Download (Idiopathic) Cough

Differential Diagnosis And Treatment
In Adults
MÜNEVVER ERDİNÇ
Department of Chest Diseases
Ege University Faculty of Medicine
Acute Cough
lasting less than 3 weeks
Subacute Cough
lasting 3 to 8 weeks
Chronic Cough
Lasting more than 8 weeks
Morice AH.Eur Respir J 2004 :24:481-492
Fontana GA.Thorax 2003;58:1092-1095
Irwin RS.NEJM 343(23): 1715-1721,2000
Irwin RS. Chest 1998; 114(suppl1) :133S-181S
Differantial Diagnosis
of Chronic Cough in Adults
• PNDS
– Allergic rhinitis
– Chronic sinusitis
• GERD
• Cough variant asthma
• ACEI induced cough
• Pertusis
• Neurogenic
– Traumatic
– Postinfectious cough
• Phychogenic cough
• Chronic aspiration
• Zenker diverticulosis
•
•
•
•
•
•
•
•
•
•
Foreign body
Chronic bronchitis
Bronchiectasis
Lung cancer
Subglottic stenosis
Tracheomalasie
Tracheoesophageal fistul
Tuerculosis
Sarcoidosis
Congestive heart failure
Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700
In prospective studies in adults,
chronic cough is most commonly
due to 6 disorders :
Upper Airway Cough Syndrome (UACS)
Asthma
GERD
Chronic Bronchitis
Bronchiectasis
Non-asthmatic Eosinophilic Bronchitis
Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S
New Considerations
 Eosinophilic bronchitis
 Atopic cough
 Non acid(volume)/ weakly acid reflux
 Idiopathic (unexplained) öksürük
Diagnosis and Management of Cough
ACCP Evidence-Based CPG 2006
Postnasal drip syndrome (PNDS) renamed upper airway cough
syndrome (UACS)
Upper airway afferents may reflexly enhance coughing
Nonasthmatic eosinophilic bronchitis recognized as a common
cause of chronic cough
Idiopathic cough renamed unexplained cough
The term acid reflux disease, unless it can be definitively shown to
apply, replaced by reflux disease
Update of current diagnostic and therapeutic approaches
Common diseases, Uncommon diseases
New algorithms for the management of cough in adults and
children
An empiric integrative approach is recommended
Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S
Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235
PNDS
ASTHMA
12
16
6
13
12
4
GERD
10
1. Gastroesophageal reflux disease (21-41%)
2. Cough variant asthma (24-59%)
3. Postnasal drip syndrome (41-58%)
Chest 1999;116:279-284
Percentage of Cases Presenting 1,2,3 and 4 Causative factors
Percentage of Cases Presenting 1,2,3, and 4 Causative Factors
8,9%
16,7%
38,5%
1
38,5%
2
3
4
1
2
3
4
35,9%
Chest 1999;116:279-281
Asthma and/or GERD, PNDS
responsible for 93.6% of the cases
of chronic cough





