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  1. Bronchial Asthma Lecturer Pavlova J.M.
  3. Normal lung
  4.  The right and left main bronchi divide into lobar bronchi.  The lobar bronchi divide into tertiary/segmental bronchi, each of which supplies a bronchopulmonary segment.  The segmental bronchi divide into primary bronchioles which divide into terminal bronchioles and then divide into respiratory bronchioles, which go on to divide into alveolar ducts.  Each alveolar duct divides into five or six alveolar sacs.  The alveolar sacs are made up of alveoli. The alveolus is the basic anatomical unit of gas exchange in the lung.  Beyond terminal bronchiole gas exchange occurs  The distal airspaces are kept open by elastic tension in alveolar walls
  5. Function of lungs • Gas exchange (O2, CO2) – Depends on compliance (stretchability) of lungs – Can only occur in alveoli that are both ventilated and perfused
  6. Spirometer  is an equipments used for measuring the volume of air inspired and expired by the lungs ( Pulmonary Function Tests)
  7. Spirometry (pulmonary physiology) • Forced expiratory volume (FEV1): volume of air blown out forcibly in 1 second. A function of large airways. Dependent on body size. • Vital capacity (VC): total volume of expired air. • Diffusing capacity or Transfer factor of the lung for carbon monoxide (DLCO or TLCO): absorption of carbon monoxide in one breath (gas exchange). It is dependent on the concentration of blood haemoglobin, which has a strong affinity for CO and it assesses the ability of the lungs to exchange gas efficiently.
  8. Definition • According to the modern view, BA of any severity is a chronic inflammatory disease accompanied by hyper-responsiveness and hypersensitivity of the bronchi. • Clinical manifestations of the disease include periodical expiratory or mixed dispnea (asphyxia) due to obstruction of the airways caused by constriction of the bronchi, excessive mucus secretion, and pulmonary edema.
  9. • At least 300 million patients worldwide suffer from BA. • In 2019 asthma affected approximately 262 million people and caused approximately 461,000 death • In the Russian Federation, according to a recent epidemiological study, the prevalence of BA among adults is 6.9% , and among children and adolescents – about 10%
  10. ICD-10 J45 Asthma • J45.0 Predominantly allergic asthma • J45.1 Nonallergic asthma • J45.8 Mixed asthma • J45.9 Asthma, unspecified J46 Status asthmaticus
  11. • Asthma is a long-term inflammatory disease of the airways of the lungs. • It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. • Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. These may occur a few times a day or a few times per week. • Depending on the person, asthma symptoms may become worse at night or with exercise
  12. Hygiene hypothesis • The hygiene hypothesis attempts to explain the increased rates of asthma worldwide as a direct and unintended result of reduced exposure, during childhood, to non-pathogenic bacteria and viruses. It has been proposed that the reduced exposure to bacteria and viruses is due, in part, to increased cleanliness and decreased family size in modern societies. Exposure to bacterial endotoxin in early childhood may prevent the development of asthma, but exposure at an older age may provoke bronchoconstriction. Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets. • Use of antibiotics in early life has been linked to the development of asthma. Also, delivery via caesarean section is associated with an increased risk (estimated at 20–80%) of asthma – this increased risk is attributed to the lack of healthy bacterial colonization that the newborn would have acquired from passage through the birth canal. There is a link between asthma and the degree of affluence which may be related to the hygiene hypothesis as less affluent individuals often have more exposure to bacteria and viruses.
  13. Genetic • Family history is a risk factor for asthma, with many different genes being implicated. If one identical twin is affected, the probability of the other having the disease is approximately 25%. By the end of 2005, 25 genes had been associated with asthma in six or more separate populations, including GSTM1, IL10, CTLA-4, SPINK5, LTC4S, IL4R and ADAM33, among others.Many of these genes are related to the immune system or modulating inflammation. • Some genetic variants may only cause asthma when they are combined with specific environmental exposures. An example is a specific single nucleotide polymorphism in the CD14 region and exposure to endotoxin (a bacterial product). Endotoxin exposure can come from several environmental sources including tobacco smoke, dogs, and farms. Risk for asthma, then, is determined by both a person's genetics and the level of endotoxin exposure.
