OBSTRUCTIVE AIRWAY DISEASE Airways - obstructive disease Lungs - restrictive disease
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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
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
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