World Allergy Organization Cancun, Mexico 2011 Pediatric Cough Pramod Kelkar, MD Past Chair, Cough Committee, American Academy of Allergy, Asthma & Immunology Founder, National Cough Clinic Private Practice: www.allergy-care.net www.nationalcoughclinic.com Minneapolis, MN, USA

Disclosures None

ChrCough is a Multi-Disciplinary Symptom Pediatrician Allergy/Immunology Pulmonary Otolaryngology Gastroenterology Speech therapy Behavior counseling Psychiatrist

Etiology of Pediatric Chronic Cough

Cough in Children Important protective defensive mechanism, necessary for effective airway clearance AND Common symptom of respiratory disease Most common symptom for visit to MD office in US (3.4%) Parental reporting of cough correlates poorly w/ objective measures (frequency, duration, intensity) Chang , Arch Dis Child 2003 Cough known to cause anxiety and depression in parents Chang , Arch Dis Child 2003; Marchant, Chest 2008

History Triggers: Talking, laughter, walking, running, strong smells, perfumes Timing: Daytime Vs nighttime Relationship with meals Preceding Events: Viral URI, Recent Immigration from a developing country, foreign travel Cough triggered by swallowing: aspiration, tracheoesophageal fistula, laryngeal abnormalities Review of systems is very important

Analysis of cough sound Barking or brassy cough: Croup, tracheomalacia, habit cough Honking: Psychogenic Paroxysmal with or without whoop: pertussis and parapertussis Staccato: Chlamydia in infants

Physical Examination Thick, yellow postnasal drip visible in oropharynx: think chronic sinusitis Look into ears to rule out wax impaction and other causes (Arnold’s Nerve) Look at nails for clubbing (CF, etc.) Check for thyroid masses Look for signs of atopy

Cough Reflex Sensitivity Can be modulated by disease or drugs Heightened CRS can occur in post-viral cough, asthma, GERD, ACE-inhibitor therapy CRS more common in women Cough Receptor Hypersensitivity Syndrome is an important concept! Good resource: www.coughjournal.com

Normal Cough Normal Children Cough Healthy school-age children can have up to 34 cough episodes per day Can at times appear prolonged or nocturnal Recurrent viral URI may seem like persistent cough Post-infectious cough can last 10 days or longer after a viral infection

Abnormal Cough Chronic cough- lasts > 4 to 8 weeks Character/Quality of cough- spasmodic (pertussis), barking/brassy (croup) Wet or dry Nocturnal- asthma, sinusitis Age of the child- infants and young children have anatomic abnormalities of respiratory and GI tract

Classification Of Cough in Children Dry nl CXR 10-11 cough episodes/day (range up to 34) Abnormal chest exam/ XR Dyspnea Hemoptysis Recurrent pneumonia FTT Swallowing problems Wet > Dry Chang, Cough 2005

Specific Cough Associated with underlying respiratory or systemic disease Obvious symptoms or signs/physical examination, abnormal CXR, abnormal laboratory results Example- Bronchiectasis, Pertussis

Nonspecific cough Isolated cough as the sole symptom Usually dry In adults- UACS, Asthma, Eosinophilic bronchitis, GERD In children- UACS, Asthma and GERD account for <10% of causes Most common cause in children- Protracted Bacterial Bronchitis

Protracted Bacterial Bronchitis Most common ( up to 40%) cause of nonspecific chronic wet cough in children Resolves with antibiotic therapy Misdiagnosed or underdiagnosed Bronchoscopy shows neutrophilic inflammation S. pneumoniae, H. influenzae, M. catarrhalis Amoxicillin and clavulanate for two weeks Donnelly D, et al. Thorax 2007;62:80-4

GERD Far less common in children than adults Aspiration with swallowing in the absence of GERD may cause cough Silent reflux often associated with asthma A positive response to empiric therapy with thickened feedings in infants and an acid-suppressive regimen suggests GERD Nonacid reflux detected by impedance measurement

Habit Cough Syndrome Dry, barking or honking Absent at night, improves with distraction Sounds very annoying but the child is unperturbed (la belle indifference) Very disturbing to parents, teachers, caregivers May start after a viral infection Can be difficult to differentiate from a tic disorder/Tourette’s syndrome

Treatment of Habit Cough Accurate diagnosis is important to avoid unnecessary exhaustive work-up Self hypnosis Biofeedback Breathing exercises/Speech therapy Suggestion therapy Lidocaine via nebulization

Upper Airway Cough Syndrome Old terminology was postnasal drip syndrome Includes allergic and nonallergic rhinitis, sinusitis, tonsillar hypertrophy causing tissue impingement on the epiglottis Limited CT sinus is helpful for sinusitis Treat the cause Older/first-generation antihistamines like brompheniramine can be helpful

