Asthma .pdf

Asthma ILOs At the end of this session, the student will be able to: ▪ Define asthma and its pathogenesis. ▪ Identify the different phenotypes of asthma and its risk factors. ▪ Describe the clinical picture of asthma. ▪ Identify the management plan of different asthm...

Asthma ILOs At the end of this session, the student will be able to: ▪ Define asthma and its pathogenesis. ▪ Identify the different phenotypes of asthma and its risk factors. ▪ Describe the clinical picture of asthma. ▪ Identify the management plan of different asthma stages. ▪ Identify asthma exacerbation. ▪ Describe the management plan of asthma exacerbation. Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. In susceptible individuals, this chronic inflammation is associated with airway hyperresponsiveness that causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The prevalence of asthma increased steadily over the latter part of last century. As asthma affects all age groups, it is one of the most common and important long- term respiratory conditions in terms of global years lived with disability. Pathogenesis of asthma ❖ Airway Inflammation has a central role in the pathogenesis of asthma. Inflammation involves a complex interaction of inflammatory cells (e.g., mast cell, CD4-T lymphocyte, eosinophil, and airway epithelial cell). ❖ Triggers of asthma (Box 1. And figure 1) lead to activation of mast cells and Th2 cells in the airway. They in turn induce the production of mediators of inflammation such as histamine and leukotrienes and cytokines. These mediators result in stimulation of mucous secretion and smooth muscle contraction, as well differentiation & migration of eosinophils to the lung. On activation, the eosinophils release inflammatory mediators & enzymes that injure airway tissues, prolong eosinophil survival, and contribute to persistent airway inflammation. Page 1 of 17  BOX 1: Asthma triggers: Tobacco Smoke. Dust Mites. Outdoor Air Pollution. Pests (e.g., cockroaches, mice) Pets. Mold Cleaning and Disinfection Infection Figure 1: Pathway of asthma ❖ Airway inflammation leads to development of airway hyperresponsiveness which is the tendency for airways to narrow excessively in response to triggers that have little or no effect in normal individuals. Airway hyper-responsiveness is integral to the diagnosis of asthma and responsible for respiratory symptoms. ❖ Chronic airway inflammation results in airway remodeling, that is defined as changes in the composition, content, and organization of the cellular and molecular constituents of the airway wall. These permanent structural changes include: Epithelial detachment Subepithelial fibrosis Increased airway smooth muscle (ASM) mass Goblet cell and mucus gland hyperplasia Proliferation of blood vessels (angiogenesis) and airway edema Increased matrix deposition in the airway wall. Wall thickening and abnormalities in elastin Changes in the cartilage Page 2 of 17 Remodeling of the airway leads to fibrosis of the airway wall, fixed narrowing of the airway and a reduced response to bronchodilator medication. Figure 2 shows the difference between normal and asthmatic airways. Figure 2: difference between normal and asthmatic airways Page 3 of 17  Risk factors that lead to asthma development: Host factors: o Genetic predisposition (positive family history of asthma as asthma runs in families), atopy, gender. Environmental factors: o Allergens (pets, dust mites, cockroach, molds, and pollens), air pollution, respiratory infections especially viral, change in weather (cold and dry weather, high humidity), tobacco smoke, diet, drugs (NSAID, aspirin, beta- blockers) and emotions. Types and phenotypes of asthma Previously asthma was classified as extrinsic (allergic) or intrinsic asthma. However, nowadays intrinsic asthma is replaced by non-allergic asthma and further subclassified into various phenotypes. Table 1: Phenotypes of asthma Natural Clinical and Pathobiology Genetics Response to history physiological and biomarkers therapy features Early-onset Early Allergic Specific IgE; 17q12; Corticosteroi allergic onset; symptoms and Th2 cytokines; Th2- ds- (extrinsic mild to other diseases thick SBM related responsive; asthma) severe (e.g., eczema, genes Th2-targeted urticaria, nasal allergy, eye allergy) Late-onset Adult Sinusitis, less Corticosteroids Response to eosinophilic onset; allergic -refractory antibody to often eosinophilia; Il-5 and severe Il-5 cysteinyl leukotriene modifiers; corticosteroid s refractory Exercise Mild Mas-cell Response to induced intermittent activation; Th2 cysteinyl with exercise cytokines; leukotriene modifiers; Page 4 of 17  cysteinyl beta agonists leukotrienes and antibodies to IL-9 Obesity Adult Women Lack of Th2 Response to related onset mainly cytokines weight loss affected, very symptomatic, airway hyperresponsi ve less clear Neutrophilic Low FEV1, Sputum Possible more air