Asthma

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Asthma

  1. 1. BRONCHIALASTHMABRONCHIALASTHMA Dr. Usama Asad KhatriDr. Usama Asad Khatri
  2. 2. ObjectivesObjectives  At the end of the lecture students should beAt the end of the lecture students should be able to:able to:  ID signs and symptoms of asthmaID signs and symptoms of asthma  Differentiate the various severities of asthmaDifferentiate the various severities of asthma  Summarize an appropriate treatment regimen forSummarize an appropriate treatment regimen for asthma of various severities.asthma of various severities.
  3. 3. Definition of AsthmaDefinition of Asthma  Chronic inflammatory disorder of the airways inChronic inflammatory disorder of the airways in which many cells and cellular elements play awhich many cells and cellular elements play a role.role.  In susceptible individuals, this inflammationIn susceptible individuals, this inflammation causes recurrent episodes of wheezing,causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing,breathlessness, chest tightness, and coughing, particularly at night or in the early morning.particularly at night or in the early morning. These episodes are associated with widespreadThese episodes are associated with widespread but variable airflow obstruction that is reversiblebut variable airflow obstruction that is reversible either spontaneously, or with treatment.either spontaneously, or with treatment.
  4. 4. AsthmaAsthma  Most common chronic condition in childrenMost common chronic condition in children  #1 cause of school absenteeism#1 cause of school absenteeism  Morbidity and mortality highly correlated withMorbidity and mortality highly correlated with poverty, urban air quality, indoor allergens,poverty, urban air quality, indoor allergens, lack of patient education, and inadequatelack of patient education, and inadequate medical caremedical care  About 5000 deaths annuallyAbout 5000 deaths annually
  5. 5. AsthmaAsthma  Every day in the US, because of asthma:Every day in the US, because of asthma:  40,000 people miss school or work40,000 people miss school or work  30,000 people have an asthma attack30,000 people have an asthma attack  5,000 people visit the emergency room5,000 people visit the emergency room  1,000 people are admitted to the hospital1,000 people are admitted to the hospital  14 people die14 people die  (Asthma and Allergy Foundation of America)(Asthma and Allergy Foundation of America)
  6. 6. AsthmaAsthma  In 2000, 11 million peoples reported havingIn 2000, 11 million peoples reported having asthma attacksasthma attacks  In 1999, 2 million ER and 478,000In 1999, 2 million ER and 478,000 hospitalizations with asthma as the primary dxhospitalizations with asthma as the primary dx  Mortality in Black males 3X that of whiteMortality in Black males 3X that of white  Mortality in Black females 2.5X that of whiteMortality in Black females 2.5X that of white
  7. 7. AsthmaAsthma  Usually associated with airflow obstruction ofUsually associated with airflow obstruction of variable severity.variable severity.  Airflow obstruction is usually reversible,Airflow obstruction is usually reversible, either spontaneously, or with treatmenteither spontaneously, or with treatment  The inflammation associated with asthmaThe inflammation associated with asthma causes an increase in the baseline bronchialcauses an increase in the baseline bronchial hyper responsiveness to a variety of stimulihyper responsiveness to a variety of stimuli  Clinical DiagnosisClinical Diagnosis
  8. 8. Asthma TriggersAsthma Triggers  AllergensAllergens  Dust mites, mold spores, animal dander,Dust mites, mold spores, animal dander, cockroaches, pollen, indoor and outdoorcockroaches, pollen, indoor and outdoor pollutants, irritants (smoke, perfumes, cleaningpollutants, irritants (smoke, perfumes, cleaning agents)agents)  Pharmacologic agents (ASA, beta-blockers)Pharmacologic agents (ASA, beta-blockers)  Physical triggers (exercise, cold air, sulfurPhysical triggers (exercise, cold air, sulfur dioxide)dioxide)  Physiologic factorsPhysiologic factors  Stress, GERD, viral and bacterial URI, rhinitisStress, GERD, viral and bacterial URI, rhinitis
  9. 9. Diagnostic TestingDiagnostic Testing  SpirometrySpirometry  Recommended to do spirometry pre- and post- useRecommended to do spirometry pre- and post- use of an albuterol MDI to establish reversibility ofof an albuterol MDI to establish reversibility of airflow obstructionairflow obstruction  >> 12% reversibility or an increase in FEV1 of12% reversibility or an increase in FEV1 of 200cc is considered significant200cc is considered significant  Obstructive pattern: reduced FEV1/FVC ratioObstructive pattern: reduced FEV1/FVC ratio  Restrictive pattern: reduced FVC with a normalRestrictive pattern: reduced FVC with a normal FEV1/FVC ratioFEV1/FVC ratio
  10. 10. Diagnostic TestingDiagnostic Testing  SpirometrySpirometry  Can be used to identify reversible airwayCan be used to identify reversible airway obstruction due to triggersobstruction due to triggers  Can diagnose Exercise-induced asthma (EIA) orCan diagnose Exercise-induced asthma (EIA) or Exercise-induced bronchospasm (EIB) byExercise-induced bronchospasm (EIB) by measuring FEV1/FVC before exercise andmeasuring FEV1/FVC before exercise and immediately following exercise, then for 5-10immediately following exercise, then for 5-10 minute intervals over the next 20-30 minutesminute intervals over the next 20-30 minutes looking for post-exercise bronchoconstrictionlooking for post-exercise bronchoconstriction
