Eosinophilic bronchitis

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Eosinophilic bronchitis(EB)
???? ????? ? ? ?
2
Eosinophilic bronchitis(EB)
3
??

• ?????? ????? ?? 14-23
• ?? ?? ?????? 5??? ?? ??
• ?? ?? ??? ??
• ?? ??( Chronic cough) vs Acute cough
• ??? 3? ??? ????? ???? ??
• Acute, subacute and chronic cough gt 8wks
• NEJM
  343(23)1715-21,2000

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Acute cough URI(common cold) m.c. Acute
bacterial sinusitis Pertussis Exacerbations
of COPD Rhinitis(allergic or nonallergic)
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Subacute cough Postinfectious cough
Begins with RTI without pneumonia and resolves
without Tx May result from PND or
clearing of the throat d/t rhinitis
? tracheobronchitis ?
transient bronchial hyperresponsiveness
Bacterial sinusitis Asthma
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????? ??

• 3? ??(85-90 )
• 1. PND (Post Nasal Drip syndrome) 35-50
• 2. GERD (Gastroesophageal Reflux Disorder)
  20-40
• 3. Bronchial asthma 15-30
• 4. Chronic bronchitis 5
• ??
• ACE inhibitor, Aspiration, Bronchiectasis,
  Occult pulm. infection
• Industrial bronchitis, Lung neoplasm, ILD,
  Occult CHF
• Disorders of external auditary meatus,
  diaphragm, pleura
• or pericardium, or esophagus or stomach
• Nasal polyps, Rhinoliths, Uvular or
  tonsillar enlargement
• Thyroid disorder
• Psychogenic cough

7
??? ?? ??

• D'Urzo A. Chronic cough three most common
  causes. Can Fam Physician August 2002481311

8
100
86
Causes of Chronic Cough ()
75
50
41
24
21
25
5
5
4
0
PND Asthma GERD
PND Asthma GERD CB B.E Misc

(Irwin, et al. ARRD 1990 141640-7)
9
100
85
Causes of Chronic Cough ()
75
48
50
25
20
17
15
0
PND GERD Asthm Misc.
PND Asthma GERD
(Nicholas et al. Arch Int Med 1998 1581222-8)
10
100
Causes of Chronic Cough ()
75
52
50
25
16
9
11
8
4
0
Misc.
PND Asthm GERD Bronchitis PND

BA
(? ?. ?? ? ??? ?? 199946555)
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n92
The Korean Journal of Internal Medicine 2002
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History and P/Ex
No suggestive etiology or postviral
Suggestive of specific etiology (PND, GERD,
CHF, inciting exogenous factor)
Discontinue inciting agent or treat underlying
disorder
Spirometry
No relief
Reversible airflow obstruction
No reversible airflow obstruction
Treat for CVA
Chest X-ray
Relief of cough
Normal
Parenchymal Lung disease
Mass
Treat for PND
Bronchoscopy
Evaluation based on specific pattern (bronchosco
py, CT)
No further evaluation
No relief
Cf. CVA Cough Variant Asthma
24Hr esophageal pH probe
(Harrisons principle of internal medicine, 14th
ed)
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Chronic Dry cough
Clinical Assesment Simple spirometry, Chest X-ray
No suggestive diagnosis
Abnormal Chest X-ray
PNS view ENT exam
24Hr Esophageal pH monitor
Methacholine provocation
Possible diagnosis
Investigate further
Specific Tx or empiric Tx
PND
Asthma
GERD
ACE-I
URI
Antihistamine Inhaled steroid H2
antagonist Stop drug observe steroid drop
Bronchodilator Proton pump

inhibitor
(Chung KF, et al. Postgraduate Med J
199672594-8)
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??? ? ? ?? ?? ?? ??? ??? ?? ???
?? ?????? ?? ( ? ?. ?? ? ????? 199946372)
(n25)
Cough subject
Bronchoscopic mucosal Bx
(n21)
(n4)
Eosinophil dominant
Lymphocyte dominant
BCT (-)
BCT
_

CVA
Eosinophilic Bronchitis
Lymphocytic bronchitis
(n7) (n14)
(n4)
Prednisone 20-30mg/day for 1-2 weeks
Steroid Response
7 12
3 (100)
(85.7) ( 75)
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Normal range of Sputum Eosinophil

• ? Rytila et al, Eur Resp J(2000) 0 - 0.7
• ? P G Gibson, Thorax(2001) 0 2.5

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Etiology of sputum eosinophilia

• ? Exposure to allergen
• ? Occupational chemicals
• ? DRUG
• ? GERD
• ? Viral infection

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Prevalence of Sputum eosinophilia
Prevalence()
Healthy Asthma Rhinitis with AHR Cough Episodic symptoms without asthma(ESWA) Cough variant asthma COPD 5.5 (1.5 9.6) 72 (66.3 77.6) 77 (66.7 90.1) 31 (26.1 35.3) 29 (18.6 39.8) 50 (34.1 65.9) 29.6(23.3 35.9)
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Sputum eosinophilia

• ? Bronchial asthma
• ? COPD
• ? EB in chronic cough
• ? Episodic respiratory symptoms without
• asthma(ESWA)
• ? Allergic rhinitis
• ? Cough variant asthma