İmmunocompetent patients
Not exposed to enviromental irritants
Chest radiograph is normal
Not taking an ACE inhibitor
Not a current smoker
Harding SM .Chest 2003;123:659-660
Diagnosis (%)
Percentage
Percentageof
of Diagnoses
Changing Trends in Diagnosis
GERD
REFLUX
ASTHMA
ASTHMA
RHINITIS
RHINITIS
90
80
70
60
50
40
30
20
10
0
1998
1999
2000
2001
2002
2003
GERD ?
Heartburn (pyrosis) and regurgitation
At least weekly symptoms
extraesophageal reflux symptoms
and/or esophageal mucosal damage /
Functional
defect in LES
syphincter
Delayed gastric
emptying
Decreased
saliva
Impaired
esophageal
clearance
Hiatal hernia
İncreased intra-abdominal
pressure Katzka & DiMarino 1995
FLR
Signs
•Edema and hyperemia of larynx
•Vocal cord erythema, polyps, granulomas, ulcers
•Hyperemia and lymphoid hyperplasia
of posterior pharynx
•Interarytenoid changes
•Subglottic stenosis
GERD-related cough incidence
5 - 55%
ARRD 1981;123:413-417
Arch Intern Med 1996;156:997
Chest 1993;104:1511-1517
El Hennawi, 2004 OHNS
May be the sole presenting symptom(1/3)
Association between cough and reflux is important
 Esophageal-tracheal-bronchial reflex
 Microaspiration
Nonacidic factors?
Esophageal dismotility?
Thorax 2003:58;1092-1095)
(Chest 1997; 111: 1389-1402)
Irwin RS. Chest 2006;129:80S-94S
Esophagus
Tracheobronchial
Tree
REFLUX
Microaspiration
Esophageal
Vagal
Afferents
Airway Vagal
Afferents
CNS
Airway Vagal
Efferents
Airway
. Mediator
Release
. Inflammation
. Edema
. Mucus
. Smooth
Muscle
Bronchial Hyperreactivity
Stein MR.Am J Med 2003
Chest 1997;111: 1389-1402
Oesophagus
Stomach
Pharyngeal pHmetry
Not GERD
Clinical GERD symptoms ?
Nonacid, weakly acid reflux?
+
Increase dose PPI
+ alginate
İmproved
Consider

Simultaneously
dual probes
24 hours pHmonitoring
and
intraesophageal impedance
Not
improved
Continue
pHmetry
under treatment
Irwin RS.AJRCCM 165:1469-74,2002
McGarvey LPA.Thorax 59:342-346,2004
Multichannel intraluminal
impedance-pH catheter
6 impedance channels
17 cm
15 cm
9 cm
+
7 cm
1 pH electrode
5 cm
3 cm
Adult Standard
Model ZAN-S61C01E
pH - 5 cm
Non acid reflux
On going reflux of ‘non-acid’ material may be
responsible for continuing symptoms while on
acid-suppressing medications
Therapy in Esophageal-pulmonary reflux



Conservative and lifestyle measures
Ampirical therapy: Acid suppression
Proton pump inhibitors
 PPI x 2 / 3 months
Therapy failure  24 hour intraesophageal pHmetry
( pharyngeal pHmetry )

GERD (+)
High dose PPI
+ H2 blocker agent
Surgery(Fundoplication)
Pulmonary and Crit Care Update 1994; Vol 9
Morice AH. ERJ 2004;24:481-492
Cumulative Response to GERD Therapy
Weeks of antireflux therapy
Patients responded
No
No (%)
2
16 (41)
4
38 (86)
6
42 (95)
8
43 (99)
12 weeks
44 (100)
Poe RH.Chest 2003;123:679-684
Preop
pH <4: %23.6
De Meester:
85
Postop
pH <4: %2.4
De Meester:
9.9
Clinical Profile That Chronic
Cough İs Likely Due To ‘Silent GERD’
1. Chronic cough for at least 2 months
2. Immunocompetent patients
3. Chest radiograph is normal
4. Not exposed to enviromental irritants nor a present smoker
5. Not taking an ACE inhibitor
6. Symptomatic asthma has been ruled out
7. Rhinosinus diseases has been ruled out:
8. ‘Silent sinusitis’ has been ruled out
9. Nonasthmatic eosinophilic bronchitis
has been ruled out:
BPT is negative
Cough has not improved
with asthma therapy
First generation
H1 antagonists has been used
Eo 3%
in induced sputum
Cough has not improved
with steroids
Irwin RS. Chest 2006;129:80S-94S
İrwin RS. AJRCCM Vol 165; 1469-1474, 2002
Postnasal Drip Syndrome (PNDS)
• Prevalence : 8 – 87%
• Pathogenesis : The sensation of drainage of secretions
from the nose or paranasal sinuses into the pharynx
• Clinical Presentation:
Dripping sensation
Tickle in the throat
Nasal congestion
Mucus in oropharynx
Cobblestone appearence of oropharynx
ACCP consensus. CHEST 1998; 114: 133-181
ERS Task Force. ERS Journal ; 24: 553-566
Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284
Evaluation of chronic cough. UPTODATE 2005
In patient with chronic cough that is
related to upper airway abnormalities
Upper Airway Cough Syndrome
Chest 2006;129:63S-71S
UACS Treatment
Antihistamines / decongestant combinations
- “Older” sedating antihistamines more effective
- Treatment effect should be observed in 1 week
Additional / Alternative treatments :
Ipratropium nasal spray : 2-7 days
Nasal steroids (such as BDP, FP,BUD) :
2-3 days - 2 week
3 months prescribed
NO
YES
Bronchial hyperreactivity
Asthmatic Coughs
Eosinophilic
Eronchitis
Cough
Variant Asthma
NO
Asthma
YES
Airway obstruction
Cough Variant Asthma