  11. 11. Diagnostic TestingDiagnostic Testing  SpirometrySpirometry  National Asthma Education and PreventionNational Asthma Education and Prevention Program (NAEPP) recommends spirometry:Program (NAEPP) recommends spirometry:  For initial assessmentFor initial assessment  Evaluation of response to treatmentEvaluation of response to treatment  Assessment of airway function at least every 1-2 yearsAssessment of airway function at least every 1-2 years
  12. 12. Diagnostic TestingDiagnostic Testing  Methacholine challengeMethacholine challenge  Most common bronchoprovocative test in USMost common bronchoprovocative test in US  Patients breathe in increasing amounts ofPatients breathe in increasing amounts of methacholine and perform spirometry after eachmethacholine and perform spirometry after each dosedose  Increased airway hyperresponsiveness isIncreased airway hyperresponsiveness is established with a 20% or more decrease in FEV1established with a 20% or more decrease in FEV1 from baseline at a concentration < 8mg/dlfrom baseline at a concentration < 8mg/dl  May miss some cases of exercise-induced asthmaMay miss some cases of exercise-induced asthma
  13. 13. Diagnostic testingDiagnostic testing  Diagnostic trial of anti-inflammatoryDiagnostic trial of anti-inflammatory medication (preferably corticosteroids) or anmedication (preferably corticosteroids) or an inhaled bronchodilatorinhaled bronchodilator  Especially helpful in very young children unable toEspecially helpful in very young children unable to cooperate with other diagnostic testingcooperate with other diagnostic testing  There is no one single test or measure that canThere is no one single test or measure that can definitively be used to diagnose asthma in everydefinitively be used to diagnose asthma in every patientpatient
  14. 14. Goals of Asthma TreatmentGoals of Asthma Treatment  Control chronic and nocturnal symptomsControl chronic and nocturnal symptoms  Maintain normal activity, including exerciseMaintain normal activity, including exercise  Prevent acute episodes of asthmaPrevent acute episodes of asthma  Minimize ER visits and hospitalizationsMinimize ER visits and hospitalizations  Minimize need for reliever medicationsMinimize need for reliever medications  Maintain near-normal pulmonary functionMaintain near-normal pulmonary function  Avoid adverse effects of asthma medicationsAvoid adverse effects of asthma medications
  15. 15. Treatment of AsthmaTreatment of Asthma  Global Initiative for Asthma (6-point plan)Global Initiative for Asthma (6-point plan)  Educate patients to develop a partnership in asthmaEducate patients to develop a partnership in asthma managementmanagement  Assess and monitor asthma severity with symptomAssess and monitor asthma severity with symptom reports and measures of lung function as much asreports and measures of lung function as much as possiblepossible  Avoid exposure to risk factorsAvoid exposure to risk factors  Establish medication plans for chronic management inEstablish medication plans for chronic management in children and adultschildren and adults  Establish individual plans for managing exacerbationsEstablish individual plans for managing exacerbations  Provide regular follow-up careProvide regular follow-up care
  16. 16.  CLASSIFICTION OF DRUGS USED INCLASSIFICTION OF DRUGS USED IN ASTHMAASTHMA  A)Short term relievers used for relief of acuteA)Short term relievers used for relief of acute bronchoconstriction:bronchoconstriction:  1 Beta Adrenergic agonists1 Beta Adrenergic agonists  2 Methylxanthines2 Methylxanthines  3 Antimuscrinic agents3 Antimuscrinic agents
  17. 17.  B)Long term controllers for reduction ofB)Long term controllers for reduction of symptoms and prevention of attacks:symptoms and prevention of attacks:  1 Corticosteroids1 Corticosteroids  2Leukotriene pathway antagonist2Leukotriene pathway antagonist  3 Inhibitor of mast cell degranulation3 Inhibitor of mast cell degranulation
  18. 18. PharmacotherapyPharmacotherapy  Beta2-receptors are the predominant receptors inBeta2-receptors are the predominant receptors in bronchial smooth musclebronchial smooth muscle  Stimulate ATP-cAMP which leads to relaxation ofStimulate ATP-cAMP which leads to relaxation of bronchial smooth muscle and inhibition of releasebronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivityof mediators of immediate hypersensitivity  Inhibits release of mast cell mediators such asInhibits release of mast cell mediators such as histamine, leukotrienes, and prostaglandin-D2histamine, leukotrienes, and prostaglandin-D2  Beta1-receptors are predominant receptors in heart,Beta1-receptors are predominant receptors in heart, but up to 10-50% can be beta2-receptorsbut up to 10-50% can be beta2-receptors
  19. 19.  Beta adrenergic agonistsBeta adrenergic agonists  a) Non selective beta adrenergic agonistsa) Non selective beta adrenergic agonists  Epinephrine it stimulates alpha and beta1as wellEpinephrine it stimulates alpha and beta1as well as beta2 receptors. It is an effective rapid actingas beta2 receptors. It is an effective rapid acting bronchodilator when injected S/C (.4 mL ofbronchodilator when injected S/C (.4 mL of 1:1000 solution ) or inhaled as a microaerosol1:1000 solution ) or inhaled as a microaerosol from a pressurised canister (320 mcg/ puff).from a pressurised canister (320 mcg/ puff).  Adverse effects tachycardia, arrythmias andAdverse effects tachycardia, arrythmias and worsening of angina pectoris.worsening of angina pectoris.
