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

Common Pulmonary Clinical Syndromes I: Cough

Trans Number: 11

Aileen Wang, MD, FPCCP


OUTLINE
Introduction
A. Definition of Cough
B. Impact of Cough
II.
Epidemiology of Cough
III.
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
Characteristics
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
or
Non-Specific
Cough
Therapy
C. Examples of Non-Specific Cough Therapy
D. Mucoactive Agents
VIII. Specific Disorders causing Cough
I.

- important to note
NTK nice to know :)
I. INTRODUCTION
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
attention

EXAM 2
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.
II. EPIDEMIOLOGY OF COUGH
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
bronchitis
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
III. MECHANISM OF COUGH
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
receptor.
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
Sensitivity)

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


cough
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


nerves

with terminals in and around the mucosa surface of the


airways

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
receptors,
e.g.,
bradykinin
B2and

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


TRPA1 or TRPV1.
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
nerve

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

Inspiratory
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

Recovery
o Restorative inspiration
Flow and Subglottic Pressures During the Phases of
Cough

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)

Guillan-Barre,
stroke
patients
(aspiration
pneumonia)

Polio

Altered mucuous rheology (anything that causes


secretions)
o Adhesiveness
o Cohesiveness
o Examples:

Cystic Fibrosis

Pseudomonas

COPD

Asthma

Chronic Bronchitis

Altered mucociliary function


o Examples:

Smoking

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,
electrolytes,
enzymes,
anti-enzymes,
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,
stickiness
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


diseases.
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


d.

Cystic fibrosis epithelialization (presence of cells in the


mucus)

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

V. APPROACH TO PATIENTS WITH COUGH


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

Infections

Obstructed bronchioles leads to atelectasis


IV. COUGH REFLEX SENSITIZATION

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


reflex

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


therapy

Standard of evaluation and management since 1981

Adapted by ACCP Consensus Panel in 1998


Laboratory Work Up of Cough

Persistent Cough Reflex Hypersensitivity

Innocuous
Stimuli

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
abnormalities
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


o

AFB smears: initial lab recommended for a Filipino


with >2wks cough, esp. if with constitutional
symptoms

Purulent

Blood
Eosinophilia

- Indicative of bacterial infection


- Chronic
bronchitis,
bronchiectasis,
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


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

cough

Gastroesophageal
Reflux
Disease (GERD)
Cough-Variant Asthma
Differentiate Restrictive and
Obstructive DOs
Detect Reversible versus
Non-reversible
Airflow
Obstruction
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

Symptoms
Hemoptysis
Breathlessness
Fever
Chest Pain
Weight Loss

Signs
Tachypnea
Cyanosis
Dull chest
Bronchial breathing
Crackles

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
Guidelines

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


disease

DISEASE
Upper
airway
syndrome (UACS)

o
o

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
pre-existing
condition
(e.g. COPD, bronchiectasis, allergic rhinitis in acute
exacerbation)

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


bronchospasm

Expect that the wheezing will subside in 6 to 8


weeks
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


Philippines

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
present.
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:

Asthma

Upper airways cough syndrome/ Post nasal drip syndrome

GERD
From 2018:

The recommended approach is to undertake a


systematic, integrated, algorithmic evaluation of the
patient
1.

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
specificity
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
al):

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
2. PNDS
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)

VI. COMPLICATIONS OF COUGH


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

VII. TREATMENT OF COUGH


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
well-being.
Q. Specific Cough Therapy

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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


possible

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


center
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


Protrussive

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.
mucolytics)

Indicated in cystic fibrosis, bronchiectasis, pneumonia


and post-operative atelectasis

Pharmacologic agents (e.g. Nebulized saline solution,


Erdosteine)
S. Mucoactive Agents
Expectorants

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)
Mucoregulators

Decrease neurogenic/airway inflammation

Affect mucus physiology and secretion

Anticholinergics, Steroids, Macrolides


Mucokinetics

Increase the transportability of mucus through cough

Improve mucociliary transport

Bronchodilators, surfactants, Ambroxol, certain


mucolytics
Mucolytics

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
bonds

have blocked sulfhydryl groups


o Carbocysteine, Erdosteine that are exposed upon
metabolism

Proteolytic enzymes and rhDNAse also break up mucus


via depolymerizing DNA/F-actin networks (not strictly
mucolytic)
VIII. SPECIFIC DISORDERS CAUSING COUGH

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

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
membrane
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

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
sinusitis
Pathophysiology

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

Hoarseness

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


Diagnostics

Do sinus imaging if with persistent symptoms or suspect


chronic/acute sinusitis
Management

Cause is apparent, specific therapy must be instituted


(Grade B)

With chronic cough prior to extensive testing (Grade B)


Treat
empirically
with
first
generation
antihistamine/decongestant (Grade C)

Patient has persistent nasal symptoms Add topical nasal


steroids, nasal anticholinergic agents or nasal
antihistamine

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

Dyspnea

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
Diagnostics

Bronchoprovocation testing (BPT)

if PE and spirometry are nondiagnostic and if it is


available (Grade A)
Management

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


Pathophysiology

Regurgitated acid enter the airways


are irritated
Presenting Signs and Symptoms

Heartburn

Regurgitation

Acidic taste

Dysphagia

Epigastric pain

Hoarseness

Sore throat

Throat clearing

cough receptors

Laryngoscopic Findings

Edema

Erythema

Ventricular obliteration

Pseudosulcus

Postcricoid hyperplasia
Aggravating Factors

Lying supine

Coffee/Tea

Carbonated drinks

Citrus fruits
Diagnostics

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)
Management

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


B)
W.
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


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
Pathophysiology

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
Management

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)

Pathophysiology

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


Management

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


cough)

Consider tic cough (formerly habit cough)

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


END OF TRANSCRIPTION
BLOCK #4BIDDEN 4EVER! HAHA
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
etiology
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:


1.

True/False: One can voluntarily inhibit himself from


coughing

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
B. CBC
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
disease

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
E. AOTA
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?
A. CBC
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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