  14. Medical conditions • A triad of atopic eczema, allergic rhinitis and asthma is called atopy. The strongest risk factor for developing asthma is a history of atopic disease; with asthma occurring at a much greater rate in those who have either eczema or hay fever. Individuals with certain types of urticaria may also experience symptoms of asthma. • There is a correlation between obesity and the risk of asthma with both having increased in recent years. Several factors may be at play including decreased respiratory function due to a buildup of fat and the fact that adipose tissue leads to a pro-inflammatory state. • Beta blocker medications such as propranolol can trigger asthma in those who are susceptible. Cardioselective beta-blockers, however, appear safe in those with mild or moderate disease. Other medications that can cause problems in asthmatics are angiotensin-converting enzyme inhibitors, aspirin, and NSAIDs. Use of acid suppressing medication (proton pump inhibitors and H2 blockers) during pregnancy is associated with an increased risk of asthma in the child.
  15. • Different individuals react to various factors in different ways. Most individuals can develop severe exacerbation from a number of triggering agents. • Home factors that can lead to exacerbation of asthma include dust, animal dander (especially cat and dog hair), cockroach allergens and mold. Perfumes are a common cause of acute attacks in women and children. Both viral and bacterial infections of the upper respiratory tract can worsen the disease. Psychological stress may worsen symptoms – it is thought that stress alters the immune system and thus increases the airway inflammatory response to allergens and irritants. • Asthma exacerbations in school‐aged children peak in autumn, shortly after children return to school. This might reflect a combination of factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance.
  16. Factors affecting the development and manifestations of BA Domestic factors • Genetic predisposition to atopy • Genetic predisposition to bronchial hyperactivity • Gender (in childhood, BA develops more often in boys; in adolescence and adulthood-in women) • Obesity
  17. Factors affecting the development and manifestations of BA Environmental factors • Allergens: house dust mites, pet allergens, cockroach allergens, fungal allergens, plant pollen, fungal allergens • Infectious agents (mainly viral) • Professional factors • Aeropollutants: ozone, sulfur and nitrogen dioxides, diesel fuel combustion products, tobacco smoke (active and passive smoking) • Diet: increased consumption of highly processed foods, increased intake of omega-6polyunsaturated fatty acid and reduced intake of antioxidants (in the form of fruits and vegetables) and omega-3polyunsaturated fatty acid (as part of fatty acids varieties of fish)
  18. Pathogenesis • Asthma is the result of chronic inflammation of the conducting zone of the airways (most especially the bronchi and bronchioles), which subsequently results in increased contractability of the surrounding smooth muscles. • This among other factors leads to bouts of narrowing of the airway and the classic symptoms of wheezing. • The narrowing is typically reversible with or without treatment.
  19. • Other cell types involved include: T lymphocytes, macrophages, and neutrophils. There may also be involvement of other components of the immune system including: cytokines, chemokines, histamine, and leukotrienes among others.
  20. • Typical changes in the airways include an increase in eosinophils and thickening of the lamina reticularis. • Chronically the airways' smooth muscle may increase in size along with an increase in the numbers of mucous glands. Obstruction of the lumen of a bronchiole by mucoid exudate, goblet cell metaplasia, and epithelial basement membrane thickening in a person with asthma.
  21. BRONCHIAL ASTHMA • It is a triad of: 1. intermittent and reversible airway obstruction 2. chronic bronchial inflammation with eosinophils 3. bronchial smooth muscle cell hypertrophy and hyper- reactivity • Primarily targets the bronchi and terminal bronchioles • Most common chronic respiratory disease in children. • More common in children than adults
  22. Pathogenesis of Bronchial Asthma complex and involves the following components: 1. Chronic airway inflammation 2. Intermittent airflow obstruction. Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling 3. Bronchial hyper-responsiveness causes exaggerated bronchoconstriction. The degree of airway hyper-responsiveness generally correlates with the clinical severity of asthma.
  23. Pathogenesis of Bronchial Asthma Principal cells in asthma: mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes (TH2 subset) and neutrophils. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines The pathogenetic mechanisms have been best studied in atopic asthma
  24. Classification of BA by severity Mild Intermittent Mild Persistent Moderate Persistent Severe Persistent Daily symptoms Symptoms < 1 times a week or asymptomatic between exacerbations Symptoms > 1 times a week but <1 time a day Daily use of inhaled short- acting beta2-agonists. Continual symptoms. Limited physical activity Nighttime Symptoms ≤ 2 times a month > 2 times a month > 1 time a week Frequent Asthma flare-ups (exacerbations) short periods Exacerbations affect activity. Lung Function PEF ≥80% predicted, PEF variability <20% PEF ≥80% predicted PEF variability 20-30% PEF >60%-<80% predicted PEF variability >30% PEF ≤60% predicted PEF variability >30% Peak expiratory flow (PEF)
  25. Clinical Evaluation of the Patient History • Common respiratory symptoms in asthma include wheezing, dyspnea, and cough. • These symptoms often vary widely within a particular individual, and they can change spontaneously or with age, season of the year, and treatment. • Symptoms may be worse at night, and nocturnal awakenings are an indicator of inadequate asthma control.
