3. How long?
• Sudden - ? Foreign body
• Days - infection
• Weeks – bronchitis/pneumonia/TB/cancer
• Months/years – chronic bronchitis/reflux
• Variable - asthma
4. Cough - History
Cough
Acute Subacute Chronic
Less than 3
Less than 3 3 to 8 weeks
3 to 8 weeks More than
More than
weeks
weeks 3 weeks
3 weeks
Richard Irwin, NEJM, Volume 343, Dec 7, 2000
5. Cough - Acute
• Most common causes
– Common cold [viral]
– Acute bacterial sinusitis
– Pertussis
– Exacerbation of COPD
– Allergic rhinitis
– Rhinitis secondary to environmental irritants
6. Cough – Viral Infection
• Upper respiratory viral infections are the
most common cause of cough
– 83% within first 48 hours
– 26% on day 14
• Arises from the stimulation of the cough
reflex in upper airway by postnasal drip
and/or clearing of the throat
7. Cough – Viral Infection
• Signs and symptoms include: rhinorrhea,
sneezing, nasal obstruction, post nasal
drip, irritation of the throat, +/- fever and
normal chest exam
– Diagnostic testing is not indicated in a
immunocompetent patient as there is a very
low yield — over 97% of CXR are normal
8. Cough - Acute
• Remember:
– Think bacterial bronchitis & use antibiotics if exacerbation
of COPD with worsening SOB or wheezing is present
– Cough and vomiting is suggestive of Bordetella pertussis
– Bacterial sinusitis can present like a viral rhinitis but use
antibiotics only two of the following are present:
• Maxillary toothache
• Purulent nasal discharge, discolored nasal discharge
• Abnormal transillumination of any sinus
9. Cough - Acute
• In elderly, classic signs and symptoms
may be minimal, so consider
– Pneumonia
– CHF
– Asthma
– Aspiration
10. Cough - Subacute
• Most common etiologies
1. Post-infectious cough
• Begins with respiratory tract infection
• NOT pneumonia
• Ultimately resolves without treatment
• Results from PND or clearing of throat
• With or without bronchial hyper-responsiveness
1. Bacterial sinusitis
2. Asthma
11. Postinfectious Cough -
Treatment
• Begin with treatment similar to the
common cold
• If wheezing – use bronchodilators
– This does not make the diagnosis of asthma
• If not resolved in one week
• Nasal decongestant for 5 days
• Antibiotics till total disappearance of cough
12. Chronic Cough
• In immunocompetent patients, 95% caused by
– Postnasal drip
– Asthma
– Gastroesophageal reflux
– Chronic bronchitis due to cigarette smoking
– Bronchiectasis
– Use of angiotensin-converting enzymes inhibitors
14. Evaluation of Chronic Cough
• History
– Character of cough, quality of the sound and
the timing of cough (except the absence
during sleep) have not shown to be useful
• Physical
– Oropharyngeal mucous or cobblestone
appearance suggests postnasal-drip
syndrome
– “silent” postnasal-drip syndrome
15. Evaluation of Chronic Cough
• Heartburn and regurgitation suggest
Gastroesophageal reflux disease
– “silent”GERD in up to 75% of patients
• Irwin,Chest 1993;104:1511-1517
• Wheezing suggests asthma
– “silent”asthma (cough variant asthma) in up to
57% of cases
• Irwin, Am Rev Respir Dis 1981;123:413-417
16. Evaluation of Chronic Cough
• Where to start
– CXR: normal is consistent with PND, GERD,
asthma, chronic bronchitis.
• Unlikely : bronchogenic carcinoma, sarcoid, TB
and bronchiectasis
– Since PND syndromes are most common---
start there
• Sinusitis or rhinitis of the following varieties:
nonallergic, allergic, postinfectious, vasomotor,
drug-induced and environmental-irritant induced
17. Chronic Cough - PND
• PND is by far the most common cause of
chronic cough
• Since the signs and symptoms are
nonspecific, the definitive diagnosis
cannot be made by History and Physical
examination alone
• Therapy
– 1st generation antihistamine + a decongestant
18. Therapy
• Remember
– “The newer-generation H1 antagonist do not
appear to be effective when cough induced by
postnasal drip is not mediated by histamine”
• Irwin, Consensus Report of the American College of Chest
Physicians. Chest 1998;114:suppl:133S-181S.
