C hronic inflammatory disorder of the airways - PowerPoint Presentation

1.

2. Chronic inflammatory disorder of the airways which occurs in susceptible individuals; causing cough, wheeze, chest tightness and shortness of breath, often worse at night.Prevalence Asthma is increasing, particularly in the second decade of life This disease affects 10-15% of the population. The asthma being common in more developed countries,Asthma

3. AsthmaCharacteristics: Airflow limitation which is usually reversible spontaneously or with treatment. Airway hyper-responsiveness to a wide range of stimuli. Inflammation of the bronchi with eosinophils, T-lymphocytes and mast cells (associated with plasma exudation, oedema, marked smooth muscle hypertrophy, mucus plugging and epithelial damage).In chronic asthma, inflammation may be accompanied by irreversible airflow limitation

4. Classification of asthmaAsthma can be divided into: - Extrinsic - implying a definite external cause - Intrinsic or cryptogenic - when no causative agent can be identified. Extrinsic asthma - Occurs in atopic individuals who show positive skin-prick reactions to common inhalant allergens. - Positive skin-prick tests to inhalant allergens are shown in 90% of children and 50% of adults with persistent asthma.- Childhood asthma is often accompanied by eczema .- A cause of late-onset asthma in adults is sensitization to chemicals or biological products in the workplace.

5. Intrinsic asthma Develops in adulthood ('late onset'), with symptoms triggered by non-allergenic factors such as a viral infection, irritants which cause epithelial damage and mucosal inflammation, emotional upset &exercise.Show positive skin tests and may give a history of respiratory symptoms compatible with childhood asthma.Non-atopic individuals may develop asthma in middle age from extrinsic causes such as sensitization to occupational agents or aspirin intolerance, or because they were given β-adrenoceptor-blocking agents for concurrent hypertension or angina.Extrinsic causes must be considered in all cases of asthma and, where possible, avoided. Classification of asthma

6. Aetiology The two main causes of asthma symptoms are airway hyperresponsiveness and bronchoconstriction:Hyperresponsiveness is an increased tendency of the airway to react to stimuli or triggers to cause an asthma attack.Bronchoconstriction is a narrowing of the airways that causes airflow obstruction. A wide variety of non-specific direct and indirect stimuli: - Cold air and exercise - Diet - Emotion - Drugs Non-steroid anti-inflammatory drugs (NSAIDs) & Beta-blockers. Asthma

7. Allergen-induced asthma - Immediate asthma (early reaction) Airflow limitation begins within minutes of contact with the allergen, reaches its maximum in 15-20 minutes and subsides by 1 hour. - Dual and late-phase reactions Following an immediate reaction many asthmatics develop a more prolonged and sustained attack of airflow limitation that responds less well to inhalation of bronchodilator drugs such as salbutamol. Isolated late-phase reactions with no preceding immediate response can occur after the inhalation of some occupational sensitizers such as isocyanates. Asthma

8. Recurrent asthmatic reactions The development of the late-phase reaction is associated with an increase in the underlying level of airway hyper-responsiveness such that individuals may show continuing episodes of asthma on subsequent days. Asthma

9.

10. AsthmaPathogenesis - The pathogenesis of asthma is complex and not fully understood - It involves a number of cells, mediators, nerves and vascular leakage that can be activated by several different mechanisms, of which, exposure to allergens is among the most significant. - The varying clinical severity and chronicity of asthma is dependent on an interplay between airway inflammation and airway wall remodeling.

11. AsthmaInflammatory cell infiltration; sub-basement fibrosis, mucus hyper-secretion, epithelial injury, smooth muscle hypertrophy, angiogenesis .(The inflammatory component is driven by Th2-type T-lymphocytes which facilitate IgE synthesis through production of IL-4, and eosinophilic inflammation through IL-5)Remodeling of airways may occur; alteration of structure and functions of the formed elements of the airways.

12.

13. Clinical features of asthma The principal symptoms of asthma are wheezing attacks and episodic difficulty in breathing (dyspnoea)Symptoms are usually worst during the night. Cough is a frequent symptom that sometimes predominates and is often misdiagnosed as bronchitis. Nocturnal cough can be a presenting feature. There is a tremendous variation in the frequency and duration of the attacks. Some patients have only one or two attacks a year that last for a few hours, whilst others have attacks lasting for weeks. Some patients have chronic symptoms.Attacks may be precipitated by a wide range of triggers. Asthma cause impaired quality of life with impact on work, recreational, as well as physical activities and emotions.

