5/18/2011

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

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Physiologic or pathologic?
Cough
Physiologic Pathologic

Pathologic: intensity, frequency, cough characteristic, sputum characteristic Cough without receptor stimulation: psychogenic, habitual cough

Cough Model Reflex

Cerebral cortex Voluntary control of cough Sensation of irritation Cough control centre Endogenous opioids Placebo effect

+ve

-ve

Exogenous opioids

Respiratory area of brainstem

Vagus nerve

Airway irritation

Respiratory muscles COUGH

4

Widdicombe J. Cough. Blackwell publishing 2003; 20

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Cough Reflex Arc

Receptor
Larynx Trachea Bronchus Ear Gastric Vagal nerve

Afferent
Vagal nerve branch

Cough center

Efferent

Efector

Muscle, Larynx, trachea, and bronchus

Distributed evenly in medulla near by the respiratory center: Under the higher control center
Trigeminal nerve

Nose Sinus paranasal

Nerve Phrenicus, Intercostal & lumbaris

Diaphragm; Intercostal, Abdominal & lumbal muscles

Respiratory tract muscles Muscles involve in respiration

Pharynx Pericardium diaphragm

Glossopharyngeal

nerve Nerve phrenicus

Trigeminal, Facial Hippoglosus nerve, etc

5 Chang AB. Cough 2003;7:1-15.

How do we cough ?
Inspiratory
Deep inspiration (150-200% tidal volume) Maximal dilation of tracheo-bronchial tree

Compressive

Expiratory

Inspiratory muscles contraction Glottic closure 0.2 Expiratory muscles contraction Contraction of thoracic & abdminal Sudden glottic muscles vs fixed opening diaphragm Explosive release of Intrathoracic intrathoracic air pressure

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

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Mechanism of Cough
6.0 5.0 4.0 3.0 2.0 1.0 0.0 Air volume Subglottic pressure

Sound 50 40 30 20 10 0

Flow rates

1 2 3 Negative Min flow positive Flow phase phase Flow phase Inspiratory glottis Expiratory phase (explosive) phase closure
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

cmH2O
8

L/s

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Diagnosis of Asthma
Cough

and/or wheezing that:

Hyperreactivity Nocturnal (variability) Reversibility Episodic

Atopic family
9

Inflammatory processes
Desquamation of epithelium Hyperplasia of Mucos glands Mucus plug

Basement Membrane thickening

Oedema Smooth muscle Hypertrophy and contraction

Barnes PJ

Neutrophil and eosinophil infiltration

10

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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

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Pathogenesis
Environment
Genetic susceptibility

Chronic allergic inflammation

(Mast cells, T-Cells, Eosinophils)

AIRWAY WALL THICKENING

13

Classification of asthma
Severity of attacks (Acute)
Mild Moderate Severe Respiratory arrest imminent

Class of disease (Chronic)

Infrequent episodic asthma Frequent episodic asthma Persistent asthma

14

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

Chronic Asthma

Asthma
Acute Asthma

Asthma management
Acute asthma
Attack
Chronic asthma

management
Algorithm attack

Long term management Algorithm diagnosis & treatment

management

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Asthma medication, function category

Reliever
To relieve / reduce symptoms and/ attack As needed use Bronchodilators 2-agonist, xanthenes, systemic steroid Oral, inhalation, injection

Controller
To control / prevent symptoms and/ attack Long term use Anti-inflammations Inhaled steroid, ALTR Oral, inhalation, For FEA & PA, not for IEA

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)

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Asthma Attack

19

Why happened ??

10

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Asthma
Triggers Longterm management failure
House dust mite (HDM) Smoke (polution) Food Infection

Attack

11

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Pathophysiology
Trigger

Bronchocontriction, Mucosal edema, Excessive secretion

Airway obstruction

Nonuniform ventilation Atelectasis Decreased surfaktant Acidosis Pulmonary vasoconstriction Mismatching of ventilation and perfution

Hyperinflation

Decreased compliance

Alveolar hypoventilation

Increased work of breathing

PaCO2 PaO2

Severity of asthma attack

Mild Moderate 11.7% 3.9% Severe

84.4%

12

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Estimation of severity of asthma attack

Sign/ Symptom
Activities (infant) Talking Position Alertness Cyanotic Wheezing Breathing difficulties

Mild
Walking (loudly cried) Complete sentences Can lie down

Moderate
Talking (weak cried) Phrasesor or partial sentences Prefer to seat

Severe
Rest (stop eating)

Imminent respiratory arrest

Maybe agitated Usually agitated Absent Moderate, end of eksp. Minimal Absent

Single words or short phrases Tripod-like sitting positions Usually Confused agitated Present Difficult/ cant be heard

Loud, eksp. + Audible insp. Moderate Severe

Acessory Muscle of respiration Retraction

Usually not

Usually yes

Yes

Paradoxical movement

Respiratory rate Pulse rate Pulsus paradoxus PEF / FEV1 - pre-b.dilat. - post-b.dilat SaO2 PaO2 PaCO2

No intercostal to mild retraction Tachypnea Normal Absent (<10 mmHg)

Moderate +, Deep +, +, Decrease/ tracheosterna nassal flaring none l retraction Tachypnea Tachypnea Decreasing Tachycardia Present 10-20 mmHg Tachycardia Present >20 mmHg Bradicardia absent (Fatique resp. muscle)

