Reference:

    NEJM 2010, "Outpatient Management of COPD",

    MKSAP16

    Respiratory Guidelines 2003 - Acute Exacerbations of COPD

    Respiratory Guidelines 2013 - Prevention of Acute Exacerbations of COPD

    Introduction

    • Defined as: Progressive partially reversible airway osbruction and lung hyperinflation.  Increasing frequency and severity of exacerbations.
      • Expiratory flow limination with dynamic collapse of small airways compromises the ability of patients eo xpel air, resulting in air trapping and hyperinflation.
    • 3rd most common cause of death.
      • 50% of COPD not yet diagnosed. 

     

    Pathophysiology

    • Slowly progressing inflammatory disease of the airways and parenchyma
    • Gradual loss of lung function, increasing obstruction to expiratory airflow. Causing:
      • 1. Inflammatory narrowing of small airways (bronchitis)
        AND
      • 2. Protyolytic digestion of lung tissue adjacent to these airways (emphysema)
    • As disease progresses, inflammation intensifies, exacerbations worsen etc..
    • Inflammation damage and thicken small airways, causing scarring of small airways.  Proteases released to dissolve adjacent lung tissue, which generally tethers small airways to keep them open.  Small airways collapse, decreased elastic recoil of lungs.
      • Causes lung hyperinflation.  Often "dynamic hyperinflation", as they exercise they need to take bigger breaths.
    • COPDpathophys.png
    • (From NEJM 2010 "Outpatient Management of severe COPD")
    • Notice that the lung volume in COPD exercising is going up.  This is called dynamic hyperinflation as there is breath stacking.  Size of the breaths is decreasing.

     

    • Complications:
      • Pulmonary HTN
      • Cor pulmonale
      • Pneumonia
      • Pneumothorax
      • Bronchiectasis
      • Atelectasis
      • Lung Cancer

     

    Risk Factors

    • ***Tobacco Smoking***
      • Once stop smoking, rate of decline of FEV1 will go back to the normal rate.
      • Not everyone who smokes gets COPD, associated with some predisposition.
      • Only 20% of chronic heavy smokers get COPD
      • Smoking cessation improves survival, slows progression of COPD
    • Environmental:
      • Vapours / Irritants / Fumes / Dust / Chemicals
      • Biomass fuel burning (oils, organic fuels, wood etc..)
    • Genetics
      • Alpha-1-antitrypsin Deficiency
        • Consider if <45yo or has COPD with no smoking hx.
        • Basillar rather than upper lobe predominant.
        • Often concominant liver disease.
      • Other Genes:
        • Alpha-1-antichymotrypsin, alpha-2-macroglobulin, Vitamin D Binding Protein, some blood group antigens.
    • Poor SES, low educational attainment, poor nutrition
    • Low SES women inhaling biomass via indoor cooking (organic fuels from wood, coal) and animal feces.
      • Effort to provide cook stoves.

     

    • Note 1 in 5 pts with COPD never smoked.
      • Often idiopathic.
      • Dusts? Chemicals? Biomass smoke? 

    Symptoms

    • Dyspnea, chronic cough, wheezing
      • Sputum production
      • Decreased exercise tolerance
      • Smoking hx.
      • Etc

     

    Assessment

    • Spirometry testing in all patients with suspected COPD.
    • FEV1/FVC < 0.7 post-bronchodilator --> Non-reversible airway obstruction (most important)
      • COPD Diagnostic Criteria:

        1. FEV1 < 80% pred post-bronchodilator
          AND
        2. FEV1/FVC < 0.7 post-bronchodilator 
           

        Notes:

        • This cutoff = false positives in elderly
        • Compare ratio to predicted based on age/height. (more accurate)

         
    • Decrease in DLCO correlates to level of emphysema. 
    • Spirometry Severity

      • Classification of Lung Function Impairment
        GOLD COPD Stage   FEV1 on Spirometry 
        (Postbronchodilator)
        GOLD 1 Mild ≥80%
        GOLD 2 Moderate 50% - 79.9%
        GOLD 3 Severe 30% - 49.9%
        GOLD 4 Very Severe < 30 %
      • GOLD = Global Initiative for Chronic Obstructive Lung Disease
         
    • Functional Assessment:

      • M-MRC Dyspnea Scale (Prognosticates survival in COPD)
        Modified Score Old Grade Bottom Line CTS Guideline Wording
        0 Grade 1 Only during exercise

        "Not troubled by breathlessness except with
        strenuous exercise."

