5 Pearls on COPD

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Pearl 1: Diagnosis and Empiric Therapy

• COPD label without spirometry is very common
  • About 33% of patients are diagnosed empirically and do NOT receive spirometry
  • You cannot diagnose COPD without spirometry
• “History and physical examination are poor predictors of airway obstruction and its severity” - Joint statement from 2011 from  ACP, ACCP, ATS, and ERS 
  • 1 in 3 patients empirically diagnosed with COPD do NOT have airflow obstruction (AFO) on PFTs.
  • Despite not having obstruction on PFTs, 1 in 4 patients who are empirically treated continue to be treated a year and a half later!
• A note on defining airflow obstruction (AFO):
  • Historically (and currently, by GOLD), defined as post-bronchodilator FEV1/FVC < 0.7 or by FEV1 < 80% of predicted. 
  • However, there are concerns that this can ignore normal, age-associated decreases in FEV1/FVC and lead to overdiagnosis. 
  • The ERS/ATS are now recommending using the lower limit of normal (defined as the 5th percentile) to define AFO.
• Empiric initiation of maintenance inhalers for COPD generally shouldn’t be done
  • However, in patients with radiographic evidence of emphysema/COPD and with symptoms consistent with the diagnosis, it’s probably ok to start maintenance inhalers so long as outpatient PFTs are ordered for confirmation

Pearl 2: The Initial Visit–Blood Work and Initial Treatment Choices

• Blood work in COPD:
  • 1) Every new diagnosis of COPD should be checked for alpha-1-antitrypsin deficiency
  • 2) Every COPD patient should have a CBC with diff checked at least once to look at their eosinophils. Specifically, do not interpret eosinophils when they’re taking systemic steroids or have an acute infection.
    • The idea behind this is that COPD patients with higher eosinophils may have an allergic or inflammatory phenotype that an ICS will directly treat and therefore reduce exacerbations.
      •  Exact values differ between studies and individual’s practice patterns, but there’s evidence that peripheral eosinophils >100 cell/microL predicts 
        • a patient's risk of exacerbation and 
        • More likely to respond to an ICS. 
    • On the other hand, patients without high eosinophils don’t have an inflammatory phenotype and so are only getting the risk for immunosuppression and pneumonia with ICS use. 
      • ICS use is associated with an increased risk of PNA
      • Data supports that if eos are < 100, patients may have a higher rate of PNA and so at higher risk of harm from ICS use.
• Simplify inhalers by remembering that there are only 3 classes of medications:
  • 1) Beta agonists 
    • Generally end with “-ol”
    • E.g. formoterol, salmeterol
  • 2) Muscarinic antagonists
    • Generally end with “-ium”
    • E.g. tiotropium, aclidinium, the umeclidinium
  • 3) Inhaled corticosteroids 
    • Generally end with “-one”
    • E.g., fluticasone, beclomethasone
• The most widely used staging/grouping schema (see infographic) is described by GOLD, which uses a combination of spirometry, symptom burden, and history of exacerbations over the last year to determine grade and group. 
  • COPD grade informs prognosis 
  • COPD group informs initial therapy. 
    • Memorization of specific cutoffs isn’t necessary, and can be looked up.
• The way you assess symptom burden matters. 
  • COPD is more than a disease of breathlessness!
  • Consider using a standardized instrument to assess your patients-  a significant number of symptomatic patients will underreport dyspnea otherwise. 
    • The modified medical research council (mMRC) score has been used quite broadly due to its simplicity, but The GOLD recommended mMRC cutoff of 2 may be too high/cause understaging.
    • This matters because it can lead to under-treatment!
  • GOLD recommends the COPD Assessment Test (CAT), which assesses symptoms across 8 different dimensions, for its wide availability, predictive utility, simplicity, sensitivity to difference in state, and its correlation with scores on more comprehensive but unwieldy measures like the St George’s Respiratory Questionnaire (SGRQ).
• For Group A and B, you can start with either a LAMA or a LABA.
• For Group C, LAMAs are recommended over LABAs because they are more effective in reducing exacerbation rates
• For Group D, start with a combination of LAMA/LABA or LAMA/ICS, if the patient has the inflammatory phenotype and has higher eosinophil count.

