Asthma

1. Asthma John Noviasky, PharmD

2. Background • At least 15 million Americans have asthma • Cost $12 billion annually • Leading cause of lost school days and common cause of lost workdays

3. Etiology • Childhood asthma • usually associated with IgE response • Common presentation - allergy to tree/grass pollen, house dust mites, pets, molds and family history asthma • Adult asthma • adults presenting with asthma may have atopy but may not have family history and negative allergy tests. • May have nasal polyps, asa sensitivity, sinusitis

4. Etiology • Adult asthma • May have exposure to wood dusts, chemicals • Intrinsic Asthma • Extrinsic Asthma - Atopic asthma • Risk Factors - atopy, chemical sensitizer exposure, viral infections, small size at birth, exposure to tobacco, pollutants

5. Etiology • Hygiene Hypothesis • Imbalance of TH2/TH1 T lymphocytes • TH1 (protective immunity) activators- older siblings, exposure to day care, childhood infections • TH2 (produces cytokines that mediate allergic inflammation) - antibiotic use, urban environment, Western lifestyle - more likely to develop asthma

6. Pathophysiology • Complex interaction between inflammatory cells and mediators • Involves mast cells, eosinophils, T lymphocytes, neutrophils • TH2 cells release cytokines (IL4, IL5) that activate eosinophils • Table 23-1

7. Pathophysiology • Airway remodeling • structural changes, alteration in amount and composition of extracellular matrix in airway wall • Hyperreactivity • exaggerated response of bronchial smooth muscle to trigger stimuli • to physical, chemical, immunologic, and pharmacologic stimuli (e.g. allergens, RSV, cold air, dry smoke, pollutants)

8. Pathophysiology • Endogenous stimuli • rhinitis, sinusitis, GERD, premenstrual asthma • Primary Process in Bronchial hyperreactivity • Inflammation • Methacholine- can be used to measure hyperreactivity

9. Pathophysiology • Pathologic changes secondary to chronic inflammation • marked hypertrophy and hyperplasia of bronchial smooth muscle • mucus gland hypertrophy = excessive mucus secretion

10. Symptoms • Varied but can include • Intermittent episodes of expiratory wheezing, coughing and dyspnea • Severity of disease • occasional, mild bouts of breathlessness • daily wheeze in spite of multiple medications • may be triggered by environmental factors (e.g. seasonal allergens)

11. Symptom Classification • Figure 23-3 • Mild Intermittent • Mild Persistent • Moderate Persistent • Severe Persistent

12. Symptom Classification • Figure 23-3 • Mild Intermittent • Mild Persistent->2 times/week, >2 nights/month • Moderate Persistent • Severe Persistent • Frequency of symptoms is key component to asthma classification

13. Symptom Classification And Goals • Figure 23-3 • Mild Intermittent • Mild Persistent->2 times/week, >2 nights/month • Moderate Persistent • Severe Persistent • Frequency of symptoms is key component to asthma classification

14. Diagnosis-History • Based on intermittent symptoms of wheezing, chest tightness, shortness of breath, and coughing • May worsen seasonally-spring, fall • May worsen with exercise • Note any triggers • cats, perfume, tobacco • Family history

15. Pulmonary Function Tests-Spirometry • Pulmonary disease affects volume of inhaled and exhaled air • Tidal volume • volume of air inspired or expired during normal breathing • Vital capacity • volume of air blown off after maximal inspiration to full expiration

16. Pulmonary Function Tests-Spirometry • Residual volume (RV) • volume of air left in lung after maximal expiration • Total Lung capacity(TLC) • Vital capacity plus RV • Obstructive lung disease-difficulty with expiration • decreased VC, increased RV, normal TLC • Restrictive Lung Disease - • Decrease in all lung volumes

17. Pulmonary Function Tests-Spirometry • FEV • Patient exhales into spirometer as forcefully and completely as possible after maximal inspiration • FEV1 • is that volume of air exhaled in 1 second • Young adult male ~ 3-4L • FVC • Forced vital capacity - volume of air exhaled with maximal forced effort

18. Pulmonary Function Tests (PFTs)-Spirometry • FEV1:FVC ratio • Most reproducible of the PFTs • measures the dynamic performance of the lung in moving air • Healthy individuals can exhale 75-80% of VC in 1 second and almost all in 3 seconds • Normal ratio is 80% • Patients actual ratio is compared against “predicted” based on age, race, gender, height and weight

19. PFTs-Peak Expiratory Flow (PEF) • Maximal rate of flow that can be produced during forced expiration • Can use handheld Peak Flow (PF) Meters • Useful in ED, at home, at clinic • Changes in PF usually correlate with change in FEV1 • However, PEF is less reproducible than FEV1 • Healthy young adult has PEF - 550-700L/min

20. Obstructive versus Restrictive Airway Disease • Obstructive disease- limits airflow during expiration (e.g. bronchitis, asthma) • narrow air passages, create air turbulence and increase resistance to airflow • Restrictive disease - results from loss of elasticity (e.g. fibrosis, pneumonia) or physical deformity (kyphoscoliosis) which doesn’t allow lung expansion and reduces TLC

21. Reversible Airway Obstruction • FEV1 is gold standard for determining reversibility of airway disease and bronchodilator efficacy • Significant Clinical Reversibility • 12% improvement in FEV1 after administration of bronchodilator • 20% improvement in FEV1- noticeable subjective relief in most patients • IF patient with low FEV1 (e.g. <1L) improvement of 250ml may indicate benefit