        1 Grade 2    Exertion affected
        (walking fast/uphill)

        "Troubled by shortness of breath when hurrying on
        the level or walking up a slight hill"

        2 Grade 3 Walking affected
        (slow, stops for breath)

        "Walks slower than people of the same age on the
        level because of breathlessness or has to stop for
        breath when walking at own

        pace on the level"

        3 Grade 4 Walking affected
        (stopping frequently)

        "Stops for breath after walking about 100 yards
        (90 m)or after a few minutes on the level"

        4 Grade 5 ADLs affected

        "Too breathless to leave the house or breathless
        when dressing

        or undressing"

      • Modified Medical Research Council Criteria
         
    • Also "GOLD Classification system for COPD severity" exists, though not as popular.
       
    • BODE Severity Index
      • Advantage: takes into account spirometry and functional class.
      • Takes into account:
        • Bmi
        • airflow Obstruction
        • Dyspnea
        • Exercise capacity
      • Best predictor of mortality.
        • Mostly used for lung transplants (i.e. if ≥7, then 4-yr survival <20%.)
      • More involved
      • Variable

        Points

         

        0

        1

        2

        3

        FEV1 (% of predicted)

        ≥65

        50-64

        36-49

        ≤35

        6-Minute walking distance (meters)

        ≥350

        250-349

        150-249

        ≤149

        MMRC

        0-1

        2

        3

        4

        BMI

        >21

        ≤21

         

         

    Management

    Approach to Management

     

    1. Assess COPD severity, symptoms (MRC)
    2. Assess Therapy
      • Adherence to therapy
      • Inhaler technique (esp if "not responding")
    3. Non-Pharmacologic
      • Smoking Cessation most important, should be addressed at every visit.
      • Vaccinations: Influenza, Pneumococcal
      • Pulmonary Rehab
        • Recommended for symptomatic COPD with  FEV1 < 50% who can walk.  (If FEV1>50% can do pulm. rehab, but not as much benefit)).
          • NOT recommended if unstable angina, recent MI
          • Strengthens muscles, decreases air trapping, improves hyperinflation.
          • Study: Improvement in exercise capacity, less breathlessness, QOL, less psychiatric sx (anxiety/depression), less hospitalizations and shorter hosp. stay.
        • Pulmonary rehab is recommended for mod, severe, or very severe COPD with AECOPD in last 4 weeks to PREVENT future exacerbations (If last AECOPD >4w ago, not recommended to decrease exacerbations) (Respiratory Guidelines 2013 - Prevention AECOPD)
    4. Pharmacologic
      • (See Pharmacotherapy section)
    5. Oxygen therapy (only survival benefit if >12hrs/day of O2 use, so aim for 24hrs/day or none)

     

    Pharmacotherapy

    • Can reduce frequency of exacerbation, hospitalizations, symptoms, exercise tolerance.
    • (Note: smoking is the only way to stop progression)
    • Unlikely asthma, ICS aren't as effective.  ICS aren't even FDA approved for COPD, but used anyway.
    • COPDTx.png
    • CHEST COPD guidelines.
    • NOTE: Latest US guidelines: stable COPD patients with FEV1 < 60% should still get LA bronchodilator (i.e. LAAC)
      • <50% --> Pulmonary rehab.
      • LAAC = LABA (same efficacy), many pts prefer tiotropium. 
      • Montelukast (LTRA) not evaluated in COPD

     

