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Management of Asthma and Management of Asthma and COPDCOPD
W.S. Krell M.D.W.S. Krell M.D.
Wayne State UniversityWayne State University
NIH Statement (1992, ‘97)NIH Statement (1992, ‘97)
Chronic inflammatory disorderChronic inflammatory disorder multiple cellular components, mediatorsmultiple cellular components, mediators recurrent wheeze, shortness of breath, recurrent wheeze, shortness of breath,
chest tightness, cough (pm & early am)chest tightness, cough (pm & early am) reversible airflow obstructionreversible airflow obstruction secondary: hyperresponsivenesssecondary: hyperresponsiveness Sub-basement membrane fibrosisSub-basement membrane fibrosis
Treating AsthmaTreating Asthma Medications:Medications:
– long term or controller medicationslong term or controller medications– quick relief medicationsquick relief medications
Stepped therapy: start high, back Stepped therapy: start high, back downdown
Asthma monitoring and action plansAsthma monitoring and action plans Environmental controlsEnvironmental controls
Overview of MedicationsOverview of Medications
Controller medicationsController medications– control inflammationcontrol inflammation– long duration bronchodilationlong duration bronchodilation– multiple medicationsmultiple medications
Quick relief medicationsQuick relief medications– for intermittent or breakthrough for intermittent or breakthrough
symptomssymptoms
Controller AgentsController Agents
Inhaled corticosteroidsInhaled corticosteroids Systemic corticosteroidsSystemic corticosteroids Long acting Long acting 22 agonists agonists Cromolyn and derivativesCromolyn and derivatives MethylxanthinesMethylxanthines Leukotriene ModifiersLeukotriene Modifiers
Inhaled CorticosteroidsInhaled Corticosteroids
Control airway inflammation locallyControl airway inflammation locally Ideal: control asthma (high local Ideal: control asthma (high local
potency); no side effects (low potency); no side effects (low systemic effects)systemic effects)
fluticasone, budesonide ****fluticasone, budesonide **** beclomethasone *beclomethasone * (triamcinolone, flunisolide)(triamcinolone, flunisolide)
Systemic CorticosteroidsSystemic Corticosteroids
May be needed initiallyMay be needed initially Side effect profile well knownSide effect profile well known Step down therapyStep down therapy Alternatives: high dose inhaled Alternatives: high dose inhaled
corticosteroids; methotrexate; corticosteroids; methotrexate; other immunosuppressive drugs; other immunosuppressive drugs; OmalizumabOmalizumab
Omalizumab (Xolair)Omalizumab (Xolair)
Recomb. DNA derived IgG - Recomb. DNA derived IgG - selectively binds human IgEselectively binds human IgE
Indication: mod. to severe Indication: mod. to severe persistent asthma not controlled persistent asthma not controlled w/inhaled CS w/inhaled CS
IgE > 30, RAST A or skin tests +IgE > 30, RAST A or skin tests + Given SQ/ mo. or biweekly Given SQ/ mo. or biweekly Dose based on wt. and IgE levelDose based on wt. and IgE level
Long acting ßLong acting ß22 Agonists Agonists
SalmeterolSalmeterol FormoterolFormoterol Prolonged durationProlonged duration Potentiate steroid effects? Potentiate steroid effects? Should we be using them????????Should we be using them????????
