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OS 213 [A]: Circulation and Respiration (Pulmonology)

Common Pulmonary Clinical Syndromes I: Cough

Trans Number: 11

Aileen Wang, MD, FPCCP

A. Definition of Cough
B. Impact of Cough
Epidemiology of Cough
Mechanisms of Cough
A. The Cough Reflex
B. Initiation of Cough
C. Irritant Triggers
D. Peripheral Mechanisms of Cough
E. Cough Reflex: Afferent Pathway
F. Sensory Nerves Regulating Cough
G. Reflex Pathway
H. Production of Cough
I. Factors Contributing to Cough Inefficiency
J. Structure and Composition of Mucin
K. Mucus Accumulation within the Airway
L. Airway Mucosal Disease and Mucus
M. Sequelae of Increased Mucus Production
IV. Cough Reflex Sensitization
V. Approach to Patients with Cough
A. Etiology of Cough
B. Diagnostic Approach
C. Approach to Different Durations of Cough
VI. Complications of Cough
VII. Treatment of Cough
A. Specific Cough Therapy
B. Symptomatic
C. Examples of Non-Specific Cough Therapy
D. Mucoactive Agents
VIII. Specific Disorders causing Cough

- important to note
NTK nice to know :)
A. Definition of Cough

A forced expulsive maneuver usually against a closed

glottis, which is associated with a characteristic sound

The distinctive sound is generated by the explosive

release of trapped and pressurized intrathoracic air from
the sudden opening of the vocal folds
B. Impact of Cough

An important airway defense mechanism

Helps clear excessive secretions and foreign objects from

the airways

Coughing helps protect the lungs against aspiration

o Broncholiths- cough pellets that are expelled, which is
very irritating

Figure 1. Broncholiths

An important factor in the spread of infection

A patient-initiated tactic to provide CPR and to maintain
consciousness during a potentially lethal arrhythmia
and/or convert arrhythmias to a normal rhythm
An explosive expiration that provides a normal protective
mechanism for clearing the tracheobronchial tree
of secretions and foreign material
When excessive or bothersome, cough is one of the most
common complaints motivating patients to seek medical
attention throughout the world
A common symptom for which patients seek medical

April 4, 2016

May herald a disease or disorder

U.S. and Australian surveys: cough of undifferentiated
duration is the single most common complaint for which
patients of all ages seek medical care from primary care
physicians in the ambulatory setting
Discomfort from the cough itself and its complications
Associated with a marked deterioration in quality of life
and interference with normal lifestyle
Psychosocial dysfunction returns to normal with
successful treatment.
Impact of CAP: A Considerable Proportion of Patients with
CAP Require Hospitalization
A common cause of cough
No. 1 among top illnesses based on PHIC claims in 2013
519,000 insurance claims among patients hospitalized
Cost: PHP 7.9 B
Magnitude of the Problem
o 1989 Rural Survey (Victoria, Laguna): 10% chronic
o 1991 Urban Survey (Paco, Manila): 24.6% had cough
which was chronic or present at time of interview
o 2002: 3 Urban Cities (Manila, Cebu and Davao)
young patients: 13% had cough persisting for >2 wks
o Chronic cough is a common problem among Filipinos
Of all the highly complex defense mechanisms, cough is
the only one we can mimic voluntarily and accurately and
can inhibit voluntarily
Voluntary cough and habit cough seem to originate in the
cerebral cortex (urge to cough)
Most sensitive sites for initiating cough: larynx and
tracheobronchial tree, esp. carina and branching

A. The Cough Reflex

Cough arises following activation of a complex

sensorimotor reflex arc that begins with irritation of a
B. Initiation of Cough

Inflammatory or mechanical changes in the airways

Inhalation of chemical and mechanical irritants:

polymodal sensory nerve receptors

Rapid and large changes in lung volumes

Psychological factors, e.g laughter

C. Irritant Triggers

Exogenous Source
o Smoke
o Dust
o Fumes
o Foreign bodies

Endogenous Source
o Upper airway mucus (i.e. post nasal drip)
o Gastric contents (i.e. GERD)

Prolonged exposure to such irritants may initiate airway

inflammation, which can itself precipitate cough and
sensitize the airway to other irritants (Hyperreflex

Cough Sensor Plasticity: exaggerated response to

harmless or mildly irritating stimuli


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OS 213: Common Pulmonary Clinical Syndromes I: Cough

D. Peripheral Mechanisms of Cough

A dual primary sensory neurons stimulation model to

induce cough

CNS, activating efferent motor neurons and leading to

G. Reflex Pathway

Figure 2. Dual mechanism of cough showing the nociceptor

and mechanical pathways.

Figure 3. Afferent and efferent limbs of the cough reflex arc. The
cough center is still not well studied but believed to be integrated in the
medulla oblongata.

