#86: COPD: Diagnosis, treatment, PFTs, and nihilism

March 12, 2018 | By Leah Witt

Take a deep breath and tune in to this week’s episode full of COPD diagnosis and management pearls, with expert Dr. Denitza Blagev, a pulmonologist, intensivist, and Medical Director for Quality, Speciality Care at Intermountain Healthcare in Utah with a particular interest in physician wellness and issues related to women in medicine. We cover: history taking, interpreting PFTs, patient counseling, inhalers and medications, exacerbations, antibiotics, steroids, and who needs BIPAP…so basically everything you ever wanted to know about chronic obstructive pulmonary disease. Take our self assessment here.

Written and produced by: Leah Witt, MD, Cyrus Askin, MD. Edited by Matthew Watto, MD

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Test your knowledge

Self assessment questions.

Clinical Pearls:

1. Key indicators for COPD diagnosis include: dyspnea, chronic cough, chronic sputum production, recurrent lower respiratory tract infections, and smoke exposure in patient >40 yo (GOLD guidelines COPD 2017). Tobacco use is a key part of the history. Spirometry is confirmatory testing (NOT diagnostic in and of itself!).
2. Supplemental oxygen and tobacco cessation reduce mortality in COPD.
3. Smokers can be hypoxic despite normal resting O2 saturation because pulse oximeter cannot tell the difference between oxy- and carboxyhemoglobin. Check an ABG to determine pO2 and need for oxygen therapy.
4. Inhalers for COPD improve symptoms and exacerbations, NOT mortality. Patients w/o symptoms and exacerbations can get by w/albuterol as needed.
5. Consider azithromycin or roflumilast in patients with moderate/severe COPD (despite inhaler use) with the goal of decreasing exacerbation frequency.
6. The only thing you should NOT do in COPD is inhaled corticosteroids as monotherapy. -Dr Blagev
7. The only thing you should NOT do in Asthma long acting beta agonist monotherapy. -Dr Blagev
8. A significant change between pre- and post-bronchodilator spirometry suggests how much room for improvement exists with the addition of inhaled therapies. Once controlled, a significant post-bronchodilator response may be absent on subsequent spirometry.
9. Spirometry values are no longer at the center of how we stage/assess COPD. It is much more important to assess/manage other contributing factors like dysphagia, heart failure, and need for CPAP or BIPAP in order to prevent symptoms and exacerbations.

Case from Kashlak Memorial:

Part I: Mr. T is a 64 year-old man with coronary artery disease,  benign prostatic hyperplasia and urinary incontinence, who presents to the Pulmonary clinic at Kashlak as a referral from his primary care doctor with shortness of breath. He has had a cough with mucus production for the last several years, that worsens a few times per year usually when he has a cold. He is currently smoking, but is cutting back. He has been hospitalized for “asthma” 3 times in the last year, and treated with antibiotics. He has smoked 2 packs per day for 40 years. He is able to walk two blocks before becoming short of breath. His resting O2 saturation is 93%. He has an albuterol inhaler that he uses once a day.

Background:

Epidemiology

COPD is the 3rd leading cause of death in the US and 4th in the world (WHO 2016). In countries with significant air pollution (e.g. indoor wood burning cooking stoves), mortality is even higher.

Diagnosis (GOLD guidelines 2017)

History

Symptoms typically include progressive shortness of breath, cough with or without sputum production, intermittent exacerbations of symptoms often triggered by viral infections, and most patients have a personal history of tobacco smoking (or significant second-hand smoke or air pollution exposure).

Occasionally, patients will not report dyspnea or exacerbations in spite of a high suspicion for COPD– Dr. Blagev recommends asking very detailed questions about function (e.g. avoidance of exertion), prolonged respiratory viral infections, or symptoms related to cooking, chemical fumes, cleaning sprays, or air pollution.

If the history is atypical (e.g. patient has no smoking history), broaden the differential diagnosis (e.g asthma, congestive heart failure, and bronchiectasis) and seek additional work-up. Question COPD as a diagnosis if patients do not symptomatically improve with treatment (see below for management). Comorbidities affect symptoms and should be also be targeted for treatment (morbid obesity, pulmonary hypertension, OSA, diastolic dysfunction and renal failure).