19. Chronic Cough – Asthma
• Cough can be the only symptom of
asthma in up to 57% of patients—cough-
variant asthma
• +/- airflow obstruction on PFT’s
• Therapy
– If severe, PO steroids followed by inhaled
steroids for 6-8 weeks with β2 agonist
– If mild, inhaled steroids with β2 agonists
21. Chronic Cough -- GERD
• When GERD is cause of chronic cough, up
to 75% of patients have no GI symptoms
• Empiric therapy can if tried if
– GI complaints compatible with GERD or
– No GI complaints with normal CXR, no ACEI,
patients who do not smoke and in whom PND
and asthma have been eliminated.
• Improvement may take 2-3 months to begin
• MEAN TIME TO RECOVERY IS 161-179
DAYS.
22. Chronic Cough -- ACEI
• Class effect of drug; not drug related
• Incidence of 0.2 to 33%;
– True incidence ≈ 10%
• Cough may appear within a few hours up to
months after taking the first dose
– Pathogenesis seems be an accumulation of
inflammatory mediators: bradykinin, substance
P and/or prostaglandins.
• Therapy
– STOP ACEI
– Other therapies include oral sulindac, ASA,
indomethacin and even oral iron.
26. Treatment of cough
• Cough is a useful physiological mechanism
that serves to clear the respiratory passages
of foreign material and excess secretions.
– It should not be suppressed indiscriminately.
• There are, however, many situations in
which cough does not serve any useful
purpose
– Instead it only annoys the patient or prevents
rest and sleep.
• Cough may be
– i) Un productive (dry) cough OR
27. Treatment of cough
• It is suggested that
irritation of the
bronchial mucosa
causes
bronchoconstriction:
• This, stimulates cough
receptors.
– ( which probably
represent a specialized
type of stretch receptor)
located in the
tracheobronchial
passages.
30. Antitussives (cough centre
suppressants)
• Drugs suppress cough & produces
symptomatic relief
• MOA
– Mainly suppress cough centre in medulla (both
central & peripheral effects)
• E.g., Opoid drugs (codeine, pholcodeine, noscapine,
dextromethorphan)
– Opioid = most effective for cough.
31. Codeine
• Codeine= prodrug ⇒ metabolized to
morphine
– It is an alkaloid found in Opium poppy plant
• Has less addiction + resp. centre depressant
action
– Has useful antitussive action at low doses (<15
mg)
• Produce drowsiness, thickening of sputum &
• constipation
32. Noscapine & Pholcodeine
• Related to papaverine
• Do not have addictive, analgesic &
constipating properties
• Do not interfere with mucocilliary movement
– Noscapine (15 mg) &
– pholcodeine (10 mg)=syrup
33. Dextromethorphan
• Available in syrup, tablets, spray forms
• MOA
– NMDA receptor antagonist
• Uses
– Cough suppressant, temporary relief of cough
caused by minor throat & bronchial irritation
(accompanies with flu & cold), pain relief
• Adverse Effects
– Nausea, vomiting, drowsiness, dizziness, blurred
vision.
34. Antihistamines
• Added to antitussives / expectorant
formulation
– Due to sedative & anticholinergic actions
produce relief in cough but lack selectivity for
cough centre
– No expectorant action =▼secretions
(anticholinergic effect)
• Suitable for allergic cough (not for asthma)
– E.g., Chlorpheniramine, diphenhydramine,
promethazine.
35. Bronchodilators
• Bronchospasm or stimulation of
pulmonary receptors = induce or
aggravate cough + bronchoconstriction
• e.g. β2-agonist (salbutamol, terbutaline)
• MOA of bronchodilators in cough
– ▲surface velocity of air flow during cough→
Clear secretions of airway
– Not used routinely for every type of cough but
only when bronchoconstriction is present
36. Pharyngeal demulcents
• Soothe the throat (directly & also by
promoting salivation)
– ▼ afferent impulses from inflamed/irritated
pharyngeal mucosa
• Provide symptomatic relief in dry cough
arising from throat
– E.g. lozenges, cough drops, glycerine, liquorice,
honey
44. Mucus Layer
• Gel (1 to 2 µm): Gelatinous and sticky (flypaper)
• Sol (4 to 8 µm): Watery, Cilia in this layer
– Total layer thickness: 5 to 10 µm thick
• Surface Epithelial Cells
– Pseudostratified ciliated columnar
– Surface goblet cells (6,800/mm 2)
– Serous cells – Sol layer
– Clara cells – Unknown function (enzymes?)