Unmyelinated C-fiber nociceptors

composes most of the bronchopulmonaryvagal afferent


with terminals in and around the mucosa surface of the


sensitive to a wide variety of inhaled or locally produced

chemical mediators, which may either activate or sensitize
nociceptor nerve endings irritant receptors

sensitive to bradykinin and activators of the ion channels,

TRPV1 (eg, capsaicin, protons), and TRPA1 (eg, ozone;
spices , mustard, wasabi-allylisothiocyanate)

Other selective irritants: prostaglandin E2, ozone, nicotine,

adenosine, and serotonin
Note: (TRPA1= transient receptor potential A1; TRPV1= transient receptor
potential vanilloid1)

Mechanically sensitive cough receptors

found beneath the epithelium in the large airways

relatively insensitive to most chemical mediators (with the

exception of low pH)

exquisitely sensitive to punctate stimuli delivered to the

mucosal surface (for example, inhaled particulate matter)
and mechanical forces

Include Widdicombecough receptors and lung stretch

receptors (characterized by their responses to sustained
lung inflation)-rapidly adapting receptors (RARs) and
slowly adapting receptors (SARs)
E. Cough Reflex: Afferent Pathway

Vagus nerve is the major afferent pathway

Stimuli arise from:

o Ear
o Pharynx
o Larynx
o Trachea
o Carina
o Large intrapulmonary bronchi
o Heart
o Pericardium
o Esophagus
F. Sensory Nerves Regulating Cough

Involuntary cough appears to be initiated only from

vagalinnervation of the airways

Airway afferent nerve fibers originate in the nodoseand

jugular ganglia and are carried via the vagusnerve, where
they terminate both in and under the airway epithelium.

Airway afferents are stimulated by irritants or

inflamatorymediators (often via activation of G-proteincoupled

prostanoidEP3receptors) and open ion channels, e.g.,

Information is then carried along the vagusnerve to the
solitary tract nucleus (NTS), located in the medulla. Here,
the nerves synapse, and second-order neurons relay the
message to a respiratory pattern generator within the

Cough involves a complex reflex arc that begins with the

stimulation of an irritant receptor.
Most receptors are probably located in the respiratory
system; the existence of a discrete central cough center
has not been demonstrated.
Evidence to date suggests that the cough center is
diffusely located in the medulla
RARs: Rapidly adapting receptors which are normally
quiescent in the body until activated by stimuli
SARs: slow adapting receptors
Innervated mainly by vagus nerve but also by the phrenic

H. Production of Cough

When your body senses that there is something in your

airway that shouldn't be there,
o you automatically take a deep breath,
o momentarily close your glottis
o push air against the closed glottis by contracting lung
muscles to build up extra pressure, and then open
your glottis.
o Once the glottis opens, the large pressure differential
between the airways and the atmosphere coupled
with tracheal narrowing produces rapid flow rates
through the trachea. The shearing forces that develop
aid in the elimination of mucus and foreign materials.

You can also cough whenever you want to, whether to

clear your throat or for other reasons.
Production of Cough: Phases

o Negative flow rate

Compressive/ Glottic closure

o Zero flow rate

Expulsive (Expiratory or Explosive)

o 1st cough sound heard
o Growing, constant, decreasing sub-phases
o Positive flow rate

o Restorative inspiration
Flow and Subglottic Pressures During the Phases of

Figure 4. This shows the flow of air and pressure in the subglottis
during the different phases of cough. Note that the pressure is
highest at the start of the expiratory phase.


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OS 213: Common Pulmonary Clinical Syndromes I: Cough

Glottis closure is not necessary for effective coughing

since a person can still cough even with the glottis open
(e.g. patients who are intubated/had tracheostomy. These
patients expel foreign materials through huffing.)

I. Factors Contributing to Cough Inefficiency

Altered cough mechanics

o Expiratory muscle weakness
o Inspiratory muscle weakness
o Abdominal wall muscle weakness
o Examples:

Myasthenia Gravis (muscle problem)



Altered mucuous rheology (anything that causes

o Adhesiveness
o Cohesiveness
o Examples:

Cystic Fibrosis




Chronic Bronchitis

Altered mucociliary function

o Examples:


Kartageners syndrome with ciliary dyskinesia,

Primary ciliary dyskinesia

J. Structure and Composition of Mucus

Composition of Normal Mucus

o 95% water
o 3% mucin
o 1% lipids
o <.03% DNA
o Others,
oxidants, anti-oxidants, mediators, bacterial products,
antibacterial secretions.

Mucin confers viscosity and elasticity- Influences

tenacity of sputum
o Viscosity- liquid-like property that resists flow,
o Elasticity- solid-like capacity to store energy that
moves or deforms the fluid, stringiness
Components of Mucin. NTK

20 human MUC genes

9 are expressed in the human respiratory tract

Membrane tethered mucin (eg. MUC 1, MUC 4, MUC 16)

Only 3 are classic gel-forming mucins found in airway

secretions. NTK
o MUC 2
o MUC5AC- produced mostly at proximal airways by
goblet cells
o MUC5B- Produced by goblet cells throughout airways
and by submucosal glands

Complex of glycoproteins.