14. AsthmaInvestigationsRespiratory function tests: Measurements of peak expiratory flow (PEF) on waking, prior to taking a bronchodilator and before bed after a bronchodilator. Asthma can be diagnosed by improvement of PEF following the inhalation of a bronchodilator.  The useful test for abnormalities in airway function is the forced expiratory volume (FEV).  The FEV1 is a measure of the FEV in the first second of exhalation (expressed as a percentage of the total volume of air exhaled) = Asthma can be diagnosed by demonstrating a greater than 15% improvement in FEV1

15. AsthmaThe forced vital capacity (FVC) can also be measured, which is an assessment of the maximum volume of air exhaled with maximum effort after maximum inspiration.  FEV1/FVC ratio. This ratio is a useful and highly reproducible measure of the capabilities of the lungs.  Normal individuals can exhale at least 70% of their total capacity in 1 s. In obstructive lung disorders, such as asthma, the FEV1 is usually decreased, the FVC normal or slightly reduced and the FEV1/FVC ratio decreased, usually <0.7.

16. AsthmaThe diurnal variation in PEF is a good measure of asthma activity. A diurnal variability of (more than 20%) is highly suggestive of asthmaTo assess possible occupational asthma, peak flows need to be measured for at least 2 weeks at work and 2 weeks off work.Spirometry is useful, especially in assessing reversibility.The carbon monoxide transfer test is normal in asthma.

17.

18. AsthmaExercise tests These have been widely used in the diagnosis of asthma in children. Alternative methods use cold air challenge, isocapnoeic hyperventilation (forced over-breathing with artificially maintained PaCO2) or aerosol challenge with hypertonic solutions. A negative test does not automatically rule out asthma. Blood and sputum tests Patients with asthma may have an increase in the number of eosinophils in peripheral blood (> 0.4 × 109 /L). The presence of large numbers of eosinophils in the sputum is a more useful diagnostic tool.

19. AsthmaChest X-ray A chest X-ray may be helpful in excluding a pneumothorax (abnormal collection of air or gas in the pleural space), which can occur as a complication, or in detecting the pulmonary shadows associated with allergic bronchopulmonary aspergillosis. Skin tests Skin-prick tests should be performed in all cases of asthma to help identify allergic causes. Allergen provocation tests Allergen challenge is used in cases of suspected occupational asthma. Another controversial exception is the investigation of food allergy causing asthma.

20. Treatment of asthmaThe aims of treatment are to: Abolish symptoms = a lack of day and nighttime symptomsRestore normal or best possible lung function Reduce the risk of severe attacks = asthma exacerbationsEnable normal growth to occur in children No need for rescue medication. Normal PEFsNo unwanted side effects from medication

21. AsthmaCommon therapeutic and practice problems encountered in the management of asthma are: Box 25.1 Reducing exposure to trigger risk factors may help to improve asthma control.Successful management of asthma requires a partnership between the patient and the health care provider.Aim to give patients the ability to control their asthma by supporting guided self-management.Individualized action plans improve health outcomes, particularly in moderate to severe disease.Increased use of reliever medication is a warning of deterioration of asthma control.

22. AsthmaAssessment of asthma control is essential when deciding to step up or step down treatment.At each treatment review, inhaler technique and adherence to treatment should be checked.The main treatments for exacerbations of asthma include repeated β2-agonists, early use of corticosteroids and oxygen to raise S aO2 above 92%.After exacerbations, patients should be reviewed early to identify possible triggers and review the action plan.

23. AsthmaChronic asthmaFour major classifications of asthma severity used primarily to initiate therapy:Intermittent: Symptoms ≤2 days/week, night-time awakenings ≤2/month, short-acting β-agonist use ≤2 days/week, no interference with normal activity, and normal FEV1 between exacerbations with FEV1 (predicted) >80% and FEV1/FVC >85%

24. AsthmaMild persistent: Symptoms >2 days/week but not daily, night-time awakenings 1–4/month, short-acting β-agonist use >2 days/week but not daily, minor limitations in normal activity, and FEV1 (predicted) >80% and FEV1/FVC >80% Moderate persistent: Daily symptoms, night-time awakenings 3–4/month or ≥1/week but not nightly, depending on age, daily use of short-acting β-agonist, some limitation in normal activity, and FEV1 (predicted) 60–80% and FEV1/FVC 75–80%

25. AsthmaSevere persistent: Symptoms throughout the day, night-time awakenings >1/week, short-acting β-agonist use several times a day, extremely limited normal activity, and FEV1 (predicted) <60% and FEV1/FVC <75%

26. AsthmaFig. 25.3 Summary of stepwise management in adults STEP 1: MILD INTERMITTENT ASTHMA STEP 2: REGULAR PREVENTER THERAPY STEP 3: ADD-ON THERAPY STEP 4: PERSISTENT POOR CONTROL STEP 5: CONTINUOUS OR FREQUENT USE OF ORAL STEROIDS

27.

