1. Advanced Asthma Training Course Mechanisms Of Asthma Part II Dr.Hadeel A.K AlOtair ABIM,MRCP(UK),FCCP Assisstant professor of Medicine consultant pulmonologist King Khalid University Hospital

2. Advanced Asthma Training Course Airway Hyperresponsiveness It is the characteristic functional abnormality of asthma. It results in (exaggerated) airway narrowing in response to a stimulus. This leads to variable airflow limitation and intermittent symptoms. It is partially reversible with therapy.

3. Advanced Asthma Training Course Source: Peter J. Barnes, MD Mechanisms: AHR is linked to Inflammation

4. Advanced Asthma Training Course Mechanism of airway Hyper responsiveness Gene(s) responsible for AHR is located near a major locus that regulates serum IgE levels on chromosome 5q. Useful in the diagnosis of asthma

5. Advanced Asthma Training Course Mechanism of airway Hyper responsiveness Uncouplingof airway contraction May lead to excessive narrowing of the airways with loss of the maximum plateau of contractionfound in normal airways Thickening of the airway wall by edema and structural changes amplifies airway narrowing

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7. Mechanism of airway Hyper responsiveness  Sensory nerves may be sensitised by inflammation,leading to exaggerated bronchoconstriction  Excessive contraction of airway smooth muscle may result from increased Volume and/or airway smooth muscle cells

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10. Acute exacerbations Transient worsening of Asthma may occur as a result of exposure to certain triggers. e,g Exercise,air,pollutants or certain weather conditions. Prolonged worsening is usually due to viral infection of the upprt respiratory tract (Rhino virus, respiratory syncytial virus) or allergen exposure.

11. Advanced Asthma Training Course Virus Induced Asthma Exacerbation:Possible Mechanisms 2- Mediator production : Kinnin,complement, arachiodonic acid metabolite 1-Epithelial disruption :Reduced ciliary clearance, permeability, loss of protective function 3-Induction of inflammation :cytokines, chomokines 3-Induction of inflammation :cytokines, chomokines 4-Alteration of neural Responses : increased cholinergic activity 4-Alteration of neural Responses : increased cholinergic activity 5-IgE- dysregulation : increased total IgE

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13. Nocturnal Asthma Nocturnal Worsening of asthma May be related to the circadian rhythm of circulating hormones :epinephrine,cortisol,melatonin Neural mechanism: Cholinergic tone Increase in airway inflammation

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17. Irreversible airflow limitation Progressive airflow limitation that is not fully reversible. It develops in some patients with severe asthma It may reflect changes in airway structure in chronic asthma Can result in accelerated fall in lung function

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22. Difficult- to- treat asthma Confirm the diagnosis: Viral bronchiolitis Vocal cord dysfunction COPD Poor compliance to treatment Complicating conditions (Chronic sinusitis, GERD. smoking, OSA/obesity) Psychological and psychiatric disorders Genetic factors: poor response to glucocorticoid

23. Advanced Asthma Training Course Difficult- to- treat asthma Many are difficult to treat from the onset of the disease Airway closure leads to air trapping and hyperinflation Pathology: increase in neutrophils more small airway involvement more structural changes.

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25. Smoking and Asthma The cigarette burns out but the inflammation rages on. S-Shapiro

26. Advanced Asthma Training Course Smoking and Asthma Asthma is more difficult to control more frequent exacerbations more hospital admissions more rapid decline in lung function Fixed airway obstruction increase risk of death

27. Advanced Asthma Training Course Smoking and Asthma They may have neutrophil predominant inflammation in their airway poorly responsive to inhaled & oral glucocorticoids.

28. Advanced Asthma Training Course Y Y Y Mast cell CD4+ cell (Th2)Eosinophil Allergens Ep cells ASTHMA BronchoconstrictionAHR Alv macrophage Ep cells CD8+ cell (Tc1) Neutrophil Cigarette smoke Small airway narrowing Alveolar destruction COPD Reversible Irreversible Airflow Limitation Source: Peter J. Barnes, MD

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