Cysteine-rich secretory mucins stabilized by

multiple disulfide bonds entangled in a mesh.

K. Mucus Accumulation within the Airways

Figure 7. Pathophysiology of Mucus accumulation

Airway inflammation (Asthma, COPD, etc.)-> Mucus

hypersecretory phenotype
o Decreased mucociliary clearance

Goblet cell hyperplasia/mucus metaplasia

Increased plasma exudation

o Increased luminal mucus

Increased mucus synthesis and secretion

Reduced mucin degradation within the airways

o Submucosal gland hypertrophy

Secretion of inflammatory mediators.

L. Airway Mucosal Disease and Mucus Characteristics

Figure 8. Diagramatic representation of the various airway mucosal

diseases and accompanying mucus characterization. This only shows
the similarity in the pathophysiology of various diseases managed in
different ways.

Mucus Plugs in Airway Lumen in Airway Diseases

Figure 5. Mucin in goblet cell (L) and mucus tethering in asthma (R)

Figure 6. Structure of Mucin. Note the abundance of disulfide bonds

Figure 9. Gross and microscopic findings of mucus in various

a. Severe Asthma
b. Airway mucus tethering in asthma dont give mucolytics
because it promotes bronchospasm
c. COPD - purulent


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OS 213: Common Pulmonary Clinical Syndromes I: Cough


Cystic fibrosis epithelialization (presence of cells in the


Figure 10. Specimen of mucus plug taken from an asthmatic patient

(status asthmaticus)

Mucus Hypersecretion in Bronchiectasis

Figure 13. Diagram of Triggering and Maintenance of Cough Reflex

Sensitivity. NTK


N. Etiology of Cough

Any disorder resulting in inflammation, constriction,

infiltration or compression of the upper or lower airways
and the lung parenchyma can be associated with cough.

Figure 11. Specimens of mucus showing the notable mucus

hypersecretion from a patient with bronchiectasis with respect to the
other specimen

Mucus Hypersecretion of COPD

Major symptom in chronic bronchitic phenotype

Greater burden of respiratory symptoms and worse QOL

Frequent lower airway infection

Frequent hospitalization

Increased FEV1 decline

Risk factor for respiratory-related deaths

M. Sequelae of Increased Mucus Production

Viscosity of mucus

Ciliary effectiveness

Mucus plugs

Airway Resistance


Obstructed bronchioles leads to atelectasis


O. Diagnostic Approach
Determine Duration of Cough

Estimating the duration of cough is crucial in narrowing the

list of etiologies. ACCP/ERS Consensus Guidelines
o Acute cough : < 3 weeks
o Sub-Acute cough : lasting 3-8 weeks
o Chronic cough: > 8 weeks

Note: time periods were arbitrarily determined

The Approach to the Evaluation of Cough: The Anatomic
Diagnostic Protocol

Systematic evaluation of the afferent limb of the cough


Detailed history to obtain valuable points, with attention to

associated symptoms and includes occupational history
and environmental exposure

Thorough physical examination, including Eye-NoseThroat examination

Targeted laboratory examination; at least a chest X-ray for

patients with chronic cough

Narrows down the differential diagnosis to specific ENT,

pulmonary and extra-pulmonary causes

Provides recommendations for targeted and successful


Standard of evaluation and management since 1981

Adapted by ACCP Consensus Panel in 1998

Laboratory Work Up of Cough

Persistent Cough Reflex Hypersensitivity


Noxious Stimuli

Figure 14. Chest X-ray with a mass with striated borders. It turned out
to be lung cancer as the cause of the cough of the patient
Figure 12. Diagram on cough reflex sensitization. Y-axis: cough
reflex sensitivity, X-axis: Time point viral infection

Chest Radiograph
o Can identify the presence of chest wall,
pleural, lung parenchymal and mediastinal lesions or
o Note: Check if pulmonary involvement or not.

Sputum Analysis (very important!)

o Gross and microscopic examination


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OS 213: Common Pulmonary Clinical Syndromes I: Cough


AFB smears: initial lab recommended for a Filipino

with >2wks cough, esp. if with constitutional



- Indicative of bacterial infection

- Chronic
pneumonia, or lung abscess
- Presence of strep. pneumoniae
- Do gram staining or culture
- Rule out endobronchial tumor
- Asthma or non-asthmatic eosinophilic
bronchitis (NAEB)

Color (if Rusty)

Specialized Laboratory Studies. NTK

Paranasal/Sinus X-Ray Series /
Screening CT Scan of the
24-hour Esophageal pH
Bronchoprovocation Test
Pulmonary Function Test /
Fibreoptic Bronchoscopy
High-resolution CT Scan of the
2-D Echocardiography with or
without Doppler Studies


