Bronchial Asthma - Lecture Notes PDF

‫بسم الله الرحمن‬ ‫الرحيم‬ Bronchial asthma By Professor Dr. Amany Elbanna Faculty of Medicine Alexandria university  Definition Common chronic inflammatory airway disease associated with airway hyper-responsiveness to a wide range of stimuli, leading t...

‫بسم الله الرحمن‬ ‫الرحيم‬ Bronchial asthma By Professor Dr. Amany Elbanna Faculty of Medicine Alexandria university  Definition Common chronic inflammatory airway disease associated with airway hyper-responsiveness to a wide range of stimuli, leading to recurrent airflow obstruction manifest clinically as wheezing, cough, and difficulty in breathing reversible spontaneously or with treatment. Occur particularly at night or in the early morning,  Definition Inflammation of the bronchi is brought about by different inflammatory cells [eosinophils, mast cells and T lymphocytes cells (CD4)] associated with plasma exudation, edema, smooth muscle hypertrophy, mucus plugging and epithelial damage. - In chronic asthma, inflammation may lead to irreversible airflow limitation (airway remodeling)  Prevalence: In most countries asthma prevalence is increasing particularly in children and adolescents where the disease affects 10-15% of the population.  Classification: Asthma can be divided into: « Extrinsic: implying a definite external cause. « Intrinsic: where no causative agent can be identified.  Classification: Intrinsic Asthma: - Starts usually in middle age (late onset) - Show a negative skin prick test. - Not associated with other atopic diseases. Extrinsic atopic Asthma: - Occur most frequently in atopic individuals — onset usually in childhood. - Show positive skin prick tests to common inhalant allergens - Frequently associated with other atopic diseases e.g. atopic dermatitis and allergic rhinitis. Extrinsic non-atopic asthma: A subgroup of patients with late-onset asthma in adults caused by sensitization to chemicals or biological products in the workplace. Differences between atopic and non atopic asthma  Special forms of asthma - Nocturnal asthma - Occupational asthma - Exercise-induced asthma - Aspirin-induced asthma - Steroid – resistant asthma - Cough-variant asthma - Asthma in pregnancy  Pathogenesis of asthma Airway Inflammation has a central role.  Inflammation involves a complex interaction of inflammatory cells (e.g, mast cell, CD4 T lymphocyte, eosinophil, and airway epithelial cell) and resident airway cells. Triggers of asthma as infection, allergens and air pollution 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.  Pathogenesis of asthma 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. Airway inflammation leads to development of airway hyper-responsiveness, airflow limitation, respiratory symptoms, and disease chronicity.  Chronic airway inflammation results in airway remodeling  Airway remodeling 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 and airway edema Changes in the cartilage  Risk factors that lead to asthma development: 1. Host factors: Genetic predisposition , Atopy, Gender 2. Environmental factors: Allergens, air pollution, respiratory infections, tobacco smoke, diet, drugs (NSAID, aspirin, beta- blockers).  Important definitions Atopy: A genetic tendency for exaggerated IgE antibody responses, defined clinically by the presence of one or more positive skin prick tests to common inhaled allergens ie. a predisposition to develop allergy. Allergy: Theclinical expression of atopic disease including asthma, rhinitis, atopic dermatitis and food allergy.  Clinical Picture Typical symptoms include wheezes, dyspnea, cough and sensation of chest tightness. symptoms may occur for the first time at any age and may be episodic or persistent. Children or young adults who are atopic have episodic asthma and are asymptomatic between exacerbations Exacerbations occur during viral respiratory tract infections or after exposure to allergens. Symptoms worsen at night and may occur or worsen in seasonal pattern, improve with anti-asthma therapy.  Clinical Picture Other patients have persistent asthma with chronic wheeze and breathlessness. This pattern is more common intrinsic asthma. Common triggers for asthmatic symptoms include exposure to allergens (pets, dust mites, cockroach, molds, and pollens), exercise, change in weather (cold and dry weather, high humidity) viral infections, Tobacco smoke and emotions.  