Asthma-COPD overlap (Postma and Rabe. NEJM. 2015): consider if patient has peripheral eosinophilia, childhood history of asthma, or allergic triggers (e.g. seasonal allergies or animals).  

Consider evaluation for alpha-1-antitrypsin deficiency in patients with emphysema, which may be useful particularly for counseling family members. Replacement therapy is expensive with limited evidence (Cochrane 2010), but could be indicated in patients with mild/moderate obstruction or disease progression (follow spirometry at least annually) (Sandhaus et al. COPD Foundation. 2016).

Part II: Mr. T was sent for spirometry. He is 5’5” and 126 lbs.

Forced vital capacity (FVC): Actual 2.00L, Predicted 3.77L (53% predicted); post-bronchodilator 2.03L (53% predicted, change +1%)

Forced expiratory volume in 1 second (FEV1): Actual 0.80L, Predicted 2.66L (30% predicted); post-bronchodilator 0.78L (29% predicted, change -3%)

FEV1/FVC ratio (ACTUAL): 0.80L/2.00L (40%)

Spirometry

Not pathognomonic for a COPD diagnosis, and should be used as a confirmatory test if you have a high suspicion for the diagnosis by history.

Spirometry should be performed pre- and post-bronchodilator. A patient with COPD will have obstruction both before and after bronchodilators, and may or may not have a bronchodilator response (defined as increase in 12% AND 200mL in FEV1 or FVC).

The definition of pulmonary function testing (PFT) varies by PFT lab/institution, but typically includes spirometry, plethysmography assessment of lung volumes (“body box” measurements) and diffusing capacity of the lung for carbon monoxide (DLCO). Spirometry is sufficient to evaluate for COPD (and it is typically cheaper/more readily available), but if the diagnosis is more complicated PFTs can provide useful additional data. There’s no need to repeat spirometry at scheduled intervals unless you have a specific clinical question.

To complicate matters, some patients, typically with a tobacco history, may have COPD symptoms, but “preserved lung function” (Woodruff, et al. NEJM. 2016). These patients can be diagnosed with COPD based on the history and clinical features (including exacerbations) being compatible with COPD.

Dr. Blagev’s approach to interpret spirometry:

1. Look at the curve so to not miss the “forest for the trees”. FEV1/FVC ratio <70% should look curvilinear on the accompanying spirometry graph (see example below). Or check out this figure from Sketchy Med.
2. If ACTUAL FEV1/FVC ratio is <70%, obstruction confirmed.
3. Grade degree of obstruction is based on FEV1% predicted (predicted values are based on age, sex, and height) (ATS 2017).
4. Look at FVC. If it is normal, you’re done. If it is low, you might consider restriction in addition to obstruction, but this cannot be diagnosed on spirometry alone so full PFTs are needed. A low FVC could also mean that the patient has so much air trapping that they couldn’t exhale long enough.
5. Evaluate for bronchodilator response (defined as increase in 12% AND 200mL in FEV1 or FVC). The post-bronchodilator value gives you an idea of what optimal lung function could be with treatment.

Figure 1. Flow Volume Loop

FEV1: forced expiratory volume in 1 second
FVC: forced expiratory volume
TLC: total lung capacity
RV: residual volume

Grading severity

Traditionally, COPD staging was by FEV1 impairment alone (GOLD 1-4). However, newer staging incorporates exacerbation history and severity of dyspnea symptoms (GOLD A-D).

By spirometry: by FEV1% predicted

GOLD 1:  >80%
GOLD 2: 50-79%
GOLD 3: 30-49%
GOLD 4: <30%

By symptoms: increased recognition of outcome/mortality/hospitalization, driven by symptoms & exacerbation frequency.

GOLD A: mMRC 0-1 or CAT <10; 1 exacerbation not leading to hospital admission
GOLD B: mMRC ≥2  or CAT ≥10; 1 exacerbations not leading to hospital admission
GOLD C: mMRC 0-1 or CAT <10; 2+ exacerbations or 1 with  hospital admission
GOLD D: mMRC ≥2  or CAT ≥10; 2+ exacerbations or 1 with hospital admission

Counseling & Prognostication

Consider advance care planning conversations with all patients with COPD.

BODE index (Celli NEJM 2004): predictive score for 4-year survival

BMI: point assigned for BMI ≤ 21
Obstruction: defined by FEV1 % predicted
Dyspnea: assessed via the mMRC dyspnea scale
Exercise: measured via distance walked in the 6-minute walk test

Part III: Mr. T presents in January, and has developed increased shortness of breath, sputum production and decreased exercise tolerance. He is using his albuterol inhaler every 4 hours.

