Asthma Dr. Gerrard Uy

Asthma Asthma is a serious health problem throughout the world, affecting people of all ages When uncontrolled, asthma can place severe limits on daily life, and is sometimes fatal In 1993, GINA was introduced

What is Asthma Chronic inflammatory disorder of the airways Associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, coughing, particularly at night or early in the morning Clinical manifestations can be controlled with appropriate treatment

What is Asthma Wheezing is the most common physical finding in asthma Main physiological feature is episodic airway obstruction characterized by expiratory airflow limitation Dominant pathological feature is airway inflammation, sometimes associated with structural changes Strongly associated with atopy

Burden of Asthma Asthma is a problem worldwide with an estimated 300 million affected individuals Ranges for 1 – 18% of the population in different countries Annual worldwide deaths from asthma have been estimated at 250,000

Factors influencing the development and expression of asthma Host Factors: – Genetics – Obesity (BMI > 30 kg/m2) – Sex Environmental Factors: – Allergens – Infections – Occupational sensitizers – Tobacco smoke – Outdoor/Indoor pollution – Diet

Mechanism of asthma Airway inflammation – Remains to be a consistent feature – Persistent even though symptoms are episodic – Inflammation affects all airways but is most pronounced in medium sized bronchi – Inflammatory cells found in asthma Mast cells Eosinophils T lymphocytes Dendritic cells Macrophages Neutrophils

Mechanism of asthma Airway structural cells involved in asthma: – Airway epithelial cells – Airway smooth muscle cells – Endothelial cells – Fibroblast and myofibroblast – Airway nerves

Mechanism of asthma Structural changes in asthma – Subepithelial fibrosis – Airway smooth muscle hypertrophy and hyperplasia – Blood vessels increase in number – Mucus hypersecretion

Pathophysiology Airway narrowing is the common final pathway leading to symptoms and physiological changes in asthma Airway hyperresponsiveness is the characteristic functional abnormality in asthma

Diagnosis Episodic breathlessness, wheezing, cough, and chest tightness History of atopy or allergic rhinitis Symptoms occurring at night Precipitation by exposure to certain allergens Resolves/improves after appropriate asthma medication

Lung Function Test Spirometry – Recommended method of measuring airflow limitation and reversibility – Measures FEV1 and FVC – FEV1/FVC is normally > 0.75 – 0.80 – The degree of reversibility in FEV1 is generally accepted as 12% or 200 ml from the pre bronchodilator value

Lung Function Test Peak Expiratory Flow Measurement (PEF) – Measurements are made using a peak flow meter – Relatively inexpensive, portable, ideal for patients in home settings – PEF can underestimate degree of airflow limitation – Most commonly, PEF is measured first thing in the morning before treatment is taken – 60 ml/L or 20% improvement from prebronchodilator suggests a diagnosis of asthma

Differential Diagnosis Children 5 yrs and younger – Transient early wheezing – Persistent early onset wheezing – Late onset wheezing/asthma Older children and adults – Hyperventilation syndrome – Foreign body aspiration – Vocal cord dysfunction – COPD – heartfailure

Treatment The goal of asthma treatment is to achieve and maintain clinical control Medications to treat asthma is divided into 2 – Controllers and relievers Different routes of administration: – Inhaled, orally, parenterally (IV, SC, IM) – The major advantage of inhaled route is that the medication is delivered directly into the airways, producing higher local concentrations with less risk of systemic side effects

Controller Medications Inhaled glucocorticoids – Currently the most effective anti-inflammatory medication for the treatment of persistent asthma – Budesonides, fluticasone, mometasone, etc. – To reach clinical control, add on therapy with another class of drug is preferred over increasing the dose of inhaled glucocorticoids – Side effects: Oropharyngeal candidiasis Dysphonia Coughing from upper airway irritation

Controller Medications Inhaled glucocorticoids – Systemic side effects of long term high dose glucocorticiods: Easy bruising Adrenal suppression Decreased bone mineral density Cataracts/glaucoma *there is no evidence that the use of inhaled glucocorticoids increases the risk of pulmonary infections

Controller Medications Leukotriene modifiers – Small and variable bronchodilator effect – Maybe used as an alternative treatment for patients with mild persistent asthma – Usually used as an add on therapy – Less effective compared to long acting B2 agonist as an add on therapy – Montelukast, zileuton, etc

Controller Medications Long acting inhaled B2 agonist – Should not be used as monotherapy because they do not influence airway inflammation – Salmeterol, Formoterol, etc – Side effects: Cardiovascular stimulation Skeletal muscle tremor hypokalemia

Controller Medications Others: – Theophylline – Cromones (Sodium cromoglycate/Nedocromil Na) – Long acting oral B2 agonist (Salbutamol, bambuterol, terbutaline) – Anti IgE (Omalizumab) – Systemic glucocorticoids

Reliever Medications Rapid acting inhaled B2 agonist – Medication of choice for relief of bronchospasm during acute exacerbations of asthma and for pretreatment of exercise induced bronchoconstriction – Salbutamol, formoterol, terbutaline, etc – Side effects: tremor and tachycardia

