GOLD Goals for COPD treatmentDisease Management should now be focusing on 2 key areas1. Reducing Symptoms2. Reducing Risk. Adapted from GOLD 2013
GOLD 2013 Combined assessment of COPD GOLD 4 ≥2 GOLD 3 Less symptoms More symptomsSPIROMETRIC CLASSIFICATION EXACERBATION /YEAR High risk high risk GOLD 2 <2 Less symptoms More symptoms GOLD 1 Low risk low risk mMRC 01 mMRC ≥2 CAT <10 SYMPTOMS CAT ≥10 Adapted from GOLD 2013
Pharmacological Treatment Patient Recommended Alternative Choice Other possible treatments First Choice LAMA SAMA prn or A or LABA Theophylline SABA prn or SABA and SAMA LAMA SABA and/or SAMA B or LAMA and LABA Theophylline LABA ICS + LABA LAMA and LABA SABA and/or SAMA C or LAMA + PDE4-inh. Theophylline LAMA LABA + PDE4-inh. ICS + LABA ICS + LABA and LAMA or Carbocysteine And/ or ICS+LABA and PDE4-inh. or D SABA and/or SAMA LAMA LAMA and LABA or Theophylline LAMA and PDE4-inh.(Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.)*Alternative medications can be used alone or in combination with other options in the First and Second columns Adapted from GOLD 2013
Patient Type (A) Treatment Options 1st Recommended choice : <2 • SABA Prn Or SAMA Prn GOLD 2 EXACERBATION /YEAR Alternative Choice: • LABA Or LAMA Or GOLD 1 Less symptoms •SABA and SAMA Low risk Other Possible treatments *: mMRC 01 • Theophylline CAT <10* Medications can be used alone or in combination with other options in the First recommended or alternative choices Adapted from GOLD 2013
Short acting bronchodilatorsUsed as reliever medicationTypes: ▫ Β2 agonists Salbutamol ▫ Anlicholinergics: Ipratroium
Potential Side Effects of COPDtherapy: β2 AgonistsSide effects include: ▫ Resting sinus tachycardia ▫ Ventricular arrhythmias (rare) ▫ Somatic tremor ▫ Hypokalemia ▫ Mild falls in PaO2
Potential Side Effects of COPDTherapy: Anticholinergic AgentsSide effects are less common versus systemic agents (e.g., atropine) ▫ Dry mouth is most commonly reported adverse event (related to local deposition of agent) ▫ Possible worsening of glaucoma ▫ Occasional prostatic symptoms
Patient Type (B) Treatment Options 1st Recommended choice : <2 LABA or LAMA EXACERBATION /YEAR GOLD 2 Alternative Choice: • LABA and LAMA GOLD 1 More symptoms Other Possible treatments *: low risk • SABA and/or SAMA • Theophylline mMRC ≥2 CAT ≥10* Medications can be used alone or in combination with other options in the First recommended or alternative choices Adapted from GOLD 2013
Long-acting Bronchodilators inCOPDPatients with dyspnea that is not relieved by the as-needed use of a short-acting bronchodilator should have a long acting Inhaled bronchodilator added to therapyThese agents include: ▫ Formoterol ▫ Indacaterol ▫ Tiotropium ▫ Salmeterol
LABAs in COPD guidelines British Thoracic Society suggest that long-acting bronchodilator therapy should always be considered when patients with COPD are symptomatic GOLD treatment recommendations for patients with stable COPD are characterized by a stepwise increase in therapy according to disease severity ATS/ERS COPD guidelines have indicated the importance of starting regular maintenance therapy based on the presence of persistent symptoms, regardless of the disease stage. The choice of agents may be based primarily on individual response, cost, side-effect profile and availability. International Journal of COPD 2008:3(4) 521–529
Patient Type (C) Treatment Options 1st Recommended choice : LABA + ICS ≥2 Or EXACERBATION /YEAR •LAMA GOLD 4 Alternative Choice: •LABA and LAMA Less symptoms GOLD 3 •LAMA + PDE4-inh. High risk •LABA + PDE4-inh. mMRC 01 Other Possible treatments *: CAT <10 •SABA and/or SAMA •Theophylline* Medications can be used alone or in combination with other options in the First recommended or alternative choices Adapted from GOLD 2013
