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Coughing and Kids:When It’s Not Just Asthma

Coughing and Kids:When It’s Not Just Asthma

Produced by the Alabama Department of Public HealthVideo Communications and Distance Learning DivisionProduced by the Alabama Department of Public HealthVideo Communications and Distance Learning Division

Satellite Conference and Live WebcastThursday, May 16, 2013

12:00 – 2:00 p.m. Central Time

Satellite Conference and Live WebcastThursday, May 16, 2013

12:00 – 2:00 p.m. Central Time

FacultyFaculty

Kristin BradfordParent of a Child with a

Chronic Respiratory Condition

Kristin BradfordParent of a Child with a

Chronic Respiratory Condition

FacultyFaculty

Wynton C. Hoover, MD, FAAPAssociate Professor of Pediatrics

Division of Pediatric Pulmonary and Sleep Medicine

Director Pediatric Pulmonary Center

Wynton C. Hoover, MD, FAAPAssociate Professor of Pediatrics

Division of Pediatric Pulmonary and Sleep Medicine

Director Pediatric Pulmonary CenterDirector, Pediatric Pulmonary CenterDirector, Pediatric Pulmonary

FellowshipAssociate Director, Pediatric CF

Care CenterUniversity of Alabama at Birmingham

Director, Pediatric Pulmonary CenterDirector, Pediatric Pulmonary

FellowshipAssociate Director, Pediatric CF

Care CenterUniversity of Alabama at Birmingham

Presentation OverviewPresentation Overview• Case Presentation and Parent

Interview

– 20 minutes

• Functional and Pathophysiologic

• Case Presentation and Parent

Interview

– 20 minutes

• Functional and Pathophysiologic• Functional and Pathophysiologic

Cough

• Airway Clearance – Innate Defense

• Functional and Pathophysiologic

Cough

• Airway Clearance – Innate Defense

Presentation OverviewPresentation Overview• Diagnostic Evaluation of Cough

– 40 minutes

– Break (15 minutes)

• Diagnostic Evaluation of Cough

– 40 minutes

– Break (15 minutes)

• Case Reviews

– 25 minutes

• Questions

– 5 minutes

• Case Reviews

– 25 minutes

• Questions

– 5 minutes

DisclosuresDisclosures• Dr. Hoover

– No personal disclosures

– Cystic Fibrosis Research Funding

• Dr. Hoover

– No personal disclosures

– Cystic Fibrosis Research Funding

• Cystic Fibrosis Foundation

• Gilead Pharmaceuticals

– Will indicate non-FDA approved

treatment strategies (**)

• Cystic Fibrosis Foundation

• Gilead Pharmaceuticals

– Will indicate non-FDA approved

treatment strategies (**)

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DisclosuresDisclosures• Ms. Bradford has no disclosures• Ms. Bradford has no disclosures

ObjectivesObjectives• Explore the parental experience of

dealing with chronic cough and

undiagnosed illness

• Identify the functional nature of

• Explore the parental experience of

dealing with chronic cough and

undiagnosed illness

• Identify the functional nature ofIdentify the functional nature of

coughing

• Associate the relationship of

coughing to pathologic states in the

respiratory tract

Identify the functional nature of

coughing

• Associate the relationship of

coughing to pathologic states in the

respiratory tract

ObjectivesObjectives• Identify differential diagnoses

associated with chronic coughing

that may indicate diagnoses other

than asthma

• Identify differential diagnoses

associated with chronic coughing

that may indicate diagnoses other

than asthma

Chronic Cough: A Parent’s Perspective

Chronic Cough: A Parent’s Perspective

Jacob’s Medical JourneyJacob’s Medical Journey• Concern

• Frustration

• Disappointment

• Concern

• Frustration

• Disappointment

• Hope

• Resolution

• Maintenance

• Hope

• Resolution

• Maintenance

Jacob’s CoughJacob’s Cough• Began at age two

• Rarely productive but occasionally

produces green sputum

• Began at age two

• Rarely productive but occasionally

produces green sputum

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Jacob’s CoughJacob’s Cough• Multiple visits with few answers and

little improvement

– Recurrent use of antibiotics, cough

and cold medicines allergy

• Multiple visits with few answers and

little improvement

– Recurrent use of antibiotics, cough

and cold medicines allergyand cold medicines, allergy

medicines, inhalers

• Nothing seemed to work

and cold medicines, allergy

medicines, inhalers

• Nothing seemed to work

FrustrationFrustration

“I knew something was wrong with him

but did not know where to turn.”

“I knew something was wrong with him

but did not know where to turn.”

DisappointmentDisappointment“I figured that a doctor,

if there was something really wrong,

would find it and fix it.”

“I figured that a doctor,

if there was something really wrong,

would find it and fix it.”

Chronic Fever and CoughChronic Fever and Cough• Jacob, age 12, experienced fevers

over 9 months up to 103F associated

with cough

• Ultimately he was evaluated by a new

• Jacob, age 12, experienced fevers

over 9 months up to 103F associated

with cough

• Ultimately he was evaluated by a newUltimately he was evaluated by a new

physician and referred to infectious

disease specialist following a CT

scan demonstrating bronchectasis

Ultimately he was evaluated by a new

physician and referred to infectious

disease specialist following a CT

scan demonstrating bronchectasis

Chronic Fever and CoughChronic Fever and Cough• Subsequent referral to pulmonary

for evaluation of chronic cough

March 2012

• Subsequent referral to pulmonary

for evaluation of chronic cough

March 2012

HopeHope“This was the first time I thought that a

doctor actually cared about my child.”

