Bronchial provocation test in clinical practice

Methacholine Challenge Test

1. Bronchial
PROVOCATION TEST

In Clinical Practice

Alfian Nur Rosyid

MD, Pulmonologist, FAPSR

h Department of Pulmonary and Respiratory Medicine
7) Airlangga University Hospital

2. Menu

Bronchial Hyper responsiveness

Banken Provocation test

+ Airway Smooth Muscle

aod esis Diseases with BHR

Indication
Contra Indication

Spirometer
Direct/ Indirect
Tidal / Five Breathing

+ Result

Interpretation + Analysis

3. Definition

AHR / BHR:
Airway / Bronchial Hyper Responsiveness:

“Over / Hyper Response of bronchus to external agent,

occur bronchoconstriction”

(Brannan, JD and Lougheed, MD, 2012)

4. Definition

Bronchial provocation tests (BPTs)

are objective tests for AHR that are clinically useful to aid in

the diagnosis of asthma in both adults and children.

BPTs = Bronchial Provocation Test

BCTs =Bronchial Challenge Tests

Ex: Methacholine Challenge test (MCT)
Exercise Challenge test

(Brannan, JD and Lougheed, MD, 2012)

5. Pathogenesis

a Ligne dc Era

Vesicies with
neurotransmitters
‘Autonomic neuron

| A = ‘Smooth muscle cells
| it

James. Swiss Med Weekly, 2010; 140:1-6 —

6. Normal Asthma
Narrowed Y ; N N

airway

(limited MA
air flow) Y \
N Tightened 0

muscles
constrict
airway

Inflamed/
thickened
airway wall

Mucus

Thickened
airway wall

Muscle Mucus

Doeing DC and Solway, 2013 —

7. Pathogenesis

NOVEL ROLES OF AIRWAY SMOOTH MUSCLE

Collagen III V Environmental
Fibronectin Collageniv Allergens ei a Factors
Tenascin 9

Elastin = .n
Hyaluronan ‘ Po ¿xo = Cytokines

Jean es ie at A Growth Factors
erlecan Angiogenic Factors
MES „7 Anal
TIMPs

Mechanical TNFa STIM1 CysLTs
Stretch IL4 Oral PGs
ETI oma IL-5 miRNAs EGF
TGFB Ab! 1-13 VEGF
PPARy IL-7 BDNF

itamin D TSLP
Vitamin TGF

Hypertrophy

Hyperplasia

kash. Am Physiol Lung Cell Mol Physiol, 2013; 305: L912-L933.

8. Allergens

Les
Kar

4

AA

Fibroblasts

Normal Airway
Microbes Viruses

Y o
A —
A Epi hong

..... Et

A
ECM

Environmental Factors

Asthmatic oo
ee a ¿0

A PE En
rer @ cere ee

eo @

Altered ECM Composition and Deposition

Prakash. Am J Physiol Lung Cell Mol Physiol, 2013; 305: L912-L933.

9. Pathogenesis

INNERVATION

\

acetylcholine, substance P, etc.

INFLAMMATORY,

CELLS TAN leukotrienes, histamines

cytokines, ete

NS 7 endothelin, etc. p>,

EPITHELIUM

Janssen. Respiratory Research, 2006; 7(123): 1-6.

Rho/ROCK

AIRWAY SMOOTH MUSCLE

10. Methods
Bronchial provocation tests (BPTs)
- stimulus mediates bronchoconstriction.

- can be either “direct” or “indirect,”

Direct: stimulus act on specific receptors on the ASM

Indirect: stimulus causes the release of mediators of
bronchoconstriction from inflammatory cells

(Brannan, JD and Lougheed, MD,, 2012)

11. Type

Direct
2

Methacholine

Histamine

Indirect
SA

Exercise

Manitol

Hypertonic Saline

Adenosine monophosphate (AMP)
Eucapnic Voluntary
Hyperventilation (EVH)

Food additive challenge

Antigen challenge

12. Aschematic demonstrating the mechanism of action

+ r

Respiratory Water Loss Allergen Inhalation

| |

Mucosal Dehydration Mucosal presentation of allergen

| |

Increase in osmolarity Allergen-IgE complex

* of airway surface liquid ——, Epithelium,
+

Submucosa
+

Presence of increased cellular inflammation
---» eg. Mast cells (Fc epsilon R1, A2B receptors), eosinophils

| Feared mg

lato airway
response to
allergen

Mediator Release from cellular inflammation

Methacholine or =|==4=============================» Bronchial smooth muscle sensitivity
Histamine |

(Brannan, JD and Lougheed, MD, 2012

13. Where is Better?

- Histamine

- Methacholine

» Exercise

+ Hypertonic saline
+ Mannitol

+ Allergen

14. Methods

Methacholine challenge testing (MCT)
- is one method of assessing airway responsiveness.

