World Allergy Organization Cancun, Mexico 2011

Pediatric Cough

Pramod Kelkar, MDPast Chair, Cough Committee, American

Academy of Allergy, Asthma & ImmunologyFounder, National Cough Clinic

Private Practice:www.allergy-care.netwww.nationalcoughclinic.comMinneapolis, 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

Chang, Cough 2005

Abnormal chest exam/ XR

Dyspnea

Hemoptysis

Recurrent pneumonia

FTT

Swallowing problems

Dry

nl CXR

Wet > Dry

10-11 cough episodes/day

(range up to 34)

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 testIn 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):1715-1721JAMA 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)

CXR, spirometry abnormal?

Sx and signs of respiratory disease?

Is cough characteristic?

NON-SPECIFIC COUGH

1. Watch, wait, review • Usually post-infectious2. Evaluate• Tobacco smoke• Environmental exposures• Child’s activity• Parent concerns, expectations3. Treat obvious illness

Yes

No

No

No

EVALUATE FOR SPECIFIC COUGH

Discuss options with parents

Review in 1-2 wk

Sx and signs suggestspecific cough

Resolving, resolved Persistent cough

Watch, wait, reviewTrial of therapy

Dry cough: ICS 4-8 wk

Wet cough: Antibiotic 10-21 d

Yes

SPECIFIC COUGH

Bronchiectasis or recurrent pneumonia

Aspiration

Chronic or less common infections

Interstitial lung disease

Airway abnormality

Other less common pulmonary conditions

Cardiac disease

Assess risk factors for:

Reversible airwayobstruction?

Yes

No

ASTHMA

Confirm with 4-8 wk trial of medication

Investigations as outlinedOr

Consider referral to allergy or pulmonary

specialist

Algorithm for evaluating chronic cough in children (modified from Chang 2006)

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 spirometryis completely normal?

(A)Yes(B) No

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 completelyRelieved by a course of Prednisone.

Is this diagnostic of asthma?

Chronic cough relieved by prednisone

Possibilities:

(1) Allergic rhinitis

(2) Asthma

(3) Eosinophilic bronchitis

(4) 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

Ear, Nose, Throat J 2002;82 (9 Suppl 2): 10-13

Pseudosulcus vocalis

Posterior commissure hypertrophy

Vocal fold edema

Ventricular obliteration

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 CoughRule out all the possible causes firstVery challenging to treatExperimental 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• BronchiectasisAnn Med 1989;21(6):425-7Otolaryngol Head Neck Surg 2001;125:433-4J Allergy Clin Immunol 2001;108(1):143

Take Home Points

• Individualize the treatment• Flow diagrams/ Suggested reading

(1) Ramanuja S, Kelkar P. Ann Allergy Asthma Immunol. 2009 Feb;102(2):91-5; quiz 95-7, 115.

(2) Rank MA, Kelkar PS, Oppenheimer JJ. Ann Allergy Asthma Immunol. 2007;98:305-313

(3) Morice AH. ERJ 2004;24:481-492 (European)

(4) Irwin RS, et al. Chest 2006;129 (American)

(4) 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, MDPast- Chair, Cough Committee, American Academy of

Allergy, Asthma & ImmunologyFounder, National Cough Clinic

Private Practice:www.allergy-care.netwww.nationalcoughclinic.comMinneapolis, MN, USA