µgrx2 days • Short acting β2 agonists, for every 4 hours 1-2 puff when needed • LTRA as a monotherapy in intermittent and mild persistent patients instead of ICS • If not fully controlled with ICS, add LTRA • If not still well controlled, add LABA according to age. Increase ICS dosage. Add theophylline. PRACTALL.ALLERGY 2008:63;5-34 Well-controlled Asthma • Daytime symptoms twice or less per week (not more than once on each day) • No limitations of activities due to asthma • Night-time symptoms 0-1 per month • Reliever/rescue medications twice or less per week • Normal lung function (if able to measure) • 0-1 exacerbations in the last year PRACTALL Allergy. 2008: 63;5-34 Result • Inhale steroids are the main drugs in the treatment. Should be used. • LTRA can be used as a monotherapy or with ICSs in post-infectious (viral) wheezings. • Bronkodilatators can be used in acute period or if needed. PRACTALL 2008-GINA 2006 Treatment of Atypic Wheezing • The underlying disease should be treated. Thanks...