Paediatric Update. Pre-School Wheeze: Decrees and pleas for the under three s. Julian Vyas Respiratory Paediatrician STARSHIP HOSPITAL

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1 Pre-School Wheeze: Decrees and pleas for the under three s Julian Vyas Respiratory Paediatrician STARSHIP HOSPITAL 8th July 2015

2 No Conflicts of Interest to Declare

3 what is wheeze? Definition: A wheeze is a high-pitched, musical, adventitious lung sound produced by airflow through narrowed airways.

4 what does wheeze mean? wheeze indicates turbulent i.e. abnormal airflow through an airway. Can be: acute or chronic focal or diffuse different monophonic or polyphonic Indicates underlying pathology see later

5 what is wheeze? Parental use of terminology is unreliable whistling, squeaking, gasping, abnormal rate or style of breathing, or same as cough (1-5) Tokelau (Crane, ISAAC Study) - video questionnaire - wheeze also used for SOB, and (6) cough terminology used by parents to describe noisy breathing Elphick, ADC : Elphick, ADC : Michel, ERJ : Elphick ERJ : Cane ADC : Cane, ADC : Crane, ERJ 2003

6 what is wheeze? Physician diagnosed wheeze Murray (2004): wheeze vs ipft (sraw) - <4y 458 children. 41% Parents reported wheeze in 1st year of life sraw: Never wheezed = parental observed but unconfirmed wheeze sraw: signif incr in those w Dr confirmed wheeze vs never, or unconfirmed (p<0.001) A proportion of parents may have limited understanding of what medical professionals mean by the term wheeze Murray, ADC, 2004, 89, 540

7 what is wheeze? Physician diagnosed wheeze Elphick (2004): 2 experienced Drs - compared wheeze heard by steth vs computerised acoustic analysis Both could discriminate between wheeze, crackles and rattle W: Convergent Validity k=0.07 (-0.13 to 0.26) - poor R: CV k= 0.11 (-0.05 to 0.27) - poor C: CV k= 0.36 ( ) - fair Wheeze: agreement between observers was poor stethoscope is unreliable for assessing Elphick, ADC, 2004, 89,1059 respiratory sounds in infants.

8 how common is wheeze? ALSPAC Study 1 : 26% of 6265 by 18/12 Tucson Study 2 : c33% by 3y 50% cumulative by 5y 3 1:4 Kiwi kids have asthma > 1:6 Kiwi adults 1. Henderson. Thorax 2008; 2. Martinez. NEJM, 1995; 3. Bisgaard, Ped Pulmonol 2007;

9 Wheeze Phenotypes Episodic Viral Wheeze Wheeze during discrete time periods - often assoc with viral RTI s. Symptom free between RTI s Less responsive to ICS Paul BRAND. ERS Taskforce on Pre-school wheeze. ERJ 2008; update ERJ 2014

10 Wheeze Phenotypes Multi Trigger Wheeze Wheeze with discrete exacerbations - as per episodic wheeze Also symptoms between episodes other triggers: exercise, smoke, allergens ICS responsive Paul BRAND. ERS Taskforce on Pre-school wheeze. ERJ 2008; update ERJ 2014

11 Wheeze Phenotypes Multi Trigger Wheeze vs Episodic Viral Wheeze Multi Trigger Wheeze Wheeze with discrete exacerbations - as per episodic wheeze Also symptoms between episodes other triggers: exercise, smoke, allergens ICS responsive Episodic Viral Wheeze Wheeze during discrete time periods - often assoc with viral RTI s. Symptom free between RTI s? less responsive to ICS Paul BRAND. ERS Taskforce on Pre-school wheeze. ERJ 2008; update ERJ 2014

12 Wheeze Phenotypes Long Term Outcomes Transient Children grow out of symptoms Persistent continue with symptoms Frequency /severity best predictor of ongoing Sx Various types Asthma Predictive Index proposed: Negative predictive value >> Positive pred value EVW vs MTW = rel poor predictor of long term outcome Neither EVW nor MTW considered as a de facto precursor for asthma.

