Cough- What’s New

Diagnosis and Management

Dr ANIMESH ARYA
Consultant Chest Physician

.
 Facts of Cough in Real Life
• Cough 20 % of G.P. consult
• Harbinger of serious disease
• HRQOL issues
• 270 Crs. Cough mixtures
• OTC local prescription market separate
• Newer causes –GERD , UACS etc
• Newer medications
I’m Coughing my lungs up Doc
 Areas To Cover
• Why do we Cough? • When and How to
Investigate
• Classification and
Causes of Cough • Management
– Acute
– Subacute • Case Study
– Chronic
 What is Cough?
‘A Cough is a forced expulsive manoevere,
usually against a closed glottis and which is
associated with a characteristic sound’
CONSEQUENCES OF COUGH
• Persistent cough may be associated with
considerable morbidity including
 sleep loss, exhaustion, considerable social
disability
irritability, impaired performance in daily
activities
cough syncope, physical and psychological
effects
Although not life threatening, cough can cause
weakness and social embarrassment, which
contribute to a deterioration in quality of life.
COMPLICATIONS OF COUGH
• The magnitude of pressures, velocities, energy
generated during vigorous coughing can cause
a variety of profound physical and
psychosocial complications including ↓
HRQoL
 Intrathoracic pressures up to 300 mm Hg
Expiratory velocities up to 28,000 cm/s or 500
miles/hour (85% of the speed of sound)
 TYPES OF COUGH

Non productive cough

COUGH no sputum- antitussives

Productive
sputum - expectorants
 Classification of Cough

Three Categories of Cough

• Acute Cough = < 3 Weeks Duration
• Subacute Cough = 3 – 8 Weeks Duration
• Chronic Cough = > 8 Weeks Duration
Acute Cough
 Acute Cough <3/52 Duration
Differential Diagnosis

• Upper Respiratory Tract infections:

Viral syndromes, sinusitis viral / bacterial

• URTI triggering exacerbations of Chronic Lung

Disease eg Asthma/ COPD
• Pertusiss
• Pneumonia
• Left Ventricular Heart Failure
• Foreign Body Aspiration
 Acute Cough
Epidemiology
• Symptomatic URTI
– 2-5 per adults per year
– 7-10 per child per year
• 40-50% will have cough
• Self medication common -£24million per
year
• 20% consult GP (2F:1M)
• Most resolve within 2 weeks
 Treatment of Simple Acute Cough

• Benign course -reassure

• Cough can distress
• Patients report OTC
medication helpful
• Voluntary cough suppression -
linctuses/ drinks
• Suppression of cough -
dextromethorphan, menthol,
sedating antihistamines &
codeine
 Managing Acute Cough
Identify High Risk groups

Acute Cough Can be 1st

Indicator of Serious
Disease
eg Lung ca, TB, Foreign
Body, Allergy, Interstitial
Lung disease

‘Chronic cough always

preceded by acute
cough’.
 Red Flags in Acute Cough

Symptoms Signs
• Haemoptysis Tachypnoea
• Breathlessness Cyanosis
• Fever Dull chest
• Chest Pain Bronchial Breathing
• Weight Loss Crackles

THINK pneumonia, lung cancer, LVF

GET a CHEST X-Ray
 Duration of Cough in URTI
Primary Care Setting
No antecedent or chronic lung disease

End of Week % Coughing

3 58
4 35 Sub-acute
5 17 Cough
6 8 -Post viral
cough
*Jones FJ and Stewart MA, Aust Family
Physician Vol. 31, No. 10, October 2002
Sub-Acute Cough
 Sub-acute Cough 3-8 weeks
Likely Diagnoses
ACTIONS
• Postinfectious
• Bacterial Sinusitis •Examine Chest

• Asthma •Chest X-Ray if signs or smoker

• Start of Chronic •Measure of airflow obstruction

Cough ie peak flow -one off
peak flow -serial
• Don’t want to miss spirometry
lung cancer
 Post Infectious Cough

A cough that begins with an acute

respiratory tract infection and is not
complicated* by pneumonia

*Not complicated = Normal lung exam and normal chest X-ray

Post Infectious cough will resolve without treatment

Cause = Postnasal drip or Tracheobronchitis

Chronic Cough
 Chronic Cough
Epidemiology
Epidemiology difficult -acute vs chronic

Cullinan 1992 Respir Med 86:143-9

n=9077
16% coughed on >50% days of year
13% coughed sputum on >50% days of year
54% were smokers
 Chronic Cough
Epidemiology
Associations with:
Smoking (dose related)
Pollutants (particulate PM10) -occupation
Environmental irritants (eg cat dander)
Asthma
Reflux
Obesity
Irritable bowel syndrome
Female
 Making the Diagnosis
Common Differentials

Lung Disease Gastro

-normal CXR -Oesophageal
-abnormal CXR Reflux

Post-nasal Drip
-allergic rhinitis Non-structural
-bacterial sinusitis ACE-Inhibitors
Tobacco
Habit Cough
 RARE CAUSES OF CHRONIC COUGH