  20. 20.  The beta2 selective adrenoceptor agonist drugsThe beta2 selective adrenoceptor agonist drugs  Short acting drugs eg albuterol,terbutaline, andShort acting drugs eg albuterol,terbutaline, and perbuterol are available as metered-doseperbuterol are available as metered-dose inhalers. They are potent bronchodilators.inhalers. They are potent bronchodilators. Bronchodilation is maximal within 15-30Bronchodilation is maximal within 15-30 minutes and persists for 3-4 hours.minutes and persists for 3-4 hours.  Toxic effects are minimized when these drugsToxic effects are minimized when these drugs are delivered by inhalation.are delivered by inhalation.
  21. 21.  Albuterol and terbutaline are available in tabletAlbuterol and terbutaline are available in tablet form ,one tablet 2or 3 times daily is the usualform ,one tablet 2or 3 times daily is the usual regimen but this route is rarely prescribed.regimen but this route is rarely prescribed.  Terbutaline is available for S/C injection (0.25Terbutaline is available for S/C injection (0.25 mg) The indication for this route are severemg) The indication for this route are severe asthma requiring emergency T/M whenasthma requiring emergency T/M when aersolized therapy is not available or has beenaersolized therapy is not available or has been ineffective.ineffective.
  22. 22.  Long acting beta2 selective agonistsLong acting beta2 selective agonists  Salmeterol a potent selective beta2 agonist thatSalmeterol a potent selective beta2 agonist that achieves its long duration of action as a resultachieves its long duration of action as a result of high lipid solubility. This increaes theof high lipid solubility. This increaes the affinity of the drug for the beta adrenoceptors.affinity of the drug for the beta adrenoceptors. The drug appears to interact with inhaledThe drug appears to interact with inhaled corticosteroids to improve asthma control.corticosteroids to improve asthma control. They should not be used in acuteThey should not be used in acute bronchospasmbronchospasm
  23. 23. PharmacotherapyPharmacotherapy  METHYLXANTHINESMETHYLXANTHINES  TheophyllineTheophylline  Narrow therapeutic index/Maintain 5-20 mcg/mLNarrow therapeutic index/Maintain 5-20 mcg/mL  Variability in clearance leads to a range of dosesVariability in clearance leads to a range of doses that vary 4-fold in order to reach a therapeutic dosethat vary 4-fold in order to reach a therapeutic dose  Mechanism of actionMechanism of action  Smooth muscle relaxation (bronchodilation)Smooth muscle relaxation (bronchodilation)  Suppression of the response of the airways to stimuliSuppression of the response of the airways to stimuli  Increase force of contraction of diaphragmatic musclesIncrease force of contraction of diaphragmatic muscles  Interacts with many other drugsInteracts with many other drugs
  24. 24.  The bronchodilation produced by theophyllineThe bronchodilation produced by theophylline is the major therapeutic action in asthma.is the major therapeutic action in asthma.  Most preparations of theophylline are wellMost preparations of theophylline are well absorbed from GIT.absorbed from GIT.  For oral therapy with prompt- releaseFor oral therapy with prompt- release formulation the typical dose is 3-4 mg/kgformulation the typical dose is 3-4 mg/kg every 6hours.every 6hours.
  25. 25.  Adverse effectsAdverse effects  Anorexia, nausea, vomiting, abdominalAnorexia, nausea, vomiting, abdominal discomfort, headache and anxiety may occur.discomfort, headache and anxiety may occur.  Higher levels may cause seizures orHigher levels may cause seizures or arrythmias.arrythmias.  Toxic levels may occur in patients with liverToxic levels may occur in patients with liver disease.disease.  Previously used to be main-stay of asthmaPreviously used to be main-stay of asthma therapy.therapy.