Leukotriene ModifiersLeukotriene Modifiers
Anti-inflammatoryAnti-inflammatory Precursor step affectedPrecursor step affected Compliance may be better than Compliance may be better than
MDIsMDIs Few side effectsFew side effects
Other ControllersOther Controllers
Cromolyn derivativesCromolyn derivatives– Safe, effectiveSafe, effective– Less predictable, frequent dosingLess predictable, frequent dosing
MethylxanthinesMethylxanthines– Mechanism not fully understoodMechanism not fully understood– Therapeutic/Toxic ratio highTherapeutic/Toxic ratio high– Multiple drug interactionsMultiple drug interactions
Quick Relief MedicationsQuick Relief Medications
ßß22 Agonists Agonists Systemic corticosteroidsSystemic corticosteroids
Exacerbation of AsthmaExacerbation of Asthma
History: Sudden (exposure) vs History: Sudden (exposure) vs gradual worsening vs viral infection gradual worsening vs viral infection vs non-compliancevs non-compliance
Tachypnea, tachycardiaTachypnea, tachycardia Accessory musclesAccessory muscles Wheezing, prolonged expiration, Wheezing, prolonged expiration,
silentsilent Speaking ability compromisedSpeaking ability compromised
ABGs - Asthma ABGs - Asthma
Respiratory alkalosis Respiratory alkalosis Normal PCO2 is worrisomeNormal PCO2 is worrisome Rising PCO2 is near respiratory Rising PCO2 is near respiratory
failurefailure Note: O2 doesn’t fall until late so Note: O2 doesn’t fall until late so
pulse oximetry is not very pulse oximetry is not very sensitivesensitive
Emergency ManagementEmergency Management
Nebulized albuterol x 3Nebulized albuterol x 3 Monitor exam, peak flows, ABGsMonitor exam, peak flows, ABGs If no improvement, start IV If no improvement, start IV
corticosteroids and admitcorticosteroids and admit DOSE?? (30 to 180 mg/day)DOSE?? (30 to 180 mg/day) Asthma: CXR not likely helpfulAsthma: CXR not likely helpful
Further Mgt of AsthmaFurther Mgt of Asthma
Continue bronchodilatorsContinue bronchodilators Q 6 hour steroidsQ 6 hour steroids HydrationHydration Mucomyst may exacerbateMucomyst may exacerbate If failing: consider anticholinergics, If failing: consider anticholinergics,
theophylline, single isomer theophylline, single isomer ββ22, , MgMg2+2+
Impending Respiratory Impending Respiratory FailureFailure
Respiratory acidosisRespiratory acidosis Decreasing mental statusDecreasing mental status Asthma: PCO2 above 40 or rising Asthma: PCO2 above 40 or rising
despite therapydespite therapy
Outpatient Asthma Outpatient Asthma ManagementManagement
Classify by severityClassify by severity Step up and down number of Step up and down number of
medications based on symptoms medications based on symptoms and peak flowsand peak flows
Severity of AsthmaSeverity of Asthma
Mild Intermittant:Mild Intermittant:– symptoms < 2X/wksymptoms < 2X/wk– nights<2/monthnights<2/month
Mild persistent:Mild persistent:– > 2X/wk but < 1/day > 2X/wk but < 1/day – Nights > 2/monthNights > 2/month
(cont.)(cont.)
Moderate:Moderate:– Daily symptomsDaily symptoms– Nights > 1/weekNights > 1/week
SEVERE:SEVERE:– Continual symptomsContinual symptoms– Frequent nighttime symptomsFrequent nighttime symptoms
Rules of 2Rules of 2
Sx > Sx > 22/week/week
PM sx > PM sx > 22 nights/month nights/month
> > 22 rescue MDIs/year rescue MDIs/year
Stepped TherapyStepped Therapy
Inhaled beta agonistInhaled beta agonist Inhaled corticosteroidInhaled corticosteroid Long acting beta agonistLong acting beta agonist Leukotriene modifiersLeukotriene modifiers (Cromolyn derivatives)(Cromolyn derivatives) (Theophyllines)(Theophyllines) Systemic corticosteroidsSystemic corticosteroids
Patient EducationPatient Education
Avoid triggersAvoid triggers Home monitoringHome monitoring Proper inhaler techniquesProper inhaler techniques SpacersSpacers ““Asthma Action Plan”Asthma Action Plan”
Compliance?Compliance?
Few patients continue to documentFew patients continue to document Always give them Action PlansAlways give them Action Plans Simple in office questionnaireSimple in office questionnaire
– validated in testingvalidated in testing– Snap shot of asthma controlSnap shot of asthma control
Asthma vs. COPDAsthma vs. COPD
Sensitizing agentSensitizing agent
↓↓ InflammationInflammation CD4 T-lymphocytesCD4 T-lymphocytes EosinophilsEosinophils
↓↓ Completely Completely
reversiblereversible
airflow limitationairflow limitation
Noxious agentNoxious agent
↓↓ InflammationInflammation CD8 T-lymphocytesCD8 T-lymphocytes Macrophages, PMNsMacrophages, PMNs
↓↓ Irreversible airflow Irreversible airflow
limitationlimitation
Treating COPDTreating COPD
Step up Step up Long acting AnticholinergicsLong acting Anticholinergics Long acting beta agonistsLong acting beta agonists Short acting bronchodilatorsShort acting bronchodilators (steroids: inhaled and oral)(steroids: inhaled and oral) Soon: Cilomalist?Soon: Cilomalist?