“This was the first time I thought that a

doctor actually cared about my child.”

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Jacob’s Cough and Bronchiectasis

Jacob’s Cough and Bronchiectasis

• Jacob’s differential diagnosis

– Asthma

– Cystic Fibrosis

• Jacob’s differential diagnosis

– Asthma

– Cystic Fibrosisy

– Immune Deficiency

– Primary Ciliary Dyskinesia

– Hypersensitivity Pneumonitis

– Aspiration of foreign body

y

– Immune Deficiency

– Primary Ciliary Dyskinesia

– Hypersensitivity Pneumonitis

– Aspiration of foreign body

EvaluationEvaluation• History and PE

– Chronic wet productive cough

• PFTs confirm asthma

• History and PE

– Chronic wet productive cough

• PFTs confirm asthma

• CT sinuses: Pan Sinusitis

• Immune w/u negative

• Sweat CL: negative

• CT sinuses: Pan Sinusitis

• Immune w/u negative

• Sweat CL: negative

EvaluationEvaluation• IgE elevated 531 and Rast c/w

Environmental Allergies (ABPA neg)

• Admitted with pneumonia May 2012

Bronchoscopy: Purulent

• IgE elevated 531 and Rast c/w

Environmental Allergies (ABPA neg)

• Admitted with pneumonia May 2012

Bronchoscopy: Purulent– Bronchoscopy: Purulent

Bronchitis

– Bronchoscopy: Purulent

Bronchitis

BronchoscopyBronchoscopy• Aleveolar Lavage

– G+ Cocci

– 12,815 WBC/uL

• Aleveolar Lavage

– G+ Cocci

– 12,815 WBC/uL

– 440 RBC/uL

– 93% PMNs

– 500,000 CFU

• Strep Pneumonia

– 440 RBC/uL

– 93% PMNs

– 500,000 CFU

• Strep Pneumonia

Ciliary DyskinesiaCiliary Dyskinesia• Electron Microscopy Revealed

Normal Ultrastructure

• PCD Gene Sequence Identified

Heterozygous Mutation in DNAH11

• Electron Microscopy Revealed

Normal Ultrastructure

• PCD Gene Sequence Identified

Heterozygous Mutation in DNAH11Heterozygous Mutation in DNAH11– Zariwala MA, Omran H, Ferkol TW. MA, Omran H, Ferkol TW. The emerging genetics of primary The emerging genetics of primary ciliaryciliary

dyskinesiadyskinesia. Proc Am . Proc Am ThoracThorac Soc. 2011 Sep;8(5):430Soc. 2011 Sep;8(5):430--3.3.

Heterozygous Mutation in DNAH11– Zariwala MA, Omran H, Ferkol TW. MA, Omran H, Ferkol TW. The emerging genetics of primary The emerging genetics of primary ciliaryciliary

dyskinesiadyskinesia. Proc Am . Proc Am ThoracThorac Soc. 2011 Sep;8(5):430Soc. 2011 Sep;8(5):430--3.3.

Ciliary DyskinesiaCiliary Dyskinesia

Zariwala MA, Omran H, Ferkol TW. The emerging genetics of primary ciliary dyskinesia. Proc Am ThoracSoc. 2011 Sep;8(5):430-3.

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Diagnosis of PCDDiagnosis of PCD• Difficult diagnosis with emerging

tools

– Gold standard: nasal brushing and EM

• Difficult diagnosis with emerging tools

– Gold standard: nasal brushing and EM

• Demonstrating ultrastructuralabnormality has a high specificity for disease

• Normal structure does NOT rule our PCD

• Demonstrating ultrastructuralabnormality has a high specificity for disease

• Normal structure does NOT rule our PCD

Diagnosis of PCDDiagnosis of PCD– Emerging tools

• Genetics

–Ready for prime time?

– Emerging tools

• Genetics

–Ready for prime time?

–Much debate

• Nasal NO

–Good NPV / limited availability

–Much debate

• Nasal NO

–Good NPV / limited availability

Diagnosis of PCDDiagnosis of PCD• Ciliary motility study

–Difficult / affected by virus

• See references for further

reading

• Ciliary motility study

–Difficult / affected by virus

• See references for further

readingreadingreading

Treatment for PCD and AsthmaTreatment for PCD and Asthma• Daily chest physiotherapy

• Mometosone / Fomoterol 100/5mcg 2

puffs BID with spacer

• Montelukast 5mg QHS

• Daily chest physiotherapy

• Mometosone / Fomoterol 100/5mcg 2

puffs BID with spacer

• Montelukast 5mg QHS• Montelukast 5mg QHS

• Albuterol HFA 2-4 puffs prn with

spacer

• Montelukast 5mg QHS

• Albuterol HFA 2-4 puffs prn with

spacer

Treatment for PCD and AsthmaTreatment for PCD and Asthma• Azithromycin 250mg Mon., Wed.,

and Fri.**

• Gentamicin 80mg nebulized BID

QOM**

• Azithromycin 250mg Mon., Wed.,

and Fri.**

• Gentamicin 80mg nebulized BID

QOM**QQ

“Relieved”“Relieved”

“Now I finally know what

is wrong with Jacob.”

