APPROACH TO COUGHJerry V. Pua MD2nd year Resident

It’s the simple things in life we forgetYou hear her talkin’ but don’t hear what she saidWhy do you make something so easy so complicated?Searching for what’s right in front of your face..

- Simple Things by Usher

Objectives

To discuss etiology, differential diagnosis and work up for children presenting with cough

To discuss approach, diagnosis, management, recommendations and prevention of B. pertussis infection

General Data

A.E. 6 month old, Female Filipino, Catholic Brgy. Batasan Hills, Quezon City

Consulted at ER last June 15, 2013

Informant: Grandmother Reliability: 80%

Chief Complaint

Cough – 2 weeks duration

History of Present Illness

2 weeks PTA•Non productive cough•No fever nor other associated symptoms•No consult done

5 days PTA•Persistence of recurring bouts of cough•No other associated symptoms•Consulted LHC – Carbocisteine and Amoxicillin (40mkday)

History of Present Illness

3 days PTA • Persistence of continous non productive cough followed by facial cyanosis• Difficulty breathing – alar flaring, tachypnea, ‘seesaw’ breathing

Few hours PTA

•Persistence of symptoms prompted consult at Local Clinic•A> Bronchopneumonia rule out Pertussis•Advised consult at a tertiary institution

Review of Systems

Decrease appetite

No failure to thrive, feeding interruption

No skin lesions No diaphoresis,

no fainting spells

No vomiting, no diarrhea nor constipation

No pallor No facial

redness during bouts of cough

No convulsion No limitation of

movements No bleeding

manifestations

Family History

No heredo-familial disease on both sides of the family

(+) (+)(+) cough

Birth and Maternal History

Born to 39 year old G5P4 (4014) non smoker, non alcoholic beverage drinker mother

No pre natal check up, denies maternal illness

Multivitamins, Ferrous Sulfate intake

Delivered Full term via NSD at home assisted by traditional birth attendant

No feto-maternal complication during and after the delivery

Immunization History

No immunization received

Nutritional History

Milk Formula – since birth No milk formula intolerance

Complimentary feeding – 6 months old No interrupted feeding No feeding problems

Growth and Development

Motor Head control – 2 mos. rolls over – 4 mos. sits

with support – 6 mos. Language

Imitates sounds – 5mos Daily Living

Put anything at the mouth – 4 mos. Social/Adaptive

Social smile – 2 mos. plays with caregiver – 6 mos

Past Medical History

No routine check up No previous hospitalization No previous surgical intervention done. No allergies

Physical Examination

Awake, irritable, in mild respiratory distress. Well hydrated.

Weight: 6 kg (z score below 0 ) Height: 65 cm (z score 0 ) BP 80/50HR 122 RR 38 T 37.1

Skin: Warm, Moist, No rashes or other dermatosis. No cyanosis.

Physical Examination

HEENT: Normocephalic. Aniceteric sclera; pink palpebral conjunctivae; no eye discharge

(+) intermittent alar flaring. No nasal discharge nor bleeding. No tragal tenderness, no aural discharge

Non hyperemic posterior pharyngeal wall, no exudates, uvula midline

(+) cervical lympadenopathy, bilateral

Chest and Lungs: No chest deformity nor skin lesions at the chest. Symmetrical chest expansion, (+) subcostal and intercostals retractions (+) crackles on both lung fields

Physical Examination

Heart: Adynamic precordium, Apex beat at 4th ICS LMCL, normal rate regular rhythm, no murmur

Abdomen: Globular, No visible veins. Normoactive bowel sounds. Soft, non tender, no organomegaly.

Genitalia: Grossly female Extremities: No preferential movement. Pulses on

all extremities are full and equal. No clubbing, cyanosis of fingers or toes. CRT <2 seconds. No deformities.

