Approach to the Vexing Cough
Syndrome
Ross Summer M.D.
Pulmonary/Critical Care Medicine
No conflicts of interest
Learning Objectives
• Learn the anatomy and neurophysiology of
the cough reflex.
• Learn the common classification system for
cough.
• Learn to manage the most common
conditions causing cough in the outpatient
setting.
• Learn the most effective treatments for
cough.
Cough is common
• 5th most common symptom presenting to
the primary care setting.
• Represents up to 40% of all office visits to a
general pulmonary clinic.
• Results in 30 million office visits/year in the
United States.
Braman SS, Prim Care. 1985;12:217–25
Cough is associated with
significant morbidity
• Health-related effects
– Physical - conjunctiva hemorrhage, sleep
disturbance, GERD, hernia, rib fractures,
intracranial hemorrhage.
– Psychological – anxiety, frustration, social
stigma.
Cough is a costly condition
• Decreased productivity (e.g. absenteeism)
• 600 million spent/year on OTC cough
medications.
Anatomy and neurophysiology of the cough
reflex
Receptors
“Cough center”
Afferent
GN Glossopharyngeal Nerve
PN Phrenic Nerve
TN Trigeminal Nerve
VN Vagus Nerve
?N Cortical Input
Efferent
RL
Recurrent Laryngeal
PN
Phrenic nerve
SMN Spinal Motor nerves
Irritants
Mechanical
Pollutants
Tumor
Stomach acid
Foreign body
Cigarette smoke
Fibrosis
Drugs
Airway stricture
Enlarged lymph
node
Cerumen
Enlarged Heart
Inflammatory
Cigarette smoke
Asthma, chronic bronchitis
Eosinophilic bronchitis
Bronchiectasis
Post-infectious
Upper airway cough syndrome
ACE-I , other drugs
Common classification system
Based on duration of symptom
1. Acute - less than 3 weeks
• Most commonly due to an acute respiratory tract infection.
2. Subacute – exists longer than 3 weeks but less
than 8 weeks
• Most commonly due to a post-infectious process.
3. Chronic - exists greater than 8 weeks
• Non-smokers it is most commonly due to drug side effect,
chronic rhinitis, asthma or gerd.
• In smokers – add COPD and lung cancer
Case presentations
Chief compliant: “Cough for 6 days”
HPI: 75 year-old man presents with acute cough. Initially associated with
rhinitis, sore throat, subjective fever but other symptoms have since
resolved. Pt states cough occurs throughout the day, but worse at night
and it is productive of white-yellow sputum. No post-tussive emesis or sick
contacts.
ROS: negative
PMH: HTN, hypercholesterolemia, osteoarthritis
SH: Non-smoker
MEDS: HCTZ, lipitor, NSAIDs prn
EXAM:
Afebrile, hr 80’s, BP 125/80, sats 98%
HEENT: boggy nasal mucosa.
Chest: clear, normal expiratory time, no crackles, no egophony
Heart: normal
Abd: unremarkable.
Ext: no edema
WHAT IS THE MOST APPROPRIATE DIAGNOSIS?
A.
B.
C.
D.
Lower respiratory tract infection
Post-infectious cough
Common cold
Acute bronchitis
Pratter Cough and the Common Cold
ACCP Evidence-Based Clinical Practice Guidelines 2006.
Wenzel, R. Acute Bronchitis. NEJM 2006.
WHAT MICROBES ARE LIKELY RESPONSIBLE FOR
PT’S ACUTE BRONCHITIS?
• Viral (>90%)
–
–
–
–
–
–
Influenza
Parainfluenza
Metapneumovirus
Adenovirus
Rhinovirus
Coronavirus
• Bacterial
– Chlamydia pneumoniae
– Mycoplasma pneumoniae
– Bordetella pertussis
Wenzel, R. Acute Bronchitis. NEJM 2006.
WHAT IS THE ROLE FOR PATHOGEN TESTING
IN ACUTE COUGH?
• No role except when Bordetella pertusis is
suspected.
• This assumes pt is a non-smoker and does
not have a history of bronchiectasis.
Wenzel, R. Acute Bronchitis. NEJM 2006.
IS A CXR NECESSARY IN THE WORK-UP OF
ACUTE BRONCHITIS?
• No need for CXR unless:
–
–
–
–
Fever
Tachycardia
Low oxygen sats
Abnormal lung exam
• Elderly
– 30% with pneumonia do not report a fever.
– Only 37% of elderly patients with pneumonia have tachycardia at
presentation to the doctor.
• Productive cough should not influence your decision
– 50% of patients with acute bronchitis will report a productive cough.