“Now I finally know what

is wrong with Jacob.”

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Staying Healthy is Hard Work!Staying Healthy is Hard Work!“I don’t feel Jacob’s care is a burden.

He is able to actively play sports and

lead an almost normal life.”

“I don’t feel Jacob’s care is a burden.

He is able to actively play sports and

lead an almost normal life.”

Mechanical Defensesof the Lung

Mechanical Defensesof the Lung

• Nasal and upper airway filtration of

larger particles (>10um)

• Muscosal surface and mucous

• Nasal and upper airway filtration of

larger particles (>10um)

• Muscosal surface and mucous

secretion

• Mucociliary clearance

secretion

• Mucociliary clearance

Mechanical Defensesof the Lung

Mechanical Defensesof the Lung

• Neurally mediated responses

– Cough

– Sneezing

• Neurally mediated responses

– Cough

– Sneezing– Sneezing

– Bronchoconstriction

– Sneezing

– Bronchoconstriction

Mucociliary ClearanceMucociliary Clearance• Ciliated cells present at 13 WGA

• Present on mucosal surfaces with up

to 200 cilia present per cell

• Beat in frequency at 12-22 hz to

• Ciliated cells present at 13 WGA

• Present on mucosal surfaces with up

to 200 cilia present per cell

• Beat in frequency at 12-22 hz toBeat in frequency at 12 22 hz to

sweep mucous along mucosal

surfaces

• Ciliary function can be disrupted due

to structural or dyskinetic beat

Beat in frequency at 12 22 hz to

sweep mucous along mucosal

surfaces

• Ciliary function can be disrupted due

to structural or dyskinetic beat

Mucociliary ClearanceMucociliary ClearanceCiliated columnar epithelial cell

Goblet cell

Movement of mucus

to pharynx

Cilia

Mucus layer

Lamina Propria

Foreign particle

Neurally Mediated ClearanceNeurally Mediated Clearance• Sneezing

– Response to particulate matter or

irritants in the nose or

nasopharnyx

• Sneezing

– Response to particulate matter or

irritants in the nose or

nasopharnyxnasopharnyx

• Cough

– Response generated to stimulation

of laryngeal or airway receptors

nasopharnyx

• Cough

– Response generated to stimulation

of laryngeal or airway receptors

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Neurally Mediated ClearanceNeurally Mediated Clearance• Bronchoconstriction

– Increased lower airway tone in

response to receptor stimulation to

limit dispersion of inspired

• Bronchoconstriction

– Increased lower airway tone in

response to receptor stimulation to

limit dispersion of inspiredlimit dispersion of inspired

particles

limit dispersion of inspired

particles

Why Cough?Why Cough?• Larnyx

– Irritant

– Thermal

• Larnyx

– Irritant

– Thermal

• Trachea

– RARs - Irritant

– SARs - Facilitate

• Trachea

– RARs - Irritant

– SARs - Facilitate

Why Cough?Why Cough?• Lower Airways

– C-Fibers

• Esophagus

• Lower Airways

– C-Fibers

• Esophagus

Why Cough?Why Cough?

Cough centre

Superior laryngeal nerve

Vagus (x) nerve

Cerebral cortex

Pharynx

Larynx

Trachea

CarinaCarina

Main bronchi

Oesophagus

Diaphragm

Intercostals

Chung, KF et al. Prevalence, pathogenesis, and causes of chronic cough. The Lancet. 371:1364-1374 2008

What Is a CoughWhat Is a Cough• Coughing is a physiologic reflex that

augments airflow thus enhancing

mucociliary clearance and expelling

large accumulations of mucous

• Coughing is a physiologic reflex that

augments airflow thus enhancing

mucociliary clearance and expelling

large accumulations of mucous

• Coughing is in effect a normal

response to a pathophysiologic state

• Cough can be both reflexive and

controlled

• Coughing is in effect a normal

response to a pathophysiologic state

• Cough can be both reflexive and

controlled

How Do We CoughHow Do We Cough• Initial inspiration above tidal

breathing to a point in IRV but below TLC

• Glotic closure with contraction of

• Initial inspiration above tidal breathing to a point in IRV but below TLC

• Glotic closure with contraction of abdominal and thoracic muscles raises transpulmonary pressure

• Opening / closing glotis in repetition allows high velocity air flow transients to propel mucous

abdominal and thoracic muscles raises transpulmonary pressure

• Opening / closing glotis in repetition allows high velocity air flow transients to propel mucous

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High Velocity Air Flow Moves Liquids!

High Velocity Air Flow Moves Liquids!

