1. 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:
Minneapolis, MN, USA

2. Disclosures
None

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

6. Etiology of Pediatric Chronic Cough

7. 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

8. 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

9. 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

10. 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

11. 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:

12. 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

13. 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

14. 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

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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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:

32. 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

33. 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):
JAMA 1995;273:

34. 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

35. 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 d 35

36. 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

37. 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.

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

39. 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

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

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

42. Eosinophilic bronchitis

43. 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:

44. 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)

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

46. 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

47. 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:
Yang YX, et al. Long-term PPI therapy and risk of hip fracture JAMA Dec 27;296(24):

48. 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:

49. 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 Feb;102(2):91-5; quiz 95-7, 115.

50. 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:

51. 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

52. 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

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

54. 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):
Chang AB. Cough guidelines for children : can its use improve outcomes. Chest 2008;134:

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