Disease (GERD)
Cough-Variant Asthma
Differentiate Restrictive and
Obstructive DOs
Detect Reversible versus
Endobronchial tumors
Chest tumor
interstitial lung disease

Approach to Acute Cough (<3 Weeks)

1. Is it life threatening? Or transient?
2. Are antibiotics needed?

Red Flags in Acute Cough

Transers note: this part will most probably going to be asked in the
exam. J

Chest Pain
Weight Loss

Dull chest
Bronchial breathing

2. Approach to Sub-acute Cough (3-8 weeks)

1. Does it follow an obvious preceding respiratory infection?
2. Are antibiotics needed?
3. Is it likely to become chronic?

Congestive heart failure

P. An Empiric, Integrative Approach to the Management of

Cough: ACCP Evidence-Based Clinical Practice

Algorithms that provide a road map that the clinician can

follow are useful for acute, subacute, and chronic cough.

An effective approach to successfully manage chronic

cough is to sequentially evaluate and treat for the common
causes of cough using a combination of selected
diagnostic tests and empiric therapy

Pulmonary embolus
Congestive heart failure

Note: Acute cough may be a manifestation of a serious


syndrome (UACS)


Figure 15. Diagram showing approach to Acute Cough

The most important first step is to decide whether the
acute cough is potentially a reflection of a serious
illness (e.g., pulmonary embolism, acute CHF,
pneumonia), or, as is usually the case, a manifestation of
a non-life- threatening, transient condition
Possible causes:
o URTI most common cause of acute cough;
including the common viral cold, acute bacterial
sinusitis, pertussis (whooping cough, especially in
pediatric patients that have poor vaccination), no
need for antibiotics
o Lower respiratory tract infection / Pneumonia
o Exacerbation of a
(e.g. COPD, bronchiectasis, allergic rhinitis in acute

Figure 16. Diagram showing approach to subacute Cough

From 2018:

Post-infectious is the most common cause of a sub-acute

cough; resulting from persistent airway inflammation
and/or postnasal drip following viral infection, pertussis or
infection with Mycoplasma or Chlamydia.

Common complaint: Doc, inuubo ako 4 weeks na. Nung

first week, nagka-fever ako, tapos sumasakit ang muscles
(myalgia), nanghihina, at walang gana kumain. Wala na
yung sipon, wala na yung lagnat, mas nakakagalaw na
ko, pero inuubo parin ako. DIAGNOSIS: Postinfectious (or post-viral) cough

Tell the patient that it will subside in 6 to 8 weeks, but if it

really bothersome, then prescribe medications.

The first step is to determine whether or not the cough

has followed causes an obvious preceding
respiratory infection (i.e. post infectious cough)

If post-infectious, you only have a few to consider:

o Post-Infectious Cough with bronchial
hyperresponsiveness (BHR) (6-8 weeks) like in
cases of Flu

The patient may present with wheezing, but with

no asthma and the reason for that is, the
influence of the virus is so bad that it can
slough off the epithelium, because of airway
inflammation -> neurogenic inflammation

Even the mildest stimulus can cause


Expect that the wheezing will subside in 6 to 8

o Atypical (3-4 wks) causes of Respiratory Tract
Infection (RTI)

Pneumonia including Pertussis, PTB, atypical

pneumonia, parasitic (ascaris, strongyloides,
paragonimus, legionella, mycoplasma)

Parasitic causes are common in PGH/the


Paragonimiasis is a great mimic of TB.

o Exacerbation of a pre-existing condition

If the sub-acute cough does not appear to be post

infectious in nature, it should be evaluated and managed


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OS 213: Common Pulmonary Clinical Syndromes I: Cough

as if it were a chronic cough
o After 3-8 weeks, virus can cause epithelial
degradation; airway is denuded, exposing the nerves
leading to persistence of cough.

(UACS) formerly known as Postnatal Drip

Syndrome (PNDS)

Cough-Variant Asthma

Pulmonary Tuberculosis (PTB): Cough persists

for >3 wks and the patient presents with an
abnormal CXR (*In Canada, the 3rd most
common is GERD.)
4. Institute specific therapy for all identified causes,
sequentially or in combination.
o Sequential and additive therapy is often crucial
because more than one cause of cough is frequently
o Approach is effective in the majority of patients.

