Asthma

1. Asthma

2. Asthma is a chronic inflammatory disorder of airways. • The expression of asthma results of a complex interrelationship of genetic susceptibility & environmental influences. • Multiple factors that trigger bronchospasm, include: -allergens -emotions -environment(weather changes, smoke) -exercise -respiratory infections

7. Signs & Symptoms : • Chronic Asthma: - Shortness of breath/ dyspnea - Wheezing - Cough - Sputum - Chest tightness **Occur continuously or episodic.

8. Treatment recommendation of chronic asthma is based on its classification: * Mild intermittent * Mild persistent * Moderate persistent * Severe Persistent

9. 2. Acute Asthma: • Signs/symptoms are similar to chronic . • Additional S/S may also be present, i.e.: -Tachypnea -Tachycardia -Retractions -Cyanosis -Hypoxemia • Sudden onset occurs in :acute, exacerbations, status asthmaticus.

10. S/S may progress over hours, days, weeks before reaching functional deterioration. • Eosinophils in the airways indicates allergic component. • Typical triggers: * Allergens * Exercise * Psychological stress

11. 3. Exercise-Induced Bronchospasm: • Transient narrowing of airways after vigorous exercise. • Cold-dry air provokes EIB. • In EIB, a reduction of @ least 15% in FEV1 following exercise.

12. 4. Nocturnal Asthma: • In normal diurnal variation, the lung function reaches its peak @ 4 PM & reaches its minimum @ 4 AM. • Symptoms of dyspnea & cough may waken the patient requiring a bronchodilator treatment. • GERD, Obesity, & increased age are associated with nocturnal asthma. • Evaluation is important for treatment guidelines.

13. 5. PMS Asthma: • Asthma symptoms increase in days before & during menses in asthmatic patient by an unknown mechanism. • May be due to usual increase in Beta-2 receptor density during the Luteal phase of the menstrual cycle in non-asthmatic females which is absent in PMS asthma. • Treatment includes: -Hormones -Leukotriene antagonists -ICS -LABA

14. Diagnosis: - Based on : 1.Clinical History 2.PFTs ( Objective Measures ) -Recurrent Exacerbations may be provoked by: *Viral Resp. Infections *Psychological Factors *Allergens *Irritants (Dry powders, Chemicals,…) *Exercise *Hx of nocturnal Symptoms *Meds. ( ASA, NSAID,…) -Physical exam maybe normal.

15. Other allergic symptoms may be present with allergic (atopic) asthma, include: -Rhinitis -Sinusitis -Eczema -Blood eosinophilia -Sputum eosinophilia • Allergen exposure leads to: • Immediate (Early) asthmatic response (IAR): decreased PFT within minutes b. Late asthmatic response (LAR): 2nd decrease in PFT several hours of exposure.

16. Spirometry: • FEV1: - Most commonly used spirometric evaluation of pulm. function. - Volume of air expelled within 1st second of forced expiration after max. inhalation. • PEF: - Max. rate @ which air is exhaled from lungs with forced expiratory maneuver. - Correlates well with FEV1 - Accurate & obj. self-monitoring of pulm. functions by simple portable inexpensive peak flow-meter. Disadvantage: Dependent of patient effort.

17. Assessment of Allergy: • 60-78% of asthma in adults has allergic component. • Up to 93% of asthma in children has allergic component. * Allergen prick skin is the most commonly diagnostic test for atopy, & patient should take oral antihistamine before test. * Tx : Anti IgEMonoclonial Antibody.

18. Chest X-Ray: • Normal in mild disease. • Hyperinflation in severe chronic asthma. Therapeutic Plan: Treatment Guidelines: 4 Major Components of Asthma Management: 1.Use of objective measures to assess & monitor 2.Control factors contributing to severity. 3.Use of optimal pharmacological therapy. 4.Provide patient education & develop partnership in asthma care.

19. Goals of Asthma Management: • Maintain normal activity levels. • Maintain (near) normal PFTs. • Prevent chronic & troublesome symptoms. • Prevent recurrent exacerbation of asthma & min. need for emergency dept. visits or hospitalization. • Provide optimal pharmacotherapy with min. or no side effects. • Meet patients’ & families’ expectations of satisfaction with asthma care.