  26. 26.  ANTIMUSCRINIC AGENTSANTIMUSCRINIC AGENTS  MOAMOA  Muscarinic antagonists competitively inhibitMuscarinic antagonists competitively inhibit the effect of acetylcholine at muscarinicthe effect of acetylcholine at muscarinic receptors ie block the contraction of airwayreceptors ie block the contraction of airway smooth muscle and the increase in thesmooth muscle and the increase in the secretion of mucus.secretion of mucus.
  27. 27.  Ipratropium bromide a quaternary ammoniumIpratropium bromide a quaternary ammonium derivative of atropine is used .It is deliveredderivative of atropine is used .It is delivered in high doses by inhalation route.in high doses by inhalation route.  Clinical usesClinical uses  Addition of Ipratropium enhances theAddition of Ipratropium enhances the bronchodilation produced by nebulizedbronchodilation produced by nebulized Albuterol in acute severe asthma.Albuterol in acute severe asthma.  In patients intolerant of inhaled beta agonistIn patients intolerant of inhaled beta agonist agents.agents.
  28. 28.  LONG TERM CONTROLLERSLONG TERM CONTROLLERS  CORTICOSTEROIDSCORTICOSTEROIDS  They reduce bronchial reactivity, causeThey reduce bronchial reactivity, cause contraction of engorged vessels in bronchialcontraction of engorged vessels in bronchial mucosa, and inhibition of the infiltration ofmucosa, and inhibition of the infiltration of asthmatic airways by lymphocytes ,asthmatic airways by lymphocytes , eosinophils and mast cells.eosinophils and mast cells.  Oral and parenteral corticosteroids areOral and parenteral corticosteroids are reserved for patients who require urgent T/M.reserved for patients who require urgent T/M.
  29. 29.  Urgent T/M is often begun with an oral doseUrgent T/M is often begun with an oral dose of 30-60 mg prednisone /day. Or an I/V doseof 30-60 mg prednisone /day. Or an I/V dose of 1mg/kg methylprednisolone every 6 hours.of 1mg/kg methylprednisolone every 6 hours. The daily dose is decreased after air wayThe daily dose is decreased after air way obstruction is relieved and it is customary toobstruction is relieved and it is customary to administer corticosteroids early in theadminister corticosteroids early in the morning .morning .  In most patients this systemic corticosteroidIn most patients this systemic corticosteroid therapy can be discontinued in a week or 10therapy can be discontinued in a week or 10 days.days.
  30. 30.  INHALED CORTICOSTEROIDSINHALED CORTICOSTEROIDS  AerosolT/M is the most effective way toAerosolT/M is the most effective way to avoid the systemic effects. An average dailyavoid the systemic effects. An average daily dose of 4 puffs twice daily of Beclomethasonedose of 4 puffs twice daily of Beclomethasone (400mcg/day) is usually given. In switching(400mcg/day) is usually given. In switching patients from oral to inhaled corticosteroidpatients from oral to inhaled corticosteroid therapy oral therapy is slowly tapered off.therapy oral therapy is slowly tapered off.
  31. 31.  Adverse effects of inhaled coticosteroidsAdverse effects of inhaled coticosteroids  High doses of inhaled steroids may causeHigh doses of inhaled steroids may cause adrenal suppression .adrenal suppression .  Oropharyngeal candidiasis.Oropharyngeal candidiasis.  HoarsenessHoarseness  Risks of cataracts and osteoporosis in adultsRisks of cataracts and osteoporosis in adults over the long term use.over the long term use.  Transient slowing of rate of growth inTransient slowing of rate of growth in children,children,
  32. 32.  Clinical usesClinical uses  Chronic use of inhaled corticosteroids:Chronic use of inhaled corticosteroids:  1.Reduces symptoms and improves1.Reduces symptoms and improves pulmonary function in mild asthma.pulmonary function in mild asthma.  2.Reduces or eliminates the use of oral2.Reduces or eliminates the use of oral corticosteroids in severe asthma.corticosteroids in severe asthma.  CautionCaution  Inhaled corticosteroids are effective only soInhaled corticosteroids are effective only so long as they are taken.long as they are taken.
  33. 33. DRUGS OF ASTHMA-II
  34. 34. PharmacotherapyPharmacotherapy  Mast cell stabilizers (cromolyn/nedocromil)Mast cell stabilizers (cromolyn/nedocromil)  Inhibits release of mediators from mast cellsInhibits release of mediators from mast cells (degranulation) after exposure to specific antigens(degranulation) after exposure to specific antigens  Blocks Ca2+ ions from entering the mast cellBlocks Ca2+ ions from entering the mast cell  Safe for pediatrics (including infants)Safe for pediatrics (including infants)  Should be started 2-4 weeks before allergy seasonShould be started 2-4 weeks before allergy season when symptoms are expected.when symptoms are expected.  Can be used before exercise (not as good as ICS)Can be used before exercise (not as good as ICS)  Alternate med for persistent asthmaAlternate med for persistent asthma
  35. 35.  Mast cell stabilizersMast cell stabilizers  Cromolyn and NedocromylCromolyn and Nedocromyl  MOAMOA  An alteration in the function of delayed chlorideAn alteration in the function of delayed chloride channels in the cell membrane results in:channels in the cell membrane results in:  Inhibition of the early response to an antigenicInhibition of the early response to an antigenic challenge of mast cellschallenge of mast cells  Inhibition of the inflammatory response ofInhibition of the inflammatory response of eosinophils to inhalation of allergens.eosinophils to inhalation of allergens.