    Surgery

    • Lung Volume Reduction Surgery
      • Indications:  (Only SEVERE COPD with maximal medical mgmt, severe air trapping with upper lobe emphysema)
        • ***Often considered those with apical bullae that can be resected***
      • Generally considered palliative.
          • Severe COPD, on maximal medical treatment
          • Completed pulmonary rehab
          • Evidence of bilateral predominant upper lobe emphysema on CT
          • Postbronchodilator TLC > 100% AND Residual Volume > 150% predicted
          • Maximum FEV1 > 20% and ≤45% predicted  (higher mortality if FEV1 < 20)
          • Ambient air arterial Pco2 ≤ 60 mmHg and Po2 ≥ 45 mmHg
      • Very rarely indicated: typically surgeon removes areas of both lungs that are severely damaged.
        • Does not improve survival
        • Improve lung mechanics
    • Lung Transplant
      • Bottom Line: very high BODE index with 4-yr survival ≤20% (and not too sick).
        • NOT shown to have survival benefit, but does improve QOL.
      • Patients must have a BODE Index of 7 to 10 AND

        History of hospitalization for an exacerbation associated with acute hypercapnia (PCO2 >50 mm Hg [6.7 kPa])

        Pulmonary hypertension, cor pulmonale, or both despite oxygen therapy

        FEV1 <20% of predicted and one of the following:

        DLCO <20% of predicted

        Homogeneous distribution of emphysema

        Arterial PO2 <55 mm Hg (7.3 kPa)

        Exclusion Criteria

        Age >65  && presence of comorbid conditions (Relative Contraindications)

        Infection with HepB/C with histologic evidence of significant liver damage
        Active or recent cigarette smoking, drug, or alcohol abuse, severe psychiatri cillness, documented non-adherence ot medical care, absence of social support. 
      • Survival Data:  (no survival benefit after 2 years)
        • 83% @ 1 year, 60% @ 3y, 43% @5y.
      • Criteria for referral for lung transplant evaluation include one of the following: pulmonary hypertension, cor pulmonale, or both despite oxygen therapy; history of exacerbation associated with acute hypercapnia; and FEV1 less than 20% of predicted with DLCO less than 20% of predicted or homogeneous distribution of emphysema. This patient has an FEV1 greater than 20% of predicted, a DLCO greater than 20% of predicted, and emphysema in the upper lobes; therefore, he is not a candidate for lung transplantation.

    Prevention of AECOPD

    • In addition to therapies mentioned above

     

    • PDE4 inhibitors
      • Roflumilast
        • Indication: Patient with severe COPD with frequent exacerbations with component of chronic bronchitis.  
        • S/E: Diarrhea, weight loss, nausea, headache, psych (anxiety, insomnia, depression).
          • Contraindicated in liver impairment.
          • P450 induction, careful with phenobarb, rifampin, phenytoin, etc..
        • Small improvements in lung function if roflumilast added to LABD
    • Azithromycin
      • For inflammatory effect
      • Albert et al - NEJM 2011
      • Randomized 1577pts with dx of COPD (FEV1<80%) to azithromycin 250mg po daily vs. placebo
      • Patients should have >40yo, were either on home O2, or had exacerbation requiring steroids in past 1 year.  Excluded those with exacerbations in past 4 weeks, tachycardia > 100bps, QTc > 450ms, hearing impairment on audiometry.
      • Result: Decreased exacerbations, improved QOL, but caused hearing deficits
      • GOLD Guidelines not yet recommending it because --> increased resistance, and side effects (hearing loss, QTc)
    • Alpha-1-Antitrypsin
      • Replacement indicated for those with relatively preserved lung function who is declining rapidly.
      • If advanced disease: too late! and someone with mild disease won't benefit either.
    • Cor Pulmonale patients
      • PDE5 inhibitors not studied much.  
      • Likely will decrease PA pressures, decrease cardiac output.
      • Downside: worsens V/Q mismatch, cause hypoxemia.  AVOID in COPD, only if carefully monitored.
    • Morphine
      • Central respiratory effect: reduces air hunger, dyspnea.
      • Can worsen CO2 retention, decreases drive to breathe.
      • Only used in palliative setting.
    • Antibiotics
      • Can be indicated for patients in ICU intubated or NIPPV.
      • A bit of research for using azithromycin on daily basis for anti-inflammatory effect. (some select patients who are colonized with bacteria)

