Potenciais alvos de distúrbios patológicos do

aparelho respiratório

Doença Pulmonar

Obstrutiva: aumento na resistência ao fluxo aéreo.

1. Asma

2. Doença pulmonar obstrutiva crônica

a) Bronquite crônica

b) Enfisema pulmonar

Restritiva: redução da expansão do parênquima pulmonar

1. Síndrome do desconforto respiratório agudo (SDRA)

Asma

© Global Initiative for Asthma

Asthma is one of the most common chronic diseases worldwide

with an estimated 300 million affected individuals

Prevalence is increasing in many countries, especially in

children

Asthma is a major cause of school and work absence

Health care expenditure on asthma is very high

Burden of asthma

GINA 2014

© Global Initiative for Asthma

Asthma is a common and potentially serious chronic disease

that can be controlled but not cured

Asthma causes symptoms such as wheezing, shortness of

breath, chest tightness and cough that vary over time in their

occurrence, frequency and intensity

Symptoms are associated with variable expiratory airflow,

i.e. difficulty breathing air out of the lungs due to

Bronchoconstriction (airway narrowing)

Airway wall thickening

Increased mucus

Symptoms may be triggered or worsened by factors such as

viral infections, allergens, tobacco smoke, exercise and stress

What is known about asthma?

GINA 2014

© Global Initiative for Asthma

Asthma is a heterogeneous disease, usually characterized

by chronic airway inflammation.

It is defined by the history of respiratory symptoms such as

wheeze, shortness of breath, chest tightness and cough

that vary over time and in intensity, together with variable

expiratory airflow limitation.

Definition of asthma

NEW!

GINA 2014

© Global Initiative for Asthma

The diagnosis of asthma should be based on:

A history of characteristic symptom patterns

Evidence of variable airflow limitation, from bronchodilator

reversibility testing or other tests

Document evidence for the diagnosis in the patient’s notes,

preferably before starting controller treatment

It is often more difficult to confirm the diagnosis after treatment has

been started

Asthma is usually characterized by airway inflammation

and airway hyperresponsiveness, but these are not

necessary or sufficient to make the diagnosis of asthma.

Diagnosis of asthma

GINA 2014

© Global Initiative for Asthma

Note: Each FEV1 represents the highest of

three reproducible measurements

Typical spirometric tracings

Time (seconds)

Volume

FEV1

1 2 3 4 5

Normal

Asthma

(after BD)

Asthma

(before BD)

GINA 2014

© Global Initiative for Asthma

The long-term goals of asthma management are

1. Symptom control: to achieve good control of symptoms

and maintain normal activity levels

2. Risk reduction: to minimize future risk of exacerbations,

fixed airflow limitation and medication side-effects

Goals of asthma management

GINA 2014

Eosinófilos

Eosinófilos e asma

Asmatico Normal

Busse & Lemanske, N. Engl. J. Med, 2001,

Reação alérgica e asma

Dose-response curves to inhaled direct agonists (histamine or methacholine) in normal, mild,

or severe asthma.

Busse W W Chest 2010;138:4S-10S

Hiperreatividade brônquica – Asma

Mecanismos indutores de hiperreatividade

Receptores muscarínicos

e hiperreatividade

Doença Pulmonar

Obstrutiva: aumento na resistência ao fluxo aéreo. 1. Asma

2. Doença pulmonar obstrutiva crônica

a) Bronquite crônica

b) Enfisema pulmonar

Restritiva: redução da expansão do parênquima pulmonar

1. Síndrome do desconforto respiratório agudo (SDRA)

Global Strategy for Diagnosis, Management and Prevention of COPD

Definition of COPD

COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.

.

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Mechanisms Underlying

Airflow Limitation in COPD

Small Airways Disease

• Airway inflammation • Airway fibrosis, luminal plugs • Increased airway resistance

Parenchymal Destruction

• Loss of alveolar attachments • Decrease of elastic recoil

AIRFLOW LIMITATION © 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Burden of COPD

COPD is a leading cause of morbidity and mortality worldwide.

