Chronic Recurrent Cough and

Childhood Asthma
Helmi Lubis
Ridwan M. Daulay
Wisman Dalimunthe
Rini S. Daulay 1
Definition of cough
a sudden explosive expiratory maneuver
that tends to clear materials from the
airways and prevent aspiration of food or
fluid

2
Physiologic or pathologic?
Cough

Physiologic Pathologic

Pathologic: intensity, frequency, cough characteristic, sputum

characteristic
Cough without receptor stimulation: psychogenic, habitual cough

3
Cough Model Reflex
Cerebral cortex
Voluntary control Placebo effect
of cough

Sensation of
irritation

Cough control Endogenous

centre opioids
+ve -ve Exogenous opioids

Respiratory area of brainstem

Vagus nerve

Airway irritation Respiratory muscles

COUGH 4

Widdicombe J. Cough. Blackwell publishing 2003; 20

Cough Reflex Arc
Receptor Afferent Cough center Efferent Efector

Larynx
Vagal nerve
Muscle,
branch
Trachea Larynx, trachea,
and bronchus
Bronchus Vagal nerve

Distributed evenly
Ear in medulla near by
the respiratory
Gastric center:
Under the higher
control center Diaphragm;
Nerve Phrenicus,
Nose Intercostal,
Trigeminal nerve Intercostal &
Abdominal & lumbal
Sinus paranasal lumbaris
muscles

Glossopharyngeal Respiratory tract muscles

Trigeminal, Facial
Pharynx Muscles involve in
nerve Hippoglosus nerve, etc
respiration

Pericardium
Nerve phrenicus
diaphragm
5
Chang AB. Cough 2003;7:1-15.
 How do we cough ?
Inspiratory Compressive Expiratory

 Inspiratory muscles contraction

Deep inspiration Glottic closure 0.2’  Expiratory muscles
(150-200% tidal contraction
Contraction of
volume)
thoracic & abdminal  Sudden glottic
 Maximal dilation of muscles vs fixed opening
tracheo-bronchial tree diaphragm
Explosive release of
 Intrathoracic intrathoracic air
pressure

Cloutier MM: Cough, in : Loughlin GM ed Resp dis in children, 1994

 Mechanism of Cough
Sound
6.0 Air
volume 50
5.0

cmH2O
4.0 40
L/s

Subglottic Flow rates

3.0 30
2.0 pressure 20
1.0 10
0.0 0
1 2 3
Negative Min flow positive
Flow phase phase Flow phase
Inspiratory glottis Expiratory phase
phase closure (explosive)

Figure 1. Diagrammatic representation of the changes of the following variables during

a representative cough: flow rate, volume, subglottic pressure and sound level.
7
McCool FD. Chest 2006;129:48S-53S.
 IPS(IDAI): Chronic Recurrent Cough or
(Batuk Kronik Berulang / BKB)
Chronic: > 2 weeks AND/OR
Recurrent: > 3 episodes in 3 months

 BKB is not a final diagnosis, but lead to

a group of diseases with the same
manifestation

8
Diagnosis of Asthma

“Cough and/or wheezing that:

•Hyperreactivity
•Nocturnal (variability)
•Reversibility
•Episodic
•“Atopic family” 9
 Inflammatory processes
Desquamation of
epithelium

Hyperplasia of Mucus plug

Mucos glands

Basement
Membrane
thickening

Oedema
Neutrophil and
Smooth muscle eosinophil infiltration
Hypertrophy and contraction 10
Barnes PJ
Getting to asthmatic inflammation
– what does it take ???
Normal Asthma

11
 Inflammation in asthma
Acute
inflammation

Steroid
response

Chronic inflammation

Structural changes

Time

12
Barnes PJ
 Pathogenesis
Environment Genetic susceptibility

Chronic allergic inflammation

(Mast cells, T-Cells, Eosinophils)

AIRWAY WALL THICKENING

13
 Classification of asthma
• Severity of attacks • Class of disease
(Acute) (Chronic)
Mild Infrequent episodic
Moderate asthma
Severe Frequent episodic
Respiratory arrest asthma
imminent Persistent asthma

14
 2 aspect of asthma
Asthma : chronic respiratory disease, that can
have acute exacerbation