20. Recommended Use of Spirometry: • At the time of diagnosis (for pts. >5 y.o.) for assessing severity & reversibility. • Following initiation of treatment after S/S stabilize (effectiveness & response). 3. At least every 1-2 yrs. to monitor disease progression.

23. Long-Term Treatment: • Recommended treatment is based on : Persistence & Severity of symptoms. **Refer to Guidelines of Stepwise approach to Treatment of Chronic Asthma.

27. Only Mild intermittent (Step1) does not require long-term treatment. • All asthma patients should use SABA for acute symptoms. • Recommendation: All asthma patients should receive action plan for daily long-term meds. & for what to do in acute exacerbation of asthma.

28. Anti-inflammatory meds. esp. ICS are the cornerstone of long-term daily therapy for persistent asthma. • As monotherapy, ICS is > effective than cromoly, leuk. Modifiers, nedocromil, & theophylline. • Rescuers: SABA & systemic corticosteroids • Controllers: All others & oral corticosteroids

29. ICS : the only long-term controller shown to reduce risk of death from asthma. • Persistent asthma pts. should not use regular administration of SABA or LABA as long-term controller monotherapy. • ICS + LABA combination is more effective than doubling ICS dose. • If the pt. has hx of frequent severe exacerbations  increase ICS dose + LABA

30. 4 times increase in ICS dose may be required to produce significant reduction in asthma exacerbation. • Adding any one of the alternatives to ICS ( if pt. can not tolerate LABA ) is as effective as doubling the ICS dose.

31. Many prescribe severe persistent asthma pt. a 3rd long-term controller before starting oral corticosteroid. • Current Evidence does not support additional benefit from adding 3rd or 4th long-term controllers. • Patients with severe atopic (allergic) asthma & high IgE conc. could discontinue oral corticosteroid following Omalizomab therapy.

32. II. Acute Asthma: • All levels of severities are @ risk of acute exacerbation even if well-controlled on long-term controllers ( if exposed to specific triggers). • Fig. 34.5 p.889: Home Management of Acute Exacerbation. • Fig. 34.6 p. 891: Treating Acute Exacerbation of Asthma in E.R. or Hospital. • Table 35.4 p.894: Recommended Doses for Severe Acute Asthma

35. SABAs are the most effective quick relief (rescue) meds. • No advantage of nebulizer over MDI + spacer. • Parenteral SABA should NOT be used due to increased S/Es without increasing efficacy. • Short Acting AnticholinergicIpratropium Br. is used only for those: 1)intolerant to SABA or 2)not completely responding to usual doses of SABA in E.R., adding Ipratropium Br. to SABA reduces the risk of hospitalization.

36. Most asthma exacerb. pts. @ E.R. or clinic respond adequately to 1st 3 doses of SABA & can be discharged. • It is recommended that inadequate response to initial bronchdilators (SABA & Ach) should be started on systemic corticosteroid p.o. or I.V. (No advantage in efficacy of either one). • ICS is NOT as effective as systemic corticosteroid in severe acute asthma, but adding ICS to the usual short course systemic corticosteroid, prevents relapse following discharge from E.R.

37. Nondrug Management of Severe Acute Asthma: • Low flow O₂ therapy by nasal canulae to prevent hypoxemia. • Pulse oximetry • O₂ flow to mainaitn O₂ Saturation≥90%. • In very severe cases, ABGs are used to monitor pCO₂ if it is normal to increased after intensive therapy due to risk of resp. failure. • All pts. should measure their PEF after initial SABA.

38. Pediatric Treatment in Acute Asthma: • In acute severe asthma, treatment is similar to adults with dose differences. • As alternatives in pediatric treatment of chronic asthma, leuk.modifiers & cromolyn are safer than theophylline.

39. Pharmacotherapy: • Treatment includes providing optimal pharmacotherapy with min. or no ADRs. • Meds. for asthma:1. Bronchdilators &2. Anti-inflammatory *Rescuers/ “Quick- relief agents”: 1. SABA 2. Acholinergic 3. Short-term systemic corticosteroids * Controllers / “Long-term control agents”: Inhaled or oral corticosteroids, cromolyn, nedocromil, LABA, theoph., leukot. modifiers.