• TRACHEOBRONCHIAL • LVF
COLLAPSE- COPD • ILD
• CA LUNG • SECONDARIES
• TUBERCULOSIS CARCINOMATOSIS
• LUNG INFECTION • HYPERTHYOIDISM
• OCCUPATIONAL LUNG • CARCINOID
DISEASE • RETAINED FB
• BRONCHIECTASIS • HODGKIN
• SARCOIDOSIS • TOF
 CAUSES OF CHRONIC COUGH IN CHILDREN
INFANCY EARLY CHILDHOOD
• GERD • POST VIRAL
• RTI • ASTHMA
• CONGENITAL • PASSIVE SMOKING
• CHD • GERD
• PASSIVE SMOKING • FB
• ENVIRONMRNTAL TRIGGER • BRONCHIECTASIS
ASTHMA
LATE CHILDHOOD
• ASTHMA
• TB
• SMOKING
• PND
• BRONCHIECTASIS
• PSYCHOGENIC COUGH
 Chronic Cough
Investigating Chronic Cough

Purpose:
• To exclude structural disease
• To identify cause
How
History & Examination inc occupation
& Spirometry
ALWAYS GET A CHEST X-RAY
IN CHRONIC COUGH
 TESTS FOR COUGH AND
THEIR PPV
• SINUS X RAY --50 %
• CHEST XRAY -- 25%
• BARIUM SWALLOW -- 60%
• SPIROMETRY --40%
• BRONCHOSCOPY --50%
• PH PROBE --100%
 Chest X-Ray
and Differential of Cough
Normal CXR Abnormal CXR
• Gastro-oesophageal reflux • Left ventricular failure
• Post-nasal Drip • Lung cancer
• Smokers cough/ Chronic • Infection/ TB
Bronchitis • Pulmonary fibrosis
• Asthma • Pleural effusion
• COPD
• Bronchiectasis
• Foreign body
 ACE-Inhibitors and Chronic
Cough
Incidence: 5-20%
Onset: one week to six months
Mechanism
Bradykinin or Substance P increase
Usually metabolized by ACE)
PGE2 accumulates and vagal stimulation.
Treatment: switch to Angiotensin II Receptor
Blockers (ARBs)
 Gastro-oesophageal Reflux
GORD accounts alone or in
combination for 10-40% of
chronic cough

Two Mechanisms
a. Aspiration to larynx/ trachea
b. Acid in distal oesophagus
stimulates vagus and cough
reflex
 Gastro-oesophageal Reflux
Symptoms
Cough Features GI Symptoms

Throat clearing If Aspiration main mechanism

Worse at night / rising Heart burn
On eating Waterbrash/ Sour taste
Regurgitation
Reflex hypersensitivity
Morning Hoarseness

CXR -normal or hiatus If Vagal - NO GI symptoms

hernia
Spirometry normal
 Gastro-oesophageal Reflux
Reflux may be due to Medications or Foods

Drugs and foods that reduce lower esophageal

sphincter (LES) pressure and can cause increased
reflux include:

Theophylline Chocolate
Oral β adrenergic agonists Caffeine
NSAIDs Peppermint
Ascorbic acid Alcohol
Calcium Channel Blockers Fat
Endoscopy can show GORD, but cannot
confirm GORD as the cause of cough.

© Slice of Life and Suzanne S. Stensaas

GED
GED
 Gastro-oesophageal Reflux
Treatment
Trial of Therapy
• High dose twice daily PPI for min 8weeks
• + prokinetic eg domperidone or metoclopramide
• Eliminate contributing drugs.
• Baclofen rarely

Improves in 75-100% of cases

 Post-Nasal Drip
Symptoms: Causes
• ‘something dripping’ • Allergic rhinitis
• frequent throat • Non-allergic rhinitis
clearing • Vasomotor rhinitis
• nasal congestion / • Chronic bacterial
discharge sinusiits
• posture
Left Ventricular Failure
Idiopathic Pulmonary Fibrosis
TB
Lung Cancer
 Conclusions
Acute Cough < 3/52 Chronic Cough >3/12
Usually URTI CXR and Spirometry
CXR if worried
Symptomatic therapy Consider
GORD
Subacute Cough 3-8/52 Post -Nasal Drip
Usually post-viral Lung - Abnormal CXR
CXR if smoker or - Normal CXR
worried (asthma/ COPD)
New treatment Approach for
Dry Cough
 ANTITUSSIVE
CENTRAL
Opioids – Codeine
Non Opioids – Dextromethorphan

 PERIPHERAL
 Levodropropizine
CENTRAL ANTITUSSIVES
 NT AND EFFECT ON COUGH
CENTER
NT NT
BY CENTRAL
EFFECT
ANTITUSSIVE
REACTION DRUGS
Glutamate Excitatory Increase conc
Stimulates cough Codeine inhibits
Stimulates cough them via μ receptor
only for analegesia
Glycine
Glycine Inhibitory
Inhibitory Increase conc
Inhibits cough -
Inhibits cough