Prevalence : 24 – 59%

Clinical Diagnosis
Gold standard  History
- Episodic symptoms, Family history
Reversibility testing
PEF monitoring
Bronchoprovocation test

Differential Diagnosis:
Decreased of cough with
classical asthma therapy
ACCP consensus. CHEST 1998; 114: 133-181
ERS Task Force. ERS Journal ; 24: 553-566
The Journal of Respiratory Disease; 25; 310-315
THORAX 59; 342-346
Eosinophilic Bronchitis
•
•
•
•
•
•
Isolated chronic cough,  productive of sputum
Normal lung function without variable airflow limitation
Airway hyperresponsiveness absent
Eosinophilia in sputum and BAL
Cough reflex to capsaicin increased
Normal daily variability in peak expiratory flow (<20%)
Middle age patients
Smoking is unusual, occupational ?
Prevalence of atopy similar population
Good respond to inhaled steroids
Gibson et al. Lancet 1989
Chest 2006;129:116S-121S
Eosinophilic Bronchitis
A Worldwide Disease
13% UK
91patients, 19992
15% Korea
14% USA
92 patients, 20023
37patients 20031
33% Turkey
36 patients, 20036
20% China
10% Australia
86 patients 20035
30 patients, 20004
1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10,
3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6,
5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701
Causes of chronic cough
Primary cause of cough
No. of patients (%)*
Eosinophilic bronchitis
12 (33.3%)
Postnasal drip syndrome
8 (22.2%)
Gastroesophageal reflux
8 (22.2%)
Idiopathic chronic cough
8 (22.2%)
Postinfectious cough
2 (5.6%)
Cough-variant asthma
1 (2.8%)
Ayık SÖ, Başoğlu ÖK, Erdinç M.
Respir Med Vol. 97 (2003) 695-701
Causes of Isolated Chronic Cough
Primary cause of chronic cough
Patients (%)
Rhinitis/PND
24
Asthma
Post-viral
17.6
13.2
Eosinophilic bronchitis
13.2
GERD
7.7
Unexplained (Idiopathic)
COPD
Bronchiectasis
6.6
6.6
5.5
ACE inhibitor-induced cough
4.4
Lung cancer
2.2
Cryptogenic fibrosing alveolitis
1.1
Brightling CE et al. AJRCCM 1999
Asthmatic Cough
Airway obstruction
Reversibility
PEF değişkenliği
Yes
Asthma
İnhaled steroid
β2-agonist
No
Bronchial provocation test
Eosinophilic
Bronchitis
İnhaled steroid
Negative
Positive
PEF
monitoring
Induced sputum
(3%  eosinophilia
Increased NO all of them
Cough
Variant Asthma
İnhaled steroid
β2-agonist
Chronic Unexplained
(Idiopathic) Cough
• Prevalence: 0-50%
• More agressive diagnosis and treatments
UACS, GERD and postinfectious cough leads
to lower incidence ‘unexplained’.
• Airway inflammation
Mast cell, histamin, cysteinil LTs, PD2, PE2
Irwin RS,et al. Chest 2006;130:362-370
Chronic Unexplained
(Idiopathic) Cough
Potential Reasons