Chronic Asthma
Asthma
Acute Asthma
 Asthma management

Acute asthma Chronic asthma

• Attack • Long term

management management

• Algorithm attack • Algorithm diagnosis

management & treatment
 Asthma medication, function category
Reliever Controller
• To relieve / reduce • To control / prevent
symptoms and/ symptoms and/
attack attack
• Long term use
• As needed use
• Anti-inflammations
• Bronchodilators • Inhaled steroid, ALTR
• 2-agonist, • Oral, inhalation,
xanthenes, systemic • For FEA & PA, not for
steroid IEA
• Oral, inhalation,
injection
 Acute asthma management
Asthma attack / symptoms present:
– First line therapy
• 2 agonist
• Ipratropium bromide
Chronic asthma (long term management):
– First line therapy
• Inhaled steroid
• Long-acting 2 agonist (LABA)
Asthma Attack

19
Why happened ??
 Asthma
Triggers

• House dust mite

Longterm (HDM)
management • Smoke (polution)
failure • Food
• Infection

Attack
 Pathophysiology
Trigger

Bronchocontriction, Mucosal edema, Excessive secretion

Airway obstruction

Nonuniform Hyperinflation
ventilation

Atelectasis Mismatching of Decreased

ventilation and perfution compliance

Decreased
surfaktant Alveolar hypoventilation Increased work
Acidosis of breathing

Pulmonary
vasoconstriction  PaCO2
 PaO2
 Severity of asthma attack

Mild

Moderate
3.9%
11.7% Severe

84.4%
 Estimation of severity of asthma attack
Sign/ Mild Moderate Severe Imminent
Symptom respiratory
arrest
Activities Walking Talking Rest
(infant) (loudly cried) (weak cried) (stop eating)

Talking Complete Phrasesor or Single words

sentences partial or short
sentences phrases
Position Can lie Prefer to seat Tripod-like
down sitting
positions
Alertness Maybe agitated Usually Usually Confused
agitated agitated
Cyanotic Absent Absent Present

Wheezing Moderate, Loud, eksp. + Audible Difficult/ can’t

end of eksp. insp. be heard
Breathing Minimal Moderate Severe
difficulties
Acessory Usually not Usually yes Yes Paradoxical
Muscle of movement
respiration
Retraction No intercostal Moderate +, Deep +, +, Decrease/
to mild tracheosterna nassal flaring none
retraction l retraction
Respiratory Tachypnea Tachypnea Tachypnea Decreasing
rate
Pulse rate Normal Tachycardia Tachycardia Bradicardia

Pulsus Absent Present Present absent

paradoxus (<10 mmHg) 10-20 mmHg >20 mmHg (Fatique resp.
muscle)
PEF / FEV1 (% predictive- value/ % good -value)
- pre-b.dilat. >60% 40-60% <40%
- post-b.dilat >80% 60-80% <60%
SaO2 >95% 91-95% <90%

PaO2 Normal >60 mmHg <60 mmHg

PaCO2 <45 mmHg <45 mmHg >45 mmHg

 Algorithms asthma attack
Clinic/ ER
Rate attack severity

First management
• 2-agonist nebulization (neb) 3x, 20’ interval
• 3rd neb + anticholinergic

Mild attack Moderate attack Severe attack

(neb 1x, (neb 2-3x, (neb 3x,
good response partially response) bad/ no response)
• Hold out 1-2 hours, • Give O2 • O2 since beginning
may go home • Reevaluate  moderate • IV line
• Attack reappear   One day care (ODC) • Chest X ray
moderate attack • IV line
• Reevaluate→severe
→hospitalized
 Hospital Room
May go home
One Day Care (ODC) • O2 continued
• Give 2-agonist • O2 continued • Overcome dehidration
(inhalation / oral) • gGve oral steroid and acidosis
• Patient with • Neb every 2 hrs • IV steroid every
controller, continued • Improve in 8-12 hrs, 6-8 hrs
• Viral ARI as trigger stable may go home • Neb every 1-2 hrs
steroid oral may given • No improve within 12 hrs,• IV aminophylline, initial-
• Visit outpatient clinic hospitalized maintenance
in 24 hours • Improve neb every 4-6hrs
• Stable within 24 hrs,
Note: may go home
• severe attack from beginning, directly neb with • No improvement,
ipratropium impending resp failure -
• neb can be replaced by adrenalin sc 0.01 ml/kgBw/x, PICU
max 0.3ml/x
• O2 2-4L/mnt from the start, including during neb
 Goals of management for
asthma attack

• Relieve the symptoms quickly and

precisely
• Reduce hypocxemic
• Lung function, back to normal
• After attack: reevaluation
 Asthma attack

Nebulization 1-2 x

Good responses Poor responses

ODC
Discharge Oxygen
Nebulization Wards
Oral Steroid Oxygen
Bronchodilator
IVFD Nebulization
IVFD
IV/oral Steroid
Good Response Poor Response Rehydration
Amynophylline
Discharge
 Why no response ???