3. Approach to Chronic Cough (>8 weeks)

Note: Patient with chronic cough with normal chest X-ray:

Asthma, GERD
Tools for Assessing Outcomes in Chronic Cough Studies. NTK

Figure 17. Approach to management of chronic cough

NOTE: If a patient is young, comes with a normal X-ray (no
findings), and has chronic cough, consider:


Upper airways cough syndrome/ Post nasal drip syndrome

From 2018:

The recommended approach is to undertake a

systematic, integrated, algorithmic evaluation of the

The starting point is the detailed, careful medical history,

physical examination, and CXR (and / or Sputum AFBs)
via the anatomic diagnostic protocol
o The timing and characteristics of the cough have
been shown to lack both diagnostic sensitivity and
o Remember to take down environmental exposure,
place of work, hobbies, and travel history
o E.g, Sorsogon travel history, ate a lot of snails
diagnose with Paragonimiasis
o E.g, MERS-CoV Middle East Respiratory
Syndrome caused by Coronavirus:
o E.g, Patient presented with very bad pneumonia,
went to caves was diagnosed with acute
histoplamosis, otherwise known as cave disease
which is very rare in the Philippines.
o Ask: ubo, lagnat? Saan po kayo galing?
2. Early on in the work-up: ASK FOR MEDICATIONS
o Kung pril pril pril: Rule out ACEI-included cough
early on in the work up (e.g. if on Captopril, Enalapril
for HTN) accumulation of bradykinin in the upper
airway and manifests as cough symptoms (parang
fullness/punong-puno sa throat); stopping the ACEI
will relieve the Px of the cough; prescribe other meds
for the HTN.
o Identify irritant-induced cough (including smoking),
and initiate avoidance measures when possible
o Rule out post-infectious cough
3. Do baseline investigations followed by combination of
targeted diagnostic testing or empiric treatment of highprobability diseases
o Therapeutic trials based on a suspected cause
o Avoid identifiable irritants, when possible (e.g.
smoking chronic bronchitis is most common cause
of chronic cough; environmental, industrial)
o Evaluate and treat for the 3 most common
conditions, singly or in combination in the Philippines
(from a study of Dr. Wang, Dr. Roa, Dr. Balgos, et

Chronic Upper Airway Cough Syndrome

Figure 18. Tools for assessing chronic cough

Local Modifications to Chronic Cough Algorithm

Top Causes of Chronic Cough in the Philippines (DavidWang AS, Balgos A, Roa Jr. CC, Dantes R, et. al., Chest
130:199S, 2006.)
1. Asthma
3. PTB
4. COPD / CB
5. Post-infectious cough

Sputum AFB smears must be ordered early on especially

if the clinical probability of PTB is high

Chest radiographs can narrow the differential diagnosis

and thus must also be ordered earlier whenever possible

Empiric drug therapy for asthma, PNDS and GERD can be

tried if the clinical probability is high (no need for labs)


Chest and abdominal wall SORENESS
o Most important
o May induce vasovagal reflex and death
Cough rib FRACTURES,
o May induce pneumothorax
Tracheobronchial trauma
Lifestyle change
Urinary incontinence


To treat or not to treat cough
The contrasting functions and consequences of cough
highlight the importance of balancing therapy targeting
cough, such that the defensive functions of the reflex are
preserved, while limiting the role of cough in spreading
harmful illnesses and adversely impacting patient sense of
Q. Specific Cough Therapy


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OS 213: Common Pulmonary Clinical Syndromes I: Cough

Definitive treatment: treat the underlying cause

Elimination of the inciting agent, whenever possible
Refer to Section VIII: Specific Disorders causing cough

R. Symptomatic or Non-specific Cough Therapy

Done when cause is unknown or specific treatment is not


The cough performs no useful function or causes marked

discomfort or sleep disturbance
Clinical scenarios when non-specific cough therapy is applied:
o Lung cancer, Stage IV
o Cystic Fibrosis
o Fibrothorax
o Bronchiectasis
o Sever TB producing complications in the lungs even
when the infection is inactive
o Malignant effusions
Antitussive or Cough Suppressant

drugs that increase the latency or threshold of the cough

o codeine
o dextromethorphan

drugs that affect the afferent limb of the cough reflex

o levodropropizine (available in the Phil)

centrallyactingneurokinin1 (NK-1) receptor antagonists

o aprepitant for lung cancer

for irritative, nonproductive cough


Mechanical aids for patients with neuromuscular or

neurologic diseases Example: Cough Assist Machine

A cough productive of significant quantities of sputum

should usually not be suppressed, since retention of the
sputum in the tracheobronchial tree may interfere with the
distribution of alveolar ventilation and the ability of the lung
to resist infection

Enhance cough effectiveness by promoting the

clearance of airway secretions and loosen mucus (e.g.