13 Wheeze Phenotypes Evidence suggests: Distinction between EVW and MTW is not clear cut. Symptom patterns can change over time. Severity and frequency of episodes are important in deciding Rx. Optimal treatment may differ

14 Wheeze Phenotypes EVW? MTW Goes by age 6 Transient Where does Asthma sit in all this? Persistent Lasts beyond age 6

15 Phelan. JACI 2002 Paediatric Update

16 1. Asthma: 3/4 children with asthma before age 7 no longer have symptoms by age : Illi. Lancet 2006; 2. Global Asthma Report 2014

17 DECREE 1 A PREVIOUS DX OF EVW OR MTW SHOULD NOT BE SLAVISHLY ADHERED TO

18 What causes wheezing w viral RTI? Virus affects epithelium airway inflam neutrophils eosinophils macrophages/ monocytes lymphocytes cytokine release IgE parasymp hyperresponsiveness what-when-how.com Asthma part I

19 What causes wheezing w viral RTI? Viral effects in lung cells epithelium - viral replication, chemokines, cytokines airway inflam - rhinov colds -> incr lymps and eos in airways eosinophils - rhinov activates, incr leukotrienes macrophages/monocytes - amplify inflam lymphocytes - T cell activn = Ag independent incr IFNγ,? transient BCG priming effect cytokine release - VIW assoc decr IFN IgE - RSV, paraflu -> incr virus specific IgE - correlates w VIW parasymp hyper-responsiveness - (rodents) incr bronch reactivity Many of the cellular effects seen occur in acute viral infection, regardless of the long term recurrence of wheezing, or not. WHEEZE

20 EVW vs MTW : pathology Histology MTW:? assoc with eosinophilic inflam + basement membrane thickening - akin to asthma Findings variable -? neuts,? no difference Severe wheezers: basement membrane thickening school age children > pre-schoolers. EVW vs MTW: no differences Airway smooth muscle in pre-schoolers incr in assoc w atopy NO REAL HELP 1: Saglani, AJRCCM 2007; 2. Wildhaber Eur Respir Mon 2006; 3. Lezmi, AJRCCM online May 2015

21 So far possibility of mistaken symptoms paradigm which has high possibility of short term acute phenotypic crossover and paradigm does not lend strictly to long term prognosis no reliable histological evidence to differentiate

22 So what? Axiomatic in medicine: correct diagnosis = optimal treatment = best chance of recovery

23 So what? Axiomatic in medicine: correct diagnosis = optimal treatment = best chance of recovery

24 Treatment EVW/MTW: no smoke exposure? air pollution? drugs to prevent development of asthma - not yet

25 Treatment EVW: prn salbutamol - if empirically beneficial? intermittent leukotriene antagonists -??? 1: Preempt Study: decr unscheduled consultations, decr time off school/ daycare/parents work 2: cont M vs int M vs placebo - no difference 3: int M vs int Budes vs std Rx 4: int M vs placebo: no difference overall;? ALOX5 genes favour efficacy Overall? trial monteleukast in child with troublesome Sx.? continue til child better. 1. AJRCCM 2007; 2. Ann Allergy Asthma Immunol 2011; 3. J Allergy Clin Immunol 2008; 4. Lancet Resp Med 2014

26 Treatment PHARMAC: SA 1421 July 2015

27 Treatment EVW: ICS no evidence to support use of ICS in pre schoolers who do not wheeze between viral RTI 1. AJRCCM 2007; 2. Ann Allergy Asthma Immunol 2011; 3. J Allergy Clin Immunol 2008

28 Treatment Oral steroids: Studies - mild episodes - suggest no benefit for OCS in preschool wheeze who don't need admission 1,2 1. NEJM 2011; 2. NEJM 2009