Is a Cough Always BadIs a Cough Always Bad• Coughing is a normal and protective

physiologic defense

• Chronic coughing represents

ongoing response to a

• Coughing is a normal and protective

physiologic defense

• Chronic coughing represents

ongoing response to aongoing response to a

pathophysiologic state

• Generally a cough lasting more than

four weeks requires further

investigation

ongoing response to a

pathophysiologic state

• Generally a cough lasting more than

four weeks requires further

investigation

Is a Cough Always BadIs a Cough Always Bad• A cough that is acutely worsening

likewise requires more attention

• A cough that is acutely worsening

likewise requires more attention

Cough: Efficient Accurate Diagnosis

Cough: Efficient Accurate Diagnosis

• Chronic cough in association with

chronic lower airway inflammation

results in permanent lung injury

• Chronic cough in association with

chronic lower airway inflammation

results in permanent lung injury

– Bronchiectasis is permanent and

progressive

– Bronchiectasis is permanent and

progressive

Cough: Efficient Accurate Diagnosis

Cough: Efficient Accurate Diagnosis

• Morbidity and physiologic limitations

associated with chronic coughing

significantly disrupts daily activity

• Morbidity and physiologic limitations

associated with chronic coughing

significantly disrupts daily activity

– School, sleep, activity, parental

concern

– School, sleep, activity, parental

concern

So Many Coughs: Where to Start?

So Many Coughs: Where to Start?

• History is the key!• History is the key!

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Characterize It:Types of CoughCharacterize It:Types of Cough

• Clinical descriptors of cough help

tremendously

• Character

• Clinical descriptors of cough help

tremendously

• Character

– Wet or productive?

– Dry and hacky?

– Barking or seal-like?

– Wet or productive?

– Dry and hacky?

– Barking or seal-like?

Characterize It:Types of CoughCharacterize It:Types of Cough

• Setting and stimulus

– During wakefulness or asleep?

– During exercise or at rest?

• Setting and stimulus

– During wakefulness or asleep?

– During exercise or at rest?– During exercise or at rest?

– Following meals or drinking?

– Continuous or disruptive in

nature?

– During exercise or at rest?

– Following meals or drinking?

– Continuous or disruptive in

nature?

Wet and ProductiveWet and Productive• Generally associated with excessive

mucous production, ineffective

clearance, and inflammation

– Asthma: “wet” asthma vs “dry”

• Generally associated with excessive

mucous production, ineffective

clearance, and inflammation

– Asthma: “wet” asthma vs “dry”Asthma: wet asthma vs. dry

asthma

– Bronchitis: chronic or acute

– Pneumonia: infectious or non-

infectious

Asthma: wet asthma vs. dry

asthma

– Bronchitis: chronic or acute

– Pneumonia: infectious or non-

infectious

Wet and ProductiveWet and Productive– Impaired airway clearance: innate

or acquired

– Consider CF, PCD, foreign bodies

and focal airway obstructions

– Impaired airway clearance: innate

or acquired

– Consider CF, PCD, foreign bodies

and focal airway obstructionsand focal airway obstructions

• Intrinsic / extrinsic mass

and focal airway obstructions

• Intrinsic / extrinsic mass

Dry and HackyDry and Hacky• Generally associated with upper

airway stimulation

– Asthma

– Allergic rhinitis

• Generally associated with upper airway stimulation

– Asthma

– Allergic rhinitis g

– Sinusitis

– Gastroesophageal reflux

– Post infectious hypersensitivity

• Psychogenic

g

– Sinusitis

– Gastroesophageal reflux

– Post infectious hypersensitivity

• Psychogenic

Barking or Seal-likeBarking or Seal-like• Generally not a chronic finding but

more a qualitative descriptor – think

acute

– Croup / laryngotrachobronchitis

• Generally not a chronic finding but

more a qualitative descriptor – think

acute

– Croup / laryngotrachobronchitisp y g

– Characteristic of tracheomalacia

• History of T-E fistula

p y g

– Characteristic of tracheomalacia

• History of T-E fistula

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Barking or Seal-likeBarking or Seal-like– External / internal airway

compression

– Psychogenic – honking quality

– External / internal airway

compression

– Psychogenic – honking quality

Setting or StimulusSetting or Stimulus• Awake or asleep?

– Pathologic coughing usually

continues and disrupts sleep

A cough that resolves during sleep

• Awake or asleep?

– Pathologic coughing usually

continues and disrupts sleep

A cough that resolves during sleep– A cough that resolves during sleep

and resumes on awakening raises

concern of psychogenic etiology

**diagnosis of exclusion

– A cough that resolves during sleep

and resumes on awakening raises

concern of psychogenic etiology

**diagnosis of exclusion

Setting or StimulusSetting or Stimulus• During exercise or rest

– Coughing only with exercise represents a physiologic change

• Asthma, EIB, GERD,

• During exercise or rest

– Coughing only with exercise represents a physiologic change

• Asthma, EIB, GERD, , , ,environmental factors

– A cough that occurs at rest is most common in the pathologic state and usually is exacerbated by activity

, , ,environmental factors

– A cough that occurs at rest is most common in the pathologic state and usually is exacerbated by activity

Setting or StimulusSetting or Stimulus• Continuous or disruptive in nature

– Coughing that is seemingly uncontrollable or disruptive is often psychogenic in nature

• Continuous or disruptive in nature

– Coughing that is seemingly uncontrollable or disruptive is often psychogenic in nature