Reliever Medications Systemic glucocorticoids – Important in the treatment of severe acute attacks – Prevent progression of the exacerbation, reduce the need for referral to emergency departments and hospitalization, reduce morbidity of the illness – Main effect are only evident after 4-6 hrs – Prednisone, hydrocortisone, etc

Reliever Medications Anti-cholinergics – Alternative bronchodilator in patients who experience side effects of B2 agonist – Side effect: dryness of the mouth and bitter taste – Ipatropium bromide

Reliever Medications Others – Theophylline – Rapid acting B2 agonist – Alternative medicine

COPD (Chronic Obstructive Pulmonary Disease) Dr. Gerrard Uy

COPD Major cause of chronic morbidity and mortality throughout the world GOLD was created to increase awareness of COPD among health professionals, public health authorities, and the general public, and to improve prevention and management through a concerted worldwide effort

COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) a disease state characterized by airflow limitation that is not fully reversible The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles and gases – Includes: emphysema, chronic bronchitis, and small airways disease

COPD Emphysema – an anatomically defined condition characterized by destruction and enlargement of the lung alveoli Chronic Bronchitis – a clinically defined condition with chronic cough and phlegm Small airways disease – a condition in which small bronchioles are narrowed

Symptoms of COPD Cough Sputum production Dyspnea on exertion * chronic cough and sputum production often precede the development of airflow limitation by many years

Risk Factors Cigarette/tobacco Smoking – Intensity: pack years (sticks/day for years) – most highly significant predictor of FEV 1 Occupational Exposures – general exposure to dust at work – coal mining, gold mining, and cotton textile dust

Risk Factors Indoor Air pollution – Biomass fuel used for cooking Outdoor Air Pollution Genetic Considerations (alpha 1 antitrypsin deficiency)

Natural History Effect of cigarette smoking depends on intensity, timing during growth, basal function

Pathophysiology Airflow obstruction – Determined by spirometry: FEV1 and FVC – chronically reduced ratio of FEV 1 /FVC – seldom shows large responses to inhaled bronchodilators Hyperinflation – "air trapping“ – helps to compensate for airway obstruction

Pathophysiology Gas Exchange – Nonuniform ventilation and ventilation-perfusion mismatching

Pathology Large Airway – Cigarette smoking often results in mucous gland enlargement and goblet cell hyperplasia – proportional to cough and mucus production Small Airways major site of increased resistance in most individuals with COPD is in airways 2 mm diameter goblet cell metaplasia and replacement of surfactant- secreting Clara cells with mucus-secreting and infiltrating mononuclear inflammatory cells

Pathology Lung Parenchyma – destruction of gas-exchanging airspaces – walls become perforated and later obliterated with coalescence of small distinct airspaces into abnormal and much larger airspaces – Macrophages accumulate – Centriacinar emphysema- most frequently associated with cigarette smoking – Panacinar emphysema - usually observed in patients with alpha 1 AT deficiency

Diagnosing COPD Considered in any patient who has dyspnea, chronic cough with or without sputum production and/or history of exposure to risk factors for the disease Preform spirometry for confirmation

Stages of COPD Stage 1: Mild COPD – Mild airflow limitation (FEV1/FVC 80% predicted) Stage 2: Moderate COPD – Worsening airflow limitation (FEV!/FVC <70%, FEV1 < 80% predicted) Stage 3: Severe COPD – Further worsening (FEV1/FVC <70%, FEV1 < 50% predicted) Stage 4: Very severe COPD – FEV1/FVC <70%, FEV1 < 30% predicted or < 50% with chronic respiratory failure

Clinical presentation History cough, sputum production, and exertional dyspnea exertional dyspnea, often described as increased effort to breathe, heaviness, air hunger, or gasping, can be insidious patient's ability to perform them has changed

Clinical presentation Physical Findings – entirely normal physical examination – early – signs of active smoking, including an odor of smoke or nicotine staining of fingernails – prolonged expiratory phase and expiratory wheezing- more severe – signs of hyperinflation include a barrel chest and enlarged lung volumes

Laboratory Findings hallmark of COPD is airflow obstruction Pulmonary function testing shows airflow obstruction with a reduction in FEV 1 and FEV 1 /FVC lung volumes may increase

COPD Management Goals: – Relieve symptoms – Prevent disease progression – Improve exercise tolerance – Improve health status – Prevent and treat complication – Prevent and treat exacerbations – Reduce mortality – Prevent or minimize side effects from treatment

COPD Management In addition to spirometry, other test maybe considered for the assessment of stage 2 – 4 COPD – Bronchodilator reversibility testing To rule out a diagnosis of asthma – Chest xray – Abg Performed in patients with FEV1 <50% – Alpha 1 antitrypsin deficiency Performed in patients of caucasian descent under 45 y.o. with a strong family hx of COPD

Treatment SMOKING cessation Bronchodilators Anticholinergic agents Beta agonists Inhaled Glucocorticoids Oral Glucocorticoids Theophylline Oxygen

Treatment General Medical Care Pulmonary Rehabilitation Lung Volume Reduction Surgery Lung Transplantation