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bronchial asthmaCOPDEB
IL-5 gene expression
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Eotaxin(I,II) RANTES

Eosinophilic airway inflammation
Airway remodelling(MMP)
Regulated and activated normal T cells expressed
and secreted Matrix metalloproteinase
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Response to Development Airway CAO Corticosteroid of asthma remodelling
Asthma Rhinitis Cough CVA COPD ESWA ? ? ? ? ?/ ? ? ? ? ?
CAO Chronic airway obstruction CVA
cough variant asthma ESWA Episodic symptoms
without asthma
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Clinical manifestation B.A(I)
DDx-1

• ? Definition
• ?Episodic respiratory symptoms
• ? Evidence of bronchodilator responsiveness
• ? Increased diurnal variablity of PEF
• ? Evidence of airway hyperresponsiveness

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B.A(II)

• ? EB in asthma
• ? EB AHR and asthma symptoms? ??.
• ? In National institutes of heath report(1997)

Focus
EB
Severity of BA
Exacerbations of Asthma
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COPD
DDx-2

• ? Definition
• ? Persistnet airway obstruction
• ? Predictive FEV lt 80
• ? FEV1 / FVC ratio lt 70

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Episodic respiratory symptoms without asthma(ESWA)
DDx-3

• ? Definition
• ? Episodic cough, wheeze, dyspnea attack
• ? Normal PFT
• ? no evidence of variable airflow obstruction
• ? ???? 1/3 ?? 2??? clinical asthma
• ? inhaled beclomethasone? ? ???? 13?? asthma
  ? ??.

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Cough variant asthma(CVA)
DDx-4

• ? Definition
• ? Chronic cough
• ? Evidence of AHR
• ? Responsivenss of anti-asthma treatment

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CVA(2)

• ? Significance
• ? In Miimi A et al study
• airway wall remodelling ? ??
• -gt severity? classic asthma ? ?? less
• severe
• ? In Iwanaga, Braman et al study
• 17-37? ???? typical asthma? ??.

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Allergic rhinitis
DDx-5

• ? Significance
• ? In Alvarez MJ et al study
• Airway responsiveness ?? ???? ??
• ? In Djukanovic R et al study
• Histologic remodelling ? ??? ??

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Eosinophilic bronchitis
Gibson PG et al. Lancet 1989 11346 Chronic
cough Eosinophilic bronchitis without asthma 7
out of 180 patients . nonsmokers with
corticosteroid reponsive chronic productive
cough . Age 46yr(36-67yr), MF34 ,
normal PFT and metacholine test . Case 3 5
had PND . No PB eosinophilia(136 /- 33,
range 30-312) . Sputum eosinophilia(38.9,
range 11.5-85.9) --- no difference vs
nonsmoker with asthma
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continued
. 2wks ICS(beclomethasone 400ug bid), oral PD
30mg in case 4 7) --- no sputum in all
pts --- completely resolved in case 5
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Gibson PD et al. Clin Exp Allergy 199525127 4
cases of year 1989 report new 5 cases age
48yr(22-67yr), MF 45 atopy 3/9 cases,
normal PFT and metacholine test Duration of
sputum 26 months(5-96) 6 rhinitis (3 PND)
sputum eosinophilia 12-86 after TX 4 /-
1,7
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Eosinophilic bronchitis
F/U data(n12), Lancet 2001, 3589287 3 pts
F/U loss 1 died of PTE, ICS? ?? PFT, ???? ??
???? ?? 6 among remaning 8 pts ????, ?????? ?
???? ?? 1? 6??? ICS, 2??? ????? ??, ? ? ????.
4??? ??? ?? ?? 4??? ???? --- 2 GERDPND, 1 PND
1 mild
localized bronchiectasis with mild obstruction
No AHR, sputum eosinophilia lt 2 generally
benign and self-limiting disorder
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Eosinophilic bronchitis

• ? Recent Definition
• Chronic cough with
• ? Sputum eosinophilia gt 3
• ? normal of PFT
• ? Absence of AHR
• ? Corticosteroid responsive cough
• ? normal CXR and PNS

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Eosinphilic bronchitis

BRIGHTLING et al. AJRCCM.1999
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Symon et al. Thorax 2003
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EB, Asthma and controls
Symon et al. Thorax 2003
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Cont
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• ? Treatment
• ? Inhaled / oral corticosteroid

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Sputum eosinophils after ICS 7wks Tx
Eoshinophil count()
Before Tx After Tx
Ju et . Korean Journal of Internal Medicine 2002
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Changes of FEV1 after ICS
?FEV(ml)
Before Tx After Tx
Ju et . Korean Journal of Internal Medicine 2002
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Sputum eosinophils after ICS stop
Sputum Eoshinophil ()
Jae hak Ju et . Korean Journal of Internal
Medicine 2002
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Case report of Irreversible obstruction of EB
Brightling et al, Eur Respir J 1999
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Possible pathway of EB

Eosinophilic airway inflammation
corticosteroids
AHR
Asthma
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Further study area

• ? Does cough with EB progress to asthma?
• ? Does cough with EB cause airway remodeling?
• ? Does cough with EB cause chronic airway obstru
• ction ?
• ? How should cough with EB be treated?