Happy Wheezer/Happy Parent/ Happy Doctor (?) Andrew Bush MD FRCP FRCPCH FERS Imperial College & Royal Brompton Hospital a.bush@imperial.ac.uk
Conflict of Interest AB has no financial or other COI There will be discussion of off-label and unlicensed use of asthma medications
Aims of the Presentation Discuss the clinical approach to the pre-school child with wheeze Show how recent advances in understanding preschool wheeze impact on treatment Suggest approaches to the unhappy child, the unhappy parent, and the unhappy Dr I will NOT discuss epidemiology many scientific insights, but does not help me decide on treatment
Everyone happy? No treatment without a diagnosis What are the possibilities lessons from pathology Cui bono? (or for the classically challenged, who s it all for?) Summary and conclusions
Is it true wheeze? < 50% agreement between parents and clinicians on whether child wheezed; only 11% parents mentioned whistling Arch Dis Child 2000; 82: 327-32 Only 32% agreement between parents and physicians Objective recording correlated with physician report Nurses and parents were not reliable J Asthma 2004; 41: 845-53 Video-questionnaire: 30% parents used words other than wheeze to describe wheeze, or wheeze to describe non-wheeze sounds Arch Dis Child 2001; 84: 31-4 Video-questionnaire helps identify UA abnormalities Arch Dis Child 2005; 90: 961-4
All that wheezes is not asthma! Take a good history, detailed physical examination Targeted investigations Many need none Selective approach THEN, consider phenotypes and what treatment should be given (if any)
Isolated chronic cough is rarely if ever due to asthma Cough variant asthma is overdiagnosed and over-treated, to the detriment of children!
Coughs and Wheezes... Fall into one of five categories! Normal child (hardest diagnosis) Serious illness - eg CF, TB (rare, but essential to get right) An asthma syndrome Minor problems (rhinitis, reflux) which may mimic or exacerbate wheezing syndromes Overanxious, psychological
Normal Childhood Respiratory Symptoms Normal Cough Post-viral/bronchiolitic cough Viral colds: 10% children have >10/year, may have symptoms >2 weeks Acute otitis media: many children have >3/year Pertussis and its relatives Nursery School Syndrome Usually 1 st Child Early placement in child care facility Repeated viral infections, one viral cold merging into another No response to antibiotics, bronchodilators, ICS, etc.
Right sided aortic arch Diverticulum of Kommerel (arrow) Anomalous left subclavian artery
Points in the History - 1 Is it really wheeze? Upper airway symptoms prominent? Symptoms from first day of life Sudden onset symptoms Chronic moist cough/sputum reliable!
Points in the History - 2 Worse after meals, irritable feeder, arches back, vomits Systemic illness or immunodeficiency Continuous, unremitting symptoms
Physical Examination Clubbing, weight loss, failure to thrive Upper airway disease tonsils, rhinitis, NASAL POLYPS Unusually severe chest deformity Fixed monophonic wheeze, stridor, asymmetrical signs Signs of cardiac or systemic disease
Everyone happy? No treatment without a diagnosis What are the possibilities lessons from pathology Cui bono? (or for the classically challenged, who s it all for?) Summary and conclusions
Symptom Patterns Episodic (viral) wheeze Wheeze in association with (usually) clinically diagnosed viral URTI NOT the same as transient wheeze (Colt Ashford) Multi-trigger wheeze Wheeze both with viral URTI and with other triggers between URTIs Not the same as multiple trigger wheeze BUT PLEASE NOTE Phenotypes may not be stable (nor is any form of childhood asthma) There may be overlaps Parents may not appreciate interval symptoms
What about Pathology Helsinki Cohort Infants 3-26 months sgaw and BDR Clinically indicated rigid bronchoscopy A (reduced sgaw, BDR, n=16); B (reduced sgaw, no BDR, n=22); C (normal sgaw, n=15) RBH Cohort Children age 7-58 months Video-questionnaire (confirmed vs. reported vs. none) Clinically indicated FOB Confirmed wheeze (n=16), reported (unconfirmed) wheeze (n=14), control (n=10)
Infants (median age 1 year) Preschool children (median age 3 years) Eosinophils (%) 1.25 1.00 0.75 0.50 0.25 0.00 Reversible airflow obstruction NS Normal lung function EG2 volume density (%) 4 3 2 1 0 Confirmed wheeze p < 0.05 Controls 10.0 NS 10.0 p < 0.01 RBM (µm) 7.5 5.0 2.5 RBM (µm) 7.5 5.0 2.5 0.0 Reversible airflow obstruction Normal lung function 0.0 Confirmed wheeze Controls Saglani et al AJRCCM 2005 Saglani et al AJRCCM 2007
EVW & MTW: Different Pathology Severe pre-school wheezers divided on history into: Episodic viral wheeze (EVW) Multiple trigger wheeze (MTW) Controls EG2+ volume density (%) 4 * 3 2 1 0 VW IW Ctrl EVW MTW Controls RBM thickness (µm) 8 7 6 5 4 3 2 1 0 VW IW Ctrl EVW MTW Controls *
Symptom Patterns Episodic (viral) wheeze Wheeze in association with (usually) clinically diagnosed viral URTI NOT the same as transient wheeze! NO eosinophilic inflammation ICS???? Multi-trigger wheeze Wheeze both with viral URTI and with other triggers between URTIs NOT the same as persistent wheeze! Eosinophilia and remodelling ICS!