Neurologic Examination

Mental Status: Awake, irritable. GCS 15 Cranial Nerves: Intact Motor: Good muscle tone, no

fasciculation or atrophy, no involuntary movement. MMT 5/5 on all extremities. DTR’s 2++

Sensory: No deficit. No babinski or clonus.

Cerebellar: No nystagmus Meningeal signs: No Kernig’s, No

Brudzinski, No nuchal rigidity

BRONCHOPNEUMONIARULE OUT PERTUSSISNO STUNTING NO WASTING

Admitting Impression

SYMPTOMS, SIGN, OR LABORATORY FINDINGS PATHOGNOMONIC OF A DISEASE

Approach to Diagnosis

COUGH

Most common symptom presenting to medical practitioners

Cough is a forced expulsive maneuver, usually against a closed glottis

Sound of a cough is due to vibration of larger airways and laryngeal structures during turbulent flow in expiration

Cough quality in children: a comparison of subjective vs. bronchoscopic findingsAnne Bernadette Chang, et. alDept of Paediatrics & Child Health, University of QueenslandDept Respiratory Medicine, Royal Children's Hospital, Brisbane

COUGH

Estimating the duration of cough is the first step in narrowing the list of possible diagnoses

THE DIAGNOSIS AND TREATMENT OF COUGHRICHARDS. IRWIN, M.D.,AND J. MARK MADISON, M.D.The New England Journal of Medicine

Types of Cough (Duration)

Acute Cough -- a recent onset of cough lasting <3 weeks

Subacute Cough (Prolonged acute cough) -- cough slowly resolving over a 3–8-week period

Chronic Cough -- A cough lasting >8 weeks Recurrent Cough -- cough without a cold is

taken as repeated (>2/year) cough episodes, apart from those associated with colds, that each last more than 7–14 days

Recommendations for the assessment and management of cough in childrenM D Shields, A Bush, M L Everard, S McKenzie, R Primhak, on behalf of the British Thoracic Society Cough Guideline Group

ACUTE COUGH

Cough lasting for a maximum of 3 weeks Common caused: URTI, acute bronchitis or

tracheobronchitis (bacterial or viral) Such infections is usually self limited and

subsides within one to two weeks along the clearing of the infection

No targets or reliable measures to predict the duration of cough at its onset, also to predict which will persist into sub acute or chronic cough

COUGH MANAGEMENT: A Practical ApproachF. De Blasio, et. al

COUGH MANAGEMENT: A Practical ApproachF. De Blasio, et. al

COUGH MANAGEMENT: A Practical ApproachF. De Blasio, et. al

Types of Cough (Causes)

Specific Cough -- one in which there is a clearly identifiable cause

Non specific isolated Cough -- typically have a persistent dry cough, no other respiratory symptoms, well with no signs of chronic lung disease and have a normal chest radiograph

Post viral Cough -- cough originally starting with an upper respiratory tract infection but lasting <3 weeks

Recommendations for the assessment and management of cough in childrenM D Shields, A Bush, M L Everard, S McKenzie, R Primhak, on behalf of the British Thoracic Society Cough Guideline Group

Types of Cough (Quality)

Classic Recognizable Cough Certain cough characteristics classically

taught to point to specific etiologies Dry Cough Wet Cough

Cough in children: definitions and clinical evaluationPosition statement of the Thoracic Society of Australia and New Zealand

Salient Features

6 months old 2 weeks history of

cough No fever Cyanosis at bouts of

cough Difficulty of

breathing Siblings with cough No immunization

received

In mild respiratory distress

Intermittent alar flaring

Intercostal and subcostal retractions

Crackles on both lung fields

Patient: A.E.