Asthma Accurate diagnosis is critical Cough-variant asthma- over-diagnosed or under-diagnosed? A time-limited (4-6 weeks) empiric trial of ICS +/- leukotriene modifiers By itself, a response to ICS does not confirm a diagnosis of asthma Presence of multiple causes may delay the response

Interesting Facts While children with asthma can present with chronic cough, most children with isolated cough do not have asthma Environmental Tobacco Smoke (ETS) exposure is associated with increased coughing illnesses and an imprtant contributing factor, ETS alone is not the sole etiology

Methacholine Challenge test In a setting of adult chronic cough patients: Positive predictive value:60-88% Negative predictive value:100% Chest 1999;116(2):279-84

Natural history of cough-variant asthma Not entirely clear due to lack of sufficient data In one 4-year retrospective study of 42 patients, 7 went into remission, and 13 developed classical asthma Matsumoto H, et al. J Asthma. 2006;43(2): 131-5

Recurrent Cough What is the likelihood of asthma in a child presenting with recurrent cough In a child with asthma, is cough severity a reflection of asthma severity Recurrent cough in the absence of wheeze is generally not from asthma Children with recurrent cough have an increased cough receptor sensitivity to capsaicin

Treatment of recurrent cough Usually self-limiting A short therapeutic trial with asthma meds can be considered (4 weeks) If a child doesn’t respond, then avoid escalating treatments but rather take a step back to reassess Is the child any worse without the treatment

Cough in an asthmatic child Cough in an asthmatic child is often due to increased cough receptor sensitivity Cough severity may not reflect asthma severity Cough should not be used as the major indicator for the level of asthma treatment especially in an acute episode Complete absence of cough may not be essential for asthma control. Avoid overtreatment

General Principles in Management Clinical history and physical exam are used to guide testing Recommendations are based primarily on expert opinion, due to lack of controlled pediatric studies No evidence supporting the use of medications for symptomatic relief of acute or chronic cough in children; some data suggests potentially harmful effects

Are we missing pertussis? 75 adults, cough for more than 14 days Pertussis diagnosis based on culture and PT or FHA titer 21% of adults had evidence of B. pertussis infection Clinical features and routine lab tests were of limited value in making the diagnosis JAMA 1995;273:1044-1046

Pertussis: Laboratory Diagnosis Leukocytosis with absolute lymphocytosis (Posterior) Nasopharyngeal swab and aspirate DFA testing: quick results but unreliable PCR: results in 48 h, false positives possible Culture of swab: takes 7 days for results Negative culture does not rule it out! Serology: IgG and IgA to fimbria, pertussis toxin and filamentous hemagglutinin (not standardized) Blood cultures: not useful

Pertussis When to suspect & Whom to treat? Suspect and treat if a clear cut history of exposure Suspect and treat if cough and vomiting (?) Erythromycin is the drug of choice; however, unless administered early, it does not alter the course of the disease NEJM 2000;343(23):1715-1721 JAMA 1995;273:1044-1046

Foreign Body Aspiration Onset after an episode of choking, or sudden onset while eating or playing Toddler age range Parents may have forgotten about aspiration episode

Algorithm for evaluating chronic cough in children (modified from Chang 2006) Sx and signs of respiratory disease? Yes No EVALUATE FOR SPECIFIC COUGH Yes CXR, spirometry abnormal? No Is cough characteristic? Sx and signs suggest specific cough No NON-SPECIFIC COUGH Review in 1-2 wk 1. Watch, wait, review Usually post-infectious 2. Evaluate Tobacco smoke Environmental exposures Child’s activity Parent concerns, expectations 3. Treat obvious illness Resolving, resolved Persistent cough Discuss options with parents Trial of therapy Watch, wait, review Dry cough: ICS 4-8 wk Wet cough: Antibiotic 10-21 d 35

Algorithm for evaluating chronic cough in children (modified from Chang 2006) SPECIFIC COUGH Reversible airway obstruction? Yes ASTHMA Confirm with 4-8 wk trial of medication No Assess risk factors for: Bronchiectasis or recurrent pneumonia Aspiration Chronic or less common infections Interstitial lung disease Airway abnormality Other less common pulmonary conditions Cardiac disease Investigations as outlined Or Consider referral to allergy or pulmonary specialist 36

OTC Cough and Cold Medications in Children Ten percent of U.S. children were taking OTC CCM/week. Approved for adults, testing for efficacy and safety in children not adequate. Adverse events documented; rare deaths. 2007 AAP position statement questioning efficacy and safety <6 years. 2008 FDA Public Health Advisory OTC CCM. 2009 FDA recommended avoiding in <2 years. 2010 Consumer Health Product Association avoid <4 years. March 2011 FDA--removal of 500 unapproved Rx cough, cold and allergy meds.