RAÚL RIQUELME et al Am. J. Respir. Crit. Care Med.1997
Community-acquired Pneumonia in the Elderly
WHAT IS THE PRIMARY OBJECTIVE
WHEN TREATING ACUTE BRONCHITIS?
Patient
perspective
Get symptom
relief
Physician
perspective
Manage expectations.
TREATMENT OPTIONS FOR ACUTE
BRONCHITIS
• Antibiotics
• Beta-2 agonists/steroids
• Anti-tussive agents (e.g. tesselon pearles,
codeine, dextromethorphan).
• Anti-inflammatory medications (e.g. steroids,
NSAIDS)
• Expectorants (e.g. guaifenesin)
Antibiotics in acute bronchitis
• Little to no role in acute cough in patients
without pre-existing lung disease (e.g. COPD,
bronchiectasis).
– 60% of all patients receive antibiotics
– 85% of all elderly patients
– 90% of all smokers without COPD
• Possible role in early Bordetella pertussis
Other treatments in acute bronchitis
• Beta-2 agonists
– No clear benefit
– Viral infections can be a trigger of asthma
exacerbations
– 40% of all patients have evidence of airflow obstruction
• Anti-tussive agents – benefit but studies are mixed.
– Codeine – central acting opioid
– Dextromethorphan (DM) – central acting non-opioid
– Benzonatate (Tessalon pearles) – peripheral-acting
anesthetizing agent
– Anti-histamines – anticholinergic side effects
Other treatments in acute bronchitis
• Anti-inflammatory medications
– No clear benefit of steroids
– Naprosyn – Sperber et al Ann Intern Med 1992
• Expectorants
– Guaifenesin (Mucinex) – no evidence to support
its use
Chief complaint: “Cough is driving me crazy”
HPI: Mr W returns to clinic 3 weeks later for further evaluation.
States cough is present at all times of day but is made worse by
cold air and deep inspiration. Cough is non-productive, and patient
denies hemoptysis, fever, chills, rhinitis, shortness of breath, postnasal drip or gastroesphageal reflux symptoms.
ROS- frustration, anxiety, chest wall pain, headaches
Exam:
afebrile, vitals normal
HEENT: normal nasal mucosa, no cobblestoning noted.
Chest: few wheezes, normal expiratory time.
Heart: rrr, no murmurs
Abd: unremarkable.
Ext: no edema
Dx: POST-INFECTIOUS COUGH
• Cough lasting > 3 weeks.
• It is basically a fancy term for “acute
bronchitis that won’t go away.”
• Patients are often very frustrated at the time
of diagnosis.
• Managing frustration is the major challenge
for the treating physicians.
MANAGE EXPECTATIONS EARLY
• Patients with acute bronchitis should be told
that cough may last a long time.
– 50% of patients with acute bronchitis (>5 days)
will still be coughing at 3 weeks (NEJM 2005).
– 5-10% of patients will still be coughing at 8
weeks.
Braman, S. Postinfectious Cough
ACCP Evidence-Based Clinical Practice Guidelines. 2006
WHAT IS THE ROLE FOR CXR IN POSTINFECTIOUS COUGH?
• No role unless
– Smoker
– Immunocompromised
– Elderly
WHAT IS THE ROLE FOR ANTIBIOTICS IN
POST-INFECTIOUS COUGH?
• No role unless suspect sinus disease.
WHAT IS THE TREATMENT FOR POSTINFECTIOUS COUGH?
• Airway injury
• Hypersensitive cough reflex – cough often worse with
deep inspiration.
• Treat with peripheral or central acting anti-tussive
agents . (I use chlorpheniramine 4mg tid)
• Airway inflammation
• Lower airway leading to bronchospasm (e.g.
bronchdilators) – cough associated with chest tightness.
• Upper airway inflammation leading to upper airway
cough syndrome (e.g. inhaled steroids).
• Secondary complication
• GERD (anti-acid therapy) – cough worse at night
HPI: 75 yo man with presents for evaluation of chronic cough. Cough
began 2 months ago. Pt doesn’t recall any inciting events. Cough is
productive of whitish sputum. Denies association with meals or position.
Denies hemoptysis, weight loss, fever, chills, night sweats, nasal
congestion, reflux symptoms, shortness of breath or wheezing.
ROS: Denies prior lung infections.
PMH: HTN, DM, mild proteinuria
ALL: NKDA
SH: Currently unemployed. Previously worked in construction. Divorced.
Lives alone. Never smoked cigarettes.
MEDS: enalapril for 10 years
Exam:
afebrile, hr 80’s, BP 125/80, sats 98%
General: well nourished, well developed.
HEENT: unremarkable
Chest: clear, slightly prolonged expiratory time.
Heart: rrr, no murmurs
Abd: unremarkable.