Asthma Diagnosis Diagnosis of asthma depends on: ❖ History and pattern of symptoms and physical examination ❖ Physiological assessment: Pulmonary function tests: Obstructive pattern during the attack, normal in between attacks (except in moderate & severe persistent asthma). Skin Prick test: to assess the allergic status  Asthma Diagnosis ❖ Laboratory tests: Peripheral blood eosinophilia >4% and Sputum eosinophilia Serum IgE increased ❖ ABG measurement : for staging acute severe attack ❖ Chest X-ray is normal in bronchial asthma except during an acute attack, there will be hyperinflation or complications as pneumothorax, and atelectasis due to mucous plugs. ECG: arrythmia,  Bronchial asthma during Normal chest X ray attack  Differential Diagnosis “Not every wheezer is asthmatic” 1. COPD & other obstructive AW diseases (FB, tumour, LNs,....) 2. Bronchitis 3. Bronchopneumonia 4. GERD 5. congestive heart failure Levels of asthma symptoms control  Treatment Goals of treatment: Achieve and maintain control of symptoms Prevent asthma exacerbations Maintain pulmonary function as close to normal levels as possible Maintain normal activity levels, including exercise Avoid adverse effects from asthma medications. Prevent development of irreversible limitation and prevent mortality  Treatment Components of asthma treatment: 1. Patient and family education 2. Assessment and monitoring of asthma severity with both symptom reports and measurement of lung functions 3. Environment control and avoidance of risk factors (triggers) 4. Establish individual medication plan for long-term management 5. Establish individual plans for managing exacerbations. 6. Provide regular follow-up care. MEDICATIONS USED FOR ASTHMA TREATMENT ARE CLASSIFIED AS EITHER RELIEVERS OR CONTROLLERS. I- Relievers: II. Controllers II. Controllers  Immunomodulators therapy for bronchial asthma: Immunomodulators are used for the management of severe asthma refractory to a high-dose inhaled corticosteroids with a long-acting beta2-adrenergic receptor agonist, and primarily characterized by elevated allergic inflammation biomarkers (serum IgE, blood eosinophil count). Immunomodulators include: Omalizumab, an anti-IgE antibody Antibodies to IL-5 (benralizumab, mepolizumab, reslizumab) A monoclonal antibody that blocks IL-4 receptor-alpha to inhibit IL-4 and IL-13 signaling (dupilumab). Inhaled corticosteroids  Simplified approach to initial asthma Therapy: Intermittent asthma (step 1): Low dose ICS- formaterol combination inhaler as needed or SABA (short acting beta agonists) as needed. Mild persistent asthma (step 2): Low dose ICS - formaterol combination inhaler as needed or low dose ICS daily and a separate SABA as reliever. NB: there is no distinction between mild intermittent and mild persistent asthma, inhaled corticosteroid (ICS) containing therapies are recommended for both. ICSformoterol is recommended as the preferred reliever inhaler  Simplified approach to initial asthma Therapy: Moderate persistent asthma (step 3): Low dose ICS- formoterol combination inhaler as maintenance and reliever therapy or Low dose ICS-LABA (long acting beta agonist) combination inhaler daily and separate SABA as reliever. Severe persistent asthma (step 4): Medium dose ICS-formoterol combination inhaler as a maintenance and reliever therapy or Medium dose ICS-LABA combination inhaler daily and separate SABA as reliever. Severe persistent asthma (step 5): Uncontrolled patients at step 4, high dose ICSformoterol (LABA) combination inhaler, add long acting anti-muscarinic agent (LAMA). Biologics are considered for uncontrolled patients with moderate-to-severe asthma based on phenotype.  Acute severe asthma ‘StatusAsthmaticus’ was defined as asthma that had failed to resolve with therapy in 24 hours. Thisterm has now been discarded and replaced by ‘acute severe asthma’, i.e. severe asthma that has not been controlled by the patient’s use of medication. Clinical picture (Signs of severe asthma): - Inability to complete a sentence in one breath - Respiratory rate > 25 breaths per minute - Tachycardia > 110 beats /min. Marked decrease air entry by auscultation  Acute severe asthma Features of life threatening attacks: - Silent chest (no air entry by auscultation) - Cyanosis or feeble respiratory effort - Exhaustion, confusion or coma - Bradycardia or hypotension Features suggesting very severe life-threatening attacks are: a. High PaCO2 > 45 mmHg b. Severe hypoxaemia PaO2 < 60 mmHg despite treatment with oxygen c. Low and falling arterial PH.  