AIRWAY NEURAL CONTROL IN ASTHMA AND COPD

BrendanJ.Canning,Ph.D.JohnsHopkinsAsthmaandAllergyCenter

Bal;more,Maryland

Definintion of Asthma: “Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role … In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli.”

NIH Guidelines for the Diagnosis and Management of Asthma

Definintion of Asthma: “Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role … In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli.”

NIH Guidelines for the Diagnosis and Management of Asthma

ChestTightness

ReversibleAirwaysObstruc;onCough

Dyspnea

AirwaysHyperresponsiveness

NERVES

The Nervous System Plays an Essential Role in the Pathogenesis of Asthma and COPD.

Airway Smooth Muscle Contraction

Mucus Secretion

Control of Vascular Tone

4804203603002401801206000

100200300400500600700800

Salbutamol (200 µg)Ipratropium Bromide (40 µg)

TIME (minutes)

INC

REA

SE IN

FEV

1 A

BOV

E BA

SELI

NE

(ml B

PTS)

(25 patients studied)

(Modified from Ruffin et al. 1977)

*

***

*

Reversible Airways Obstruction in Asthma is Largely Dependent Upon Cholinergic Nerves.

3603002401801206000

5

10

15

20

25

30Metaproterenol (1.5 µg)

Ipratropium Bromide (36 µg)

Minutes After Treatment

MEA

N F

EV1,

% C

HA

NG

E

(107 Patients)

(90 Patients)* *

*

*

*

*

*

(Modified from Tashkin et al. 1986)

Reversible Airways Obstruction in COPD is Dependent Upon Cholinergic Nerves.

Airways Hyperresponsiveness in Asthma is Largely Dependent Upon Cholinergic Nerves.

(from Canning et al., 2012)

Riccardo Pellegrino et al. J Appl Physiol 2001;91:2190-2198

Inhaled Drugs for Asthma and COPD Will Only Work in the Airways that are Accessible to Aerosols.

ChestTightness

ReversibleAirwaysObstruc;onCough

Dyspnea

AirwaysHyperresponsiveness

NERVES

The Nervous System Plays an Essential Role in the Pathogenesis of Asthma and COPD.

Airway Smooth Muscle Contraction

Mucus Secretion

Control of Vascular Tone

X X

X

X

X

X

X

X

X Anticholinergics

Anticholinergics are NOT universal nerve blockers/ neuromodulators

Trachea

Le)bronchus

Rightvagusnerve

Upperlobebronchus

Middlelobebronchus

Lowerlobebronchus

Notconnected

branching

Rightbronchus

Extrinsic Vagal Innervation of the Human Airways

from Molfino et al., 1993

Hypoxia-induced Airway Narrowing: Increased in Asthmatics and Absent in Lung Transplant Patients

from Duarte et al., 2008

Loss and then Restoration of the Cough Reflex in Lung Transplant Patients

Mechanical Stimulation Chemical Stimulation

Thank you