Can asthma be a possibility if a pre- and post-bronchodilator spirometry is completely normal? Yes No

More studies needed to clarify this further Methacholine Challenge test and allergy skin test correlative study in the diagnosis of asthma N= 175 Allergy skin tests are simple, safe, inexpensive and reliable and there was an excellent correlation between these two tests More studies needed to clarify this further Graif Y, Yigla M, Tov N, et al Chest 2002 Sep;122(3):821-5

Chronic cough completely Relieved by a course of Prednisone. Is this diagnostic of asthma?

Chronic cough relieved by prednisone Possibilities: Allergic rhinitis Asthma Eosinophilic bronchitis Others

Eosinophilic bronchitis

Asthma Eosinophilic bronchitis Sputum eosinophilia Airway hyperresponsiveness Treatment is inhaled or oral steroids Sputum eosinophilia No airway hyperresponsiveness Treatment is inhaled or oral steroids Natural history unclear Am J Respir Crit Care Med 1999;160:406-410

Causes of cough: single or multiple? Multiple causes were found in more than 60% when a large number of diagnostic tests are performed (US experience) Multiple causes were found in <26% when investigations were tailored to presenting features (European experience)

Reasons for misdiagnosis of chronic cough Failure to consider common extrapulmonary causes Insufficient dose of medication or duration of therapy

GERD/Laryngopharyngeal Reflux Kaufman score? Vocal fold edema Ventricular obliteration Pseudosulcus vocalis Posterior commissure hypertrophy Ear, Nose, Throat J 2002;82 (9 Suppl 2): 10-13

Risks of proton-pump inhibitor therapy Community-acquired pneumonia Calcium malabsorption and hip fractures Vitamin B-12 malabsorption (assess vitamin B-12 levels in patients on long-term PPI Community-acquired C diff. infection Atrophic gastritis (PPI+ H. pylori) Dose and duration- dependent! Bradford GS, Taylor CT. Omeprazole and vitamin B-12 deficiency. Ann Pharmacother 1999, 33: 641-643 Yang YX, et al. Long-term PPI therapy and risk of hip fracture JAMA. 2006 Dec 27;296(24):2947-53

What is the clinical utility of flexible bronchoscopy Adds little to the diagnosis of chronic cough in the context of normal CXR or CT Useful to detect and assess endobronchial lesions (tumors, foreign bodies): very rare Always get a Chest CT before bronchoscopy If you are checking a Chest CT: include neck (speaker’s experience) Barnes TW, et al. Chest 2004;126:268-272

Psychogenic (Habit) cough True incidence unknown Overdiagnosed by physicians Diagnosis of exclusion Patient education is the key Ramanuja S, Kelkar P. Ann Allergy Asthma Immunol. 2009 Feb;102(2):91-5; quiz 95-7, 115.

Refractory Idiopathic Cough Rule out all the possible causes first Very challenging to treat Experimental therapies: Lidocaine nebulization, Water and salt irrigations of nose and sinus, Neurontin, Pamelor, Xanax, Baclofen, speech therapy evaluation and breathing exercises Patient and family education and counselling Am J Respir Crit Care Med 1995;152:2068-75

Zebras to watch for “Clinically silent” suppurative airway disease Congestive heart failure Cancer: bronchogenic, esophageal, metastasis Cystic fibrosis Interstitial lung disease Foreign bodies Pneumonia, Recurrent aspiration, pharyngeal dysf. Sarcoidosis Chest 1995;108(4):991-7

Zebras to watch for cont… Pressure from an intrathoracic mass Primary ciliary dyskinesia (infertility) Lingual thyroid (hypothyroidism) Sleep apnea Vocal cord dysfunction Pulmonary tuberculosis Bronchiectasis Ann Med 1989;21(6):425-7 Otolaryngol Head Neck Surg 2001;125:433-4 J Allergy Clin Immunol 2001;108(1):143

Take Home Points Individualize the treatment Flow diagrams/ Suggested reading Ramanuja S, Kelkar P. Ann Allergy Asthma Immunol. 2009 Feb;102(2):91-5; quiz 95-7, 115. Rank MA, Kelkar PS, Oppenheimer JJ. Ann Allergy Asthma Immunol. 2007;98:305-313 Morice AH. ERJ 2004;24:481-492 (European) Irwin RS, et al. Chest 2006;129 (American) Morice AH, McGarvey L, Pavord I. Thorax 2006; 61:suppl 1 (British)

Bibliography continued… Ramanuja V, Kelkar P. Pediatric Cough. Annals of Allergy Asthma and Immunology 2010;105(1):3-8 Goldsobel A, Chipps B. Cough in the pediatric population. The Journal of Pediatrics 2010;156(3): 352-358 Chang AB. Cough guidelines for children : can its use improve outcomes. Chest 2008;134:1111-1112

Thank you! Pramod Kelkar, MD Past- Chair, Cough Committee, American Academy of Allergy, Asthma & Immunology Founder, National Cough Clinic Private Practice: www.allergy-care.net www.nationalcoughclinic.com Minneapolis, MN, USA