CHRONIC COUGH
description
Transcript of CHRONIC COUGH
MÜNEVVER ERDİNÇDepartment of Chest Diseases
Ege University Faculty of Medicine
Differential Diagnosis And Treatment In Adults
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
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, In prospective studies in adults, chronic cough is most commonly chronic cough is most commonly
due to 6 disorders :due to 6 disorders :
Upper Airway Cough Syndrome (Upper Airway Cough Syndrome (UACSUACS))
AstAsthmahma
GGERDERD
Chronic BronchitisChronic Bronchitis
BronBronchiectasischiectasis
Non-astNon-asthhmatimaticc EEoosinophilic Bronchitissinophilic Bronchitis
In prospective studies in adults, In prospective studies in adults, chronic cough is most commonly chronic cough is most commonly
due to 6 disorders :due to 6 disorders :
Upper Airway Cough Syndrome (Upper Airway Cough Syndrome (UACSUACS))
AstAsthmahma
GGERDERD
Chronic BronchitisChronic Bronchitis
BronBronchiectasischiectasis
Non-astNon-asthhmatimaticc EEoosinophilic Bronchitissinophilic Bronchitis
Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S
New New ConsiderationsConsiderations
Eosinophilic bronchitis
Atopic cough
Non acid(volume)/ weakly acid reflux
Idiopathic (unexplained) öksürük
Diagnosis and Management of Cough Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006ACCP Evidence-Based CPG 2006
Guidelines Writing Committee. Guidelines Writing Committee. ChestChest 2006; 129 (Suppl. 1): 1S-292S 2006; 129 (Suppl. 1): 1S-292SPlevkova, et al. Plevkova, et al. Respir Physiol NeurobiolRespir Physiol Neurobiol 2004; 142: 225-235 2004; 142: 225-235
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 coughThe term acid reflux disease, unless it can be definitively shown to
apply, replaced by reflux diseaseUpdate of current diagnostic and therapeutic approaches
Common diseases, Uncommon diseasesNew algorithms for the management of cough in adults and
childrenAn empiric integrative approach is recommended
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 coughThe term acid reflux disease, unless it can be definitively shown to
apply, replaced by reflux diseaseUpdate of current diagnostic and therapeutic approaches
Common diseases, Uncommon diseasesNew algorithms for the management of cough in adults and
childrenAn empiric integrative approach is recommended
10
12
1312
16
64
ASTHMA
PNDS
GERD
Chest 1999;116:279-284
1. Gastroesophageal reflux disease (21-41%)
2. Cough variant asthma (24-59%)
3. Postnasal drip syndrome (41-58%)
38,5%
35,9%
16,7%
8,9%
Chest 1999;116:279-281
Percentage of Cases Presenting 1,2,3, and 4 Causative Factors
1
2
3
4
İmmunocompetent patients Not exposed to enviromental
irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker
Asthma and/or GERD, PNDS
responsible for 93.6% of the casesof chronic cough
Harding SM .Chest 2003;123:659-660
Changing Trends in Changing Trends in DiagnosisDiagnosis
0
10
20
30
40
50
60
70
80
90
1998 1999 2000 2001 2002 2003
Perc
en
tag
e o
f D
iag
no
ses
REFLUX ASTHMA RHINITIS
Perc
en
tag
e o
f D
iag
nosis
(%
)
GERD ASTHMA RHINITIS
Impaired esophageal clearanceFunctional
defect in LES syphincter Hiatal hernia
Delayed gastric emptying İncreased intra-abdominal
pressure
GERD ?