28. AsthmaDrug treatmentThe stepwise treatment of asthma based on three principles: Asthma self-management with regular asthma monitoring using peak flow meters and individual treatment plans discussed with each patient and written down.The appreciation that asthma is an inflammatory disease and that anti-inflammatory (controller) ‘controllers’ or ‘preventers’ therapy should be started even in mild cases. Use of short-acting inhaled bronchodilators (e.g. salbutamol and terbutaline) only to relieve ‘Reliever’ breakthrough symptoms. Increased use of bronchodilator treatment to relieve increasing symptoms is an indication of deteriorating disease.

29. AsthmaThe mainstay of asthma therapy is the use of therapeutic agents delivered as aerosols or powders directly into the lungs. The advantages of this method :delivered direct to the lung (the first-pass metabolism is avoided), lower doses are necessary and systemic unwanted effects are minimized.Inhaled oral steroidsShort-acting relievers (salbutamol, terbutaline) Long-acting relief/disease controllers Long-acting β2 agonists - salmeterol, formoterol Sodium cromoglicate Leukotriene modifiers - montelukast, zafirlukast, pranlukast, zileuton

30. Other agents with bronchodilator activity Antimuscarinic agents (ipratropium, oxitropium) Theophylline preparations Steroid-sparing agents: (Immunosuppressive agents can be tried in an attempt to reduce a regular steroid dose).Methotrexate Ciclosporin Gold Anti-IgE monoclonal antibody - omalizumab Asthma

31. AsthmaReliever medicationShort-acting β-agonist bronchodilators (SABA):β-Adrenoceptor agonists Salbutamol and terbutaline are selective β2-agonists) are the mainstay of asthma management. An inhaled β2-agonist salbutamol 200 μcg when required is the first-line agent in the management of asthma. This may be the only treatment necessary for those with infrequent symptoms.

32. AsthmaAdditional bronchodilators may be required if the above therapy does not adequately control symptoms Inhaled anticholinergic agents. Ipratropium has a slower onset of action than β2-agonists but a longer duration of action. Anticholinergics may be helpful in patients who also have a degree of obstructive airways disease.

33. AsthmaLong acting β-agonist bronchodilators (LABA): When low-dose inhaled steroids fail to control asthma symptoms adequately at step 3, long-acting β2-agonists should be added instead of increasing the steroid dose. Symptom relief after a trial period, for example, 4-6 weeks, must then be assessed to see if the LABA has been effective and whether further treatment needs to be added to or existing treatment changed.

34. AsthmaIt is advised that LABAs should:only be added if regular use of standard-dose ICS has failed to control asthma adequately.not be initiated in patients with rapidly deteriorating asthma.be introduced at a low dose and the effect properly monitored before considering dose increase.be discontinued in the absence of benefit.be reviewed as appropriate; stepping down therapy should be considered when good long-term asthma control has been achieved.

35. AsthmaCombination ICS/LABA inhalers; formoterol and budesonide combination inhaler shows that this dosing method is an alternative at step 3 for adults who are: Poorly controlled on SABA and ICS, Have experienced one or more severe exacerbations in the previous 12 months.or as an alternative to increasing the ICS dose to above 2 mg/day at step 4.

36. AsthmaOral bronchodilators. Theophylline Oral bronchodilators can also be added, at steps 3–4 or β2-agonists tablets at step 4 Slow-release forms should be used, usually twice daily, although these can be used in a single night-time dose if nocturnal symptoms are troublesome.Theophylline should be started at a dose of 400–500 mg/ day in adults and, if required, increased after 7 days to 800–1000 mg/day.

37. AsthmaIn children, higher doses may be required but this will be determined by the age of the child.Theophylline has a narrow therapeutic index and its hepatic metabolism varies greatly between individuals. Theophylline clearance is affected by a variety of factors, including disease states and concurrent drug therapy.

38. AsthmaHigh-dose β2-agonists. High-dose β2-agonists are only considered if conventional doses do not achieve adequate symptom control. Nebulised drugs such as salbutamol 2.5–5 mg per dose are given. Terbutaline has been given by continuous subcutaneous infusion in the maintenance treatment of difficult to treat asthma.

39. AsthmaPreventer medicationAnti-inflammatory agents. Corticosteroids are the most commonly used anti-inflammatory agents for patients who are not controlled on a SABA alone, but others such as the cromones are available.Inhaled corticosteroids. ICSs are the initial drugs of choice, with a starting dose for an adult of beclometasone or budesonide 400 μcg/day (or an equivalent) given in divided doses.

