4/19/2011

FacultyFaculty J.P. Clancy, MD Children with Chronic Tom Boat Chair and Director of Cystic Respiratory Complaints: Fibrosis Clinical and Translational When Does Normal Research Cincinnati Children’s Hospital and Medical Become Abnormal? Center Cincinnati, Ohio Satellite Conference and Live Webcast Wednesday, April 27, 2011 Angela Happeny 12:00 - 2:00 p.m. Central Time Parent of a Daughter Diagnosed with Immotile Ciliary Syndrome Produced by the Alabama Department of Public Health Video Communications and Distance Learning Division (Primary Ciliary Dyskinesia)

Learning Objectives Overview of Presentation • To identify when common pediatric • Case presentation and interview with respiratory symptoms become parent excessive and beyond the normal – Daughter diagnosed with primary range of care ciliary dyskinesia • To state parental perspectives into • PCD, or immotile cilia syndrome the evaluation of chronic respiratory – Kartagener’s syndrome signs and symptoms

Overview of Presentation A Parent’s Perspective: • Medical background Chronic Respiratory Complaints • Some background regarding – Chronic respiratory symptoms and daughter’s birth and early symptoms causes • The nature of dauggyphter’s symptoms • What are the factors that through childhood discriminate between normal and abnormal? – Types of evaluations – When to test and what to test for? – When to refer?

1 4/19/2011

A Parent’s Perspective: Chronic Respiratory Complaints • Stresses faced by your daughter, Part I yourself and your family Common Respiratory – Prior to diagnosis Complaints and Causes – After diagnosis – Today • Messages for health care providers

Common Respiratory Respiratory Complaints in Complaints and Causes Primary Care • Provide a general framework for • Common (up to 80% of sick patient thinking about assessment of encounters) respiratory complaints – URIs • Common symptoms – Etiologies based on symptoms – LRTIs − Cough – Segregate in broad groups – − Wheeze − Tachypnea – Allergies − Dyspnea – Noisy, spells, exercise symptoms

Chronic Respiratory Symptoms Chronic Respiratory Symptoms • Cough (> 4 weeks) • Noisy breathing – Dry – Inspiratory – Wet – Expiratory – Paroxysmal • Wheezing – Staccato • Recurrent infections – Honking • Tachypnea • Dyspnea/exercise intolerance/pain

2 4/19/2011

Chronic Respiratory Symptoms Cough: Daily, > 4 weeks • Apnea, ALTEs, and OSA • Expected – Change and Glomb. Guidelines for evaluating • Specific chronic cough in children. Chest. 129; 260s – 283s (2006) – With associated findings – TillTypically requi res further evaluation

Cough: Daily, > 4 weeks Why Do We Cough • Nonspecific • Sites of cough receptors – No associated findings – – Watchful waiting – Bifurcations – Change and Glomb. Guidelines for evaluating – Distal esophagus chronic cough in children. Chest. 129; 260s – 283s (2006)

Cerebral cortex Examples of ‘Expected’ Cough centre Chronic Cough Superior laryngeal • Known underlying disorder that nerve Larynx Vagus (X) nerve manifests with cough Carina – Infections MiMain bronchi – Asthma

Intercoastals – Mucus problem Oesophagus • , primary ciliary Diaphram dyskinesia Chung, KF et al. Prevalence, pathogenesis, and causes of chronic cough. The Lancet. 371:1364-1374 (2008)

3 4/19/2011

Examples of ‘Expected’ ‘Specific’ Chronic Cough: Chronic Cough Associated Findings – Anatomic problem • , aspiration, compression, malacia, fistula, foreign body – Airspace problem – Interstitial disease

– Chung, KF et al. Prevalence, pathogenesis, and causes

of chronic cough. The Lancet. 371:1364-1374 (2008) Change and Glomb. Guidelines for evaluating chronic cough in children. Chest. 129; 260s – 283s (2006)

Causes of ‘Non-specific’ Causes of ‘Non-specific’ Chronic Cough Chronic Cough • Lack clear etiology – Often lead to empiric trials of • Lack associated ‘pointers’ therapies • Extend beyond the expected • Unresponsive - Consideration of timeframe from post-infectious or habit cough – Chung, KF et al. Prevalence, pathogenesis, and causes exposure causes of chronic cough. The Lancet. 371:1364-1374 (2008) – > 4 weeks