  36. 36.  Clinical usesClinical uses  They are only of value when taken Prophylactically.They are only of value when taken Prophylactically.  When used as aerosols (by nebulizer or MDI) theyWhen used as aerosols (by nebulizer or MDI) they effectively inhibit both antigen-and exercise- inducedeffectively inhibit both antigen-and exercise- induced asthma. Cromolyn is taken as a single T/M prior toasthma. Cromolyn is taken as a single T/M prior to exercise or unavoidable exposure to allergen.exercise or unavoidable exposure to allergen. 
  37. 37.  Cromolyn or Nedocromil when takenCromolyn or Nedocromil when taken regularly 2-4 puffs 2-4 times daily by patientsregularly 2-4 puffs 2-4 times daily by patients with nonseasonal asthma, reduceswith nonseasonal asthma, reduces symptomatic severity and the need forsymptomatic severity and the need for bronchodilator medication particularly inbronchodilator medication particularly in young patients.young patients.  Addition of nedocromil to a standard dose ofAddition of nedocromil to a standard dose of an inhaled corticosteroid appears to improvean inhaled corticosteroid appears to improve asthma control.asthma control.
  38. 38.  Adverse effectsAdverse effects  Minor throat irritation, cough, and mouth dryness andMinor throat irritation, cough, and mouth dryness and rarely chest tightness and wheezing.rarely chest tightness and wheezing.  Serious adverse effects dermatitis, myositis, orSerious adverse effects dermatitis, myositis, or gastroenteritis occurs in less than 2% of patients.gastroenteritis occurs in less than 2% of patients.  Very few cases of pulmonary infiltration andVery few cases of pulmonary infiltration and anaphylaxis have been reported.anaphylaxis have been reported.
  39. 39. PharmacotherapyPharmacotherapy  Leukotriene receptor antagonistsLeukotriene receptor antagonists  Leukotriene-mediated effects include:Leukotriene-mediated effects include:  Airway edemaAirway edema  Smooth muscle contractionSmooth muscle contraction  Altered cellular activity associated with theAltered cellular activity associated with the inflammatory processinflammatory process  Receptors have been found in airway smoothReceptors have been found in airway smooth muscle cells and macrophages and on other pro-muscle cells and macrophages and on other pro- inflammatory cells (including eosinophils andinflammatory cells (including eosinophils and certain myeloid stem cells) and nasal mucosacertain myeloid stem cells) and nasal mucosa
  40. 40.  Leukotriene pathway inhibitorsLeukotriene pathway inhibitors  Zileuton a 5- lipoxygenase inhibitorZileuton a 5- lipoxygenase inhibitor  Montelukast, Zafirlukast LTD4 – receptorMontelukast, Zafirlukast LTD4 – receptor antagonists.antagonists.  They improve asthma control.They improve asthma control.  They are given orally can be given in patients whoThey are given orally can be given in patients who comply poorly with inhaled therapies.comply poorly with inhaled therapies.  Montelukast can be used in children as young as 6Montelukast can be used in children as young as 6 years of age. It can be taken without regards to mealsyears of age. It can be taken without regards to meals and only once-daily convenient dosage.and only once-daily convenient dosage.
  41. 41.  ANTI –IGE MONOCLONAL ANTIBODIESANTI –IGE MONOCLONAL ANTIBODIES  Omalizumab the monoclonal humanizedantiOmalizumab the monoclonal humanizedanti IgE antibody is reserved for patients withIgE antibody is reserved for patients with chronic severe asthma not controlled by highchronic severe asthma not controlled by high dose inhaled corticosteroid plus long actingdose inhaled corticosteroid plus long acting beta agonist combination T/M.beta agonist combination T/M.  It is given by twice S/C injections.It is given by twice S/C injections.