Pearl 3: Inhaler Devices

• Studies have not identified a single device or delivery method to give superior control!
  • This is true on a population level, but the individual patient in front of you may have reasons to benefit from one device type versus another.
• Patients make device use errors regardless of device type. 
  • This is associated with worse disease control!
• Using different devices for rescue and maintenance inhalers worsens outcomes in both asthma and COPD–learning one technique is hard enough, and learning two is even harder.
• We haven’t gotten better at reducing error rates in the last half century!
  • Utilize your interdisciplinary colleagues–pharmacists can be important teachers of inhaler technique for patients
• Pressurized metered dose inhalers (pMDI)
  • These are the quintessential “inhalers” that most people think of when they hear the word inhaler. 
  • Medication is stored under pressure in the canister, and is released when the canister is pushed downward
  • Pros:
    • Familiarity
    • They can be used with spacers and valved holding chambers (VHCs)--details of which are below
  • Cons:
    • These have to be shaken before each dose to ensure a consistent dose is delivered
    • Requires coordination between pushing down and inhaling
    • They need to be primed (IE, wasting doses) if the inhaler has not been used in a few days (or it may not deliver a consistent dose) 
    • Substantial amount of oropharyngeal drug deposition, which is inefficient and can cause side effects
• Spacers and valved holding chambers (VHC):
  • Spacers are basically just big reservoirs that you add on to the pMDI
  • VHCs are basically spacers with a one way valve
  • Why use spacers or valved holding chambers? 
    • 1) They slow down the drug particles and reduce particle size, which decreases oropharyngeal deposition 
    • 2) Both (though more so with VHCs) start to decouple pushing down on the canister and inhalation by holding the drug inside the reservoir
  • NOTE: Even though there’s a reservoir, patients should only use one puff at a time--using more puffs greatly reduces the fraction of the dose that is inhaled (IE 2 puffs at once is less than 1 puff followed by another puff).
• Dry powder inhalers (DPI)
  • These create an aerosol by drawing air through a dose of powdered medication
  • Pros
    • You do not need to coordinate pushing down with inhaling!
    • These devices often have a dose-counter within them
  • Cons
    • You have to be able to generate a sufficient inspiratory flow to aerosolize the drug
      • There aren’t hard and fast rules about when a patient won’t be able to do this, but more severe emphysema or hyperinflation on imaging can be signs to be cautious of this device type
      • Up to ⅓ of patients after a COPD exacerbation have peak inspiratory flow rates < 60 L/min
    • Humidity can make the powder clump, making it harder to aerosolize the drug--decreasing the lung deposition and increasing oropharyngeal deposition
      • Single dose capsules can protect against this, but then have to be loaded individually per dose
• Soft mist inhalers (SMI)
  • SMIs are devices that are shaped like tubes that work by having the patient twist part of the inhaler and then push a button that releases an aerosolized mist
  • Pros
    • Dose delivery does not depend on inspiratory flow
    • No need to shake (though you should prime them if you haven’t used them in a while)
    • The mist moves slower and lasts longer than pMDIs, which leads to more lung and less oropharyngeal deposition
    • The slower mist means patients have longer to inhale, decreasing the urgency of coordinating working the inhaler with inhalation
    • These devices also usually have a dose counter built into them
  • Cons
    • They still require coordination of working the inhaler and inhalation
    • The patient usually has to load a cartridge the first time they use it
    • Not all medications are available in this format
    • These can be more expensive because they are newer

Pearl 4: Inhaled Steroids and Inhaler Escalation

• Every visit should have a review of symptoms, exacerbations, and inhaler technique. 
• Gold recommends annual spirometry to monitor for rapid disease progression 
• It can also be useful to monitor other measurements of lung function/gas exchange such as functional capacity via a 6MWT, as this helps prognosticate
• Try and de-escalate inhaled steroids if you can–there is evidence of a dose dependent risk of systemic side effects with inhaled steroids!