+ It may vary over time, often increasing during

exacerbations and decreasing with anti inflammatory.

- Test is safety, during preparation and procedure are good.

+ Inhaled methacholine causes bronchoconstriction > few

adverse effects

Crapo. Am J Respir Crit Care Med, 2000; 161: 309-329.

15. Indication

v Excluding the diagnosis of asthma (its NPV > PPV)

v Relative risk of developing asthma

If BHR test result is
Negative, it will
v Monitor of asthma therapy exclude the

v Assess of asthma severity

. diagnosis of Asthma
Y” Occupational Asthma

Most subjects with current asthma
symptoms will have BHR

Crapo. Am J Respir Crit Care Med, 2000; 161: 309-329.

16. Indication

y Symptoms with asthma but normal PFT and no response
to a bronchodilator > mild or well-managed asthma

y Atypical symptoms of bronchospasm (i.e., nocturnal
awakening).

y Nonspecific symptoms that could asthma (i.e., cough)

y Screening test for asthma (ex: scuba divers, military
personnel, athletes or others)

Goldstein MF, Chest 1994; 105:1082.
Rubinfeld AR, Lancet 1976; 1:882
Irwin RS, Am Rev Respir Dis 1990; 141:640

17. Indication

v Asthma Bronchial

v COPD

v Congestive Heart Failure (CHF)
Y Cystic fibrosis

v Bronchitis

v Allergic rhinitis

However, bronchial hyperresponsiveness is also
seen in a wide variety of other disease

Crapo. Am ] Respir Crit Care Med, 2000; 161: 309-329.

18. Contra Indication

Severe airflow limitation (FEV1 <50 percent predicted or <1 L)

Myocardial infarction or stroke in last three months

Uncontrolled hypertension (systolic BP >200 or diastolic BP >100)
Known aortic aneurysm

Relative

Moderate airflow limitation (FEV1 <60 percent predicted or <1.5L)
Inability to perform acceptable-quality spirometry

Pregnancy

Nursing mothers

Current use of cholinesterase inhibitor medication (for myasthenia gravis)

Crapo. Am J Respir Crit Care Med, 2000; 161: 309-329.

19. Preparation

Adverse

Patient Operator Tools Effect

Good preparation > good result > minimal adverse effect

20. Preparation
/ Provocation test device

v Agents:
» Methacholine
- Histamine
» Manitol
» Hypertonic saline etc

v Spirometer

y Computer application

Crapo. Am.) Respir Crit Care Med, 2000; 161: 309-329.

21. ya. FAKULTAS KEDOKTERAN UNIVERSITAS AIRLANGGA - RSUD DR.SOETOMO
& DEPARTEMEN PULMONOLOGI DAN ILMU KEDOKTERAN RESPIRASI

METHACHOLINE

\

drAlf.net
Rekap Data Pasien Alfarina Berkah Mandiri (c) 2016

MCT.paru.ver1.0

22. Technics

Spirometer (FVC
maneuver)

z Methacholine

23. Technics

Methacholine Challenge Test

|

2-minute Tidal breathing Five-breath dosimeter

v No significance difference ofboth technics

Y” FDA approve five-breath (5 level of concentration)

v ATS prefer tidal breathing (10 level of concentration)

Crapo. Am J Respir Crit Care Med, 2000; 161: 309-329.
Cockroft. Chest, 2008, 1344: 678-680.

24. A: 16 mg/mt

B: 4 mg/mi

C: 1mg/ml

D: 0.25 mg/ml
E: 0.0625 mg/ml

25. Give Bronchodilator

Stop if FEV1 decrease
2 20% FEV1 baseline

m

FEV1 decrease
| =
Bronchoconstriction

Technics

AA

Methacholine 2 cc Provocation
Concentration: ... mg/ml device test

27. Ukur spiromet:

FEV1 >70%
prediksi?

beri pengencer atau dosis
metakolin pertama, lalu tes

spirometrisetelah beberapa menit

Y

beri dosis metakolin
selanjutnya, lalu tes spirometri
setelah beberapa menit

y

ya

tidak

tidak beri dosis

16mg/ml ?