Management
Therapies that reduce mortality:

Tobacco cessation improves mortality and slows disease progression (Godtfredsen. ERJ. 2008).

Supplemental oxygen therapy can improve mortality in select populations. There is evidence to suggest a mortality benefit in patients with severe resting hypoxemia on room air (NOTT Annals of IM. 1980). Ideally, this is determined via an arterial blood gas measurement (PaO2 ≤55 mmHg) but can also be inferred by an SpO2 ≤ 88%. The LOTT trial examined patients with moderate resting hypoxemia (SpO2 of 89-93%) and/or moderate exercise desaturation (SpO2 < 90% for ≥10 seconds and ≥80% for ≥ 5 minutes while walking) and found that supplemental oxygen did not improve mortality of exacerbations(LOTT NEJM. 2016). Supplemental oxygen must be worn continuously to confer the mortality benefit. Consider assessment of hypoxemia via arterial blood gas (ABG) if patient is a chronic tobacco user, as many pulse oximeters do not distinguish between carboxyhemoglobin and oxyhemoglobin.

Non-invasive ventilation should be recommended if the patient has a PCO2 ≥52 mmHg when stable/not in an acute exacerbation, along with nighttime hypoxemia (SpO2 ≤ 88%). Evidence on mortality benefit is mixed– studies showing benefit use significantly higher inspiratory pressures (Konlein et al. Lancet Respiratory Medicine. 2014, McEvoy et al. Thorax. 2009, Clini et al. ERJ. 2002).

Non-mortality reducing therapies (GOLD guidelines 2017)

Inhalers should be prescribed for patients with exacerbations and/or symptoms. Inhalers are very expensive and it is important to assess which inhalers are covered by a patient’s formulary.

1st line: If the patient only has symptoms from a trigger (e.g. URI), then start by prescribing a short-acting bronchodilator such as albuterol.

2nd line: For chronic symptoms, start with either a long-acting anti-muscarinic (LAMA) such as tiotropium or a long-acting beta-agonist (LABA) such as salmeterol. LAMAs outperform LABAs (Chen et al. Respirology. 2017). LABA/LAMA combination is associated with a reduced rate of COPD exacerbations annually as compared to LABA/ICS (Wedzicha et al. FLAME investigators. NEJM. 2016). LAMAs have anticholinergic side effects such as dry mouth and urinary retention. Assess for antimuscarinic symptoms (do not add it to the short-acting therapy), and consider switching to a LABA if severe.

3rd line: Consider adding an inhaled corticosteroid (ICS) for moderate/severe COPD, however this should NEVER be prescribed as monotherapy (this is the exact opposite of asthma treatment, in which LABAs should never be as monotherapy and ICS are the cornerstone of therapy). ICS may increase the risk of pneumonia (Cochrane 2014) in COPD, so do not add if exacerbations are not frequent.

Systemic corticosteroids should not be used long-term in COPD as they cause many side effects and there is no evidence they improve symptoms/exacerbations.

Pulmonary rehab can help with symptoms and functional improvement/exercise tolerance (Cochrane 2015). It also reduces hospitalization if patients have had an exacerbation within the last month.

Azithromycin taken chronically (either low-dose daily or three times a week) can reduce exacerbations, but has the risk of adverse cardiac events due to QTc prolongation or ototoxicity (Uzun et al. Lancet Respiratory Medicine. 2014). These patients should have QTc monitoring and audiology follow-up. Azithro in last year reduces exacerbation in asthma too (Gibson et al. Lancet. 2017).

Roflumilast is a selective, long-acting, PDE-4 inhibitor with anti-inflammatory properties which may also be used to reduce exacerbations, but it is often more expensive than azithromycin with the side effect of GI upset. To date, there is no data to support using azithromycin and roflumilast in combination.

COPD Exacerbations (Wedzicha et al. ERJ. 2017)
Work-up for underlying etiology should include an assessment of viral and environmental exposures. Consider pulmonary embolism (PE) as a precipitant of an acute exacerbation (Rizkallah et al. CHEST. 2009).