Acute severe asthma Investigations: - Arterial blood gases -Plain X-ray chest to detect pneumothorax or shadows (pneumonias or allergic broncho-pulmonary aspergillosis {ABPA}) - Blood and sputum eosinophilia and serum electrolytes. Treatment of acute severe asthma  Treatment of acute severe asthma Arterial blood gases is measured and if the PaCo2 is >52 mmHg, ventilation should be considered. Hospital stay for 5 days since the majority of sudden death occurs 2-5 days after admission. Further reduction of prednisolone dose should be gradual on an outpatient basis until an appropriate maintenance dose or substitution by inhaled corticosteroids can be achieved.  Chronic obstructive pulmonary disease Emphysema and chronic bronchitis are two conditions that make up COPD. Common preventable and treatable disease Characterized by persistent and progressive airflow limitation Associatedwith an enhanced chronic inflammatory response in the airways to noxious particles or gases. Exacerbations and comorbidities contribute to the severity of the disease.  1. Chronic Bronchitis Definition: A condition characterized by excessive mucous secretion from the bronchial tree, in which there is productive cough every day, or most days, for at least 3 months of the year, for at least 2 successive years when other causes as bronchiectasis and TB are excluded. Chronic Bronchitis Pathology : Excessive mucus secretion due to increase in the size and number of mucus secreting glands. Increased ratio of mucus glands to wall thickness (Reid index). Normal 40%, but in COPD, up to 70%. 2. Emphysema Definition: A pathologic term indicating abnormal permanent enlargement of the air spaces distal to the terminal bronchioles with destruction of the alveolar walls without obvious fibrosis. Emphysema Pathology: Enlargement of the air spaces distal to the terminal bronchioles destruction of the alveolar walls. Terminal respiratory unit Classification of emphysema The site of destruction within the acinus (terminal respiratory unit) is the basis for classification of emphysema 1- Centriacinar or centrilobular emphysema: Thistype involves the central part of the acinus and is associated with cigarette smoke and chronic bronchitis. 2-Panacinar or panlobular emphysema: Involvesall the acinus uniformly and is seen in patients with alpha 1- antitrypsin (AAT) deficiency. Etiology of COPD: 1- Smoking (it is the most important risk factor): - The most commonly encountered risk factor for COPD. - Role of smoking in development of COPD: a. Mucosal gland hypertrophy with increased mucus secretion b. Inhibitory effect of cigarette smoke on bronchial cilia leading to mucus accumulation. c. Respiratory infections are more frequent and severe in smokers than among non-smokers. d. Cigarettes contain many free oxygen radicals resulting in oxidative stress to the lungs. Etiology of COPD: 2- Air pollution by burning of biomass fuels. Dusty occupations: as coal and gold miners, farmers, & cotton. 3- Gender: Males are affected more than females (due to smoking).Not any more. 4- Genetic factors: homozygous α 1- antitrypsin deficiency is the most common genetic factor. 5- Recurrent bronchopulmonary infections in early childhood Clinical Features: 3 extremes of the clinical spectrum of COPD are described: 1- Chronic bronchitis which may progress to centri-acinar emphysema 2-Centriacinar emphysema or type B-COPD or the bronchitic type of COPD or Blue Bloaters. 3- Panacinar emphysema or type A-COPD or the emphysematous type of COPD or Pink Puffers Sometimes, the term emphysema is used to describe type A COPD and the term chronic bronchitis to describe type B COPD. Clinical picture : The patient is usually a male, chronic heavy cigarette smoker & above 50 years of age. I- Symptoms: 1. Prolonged history of chronic cough with mucoid or mucopurulent expectoration. Cough often presents only at first, later on cough occurs throughout the day (may be attributed by the patient to "smoker's cough"). 