40. AsthmaConsidering ICS for patients with any of the following:• Exacerbations of asthma in the past 2 years• Using inhaled β2-agonists three times a week or more• Symptoms three times a week or more• Waking one night a week with symptoms

41. AsthmaIf symptoms persist, the ICS dose is increased stepwise accordingly. The ICS dose should be reduced, if possible, once symptoms and PEF rates have improved and stabilized. If a patient's asthma cannot be controlled, the dose can be increased to a maximum of 1.5–2 mg a day. All ICSs have dose-related side effects. Adrenal suppression occurs at around doses of >1500 μcg/day of beclometasone in adults. In children, doses of 400 μcg/day of beclometasone or more are associated with growth failure and adrenal suppression.

42. AsthmaCromones.Inhaled sodium cromoglicate and nedocromil sodium are less effective than corticosteroids in asthma.  Although rarely used, they may be possible alternatives if corticosteroids cannot be tolerated. 

43. AsthmaLeukotriene receptor antagonists.Two leukotriene receptor antagonists, montelukast and zafirlukast,. Leukotriene receptor antagonists are included in step 4 as add-on therapy for adult patients but are less effective than LABAs in controlling asthma when added to ICSs. If these agents are initiated, then a 4-6 week trial should be undertaken; if there is no improvement in control, the drug should be stopped. They seem to be of particular value in aspirin-induced asthma.

44. AsthmaAnti-IgE monoclonal antibodiesOmalizumab, is used for the treatment of severe persistent IgE-mediated asthma as add-on therapy to existing optimized therapy in adults and individuals over 12 years of age who have severe unstable disease Patient response should be measured, and omalizumab discontinued after 16 weeks if no adequate response is seen.

45. AsthmaOral corticosteroids. Oral corticosteroids should only be used, at step 5, if symptom control cannot be achieved with maximum doses of inhaled bronchodilators and steroids. They should be given as a single morning dose to minimize adrenal suppression. Alternate-day dosing produces fewer side effects but is less effective in controlling asthma. Short courses (of up to 3 weeks) of high-dose oral steroids, 40-50 mg daily, can be safely used during exacerbations of asthma.

46. AsthmaSteroid-sparing agents. Immunosuppressive agents can be tried in an attempt to reduce a regular steroid dose. Methotrexate, ciclosporin and gold have been tried with varying success. All have potentially toxic side effects and need to be closely monitored.

47. AsthmaAcute severe asthmaImmediate management. The immediate treatment should take place in the patient's home if it is moderate attack. Admission to hospital is considered: If PEF drops below 50% of predicted or normal.The patient cannot complete sentences in one breath or is too breathless to talk.If life-threatening features are present.

48. AsthmaA treatment protocol for management in hospital Oxygen is administered to achieve an oxygen saturation of 92% or more. β2-agonist is administered by metered dose inhaler (MDI) with a spacer attachment (4 puffs, then 2 puffs every 2 min until 10 mg, or symptom relief) Nebulisers are used because they permit a high dose (10–20 times the dose of a MDI) Patients undergoing an acute attack often have an inspiratory rate that is too low to use an MDI effectively.

49. AsthmaCorticosteroids are also given in the acute attack; oral prednisolone (40–50 mg daily, for 5 days). Intravenous hydrocortisone (100 mg) should only be required if the patient cannot take oral medication. This reduces and prevents the inflammation that causes oedema and hypersecretion of mucus and hence helps to relieve the resultant smooth muscle spasm.

50. AsthmaIf life-threatening features are present, such as cyanosis, bradycardia, confusion, exhaustion or unconsciousness; higher dose bronchodilators are used:Nebulised salbutamol 5 mg with ipratropium bromide 500 μcg, repeated after 15 min; continuous nebulisation of salbutamol at 5–10 mg/h. Intravenous aminophylline can be given with a bolus dose of 250 mg over 30 min, followed by a continuous infusion of 500 μcg/kg/h.

51. AsthmaThe bolus should be omitted if the patient is known to take oral theophylline or aminophylline. The choice between intravenous aminophylline and β2-agonist depends on concurrent therapy and side effect profiles. The dose of intravenous aminophylline used must also take into account recent theophylline therapy in addition to other factors

52. AsthmaIntravenous magnesium sulphate, 1.2–2 g as a 20-min infusion.Antibiotics are only indicated where there is evidence of a bacterial infection.

53. AsthmaOngoing management. As the patient responds to treatment, infusions can be stopped and other treatment changed or tailed off as described above. As improvement continues, an inhaled β2-agonist is substituted for the nebulised form and the oral corticosteroids stopped or reduced to a maintenance dose if clinically necessary.

54. AsthmaPatient care The correct use of drugs and the education of patients are the cornerstones of asthma management. There are three main steps in the education of the asthmatic patient.The patient should have an understanding of the action of each of the medicines they use.The appropriate choice of inhalation device(s) should be made and the patient educated to use them correctly.An individualized action (self-management) plan should be developed for each patient.

55.