6 months old, Female

Working Impression:

Bronchopneumonia

Rule out Pertussis

Course at the Ward

1st Hospital Day

DiagnosticsArterial Blood GaspH 7.24 pCO2 26pO2 179 O2sat 99HCO3 11.1 BE - 14.7

CBC w/ PCHgb 37.7 Hct 0.42WBC 35.5 Seg 21Lympho 79 Platelet 647

Case Definitions: Pertussis (WHO) Cough lasting at least 2 wk with at least

1 of the following symptoms: paroxysms of coughing inspiratory whooping posttussive vomiting (ie, vomiting

immediately after coughing) Clinical case: a case that meets the clinical

definition, but is not laboratoryconfirmed Laboratory-confirmed case: a case that meets

the clinical case definition and is laboratory-confirmed

Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

Clinical Definitions: Pertussis (CDC) Cough illness lasting ≥ 2 weeks with 1 of

the following without apparent cause: Paroxysms of coughing Inspiratory “whoop” Posttussive vomiting

Probable case: symptoms, absence of laboratory confirmation and epidemiologic linkage to a laboratory-confirmed case of pertussis

Confirmed case: symptoms + > 1 following – PCR positive for pertussis or contact with laboratory-confirmed case of pertussis

Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

Diagnostics

Common laboratory diagnostic methods: Culture – gold standard Direct antigen detection PCR Direct fluorescent antibody (DFA) testing Serologic demonstration enzyme-linked

immunosorbent assay (ELISA) or Western blot with various B. pertussis antigens and agglutination Measuring an increase in titers between acute

and convalescence phase serum specimens or high single serum antibody values

Defining Pertussis EpidemiologyClinical, Microbiologic and Serologic PerspectivesJames D. Cherry, MD, et al Pediatr Infect Dis J 2005

Diagnostics: Serologic Testing

Proper performance of culture, PCR and ELISA to measure increases or decreases in IgG and IgA antibody titers to Pertussis Toxin in paired serum samples, the sensitivity and specificity of the laboratory diagnosis of B. pertussis infection

The greatest sensitivity is obtained when culture, PCR and serologic testing are all performed on individuals with cough illness

Defining Pertussis EpidemiologyClinical, Microbiologic and Serologic PerspectivesJames D. Cherry, MD, et al Pediatr Infect Dis J 2005

Pertussis PCR

Key factors for the successful application of PCR in the diagnosis of infection by Bordetella spp.: Sample collection and processing DNA purification Primer selection Amplification conditions

PCR as a diagnostic tool has the advantage of a much higher sensitivity compared with conventional cultureDefining Pertussis Epidemiology

Clinical, Microbiologic and Serologic PerspectivesJames D. Cherry, MD, et al Pediatr Infect Dis J 2005

Pertussis: PCR

A 2.6-fold increase in detection of B. pertussis using PCR compared with culture

PCR results were compared with serologic diagnosis; PCR had a sensitivity of 61% and a specificity of 88%

Patients with symptoms meeting the CDC clinical case definition for pertussis and who had a specimen positive by PCR or DFA were considered to have true B. pertussis infections Defining Pertussis Epidemiology

Clinical, Microbiologic and Serologic PerspectivesJames D. Cherry, MD, et al Pediatr Infect Dis J 2005

2nd Hospital Day

DiagnosticReferred to Infection Control CommitteeBlood CSNasopharyngeal Pertussis PCR2D Echo with PAP

Complete Blood Counts

06/15/13 06/16/13 06/17/13 06/18/13 06/20/13Hemoglobin 137.7 125.1 126.2 131.4 140.3Hematocrit 0.42 0.38 0.38 0.40 0.43WBC Count 35.5 27.5 25.9 19.2 16.8Diff. CountSegmenterLymphocytesMonocytes

2179

147210

166515

216214

316306

Platelet 647 523 537 539 465

Diagnotics: Complete Blood Count A total count of ≥ 20,000

WBCs/mm3 with ≥ 10,000 lymphocytes/mm3 in a young infant with coryza, cough, apnea or other respiratory distress is indicative of B. pertussis infection

A total count of ≥ 30,000 WBCs/mm3 is cause for concern and the rapidity of the WBC count rise is also an important indicator of worsening condition