• Dehidration
• Metabolic acidosis
• Atelectasis
 Severe Attack
• No/ bad response after nebulization
• Oxygen
• Parenteral, rehidration, acidosis
correction
• Steroid IV
• lnitial Aminophylline IV,
then the maintenance
• Nebulization
• Chest X-ray
• Good: May Go Home
• No/ bad response: Intensive Care
 Oxygen
• Must be given in severe attack

• In severe attack, hypocxemic

 Nebulization (severe attack)

• β2 agonist and ipratropium bromide vs

β2 agonist alone  better result:
– Decreased of hospitalization rate
– Decreased of symptom scoring
– Improve lung functions
– Drugs duration of action, longer
Combination of salbutamol and ipratropium bromide

• The use of ipratropium alone, more inferior then 2 agonist 

slow onset of action

• Combination use with 2 agonist:

– Onset of action, faster
– Prolong effect bronchodilatation
 masih kontroversi
 Watson, 1988 : if large airway is involved
 Rubin, 1996 : not routine in the beginning
of attack
 ß2 agonist + ipratropium bromide

• Not acceptable yet for

-Mild asthma attack
-Moderate asthma attack
• Already acceptable
- Severe asthma attack
 IVFD
• Redehidration
– Drink less due to breathing difficulties
– vomiting
• Acid-base and electrolyte correction
• Give parenteral medication
 Steroid
• Intravenous or oral
• Antiinflamation
• Controversy: the use of nebulizer
 Aminophylline
• Initial, 6-8 mg/kgBW/IV for 10-20 minutes
• Maintenance, 0,5-1 mg/kgBW/hours
• Need aminophylline plasma level
monitoring
• Be careful, narrow margin of safety
 Use of other medication
• Adrenaline, there is maximal dose, effect
on  and 
• Salbutamol SC, have to be careful
• MgSO4, no signiffican
• Steroid inhaler, very high dose
(1600-2000 mg)
• Antibiotic, not use
• Mucolitic, not suggest for severe attack
Longterm Management

41
 Classification of disease
Clinical parameter , Infrequent episodic Frequent episodic
Persistent asthma
And lung function asthma asthma

Freq of attacks < 1x /month > 1x /month Daily

Duration of attacks < 1 week >1 week Daily

Frequent nocturnal
Between episodes No symptoms Symptoms (+) symptoms
Sleep and activity Normal May affect Affect

Physical exam Normal May affect Abnormal

Controller No need Steroid/combination Steroid/combination

Lung function PEF/FEV1 <60%
PEF/FEV1 >80% PEF/FEV1 60-80%
(No attacks) Variability 20-30%

Variability (attacks) >15% > 30% > 50%

42
 Evolving treatment options
ICS treatment Adding
introduced LAßA to ICS therapy
Large use of 1972 Kips et al, AJRCCM 2000
Pauwels et al, NEJM 1997
short-acting
Greening et al, Lancet 1992 Single
ß2-agonists
inhaler therapy
1975
(Symbicort®)

“Fear” of
1980 short-acting
ß2-agonists

1985
2000
1990 1995

Bronchospasm Inflammation Remodelling

43
 Goal of asthma management
• Minimal (ideally no) chronic symptoms
• Minimal (infrequent) exacerbations
• No emergency visits
• Minimal (ideally no) use of as needed ß2-
agonist
• No limitations on activities (exercise)
• (Near) Normal lung function
• Minimal (or no) adverse effects from medicine
44
 Asthma management
Allergen
avoidance

Pharmaco- Immuno-
therapy COSTS therapy

Education
45
GINA, 2002
Cost ?

Availability ?

46
 Avoidance
• Avoidance of triggers : House dust
mite
• Pre and during pharmacotherapy

GINA, 2002
47
 Family Education

• Aim to:
– Increase understanding
– Increse skill
– Increse satisfaction
– Increse confidence
– Increse compliance and self management
– Patient-family-doctor relationships
GINA,2002

48
 Immunotherapy
• Desensitisation
• Controversial
• Multifactorial triggers
• Not populair

49
 Pharmacotherapy
Reliever:
• 2 agonist : inhaler, nebulized, oral
• Epinephrine : subcutan
• Theophylline : oral, I.V.
• Anticholinergic (ipratropium br) : inhaler
• Steroid : oral, I.M.
Controller:
• Steroid : inhaler
• LABA : inhaler, oral
• Leukotrien : oral

PNAA, 2002
50
 When??
Classifications Controller Reliever

Infrequent No Yes
episodic asthma
Frequent Yes Yes
episodic asthma
Persistent Yes Yes
asthma