Everyone happy? No treatment without a diagnosis What are the possibilities lessons from pathology Cui bono? (or for the classically challenged, who s it all for?) Summary and conclusions
Wheeze Treatment For All: More than just medications What else is inhaled? Where is medicine going?
Indications for Treatment Prevention of disease progression Cannot intervene SO, treat ONLY if symptoms mandate treatment Treatment of symptoms: what CAN be given Nothing Bronchodilators (β-2 agonist, anticholinergics) LTRAs (3 studies, conflicting results) Inhaled corticosteroids Oral Corticosteroids
Intermittent ICS 129 children age 1-6 years FP 750 mcg bd vs. placebo with acute episodic (viral) wheeze In 40 weeks, 8% FP vs. 18% placebo were given prednisolone (43 vs. 93; OR 0.49, 0.30-0.83) BUT: SAFETY 10% children have > 10 colds/year There was a growth effect (-0.24 Z score) Adrenal function only crudely assessed NEJM 2009; 360: 339-53
Intermittent vs. Continuous ICS 278 children aged 12-15 months randomised +ve modified API Nebulised budesonide (only FDA approved ICS in preschoolers!) Regimens: I mg neb BUD for 7 days with URTI (n=139) 0.5 mg BUD neb regularly (n=139) NO PLACEBO LIMB! N Engl J Med 2011; 365: 1990-2001
What have we learned? Continuous BUD does Not prevent exacerbations Not make them any less severe Not lead to any less acute treatment Does increase the steroid dose taken BUT, this does not tell us whether intermittent BUD was at all helpful!
Episodic Treatment for Episodic problems (if needed) FIRST CHOICE: Nothing SECOND CHOICE: Intermittent bronchodilators THIRD CHOICE: Intermittent LTRA Potentially safer than ICS Fourth: Intermittent high dose ICS Dose and duration unknown, MONITOR carefully COUNCIL OF DESPAIR: Cmbination therapy Evidence base = zero
Oral Prednisolone Parent-initiated 217 children, already one admission Hospital-initiated 687 children (atopy NOT an exclusion) Parent initiated treatment at next exacerbation No benefit seen Clinically diagnosed acute viral wheeze Time to hospital discharge Lancet 2003; 362: 1433-8 NEJM 2009; 360: 329-38
Prednisolone: Ineffective
Episodic (viral) Wheeze: The role of Prednisolone NOT a community medication NOT a routine 2 ry care medication (Possibly) multi-trigger wheeze with a severe exacerbation (Possibly) any severe episodic (viral) wheeze heading for PICU
Preschool Wheeze 3 steps USUALLY ONLY IN MULTIPLE - TRIGGER WHEEZE Step 1 Inhaled BUD 400 mcg bd OR, montelukast 4 mg od Step 2 Stop treatment after c. 8 weeks Step 3 (Only if response to Step 1) Restart BUD, titrate to lowest dose OR, restart montelukast
Everyone happy? No treatment without a diagnosis What are the possibilities lessons from pathology Cui bono? (or for the classically challenged, who s it all for?) Summary and conclusions
What OUGHT to be done? Unhappy child, unhappy parent Treat child along standard lines Happy child, unhappy parent: Find out WHY! Fear of a diagnosis? Overanxious? Disruptive symptoms? Is it right to give medications which may be ineffective to a child when the parent has the problem? 2nd opinion? Unhappy Dr Phone a friend!
Everyone happy? No treatment without a diagnosis What are the possibilities lessons from pathology Cui bono? (or for the classically challenged, who s it all for?) Summary and conclusions
Take Home Messages Make sure it is wheeze; make sure you are not missing a diagnosis (history and examination) Classify pre-school wheeze as episodic (viral) and multi-trigger There are no disease-modifying therapies, so treat episodic symptoms episodically (if they need treatment!) Do NOT use oral corticosteroids for pre-school episodic (viral) wheeze Only treat the child if the CHILD needs treatment If the parents need treatment, find out why and what And if YOU are unhappy, GET A SECOND OPINION
Thank you for listening!