Indicated in cystic fibrosis, bronchiectasis, pneumonia

and post-operative atelectasis

Pharmacologic agents (e.g. Nebulized saline solution,

S. Mucoactive Agents

Increase secretion of mucin

Increase the depth of the sol layer and hydration until it

can be coughed out

May be irritants to initiate cough reflex

Increase the expulsion of mucus

Hypertonic saline, Guaifenesin, water (one of the most

effective expectorants)

Decrease neurogenic/airway inflammation

Affect mucus physiology and secretion

Anticholinergics, Steroids, Macrolides


Increase the transportability of mucus through cough

Improve mucociliary transport

Bronchodilators, surfactants, Ambroxol, certain


Compounds with sulfhydryl groups that are able to

dissociate disulphide bonds reduce mucus viscosity

Classical mucolytic compounds have either: exposed or

free sulfhydryl groups
o N acetylcysteine - that directly break disulphide

have blocked sulfhydryl groups

o Carbocysteine, Erdosteine that are exposed upon

Proteolytic enzymes and rhDNAse also break up mucus

via depolymerizing DNA/F-actin networks (not strictly

Transers note: Dra. Wang just passed through this part due to time

Case 1:

35 y.o. businessman, Indian origin, Non-smoker, 3 weeks

of non- productive cough, No other associated Sxs

No co-morbidities except for a hairy chest, nasal,

posterior pharyngeal, chest, heart and lung

Cause of cough for this patient

o Hair in the ear canal touching the tympanic
o Cough resolved with hair plucking
Cough Evoked From the Ear (Arnold Reflex)

Afferent nerves carried by the auricular branch of the

vagus nerve (i.e., the Arnold nerve) innervate the external
auditory meatus.

In a small subset of patients (<5%), several visceral

reflexes, including cough, may be evoked by the
mechanical stimulation of the ear
Case 2:

63 y.o, male, shipping magnate with chronic cough

Cough and wheezing for the past 2 months, former heavy

smoker, 3prior consults (FP, pulmo, ENT), given ICSLABA, inhaled SABA, nasal steroid, trial of oral steroids
and antibiotics, with minimal or temporary relief

Prior chest X-ray and chest CT scan unremarkable

PFT done: result unknown

PE at consult unremarkable except for scattered


Wheezing noted to be more prominent during inspiration

over the trachea

Figure 19. Hypopharyngeal CA

T. Chronic Upper Airway Cough Syndrome (UACS)

Formerly known as Post Nasal Drip Syndrome (PND)

Related to upper airway conditions

Includes allergic/ perennial non-allergic/ vasomotor/

postinfectious/ occupational rhinitis, allergic/ bacterial

Secretion from nose/sinuses stimulate upper airway cough

receptors; inflammation increases receptor sensitivity

Unclear if due to PND, direct irritation or inflammation of

cough receptors
Presenting Signs and Symptoms

tickle in throat

Throat clearing


Nasal congestion

Cobblestone-appearance of the posterior

mucosa Classic manifestation

Cough symptom to only 20%

Signs (may be absent):

o Inflamed nasal mucosa
o Secretions in posterior oropharynx

Consider underlying causes

o Allergies
o Chronic sinusitis
o Overuse of alha-agonist nasal sprays



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OS 213: Common Pulmonary Clinical Syndromes I: Cough


Do sinus imaging if with persistent symptoms or suspect

chronic/acute sinusitis

Cause is apparent, specific therapy must be instituted

(Grade B)

With chronic cough prior to extensive testing (Grade B)

antihistamine/decongestant (Grade C)

Patient has persistent nasal symptoms Add topical nasal

steroids, nasal anticholinergic agents or nasal

Do sinus imaging if with persistent symptoms or suspect

acute/chronic sinusitis
U. Cough Variant Asthma

Cough is the main predominant complaint

Mild Persistent Asthma (old GINA Guidelines)

Previously equated to mild persistent Asthma

Presenting Signs and Symptoms

Episodic/intermittent cough

With identifiable triggers


Chest tightness or Wheezing

Relief with bronchodilators

History of childhood asthma and/or atopy

Family history of asthma/atopy

Laboratory Findings

Reversible airflow obstruction in spirometry FEV1/FVC

<75% At least 12% and 200 mL increase in FEV1 or FVC
after 2 puffs of SABA Low peak flow and at least 15%
increase after SABA

Bronchoprovocation testing (BPT)

if PE and spirometry are nondiagnostic and if it is

available (Grade A)

Empiric therapy if clinical suspicion is high (Grade A)

ICS/inhaled steroids and inhaled bronchodilators (LABA)
(Grade A)

Bronchoprovocation testing (BPT) if PE and spirometry

are nondiagnostic and if available (Grade A)

BPT in the evaluation for asthma as a cause of cough:

NPV for a negative challenge is ~100%.