Catat gejala dan tanda,
beri salbutamol, tunggu
10 menit dan tes

Crapo, Am Respir Crit Care Med, 2000; 161: 309-329. tidak

Tes selesa k

28. Faal paru |, Inhalasi
awal tidak>| NaCI0,9% 2cc } ————> fa pod

FEV1<50? 20 menit

dipak: b: FEV1 baseli ]
ipakai sebagai ‚seline ak

|

Inhalasi metakolin Faal paru FEV1
0,0625mg/mi 2 menit >| <20% baseline?

An dar ya Sa AHR sedang
Inhalasi metakolin Faal paru FEV1

L_0.25mg/ml 2 menit <20% baseline?

Ç tidak ya AHR sedang
at
[Gh mas metakoin Faal paru FEV

mg/ml 2 menit <20% baseline?

El mas neon

Faal paru FEV
L_4mg/ml 2 ment [>| <20% baseline?

tidak L—ya > AHR borderline

v
EN ms metro Faal paru FEVI
L__ 16mg/ml 2 menit <20% baseline?

y tidak: ya: > Normal AHR
y
Rawat nap <-> Inhalasi Salbutamol

tidak

Faal paru FEV!
>90% baseline?

Tes selesai < ya

29. (log C2 — log C1)(20 — R1)]
RAR

PC20 = antilog foe (oles

C1 = second-to-last methacholine concentration (concentration preceding C1).

C2 = final concentration of methacholine (concentration resulting in a 20% or greater
fallin FEV1)

R1 = percent fallin FEV, after C1

R2 = percent fallin FEV, after C2

FEV! % decrease

0 00625 025 1
Methacholine consentration (mg/ml)

Crapo. Am J Respir Crit Care Med, 2000; 161: 309-329.

30. Results

ATS 1999

PC, (mg/ml)
>16 Normal (test negative)

4-16 BHR borderline

1-4 BHR mild (test positive)

<1 BHR moderate to severe

Crapo. Am J Respir Crit Care Med, 2000; 161: 309-329.

31. Data Pasien tes Metakolin

Tanggal Tes:

Faal paru

Faal paru Awal

3030) | 85.81%
2380] | 57.14%

Kelompok Fr v

Pasien Baru

Preview Cetak

32. Data Pasien tes Metakolin Felompok

7.78% |LANJUT
11.67% [LANJUT
15.00% ||LANJUT
18.33%] Lamur

Inhalası dengan metode five-breath pada tiap konsentrasi

Linhalasi metakolin dihisap secara maksimal 1x lalu ditahan 5 detik kemudian
dihembuskan. Tehnik ini diulangi sebanyak 5x, namun tidak boleh melebihi 2menit.

2.istirahat 30-90 detik
3.lalu faal paru dilakukan 3-4x tes manuver, namun tidak boleh melebihi 3 menit Pasien Baru

4.istirahat 5 menit, lalu diulang no.1 dengan konsentrasi lebih tinggi bila hasil

MCT negatif dan instruksi tes dilanjutkan Preview Cetak

33. Data Pasien tes Metakolin

Grafik Penurunan FEVI terhadap konsentrasi Metakolin
o
-10
-2
-20

mess mo
053588583888

-40
-50
+0

Pasien Baru

Preview Cetak

34. FAKULTAS KEDOXTERAN UNYVIRSITAS AIRIANEGA -RSUO ORSOCTOMO fi
DEPARTEMEN PULMONOLOG! DAN ILMU KEDOKTERAN RESPIRASI
DEPARTEMEN PLLMONOLOGI DAN LMU KEDOKTERANRESPIRASI

LABORATORIUM FAAL PARU pe

LABORATORIUM FAAL PARU

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35. FAXULTAS FEDOKTERAN UNIVERSITAS ARLANGGA -RSUD DR SOETOMO FAXULIAS VEDOKTERAN UMVERSITAS A RLANGGA -RSUD DR SOETOMO
DEPARTEMEN PULMONOLO GI DAN ILMU KEDOKTERAN RESPIRAS! DEPARTEMEN PULMONOLOGI DAN ILMUKEDOKTERAN RESPIRASI

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36. Conclusions

» Several types of bronchial provocation test are available
to assess airway responsiveness

+ Methacholine challenge test is save with good preparation

- Five-breath dosimeter with 5 concentration (0,0625; 0,25;
1; 4; 16 mg/ml)

+ PC20 < 4 mg/ml > BHR positive

- Negative Predictive Value > Exclude Asthma

37. Thank You

» You can download this slide free in:

bit.ly/mct2017

Lui.

a: |