The burden of COPD is projected to increase in coming decades due to continued exposure to COPD risk factors and the aging of the world’s population.

COPD is associated with significant economic burden.

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Risk Factors for COPD

Lung growth and development

Gender

Age

Respiratory infections

Socioeconomic status

Asthma/Bronchial hyperreactivity

Chronic Bronchitis

Genes

Exposure to particles

Tobacco smoke

Occupational dusts, organic and inorganic

Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings

Outdoor air pollution

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Spirometry: Normal Trace Showing FEV1 and FVC

1 2 3 4 5 6

1

2

3

4

Volu

me, lit

ers

Time, sec

FVC 5

1

FEV1 = 4L

FVC = 5L

FEV1/FVC = 0.8

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Volume expiratório forçado.

Capacidade vital forçada

The characteristic symptoms of COPD are chronic and progressive dyspnea,

cough, and sputum production that can be variable from day-to-day.

Dyspnea: Progressive, persistent and characteristically worse with exercise.

Chronic cough: May be intermittent and may be unproductive.

Chronic sputum production: COPD patients commonly cough up sputum.

Global Strategy for Diagnosis, Management and Prevention of COPD

Symptoms of COPD

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Therapeutic Options: COPD Medications

Beta2-agonists

Short-acting beta2-agonists

Long-acting beta2-agonists

Anticholinergics

Short-acting anticholinergics

Long-acting anticholinergics

Combination short-acting beta2-agonists + anticholinergic in one inhaler

Combination long-acting beta2-agonists + anticholinergic in one inhaler

Methylxanthines

Inhaled corticosteroids

Combination long-acting beta2-agonists + corticosteroids in one inhaler

Systemic corticosteroids

Phosphodiesterase-4 inhibitors

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Professor Peter J. Barnes, MD

National Heart and Lung Institute, London UK

Doença Pulmonar Obstrutiva Crônica Inflamação crônica e remodelamento das vias aéreas e

destruição do parênquima pulmonar.

Bronquite Crônica

Doença Pulmonar Obstrutiva Crônica Inflamação crônica e remodelamento das vias aéreas e

destruição do parênquima pulmonar.

Bronquite Crônica Spina. D, 2011

Doença Pulmonar Obstrutiva Crônica

Enfisema

Enfisema

Metaloproteinases: degradam componentes da matriz extracelular

Patologia da DPOC

Spina. D, 2011

Global Strategy for Diagnosis, Management and Prevention of COPD

Differential Diagnosis: COPD and Asthma

COPD

• Onset in mid-life

• Symptoms slowly progressive

• Long smoking history

ASTHMA

• Onset early in life (often childhood)

• Symptoms vary from day to day

• Symptoms worse at night/early morning

• Allergy, rhinitis, and/or eczema also present

• Family history of asthma

© 2014 Global Initiative for Chronic Obstructive Lung Disease

Professor Peter J. Barnes, MD

National Heart and Lung Institute, London UK

© Global Initiative for Asthma

Definitions

Asthma

Asthma is a heterogeneous disease, usually characterized by chronic airway

inflammation. It is defined by the history of respiratory symptoms such as wheeze,

shortness of breath, chest tightness and cough that vary over time and in intensity,

together with variable expiratory airflow limitation. [GINA 2014]

GINA 2014, Box 5-1

Asthma

Asthma is a heterogeneous disease, usually characterized by chronic airway

inflammation. It is defined by the history of respiratory symptoms such as wheeze,

shortness of breath, chest tightness and cough that vary over time and in intensity,

together with variable expiratory airflow limitation. [GINA 2014]

COPD

COPD is a common preventable and treatable disease, characterized by persistent

airflow limitation that is usually progressive and associated with enhanced chronic

inflammatory responses in the airways and the lungs to noxious particles or gases.