PPV for a positive challenge is 60 -88%

Inhaled steroids and inhaled bronchodilators (Gr. A)

1-2 weeks short course systemic steroid for those with

severe and/or refractory cough (Grade B)

SABA should not be used for a long time

Patient with severe and/or refractory cough: 1-2 weeks

short course systemic steroid
V. Gastro-esophageal Reflux Disorder (GERD)

Worsens when lying supine

Frequently undiagnosed condition

3rd most common cause of cough in the Western world

Cough may be the only manifestation

Microaspiration of small amount of gastric contents


Regurgitated acid enter the airways

are irritated
Presenting Signs and Symptoms



Acidic taste


Epigastric pain


Sore throat

Throat clearing

cough receptors

Laryngoscopic Findings



Ventricular obliteration


Postcricoid hyperplasia
Aggravating Factors

Lying supine


Carbonated drinks

Citrus fruits

24 hour esophageal pH monitoring test

o most sensitive and specific test
o should be done if cough does not improve with
medical therapy
o assists in determining whether medication should be
intensified (Grade B)

Clinical suspicion is high Empiric therapy (Grade B)

Cough does not improve24 hour esophageal pH

monitoring test

Anti-reflux therapy: proton pump inhibitors (as 1st line or if

H2 blockers are ineffective

Lifestyle modification

Add prokinetic therapy if PPIs alone are ineffective (Grade

Non-asthmatic. Eosinophilic Bronchitis (NAEB)

Eosinophilic airway inflammation without variable airflow

obstruction or airway hyperresponsiveness
Diagnostic/ Therapeutic Trial

Inhaled corticosteroid for 4 weeks

Presenting Signs and Symptoms

Often associated with upper airway symptoms

Airway Eosinophilia

Normal Spirometry

No variable airflow obstruction Management


Same as asthma

First line drug inhaled steroids or short-course oral

steroids for 2-4 weeks

Unresponsive to bronchodilators
X. Post-Infectious Cough

Cough that has been present for at least 3-8 weeks

following flu-like symptoms

Includes transient post viral BHR, pertussis, cough due to

atypical organisms

Consider other diagnoses if cough > 8 weeks

Consider pertussis if:

o cough 2weeks
o in paroxysms
o with posttussive vomiting or inspiratory whooping
(even in adults)
o exposure to a sick child

Likely due to extensive inflammation and disruption of

upper and/or lower airway epithelial integrity

Often associated with the accumulation of an excessive

amount of mucus hypersecretion -> give anti-mucus dugs

Associated with transient airway and cough receptor

hyper-responsiveness -> steroids

Self-limiting Resolves in 3- 8 weeks

Pertussis -> treat with macrolides

Y. ACE Inhibitor-induced Cough


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OS 213: Common Pulmonary Clinical Syndromes I: Cough

Common among hypertensive patients you must ask if

patient is taking ACE I (e.g. Captopril, Enalapril, -prils)


ACE I intakeAccumulation of Substance P and

bradykinins in the respiratory tract (Protrussive
mediators) Production of prostaglandins Cough
Presenting Signs and Symptoms

Dry cough

Scratchy throat

Feeling of throat obstruction


Discontinue therapy regardless of the temporal relation

between the onset of the cough and the initiation of the
ACE (Grade B)

Cough resolves within 1-4 weeks (ave. 26 days) if its due

to ACE-I intake

Switch to other anti- hypertensives

Z. Idiopathic or Unexplained Cough

No etiologic explanations can be found after an

appropriate and complete diagnostic evaluation

A diagnosis of exclusion

Consider somatic cough syndrome (formerly psychogenic


Consider tic cough (formerly habit cough)

e.g. Arnold Reflex (branch of Vagus nerve)

Transers Message:

a. Deciding whether the cough is potentially a reflection

of a serious illness
b. Deciding whether the cough is caused by external
factors (e.g. drugs, pollution)
c. Deciding whether the cough is post-infectious in
D. Performing laboratory tests such as arterial blood
gases, chest x-rays and blood counts
E. Deciding whether the cough is bronchitis or not
Answer: A
3. Which of the following is a cough suppressant?
a. Ramipril
b. Metacholine
c. Histamin
d. Levodropropizine
e. Nitric Oxide
Answer: D
Samplex (Upper classes)
1. The phase of a cough is characterized by a rapid
deceleration of gas flow rates:
a. Inspiratory
b. glottis closure
c. Compressive
d. expiratory
e. recovery
Answer: D
2. Which nerve subserves both the afferent and efferect limbs
of the cough reflex pathway
a. vagus
b. trigeminal
c. glossopharyngeal
d. superior laryngeal
e. spinal motor
Answer: A

Questions from Dr. Wang during the lecture:


True/False: One can voluntarily inhibit himself from


Answer: FALSE
2. Which phase may not be critical to effective coughing?
a. Glottic closure
b. Comprehensive
c. Expiratory
Answer: A
Love Letters from Block B:
1. The following are the most common causes of chronic
cough, EXCEPT:
a. Non asthmatic eosinophilic bronchitis
b. Gastrointestinal Reflux
c. Upper airway cough syndrome
d. Lung cancer
e. Asthma induced chronic cough
Answer: D
2. What is the most important step in the diagnostic
approach to a patient with acute cough?