Pertussis in Young Infants – Guidance for Clinicians James D. Cherry MD, et. al. May 2010

Microbiology

Blood Culture and Sensitivity: No growth for 5 days of incubation

Nasopharyngeal Bordetella pertussis Polymerase Chain

Reaction POSITIVE for Bordetella pertussis DNA

PERTUSSISBRONCHOPNEUMONIANO STUNTING NO WASTING

Final Diagnosis

Pertussis

Acute respiratory infection caused by Bordetella pertussis

‘intense cough’ Extremely contagious -- attack rates as

high as 100% in susceptible individuals exposed to aerosol droplets at close range

Bordetella pertussis

Tiny, fastidious, gram-negative coccobacilli that colonize only ciliated epithelium

Expresses pertussis toxin (PT), the major virulence protein

After aerosol acquisition, pertussis organism attaches to ciliated respiratory epithelial cells

Tracheal cytotoxin, adenylate cyclase, and PT appear to inhibit clearance of organisms Responsible for the local epithelial damage

Epidemiology

Worldwide, pertussis is a significant cause of infectious mortality 20 to 40 million cases 200,000 to 400,000 death per years Most of cases and deaths occur in infancy

WHO. Pertussis vaccines. Wkly Epidemiol Rec. 1999;74:137–143

Epidemiology

Philippine Pediatric Society Registry 99 out of 1935660 cases

Philippine Children’s Medical Center 32 cases: Total probable and confirmed

pertussis cases admitted from JANUARY-JUNE 2013

Source of Infection

Rate of subclinical infection is as high as 80%

Coughing adolescents and adults -- major reservoir for B. pertussis -- usual sources of infection for infants and children

Household contact with infected adolescent and adults – major source of pertussis infection in not fully immunized infants

Infant Pertussis and Household Transmission n Korea.The Korean Academy of Medical Sciences.

Mode of Transmission

Stages of Pertussis Infection

Catarrhal stage (1-2 wk) begins insidiously after an incubation period (3-12 days)

Paroxysmal stage (2-6 wk) onset marks by coughing Cough begins as a dry, intermittent,

irritative hack and evolves into the inexorable paroxysms

Post-tussive emesis is common, and exhaustion is universal.

Convalescent stage (≥2 wk), the number, severity, and duration of cough episodes diminishes

Stages of Pertussis Infection

Pertussis in Young Infants

Catarrhal stage -- characterized by excessive sneezing or “throat clearing” -- adherence of organism in the ciliated epithelium throughout the respiratory tract – tissue necrosis, production of mucus, and inflammatory cell response

Paroxysmal stage – atypical Acute life-threatening episode is common Spells of cough leading to cyanosis or bradycardia

and limpness as well as apnea Post-tussive vomiting is common

“whoop cough” is rarely present in very young infant

Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

1st - 2nd Hospital Day

ManagementIsolationD5LR (mild)O2 at 10Lpm

Medications:Ampicillin (100)Erythromycin (40) ---- Azithromycin (10)Salbutamol nebulization every 4 hours

NPO

Goals of hospitalization

Assess progression of disease and likelihood of life-threatening events at peak of disease

Prevent or treat complications Educate parents in the natural history of

the disease and in care that will be given at home

Goals of therapy

Limit the number of paroxysms Observe the severity of the cough Provide assistance when necessary Maximize nutrition, rest, and recovery

without sequelae

MedicationsAge Primary Agents Alternate Agents

Azithromycin Erythromycin Clarithro TMP-SMZ

<1 mo 10 mg/kg/day in a single dose for 5 days

(Infantile hypertrophic pyloric stenosis)40-50 mg/kg/day in 4 divided doses for 14 days

Not recommended (safety data unavailable)

Contraindicated for infants aged <2 mo (risk for kernicterus)