– While this is a diagnosis of exclusion and requires careful assessment, a chronic cough is generally responsive to active suppression

– While this is a diagnosis of exclusion and requires careful assessment, a chronic cough is generally responsive to active suppression

Setting or StimulusSetting or Stimulus• Following meals or drinking

– Generally would be triggered by

irritant receptors independently or

in association with lower airway

• Following meals or drinking

– Generally would be triggered by

irritant receptors independently or

in association with lower airway

disease

• Think aspiration: vocal cord

paralysis, laryngeal clefts,

primary aspiration, thermal

sensitivity

disease

• Think aspiration: vocal cord

paralysis, laryngeal clefts,

primary aspiration, thermal

sensitivity

Setting or StimulusSetting or Stimulus• GERD

• Gustatory responses

• GERD

• Gustatory responses

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Evaluation of Chronic CoughingEvaluation of Chronic Coughing• History, history, history

• Physical examination

• Routine diagnostic testing

• History, history, history

• Physical examination

• Routine diagnostic testing

– What is done by the primary care

provider

• Subspecialty evaluation

– Advanced diagnostics available at

tertiary care centers

– What is done by the primary care

provider

• Subspecialty evaluation

– Advanced diagnostics available at

tertiary care centers

Physical ExamPhysical Exam• HEENT

– Chronic OM, sinusitis?

– Auscultation of the neck?

• HEENT

– Chronic OM, sinusitis?

– Auscultation of the neck?

• Cardiac

– Ccardiac and vascular

abnormalities?

• Cardiac

– Ccardiac and vascular

abnormalities?

Physical ExamPhysical Exam• Pulmonary

– Wheezing, crackles, rhonchi, tight /

prolonged expiration, auscultation

pre / during / post cough

• Pulmonary

– Wheezing, crackles, rhonchi, tight /

prolonged expiration, auscultation

pre / during / post cough

• Neurologic

– Weakness

• Extremity

– Clubbing

• Neurologic

– Weakness

• Extremity

– Clubbing

Routine Diagnostic Testing: Primary Care Setting

Routine Diagnostic Testing: Primary Care Setting

• Pulse Oximetry

• CXR

• Office Based Spirometry

• Pulse Oximetry

• CXR

• Office Based Spirometry• Office Based Spirometry

• Upper GI

• Baseline Immunologic Evaluation

• Rast Allergy Evaluation

• Office Based Spirometry

• Upper GI

• Baseline Immunologic Evaluation

• Rast Allergy Evaluation

Advanced Diagnostic Evaluation: Subspecialty Setting

Advanced Diagnostic Evaluation: Subspecialty Setting

• Advanced pulmonary function testing

• HRCT

• Advanced pulmonary function testing

• HRCT

– Capability of advanced imaging techniques

• Bronchoscopy and BAL

– A +/- ENT or GI - AerodigestiveEvaluation

– Capability of advanced imaging techniques

• Bronchoscopy and BAL

– A +/- ENT or GI - AerodigestiveEvaluation

Advanced Diagnostic Evaluation: Subspecialty Setting

Advanced Diagnostic Evaluation: Subspecialty Setting

• Nasal brushing biopsy - EM

• Genetic testing

• Advanced immunologic evaluation

• Nasal brushing biopsy - EM

• Genetic testing

• Advanced immunologic evaluationAdvanced immunologic evaluation

– Often done in collaboration with

immunology

Advanced immunologic evaluation

– Often done in collaboration with

immunology

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SummarySummary• Cough duration > four weeks

requires further intervention

• Evaluation and treatment begins in

the primary care setting

• Cough duration > four weeks

requires further intervention

• Evaluation and treatment begins in

the primary care settingp y g

• Characterization of the cough is

highly important in guiding diagnosis

p y g

• Characterization of the cough is

highly important in guiding diagnosis

SummarySummary• Advanced diagnostics and

subspecialty evaluation may be

necessary

• Primary goal is accurate diagnosis

• Advanced diagnostics and

subspecialty evaluation may be

necessary

• Primary goal is accurate diagnosis y g g

and treatment to prevent morbidity

and permanent lung damage

y g g

and treatment to prevent morbidity

and permanent lung damage

ReferencesReferences• Taussig LM, Landau LI, et al. Pediatric

Respiratory Medicine. St. Louis: Mosby, 1999

• Chung, KF et al. Prevalence, pathogenesis, and

causes of chronic cough. The Lancet. 371:1364-

1374 2008

• Taussig LM, Landau LI, et al. Pediatric

Respiratory Medicine. St. Louis: Mosby, 1999

• Chung, KF et al. Prevalence, pathogenesis, and

causes of chronic cough. The Lancet. 371:1364-

1374 2008

• Leigh MW, O'Callaghan C, Knowles MR. The

challenges of diagnosing primary ciliary

dyskinesia. Proc Am Thorac Soc. 2011

Sep;8(5):434-7.

• Leigh MW, O'Callaghan C, Knowles MR. The

challenges of diagnosing primary ciliary

dyskinesia. Proc Am Thorac Soc. 2011

Sep;8(5):434-7.