  42. 42. Various severities of asthmaVarious severities of asthma  Step-wise pharmacotherapy treatment programStep-wise pharmacotherapy treatment program for varying severities of asthmafor varying severities of asthma  Mild Intermittent (Step 1)Mild Intermittent (Step 1)  Mild Persistent (Step 2)Mild Persistent (Step 2)  Moderate Persistent (Step 3)Moderate Persistent (Step 3)  Severe Persistent (Step 4)Severe Persistent (Step 4)  Patient fits into the highest category that theyPatient fits into the highest category that they meet one of the criteria formeet one of the criteria for
  43. 43. Mild Intermittent AsthmaMild Intermittent Asthma  Day time symptomsDay time symptoms << 2 times q week2 times q week  Night time symptomsNight time symptoms << 2 times q month2 times q month  PEF or FEV1PEF or FEV1 >> 80% of predicted80% of predicted  PEF variability < 20%PEF variability < 20%  PEF and FEV1 values are only for adults and forPEF and FEV1 values are only for adults and for children over the age of 5children over the age of 5
  44. 44. Mild Persistent AsthmaMild Persistent Asthma  Day time symptoms > 2/week, but < 1/dayDay time symptoms > 2/week, but < 1/day  Night time symptoms < 1 night q weekNight time symptoms < 1 night q week  PEF or FEV1PEF or FEV1 >> 80% of predicted80% of predicted  PEF variability 20%-30%PEF variability 20%-30%
  45. 45. Moderate Persistent AsthmaModerate Persistent Asthma  Day time symptoms q dayDay time symptoms q day  Night time symptoms > 1 night q weekNight time symptoms > 1 night q week  PEF or FEV1 60%-80% of predictedPEF or FEV1 60%-80% of predicted  PEF variability >30%PEF variability >30%
  46. 46. Severe Persistent AsthmaSevere Persistent Asthma  Day time symptoms: continualDay time symptoms: continual  Night time symptoms: frequentNight time symptoms: frequent  PEF or FEV1PEF or FEV1 << 60% of predicted60% of predicted  PEF variability > 30%PEF variability > 30%
  47. 47. Pharmacotherapy for Adults andPharmacotherapy for Adults and Children Over the Age of 5 YearsChildren Over the Age of 5 Years  Step 1 (Mild intermittent asthma)Step 1 (Mild intermittent asthma)  No daily medication neededNo daily medication needed  PRN short-acting bronchodilator (albuterol) MDIPRN short-acting bronchodilator (albuterol) MDI  Severe exacerbations may require systemicSevere exacerbations may require systemic corticosteroidscorticosteroids  Although the overall diagnosis is “mildAlthough the overall diagnosis is “mild intermittent” the exacerbations themselves can stillintermittent” the exacerbations themselves can still be severebe severe
  48. 48. Pharmacotherapy for Adults andPharmacotherapy for Adults and Children Over the Age of 5 YearsChildren Over the Age of 5 Years  Step 2 (Mild persistent)Step 2 (Mild persistent)  Preferred TreatmentPreferred Treatment  Low-dose inhaled corticosteroid dailyLow-dose inhaled corticosteroid daily  Alternative Treatment (no particular order)Alternative Treatment (no particular order)  CromolynCromolyn  Leukotriene receptor antagonistLeukotriene receptor antagonist  NedocromilNedocromil  Sustained release theophylline to maintain a blood levelSustained release theophylline to maintain a blood level of 5-15 mcg/mLof 5-15 mcg/mL
  49. 49. Pharmacotherapy for Adults andPharmacotherapy for Adults and Children Over the Age of 5 YearsChildren Over the Age of 5 Years  Step 3 (Moderate persistent)Step 3 (Moderate persistent)  Preferred TreatmentPreferred Treatment  Low-to-medium dose inhaled corticosteroidsLow-to-medium dose inhaled corticosteroids  WITH long-acting inhaled beta2-agonistWITH long-acting inhaled beta2-agonist  Alternative TreatmentAlternative Treatment  Increase inhaled corticosteroids within the medium doseIncrease inhaled corticosteroids within the medium dose rangerange  Add leukotriene receptor antagonist or theophylline toAdd leukotriene receptor antagonist or theophylline to the inhaled corticosteroidthe inhaled corticosteroid
  50. 50. Pharmacotherapy for Adults andPharmacotherapy for Adults and Children Over the Age of 5 YearsChildren Over the Age of 5 Years  Step 4 (Severe persistent)Step 4 (Severe persistent)  Preferred TreatmentPreferred Treatment  High-dose inhaled corticosteroidsHigh-dose inhaled corticosteroids  AND long-acting inhaled beta2-agonistsAND long-acting inhaled beta2-agonists  AND (if needed) oral corticosteroidsAND (if needed) oral corticosteroids
  51. 51. Pharmacotherapy for Infants andPharmacotherapy for Infants and Young Children (<5 years)Young Children (<5 years)  Step 1(mild intermittent)Step 1(mild intermittent)  No daily medication neededNo daily medication needed