Patient Type (D) Treatment Options 1st Recommended choice : • LABA + ICS And / or LAMA ≥2 EXACERBATION /YEAR Alternative Choice: GOLD 4 • LABA + ICS and LAMA or • LABA + ICS and PDE4-inh. or • LABA and LAMA or More symptoms GOLD 3 high risk • LAMA and PDE4-inh. Or Other Possible treatments *: • Carbocysteine mMRC ≥2 • SABA and/or SAMA CAT ≥10 • Theophylline* Medications can be used alone or in combination with other options in the First recommended or alternative choices Adapted from GOLD 2013
Impact of Exacerbations in COPD Patients with Frequent Exacerbations Greater Airway InflammationFast Decline in lung function Higher Mortality Poorer Quality of Life
Inhaled CorticosteroidsInflammation plays central role in COPD & therapies aimed at halting or reversing inflammation are neededInhaled corticosteroids (ICS) decrease rate of exacerbation & may improve response to bronchodilators & decrease dyspnea in stable COPDNo studies show ICS reduce loss of lung functionStudies have not established a survival benefit when ICS is combined with long-acting B2 agonists
Roflumilast Overview First oral COPD specific anti-inflammatory therapy for patients with severe COPD who have symptoms of chronic cough and sputum, history of frequent exncerbations. and on maintenance bronchodilat0r therapy A potent and selective Inhibitor of the PDE4 enzyme, that targets the chronic inflammation underlying COPD Indicated in EU for maintenance treatment of severe COPD associated with chronic bronchitis in adult patients with a history of frequent exacerbations, as add-on to bronchodilator treatment Significantly reduced exacerbations and improved lung function when added to maintenance therapy with bronchodilators, in patients with severe COPD, symptoms of chronic bronchitis, a history of frequent exacerbations
Influenza Vaccination:Risk for Any ExacerbationEvaluation of results from randomized clinical trials indicates that inactivated influenza vaccine reduces exacerbations in COPD patientsThe magnitude of this benefit is similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenzaThere is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.
Selecting an Appropriate Aerosol DeliveryDevice is Critical to Successfully Tx COPDThe number of different devices- each with different characteristics, requiring different inhalation techniques -can be confusing for the patient and the clinician.Consider the unique features of the Inhaler In relation to the ventilatory nuances imposed by the disease.Multiple devices are commonly used by patients with more severe disease, but can be confusing – leading to decreased adherence.
Pressurized Metered-doseInhalers (pMDIs)Most commonly used handheld aerosol delivery deviceNewer HFA-propellants provide an aerosol with lower forward jet velocity than the older CFC-propelled MDIsPotential issues: ▫ Hand-breath coordination ▫ Taking a slow rather than rapid inhalation ▫ whether to inhale from residual volume or functional capacity ▫ Length of breath-hold at end-inspiration ▫ Priming and shaking before use
Dry Powder Inhalers(DPIs)Breath-actuated- thus, eliminate many of the problems associated with coordinating pMDI actuation and inhalationPotential issues: ▫ Need for higher inspiratory flow rate vs. pMDI ▫ Resistance can vary 10"fold depending on design ▫ Inhaler preparation and failure to hold device correctly may contribute to high error rates in some patients
NebulizersAlternate to pMDIs and DPIs for providing aerosol therapy, provided that the drug is available in liquid formMost user-friendly of the inhaler devicesFrequently prescribed for patients with COPD ▫ Minimal coordination and effort is required during Inhalation compared to pMDIs and DPIs ▫ Aerosol is continuously produced ▫ Patient can sit comfortable, using tidal-volume breathing
Manage Stable COPDKey PointsRegular treatment with inhaled glucocorticosteroids is appropriate for symptomatic COPD patients with an FEV1 <50% predicted (Stage lll: Severe COPD and Stage IV: Very Severe COPD) and repeated exacerbations e.g. 3 in the last three years (Evidence A).This treatment has been shown to reduce the frequency of exacerbations and improve health status (Evidence A).