Ext: no edema, nicotine stained fingers
Chronic cough
• Cough lasting greater than 8 weeks.
WHAT ARE THE MOST COMMON CAUSES OF
CHRONIC COUGH?
• Upper airway cough syndrome
– Allergic
– Perennial non-allergic
– Sinusitis
• Cough variant asthma
1) Non-smoker
2) Not on medication
associated with cough.
3) Normal CXR.
• GERD/Laryngopharyngeal reflux
Irwin et al. The Diagnosis and Treatment of Cough
NEJM 2000.
Surinder Birring. Controversies in the Evaluation and Management of
Chronic Cough AJRCCM 2011
WHAT IS THE ROLE FOR CHEST IMAGING IN
CHRONIC COUGH?
• All patients should have a CXR evaluation
after 8 weeks.
WHEN SHOULD AN ACE-INHIBITOR BE
STOPPED?
• Very high incidence (up to 15% with some ACE-I)
• Symptoms are sometimes a clue. Presents with a tickling,
scratchy, or itchy sensation in the throat, but can have
variable presentation.
• It usually begins within one week of instituting therapy, but
the onset can be delayed up to 1 year.
• It is a more common complication in women than in men,
and is also more common in those of Chinese ancestry.
• It does not occur more frequently in asthmatics than in nonasthmatics.
WHEN SHOULD THE COUGH GO AWAY
AFTER STOPPING ACE-I?
• Typically resolves within one to four days of
discontinuing therapy but can take up to EIGHT
weeks!
ALMOST ANY DRUG IS ASSOCIATED
WITH COUGH!
• ANTI-HYPERTENSIVES
– Beta-blockers
– Ca channel blocker – (e.g. norvasc)
– ARB (up to 3%)
Practical approach to managing chronic
cough in a non-smoker
Evaluate for
specific cause
by H&P
Cause not clearly
identified
Treatment
ineffective
Obtain CXR
CXR
normal
Initiate treatment
for 1 of the 3 most
common causes
of chronic cough
Treatment
effective
Continue treatment for
defined period
Cause
highly
suspected
Initiate treatment
Treatment
effective
CXR
abnormal
Evaluate and treat
abnormality
Continue treatment for
defined period
Treatment
ineffective
Consider referral to subspecialist
Pratter MR, Bartter T, Akers S, DuBois J. An algorithmic approach to chronic
.
cough. Ann Intern Med. 1993;119:977–83
Asthma and cough
• Paucity of randomized control trials.
• PFTs can be normal.
• Role for bronchoprovocation testing is unclear. These tests
have a low positive predictive value in healthy controls and
may be worse in patients chronic cough.
• Trial of steroid + b2 agonist is recommended, but no clear
evidence what is the right regimen.
• Failure of treatment may relate to ineffective delivery or
compliance.
UACS
• Allergic and non-allergic upper airway
symptoms are common but chronic cough is
not.
• Paucity of randomized control trials.
• Anti-histamines will suppress cough through
their anti-cholinergic side effects.
GERD and Cough
• GERD is very common but chronic cough is not.
• In patients with chronic cough + low esophageal pH treatment with PPIs
improves symptoms in less than 30% of patients (Patterson ERJ 2004).
• A Cochrane review concluded that the effect of antireflux therapy is
inconsistent and of uncertain magnitude (Chang BMJ 2006).
• Randomized control trials have not confirmed the success of earlier
uncontrolled studies (Fathi et al Thorax 2008).
• Trials rarely have a placebo.
• Surgical interventions for GERD do not effectively decrease cough
frequency over the long-term.
• New trends in treatment of non-acid related reflux.
• Skepticism over the diagnosis of laryngopharyngeal reflux is warranted.
New Paradigm: Cough reflex
hypersensitivity
• Abnormally sensitive cough reflex (stretch, cold,
flow) is a feature of most patients with chronic
cough.
• Can be assessed by history or by measuring
response to irritants (e.g. citric acid, capsaicin).
• Elevated levels of substance P, bradykinin,
prostaglandins are found in airways of patients
with chronic cough.
• Drugs that target the cough receptors need to be
developed.
Conclusion
• Cough is common
• Knowledge of anatomy and physiology of
cough reflex may prove helpful in identifying
a cause.
• Treatment is limited but a logical
pharmacological approach may prove more
effective.
Thank you
WHEN SHOULD YOU RECOMMEND THAT
PATIENTS BE REFERRED TO A
SUBSPECIALIST?
• Subacute cough –
– When primary care physician is no longer able to
manage patient expectations (usually occurs when
cough lasts > 4 weeks). Subspecialist will provide
reassurance.
• Chronic cough –
– After removal of offending agent (e.g. ACE-I) and
treatment for at least one of the most likely etiologies
has been ineffective.