Important missed history (smoking,ACEI,enviromental,drugs,allergy)

Failure to do correct diagnostic tests

Failure to use ‘empiric’ treatment

Failure to use effective therapy

Unknown disease process
« Truly idiopathic cough is rare and misdiagnosis very common,
especially if cough is provoked by sites outside the airways »
Eur Respir J 24: 481-492 2004
Idiopathic cough
%?
Studies in the 1980’s
% patients
40
30
Irwin 1981
20
Poe 1982
Poe 1989
10
0
Asthma
GERD
PNAS
Idiopathic
Idiopathic cough
%?
1990-1995
% patients
50
40
Irwin 1990
30
Hoffstein 1994
20
O Connel 1994
Smyrinos 1995
10
0
Asthma
PNAS
Idiopathic cough
%?
1996-1999
% patients
60
50
Mello 1996
40
Marchesani 1998
30
Mc Garvey 1998
20
Brightling 1999
Palombani 1999
Simpson 1999
10
0
ASTHMA OESOPH
NOSE
IDIO
Idiopathic cough
%?
2000 
50
% patients
40
Birring 2003
30
Hague 2005
20
Kastelik 2005
Matsumoto 2007
10
0
ASTHMA
NOSE
Chronic Idiopathic Cough
Haque et al Chest 2005;127:1710-1713
Chronic Idiopathic Cough
Predominantly female and
associated with BAL lymphocytosis
 Raising the possibility of a link between
autoimmune diseases
Chronic Idiopathic
Cough (n=22)
Control
(n=65)
p
Autoimmune disease
13/22 (59%)
8/65 (12%) p<0.001*
Positive autoantibody
6/15 (40%)
3/24 (13%) p<0.05
*OR: 8.8
Surinder S. Et al. Respir Med 98:242-246;2004
Chronic Idiopathic Cough
Inflammation
Birring et al AJRCM 2004
Chronic Idiopathic Cough
+ BAL lymphocytosis
•
•
•
•
•
•
•
•
•
•
Sarcoidosis
Hypersensitivity pneumonitis
Rheumatoid Arthritis
Sjögren’s syndrome
Lung tx
Inflammatory bowel disease
Hypothyroidism
Autoimmune disorders (SLE, RA)
Pernisious anemia
DM
Thorax 2003;58:1066-1070
Chronic Idiopathic Cough
It is not correct to state that “a typical
lymphocytic airways inflammation is seen in
idiopathic cough” because lymphocytic or
lymphoplasmacytic inflammation a non-specific
finding related to trauma of coughing
Irwin RS,et al. Chest 2006;130:362-370
Psychogenic Cough
• Cough is often triggered by a common cold
• Usually dissapears during sleep
• Like a dog barking
• The diagnosis of psychogenic cough is one of
exclusion, after ruling out an organic or
functional cause of cough.
• Specific or empiric treatment
• Antitussives are usually ineffective.
Respirology 2006;Suppl 4 ;S160-S174
Irwin RS et al. Chest 1998, 114:2 suppl
ERS Task Force: Eur Respir J 2004, 24:481-492
Postinfectious Cough
• Prevalence: 11-25 %
• History: After a respiratory tract infection
• Diagnosis:
Spasmodic cough
Normal chest radiograph, with/without ronchii
Respiratory viruses, m.pneumoniae,
c.pneumoniae, B.pertussis
Serum acute IgA antibody ELISA
Rarely lymphocytosis
Airway inflammation
+/- Airway hyperresponsivenes
Irwin RS et al. Chest 1998, 114:2 suppl
ACCP consensus. CHEST 1998; 114: 133-181
ERS Task Force. ERS Journal ; 24: 553-566
Postinfectious Cough
– Oral and/or inhaled steroid (2-3 weeks)
– Antibiyotic : Macrolides (Chlamydia, mycoplasma)
TMP/SMX : Pertusis (3-6 weeks)