  52. 52. Pharmacotherapy for Infants andPharmacotherapy for Infants and Young Children (<5 years)Young Children (<5 years)  Step 2 (mild persistent)Step 2 (mild persistent)  Preferred treatmentPreferred treatment  Low-dose inhaled corticosteroidsLow-dose inhaled corticosteroids  Alternative treatmentAlternative treatment  Cromolyn (nebulizer preferred)Cromolyn (nebulizer preferred)  OR leukotriene receptor antagonistOR leukotriene receptor antagonist
  53. 53. Pharmacotherapy for Infants andPharmacotherapy for Infants and Young Children (<5 years)Young Children (<5 years)  Step 3 (moderate persistent)Step 3 (moderate persistent)  Preferred treatmentPreferred treatment  Low-dose inhaled corticosteroids and long-acting beta2-Low-dose inhaled corticosteroids and long-acting beta2- agonistagonist  OR Medium-dose inhaled corticosteroidsOR Medium-dose inhaled corticosteroids  Alternative treatmentAlternative treatment  Low-dose inhaled corticosteroids with either:Low-dose inhaled corticosteroids with either:  Leukotriene receptor antagonistLeukotriene receptor antagonist  OR theophyllineOR theophylline
  54. 54. Pharmacotherapy for Infants andPharmacotherapy for Infants and Young Children (<5 years)Young Children (<5 years)  Step 4 (severe persistent)Step 4 (severe persistent)  Preferred treatmentPreferred treatment  High-dose inhaled corticosteroidsHigh-dose inhaled corticosteroids  AND long-acting inhaled beta2-agonistAND long-acting inhaled beta2-agonist  AND (if needed) Oral corticosteroidsAND (if needed) Oral corticosteroids  For young children, inhaled medications should beFor young children, inhaled medications should be given by nebulizer, dry powder inhaler (DPI), orgiven by nebulizer, dry powder inhaler (DPI), or MDI with a chamber/spacerMDI with a chamber/spacer
  55. 55. Acute ExacerbationsAcute Exacerbations  Inhaled albuterol is the treatment of choice inInhaled albuterol is the treatment of choice in absence of impending respiratory failureabsence of impending respiratory failure  MDI with spacer as effective as nebulizer withMDI with spacer as effective as nebulizer with equivalent dosesequivalent doses  Adding an antibiotic during an acuteAdding an antibiotic during an acute exacerbation is not recommended in theexacerbation is not recommended in the absence of evidence of an acute bacterialabsence of evidence of an acute bacterial infectioninfection
  56. 56. Acute ExacerbationsAcute Exacerbations  BeneficialBeneficial  Inhaled atrovent added to beta2-agonistsInhaled atrovent added to beta2-agonists  High-dose inhaled corticosteroidsHigh-dose inhaled corticosteroids  MDI with spacer as effective as nebulizerMDI with spacer as effective as nebulizer  OxygenOxygen  Systemic steroidsSystemic steroids  Likely to be beneficialLikely to be beneficial  IV theophyllineIV theophylline
  57. 57. Exercise-induced BronchospasmExercise-induced Bronchospasm  Evaluate for underlying asthma and treatEvaluate for underlying asthma and treat  SABA are best pre-treatmentSABA are best pre-treatment  Mast cell stabilizers less effective than SABAMast cell stabilizers less effective than SABA  Anticholinergics less effective than mast cellAnticholinergics less effective than mast cell stabilizersstabilizers  SABA + mast cell stabilizer not better thanSABA + mast cell stabilizer not better than SABA aloneSABA alone
  58. 58.  TREATMENT OF CHRONICTREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASEOBSTRUCTIVE PULMONARY DISEASE  Acute stage inhalation of a short acting betaAcute stage inhalation of a short acting beta agonist eg albuterol,or an anticholinergic drugagonist eg albuterol,or an anticholinergic drug eg ipratropium bromide or the two ineg ipratropium bromide or the two in combination is usually effective.combination is usually effective.  Persistent symptoms of exertional dyspnea andPersistent symptoms of exertional dyspnea and limitation of activities requires a long actinglimitation of activities requires a long acting beta agonist or long acting anticholinergic.beta agonist or long acting anticholinergic.
  59. 59.  Severe airflow obstruction or a H/OSevere airflow obstruction or a H/O exacerbations: regular use of an inhaledexacerbations: regular use of an inhaled corticosteroid reduces the incidence of futurecorticosteroid reduces the incidence of future exacerbations.exacerbations.
  60. 60.  Theophylline may be used to increaseTheophylline may be used to increase ventilatory capacity.ventilatory capacity.  Antibiotics are used in exacerbations ofAntibiotics are used in exacerbations of COPD.COPD.
  61. 61.  ANTI TUSSIVE AGENTSANTI TUSSIVE AGENTS  DEXTROMETHORPHAN AsyntheticDEXTROMETHORPHAN Asynthetic derivative of morphine , suppresses thederivative of morphine , suppresses the response of the cough centre.response of the cough centre.  CODEINE decreases the sensitivity of coughCODEINE decreases the sensitivity of cough centres to peripheral stimuli and decreasescentres to peripheral stimuli and decreases mucosal secretions.mucosal secretions.