(% predictive- value/ % good -value) >60% 40-60% <40% >80% 60-80% <60% >95% 91-95% <90% Normal <45 mmHg >60 mmHg <45 mmHg <60 mmHg >45 mmHg

13

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Algorithms asthma attack

Clinic/ ER Rate attack severity First management 2-agonist nebulization (neb) 3x, 20 interval 3rd neb + anticholinergic
Mild attack

(neb 1x, good response

Hold out 1-2 hours, , may go home Attack reappear moderate attack

Severe attack (neb 3x, (neb 2-3x, partially response) bad/ no response) O2 since beginning Give O2 IV line Reevaluate moderate One day care (ODC) Chest X ray IV line Reevaluatesevere hospitalized
Moderate attack

Hospital Room

O2 continued Overcome dehidration O2 continued (inhalation / oral) and acidosis gGve oral steroid Patient with IV steroid every Neb every 2 hrs 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, may go home Note: Note: No improvement, severe attack from beginning, directly neb with impending resp failure ipratropium neb can be replaced by adrenalin sc 0.01 ml/kgBw/x, PICU
May go home Give 2-agonist One Day Care (ODC)
max 0.3ml/x O2 2-4L/mnt from the start, including during neb

14

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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

Discharge Bronchodilator

ODC Oxygen Nebulization Oral Steroid IVFD

Wards Oxygen Nebulization IVFD IV/oral Steroid Rehydration Amynophylline

Good Response Discharge

Poor Response

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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

16

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Oxygen
Must be given in severe attack In severe attack, hypocxemic

Nebulization (severe attack)

2 agonist and ipratropium bromide vs 2 agonist alone better result:
Decreased of hospitalization rate Decreased of symptom scoring Improve lung functions Drugs duration of action, longer

17

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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

2 agonist + ipratropium bromide

Not acceptable yet for -Mild asthma attack -Moderate asthma attack Already acceptable

- Severe asthma attack

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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

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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 g) Antibiotic, not use Mucolitic, not suggest for severe attack

20

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Longterm Management

41

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

Freq of attacks Duration of attacks Between episodes Sleep and activity Physical exam Controller Lung function (No attacks)
Variability (attacks)

< 1x /month < 1 week No symptoms Normal Normal No need

> 1x /month >1 week Symptoms (+) May affect

May affect

Daily
Daily Frequent nocturnal symptoms

Affect Abnormal

Steroid/combination Steroid/combination

PEF/FEV1 >80% PEF/FEV1 60-80% >15% > 30%

PEF/FEV1 <60% Variability 20-30% > 50%

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Evolving treatment options

Large use of short-acting 2-agonists 1975 ICS treatment introduced 1972 Adding LAA to ICS therapy
Kips et al, AJRCCM 2000 Pauwels et al, NEJM 1997 Greening et al, Lancet 1992 Single

inhaler therapy (Symbicort) Fear of short-acting 2-agonists

1980

1985 1990
Bronchospasm Inflammation

2000 1995
Remodelling
43

Goal of asthma management

Minimal (ideally no) chronic symptoms Minimal (infrequent) exacerbations No emergency visits Minimal (ideally no) use of as needed 2agonist No limitations on activities (exercise) (Near) Normal lung function Minimal (or no) adverse effects from medicine 44

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Asthma management
Allergen avoidance

Pharmacotherapy

COSTS

Immunotherapy

Education
GINA, 2002
45

Cost ? Availability ?

46

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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

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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

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When??
Classifications Infrequent episodic asthma Frequent episodic asthma Persistent asthma Controller No Yes Yes Reliever Yes Yes Yes

51

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

52

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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

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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

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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

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Longterm management

Low dose steroid

Medium dose steroid

Low dose steroid + LABA

Low dose steroid + ALTR

Low dose steroid +TSR

High dose steroid

Medium dose steroid + LABA

Medium dose steroid + ALTR

Medium dose 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

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Epithelial Repair Following Steroid Treatment

Before

After
P Howarth, 1999 61

Steroid efficacy in asthma

Benefit

Steroid dose

Side-effects
62

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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

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LABAs and ICS - complementary modes of action

LABA

Smooth muscle dysfunction

Airway inflammation

CS

Bronchoconstriction Bronchial hyperreactivity Hyperplasia Inflammatory mediator release

Inflammatory cell infiltration / activation Mucosa oedem 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
Eur Respir J 2001; 18:262-8 Pediatr Pulmonol 2002; 34:342-50

Am J Respir Crit Care Med 2000; 161:996-1001

66

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Adding LABA to steroid improves FEV1

90

85

% predicted

80

75

70 -1 0 1 2 3 6 9 12

Months
Pulmicort 100 g bid
Pauwels et al, NEJM 1997

Pulmicort 400 g bid

Pulmicort 100 g bid + Oxis 9 g bid

Pulmicort 400 g bid + Oxis 9 g bid

67

Corticosteroids and LABA improves quality of life of school-age children with asthma
207 children, 57% receiving inhaled corticosteroids Placebo Salmeterol 50 g bid

Increased functional status 100

*p<0.01 vs baseline p<0.05 vs placebo * * *

Well children

Mean FSIIR score

90

Chronically ill children

80
Decreased functional status
FSIIR, functional status IIR

12
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Time (weeks)
Mahajan et al. Pediatr Asthma Allergy Immunol 1998

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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

(Low performance of Indonesian pediatricians )

Stable asthma Patient Get Patient

70

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71

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