Manage Stable COPDKey PointsChronic treatment with systemic gluco- corticosteroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A).All COPD-patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).
Bronchodilators in Stable COPDBronchodilator medications are central to symptom management in COPDInhaled therapy is preferredThe choice between beta-2 agonist, anticholinergic, theophylline, or combination therapy depends on availability and individual response in terms of symptom relief and side effects
Life-Prolonging COPD TherapiesSupplemental oxygenSmoking cessationSurgery for selected patients: predominantly upper-lobe emphysema and low exercise capacity
NOTT StudyPatients received continuous O2 or nocturnal O2O2 dose adjusted for PaO2 of 60 - 80 mm Hg; increased by 1 L/min for exercise and sleep
MRC studyTreatment group received O2 at least 15h/d (including sleeping hours) at 2 L/min; higher if needed to achieve PaO2 >60 mmHg
Indications for LTOT Based on randomized controlled Based on Less Evidence clinical trials Continuous oxygen use Intermittent oxygen use ▫ Resting PaO2≤55 mm Hg ▫ Desaturation (Spo2≤ 88%) ▫ Resting PaO2 of 56-59 mm Hg with with activity any one of the following: ▫ Desaturation (Spo2≤ 88%) Dependent Edema at night P pulmonale on the electrocardiogram(P wave exceeding 3 mm in standard lead II, III or a VF) Polycythemia( hematocrit,> 56%)Spo2 = oxygen saturation by pulse oximetry. Stoller, Chest 2010;138:179
Oxygen Source: CylindersNot practical as primary systemUsed as a backup for primary O2 system or for portability
Oxygen ConcentratorOxygen from air (≈ 90-95%)Most to 5 L/min; some to 10 L/minSimple; low maintenanceElectrically poweredBackup cylinder needed or portable concentratorLess patient phobia than other systemsConventional concentrators not portable
Portable concentrators• Maximum O2 produced and the dosing of the O2 differ by concentrator.• If the patient increases the demand with a higher dose setting orrespiratory rate, either delivered dose. %O2, or both will decrease.
Liquid OxygenMore efficientBase unitPortable unit (filled from base)Higher flows availableRequires refillingBackup cylinder neededPatient phobia (thermal injury)
Oxygen Conserving DevicesPulse dose (battery powered): fixed volume per breath; use standard cannula ▫ O2 on every breath or on alternate breaths ▫ Vary dose by peak flow or durationDemand devices (pneumatically powered): deliver oxygen only during inhalation; use dual- lumen cannulaReservoir cannulaTranstracheal oxygen
Oxygen Conserving DevicesCylinders last longerFewer complications (drying, irritation, taste)Cylinder devices: fit on any cylinderLiquid devices: incorporated into deviceDifferent devices produce different oxygenation and different devices may respond differently to varying conditions (exercise, sleep).Prescription should be device specific
Transtracheal OxygenOxygen delivered directly into the trachea through a surgically implanted catheterAdvantages: inconspicuous; lack of nasal. ear, and facial irritation; remains in place during sleep and exerciseComplications: subcutaneous emphysema, bronchospasm, and paroxysmal coughing during placement; late complications include dislodged catheters, stomal infections, mucous balls (may be fatal)
SummaryO2 therapy for the patient with COPD is life- savingO2 source can be cylinder, concentrator, or liquidPortable O2 is important (necessary!)O2 conserving devices extend the time patient can be away from fixed O2 sourceImportant for the clinician to appreciate differences between LTOT devices