Corticosteroids are first-line treatment for exacerbations. Typical therapy is prednisone 40mg x5 days. Data supports this limited course as opposed to a prolonged course for 14 days

(Leuppi et al. JAMA. 2013). However clinical judgment/symptom severity (ICU stay) may alter the prednisone course. Chronic prednisone for COPD does not reduce COPD exacerbations. Transition quickly from IV to PO corticosteroids if patient is taking PO adequately/without aspiration.

Short-acting bronchodilators may be delivered via inhaler, however if the exacerbation is so severe that a patient cannot generate adequate flow/breath holding to use the inhaler correctly, consider use of nebulized medication.

Maintenance medications: Dr. Blagev suggests continuing maintenance medication as prescribed, to maintain adherence. If the patient is hospitalized, this is an opportunity for respiratory therapy/nursing/physicians to provide additional education about how and when to use these medications. One caution is that a hospital’s formulary may not have a patient’s own maintenance medications, which can cause confusion. Assess appropriate inhaler use on rounds/in office.

Antibiotics should be considered for a COPD exacerbation if a patient has a change in sputum, increased cough, and severe exacerbation requiring hospitalization. Dr. Blagev recommends using azithromycin or doxycycline. Duration of therapy should not exceed 5-7 days (GOLD 2017). Dr Blagev recommends reserving fluoroquinolones for patients with pneumonia, or sputum culture growing pseudomonas.

Non-invasive ventilation or intubation is a CLINICAL decision, regardless of saturation. An ABG can help to characterize the degree of hypercarbia. BiPAP is generally the prefered option. High driving pressures facilitate ventilation.

Goal: Practitioners will diagnose COPD, provide patient counseling, and develop treatments plans for management of COPD in the acute and chronic setting.

Learning objectives:

After listening to this episode listeners will…

1. Diagnose COPD and grade severity
2. Have a framework for interpreting spirometry
3. Initiate medication management for patients with stable COPD and consider which therapies will improve mortality
4. Have a plan for managing COPD exacerbations

Disclosures: Dr Blagev and The Curbsiders report no relevant financial disclosures.

Time Stamps

• 00:00 NephMadness announcement
• 01:10 Disclaimer
• 01:45 Intro
• 03:50 Guest bio
• 05:03 One liner; What advice would you give our younger self?; Should I do a fellowship?; Book recommendations
• 10:30 Picks of the week
• 15:50 Case of COPD from Kashlak Memorial
• 16:55 Initial approach to a potential case of COPD
• 18:34 Misdiagnosis of COPD
• 20:10 Classic spirometry in COPD and GOLD 0
• 21:30 Diagnosis of emphysema
• 23:18 Diagnosis of chronic bronchitis
• 24:54 Counseling the patient with a new diagnosis of COPD
• 27:00 Spirometry
• 28:45 How to read PFTs
• 33:29 How to order PFTs and get what you want
• 36:00 Why does pre- and post-bronchodilator response matter?
• 38:45 Asthma COPD overlap syndrome
• 40:13 Staging of COPD, does it matter?
• 42:50 Prognosis in COPD
• 45:00 Therapies with mortality benefit
• 48:29 Therapies to improve symptoms and prevent exacerbations
• 52:00 Azithromycin as chronic therapy
• 53:00 Counseling patients on therapy
• 55:00 Short acting inhalers in COPD
• 56:20 Treatment of COPD exacerbations
• 59:18 Antibiotics, who needs them in exacerbation
• 61:52 Nebulized inhaled steroids
• 63:18 Duration of antibiotics and steroids during an exacerbation
• 66:30 Who needs BIPAP chronically?
• 69:22 Who needs BIPAP during an exacerbation?
• 71:33 How often should PFTs be repeated?
• 73:00 When should we suspect PE in COPD exacerbation?
• 74:25 Which labs should be check in the initial COPD workup?
• 76:46 Take home points

Links from the show:

1. Dr. Blagev’s book pick: Any book by Atul Gawande
2. Dr. Askin’s pick of the week: “The Barbell Prescription: Strength Training for Life After 40”
3. Dr. Watto’s pick of the week: Flashbooks— save time reading by getting audio summaries
4. Dr. Williams’s pick of the week: The Good Place (TV show)
5. Dr. Blagev’s pick of the week: Skiing! Particularly in Salt Lake City.
6. GOLD 2016 guidelines
7. Dr. Blagev’s blog