40. I. Bronchodilators: 1) Beta-2 adrenergic agonists: -Safest & most effective bronchodilators • SABA: - Albuterolb. LABA: - Salmeterol - Bitolterol - Formoterol - Metaproterenol - Pirbuterol - Terbutaline

41. Increasing the use of SABA can be a marker of poor asthma control, & ICS should be added or increased in dose. * Guidelines recommend SABA to be used as: 1) prn for intermittent symptoms. or 2) 1st line therapy for severe acute asthma. • In severe asthma, SABA is administered as: -MDI + spacer -Intermittent nebulizer -continuous nebulizer • There is NO difference in efficacy between the 3 methods. • I.V. SABA is NOT recommended • No difference was shown in the efficacy between cont. & intermittent SABA delivery for adults, however, ICU asthma children showed greater improvement with cont. nebulizer albuterol.

42. SABA : - The treatment of choice to prevent exercise-induced asthma (EIA). -Provides 4-hr duration when given just before exercise. • LABA: - Recommended for persistent asthma only in combination with ICS (NOT monotherapy). - Both LABAs are indicated for preventing EIA when used 15-30 min before long exercise. - In combination with ICS, LABA controls EIA for up to 12 hrs.

43. 2) Theophylline: -Bronchodilator & now weak anti-inflammatory. -Weak bronchodilator compared with beta2 agonists. -Administered p.o., I.V., or rectally. -Therapeutic range: 5-15ug/ml. * Addition of theophylline to optimal inhaled SABA + systemic corticosteroid in E.R. or hospital showed NO added benefit for acute severe asthma over optimal beta2 agonist + systemic corticosteroid alone.

44. I.V. theophylline: Reserved for those who fail to respond to high-dose inhaled SABA + systemic corticosteroid in severe acute asthma. • Role of theophylline in chronic asthma is reduced because: - New agents (LABA) - Its addition has similar efficacy as increasing the ICS dose. **Theophylline is reserved as a second line add-on treatment for chronic persistent asthma.

45. 3) Anticholinergics: • Ipratropium Bromide: -Short-Acting (4-8hrs) - Less bronchodilation than beta-2 agonists. • Guidelines recommend the use nebulizedIpratropium in combination with beta-2 agonists for the treatment of acute severe asthma in those who fail to respond to initial treatment with SABA. • Guidelines do NOT include anticholinergic therapy in the management of chronic asthma (more effective meds. available).

46. II. Anti-inflammatory Agents: • Cromolyn Na/ Nedocromil: • Not used for acute asthma. • Dosed 3 or 4 X daily. • Inhibit IAR & LAR • Prevent EIA (lesser extent than inhaled beta2 agonists) if used 15-30min. before exposure. • Clinical effects are seen within 1 wk. of starting therapy & 4 wks. are required to determine efficacy. • Guidelines recommend Cromolyn& Nedocromil as 2nd-line therapy only in mild persistent asthma in children & adults.

47. 2) Leukotriene Modifiers: (Newest Class): *(Zileuton:QID, Zafirlukast:BID, Montelukast:QD) *Reduce IAR & LAR. *All administered p.o. • Montelukast: Given @ bedtime to reach highest serum conc. during the night & early morning hours when symptoms tend to be worse. *Zafirlukast: Bioavailability sig. reduced w/ food. *Zileuton: Sig.DI profile& liver toxicity.

48. Montelukast: • Preferred because: 1) Once daily dosing. 2) Lack of drug & food interaction. 3) The only one approved for children as young as 1 y.o. *Montilukast + ICS has similar efficacy as doubling ICS dose.

49. Guidelines currently recommend Leukotriene Modifier : • As single drug therapy for mild-persistent asthma (step2) as alternative after therapy with ICS has been considered. 2) As 2nd line therapy in moderate-persistent asthma (step3) after LABA as add-on therapy to ICS. **Greatest advantage is the ORAL dosage form.

50. 3) Corticosteroids: • Most potent anti-inflammatory used in asthma treatment. A) ICS: • ICS : The most effective long-term control therapy for persistent asthma. • ICS use is assoc. w/ : 1. Reduced risk of hospit. & acute exacerbation. 2. Offers the only long-term control therapy assoc. w/ reduced risk of dying from asthma.