1-5 mo 10 mg/kg/day in a single dose for 5 days

40-50 mg/kg/day in 4 divided doses for 14 days

15 mg/kg/d in 2 divided doses for 7 days

Contraindicated at age <2 moFor infants aged ≥2 mo: TMP 8mg/kg/day plus SMZ 40 mg/kg/day in 2 divided doses for 14 days

Infants aged ≥6 mo and child

10 mg/kg in a single dose on day 1 (maximum 500 mg), then 5 mg/kg/day (maximum 250 mg) on days 2-5

40-50 mg/kg/day (maximum 2 g/day) in 4 divided doses for 14 days

15 mg/kg/d in 2 divided doses (maximum 1 g/day) for 7 days

TMP 8 mg/kg/day plus SMZ 40 mg/kg/day in 2 divided doses for 14 days

Pertussis Complications in Young Infants Life-threatening complications are most

common in infants younger than 3 months

Respiratory tract complications: apnea, bacterial pneumonia, and pulmonary hypertension Secondary bacterial pneumonia – leading

identified cause of pertussis-related infection

Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

Pertussis Complications in Young Infants Respiratory Failure with Pertussis may

stem from complications of Pneumonia, Pulmonary Hypertension, and Apnea Apnea – due to failure of self-rescue

breathing at the end of a paroxysm of coughing or profound vagal stimulation

Infants intubated due to respiratory failure secondary to apnea have better prognosis than those intubated due to pneumonia or pulmonary hypertension

Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

Pertussis Complications in Young Infants Severe Bordetella pertussis consist of

constellation of bronchopneumonia, extreme leukocytosis, refractory hypoxemia, and pulmonary hypertension

White blood cell counts >100 000 in the setting of B. pertussis pneumonia associated with increase mortality

Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension: Improvement in Oxygenation After a Double Volume Exchange TransfusionMichael J. Romano, et. al. Pediatrics 2004

Pertussis: Proposed Pathologic Course

Infection of tracheal epithelium with Bordetella pertussis

Ciliostasis, epithelial damage and compromised mucociliary clearance

Pulmonary Infection

Necrotizing bronchopneumonia

ARDS

PULMONARY HYPERTENSION

Cardiac Failure and Shock

apnea

hypoxemia

Pulmonary vasoconstriction

Toxin mediated leukocytosis

Increase whole blood mass

Increase vascular resistance

Pathology and Pathogenesis of Fatal Bordetella pertussis Infection in InfantsChristopher D. Paddock, et. al.

3rd -5th Hospital Day The rest of hospital stay patient

completed her antibiotics.

O2 supplementation was titrated down and eventually discontinued.

Patient discharged well and stable.

Indications for ICU referral

Infants less than or equal 3 months old with clinical deterioration

White Cell Count more than or equal to 30, 000 or rapidly rising in count (>10,000 in 6 hours)

Respiratory failure or frequent apnea Progressive pneumonic changes in CXR Persistent tachycardia/ cardiovascular

instability Neurological symptoms including seizure

South Thames Retrieval Service Guideline

ICU care

Apnea, pneumonia, and seizures are the most common presenting symptoms requiring ICU care

Leukocytes aggregate within the pulmonary circulation and form a mechanical obstruction to transpulmonary blood flow with the result being severe hypoxemia and pulmonary hypertension

Cardiac failure associated with critical pertussis is likely right sided heart failure secondary to the pulmonary hypertension

Double Volume Exchange Transfusion Multiple authors have reported double

volume exchange transfusion as an effective therapy for the pulmonary hypertension, and secondarily the hypoxemia and cardiac failure

Technique of double volume exchange utilized is the same as performed for the newborn with hyperbilirubinemia

Hypomagnesemia and especially hypocalcemia may occur thus recommended routine calcium supplementationChen H, Lee M, Tsao L. Exchange Transfusion Using Peripheral Vessels Is Safe and Effective in Newborn Infants. Pediatrics 2008

