OBSTRUCTIVE AIRWAY DISEASEOBSTRUCTIVE AIRWAY DISEASE

• Airways - obstructive diseaseAirways - obstructive diseaseLungs - restrictive diseaseLungs - restrictive disease

• Obstructive airway syndromeObstructive airway syndrome AsthmaAsthma Chronic bronchitisChronic bronchitis EmphysemaEmphysema

OBSTRUCTIVE AIRWAY DISEASEOBSTRUCTIVE AIRWAY DISEASETerminologyTerminology

• Early onset / late onsetEarly onset / late onset

• Atopic / non-atopicAtopic / non-atopic

• Extrinsic / IntrinsicExtrinsic / Intrinsic

The asthma triad

Asthma

Airway Inflammation

Airway Hyperresponsiveness

Reversible Airflow

Obstruction

Broncho-constriction

Airway remodeling

Chronicairway

inflammation

Briefsymptoms

exacerbationsBHR

fixedairway

obstruction

Dynamic evolution of asthma

Basement Membrane Submucosa Smooth Muscle

Thickening Collagen Deposition Hypertrophy

Hallmarks of Remodeling in asthma

THE INFLAMMATORY CASCADETHE INFLAMMATORY CASCADE

Genetic predisposition + Trigger factorGenetic predisposition + Trigger factor • Avoidance• Avoidance (e.g. viral, allergen, chemicals)(e.g. viral, allergen, chemicals)

Airway inflammationAirway inflammation • Anti-• Anti-inflammatory inflammatory - - corticosteroidcorticosteroid

MediatorsMediators • Anti-leukotriene • Anti-leukotriene (e.g. histamine, leukotriene)(e.g. histamine, leukotriene) AntihistamineAntihistamine

Twitchy smooth muscleTwitchy smooth muscle • Bronchodilators• Bronchodilators (Hyper-reactivity)(Hyper-reactivity) - - 22-agonists-agonists

The “Tip” of the Iceberg

Symptoms/ Exacerbations

Airflow obstruction

Bronchial hyperresponsiveness

Airway inflammation

TITANICTITANIC

NormalNormal AsthmaAsthma

desquamation

BM

eosinophilseosinophils

Inflammation in Asthma

Severe asthma –aliveEpithelial shedding

Severe asthma –autopsyMucus plugging

Normal

Allergens animal dander dust mites pollen fungi

Symptoms can occur or worsen in the presence of:

Others exercise viral infection smoke changes in temperature chemicals drugs (NSAIDs, ß-blockers)

Ask about triggers

ASTHMA - THE CLINICAL SYNDROMEASTHMA - THE CLINICAL SYNDROME

• Episodic symptoms and signsEpisodic symptoms and signs• Diurinal variability – nocturnal/early morning Diurinal variability – nocturnal/early morning • Non-productive cough, wheezeNon-productive cough, wheeze• TriggersTriggers• Associated atopy ( rhinitis , conjunctivitis, eczema)Associated atopy ( rhinitis , conjunctivitis, eczema)• Family history of asthmaFamily history of asthma• Wheezing due to turbulent airflowWheezing due to turbulent airflow

DIAGNOSIS OF ASTHMADIAGNOSIS OF ASTHMA

• History and examinationHistory and examination• Diurinal variation of peak flow rateDiurinal variation of peak flow rate• Reduced forced expiratory ratioReduced forced expiratory ratio

(FEV(FEV11/FVC < 75%)/FVC < 75%)• Reversibility to inh. salbutamol (>15%)Reversibility to inh. salbutamol (>15%)• Provocation testing Provocation testing bronchospasm bronchospasm

- exercise- exercise- histamine/allergen inhalation- histamine/allergen inhalation

High socioeconomic impact of COPD

• 1.5 million GP consultations in the UK per year

• 24 million lost working days in the UK per year

Economic impact per year

• Direct NHS costs – £486 million2

• Additional indirect costs – £1.5 billion (1995)2

COPD -A multicomponent disease process

Development of obstruction and ongoing disease

progression

Tissue Damage Mucociliary dysfunction

Inflammation

Noxious particles or gases, e.g. smoking

Characteristics of the disease:• Exacerbations• Reduced lung function

Symptoms: Breathlessness Worsening quality of life

Disease processes in COPD

Alveolar macrophage

Cigarette smoke

Neutrophil chemotatic factors,cytokines (IL-8), mediators (LTB4), oxygen radicals

Neutrophil

Proteases

CD8+lymphocyte

mucus hypersecretion(chronic bronchitis)

Alveolar wall destruction(emphysema)

-Proteaseinhibitors

?

Progressive airflow limitation

mucus

Mucociliary function in the healthy state

Damage to the respiratory mucosa due to bacterial infection

Healthy

H. influenzae

Destruction of the Alveoli

Normal Emphysema

COPD

• Chronic neutrophilic inflammation

• Mucus hypersecretion• Smooth muscle spasm

and hypertrophy• Partially reversible

• Alveolar destruction• Impaired gas exchange• Loss of bronchial support• Irreversible

Chronic Bronchitis Emphysema

PROTEASE IMBALANCE IN EMPHYSEMAPROTEASE IMBALANCE IN EMPHYSEMA

SmokingSmoking GeneticGenetic

ProteaseProtease Antiprotease Antiprotease

AlveolarAlveolar DestructionDestruction

EmphysemaEmphysema

COPD -THE CLINICAL SYNDROMECOPD -THE CLINICAL SYNDROME

• Chronic symptoms - not episodicChronic symptoms - not episodic• SmokingSmoking• Non-atopicNon-atopic• Daily productive coughDaily productive cough• Progressive breathlessnessProgressive breathlessness• Frequent infective exacerbationsFrequent infective exacerbations• Chronic bronchitis- wheezingChronic bronchitis- wheezing

Emphysema- reduced breath soundsEmphysema- reduced breath sounds

CHRONIC CASCADE IN COPDCHRONIC CASCADE IN COPD

• Progressive fixed airflow obstructionProgressive fixed airflow obstruction• Impaired alveolar gas exchangeImpaired alveolar gas exchange• Respiratory failure: Respiratory failure: PaOPaO22 PaCOPaCO22

• Pulmonary hypertensionPulmonary hypertension• Right ventricular hypertrophy/failureRight ventricular hypertrophy/failure

(i.e. cor pulmonale)(i.e. cor pulmonale)• DeathDeath

Stopping smoking arrests further decline in lung volumeStopping smoking arrests further decline in lung volume

Asthma vs COPD• Non smokers • Allergic• Early or late onset• Intermittent symptoms• Non productive cough• Non progressive • Eosinophilic inflammation• Diurnal variability• Good corticosteroid response• Good bronchodilator response• Preserved FVC and TLCO• Normal gas exchange

• Smokers• Non allergic• Late onset• Chronic symptoms• Productive cough• Progressive decline• Neutrophilic inflammation • No diurnal variability• Poor corticosteroid response• Poor bronchodilator response• Reduced FVC and TLCO• Impaired gas exchange