2. Dyspnea with wheezing. Dyspnea is gradual slowly progressive over years occurring initially on exertion but later at rest. Wheezing is usually persistent or continuous (not in attacks as bronchial asthma). Clinical picture :. Chest pain may occur due to: - Chronic cough causing strain of intercostal muscles. - Rupture of emphysematous bullae causing pneumothorax. - Complicating pneumonia causing pleurisy. 4. Manifestations of respiratory failure occur in advanced conditions 5. Oedema of lower limbs may occur due to cor pulmonale, or less commonly due to salt and water retention or DVT. 6. Symptoms of complications as weight loss, muscle wasting Clinical picture : II- Signs: Chest examination: Manifestations of hyperinflation: 1- Inspection: - Increased antero-posterior diameter. Barrel chest if - Horizontal ribs. - Wide intercosal spaces. - Wide subcostal angle. - Kyphoscoliosis Clinical picture : II- Signs: -Bilateral limitation of chest expansion. - Costal margin retraction on inspiration (Hoover's sign). - Weak or absent cardiac pulsations. 2- Palpation - TVF is decreased bilaterally. Clinical picture : II- Signs: 3- Percussion : Hyperresonance with encroachment on cardiac & hepatic dullness. 4- Auscultation: - Diminished air entry - Generalized wheezes (rhonchi). - Inspiratory crepitations due to excess mucus Signs of respiratory failure : Central cyanosis. -Drowsiness & hypersomnia (CO2 narcosis). Asterixis (flapping tremors). Increased intracranial tension & papilloedema. Coma occurs terminally. Complications 1. Repeated chest infections: increased susceptibility to bronchiectasis. 2. Respiratory failure with hypoxia (PaO, < 60 mmHg) and hypercapnea (PaCO,> 55 mmHg). 3. Cor pulmonale: pulmonary hypertension, right ventricular hypertrophy and eventually right sided heart failure. 4, Pneumothorax: due to rupture of emphysematous bulla. 5. Myocardial hypoxia can increase risk of ischemic heart disease and arrhythmia (AF) 6. Renal hypoxia can contribute to salt and water retention. Investigations: 1. Chest X-ray shows hyperinflation : Hyper-translucency of the lungs - Transverse ribs - Wide intercostal spaces. - Low flat diaphragm. -Heart shadow is elongated “ribbon- shaped heart". Investigations: 2. Respiratory function tests: A. Ventilation tests: 1. FEV1 & PEFR are decreased. 2. Forced vital capacity (FVC) is decreased Inspiratory capacity (IC) is suggested to be a more sensitive parameter than FEV 1 as it correlates better with air trapping. 3. Residual volume (RV) and total lung capacity (TLC) are increased 3. Arterial blood gases: decreased PO2, increased PCO2 & increased bicarbonate Investigations: 3. Sputum culture & sensitivity: may detect organisms especially pneumococci & H. influenzae. 4- Blood picture: may show erythrocytosis. 5. Estimation of serum alpha-l-antitrypsin: decreased in cases of primary emphysema, 6. CT chest: the best method to detect severity of emphysema. Treatment I- Smoking Cessation & vaccination. 1)Cessation of smoking: Persuading the patient to stop smoking to slow down the rate of deterioration and prolong the time before disability and death occur. 2) Vaccination: - Annual influenza vaccination is recommended in all patients with COPD. III- Drug Therapy (1) Bronchodilators: (a) Short-acting bronchodilators: - Short-acting beta agonists e.g. salbutamol (inhaled or nebulized). - Short-acting anti-cholinergic e.g. ipratropium bromide (inhaled , nebulized). - They can be given as needed to relief patient symptoms. Action: block the bronchoconstrictor effects of acetylcholine on M3 muscarinic receptors expressed in airway smooth muscle. III- Drug Therapy (b) Long-acting bronchodilators: -Long-acting beta agonists (e.g. salmeterol and formoterol) are given twice daily by inhalation (aerosol or powder forms). -Long acting anticholinergic agents (tiotropium bromide) is given once daily 18 ug dry powder formula. Side effects of beta agonists: sinustachycardia and potential to precipitate arrhythmia in susceptible patients. Exaggerated somatic tremor III- Drug Therapy © Anticholinergic bronchodilators: - interrupt vagal-induced bronchoconstriction. - Ipratropium bromide is an inhaled quaternary ammonium that blocks all three muscarinic receptors (Ml, M2, M3). - Tiotropium bromide, another quaternary ammonium, predominantly blocks the M1 and M3 