ReferencesReferences• Zariwala MA, Omran H, Ferkol TW. The emerging

genetics of primary ciliary dyskinesia. Proc Am

Thorac Soc. 2011 Sep;8(5):430-3.

• Knowles MR, Leigh MW, Carson JL, Davis SD, et

al.; Genetic Disorders of Mucociliary Clearance

• Zariwala MA, Omran H, Ferkol TW. The emerging

genetics of primary ciliary dyskinesia. Proc Am

Thorac Soc. 2011 Sep;8(5):430-3.

• Knowles MR, Leigh MW, Carson JL, Davis SD, et

al.; Genetic Disorders of Mucociliary Clearance

Consortium. Mutations of DNAH11 in patients

with primary ciliary dyskinesia with normal ciliary

ultrastructure. Thorax. 2012 May;67(5):433-41.

Consortium. Mutations of DNAH11 in patients

with primary ciliary dyskinesia with normal ciliary

ultrastructure. Thorax. 2012 May;67(5):433-41.

ReferencesReferences• Grüber C, Lehmann C, Weiss C, Niggemann B.

Somatoform respiratory disorders in children and

adolescents-proposals for a practical approach to

definition and classification. Pediatr

Pulmonol. 2012 Feb;47(2):199-205. doi:

10 1002/ppul 21533 Epub 2011 Sep 8

• Grüber C, Lehmann C, Weiss C, Niggemann B.

Somatoform respiratory disorders in children and

adolescents-proposals for a practical approach to

definition and classification. Pediatr

Pulmonol. 2012 Feb;47(2):199-205. doi:

10 1002/ppul 21533 Epub 2011 Sep 810.1002/ppul.21533. Epub 2011 Sep 8. 10.1002/ppul.21533. Epub 2011 Sep 8.

Case 1Case 1• 7-year-old female presents with

cough and chest pain worsened with

exercise

• Diagnosed as asthma

• 7-year-old female presents with

cough and chest pain worsened with

exercise

• Diagnosed as asthma

• ROS

– Constipation and abdominal pain

• PMHx

– Seen by GI and allergist

• ROS

– Constipation and abdominal pain

• PMHx

– Seen by GI and allergist

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Case 1Case 1• FAMHx

– Negative for childhood disease

• Social

• FAMHx

– Negative for childhood disease

• Social

– Outside smoking by parents– Outside smoking by parents

Previous TreatmentPrevious Treatment• Allergist diagnosed allergic rhinitis

and asthma

• Treated with multiple ICS, nasal

steroids without improvement

• Allergist diagnosed allergic rhinitis

and asthma

• Treated with multiple ICS, nasal

steroids without improvement

• Recently increased to ADVAIR 250/50

BID, flonase BID, zyrtec 10mg qd,

tessalon pearls 2-4 daily PRN

• Neg CXR by hx but no spirometry

• Recently increased to ADVAIR 250/50

BID, flonase BID, zyrtec 10mg qd,

tessalon pearls 2-4 daily PRN

• Neg CXR by hx but no spirometry

CoughCough• Dry and barky

• Often associated with clearing of

throat

• Occurs at rest and activity

• Dry and barky

• Often associated with clearing of

throat

• Occurs at rest and activity• Occurs at rest and activity

• At times seems worse after eating

• Does not occur at night during sleep

• Occurs at rest and activity

• At times seems worse after eating

• Does not occur at night during sleep

CoughCough• Chest pain is vague and difficult to

characterize

– Mostly when coughing and it is

getting worse

• Chest pain is vague and difficult to

characterize

– Mostly when coughing and it is

getting worseg gg g

ExamExam• VSS O2 Sat 99% Ht and Wt at 45%

• General: Well Appearing

• CV: RRR w/o murmur 2+ Pulses

• VSS O2 Sat 99% Ht and Wt at 45%

• General: Well Appearing

• CV: RRR w/o murmur 2+ Pulses

• Chest: Clear BS Bilaterally

• Abdomen: Benign

• Extremities: ? 1+ clubbing and

CR <2 sec

• Chest: Clear BS Bilaterally

• Abdomen: Benign

• Extremities: ? 1+ clubbing and

CR <2 sec

Endoscopy / BronchoscopyEndoscopy / Bronchoscopy• Bronchoscopy and BAL were

completely normal

• Upper endoscopy revealed severe esophagitis with white plaques

• Bronchoscopy and BAL were completely normal

• Upper endoscopy revealed severe esophagitis with white plaques

– Esophagus: mixed eosinophillicand neutrophillic microascesseswith budding yeast and pseudohyphae

– Dx: invassive candidal esophagitis

– Esophagus: mixed eosinophillicand neutrophillic microascesseswith budding yeast and pseudohyphae

– Dx: invassive candidal esophagitis

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Evaluation and TreatmentEvaluation and Treatment• Immunologic evaluation was

negative

• ICS felt to contribute in the setting of

GERD

• Immunologic evaluation was

negative

• ICS felt to contribute in the setting of

GERD

• All asthma and allergy meds stopped

with addition of BID PPI and Diflucan

• At follow up pt was symptom free

with no chest pain or cough

• All asthma and allergy meds stopped

with addition of BID PPI and Diflucan

• At follow up pt was symptom free

with no chest pain or cough

SummarySummary• While asthma is the most common

association with cough in children, this cough was NOT completely characteristic of asthma