Exacerbation of COPDExacerbation of COPD
Viral or secondary bacterial infectionViral or secondary bacterial infection Non-complianceNon-compliance Cor pulmonaleCor pulmonale Tachypnea, tachycardiaTachypnea, tachycardia Rhonchi, wheezes, prolonged Rhonchi, wheezes, prolonged
expirationexpiration Signs of right heart failure, pulmonary Signs of right heart failure, pulmonary
hypertensionhypertension
CausesCauses
Infections (bacterial)Infections (bacterial) Environmental (Environmental (↑ pollution)↑ pollution) Unknown in 1/3Unknown in 1/3
ManagementManagement
Increase bronchodilatorsIncrease bronchodilators Systemic steroids (PO if possible) Systemic steroids (PO if possible)
(A)(A)– Shortens recovery timeShortens recovery time– Quicker return to baseline functionQuicker return to baseline function– ↓ ↓ risk of early exacerbationrisk of early exacerbation– 10 day to 2 week course10 day to 2 week course
Antibiotics (B)Antibiotics (B)
Additional Management: Additional Management: COPDCOPD
Nebulized anticholinergics, Nebulized anticholinergics, ββ agonists agonists AntibioticsAntibiotics SteroidsSteroids Manage other complications: Manage other complications:
pneumonia, pneumothorax, right pneumonia, pneumothorax, right heart failureheart failure
Oxygen to keep saturation near 90%Oxygen to keep saturation near 90%
ABGs - COPDABGs - COPD
Pay more attention to pH, bicarbPay more attention to pH, bicarb PCO2 elevations more significant PCO2 elevations more significant
when acutewhen acute Expect increased (A-a)DO2Expect increased (A-a)DO2 Hypoxia must be treated, despite Hypoxia must be treated, despite
fears of hypercarbiafears of hypercarbia
Impending Respiratory Impending Respiratory FailureFailure
Non Invasive VentilationNon Invasive Ventilation– Bi-level Positive PressureBi-level Positive Pressure
– Increase inspiratory P to Increase inspiratory P to ↓ pCO↓ pCO22
– Start expiratory P at 5-6 cm HStart expiratory P at 5-6 cm H22O and ↑ if O and ↑ if
needed for oxygenationneeded for oxygenation– Evidence A for successEvidence A for success
Management of COPDManagement of COPD
Smoking cessationSmoking cessation SpirometrySpirometry Yearly influenza vaccineYearly influenza vaccine PneumovaxPneumovax Antibiotics for exacerbationsAntibiotics for exacerbations Monitor rest and exercise Monitor rest and exercise
oxygenationoxygenation
Spirometry is KEYSpirometry is KEY
FEV1FEV1 FEV1/FVC RatioFEV1/FVC Ratio Screen based on exposure and Screen based on exposure and
symptomssymptoms Follow at least yearlyFollow at least yearly Patients should KNOW THEIR Patients should KNOW THEIR
NUMBERSNUMBERS
SpirogramsSpirograms
ClassificationClassificationSTAGSTAGEE
FEV1/FEV1/FVCFVC FEV1FEV1
00 >70%>70% > 80% + Symptoms> 80% + Symptoms
II < 70%< 70% ≥ ≥ 80% ± Symptoms80% ± Symptoms
IIII < 70%< 70% ≥ ≥ 50% but < 80% ± Sx50% but < 80% ± Sx
IIIIII < 70%< 70% ≥ ≥ 30% but < 50% ± Sx30% but < 50% ± Sx
IVIV < 70%< 70%< 30% or < 50% + < 30% or < 50% + chronic respiratory chronic respiratory failurefailure
Management: All StagesManagement: All Stages
Avoidance of noxious exposuresAvoidance of noxious exposures– SMOKING CESSATION (Evidence: A)SMOKING CESSATION (Evidence: A)– Avoid occupational/environmental Avoid occupational/environmental
exposures (Evidence: B)exposures (Evidence: B) VaccinationVaccination
– InfluenzaInfluenza– PneumovaxPneumovax
Smoking Cessation Smoking Cessation StrategiesStrategies
Repeated counseling Repeated counseling Nicotine replacement agentsNicotine replacement agents Buproprion, anxiolyticsBuproprion, anxiolytics This is the ONLY measure available This is the ONLY measure available
proven to halt the decline in lung proven to halt the decline in lung functionfunction
Evidence: AEvidence: A
COPD OutpatientCOPD Outpatient
SHORT ACTING BETA AGONISTSSHORT ACTING BETA AGONISTS ANTICHOLINERGICS ****ANTICHOLINERGICS ****
– IpatropiumIpatropium– TiotropiumTiotropium
LONG ACTING BETA AGONISTSLONG ACTING BETA AGONISTS TheophyllinesTheophyllines Inhaled corticosteroidsInhaled corticosteroids
Management: Stage IManagement: Stage I
Short acting bronchodilator used PRNShort acting bronchodilator used PRN Albuterol: beta 2 agonistAlbuterol: beta 2 agonist Ipatropium: M3 anticholinergic blockerIpatropium: M3 anticholinergic blocker Both are effectiveBoth are effective Albuterol has faster onset of actionAlbuterol has faster onset of action Combination is additive for Combination is additive for