neutrophilia, response to trapping IL-8, Th17 macrolides pathway antibiotics Special forms of asthma - Nocturnal asthma - Intermittent asthma - Occupational asthma - Aspirin–induced asthma - Steroid – resistant asthma - Cough–variant asthma - Asthma in pregnancy Clinical Picture Typical symptoms of asthma include wheezes, breathlessness, cough and sensation of chest tightness. These symptoms may occur for the first time at any age and may be episodic or persistent. Patients with episodic asthma are usually asymptomatic between exacerbations, which occur during viral respiratory tract infections or after exposure to allergens. Symptoms worsen at night and may occur or worsen in seasonal pattern, improve Page 5 of 17  with anti-asthma therapy. This pattern is commonly seen in children or young adults who are atopic. In other patients, the clinical pattern is persistent asthma with chronic wheeze and breathlessness. This pattern is more common in older patients with adult-onset asthma who are non- atopic. Wheezing is usually expiratory but may be present during inspiration. Wheezing may be absent in case of very mild or very severe airway obstruction. Severe airway obstruction leads to marked limitation of airflow (silent chest). Signs of hyperinflation and diminished breath and heart sounds may be present during an acute exacerbation. Asthma Diagnosis Diagnosis of asthma depends on: ❖ History and pattern of symptoms and physical examination ❖ Physiological assessment: 1) Measurements of lung function using spirometry provide an assessment of the severity, reversibility, and variability of airflow limitation, and help to confirm the diagnosis of asthma. Pulmonary function tests: Obstructive pattern during the attack, normal in between attacks (except in moderate & severe persistent asthma). Reversibility test: If FEV1 increased by 12% and 200 ml of absolute value after inhalation of bronchodilator, indicates reversible airflow limitation consistent with asthma. Peak expiratory flow rate (PEFR) Variability test: diurnal PEFR variability >20% on at least 3 days/week for 2 weeks suggests diagnosis of asthma. 2) “Broncho-provocation test”: using metacholine, histamine, adenosine, or exercise to induce bronchospasm in patients with normal lung functions. ❖ Measurement of exhaled nitric oxide (FeNO) is a useful test for glucocorticoid - naive patients as a measure of eosinophilic airways inflammation. An elevated FeNO value (adults >50 part per billion (ppb); children >35ppb) supports the diagnosis of asthma and suggests that the patient’s symptoms are highly likely to respond to glucocorticoids. ❖ Skin Prick test: to assess the allergic status. Page 6 of 17 ❖ Laboratory tests: Peripheral blood eosinophilia Sputum eosinophilia Elevated serum IgE (total and specific) ❖ Radiological: Chest X-ray is important for excluding other diseases and should be normal in asthma except if persistent asthma or during an acute attack, there will be hyperinflation. It could be abnormal if complications detected e.g., pneumothorax, pneumomediastinum and atelectasis due to mucous plugs. Differential Diagnosis “Not every wheezer is asthmatic.” 1. COPD & other obstructive airway diseases (foreign body (FB), tumor, extrinsic compression by lymph nodes (LNs),....) 2. Bronchitis 3. Bronchopneumonia 4. Gastroesophageal disease (GERD) 5. Rhino-sinus disease 6. Congestive heart failure (CHF) 7. Pulmonary embolism Management of asthma Long-term management “In between acute attacks” The long-term goals of asthma management are symptom control and reduction. risk of exacerbations, airway damage, and medication side-effects. Page 7 of 17  These goals can be achieved by: - Medications: Every patient with asthma should have a reliever medication, and most patients with asthma should have a controller medication - Treating modifiable risk factors and co-morbidities e.g., Smoking, anxiety, depression, rhinitis, sinusitis, GERD. - Non-pharmacological therapies Pharmacological therapy includes: o Reliever drugs: (relive bronchospasm) Short-acting inhaled β2 agonists (SABA) and anticholinergics. Methylxanthines. Short-acting oral β2 agonists. o Controller drugs: (to control airway inflammation) Corticosteroids; inhaled and systemic. Long-acting inhaled β2 agonists (LABA) Leukotriene-receptor antagonists. Long-acting oral β2 agonists. Long-acting inhaled anticholinergic (LAMA) as tiotropium Methylxanthines Biological therapy as anti-IgE (omalizumab), anti-IL5 (mepolizumab) ❖ Control-based asthma management Stepwise approach for adjusting treatment: Once asthma treatment has been started, ongoing decisions are based on a cycle to: 1. Assess (Level of symptom control, risk factors, pulmonary function) 2. Adjust treatment. 