• GOLD recommends considering de-escalating from an ICS if they develop pneumonia, if it doesn’t decrease their exacerbation frequency, or if there wasn’t an appropriate indication for the ICS in the first place (IE, to reduce exacerbation frequency in someone with high eosinophils).
  • Be aware that some patients can have more exacerbations when their inhaled steroid is decreased, so this should be done carefully and with close follow up.
    • Generally speaking, this should be done gradually over an extended period of time

• Other inhaled medications are not adjusted via GOLD group. They are adjusted based on the specific issue being targeted: dyspnea or exacerbations. Gold has algorithms for both. 
  • To simplify, add either a LAMA or LABA (whatever the patient isn’t already taking) so they are on combination therapy. And think about inhaled steroids if they have high eosinophils and frequent exacerbations.
  • If they are already on a combination of inhalers and are still short of breath, check their technique. If this isn’t the issue, try adjusting the inhaler device or specific drug within that class they’re inhaling (EG, a different LABA).
  • Finally, as part of management of refractory COPD with frequent exacerbation there are roflumilast and other PDE4 inhibitors. These are for patients with an FEV1 < 50%, and are generally only prescribed for severe COPD and most patients will not be on them.
• Pulmonary rehab is incredibly important–it raises quality of life, reduces readmissions, and lowers mortality.
  • It is so effective that the Cochrane review recommended against further studies of its effectiveness.
  • Accessibility can be an issue, but there is essentially no reason not to refer a patient. It’s just like ordering outpatient physical therapy.

Pearl 5: Communication, Palliative Care, and End of Life Care in COPD

• Communication about COPD is analogous to communication about other serious illnesses like CHF or cancer. 
• The mortality rate post-hospitalization for COPD exacerbations is very high: the one year mortality ranges from 23% (post-floor admission) to 35% (post-ICU admission). The 5 year mortality rate post-hospitalization is about 50%.
• Exacerbations can often be a good trigger to talk about GOC and values with patients
• Prognosticating is hard! The classic teaching is that COPD is a disease with a gradual decline in function punctuated by acute exacerbations, but in fact progression can be very heterogeneous
• Patient death is often unanticipated by loved ones and caregivers 
• BODE index: 
  • This stands for BMI, Obstruction, Dyspnea, and Exercise, and is a composite score that is a better predictor of subsequent survival than any individual component (and than many other scores).
  • These are quantified using % predicted FEV1, mMRC score, and 6 minute walk distance. 
  • BODE scores give an estimate of 4 year survival. 
  • GOLD recommends  that, where possible, a scoring system like BODE be used a few months after discharge from a COPD exacerbation to assess prognosis 
• It’s important to discuss what quality of life and functional status things are non-negotiable early and often with a phased introduction of supportive/palliative care because our patients are going to get sicker and their functional status will almost certainly decline. 
• There is not a wrong time to do ACP or talk to your patients about their values. This isn’t just about yes or no procedural questions, but about getting to know the person you’re talking to.
• Outpatient palliative care can be a limited resource, so do not be afraid to do this yourself!

Contributors

Luke Hedrick, MD – Author/Host

Shreya Trivedi, MD, ACP Member – Author/Host

Kai Saukkonen, MD – Expert Discussant

Richard Schwartzstein, MD, FACP – Expert Discussant

Rebecca Omlor, MD – Expert Discussant

Ali Trainor, MD – Author/Host

Aaron Troy, MD – Producer/Author

Reviewers

Nick Mark, MD

Lakshman Swamy, MD

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date:  June 22, 2022

Expiration Date: June 22, 2025

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