• While asthma is the most common association with cough in children, this cough was NOT completely characteristic of asthma

• Spirometry should be used in the diagnosis of refractory asthma

– Children as young as 4-5 y/o

• Ultimately escalation of treatment contributed to nosocomial disease

• Spirometry should be used in the diagnosis of refractory asthma

– Children as young as 4-5 y/o

• Ultimately escalation of treatment contributed to nosocomial disease

Case 2Case 2• 14 y/o male with coughing, fatigue,

shortness of breath and a “racing

heart” while walking or climbing

stairs

• 14 y/o male with coughing, fatigue,

shortness of breath and a “racing

heart” while walking or climbing

stairs

• Increasing exertional dyspnea of the

last three weeks

• Cough that worsens with activity and

when supine

• Increasing exertional dyspnea of the

last three weeks

• Cough that worsens with activity and

when supine

Case 2Case 2• Nasal congestion and sinusitis

– Tx with Augmentin

• Started on ADVAIR 250/50 2 weeks

ago without improvement

• Nasal congestion and sinusitis

– Tx with Augmentin

• Started on ADVAIR 250/50 2 weeks

ago without improvementago without improvementago without improvement

ROSROS• Neuro / psych

– Baseline Asperger Syndrome

• CV

• Neuro / psych

– Baseline Asperger Syndrome

• CV

– Racing heart, dyspnea with

walking

• Pulm

– Cough which is worsened supine

– Racing heart, dyspnea with

walking

• Pulm

– Cough which is worsened supine

CoughCough• Improves with rest and sitting up

• Cannot lie supine

– Immediately starts coughing

• Improves with rest and sitting up

• Cannot lie supine

– Immediately starts coughing

• Cough is harsh and honking

• Activity also causes the cough to

worsen but not like lying down

• Cough is harsh and honking

• Activity also causes the cough to

worsen but not like lying down

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PMHxPMHx• Asthma: since childhood

• Recurrent hemolytic anemia and

thrombocytopenia

M lti l t d h ti

• Asthma: since childhood

• Recurrent hemolytic anemia and

thrombocytopenia

M lti l t d h ti• Multiple cutaneous and hepatic

hemangiomata

– Involuted at 13 months

• Resolved VSD

• Multiple cutaneous and hepatic

hemangiomata

– Involuted at 13 months

• Resolved VSD

PMHxPMHx• Asperger syndrome

– Learning disability

• Verbal and reading IQ 70

• Asperger syndrome

– Learning disability

• Verbal and reading IQ 70

• Overall IQ 85• Overall IQ 85

PSHxPSHx• Bilaterl inguinal hernia – 1991

• Left leg cellulitis w/debridement - 1996

• Bilaterl inguinal hernia – 1991

• Left leg cellulitis w/debridement - 1996

BHxBHx• Term delivery: 5lb, 14oz

• Hemolytic anemia and

thrombocytopenia

VSD

• Term delivery: 5lb, 14oz

• Hemolytic anemia and

thrombocytopenia

VSD• VSD• VSD

FHxFHx• Asthma in 9 y/o sibling

• HTN in adults

• No anemia

• Asthma in 9 y/o sibling

• HTN in adults

• No anemia

• No other cardiopulmonary disease• No other cardiopulmonary disease

SHxSHx• Lives with mother, father, and sibling

• Lives in the city

• Italian descent

• Lives with mother, father, and sibling

• Lives in the city

• Italian descent

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Feeding HxFeeding Hx• Breast fed for eight months