  26. • The classical description of bronchial asthma was given in 1838 by G. I. Sokolsky. • An attack of allergic asthma begins abruptly and acutely and usually quickly subsides. • Attacks of dyspnea developing against the background of chronic infectious diseases of the respiratory ducts (infectious-allergic asthma) are often not severe but protracted. • Attacks of dyspnea in bronchial asthma are quite similar; they arise suddenly, gradually increase in strength, and last from a few minutes to several hours and even several days. • A prolonged attack of asthma is called status asthmaticus. • Patients with uncomplicated bronchial asthma have no complaints in the periods clear of attacks.
  27. Complaints and history • Typical complaints of patients are paroxysmal attacks of expiratory dyspnea and cough especially after previous contact with allergens or irritants. • Attacks of asthma can be provoked by various odours, by some foods and medicinal preparations. • An attack of asthma can sometimes be provoked not by the allergen itself but by memory of it or by remembrance of the conditions under which the allergen acted in the past. • Endogenic allergens causing attacks of asthma include microbial antigens that are formed during various inflammatory processes, such as sinusitis, chronic bronchitis, chronic pneumonia, etc. • Products of decomposition of microbes and tissue proteins forming due to proteolytic process at the inflammatory focus (especially in chronic infections of upper airways) can act as allergens.
  28. Symptoms ■ Cough with or without sputum (phlegm) production ■ Pulling in of the skin between the ribs when breathing (intercostal retractions) ■ Shortness of breath that gets worse with exercise or activity ■ Wheezing Emergency symptoms that need prompt medical help: ■ Bluish color to the lips and face ■ Decreased level of alertness, such as severe drowsiness or confusion, during an asthma attack ■ Extreme difficulty breathing ■ Rapid pulse ■ Severe anxiety due to shortness of breath ■ Sweating Other symptoms that may occur: ■ Abnormal breathing pattern --breathing out takes more than twice as long as breathing in ■ Breathing temporarily stops ■ Chest pain ■ Tightness in the chest
  29. Physical Examination • It is important to assess for signs of respiratory distress, including tachypnea, use of accessory respiratory muscles, and cyanosis. • On lung examination, there may be wheezing and rhonchi throughout the chest, typically more prominent in expiration than inspiration. Localized wheezing may indicate an endobronchial lesion. • Evidence of allergic nasal, sinus, or skin disease should be assessed. • When asthma is adequately controlled, the physical examination may be normal. Signs of chronic bronchitis, pneumosclerosis, and lung emphysema can be revealed in such patients in periods clear of paroxysms.
  30. Survey • During such an attack, the patient has to assume a forced position; he usually sits in bed, leans against his laps, his breath is loud, often whistling and noisy, the mouth is open, the nostrils flare out. • The veins of the neck become swollen during expiration and return to norm during inspiration. • At the peak of an attack, the patient begins coughing with poorly expectorated thick and tenacious sputum. • The chest expands during an attack (to the size of the chest during inspiration due to acute emphysema). • Accessory respiratory muscles are actively involved in the respiratory act.
  31. Clinical finding • Percussion of the lungs gives the bandbox sound, the lower borders of the lungs are below normal, mobility of the lower borders is sharply limited during both inspiration and expiration. The borders of complete dullness of the heart cannot be determined because of the acute inflation of the lungs. • Auscultation reveals many whistling rales against the background of weakened vesicular respiration with a markedly prolonged expiration. The whistling rales are sometimes heard even at a distance. • Tachycardia is usually observed. • By the moment the attack reduced the sputum thins and expectoration becomes easier: high and dry rales in the lungs determined by auscultation decrease to give ways to low buzzing and often moist nonconsonant rales of various calibers; the attack of dyspnea gradually abates.
  32. • X-ray examination during an attack of asthma shows high translucency of the lung fields and limited mobility of the diaphragm. Hyperinflated lung
  33. Sputum analysis may reveal 40% to 60 %of eosinophils and often Curschmann spirals (casts of the distal airways) and Charcot-Leyden crystals. Coiled, basophilic plugs of mucus formed in the lower airways and found in sputum and tracheal Eosinophilic needle-shaped crystalline structures.