GABA Inhibitory Inhibits cough ? Dextro-

GABA Inhibitory Increase conc
methorphan
Inhibits cough

Substance P Stimulatory Stimulates cough Opioid Resistant

Substance P Excitatory Increase conc
Stimulates cough

Serotonin
Serotonin (5 HT) Inhibitory
Inhibitory Inhibits
Increasecough
conc Codeine 5HT
Inhibits cough
MECHANISM OF COUGH CONTROL

Depression of cough reflex:

OPIOIDS
 It shows good antitussive activity at doses that
do not cause analgesia.
 codeine’s antitussive properties does not
correlate closely with analgesic and other
effects (probably different receptors are involved
in the antitussive action than in analgesia).
 MAJOR SIDE EFFECTS
• Respiratory depression
• Constipation
• Serotonin syndrome
• Sedation
• Dependence
 THERAPY GAPS
• Due to little understanding of cough
physiology only central mechanism is
considered best treatment modality.

• Although dry irritating cough many times is

only a peripheral irrelevant stimulation central
antitussives are given to control them.
 THERAPY GAPS
• Associated adverse effects or disadvantages
are higher with these central antitussives than
their efficacy.

• Cough receptors are only present in lungs and

peripheral antitussives can be safely and
efficaciously used to treat dry irritating cough
 THERAPY GAPS
• Till date due to unavailability of drugs which
act by peripheral mechanism centrally acting
antitussives are taken as gold standard.

• There are resistant coughs which can be

managed only by peripheral antitussives and
not by central antitussives.
 NEED OF THE HOUR
• Approximately 20% of respiratory out-patient
referrals are for patients with chronic cough.
Failure of the cough to resolve completely is
common.
• Symptomatic cough suppressant with good
efficacy and better safety profile is required.
PERIPHERAL ANTITUSSIVES
 WHY PERIPHERAL
ANTITUSSIVE
• Cough receptors which are responsible
for initiating cough impulses or afferent
impulses are present peripherally in the
larynx and tracheo bronchial tree and
not in the brain.
• In humans, their antitussive effect is almost
certainly a central one.
• However, when used in effective antitussive
doses, opiates are associated with
unacceptable adverse effects, including
euphoria, sedation, nausea, vomiting and
respiratory depression, which are thought to
be mediated at a variety of receptors.
• The cough reflex is initiated by activation of
bronchopulmonary C fibers and the
mechanically-sensitive cough receptors.
• Stimuli initiating cough through activation of
one or both of these vagal afferent nerves
include capsaicin, acid, bradykinin,
cinnamaldehyde, cigarette smoke, and non-
isotonic aerosols.
 LEVODROPROPIZINE
• (S)-3-(4-Phenyl-1-
piperazinyl)-1,2-propanediol
• Molecular Formula
C13H20N2O2
• Molecular Weight 236.31
 LEVODROPROPIZINE
• Levodropropizine is an orally administered, non-
opioid agent with peripheral antitussive mechanism.
• In patients with pathological cough, randomized,
double-blind trials have demonstrated
levodropropizine to be efficacious compared to
dextromethorphan in non-productive cough, and
better safety profile than dihydrocodeine against
cough.
 MECHANISM OF ACTION
• It acts by inhibiting the information about
irritant sent to Medulla by sensory C-fiber
afferents.
• It acts as a peripheral antitussive, with no
action in the central nervous system and so
does not cause side effects such as
constipation or respiratory depression which
are produced by opioid antitussive such as
codeine and its derivatives.
 PHARMACOKINETICS
• It is well absorbed after oral administration

DRUG ONSET OF DURATION OF

ACTION (hr) ACTION (hr)

Levodropropizine 1 6

Codeine 1 6

Dextromethorphan ? 30 ?6
The drug is metabolized in liver and excreted
in urine.
Interactions – Alcohol, CNS depressants, and
tricyclic antidepressants may cause additive
effects
RATIONAL OF PERIPHERAL AT
USAGE
• As cough receptors are at peripheral site
action is limited to periphery.
• As no central NT altered safer than central
antitussives
• Efficacious in cough control.
• Cough resistant to central antitussives are
manageble by peripheral antitussives.
 EXPERIMENTAL
Carbamazepine,
Thalidomide, Gabapentin,
Baclofen Amitriptylline

LOCAL ANAESTHETICS
Nebulised Lidocaine
Benzonatate
PERIPHERALLY-ACTING ANTITUSSIVES
Levodropropizine, Moguisteine, Levocloperastine

OPIOIDS
Morphine/Methadone
Dextromethorphan, Codeine, Hydrocodone

CONSIDER ORAL STEROID TRIAL

2 weeks

CANCER SPECIFIC CO-

systemic chemotherapy/RT endobronchial
therapy, PDT, palliative RT
MORBIDITIES
COPD, reflux, asthma, infections
THANK

YOU