• Submucosal Gland
– Bronchial Gland
45. Mucus Layer
• Bronchial Gland
– Found in submucosa
– Found down to terminal bronchioles
– Parasympathetic control (Vagus nerve)
– Provide the majority of mucus secretion
– Total volume 40 times greater than goblet
cells
46. Function of Mucociliary
Escalator
• Protective function
– Remove trapped or inhaled particles and
dead or aging cells.
– Antimicrobial (enzymes in sol/gel)
– Humidification
– Insulation (prevents heat and moisture loss)
• NOTE: No cilia or mucus in lower airways
(respiratory bronchioles on down)
• Mucus also protects the epithelium from
toxic materials.
47. Structure and Composition of
Mucus
• Composition
– 95% water
• Need for water intake to replenish
• Mucus doesn’t easily absorb water once created
– 3% protein and carbohydrates
– 1% lipids
– Less than 0.3% DNA
48. Structure and Composition of
Mucus
• Glycoprotein
– Large (macro)molecules
– Strands of polypeptides (protein) that make
up the backbone of the molecule
• String of amino acids
– Carbohydrate side chains
– Chemical bonds “hold” mucus together
• Intramolecular: Dipeptide links
– Connect amino acids
• Intermolecular: Disulfide and Hydrogen bonds
– Connect adjacent macromolecules
49.
50. Mucus Production
• Normal person produces 100 mL of
mucus per 24 hour period
– Most is reabsorbed back in the bronchial
mucosa
– 10 mL reaches the glottis
– Most of this is swallowed
• Mucus production increases with lung
disease
52. Increased Mucus Production
↑ Viscosity of mucus
↓ Ciliary effectiveness
↑ Mucus plugs
↑ Airway Resistance
↑ Infections
Obstructed bronchioles leads to
atelectasis
53. Diseases that Increase Mucus
Production
• Chronic Bronchitis
• Asthma
• Cystic Fibrosis
• Acute Bronchitis
• Pneumonia
• Also some drugs (anticholinergics,
antimuscarinics)
54. Factors that Impair Ciliary
Activity
• Endotracheal tubes
• Temperature extremes
• High FiO2 levels
• Dust, Fumes, Smoke
• Dehydration
• Thick Mucus
• Infections
55. Viscosity and Elasticity
• Rheology
• Viscosity: Property of a liquid that measures the
resistance to movement when a force is applied.
– Increased viscosity, increased resistance to flow
• Olive oil vs. Water
• Elasticity: Property of solid whereby a solid
changes shape (deforms) when a force is
applied.
– Ideally, a solid is totally elastic, and returns to its
original shape when force is released.
• The mucus layer is ideally very elastic and has a
very low viscosity.
57. Hypoviscosity/Wetting Agents:
Saline solutions
• Normal Saline (.9%)
– Isotonic and good diluent for drugs
• Half-normal Saline (.45%)
– Hypotonic, good diluent, and can be
administered via USN
• Aerosol solutions tend to increase in
tonicity as they go deeper into the lung
because of evaporation!
58. Hypoviscosity/Wetting Agents:
Saline solutions (cont.)
• Hypertonic Saline (usually 10%)
– Wetting agent
– Bronchorrhea (draws fluid from mucosa to
dilute gel)
– May also help break up mucoprotein-DNA
bonds in mucus (mucolytic effect!)
• Limitations:
– Bronchospasm
– Hypernatremia
59. Hypoviscosity/Wetting Agents:
Sodium Bicarb
• Usually 2 – 7.5% solution
• Wetting agent and bronchorrhea
• Also alkaline pH breaks up hydrogen bonds
• Also breaks up calcium bonds
• Like hypertonic saline, it is both a wetting agent
and a mucolytic
• Can usually NOT be used as a diluent for drugs
• Has same side effects as hypertonic saline
60. Mucociliary Escalator
• Mucosal Blanket
– Sol layer
– Gel layer
• Cilia
– 200 per cell
– 6 µm in length
– Beat 1000/min
– Move mucus 2 cm/min
– Paralyzed by cigarette smoke
61. Mucus vs. Sputum
• Mucus is the total secretion from mucous
membranes including the surface goblet
cell and the bronchial glands.
• Sputum is the expectorated secretions
that contains mucus, as well as
oropharyngeal and nasopharyngeal
secretions (saliva).