Noisy Breathing Noisy Breathing • Inspiratory • Both – Extrathoracic – Fixed abnormality, or mixture • • Expiratory – Intrathoracic • Wheeze

4 4/19/2011

Noisy Breathing Noisy Breathing

Noisy Breathing Noisy Breathing • Inspiratory • Expiratory – Supraglottic, glottic, and subglottic – Airways • Laryngomalacia • , • • AtAnatom ic • Anatomic

Noisy Breathing • Inspiratory and expiratory – Fixed abnormality Voice box • , , Wind Pipe laryngeal web , large airway lesion Breathing tubes

Lung

5 4/19/2011

Noisy Breathing WheezingWheezing – Mixture of extra and intrathoracic • Commonly described sources • Expiratory • Laryngomalacia + • Airflow obstruction tracheobronchomalcia – Mucus • Croup + – Constriction – Compression – Lumenal process

WheezingWheezing WheezingWheezing • Causes – Asthma – Bronchiolitis – Atypical LRTIs – Fixed – Cardiac • Failure, vascular anomaly

Recurrent Infections • Sino-pulmonary infections – – Bronchiolitis – Bronchiectasis – Acute – Chronic sinusitis

6 4/19/2011

Recurrent Infections • Host anatomy – Failure to clear secretions • Host immunity – Failure to kill bugs – Innate or acquired immune system • Host exposures

Tachypnea • Resting respiratory rate

• Associated findings – Retractions – Flaring – Head bobbing – Accessory muscles

Normal Nostrils Flared Nostrils

7 4/19/2011

Tachypnea Dyspnea/Exercise Intolerance • Pulmonary and non-pulmonary • More common outside of infancy and

– CO2 removal/acidosis toddlers – Oxygenation • Keeping up with • VQ mismatch peers • Diffusion • Onset • Hypoventilation • Associated • Shunt symptoms • Altitude

Dyspnea/Exercise Intolerance Apnea, ALTEs, and OSA • Pulmonary • ALTEs – Primary or secondary – Apparent Life Threatening Events • Cardiac – Acute change in • Hematologic consciousness, • Endocrine tone, color • Infectious – With or without • Rheumatologic apnea • Deconditioning

Apnea, ALTEs, and OSA Apnea, ALTEs, and OSA • ALTEs • Obstructive Sleep Apnea – 2-5% of all infants – Increasing prevalence – Weak association with SIDS – Relationship to behavior and school performance – 50% with diagnosis – Central and anatomic • All organ systems causes

8 4/19/2011

Apnea, ALTEs, and OSA Summary – Etiology of Chronic Respiratory Symptoms • Pulmonary disorder – Airway or airspace – Abnormal anatomy – Infectious – Exposures • Other organ or systemic disorder • Not mutually exclusive

Normal vs. Abnormal Part II • ‘Normal’ What are the Factors – Symptoms anticipated to self- that Discriminate resolve without intervention Normal from Abnormal? • ‘Abnormal’ – Symptoms that warrant further work-up

Normal vs. Abnormal Symptoms in Combination that • Diagnostic testing Frequently Cough Warrant Further • Referral for further evaluation Work-up + • Duration Persistence

(4 weeks)weeks)(4

Change and Glomb. Guidelines for evaluating chronic cough in children. Chest. 129; 260s – 283s (2006)

9 4/19/2011

Chest Examination Abnormalities Chest Examination Abnormalities • Auscultatory • Reduced saturations – pulmonary • Productive cough • Cardiac findings • Hemoptysis – History and • Symptoms related to specific auscultatory activities

– Change and Glomb. Guidelines for evaluating chronic • Chest pain cough in children. Chest. 129; 260s – 283s (2006) • Chest deformity

Chest Examination Abnormalities Chest Examination Abnormalities • Auscultatory (pulmonary) • Cardiac findings (history and – Stridor auscultatory) – Sleeping obstructive symptoms – History – Wheeze • ‘Racing’ heart, – Rhonchi pain, syncope, – Rales poor feeding – Sidedness/localization * New onset without clear URI/LRTI prodrome

