Introduc)on

Normaly mucus produc)on / day

Sputum is mucus that is coughed up from the lower
airways
Sputum expectorated excessive secre)ons
Airways mucus hypersecre)on impaired mucus
clearance, mucus reten)on
The characteris)c of mucus change infec)on and
inamma)on
TB pa)ents produc)ve cough
1

Mucus Hypersecre)on
Sputum produc)on, excessive mucus in the
airway lumen, goblet cell hyperplasia,
submucosal gland hypertrophy
Sputum, mucus >> = hypersecre)on

 Eec)ve mucus clearance lung health

Healthy mucus gel with low viscosity and
elas-city easily transported with ciliary
ac)on
Pathologic mucus higher viscosity and
elas-city less easily cleared

 Pathologic mucus
Changes its hydra)on and biochemical
cons)tuents
Abnormal secre)ons of mucins
Inltra)on of mucus with inammatory cells
Heightened bronchovascular permeability

Overproduc-on mucus
Decreased clearance
Accumula-on persistent mucus
infec-on and inamma-on
5

 Principal symptoms of impaired mucus

clearance
Cough: s)mula)on of vagal aerents in the
intrapulmonary airways or larynx or pharynx
Dyspnea: Mucus obstruct airow of occupying the
lumen of numerous airways

Physical sign of impaired mucus clearance

Cough
Bronchial breath sounds
Rhonchi
Wheezing

ISTC Standard 1
All persons with
otherwise
unexplained
productive
cough lasting
two-three weeks
or more should
be evaluated for
tuberculosis
8

Decreased of appe)te

Produc)ve cough > 2-3 weeks

Fever

Weight loss

Pathogenesis TB

Penularan TB 210512

10

TB and mucus produc)on

TB chronic infec)on
Infec)on macrophage, Mycobacterium TB
inamma)on cells death
Bronchus Goblet cell mucus produc)on
>>
Cells death + mucus produc)on

11

 Purulent sputum contain pus, composed of

white blood cells, cellular debris, dead )ssue,
serous uid and viscous liquid (mucus)
Blood vessels bloody, streaked-sputum

12

Inamma)on
Mucus hypersecre)ons
Cilliary dysfunc)on
Changes in composi)on and biophysical
proper)es of airways secre)on

13

Inammatory cells (neutrophils)

Programmed cell death (apoptosis)

Necrosis
Pro-inammatory mediators

Damage the epithelium

Recruit more inammatory cells

Cytosceleton
DNA
F-ac)n

To form a second rigid network within airways secre)ons

14

Table 1 Differences in the stages of tuberculosis

Early primary progressive
(active)

Early infection
Immune system fights infection
Infection generally proceeds
without signs or symptoms
Patients may have fever,
paratracheal lymphadenopathy,
or dyspnea
Infection may be only subclinical
and may not advance to active
disease

Late primary progressive

(active)

Immune system does not control Cough becomes

initial infection
productive

Latent
Mycobacteria persist in the
body

Inflammation of tissues ensues

More signs and symptoms No signs or symptoms occur

as disease progresses
Patients often have nonspecific
Patients do not feel sick
signs or symptoms (eg, fatigue, Patients experience proPatients are susceptible to
weight loss, fever)
gressive weight loss,
reactivation of disease
rales, anemia
Nonproductive cough develops
Granulomatous lesions calcify
Findings on chest radioDiagnosis can be difficult: findings
and become fibrotic, become
graph are normal
on chest radiographs may be
apparent on chest radiographs
normal and sputum smears may Diagnosis is via cultures of
Infection can reappear when
be negative for mycobacteria
sputum
immunosuppression occurs

status of the patients immune sys-

Although coinfection with human

results of diagnostic tests (Table

15 2)

Treatment
Expectorant
Mucoly)c
Mucokine)cs
Mucoregulator

?
16

The aim of mucus hypersecre-ons treatment

To alter rheological proper)es of bronchial
mucus
To reduce the degree of airways obstruc)on
To enhance the func)on of the mucociliary
escalator
To promote expectora)on

17

Management of mucus secre)on

Short-term relief of symptoms
Facilita)ng mucus clearance
Changing the viscoelas)city of mucus
Increasing ciliary func)on
Encouraging cough

Long-term benet
Reversal the hypersecretory phenotype
Reducing the number of goblet cells and the size
of the submucosal glands
18

Mucokine)cs-Mucoac)ve agents
Clearance of mucus from the airways, lungs,
bronchus and trachea
Mechanism of ac)on
Expectorants
Mucoly-c agents
Hypoviscosity agents
Abhesives/surfactanas

19

Expectorant
Signaling the body to increased the amount or
hydra)on of secre)ons clearer secre)ons,
lubrica)ng the irritated respiratory tract
Increases bronchial secre)on
Reduces the thickness or viscosity of bronchial
secre)ons increasing mucus ow
removed easily by cough

20

Mucoly-c agent
Dissolves thick mucus dissolving various
chemical bonds within within secre)ons
can lower the viscosity by altering the mucin-
containing components
Break down the chemical structure of mucus
molecules loosen thick bronchial secre)ons

21

Table 4.