62. Facilitation of Mucus Clearance
• Provide adequate hydration
– Increase fluid intake orally or IV
• Remove causative factors
– Smoking, pollution, allergens
• Optimize tracheobronchial clearance
• Use Mucolytics
• Reduce Inflammation
63. Function of Mucolytics
• Weakening of intermolecular forces
binding adjacent glycoprotein chains
– Disruption of Disulfide Bonds
• Alteration of pH to weaken sugar side
chains of glycoproteins
• Destruction of protein (Proteolysis)
contained in the glycoprotein core of
proteolytic enzymes
– Breaking down of DNA in mucus
64. Function of Mucolytics
• Disruption of Disulfide Bonds
– acetylcysteine breaks the bonds by substituting a
sulfhydril radical –HS
65. Function of Mucolytics
• Alteration of pH
– 2% NaHCO3 solutions are used to increase
the pH of mucus by weakening carbohydrate
side chains
– Can be injected directly into the trachea or
aerosolized (2-5 mL)
66. Function of Mucolytics
• Proteolysis
– Dornase alfa (Pulmozyme)
– Attacks the protein component of the mucus
67. Hazard of Mucolytics
• The problem with all three mucolytics is
that they destroy the elasticity of mucus
while reducing the viscosity.
• Elasticity is crucial for mucociliary
transport.
• The patient must be able to cough
adequately to remove the mucus.
68. Mucolysis
• Mucolysis is the breakdown of mucus.
• Mucolysis is needed in diseases in which
there is increased mucus production:
– Cystic Fibrosis
– COPD
– Bronchiectasis
– Respiratory Infections
• Turberculosis
69. Mucolysis
• These diseases result in a marked slowing
of mucus transport
– Changes in properties of the mucus
– Decreased ciliary activity
– Both
73. Dairy Intake
• No evidence to support the common belief
that drinking milk increases the production
of mucus or phlegm and congestion in the
respiratory tract
• There is a loose cough associated with
milk intake
74. Secretion Management
• Increase the depth of the sol layer
– Water
– Saline
– Expectorants
• Alter the consistency of the gel layer
– Mucolytics
• Improve ciliary activity
– Sympathomimetic bronchodilators
– Corticosteroids
75. Bland Aerosols
• “Dilutes” mucus molecule
• Also known as wetting agents
– Function may be more of an irritant than a wetter
• Types
– Sterile & Distilled Water
• Humectant
• Dense aerosols and asthmatics
– Normal (isotonic) Saline
– Hypertonic Saline
• Increase mucus production
– Hypotonic Saline
76. Cough Suppressants
• Vagal stimulation causes a cough.
• Irritation of pharynx, larynx, and bronchi
lead to a reflex cough impulse.
• If the cough is dry and non-productive, it
may be desirable to suppress its activity.
• Cough suppressants depress the cough
center in medulla (?).
– Narcotic preparations (codeine)
– Non-Narcotic preparations (dextromethorphan)
• Caution in patients with thick secretions.
77. acetylcysteine
• Indications
– Mucolytic by aerosol or direct instillation into
the ET tube.
– Given orally to reduce liver injury with
acetaminophen (Tylenol) overdose.
• Mix with cola or given by NG tube.
78. Dosage of acetylcysteine
• Concentration
– 10% or 20%
• Dosage
– 3-5 mL of a 20% solution TID or QID
• Maximum dose 10 mL
– 6-10 mL of a 10% solution TID or QID
• Maximum dose 20 mL
• 1-2 mL of a 10% or 20% for direct
instillation
79. Hazards of acetylcysteine
• Bronchospasm
– Asthma – may be a problem during an acute
asthma attack.
• Anecdotal; lack of evidence
– If used with asthma, use 10% and mix with a
bronchodilator (preferably a short-acting
agent).
• Increase mucus production
– Be prepared to suction a patient who cannot
cough or who is intubated.
80. Hazards of acetylcysteine
• Do not mix with antibiotics in the same
nebulizer (incompatible).
• Nausea & Vomiting
– Disagreeable odor (smells like rotten eggs)
due to the hydrogen sulfide.
• Open vials should be used within 96 hours
to prevent contamination.
81. Expectorants (Bronchomucotropics)
• Drugs that increase and aid clearance of
respiratory tract secretions
• Act peripherally to increase expulsion of mucus from
the respiratory tract.
– Increase bronchial secretion OR
– Decrease its viscosity & facilitate its removal by coughing
– Loosen cough ► less tiring & more productive
– Hypoviscosity agents (Wetting agents)
• Aerosol hypertonic saline – increases secretion
volume and/or hydration, may decrease viscosity by
diluting the gel layer
– Mucolytics
82. Classification of Expectorants
• Classified into
• 2 types:
1. Stimulant expectorants – increase overall
mucus volume to enhance clearance.