Decreased saliva
Heartburn (pyrosis) and regurgitationAt least weekly symptoms
extraesophageal reflux symptoms and/or esophageal mucosal damage /
Katzka & DiMarino 1995
FLR Signs
•Edema and hyperemia of larynxEdema and hyperemia of larynx•Vocal cord erythema, polyps, granulomas, ulcersVocal cord erythema, polyps, granulomas, ulcers•Hyperemia and lymphoid hyperplasiaHyperemia and lymphoid hyperplasia
of posterior pharynx of posterior pharynx •Interarytenoid changesInterarytenoid changes•Subglottic stenosisSubglottic stenosis
GERD-related cough incidence GERD-related cough incidence 5 - 55% 5 - 55%
May be the sole presenting symptom(1/3)May be the sole presenting symptom(1/3)
Thorax 2003:58;1092-1095)
(Chest 1997; 111: 1389-1402)
Irwin RS. Chest 2006;129:80S-94S
Association between cough and reflux is important
Esophageal-tracheal-bronchial reflex Esophageal-tracheal-bronchial reflex MicroaspirationMicroaspiration
ARRD 1981;123:413-417 Arch Intern Med 1996;156:997Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS
Nonacidic factors?Esophageal dismotility?
.. Mediator Mediator ReleaseRelease.. I Inflammationnflammation.. Edema Edema.. Mucus Mucus .. Smooth Smooth MuscleMuscle
MicroaspirationMicroaspirationREFLUXREFLUX
EsophagealEsophagealVagalVagal
AfferentsAfferents
Bronchial HyperreactivityBronchial Hyperreactivity
Airway VagalAirway VagalAfferentsAfferents
CNSCNS
Stein MR.Am J Med 2003Chest 1997;111: 1389-1402Chest 1997;111: 1389-1402
Airway
Airway VagalAirway VagalEfferentsEfferents
EsophagusEsophagus Tracheobronchial Tracheobronchial TreeTree
Stomach
Oesophagus
Pharyngeal pHmetryPharyngeal pHmetry
+-Not GERD
Clinical GERD symptoms ?Nonacid, weakly acid reflux?
Increase dose PPI + alginate
İmproved Not improved
ContinuepHmetry
under treatment
Consider
Simultaneously dual probes
24 hours pHmonitoringand
intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002McGarvey LPA.Thorax 59:342-346,2004
3 cm
5 cm
7 cm
9 cm
15 cm
17 cm
pH - 5 cm
6 impedance channels
1 pH electrode
+
Adult Standard
Model ZAN-S61C01E
Multichannel intraluminal impedance-pH catheter
NonNon acid acid refluxreflux
On going reflux of ‘non-acid’ material may be
responsible for continuing symptoms while on
acid-suppressing medications
Therapy in Esophageal-pulmonary refluxTherapy in Esophageal-pulmonary reflux
Conservative and lifestyle measuresConservative and lifestyle measures Ampirical therapyAmpirical therapy: Acid suppression: Acid suppression
Proton pump inhibitorsProton pump inhibitors
PPI x 2 / 3 monthsPPI x 2 / 3 months Therapy failure Therapy failure 24 hour intraesophageal pHmetry 24 hour intraesophageal pHmetry
( pharyngeal( pharyngeal pHmetry pHmetry ) )
GERD (+)GERD (+)
High dose PPI High dose PPI
+ H+ H22 blocker agent blocker agent
Surgery(Fundoplication) Pulmonary and Crit Care Update 1994;
Vol 9
Morice AH. ERJ 2004;24:481-492
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
Cumulative Response to GERD Therapy
Preop
pH <4: %23.6
De Meester: 85
Postop
pH <4: %2.4
De Meester: 9.9
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 negativeCough 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-94Sİrwin RS. AJRCCM Vol 165; 1469-1474, 2002
Clinical Profile That ChronicCough İs Likely Due To ‘Silent GERD’