– Ipatropium bromid
decrease efferent limb of the cough reflex
decrease stimulation of cough receptors
– Antitussive therapy
Irwin RS et al. Chest 1998,114:2 suppl
Miyashita N. J Med Microbiol 2003, 52:3,265-269
ACEI Induced Chronic Cough
• Frequency: 0.2-33%
• Predominantly female
• Not dose related
• Appears within hours, weeks, months
• Pathogenesis: Neurokinin, Substance P, Prostoglandins,
stimulates afferent C-fibers in the airway
 increased cough reflex sensitivity
• Prefer Angiotensin II receptör antagonists
Treatment
NONSPECIFIC
Antitussive
SPECIFIC
Protussive
Codein
Hypertonic saline
Dextromethorphan
Erdostein
Difenhidramin
Amilorid
Pseudoephedrine
N asetilsistein
Dekstrobromfeniramin
Terbutalin
Ipatropium Bromide
Physiotherapy
Naproksen
Postural drainage
Causative
treatment
Irwin RS et al. Chest 1998, 114:2
Future Therapies
– Capsaicin type I Vanilloid receptor antagonists
– Selective opioid receptor agonists
– Opioid-like receptor agonists
– Tachykinin receptor antagonists
– Endogenous cannabinoids
– 5-HT receptor agonists
– Large-conductance calcium-activated
potassium channel openers
Dicpinigaitis PV.Chest 2006 ;129:284S-286S
Chronic Cough Algoritm
For the Management of Adults
Chronic cough
History,Examination,
Chest X-Ray, PFT
Abnormal
Sputum,
bronchoscopy,CT,
Cardiac tests
Normal
Smoking, ACEI , Irritants ?
Specific
yes
Stop 4 weeks
diagnosis - treatment
Chronic Cough Algoritm
For the Management of Adults
Chronic cough
History,Examination,
Chest X-Ray, PFT
Abnormal
Specific diagnosis - Treatment
Normal
No
Smoking, ACEI, Irritants ?
Yes
UACS,GERD,
Asthma, NAEB ?
Sputum,
bronchoscopy,CT,
Cardiac tests
Stop 4 weeks
Yes
Cough?
No
İmproved?
Chronic Cough Algoritm
Chronic cough
History,Examination,
Chest X-Ray, PFT
Specific diagnosis - treatment
Normal
No
Smoking, ACEI ?,
Irritants?
Therapy
Yes
Cough?
Yes
Stop 4 weeks
UACS,GERD,
Asthma, NAEB
Empiric/ Specific
Abnormal
Sputum,
Bronchoscopy,CT,
Cardiac tests
Yok
Improved
Yes
Cough?
No
Chronic Cough Algoritm
Chronic cough
History,Examination,
Chest X-Ray, PFT
Abnormal
Normal
No
Sputum,
Bronchoscopy,CT,
Cardiac tests
Specific diagnosis - treatment
Smoking, ACEI ?,
Irritants?
Yes
Cough?
Yes
UACS,GERD,
Asthma, NAEB
Empiric
Therapy
No response
Stop 4 weeks
No
Improved
ENT, Sinus CT
BPT,PEF monit., NO
Esophageal tests
Specific
Diagnosis - Treatment
UACS,GERD, Asthma, NAEB
Empiric or Specific Diagnosis and Treatment
Improved
No
Cough ?
Yes
Post infectious?
Yes
Consider uncommon causes
Sputum, HRCT, Bronchoscopy
Specific diagnosis - Treatment
No
Yes
Cough ?
Physcogenic
cough?
UACS,GERD, Asthma, NAEB
Empiric or Specific Diagnosis and Treatment
Improved
No
Cough ?
Yes
Post infectious?
Yes
Consider uncommon causes
Sputum, HRCT, Bronchoscopy
Specific diagnosis - Treatment
No
Yes
Cough ?
Improved
Specific diagnosis - Treatment
No
Chronic idiopathic cough
Physcogenic
cough?
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