    Criteria for Home O2

    • Taken from Ontario Guidelines
    • Need ABG
    • Eligibility:
      • All eligible COPD patients should be considered for O2 therapy REGARDLESS OF SYMPTOMS
      • Hypoxemia at Rest
        • PaO2 ≤ 55 mmHg OR O2Sat ≤ 88%
          OR:
        • if PaO2 is 56-60 mmHg OR O2Sat 89-90%, then maybe eligible if one of:
          • Pulmonary HTN
          • Cor Pulmonale
          • Erythrocytosis
          • Exercise limited by hypoxemia, improves with O2 therapy.
          • Nocturnal hypoxemia  (Must have sleep study to R/O sleep disordered breathing)
      • Hypoxemia on Exercise
        • PaO2 56-60mmHg (SaO2 89-90%)
          • Complicated, see guidelines.
          • Generally exercise limited by hypoxemia (O2sat <88%) on room air  AND documented improvement with supplemental O2
          • Must be motivated to improve activity level

    Bottom Lines

    • Only therapy proven to decrease rate of progression of lung function:
      • Smoking cessation
    • Only therapy shown to improve survival:
      • Home oxygen in patients with resting hypoxema.
        • Must wear O2 ≥15h/day improves survival.
      • AND smoking cessation.
    • Pulmonary rehab
      • Decreased breathlessness symptoms, increased participation, improved QOL, reduces hospitalizations and length of stay.
      • Does not help if cannot walk at baseline or if lack of motivation (if psych or other comorbidities).
      • Should have either quit smoking or be in smoking cessation programs.
    • Lung Reduction Surgery
      • LRS can improve survival in SELECTED patients (severe COPD, max therapy, w/ upper lobe emphysema, and significant air trapping).
    • Greatest Predictor of Future COPD Exacerbations:
      • 2 or more exacerbations in 1 year.
    • FEV1 does dicate treatment
      • < 60% - initiate LA bronchodilator (LAAC or LABA) even if controlled COPD (consider if >60%, weaker recommendation)
      • < 50% - consider pulmonary rehab.

    COPD Exacerbation

    • Characterized by:
      • Hallmark of COPD Exacerbation is increase dyspnea from baseline
      • Risk Factors: Baseline FEV1 in severe category (<50% pred.), 2 or more exacerbations that year, history of GERD
        (NOTE: PPI increases risk of Ventilator-Associated Pneumonia in ICU patients, but helpful in COPD patients)
      • Is a COPD exacerbation infectious?  (i.e. requiring antibiotics)

        Major Criteria  (aka Anthonisen criteria -  Recommend 2 of 3!)

        • Increase in sputum volume.
        • Increase in sputum purulence (generally yellow or green)
        • Worsening of baseline dyspnea
           

        "Additional" Criteria

        • Upper respiratory infection in the past 5 days.
        • Fever of no apparent cause.
        • Increase in wheezing and cough
        • Increase in RR or HR 20% above baseline.
        • Other non-specific signs/symptoms: fatigue, insomnia, depression, confusion.

        Mild Exacerbation = 1 major + 1 additional

        Moderate Exacerbation = 2 major criteria

        Severe Exacerbation = all 3 major criteria

     