• Directly acting
• Reflexly acting
1. Mucolytic expectorants - break down mucus
83. Expectorants
• Iodides
– Unclear function
– SSKI (Saturated Solution of Potassium Iodide)
• Guifenesin
– At high doses, stimulates bronchial gland
secretion
– Robitussin
84. Expectorants (Bronchomucotropics)
• Drugs that increase and aid clearance of
respiratory tract secretions
• Act to stimulate the cholinergic system and ↑
mucus secretion.
– Eg. Guaiphenesin - Expectorant drug usually taken by
mouth
– Available as single & also in combination
– MOA=Increase the volume & reduce the viscosity of
secretion in trachea & bronchi
• Act directly
– Ammonium chloride - Gastric irritants = reflexly↑ bronchial
secretions + sweating
– Sodium citrate &
85. Expectorants (Bronchomucotropics)
• Drugs that increase and aid clearance of
respiratory tract secretions
– Usually stimulate sol layer production by direct
irritation or indirect through vagal stimulation
• Increased sol means decreased viscosity!
– Smoke is a bronchomucotropic! Unfortunately,
it’s irritation stimulates the bronchial submcosal
glands AND the goblet cells so mucus
production increases as well as viscosity
– Spicy food causes increased sol due to vagal
stimulation!
86. N-Acetylcysteine
• Given directly into respiratory tract as 10 or
20% solution (hypertonic and alkaline pH)
• MOA of acetylcysteine
– Opens disulfide bond in mucoproteins of sputum
=↓ viscosity (most effective form of mucolysis)
– Also breaks mucoprotein bonds and hydrogen
bonds
• Bronchorrhea
87. N-Acetylcysteine
• Onset of action quick---used 2-8 hourly
• Uses
– Cystic fibrosis (to ↓viscosity of sputum)
• Adverse effects
– Nausea, vomiting, bronchospasm in bronchial
asthma.
88. Pulmozyme (Dornase Alpha or DNAse)
• Excellent aerosol mucolytic for cystic
fibrosis patients
• Lyses the DNA bonds in the sputum of
cystic fibrosis patients
– These patients have a lot of such bonds!
89. Mucolytic treatment in acute
exacerbations :
• Mucolytic drugs have a small effect in
decreasing acute exacerbations.
• Improvement of subjective complaints
– Decrease of inflammatory markers
– Bacterial eradication
– They are not effective on FEV1 decline.
– They may have some effects on frequent
exacerbators requiring hospitalization BUT no
difference on hospitalization length.
90. Mucoregulators
• Agents regulating mucus secretion or
interfere with the DNA/F-actin network
– Carbocysteine - regulates mucus visco-elasticity.
Also antioxidant, anti-inflammatory
– Anticholinergics- inhibits cholinergic system
which ↑ mucus secretion (M3 res).
– Glucocorticoids – decrease airway inflammation
and mucus secretion.
– Macrolides – ↓ airway inflammation & mucus
secretion.
91. Mucokinetics
• Agents used when secretions ↑ in amount
and/or viscosity to ↑ the mucociliary transport
– Bronchodilators - Improves cough by increasing
expiratory flow and increase in secretion
expulsion, Also antioxidant, antiinflammatory
– Bromhexine
– Ambroxol-increases in surfactant production,
inhibits chloride channels, Decrease in viscosity
of secretions
– Surfactant –decreases surface adhesion
between mucus and airway.
92. Bromhexine
• MOA of Bromhexine
– Synthetic derivative of vasicine (alkaloid=
Adhatoda vasica)
– Thinning & fragmentation of mucopolysaccaride
fibers
– ↑ volume & ↓ viscosity of sputum
93. Ambroxol
• Ambroxol Hydrochloride is the active
metabolite of Bromhexine & works as
– Secretolytic agent used in the treatment of viscid
or excessive mucus.
– Mucoactive drug with several properties
including secretolytic and secretomotoric actions
that restore the physiological clearance
mechanisms of the respiratory tract,
– Stimulates synthesis and release of surfactant by
type II pneumocytes. Surfactant acts as an anti-
glue factor by reducing the adhesion of mucus to
the bronchial wall, in improving its transport.
94. Ambroxol
• Ambroxol allows patients to breathe freely
and deeply by:
– Promoting mucus clearance,
– Facilitating expectoration and
– Easing productive cough.
• Anti-inflammatory properties of Ambroxol
lead to ↓ of redness of the sore throat and
thus, ambroxol relieves pain in acute sore
throat, with a fast onset of action and a long
duration of effect of at least 3 hours.