29 PLEA IF CHILD NEEDS ADMISSION FOR WHEEZE. GIVE ORAL STEROIDS, UNLESS PREV OBSERVED TO BE INEFFECTUAL 1. NEJM 2011; 2. NEJM 2009

30 Treatment EVW: small study 7% HTS + salbut neb. decr admission rate and LOS, not severity? palivizumab - cost prohibitive, never tried in low risk group

31 Pragmatic approach 1 1. N child, Hx nothing else, well on exam, thriving. No signif morbidity w viral infections - REASSURANCE 2. Otherwise well, but Hx vomiting, arching, GOR; or upper airway disease - INITIAL Rx, REFER IF NO RESPONSE 3. Significant history: I. cough <1/12, wet, chronic, sudden onset, continuous II.clubbed, chest deformity, stridor, fixed wheeze, other sites of infection, systemic disease - INVESTIGATE? REFER 4.Well child with recurrent wheeze only with viral infection - TREAT 5.Well child with recurrent wheeze w infection and at other times- TREAT Bush et al, BMJ 2014, 348

32 3. Significant History wheeze + Cough: <1/12, wet, chronic, sudden onset, persistent. Clubbed Chest deformity, Stridor, Fixed wheeze, Sudden onset, Barking cough, Other sites of infection, Systemic disease, FTT, Associated with feeding, Abnormal voice/cry, FH of note, PMH, Murmur, Bush et al, BMJ 2014, 348

33 3. Significant History wheeze + Cough: <1/12, wet, chronic, sudden onset, persistent. Clubbed Chest deformity, Other sites of infection, Stridor, Systemic disease, Fixed wheeze, FTT, Sudden onset, Associated with feeding, Barking cough, Abnormal voice/cry, FH of note, PMH, Murmur, Ix: CXR CF - sweat (genes) Ig s, vaccine responses FBC/WBC diffn cough suction/sputum ECG (?echo) GOR / SLT / VFSS ENT L&B? HRCT/bronchoscopy (cilia -? not < 6y) Bush et al, BMJ 2014, 348

34 Pragmatic approach 1 4.Well child with wheeze only with viral infection 5.Well child with wheeze w infection and at other times EVW: prn B2, consider monteleukast - reassess after 4-8 w No better- stop consider alt DDx incl MTW, and other res disease Acute: prednisone if needed admission/ of benefit before Bush et al, BMJ 2014, 348

35 Pragmatic approach 1 4.Well child with wheeze only with viral infection 5.Well child with wheeze w infection and at other times MTW: prn B2, consider ICS - reassess after 4-8 w No better- stop consider alt DDx incl EVW, and other res disease Acute: prednisone if needed admission/ of benefit before Bush et al, BMJ 2014, 348

36 Pragmatic approach 1 If no better- stop Rx, DONT ESCALATE. But if Sx increase/return on cessation, restart and consider escalation of treatment after further 4w Rx. If continuing Inhaled Rx - aim over time for lowest dose for Sx control. Avoid nebulisers for either wheeze phenotype Bush et al, BMJ 2014, 348

37 SUMMARY EVW vs MTW no ICS for EVW consider Monteleukast review and reassess Dx/Rx

38 DECREES 1. Satisfy yourself the child has DEFINITE WHEEZE, by your understanding. 2. Decide if the wheeze is EVW or MTW, if possible. 3. Be prepared to REVIEW the category in light of further clinical information 4. For EVW - DO NOT use ICS 5. For EVW - oral steroids ONLY if admitted 6. For MTW - ICS FIRST, then consider Monteleukast

39 PLEAS 1. Do not overlook a non-evw/mtw Dx 2. Consider trial of monteleukast for EVW 3. If infrequent, mild EVW, consider simple reassurance 4. If you are unsure of Dx, do not expect General Practitioner to make Dx for you. 5. Avoid a diagnostic label of Asthma until you know the child has persistent (>6y), wheezy episodes. 6. For either, always consider if a treatment can be at a lower dose, or even stopped.

40 Questions?