  62. 62. QuestionQuestion  Which one of the following is true concerningWhich one of the following is true concerning control of mild persistent asthma in thecontrol of mild persistent asthma in the pediatric population?pediatric population?  Cromolyn should not be used under age 5Cromolyn should not be used under age 5  Atrovent should be added if beta-agonists do notAtrovent should be added if beta-agonists do not maintain control of asthmamaintain control of asthma  LABA should be added if SABA is ineffectiveLABA should be added if SABA is ineffective  SABA may be used q2h to maintain controlSABA may be used q2h to maintain control  Initial treatment should be an inhaled anti-Initial treatment should be an inhaled anti- inflammatory such as ICS or cromolyninflammatory such as ICS or cromolyn
  63. 63. Answer EAnswer E  Initial medications for chronic asthma shouldInitial medications for chronic asthma should include an anti-inflammatory such as ICS orinclude an anti-inflammatory such as ICS or cromolyn. Cromolyn is safe for all pediatriccromolyn. Cromolyn is safe for all pediatric age groups. Atrovent is useful in COPD, butage groups. Atrovent is useful in COPD, but very limited use in asthma. Albuterol shouldvery limited use in asthma. Albuterol should be used up to every 4 hours prn. Overuse ofbe used up to every 4 hours prn. Overuse of inhaled beta-agonists has been associated withinhaled beta-agonists has been associated with an increased mortality rate.an increased mortality rate.
  64. 64. QuestionQuestion  It is estimated allergic rhinitis affects how mayIt is estimated allergic rhinitis affects how may people in the US?people in the US?  20 million20 million  40 million40 million  50 million50 million  100 million100 million  Answer: B 40 millionAnswer: B 40 million
  65. 65. QuestionQuestion  Which one of the following statements concerningWhich one of the following statements concerning the association between allergic rhinitis and asthma isthe association between allergic rhinitis and asthma is false?false?  Almost all patients with allergic asthma also haveAlmost all patients with allergic asthma also have symptoms of rhinitissymptoms of rhinitis  About 1/3 of patients with allergic rhinitis also have asthmaAbout 1/3 of patients with allergic rhinitis also have asthma  Pharmacologic treatment for allergic rhinitis will notPharmacologic treatment for allergic rhinitis will not improve the symptoms of asthmaimprove the symptoms of asthma  Patients with allergic rhinitis and patients with asthmaPatients with allergic rhinitis and patients with asthma exhibit peripheral eosinophilia and basophilia.exhibit peripheral eosinophilia and basophilia.
  66. 66. Answer: CAnswer: C  Patients with asthma should have their allergicPatients with asthma should have their allergic rhinitis treatedrhinitis treated  People with asthma and allergic rhinitis whoPeople with asthma and allergic rhinitis who are treated for their allergic rhinitis have aare treated for their allergic rhinitis have a significantly lower risk of subsequent asthma-significantly lower risk of subsequent asthma- related events than those not treated forrelated events than those not treated for allergic rhinitis.allergic rhinitis.
  67. 67. QuestionQuestion  Which one of the following findings on a nasalWhich one of the following findings on a nasal smear suggests a diagnosis of allergic rhinitis?smear suggests a diagnosis of allergic rhinitis?  > 10% neutrophils> 10% neutrophils  > 10% eosinophils> 10% eosinophils  < 10% neutrophils< 10% neutrophils  > 10% erythrocytes> 10% erythrocytes  Answer: B >10% eosinophilsAnswer: B >10% eosinophils
  68. 68. QuestionQuestion  Which of the following statements is true?Which of the following statements is true?  An acceptable strategy for eliminating sedatingAn acceptable strategy for eliminating sedating effects of 1effects of 1stst -generation antihistamines and-generation antihistamines and containing the cost of 2containing the cost of 2ndnd -generation is to use 2nd--generation is to use 2nd- generation in the AM and 1generation in the AM and 1stst -generation in the PM-generation in the PM  In most states, patients taking 1In most states, patients taking 1stst -generation are-generation are considered “under the influence of drugs.”considered “under the influence of drugs.”  Mast cell stabilizers are becoming an excellentMast cell stabilizers are becoming an excellent choice for children because of their ability to treatchoice for children because of their ability to treat symptoms after they have started and their safetysymptoms after they have started and their safety
  69. 69. Answer: BAnswer: B  Patients taking 1Patients taking 1stst -generation antihistamines-generation antihistamines are considered “under the influence of drugs.”are considered “under the influence of drugs.” The sedating effects have been shown to carryThe sedating effects have been shown to carry over to the next day even when taken only atover to the next day even when taken only at night and this type of chronic use is notnight and this type of chronic use is not recommended.recommended.  Mast cell stabilizers should be started beforeMast cell stabilizers should be started before symptoms develop, not after.symptoms develop, not after.

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