receptors. – - It reduces the frequency of exacerbations and hospitalizations, and improves dyspnea when compared with long-acting beta-agonists III- Drug Therapy (d) Methylxanthines: in stable COPD caused significant bronchodilation (2) Corticosteroids: anti-inflammatory agent - Inhaled corticosteroids (ICS) are of less benefit in COPD than in asthma. ICS therapy is not recommended as monotherapy for patients with stable COPD, should be used with long-acting bronchodilator. - ICS reduce the frequency and severity of exacerbation. They are recommended in patients with severe COPD (FEV1 Short courses of oral steroids are considered in patients with severe exacerbations III- Drug Therapy (3) Antibiotics: Antibiotics are used In moderate or severe exacerbation, which is defined as having at least two of these three symptoms increased dyspnea, increased sputum volume, or increased sputum purulence. – Azithromycin (250 mg/day or 500 mg three times per week) or erythromycin (250 mg two times per day) for one year in patients prone to exacerbations reduced the risk of exacerbations compared to usual care.  (4) Phosphodiesterase-4 inhibitors: act by inhibiting the breakdown of intracellular cyclic AMP and thus reduce inflammation. Roflumilast is a PDE4 inhibitor used for patients with severe disease (5) Mucoregulator agents: e.g. N-acetyl cysteine. They may reduce exacerbations. serve also as antioxidant. (6)Alpha 1 Antitrypsin replacement: - Weekly or monthly infusions is indicated in patient with serum levels < 310 mg/L and abnormal lung function. IV) Non-pharmacologic Therapy (1) Rehabilitation: It involves: a) Exercise training (bicycle ergometry-treadmill exercise-timed walking distance). b) Nutrition counseling. Both over-and under-weight c) Education: an essential component of rehabilitation and help patient to quit smoking and comply to medication and rehabilitation programs. IV) Non-pharmacologic Therapy (2) Oxygen Therapy: - In patients with severe resting chronic hypoxemia, long-term oxygen therapy improves survival. - Use oxygen should target a pulse oxygen saturation (SpO.) of 88 to 92 percent or an arterial oxygen tension (PaO2) of approximately 60 to 70 mmHg without unacceptable rise in PaCO2, V- Surgical treatments: a) Bullectomy: removing a large bulla that does not contribute to gas exchange, so that the adjacent lung parenchyma is decompressed. b) b) Lung volume reduction surgery (LVRS): parts of the lungs are resected to reduce hyperinflation. This will provide more room for breathing and improve mechanical efficiency of respiratory muscles. c) c) Lung transplantation: in selected patients with very advanced COPD (FEV, < 30%, PaO, < 60 mmHg, PaCO,> 50 mmHg and pulmonary hypertension). Acute exacerbation of COPD (type II respiratory failure) Acute exacerbation is characterized by an increase in symptoms and deterioration of lung functions. - They are triggered by chest infection or change in air quality. - They may be accompanied by the development of respiratory failure represent an important cause of death. Treatment: At home: increased bronchodilators therapy, a short course of oral corticosteroids and antibiotics. At hospital; indications: presence of cyanosis, peripheral edema or change of conscious level Treatment I- Oxygen therapy: in type II respiratory failure PaCo2 is elevated and the patient is dependent on hypoxic drive. Consequently, giving additional oxygen may cause respiratory depression, with a further rise in PaCo2 and worsening acidosis. Oxygen is delivered by: I.Fixed performance mask (Venturi mask) which allow administration of oxygen to spontaneously breathing patients. Oxygen is administered at a concentration of 24% or 28%. 2. Non invasive ventilation (NIV) using tight fitting facial masks to deliver bilevel positive airway pressure ventilatory support (BiPAP). NIV is save and effective in patients with an acute exacerbation of COPD complicated by mild to moderate respiratory acidosis and should be considered early in the course of respiratory failure to reduce the need for endotracheal intubation. 3. Assisted ventilation with an endotracheal tube (continuous positive airway pressure (CPAP) is used with severe respiratory failure, when there is a definite reversible precipitating factor and the overall prognosis is reasonable.