Chest Examination Abnormalities Chest Examination Abnormalities – Exam • Chest pain (cardiopulmonary, • Murmurs musculoskeletal, referred) • Gallops – Localization • RtithResting tachycardi a – Provocative activities • Right sided heart sounds

10 4/19/2011

Chest Examination Abnormalities Chest Examination Abnormalities – Nature • Chest deformity • Sharp – Typically not a ‘new’ symptom • Dull – Frequent restrictive disease • Tight • PtPectus excavatum • Inspiratory/expiratory • Pectus carinatum • Rib anomalies • Significant scoliosis

Signs of Scoliosis Uneven shoulders

Curve in spine

Uneven hips

Chest Examination Abnormalities Chest Examination Abnormalities • Reduced saturations • Diffusion abnormality – Most commonly part of an acute –Airspace (infectious) process • Hypoventilation • V/Q mismatch –Central vs. – When identified as part of chronic obstructive symptoms • Shunt –Cardiac

11 4/19/2011

Chest Examination Abnormalities Chest Examination Abnormalities • Productive cough • Considerations: – ‘Moist’, sputum – Post nasal drip, foreign body, – Rhonchi, rales or wheeze aspiration, bronchiectasis, ‘mucus (localization) problem’ – Change and Glomb. Guidelines for evaluating chronic – Asymmetric exam cough in children. Chest. 129; 260s – 283s (2006) • Diminished or phase lag

Chest Examination Abnormalities Chest Examination Abnormalities • Hemoptysis – Source? – Always concerning • Upper airway – Typically justifies evaluation • GI tract • Frequently • Lower airway or airspace not serious

Chest Examination Abnormalities Chest Examination Abnormalities • Symptoms related to specific – Stress triggers activities • Asthma, – Feeding – Exposures • GERD, aspiration • EiEnvironmen tltbtal tobacco smo ke, – Exercise viral infections • Asthma, cardiac – Sleep • Asthma, OSA

12 4/19/2011

Abnormalities Outside of Abnormalities Outside of the the Respiratory System • Failure to thrive • Failure to thrive • Infections outside of respiratory – A symptom warranting further system evaluation • Digital clubbing – Associated symptoms • Neurodevelopmental abnormalities • Respiratory • Exercise intolerance • Infections • Syncope

Abnormalities Outside of the Respiratory System • GI .. . . –Feeding, vomiting, diarrhea ... • Rashes, fevers, arthritis ......

Abnormalities Outside of Abnormalities Outside of the Respiratory System the Respiratory System • Infections outside of respiratory – Immunodeficency considerations: system • IgA deficiency, common variable – Bacterial or severe combined immune – Viral deficiency, complement deficiency, T cell defect, – Fungal neutrophil defect (CGD, LAD), Job’s syndrome, Wiskott-Aldrich syndrome

13 4/19/2011

Abnormalities Outside of Abnormalities Outside of the Respiratory System the Respiratory System • Digital clubbing • Neurodevelopmental abnormalities • Implies chronic purulent respiratory – High risk: disorder • Swallowing difficulties – CF –Aspiration – PCD • Sleeping/recumbent symptoms – Tb/post-infectious –OSA – Other causes of bronchiectasis

Abnormalities Outside of Abnormalities Outside of the Respiratory System the Respiratory System • Mucus clearance • Exercise intolerance –Poor or ineffective cough – Syncope/dizziness • Scoliosis • Cardiac or neurologic

Abnormalities Outside of the Respiratory System • General fatigue Part III Testing and Interventions – Hematologic – Infectious – Rheumatologic – Endocrine

14 4/19/2011

Testing and Interventions Next Steps in Evaluation • What types of tests can be performed “Your Office” “My Office” from the pediatrician’s office? Saturations PFTs, walk test Imaging (CT, UGI, Imaging (chest X-ray, swallow, airway • What tests are typically performed decubitus films) fluoroscopy) out of the specialists ’ office? Laboratory studies Laboratory studies -CBC, metabolic profile, -Sweat CI, cilia • Empiric therapeutic trials UA, endocrine, ESR, CRP -Quantitative immunoglobulins Skin test Pre/post anitbody titres