3. A 25 year old male call center agent complains of chronic

cough, nasal congestion, sneezing, postnatal drip, itchy throat
and watery eyes, Physical examination reveals congested
nasal mucosa and cobblestone appearance of the posterior
pharyngeal mucosa. Following the anatomic diagnostic
protocol in the evaluation of cough, which afferent limbs of the
reflex pathway are most likely involved?
a. phrenic and vagus nerves
b. trigeminal and glossopharyngeal nerves
c. spinal motor and recurrent laryngeal nerves
d. trigeminal and phrenic
Answer: B
4. 40 F form Paco complains of cough productive of whitish,
blood tinged sputum, fever, malaise, anorexia for 4 weeks
duration. Self-medication of paracetamol and lagundi provided
relief. PE is essentially normal. What lab test should be done to
confirm the diagnosis of the patient?
A. Sputum AFB smears
C. Spirometry
D. Chest radiography
E. Sputum GS, CS
Answer: B
5. Which phase in the process of cough is characterized by
rapid rise in subglottic pressure?
a. Inspiratory
b. Expiratory
c. Recovery
d. Compressive
e. Glottic Closure


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OS 213: Common Pulmonary Clinical Syndromes I: Cough

Answer: D
Answer: C
6. The afferent limb of the cough reflex includes receptors
within the sensory distribution of the following nerves except:
a. Trigeminal
b. Glossopharyngeal
c. Spinal Motor
d. Vagus
e. Superior laryngeal

12. Factors contributing to cough insufficiency, except;

a. altered mucociliary function
b. expiratory muscle weakness
c. inspiratory muscle weakness
d. reduced mucus secretion
e. increased luminal mucus

Answer: C

Answer: D

7. 30yo teacher, nonsmoker consults you for on and off again

cough production of white, occasionally yellow phlegm, 6mos
ago. Occurs night and early in them orning. 3 days PTC, cough
has become bothersome, noted blood-streaking in sputum.
She previously consulted their school physician twice and was
told she had bronchitis. She was given antibiotics and
salbutamol-guaifenesin tablets which provided temporary relief.
She recalled cough became worse when she had to write on
the board with chalk. She has no other complaints except for
chest tightness. The erst of her Hx and PE is unremarkable.
CXR done 1month ago was normal.

13. Which of the following is NOT TRUE of the laboratory

workup for cough?
a. a chest radiograph can rule out chest wall or pleural lesion
b. a sputum gram stain is necessary for pneumonic phlegm
c. spirometry is useful in ruling out cough persistent asthma
d. sputum eosinophils is supportive of asthma
e. high resolution ct scan is indicated for interstitial lung

Basing your clinical decision on the chronic cough algorithm,

what willl be your next step?
a. Start empiric inhaled steroid beta agonist combination
b. Repeat CXR
c. Do sputum AFB smears
d. Start empiric antibiotic with atypical coverage
e. Start empiric antihistamine and decongestant
Answer: A
8. Which phase in the process of cough is characterized by a
rapid deceleration of gas flow rates?
A. Inspiratory
B. Compressive
C. Expiratory
D. Recovery
E. Glottic closure

Answer: C
14. A 20 year old female with a history of prior PTB
complication of chronic cough with whitish, viscoid sputum that
causes precordial chest pain when forcefully expectorated.
She is unable to sleep at night due to the cough. At present,
she has no other complaints. She has inspiratory crackles in
the right upper lung field. Sputum AFB smear, and TB culture
are negative. Chest x-ray shows residual TB scars, and
bronchiectatic change in the upper lung field area. Which type
of medication will you prescribe to improve the quality of this
patient and reduce her symptoms?
a. an antitussive
b. a protussive
c. an anti-leukotiene
d. an inhaled corticosteroid
e. a broad spectrum antibiotic
Answer: B

Answer: C
9. 20/M complains of chronic cough, nasal congestion,
sneezing, postnasal drip, itchy throat, and watery eyes. PE
reveals congested nasal mucosa and cobblestone
appearance of posterior pharyngeal mucosa. Following the
anatomic diagnostic protocol in the evaluation of cough, which
afferent limbs of the reflex pathway are most likely involved?
A. Phrenic and vagus nerves
B. Trigeminal and glossopharyngeal nerves
C. Spinal motor and recurrent laryngeal nerves
D. Trigeminal and phrenic nerves
Answer: B
10. A 40 year old laundrywoman from Paco complains of
cough productive of whitish, blood-tinged sputum, fever,
malaise, and anorexia of 4 weeks duration. Self-medication
with paracetamol and lagundi tablets provide some relief. PE is
unremarkable. Which laboratory test will you prioritize to
determine the diagnosis of this patients condition?
B. Spirometry
C. Chest radiograph
D. Sputum GS, CS
E. Sputum AFB smears
Answer: E
11. Which phase in the process of cough is characterized by a
rapid deceleration of gas flow rates?
A. Inspiratory
B. Compressive
C. Expiratory
D. Recovery
E. Glottic closure



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