PostPostnasal Drip Syndrome nasal Drip Syndrome (PNDS)(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 throatNasal congestionMucus in oropharynx
Cobblestone appearence of oropharynx
ACCP consensus. CHEST 1998; 114: 133-181ERS Task Force. ERS Journal ; 24: 553-566
Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284Evaluation of chronic cough. UPTODATE 2005
Chest 2006;129:63S-71S
In patient with chronic cough that isrelated to upper airway abnormalities
Upper Airway Cough SyndromeUpper Airway Cough Syndrome
UACSUACS Treatment 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
EosinophilicEronchitis
Airway obstruction
Bro
nch
ial
hyp
erre
acti
vity
NO YES
Y
ES
NO
Asthmatic CoughsAsthmatic Coughs
Cough Variant Asthma
Asthma
Cough Variant Asthma Cough Variant Asthma
Prevalence : 24 – 59% Clinical Diagnosis
Gold standard History- Episodic symptoms, Family history
Reversibility testingPEF monitoringBronchoprovocation test
Differential Diagnosis:
Decreased of cough with
classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181ERS Task Force. ERS Journal ; 24: 553-566
The Journal of Respiratory Disease; 25; 310-315THORAX 59; 342-346
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 BronchitisEosinophilic 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%)
10% Australia30 patients, 20004
15% Korea92 patients, 20023
14% USA37patients 20031
33% Turkey36 patients, 20036
13% UK91patients, 19992
20% China86 patients 20035
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
Eosinophilic BronchitisEosinophilic Bronchitis A Worldwide DiseaseA Worldwide Disease
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 Causes of Isolated Chronic CoughCough
Primary cause of chronic cough Patients (%)
Rhinitis/PND 24
Asthma 17.6
Post-viral 13.2
Eosinophilic bronchitis 13.2
GERD 7.7
Unexplained (Idiopathic) 6.6
COPD 6.6
Bronchiectasis 5.5
ACE inhibitor-induced cough 4.4
Lung cancer 2.2
Cryptogenic fibrosing alveolitis 1.1
Brightling CE et al. AJRCCM 1999
Positive Cough Cough Variant AsthmaVariant Asthma
İnhaled steroidβ2-agonist
Negative
Induced sputum(3% eosinophilia
Eosinophilic Eosinophilic BronchitisBronchitis
İnhaled steroid
Asthmatic CoughAsthmatic CoughAirway obstructionReversibilityPEF değişkenliği
AsthmaAsthmaİnhaled steroid
β2-agonist
Yes
Bronchial provocation test
No
Increased NO all of them
PEF monitoring
• 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 Chronic Unexplained (Idiopathic)(Idiopathic) CoughCough
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
Potential Reasons Potential Reasons
Chronic Unexplained Chronic Unexplained (Idiopathic) (Idiopathic) CoughCough
« 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 coughIdiopathic cough%% ? ?
0
10
20
30
40
Asthma GERD PNAS I diopathic
I rwin 1981
Poe 1982
Poe 1989
Studies in the 1980’s
% p
ati
en
ts
0
10
20
30
40
50
Asthma PNAS
I rwin 1990
Hoff stein 1994
O Connel 1994
Smyrinos 1995
1990-1995
Idiopathic coughIdiopathic cough%% ? ?
% p
ati
ents
Idiopathic coughIdiopathic cough%% ? ?
1996-1999
% p
ati
en
ts
0
10
20
30
40
50
60
ASTHMA OESOPH NOSE IDIO
Mello 1996
Marchesani 1998
Mc Garvey 1998
Palombani 1999
Brightling 1999
Simpson 1999
Idiopathic coughIdiopathic cough%% ? ?