Mucoactive Agents Putative Mechanisms of Action

Mucoactive Agent
Expectorant

Mucolytic

Mucokinetic

Mucoregulator

Putative Mechanism of Action

Increases volume and/or hydration of secretions.
May also induce cough (eg, guaifenesin,
hypertonic saline)
Reduces viscosity of mucus
Non-peptide (classical) mucolytics cleave
disulphide bonds (free or blocked
sulphydryl groups).
Low-molecular-weight saccharide mucolytics
interfere with non-covalent interactions in
mucus, and may osmotically pull water into
airway lumen.
Peptide mucolytics degrade deoxyribonucleic
acid (DNA) or actin
Increases kinesis of mucus and facilitates
cough transportability of mucus
!2-adrenoceptor agonists increase airflow, ciliary
beat, Cl!/water secretion, and mucin
secretion (small effect).
Surfactant reduces mucus adherence to
epithelium.
Reduces process of chronic mucus hypersecretion
(eg, glucocorticosteroids, anticholinergics,
macrolide antibiotics)
22

Mucolytics
Mucoac)ve
a
gent
Cysteine
N-Acetylcysteine
Nacystelyn
Ethylcysteine
Nesosteine
Dithiothreitol
MESNA (2-mercaptoethanesulphonate sodium)
Thiopronine
Urea
Tasuldine
Carbocysteine*
Carbocysteine-Lys*
Erdosteine*
Fudostein*
Letosteine*
Stepronin*
Usherdex-4 (a low-molecular-weight form of dextran)
Expectorants/Mucokinetics
Ambroxol

Usherdex-4 (a low-molecular-weight for

Expectorants/Mucokinetics
Mucoactive Agent
Putati
Ambroxol
Expectorant
Increases volum
Ambroxol-theophylline-7-acetate
May also ind
Bromhexine
hypertonic
Guaiacol and derivatives
Mucolytic
Reduces viscos
Guaifenesin
Non-peptide
Guaimesal
disulphide
Hypertonic solutions (saline) sulphydryl
Inorganic iodides
Low-molecul
Organic iodides
interfere w
mucus, an
Ipecacuanha
airway lum
Sobrerol
Peptide muco
Sodium citrate
acid (DNA
Squill
Mucokinetic
Increases kine
Volatile inhalants
and balsams
cough tra
!2-Adrenoceptor agonists
!2-adrenocepto
Surfactant
beat, Cl!/w
YM-40461 (surfactant secretagogue)
secretion (
Peptide Mucolytics (Enzymes)Surfactant
23
redu

Surfactant
YM-40461 (surfactant secretagogue)
Peptide Mucolytics (Enzymes)
Bromelain
"-Chymotrypsin
Recombinant human deoxyribonoclease I (aka, dornase-alfa and
rhDNase)
Fericase
Ficin
Gelsolin
Helicidin
Leucine amino peptidase
Neuraminidase
Onopronase
Papain
Serratopeptidase
Streptodornase
Streptokinase
Thymosin beta 4
Trypsin
*Metabolized endogenously to form compounds with free sulphydryl groups

N-A

24

in
ma
res
the
Soc
alth
not
in a
to
thio
has
eve
no
the
ine
T

Bromhexine
Some types of TB have symptom like productive cough
or sputum production.
Bromhexine has a triple effect (thin, loosen, and clear)
on mucus, making it easier to cough up.
Reduction on
viscosity : -46%
(p<0.001)
Placebo : no
significant effect

Effect Bromhexine on viscosity of sputum (mucus)

25

Difficulty of expectoration (meanSE) ** p<0.01 (t-test)

Bromhexine reduce difficulty

of expectoration by approx.
59%, significant difference to
placebo (p<0.01)

26

Pada jam ke-6 setelah

inhalasi radioaktif,
pengeluaran mukus
pada pasien lebih besar
6,8% setelah
menerima
dibandingkan sebelum
menerima Bromhexine
(perbedaan signifikan,
p<0,05) atau
peningkatan 14,5%
dibandingkan kontrol.

* Penelitian menggunakan inhalasi radioaktif untuk

memperlihatkan pergerakan mukus
Thomson, M.L, et al., Bromhexine and Mucociliary Clearance in Chronic Bronchitis, Brit. J. Dis.
Chest., 1974, 68, 21-27

27

The role of mucoac)ve in TB

The role of mucoac)ve agent in TB
To help pa)ent to expectorate sputum AFB
examina)on
To reduce the respiratory problems (dyspnea due
excessive mucus produc)on)

28

Conclusion
Op)mal treatment of mucus hypersecretory
element of each disease should be disease
specic
Choose the right selec)on of mucoaca)ve
agent
The role of mucoac)ve agent in TB to reduce
accumula)on of excessive mucus

29

30