  34. Tests to measure lung function ■ Spirometry. This test estimates the narrowing of the bronchial tubes by checking how much air the patient can exhale after a deep breath and how fast he can breathe out. ■ Peak flow. A peak flow meter is a simple device that measures how hard you can breathe out. Lower than usual peak flow readings are a sign the lungs may not be working as well and that the asthma may be getting worse.
  35. • Spirometry detects FEV1 or PEF > 80% predicted, PEF variability 20–30%. • The level of bronchial obstruction increases during provocative inhalation tests (allergens, irritants, histamine, acetylcholine) and decreases after β- adrenergic agonist inhalation.
  36. Additional tests ■ Methacholine challenge. Methacholine is a known asthma trigger that, when inhaled, will cause mild constriction of the airways. If the patient reacts to the methacholine, he likely has asthma. This test may be used even if your initial lung function test is normal. ■ Imaging tests. A chest X-ray and high-resolution computerized tomography (CT) scan of the lungs and nose cavities (sinuses) can identify any structural abnormalities or diseases (such as infection) that can cause or aggravate breathing problems.
  37. Additional tests ■ Allergy testing. This can be performed by a skin test or blood test. Allergy tests can identify allergy to pets, dust, mold and pollen. If important allergy triggers are identified, this can lead to a recommendation for allergen immunotherapy. Positive wheel and flare reaction
  38. Additional tests ■ Provocative testing for exercise and cold- induced asthma. In these tests, the doctor measures the airway obstruction before and after the patient performs vigorous physical activity or take several breaths of cold air. ■ Common blood test during attacks detects moderate lymphocytosis and eosinophilia. ■ Physical, X-ray, and laboratory examinations may reveal no changes except eosinophilia of the blood at the periods clear of attacks.
  39. COMPLICATIONS OF ASTHMA  Airway remodeling: some persons with long standing asthma develop permanent structural changes in the airway with a progressive loss of lung function that increase airflow obstruction and airway responsiveness.  Superimposed infection i.e. pneumonia  Chronic bronchitis (i.e.Asthmatic bronchitis: chronic bronchitis with superimposed asthma)  Emphysema AND pneumothorax  Bronchiectasis  Respiratory failure requiring intubation in severe exacerbations i.e. status asthmaticus  In some cases cor pulmonale and heart failure develop.
  40. Some clinical variants of bronchial asthma • It has been divided into two basic types: 1. Extrinsic asthma. 2. Intrinsic asthma. • Sometimes extrinsic and intrinsic can co-exist in the same patient
  41. Extrinsic/ Allergic BA • It is also known as allergic, immune mediated, atopic or reaginic asthma. • Bronchospasm is induced by inhaled antigens, usually in children with a personal or family history of allergic disease (e.g., eczema, urticaria, or hay fever). • Atopic (allergic) asthma is the most common type and begins in childhood • Other allergic manifestation may be present: allergic rhinitis, urticaria, eczema. • Skin test with antigen is positive and results in an immediate wheel and flare reaction • Other family members are commonly also affected immune related with the involvement of TH2 subset of CD4+ T cells
  42. Allergic (extrinsic, occupational) bronchial asthma • - 2-15% of all asthmatics patients. • Respiratory symptoms, and variable airflow limitation and/or bronchial hyperresponsiveness due to exposure in a particular place separate from those outside the work/or living environment. • It should be considered in any case of adult-onset asthma or worsening asthma. • Allergic asthma characteristics are immediate and last phase allergic reactions; indoor, outdoor allergens, seasonal variation. It may be due to chemicals, metals, dusts, pollens, insects, proteins.
  43. Occupational bronchial asthma • Occupational bronchial asthma is related to industrial chemicals, animal plants and proteins. • Respiratory symptomes intensify when a worker returns from a weekend off or vacation. • It is very common with cotton dust endotoxin in byssinosis, also in sawdust, hemp, or any factory processing raw materials
  44. Nonallergic (intrinsic) bronchial asthma • Nonallergic (intrinsic) bronchial asthma is related to upper respiratory infection, purulent rhinitis, sinusitis, cold air, odors (tobacco smoke), perfumes, household cleaning agents, insecticides, fresh paint, air pollution, GERD (gastro-esophageal reflux disease).