Bronchoscopy

Next Steps in Evaluation Empiric Therapeutic Trials

• Send films prior to work-up • Antibiotics • Conversation with specialist • Asthma rescue +/- asthma controller • H2 blocker or proton pump inhibitor • Antihistamine • Leukotriene receptor antagonist

Empiric Therapeutic Trials Cochrane Reviews • ‘No role for over the counter cough Prolonged Cough in Children suppressants, particularly young • Antibiotics children’ – Randomized controlled trials with * Be syy,jstematic, not just additive ppgp()lacebo group (2) − Change and Glomb. Guidelines for evaluating chronic – Cough greater than 10 days cough in children. Chest. 129; 260s – 283s (2006) • Mean 3 - 4 weeks – Predominance of Moraxella catarrahalis in N/P cultures

15 4/19/2011

Cochrane Reviews Prolonged Nonspecific Prolonged Cough in Children Cough in Children – Treatment arms improved relative • Asthma therapy to placebo – ‘Children with nonspecific chronic – High self-resolution rate cough and asthma risk factors, a • Uncomplicated pediatric acute short trial (2 - 4 weeks) of ICS sinusitis (budesonide) may be warranted’ –Clinical improvement = 88% – Most kids with nonspecific cough with antibiotics, 60% with do not have asthma placebo Change and Glomb. Guidelines for evaluating chronic cough in children. Chest. 129; 260s – 283s (2006)

Prolonged Nonspecific Potential Side Effects of ICS Cough in Children • Many potential side effects described – Reevaluate, and don’t escalate if • Very difficult to demonstrate long- no response term side effects in children – Typicall y should be able to – HPA suppression discontinue treatment – Bone mineral density – Change and Glomb. Guidelines for evaluating chronic cough in children. Chest. 129; 260s – 283s (2006) – Growth – Cataracts

Potential Local and Systemic Side Cochrane Reviews Effects of Inhaled Corticosteroids Prolonged Cough in Children • GERD therapy – Cochrane review failed to demonstrate benefits of milk thickening, cisapride, or domperidone in pediatric GERD

– Dahl, R. Systemic side effects of inhaled corticosteroids in patients with asthma. Resp Med. 100, 1307-17 (2006)

16 4/19/2011

Cochrane Reviews Cochrane Reviews – Prolonged Prolonged Cough in Children Nonspecific Cough in Children • Separate Cochrane review of • Antihistamines metoclopramide for GERD in – Randomized controlled trials with children < 2 yo – no benefit demonstrated (did not monitor ppgp()lacebo group (3) cough) – Therapeutic studies demonstrated – No RCT has been conducted on similar improvements in active the use of PPIs for the treatment of treatment and placebo arms cough in children (n~160) – Change and Glomb. Guidelines for evaluating chronic cough in children. Chest. 129; 260s – 283s (2006)

Cochrane Reviews – Prolonged Cochrane Reviews – Prolonged Nonspecific Cough in Children Nonspecific Cough in Children – Some benefit of antihistamine in – No significant difference in all seasonal allergy (within two study endpoints between LRTA weeks) and placebo groups (n~260)

– Chang, AB et al. Antihistamines for prolonged nonspecific • Leukotriene receptor antagonists cough in children. Cochrane Reviews. April 16;(2) (2008) – Randomized controlled trials with placebo group (2)

SummarySummary SummarySummary • Listen to (don’t just hear) caregivers • Respiratory symptoms can be • Persistent respiratory symptoms primary or secondary typically warrant further evaluation • Empiric trials should have start and (> 4 wee ks ) endpointendpointendpoint • Combinations of symptoms provide evidence of more significant disorder

17 4/19/2011

Thank You • Pediatric Pulmonary Center at UAB – Nancy Wooldridge, Claire Lenker, Wyn Hoover, Brad Troxler, Heather Hathorne, and former faculty: Janet Johnston, Julie McDougal – Advisory committee members

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