Indications for DVET

White cell count more than or equal to 30,000 and rapidly rising count

White cell count more than or equal to 30, 000 with pneumonia or hemodynamic instability

White cell count more than or equal 50,000

South Thames Retrieval Service Guideline

Studies shows…

Appearance of respiratory symptoms paralleled the rise in leukocyte count

Temporal relationship between the initiation of exchange transfusion and improvement in oxygenation

Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension: Improvement in Oxygenation After a Double Volume Exchange TransfusionMichael J. Romano, et. al. Pediatrics 2004

Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension: Improvement in Oxygenation After a Double Volume Exchange TransfusionMichael J. Romano, et. al. Pediatrics 2004

Criteria for Hospital Discharge Over a 48-hr period disease severity

is unchanged or diminished No intervention is required during

paroxysms Nutrition is adequate No complication has occurred Parents are adequately prepared for care

at home

Prevention: Vaccination

Efficacy of the vaccine in reducing disease severity was 48% among children vaccinated with 3 doses of whole-cell (67%) or acellular (32%)

Pertussis vaccination substantially decrease the severity of breakthrough disease in vaccinated children (3 doses) compared to unvaccinated children Unvaccinated children twice likely to have

severe disease than vaccinated childrenEffects of Pertussis vaccination on Disease: Vaccine Efficacy in Reducing Clinical SeverityPreziosi, Marie-Pierre, et.al. Clinical Infectious Disease 2003

Prevention: Vaccination

DTaP (Diphtheria, tetenus toxoid and acellular Pertussis) contain inactivated PT and 2 or more

other bacterial components (FHA, Pn, and Fim 2 and 3)

4 doses during the 1st 2 years of life 2,4,6 and 15-18 months

5th dose of DTaP recommended for children at 4-6 yr of age

Prevention: Vaccination

Tdap (Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed) Preferred age for Tdap vaccination is 11-

12 yr Pregnant adolescents who are in their

2nd or 3rd trimester All adolescents 11-18 yr of age who

received Td, but not Tdap, should receive a single dose of Tdap to provide protection against pertussis

Vaccination of women during pregnancy and newborns

Timing of maternal Tdap immunization is important – administered during the third trimester to have maternal pertussis antigen-specific IgG levels at their peak

Immunization with DTaP or aP vaccines is not recommended in newborns -- controversial

Pertussis re-emergence in the post-vaccination eraChiappini et al. BioMedCentral Infectious Disease 2013

Cocooning strategy

Providing indirect protection to infants who are too young to be immunized or protected by vaccine through immunization of their parents and other family members, caregivers and close contacts

Pertussis re-emergence in the post-vaccination eraChiappini et al. BioMedCentral Infectious Disease 2013

Vaccination of preschool and adolescent Contributes to increase herd immunity Reduce transmission of pertussis to

susceptible population Reduce reservoir of pertussis within

population and indirectly prevent pertussis case in infants and young children

Pertussis re-emergence in the post-vaccination eraChiappini et al. BioMedCentral Infectious Disease 2013

Immunization of health-care workers Pertussis among health-care personnel

has been reported to be 1.7 times higher than the general population

Health-care personnel who have direct contact with patients should receive single dose of TdaP as soon as feasible, if they have not previously received TdaP

Pertussis re-emergence in the post-vaccination eraChiappini et al. BioMedCentral Infectious Disease 2013

Updates

Patient follow up at OPD – well, active

Received her first dose of DPT, OPV, and Hepatitis B

Relatives were educated regarding the importance of immunization as well as proper hygiene to stop the vicious cycle of transmission

Summary

A case of 6 month old unimmunized infant who presented with subacute cough with paroxysms, who after a nasopharyngeal swab PCR was confirmed with Bordetella pertussis

Started on Azithromycin per orem and eventually discharged well and stable

Recommendations for management of pertussis

Emphasized the importance of immunization on preventing vicious transmission cycle

THANK YOU!!!