  45. • Mixed bronchial asthma is combination of allergic and nonallergic bronchial asthma. • Exercise induced bronchial asthma: Contributing factors are hard exercise (>80% max heart rate for >6-8 min), cold air, low humidity (dry air), airborne particles (allergens, dust, irritants, auto exhaust, commercial pollutants like sulfur, dioxide, nitrogen dioxide, ozone). • Exacerbation of exercise induced bronchial asthma may be due to respiratory infections, fatigue, emotional stress, athletic overtraining (especially running > cycling >swimming)
  46. • Aspirin induced bronchial asthma is characterized by bronchial hypersensitivity and hyperresponsiveness to acetylsalicylic acid and to most of other non- steroid anti-inflammatory drugs (NSAID). • Aspirin triad (including acetylsalicylic acid sensitivity, chronic nasal polyps, asthma) is very typical. • Cough variant asthma are seen in 40% of those who present with isolated chronic nonproductive cough with normal chest X-ray. • These patients need in spirometry examination to precise the level of bronchial obstruction. Aspirin induced bronchial asthma
  47. Diagnosis • Diagnosis of bronchial asthma is based on clinical picture of paroxysmal syndrome of bronchial obstruction confirmed by data of spirometry demonstrating reversible airway obstruction. • Bronchial asthma should be considered in anyone who wheezes (whistling rales); it is the likeliest diagnosis when typical paroxysmal wheezing starts in childhood or early adulthood and is interspersed with asymptomatic intervals. • A family history of allergy or asthma can be elicited from most asthmatics.
  48. • The diagnosis of asthma is established by demonstrating reversible airway obstruction. Reversibility is traditionally defined as a 15% or greater increase in FEV1 after two puffs of a β-adrenergic agonist. • When the spirometry results are normal at presentation, the diagnosis can be made by showing heightened airway responsiveness to challenges with histamine, acetylcholine, or isocapnic hyperventilation of cold air. • Positive wheal-and-flare reactions to skin tests can be demonstrated to various allergens, but such findings do not necessarily correlate with the intrapulmonary events. • Sputum and blood eosinophilia and measurement of serum IgE levels are also helpful but are not specific for asthma. • Chest roentgenograms showing hyperinflation are also nondiagnostic.
  49. Management of asthma General principals: • The long-term goals of asthma management are risk reduction and symptom control • The aim is to reduce the burden of the patient and to reduce their risk of asthma-related death, exacerbations, airway damage and medication side-effect • Assessment of a patient with asthma includes not only symptom control, but also the patient’s individual risk factors and comorbidities • Medication:
  50. Medications for asthma treating 2 reliever choices across asthma severity • Track 1, with low dose inhaled corticosteroids (ICS) as the reliever, is the preferred approach • Track 2, with short-acting betta2-agonist (SABA) as the reliever, is an alternative approach
  51. Preferred therapy As needed low dose ICS or SABA Preferred therapy: Daily low dose ICS or as needed low dose ICS- SABA Other controller options: Daily leukotriene receptor antagonism (LTRA) Preferred therapy: low dose ICS-LABA Other controller options: medium dose ICS or low dose ICS+LTRA Preferred therapy: medium dose ICS- LABA Other controller options: high dose ICS, add-on tiotropium or add- on LTRA Preferred therapy: high dose ICS-LABA Refer for phenotypic assessment Other controller options: low dose OCS but consider side effect Symptoms less than twice a month Symptoms twice a month or more but less than daily Symptoms most days or waking with asthma once a week or more Symptoms most days or waking with asthma once a week or more or low lung function STEP 5
  52. Patient’s education Every patient should also be trained in essential skills and guided asthma self-management including: • Asthma information • Inhaler skills • Adherence • Written asthma action plan • Self-monitoring of symptoms and/or peak flow • Regular medical review
  53. Non-pharmacological treatment ■ Removal of allergens (especially pets with feathers or fur) ■ Structured patient education: improved self-management leading to better symptomatic control, reduction of the number of asthma attacks and emergency situations, improved quality of life, and improvement in various other parameters of disease course including days taken off from school or work and days spent in hospital ■ Physical training (reduction of asthma symptoms, improved exercise tolerance, improved quality of life, reduced morbidity) ■ Respiratory therapy and physiotherapy (e.g., breathing techniques, pursed-lip breathing) ■ Smoking cessation (with medical and non-medical aids, if necessary) ■ Psychosocial treatment approaches (family therapy) ■ For obese patients, weight loss