• Tolerated addition of fruits and

vegetables

• Developed vomiting and diarrhea

• Breast fed for eight months

• Tolerated addition of fruits and

vegetables

• Developed vomiting and diarrhea• Developed vomiting and diarrhea

with addition of cow milk and table

food which resolved after several

months and after trying soy milk

• Developed vomiting and diarrhea

with addition of cow milk and table

food which resolved after several

months and after trying soy milk

Feeding HxFeeding Hx• Doesn’t eat much meat or dairy

products

• Prefers corn, potatoes, cookies,

and chips

• Doesn’t eat much meat or dairy

products

• Prefers corn, potatoes, cookies,

and chipspp

ExamExam• VS

– Hr 125, r 18, bp 110/48 o2 96% ra

• Gen

• VS

– Hr 125, r 18, bp 110/48 o2 96% ra

• Gen

– Alert without distress

– Thin habitus

• HEENT

– Scleral icterus

– Alert without distress

– Thin habitus

• HEENT

– Scleral icterus

ExamExam• CV

– S1 with loud single s2 and a 3/6

blowing diastolic murmur 2+

peripheral pulses

• CV

– S1 with loud single s2 and a 3/6

blowing diastolic murmur 2+

peripheral pulsesp p p

• Lungs

– Clear BS but coughing with deep

inspiration and supine position

p p p

• Lungs

– Clear BS but coughing with deep

inspiration and supine position

ExamExam• AB

– Soft and NT /ND

– No hepatomegaly with spleen tip

down 3 cm

• AB

– Soft and NT /ND

– No hepatomegaly with spleen tip

down 3 cmdown 3 cm

• Ext

– Cr 2 seconds and no clubbing

down 3 cm

• Ext

– Cr 2 seconds and no clubbing

EvaluationEvaluation• ECHO: Pulmonary HTN

– Predicted pulmonary artery

pressure of 125 systolic and

55 diastolic

• ECHO: Pulmonary HTN

– Predicted pulmonary artery

pressure of 125 systolic and

55 diastolic

– RVH and LVH with diastolic

pulmonary valve insufficiency

otherwise normal intracardiac

anatomy

– RVH and LVH with diastolic

pulmonary valve insufficiency

otherwise normal intracardiac

anatomy

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17

EvaluationEvaluation• Spirometry

– Moderate obstructive and

restrictive disease

Patient had difficulty performing

• Spirometry

– Moderate obstructive and

restrictive disease

Patient had difficulty performing– Patient had difficulty performing

the test

– Patient had difficulty performing

the test

Problem ListProblem List• Severe pulmonary hypertension

• Chronic hemolytic anemia and

thrombocytopenia

L l IQ d l i di bilit

• Severe pulmonary hypertension

• Chronic hemolytic anemia and

thrombocytopenia

L l IQ d l i di bilit• Low-normal IQ and learning disability

• History of multiple hemangiomata

• Questionable dietary aversion to

protein

• Low-normal IQ and learning disability

• History of multiple hemangiomata

• Questionable dietary aversion to

protein

DDDD• Idiopathic pulmonary hypertension

• Metabolic disease

– Lysinuric protein intolerance,

gaucher etc

• Idiopathic pulmonary hypertension

• Metabolic disease

– Lysinuric protein intolerance,

gaucher etcgaucher, etc.

• Hereditary hemorrhagic

telangiectasia

• Hemoglobinopathies

gaucher, etc.

• Hereditary hemorrhagic

telangiectasia

• Hemoglobinopathies

DDDD• PVOD

• Thrombosis (chronic)

• Collagen vascular disease

• PVOD

• Thrombosis (chronic)

• Collagen vascular disease

• Arterial-venous shunting• Arterial-venous shunting

Hematologic EvaluationHematologic Evaluation• WBC 9, HgB 10 and PLT 50s

• Smear mircoangiopathic hemolysis

• INR 1.7

• WBC 9, HgB 10 and PLT 50s

• Smear mircoangiopathic hemolysis

• INR 1.7

– All coagulation factors slightly

low except fibrinogen and factor

VII activity

• LDH 1500s

– All coagulation factors slightly

low except fibrinogen and factor

VII activity

• LDH 1500s

Hematologic EvaluationHematologic Evaluation• Historical evaluation of immune and

non-immune hemolysis negative

• Historical evaluation of immune and

non-immune hemolysis negative

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Metabolic Evaluation Metabolic Evaluation • Fasting ammonia: 39

• Post-prandial ammonia: 90-120

• Urine amino and organic acids:

l

• Fasting ammonia: 39

• Post-prandial ammonia: 90-120

• Urine amino and organic acids:

lnormal

• Serum amino acids: normal

• Metabolic storage diseases: normal

• Acylcarnitine profile: normal

normal

• Serum amino acids: normal

• Metabolic storage diseases: normal

• Acylcarnitine profile: normal

Hepatic EvaluationHepatic Evaluation• AST, ALT, GGT and AlkP: normal

• Albumin: 2.0

• Prealbumin: 5

• AST, ALT, GGT and AlkP: normal

• Albumin: 2.0

• Prealbumin: 5

• TB: 3-4 (unconjugated)

• Normal electrolytes

• TB: 3-4 (unconjugated)

• Normal electrolytes

Congenital Extrahepatic Portocaval Shunts

Congenital Extrahepatic Portocaval Shunts

• The Abernathy Malformation – 1793

– Type 1

• End to side anastomosis and

• The Abernathy Malformation – 1793

– Type 1

• End to side anastomosis and• End to side anastomosis and

congenital absence of the

portal vein

– Associated with dextrocardia,

transposition, and polysplenia

• End to side anastomosis and

congenital absence of the

portal vein

– Associated with dextrocardia,

transposition, and polysplenia

Congenital Extrahepatic Portocaval Shunts

Congenital Extrahepatic Portocaval Shunts

– Type 2

• Side to side

• Not associated with other

– Type 2

• Side to side

• Not associated with other• Not associated with other

anomalies but associated with

encephalopathy − Howard E and Davenport M, J Ped Surg, 32; 494-97, 1997

• Not associated with other

anomalies but associated with

encephalopathy − Howard E and Davenport M, J Ped Surg, 32; 494-97, 1997

SummarySummary• Coughing, even as the presenting

CC can be a distracter and delay

diagnosis

• Coughing is not specific to lung

• Coughing, even as the presenting

CC can be a distracter and delay

diagnosis

• Coughing is not specific to lung g g p g

disease

g g p g

disease

SummarySummary• Focusing on basic history and

adhering to the concept that

pediatric disease is most frequently

of common primary etiology

• Focusing on basic history and

adhering to the concept that

pediatric disease is most frequently

of common primary etiology

• Always listen and hear parental

instincts

• Always listen and hear parental

instincts