51
 Medications
• Bronchodilators
• Antiinflammations
• Anti-remodelling
• Anti IgE
• Immunizations: ??

52
TREATING ASTHMA

with Bronchodilators alone

is like
Painting over rust !!!
53
 Infrequent episodic asthma
• No daily medication
• Treatment of exacerbations depend on
severity of attacks
• -2 agonist as needed

54
 Frequent episodic and persistent
asthma
• Controller medications: every day
• Corticosteroid with or without any drugs
• Combination with LABA, TSR, ALT
• Gradual reduction if stable in 6-8 weeks

55
 Anti-inflammations
• Antihistamine
• Disodium Cromoglycate (DSCG)
• Corticosteroids

56
Long-term placebo-controlled trial of ketotifen in the
management of preschool children with asthma
Loftus BG, Price JF
J Allergy Clin Immunol 1987; 79:350-5

The results suggest that:

“Ketotifen has no place in the management

of young children with frequent asthma”

57
 Inhaled disodium cromoglycate (DSCG) as
maintenance therapy in children with asthma:
a systematic review.

Tasche MJA, Uijen JHJ, Bernsen RMD, de Jongste JC, van der Wouden JC.
Thorax 2000; 55:913-20

“Insufficient evidence that DSCG has a

beneficial effect as maintenance treatment
in children with asthma”
58
 Longterm
management Low dose steroid

Medium dose Low dose Low dose Low dose

steroid steroid + LABA steroid + ALTR steroid +TSR

High dose Medium dose Medium dose Medium dose

steroid steroid + LABA steroid + ALTR steroid + TSR

ORAL
STEROID
59
 Corticosteroids
• The most effective anti-inflammatory
medications
• Improving lung function
• Airway hiperresponsiveness:
• Reducing symptoms
• Frequency and severity of
exacerbations:
• Improving quality of life
60
Epithelial Repair Following Steroid Treatment

Before After
P Howarth, 1999
61
 Steroid efficacy in asthma

Steroid
Benefit dose

Side-effects
62
Type of inhalation therapy
• Metered dose inhaler (MDI)
– With spacer
– Without spacer
• Dry powder inhaler (DPI)
– Turbuhaler, cyclohaler
• Nebulizer
– Jet
– Ultrasonic
63
Benefit of steroid inhalation
• Low dose
• Directly to respiratory tract
• Fast onset
• Minimal systemic side effects

64
LABA’s and ICS - complementary modes of action

Smooth muscle Airway

LABA dysfunction inflammation CS

 • Bronchoconstriction • Inflammatory cell 

 • Bronchial hyperreactivity infiltration / activation
 • Hyperplasia • Mucosa oedem 
• Inflammatory mediator release • Cellular proliferation 
 • Epithelial damage 
• Basement membrane thickening 

Symptoms / exacerbations
65
CS + LABA Vs CS double dose

• Increases in PEF and FEV1

• Similar improvements in asthma
symptoms
• Similar in use of rescue medications
• Similar adverse event
• Similar in sputum markers of airway
inflammation Am J Respir Crit Care Med 2000; 161:996-1001
Eur Respir J 2001; 18:262-8
Pediatr Pulmonol 2002; 34:342-50 66
 Adding LABA to steroid improves FEV1
90

85
% predicted

80

75

70
-1 0 1 2 3 6 9 12
Months

Pulmicort® Pulmicort® Pulmicort® 100 mg bid Pulmicort® 400 mg bid

100 mg bid 400 mg bid + Oxis® 9 mg bid + Oxis® 9 mg bid
67
Pauwels et al, NEJM 1997
 Corticosteroids and LABA improves quality
of life of school-age children with asthma
207 children, 57% receiving inhaled corticosteroids

Placebo
*p<0.01 vs baseline Salmeterol 50 µg bid
Increased †p<0.05 vs placebo
functional status 100
*† *† Well children
*
Mean FSIIR

* *
score

90
Chronically
ill children

80
0
Decreased 0 4 12
8
functional status
Time (weeks)
68
FSIIR, functional status IIR
Mahajan et al. Pediatr Asthma Allergy Immunol 1998
 Longterm steroid……

Adverse event
• Hoarseness
• Throat irritations
• Candidiasis
• Headaches
• Growth??

69
 Positive impact of inhalation therapy

INHALATION
Family Financial

ORAL

• Quality of life
Patient • Quality of therapy

• To another doctor
• Go abroad
- Stable asthma

(Low performance
of Indonesian Patient Get Patient
70
pediatricians )
71