2000
0
10
20
30
40
50
ASTHMA NOSE
Birring 2003
Hague 2005
Kastelik 2005
Matsumoto 2007% p
ati
en
ts
Haque et al Chest 2005Haque et al Chest 2005;127:1710-1713;127:1710-1713
Chronic Idiopathic Chronic Idiopathic CoughCough
Predominantly female and
associated with BAL lymphocytosis
Raising the possibility of a link between
autoimmune diseases
Surinder S. Et al. Respir Med 98:242-246;2004
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
Chronic Idiopathic Chronic Idiopathic CoughCough
*OR: 8.8
InflammationInflammationChronic Idiopathic Chronic Idiopathic CoughCough
Birring et al AJRCM 2004Birring et al AJRCM 2004
+ 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 Chronic Idiopathic CoughCough
Irwin RS,et al. Chest 2006;130:362-370
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
Chronic Idiopathic Chronic Idiopathic CoughCough
Psychogenic CoughPsychogenic 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 supplERS Task Force: Eur Respir J 2004, 24:481-492
• Prevalence: 11-25 %• History: After a respiratory tract infection• Diagnosis:
Spasmodic coughNormal chest radiograph, with/without ronchiiRespiratory 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 supplACCP consensus. CHEST 1998; 114: 133-181ERS Task Force. ERS Journal ; 24: 553-566
Postinfectious CoughPostinfectious 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
Postinfectious CoughPostinfectious Cough
ACEI Induced Chronic ACEI Induced Chronic Cough 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
TreatmenTreatmentt
NONSPECIFIC SPECIFIC
Antitussive Protussive Causative
treatmentCodein
Dextromethorphan
Difenhidramin
Pseudoephedrine
Dekstrobromfeniramin
Ipatropium Bromide
Naproksen
Hypertonic saline
Erdostein
Amilorid
N asetilsistein
Terbutalin
Physiotherapy
Postural drainage
Irwin RS et al. Chest 1998, 114:2
– 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
Future TherapiesFuture Therapies
Chronic cough
History,Examination, Chest X-Ray, PFT
Normal
Abnormal Sputum, bronchoscopy,CT,
Cardiac tests
Smoking, ACEI , Irritants ?Specific
diagnosis - treatment
Stop 4 weeks
yes
Chronic Cough AlgoritmChronic Cough Algoritm For the Management of AdultsFor the Management of Adults
Chronic cough
History,Examination, Chest X-Ray, PFT
Normal
Abnormal
Sputum, bronchoscopy,CT,
Cardiac tests
Smoking, ACEI, Irritants ?
Specific diagnosis - Treatment
Cough?Yes
NoUACS,GERD,
Asthma, NAEB ?
No
Yes
Stop 4 weeks İmproved?
Chronic Cough AlgoritmChronic Cough Algoritm For the Management of AdultsFor the Management of Adults
Chronic cough
Normal
Abnormal
Cough?Yes
Yok
No
Yes
Improved
Cough? NoYes
Empiric/ Specific
Therapy
History,Examination, Chest X-Ray, PFT
Sputum, Bronchoscopy,CT,
Cardiac tests
Specific diagnosis - treatment
Smoking, ACEI ?, Irritants?
UACS,GERD, Asthma, NAEB
Stop 4 weeks
Chronic Cough AlgoritmChronic Cough Algoritm
Chronic cough
History,Examination, Chest X-Ray, PFT
Normal
Abnormal
Sputum, Bronchoscopy,CT,
Cardiac tests
Smoking, ACEI ?, Irritants? Cough?
Yes
NoUACS,GERD,
Asthma, NAEB
No
Yes
Stop 4 weeksImproved
Empiric Therapy
ENT, Sinus CT BPT,PEF monit., NOEsophageal tests
No response
Specific diagnosis - treatment
Specific
Diagnosis - Treatment
Chronic Cough AlgoritmChronic Cough Algoritm
UACS,GERD, Asthma, NAEB
Empiric or Specific Diagnosis and Treatment
Cough ?No
Sputum, HRCT, Bronchoscopy
ImprovedYes Post infectious?
Yes
Consider uncommon causes
Cough ?No Yes Physcogenic
cough?
Specific diagnosis - Treatment
UACS,GERD, Asthma, NAEB
Empiric or Specific Diagnosis and Treatment
Cough ?No
Sputum, HRCT, Bronchoscopy
ImprovedYes Post infectious?
Yes
Consider uncommon causes
Cough ?No Yes
Physcogenic cough?
Specific diagnosis - Treatment
Specific diagnosis - TreatmentImproved
Chronic idiopathic cough
No
THANK YOU…THANK YOU…