3. Review response to treatment Page 8 of 17  AAP: asthma action plan - The preferred treatments at each step are based on severity and level of asthma control. The stepwise approach for adjusting treatment is summarized in (table 2). - Corner stone of asthma therapy is inhaled corticosteroids (ICS). - Inhaled SABAs are medications of choice for quick relief of asthma symptoms and bronchoconstriction. SABAs should be used only as needed at the lowest dose and frequency required. Tremor and tachycardia are commonly reported side effects with initial use of SABA. Excess use, or poor response indicate poor asthma control. - For the best outcomes, regular daily controller treatment should be initiated as soon as possible after the diagnosis of asthma is made. - Long-acting anticholinergic (tiotropium): An add-on option at Step 4 or 5 by mist inhaler for patients ≥12 years with a history of exacerbations despite ICS ± LABA. - Anti-IgE (omalizumab): An add-on option for patients with severe persistent allergic asthma uncontrolled on Step 4 treatment (high dose ICS/LABA). - Anti-IL5: An add-on option for patients aged ≥12 years with severe eosinophilic asthma uncontrolled on Step 4 treatment (high dose ICS/LABA) Reviewing response and adjusting treatment after starting initial controller treatment Page 9 of 17 - Patients should preferably be seen 1–3 months after starting treatment or according to clinical urgency and every 3–12 months after that except in pregnancy when they should be reviewed every 4–6 weeks. - Consider step down when asthma has been well-controlled for 3 months + low risk for exacerbation. - Consider stepping up if …. uncontrolled symptoms, exacerbation, or risk, but check diagnosis, inhalers technique and adherence first. Table 2: Stepwise approach to asthma treatment Decrease Increase Step 1 Step 2 Step 3 Step 4 Step 5 Select one ---------------- Low dose Low dose Medium / Refer for ICS ICS/ high ICS + add on Preferred LABA treatment. controller choice e.g. LABA Tiotropium Anti-IgE Anti-IL5 Consider low Leukotriene Medium/high Add Add Low dose inhaled receptor dose ICS Tiotropium dose OCS Other corticosteroids antagonist controller (ICS) only for (LTRA) options patients with Low dose exacerbation ICS +LTRA risk Low dose Or High dose slow-release ICS +LTRA theophylline theophylline or +theophylline As needed short acting beta As needed SABA agonist Reliever or (SABA) Low dose ICS/ formoterol Page 10 of 17  Non-Pharmacological therapy: a. Education b. Avoidance of triggers c. Smoking cessation advice d. Influenza vaccination e. Allergen Immunotherapy How to assess a patient with asthma ❖ Assessing Asthma Control Asthma control means the extent to which the effects of asthma can be seen in the patient, and accordingly the treatment is reduced, increased, or removed (step up or down in asthma treatment; table 2). Asthma control includes: 1) Symptom control: this is established through application of a simplified scheme for recognizing level of asthma control (controlled, partly controlled, and uncontrolled asthma). (Table 3) 2) Risk factors: are factors that increase the patient’s future risk of having exacerbations (flare-ups), loss of lung function, or medication side-effects. Risk factors are assessed at diagnosis and periodically. 3) Measure lung function: measure FEV1% before starting treatment, 3–6 months later, and then periodically, e.g., yearly. Lung function is most useful as an indicator of future risk. Page 11 of 17  Table (3): Level of asthma symptom control In the past 4 weeks, Well Partly Uncontrolled the patient had controlled controlled Day time symptoms more than twice /week Any night waking due to asthma? None of 1-2 of these 3-4 of these Reliever needed more these than twice/ week Any activity limitation due to asthma? ❖ Assessing severity of the underlying disease - The degree of symptoms, airflow limitation, and lung function variability have allowed asthma to be classified by severity into: o Intermittent - Mild Persistent, o Moderate Persistent - Severe Persistent Page 12 of 17 Asthma Exacerbation (acute asthma, asthma attack) Exacerbation is an acute or sub-acute worsening in symptoms and lung function from the patient’s usual status. Exacerbation severity is graded into mild, moderate, severe, and very severe (life threatening). Criteria for exacerbation severity are based on symptoms and physical examination parameters, as well as lung function and oxygen saturation. Grading of severity is essential to provide the appropriate management regarding site (primary or acute care, ICU) and plan of treatment. Clinical presentation In 85-90% of life-threatening asthma present after several days of worsening symptoms and often occurs in patients with severe and poorly controlled asthma. In 10%, the onset is more rapid, and asthma progresses over a period of minutes to hours. Patients with acute severe asthma are dyspneic (talks in words), agitated, and diaphoretic, typically sitting upright, tachycardic (pulse rate >120/ min) and tachypneic (respiratory rate (RR)>30/min), using accessory muscles, O2 saturation on room air