    • Management:
    1. ABCs (+/- assisted vent)
      • Supplemental O2.. keep O2 low 90's to maintain ventilatory drive (otherwise worsens CO2).
        • If chronic CO2 retainer/hyperinflation --> 88-92%
      • NIPPV (Non-Invasive Positive Pressure Vent) - BiPAP
        • Improves survival, length of hosp, decreases need for intubation.
          • Use early (not last ditch effort!)
    1. Bronchodilators, often via nebulizer (SABA and SAAC)
      • (NOTE: Nebs vs. Puffers is controversial.  Some studies show increased toxicity with nebs (jiggery, urinary retention, etc..), and same outcomes as puffers, but argument is that nebs can get higher levels of drug into the system.  Generally in Kingston General Hospital nebs used for SEVERE bronchoconstriction and MDI used for less severe, but most Toronto hospitals restricted nebs because it aerosolizes SARS particles and are a risk to hospital staff)
        DOSES below are examples, please verify dosing yourself!:
      • Ventolin 2.5-5 mg nebs give q4h  (if ACUTE: give q20min x3 doses)
      • Atrovent 250-500 mcg nebs give q4h  (if ACUTE: give q20min x3 doses)
        OR 
      • Ventolin HFA (MDI) [100mcg/puff] 4-8 puffs q4h  (if ACUTE: use up to 8 inh q20m for up to 3h)
      • Atrovent (MDI) [17mcg/puff] 4-8 puffs q4h  (ACUTE: use up to 8 inh q20m for up to 3h)
        ALSO can give PRN dose with standing regimen
      • Ventolin HFA (MDI) 100mcg 2 puffs PRN q1h (or q30m)
      • NOTE: Often don't need atrovent PRN if giving standing (saturates M2 receptors, just increases S/E).
      • (NOTE: stopping long-acting bronchodilators is controversial as well.  Most centers opt to stop home LAAC and LABA as we are giving standing short acting maximal therapy, and can stop inhaled steroids as we are giving systemic.  The benefit of keep them ordered is they won't be forgotten at discharge).
    2. Systemic Steroids (IV methylprednisolone or prednisone)
      • Prednisone 50mg for 5 days.
      • (Based on lecture from Dr. Lockheed (Canadian thoracic society) recommend methylprednisolone (solumedrol) IV 125mg x3 doses followed by prednisone for faster onset of action).
      • Shortens hospital stay, no effect on mortality.
    3. Antibiotics
      • (controversial, not as beneficial as steroids)
      • Use if signs of infection: rever, purulent sputum or increasing sputum, or if in ICU.
        • ICU: Levofloxacin
        • CAP: respiratory qunolone, or Macrolid + 3rd gen cephalosporin.
    4. (R/O other mimics):
      • CHF (COPDE can exacerbate HF)
      • PE
      • etc..
    • ICU level care if:
      • If severe dyspnea not responding to intense bronchodilator therapy.
      • Mental status changing
      • Worsening hypoxemia, hypercapnia, pH
      • NIPPV
    • Discharge criteria:
      • SABA given less frequently than q4h.
      • ABG stable x12-24hrs.
      • Understand correct use of medications.
    • F/U:
      • Early F/U prevents readmission rates (2-4w after discharge)
      • If left on O2, re-evaluate at 2w to see if still need O2.

    Indications for BiPAP

    • Initiate EARLY!!
    • Standard of care for moderate-to-severe COPD management.
    • Prevents intubation, helps clear CO2 (not CPAP, CPAP is for oxygenation only)
    • (Can also be used at home, rarely, for instance for better overnight breathing)
    • Indications for BiPAP

      Respiratory fatigue or increased work of breathing

      (i.e. accessory muscles of breathing,  paradoxical abdominal motion, intercostal indrawing)

      Acidosis (arterial pH <7.35) and/or hypercapnia (arterial PCO2 >45 mm Hg [6.0 kPa])

      Hypoxemia despite supplemental O2

      Contraindications

      Change in mental status or uncooperative patient

      (i.e. if too much CO2 already)

      High aspiration risk (positive pressure can cause gas in stomach)

      Viscous or copious secretions

     

    Indications for Intubation

      1. Inability to tolerate of failure of NIV
      2. RR > 35 despite aggressive medical tx.
      3. Life-threatening hypoxia (despite high FiO2)
      4. Severe acidosis (pH < 7.25) and/or hypercapnia (arterial Pco2 > 60 mmHg)
      5. Respiratory Arrest
      6. Somnolence or impaired mental status
      7. Cardiovascular complicagions (Hypotension, shock)
      8. Other (massive pleural effusion etc..)
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