bronchodilationbronchodilation Evidence: AEvidence: A
Management: Stage IIManagement: Stage II
Long acting bronchodilatorsLong acting bronchodilators– Long acting beta agonistsLong acting beta agonists– Long acting anticholinergicLong acting anticholinergic
Short acting bronchodilators PRNShort acting bronchodilators PRN EducationEducation Inhaled corticosteroids if frequent Inhaled corticosteroids if frequent
exacerbationsexacerbations Evidence: AEvidence: A
Long Acting Beta AgonistsLong Acting Beta Agonists
FormoterolFormoterol– Onset comparable to short acting agentsOnset comparable to short acting agents– Duration: 12 hoursDuration: 12 hours
SalmeterolSalmeterol– Slower onsetSlower onset– Duration: 12 hoursDuration: 12 hours– Cautions re: use without inhaled steroids Cautions re: use without inhaled steroids
applies to asthmatics not COPD patientsapplies to asthmatics not COPD patients
TiotropiumTiotropium
Duration: 24 hoursDuration: 24 hours Blocks M1 and M3 receptorsBlocks M1 and M3 receptors Stop ipatropium (M3 only)Stop ipatropium (M3 only) Few side effects (some caution Few side effects (some caution
with BPH)with BPH) Sustained improvement in FEV1Sustained improvement in FEV1
What about Theophylline?What about Theophylline?
Old drug, proven usefulOld drug, proven useful If chosen, careful monitoring If chosen, careful monitoring
requiredrequired– High toxic to therapeutic ratioHigh toxic to therapeutic ratio– Multiple drug and food interactionsMultiple drug and food interactions
Aim for levels 8 – 12 mcg/mLAim for levels 8 – 12 mcg/mL
CilomalistCilomalist
Orally active PDE4 inhibitor Orally active PDE4 inhibitor cAMP cAMP (inflam, bronchial reactivity)(inflam, bronchial reactivity)
PositivesPositives– Improved FEV1, reduced sx (SGRQ)Improved FEV1, reduced sx (SGRQ)
Negatives Negatives – Significant GI toxicitySignificant GI toxicity– Study done prior to release of Study done prior to release of
tiotropiumtiotropium Rennard, CHEST 2006Rennard, CHEST 2006
Inhaled CorticosteroidsInhaled Corticosteroids
If indicated, choose long acting If indicated, choose long acting agentsagents
FluticasoneFluticasone– Combination drug with salmeterolCombination drug with salmeterol
BudesonideBudesonide– Also available for use in nebulizerAlso available for use in nebulizer
More is better???More is better???
Combinations can produce benefitsCombinations can produce benefits Long acting agents are ALL Long acting agents are ALL
expensiveexpensive Optimal combinations not knownOptimal combinations not known
Management: Stage IIIManagement: Stage III
One or More Long acting One or More Long acting BronchodilatorsBronchodilators
Short acting bronchodilators PRNShort acting bronchodilators PRN Inhaled corticosteroids if frequent Inhaled corticosteroids if frequent
exacerbationsexacerbations Pulmonary RehabilitationPulmonary Rehabilitation Evidence: AEvidence: A
Management: Stage IVManagement: Stage IV
Long acting bronchodilatorsLong acting bronchodilators Short acting bronchodilators PRNShort acting bronchodilators PRN Inhaled corticosteroidsInhaled corticosteroids EducationEducation Evaluate need for oxygen therapyEvaluate need for oxygen therapy Nighttime non-invasive ventilation?Nighttime non-invasive ventilation? Consider surgical optionsConsider surgical options
Surgical OptionsSurgical Options
Lung transplantationLung transplantation– Upper age limit: 60 yearsUpper age limit: 60 years– Consider for younger patients without Consider for younger patients without
serious co-morbiditiesserious co-morbidities– Few last long enough to get Few last long enough to get
transplantedtransplanted Lung volume reduction surgeryLung volume reduction surgery
– Consider if no serious co-morbiditiesConsider if no serious co-morbidities– Improves diaphragmatic functionImproves diaphragmatic function
ResourcesResources
NIH Asthma Guidelines:NIH Asthma Guidelines:
www.nhlbi.govwww.nhlbi.gov/guidelines/asthma//guidelines/asthma/ Global Initiative for chronic Global Initiative for chronic
obstructive lung disease:obstructive lung disease:
www.goldcopd.comwww.goldcopd.com Resource for asthma action plans, Resource for asthma action plans,
info:info:
www.cine-med.com/asthmawww.cine-med.com/asthma//