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//