22. Limitations of Spirometry • Patient cooperation • Can’t obtain in patients • severely ill, Too old, Too young • FEV1 and PEF relatively insensitive to small airway changes so may not detect mucus plugging and inflammation in small bronchioles

23. Blood Gas Measurments • Best indicators of overall lung function are arterial blood gases • PaO2, PaCO2, pH) • Oxygen saturation (O2 sat) • Quantity of O2 bound to Hg/ Quantity of O2 that could be bound to Hg • Normal O2 sat 97.5%

24. Peak Expiratory FlowPEF • Green - 80 to 100% of “personal best” • good control • Yellow - 50 to 79% of personal best • use 2 puffs of B-agonist and call for medication adjustments if doesn’t improve • Red - <50% of personal best • call provider if use of B-agonist doesn’t bring you to yellow or green • Crisis management plan

25. Final notes • Asthma consists of bronchospasm and inflammation • therapy should be directed at both • The most common cause of death from asthma is undertreatment • For most asthmatics, this condition can be well controlled

26. Section 1 • Asthma is an obstructive lung disease, this means that airflow is limited during inspiration or expiration? • Can increased wheezing occur during effective Asthma therapy? And why? • What might the coughing found in acute asthma attacks be due to? • What is atelectasis? Can it be mistaken for pneumonia?

27. Section 1 • What symptoms result from feeling of suffocation during asthma? • What is pulsus paradoxus?

28. Section 2 • What does a local decrease in breath sounds possibly indicate? • What is a disadvantage of PFT in acute asthma?

29. Section 3 • What is most predictive test for asthma attack in determining outcome?

30. Section 4 • What is first line of pharmacotherapy for acute asthma? • Why isn’t theophylline considered first-line? • Why isn’t ipratropium considered first-line? • Can ipratropium be added on to therapy?

31. Section 5 • Is the parenteral route for B-agonist administration more effective than inhaled route? • Why shouldn’t B-agonist be given orally?

32. Section 6 • In stable asthmatics, is there any advantage of nebulized versus metered-dose B-agonist? • What are some advantage of nebulized versus Metered dose inhaler?

33. Section 8 • What is the difference between B2 specific agonists (albuterol) compared to nonspecific agonists (isopreoternol)? • What is levalbuterol?

34. Section 9 • When should systemic corticosteroids be administered in asthma exacerbation? • Figure 23-17

35. Section 10 • What are some side effects from B-agonists? • Can Albuterol cause decrease serum potassium? Why? • What can we attribute tremor with use of B-agonist?

36. Section 11 • Can tolerance to side effects of B-agonists occur? • Does tolerance to airway response occur with B-agonist use? • With long term use, does the intensity of response vary? The duration of response? • What are possible cause for variability of response?

37. Section 12 • Do the NIH guidelines suggest addition of theophylline to acute management of asthma? Why or why not?

38. Section 14 • How do corticosteroids (CS) work in relieving bronchial obstruction? • How long do CS take to work? • Can CS hasten recovery of acute exacerbations of asthma? • Once begun, how long should CS be continued for?

39. Section 15 • Which is more effective to treat acute asthma • high dose corticosteroids (CS) e.g. methylprednisolone 125mg q6h Versus low-dose CS e.g. methylprednisolone 40mg q6h? • IV CS or oral CS? • When is methylprednisolone preferred over hydrocortisone?

40. Section 18 • IS IV albuterol superior to inhaled albuterol in severe asthma? • Is inhaled ipraptropium useful in asthma? • IS IV or inhaled magnesium useful in severely ill patients?

41. Section 19 • Which is more effective in increasing PEF, inhaled albuterol or IV aminophylline? • Does the addition of IV aminophylline produce a greater response than B2 agonist alone?

42. Section 25 • After an acute asthma attack, how long should systemic corticosteroids be continued for?

43. Section 26 • What adverse effects occur with steroids?

44. Section 27 • Deaths in the Spitzer study were likely due to______? • What do most experts prefer? As needed short acting B2 agonists or scheduled B2 agonists? • When the patient needs B2agonist more than ____, the anti-inflammatory should be increased.

45. Section 33 • Table 23-6 • At what dosage range is HPA suppression a concern? • Are there major differences between the various Inhaled corticosteroid (ICS)? • What is benefit to using a spacer with ICS? • Is there a link between prolonged high doses of ICS and cataracts and glaucoma? • Is there a concern with ICS and growth suppression in children?

46. Section 34 • When should Inhaled corticosteroids (ICS) be initiated in patient also on systemic corticosteroids? • Which dosage for ICS is preferred, twice-daily or four times daily? • Is administration of ICS once daily an option?

47. Section 35 • What is the most common local side effect with Inhaled corticosteroids (ICS)? • How can these be minimized/avoided?

48. Section 36 • Has the leukotriene antagonist (e.g. montelukast) been shown to decrease utilization of Inhaled corticosteroids (ICS)? • Are leukotriene antagonist mentioned in NIH guidelines?

49. Section 44 • Can emotional upset be a trigger for asthma? • Does inhaled anticholinergic (IAC) alter this response? • What considerations should be given to use of IAC rather than B2 agonist? • When can IAC be considered an alternative to B2 agonist?

50. Section 45 • What are main mechanism to causing exercise induced asthma (EIA)? • What is the agent of choice for prophylaxis of EIA? • If using long acting B2 agonist (formoterol/salmeterol) for EIA prophylaxis, what considerations should be given?