Exacerbations and comorbidities contribute to the overall severity in individual

patients. [GOLD 2014]

Asthma

Asthma is a heterogeneous disease, usually characterized by chronic airway

inflammation. It is defined by the history of respiratory symptoms such as wheeze,

shortness of breath, chest tightness and cough that vary over time and in intensity,

together with variable expiratory airflow limitation. [GINA 2014]

COPD

COPD is a common preventable and treatable disease, characterized by persistent

airflow limitation that is usually progressive and associated with enhanced chronic

inflammatory responses in the airways and the lungs to noxious particles or gases.

Exacerbations and comorbidities contribute to the overall severity in individual

patients. [GOLD 2014]

Asthma-COPD overlap syndrome (ACOS) [a description]

Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow

limitation with several features usually associated with asthma and several features

usually associated with COPD. ACOS is therefore identified by the features that it

shares with both asthma and COPD.

Síndrome do Desconforto Respiratório Agudo

(SDRA)

Lesão capilar alveolar difusa

Insuficiência respiratória grave

Hipoxemia arterial grave (refrataria a oxigenoterapia)

Cianose

Falência múltipla dos órgãos

Andrew, et al. Am J Physiol Lung Cell Mol Physiol 306: L217–L230, 2014

Modulação farmacológica (Distúrbios patológicos - aparelho respiratório)

Pharmacological therapies for acute respiratory

distress syndrome

(SDRA)

Peter Markus Spietha and Haibo Zhang

Antagonistas de leucotrienos peptidicos (LTD4)

UTILIZADOS

PRINCIPALMENTE EM

SITUAÇÕES

EMERGENCIAIS

MUITO IMPORTANTES NA

FASE INICIAL NO

PROCESSO ASMÁTICO

METILXANTINAS

PROVAVELMENTE

ELEVANDO OS NÍVEIS

DE AMP CÍCLICO E/OU

BLOQUEANDO OS

RECEPTORES DA

ADENOSINA

ANTAGONISTAS

COLINÉRGICOS

(ANTICOLINÉRGICOS)

BLOQUEANDO RECEPTOR

COLINÉRGICO

MUSCARÍNICO

AGONISTAS

ADRENÉRGICOS

BRONCODILATAÇÃO POR

ESTÍMULO DE

RECEPTORES BETA 2

Agonistas de Receptores adrenérgicos

Metil xantinas

(Teofilina e Aminofilina)

Mecanismo de ação:

Inibição da fosfodiesterase (cAMP)

Altera concentração Ca++

Efeitos adversos

Estimulação do coração

Estimulante SNC

Náusea, vômitos, tremores

ATP cAMP 5’-AMP

Adenylyl Cyclase Phosphodiesterase

agonists

stimulate Teophylline

inhibits

inhibition of mediator release

bronchodilation

Antagonistas de Receptores de LT peptídicos

Glicocorticóides

Modulação farmacológica (Distúrbios patológicos - aparelho respiratório)

Antagonistas - receptores muscarinicos

Controle neural das vias aéreas

Colinérgico

Atropina

Brometo de ipatropio

Tiotropium

Receptores

Fármacos Anticolinérgicos

Fármacos Mucoativos

Fármacos que facilitam a eliminação do

muco das vias aéreas superiores.

Muco é um polímero de mucina altamente

oligomerizado composto de água e varias

glicoprotenas macromoleculares.

Fármacos Mucoativos

Fármacos Mucoativos

Expectorantes: Estimulam o fluxo da secreção e diminuiem a viscosidade do muco : GUAIFENESINA (Xarope Vick) Mucoreguladores: Diminuem o volume de secreção: AGENTES ANTICOLIÉERGICOS (Brometo de ipatropio) Mucolíticos: Quebram as pontes dissulfeto que ligam os polímeros de mucina: N-ACETIL CISTEINA (Fluimucil) Mucocinéticos: Estimulam a produção de surfactante e inibem os canais de sódio neuronal : AMBROXOL (Mucosolvan)