© copyright annals of internal medicine, 2011 ann int med. 154 (7): itc4-1. terms of use the in...

© Copyright Annals of Internal Medicine, 2011Ann Int Med. 154 (7): ITC4-1.

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in the clinic

Chronic Obstructive Pulmonary Disease


What is chronic obstructive pulmonary disease (COPD)?

Abnormal inflammatory response to noxious particles or gases

Characterized by progressive airflow obstruction

Variety of respiratory symptoms (chronic bronchitis) or signs of emphysema

Asymptomatic pts may meet spirometric diagnostic criteria for COPD

COPD treatable, preventable but incurable

4th leading cause of mortality almost 100% in age-adjusted mortality from 1970 to 2002 due to COPD


Which patient populations are at risk?

≈ 80 - 90% due to cigarette smoking

15% risk for clinically significant COPD among smokers; may underestimate risk

Effect of environmental (“second-hand”) smoke in development of COPD less clear

Genetic factors play role in susceptibility best defined being emphysema related to α1-antitrypsin deficiency

Pts rarely ≤35 yrs COPD develops only after inhalational exposure of sufficient intensity & duration


Should clinicians screen asymptomatic patients?

Spirometry not recommended in the absence of symptoms (USPSTF, ACP/ERS/ATS guidelines)

Some organizations (GOLD) suggest screening pts with risk factors (smoking + age > 35 y) suggesting:

Early detection = opportunity for pts to stop smoking

Informing pts of abnormal spirometry (“lung age”) may encourage smoking cessation

Conflicting data re: any change in outcomes

Likely ½ of patients with COPD have not been diagnosed

Evidence does not support screening in general population


When should clinicians consider a diagnosis of COPD?Hx of significant exposure to tobacco smoke

esp with: cough sputum production dyspnea decreased exercise tolerance

Chronic bronchitis (≥90d cough + sputum in each of 2 consecutive yrs) and Emphysema (hyperinflation on exam, imaging to confirm) commonly assoc’d w/COPD but neither required for Dx

Hyperinflation (e.g. hyperresonance, distant breath sounds) may occur in advanced disease


What is the role of pulmonary function testing in diagnosis?

Spirometry essential for COPD Dx and classification : postbronchodilator FEV1/FVC ratio <0.70 considered diagnostic threshold

FEV1 percentage predicted classifies COPD as mild (>80%) moderate (50%-80%) severe (30%-50%) very severe (<30%)

Degree reversibility (FEV1 improvement after bronchodilator or glucocorticosteroids) not recommended for Dx, DDx from asthma, or prediction of response to long-term Tx

Lung volume and diffusing capacity may support Dx


What is the role of pulmonary function testing in diagnosis?

Arterial blood gases and pulse oximetry

Determine candidates for long-term oxygen therapy

Identify chronic hypercapnia

May further characterize severity of COPD; suggest presence of emphysema, or exclude other lung diseases

Spirometry also for calculating BODE index

BMI; Obstruction (measured by FEV1); Dyspnea (Modified

Medical Research Council); Exercise (6-min walk test)

Increasing BODE = increased risk for hospitalization and poor long-term prognosis

BODE index also used to evaluate for lung transplant


How should clinicians approach drug therapy?

MMRC Dyspnea Severity Scale* for Calculation of BODE Index

Severity Score Degree of breathlessness related to activities

None 0 Not troubled w/ breathlessness except w/ strenuous exercise

Mild 1 Troubled by SOB hurrying or walking up slight hill

Moderate 2 Walks slower than people of same age due to breathlessness or has to stop for breath when walking at own pace on level ground

Severe 3 Stops for breath after walking ≈100 m or after few mins on level ground

Very severe

4 Too breathless to leave house or breathless when dressing or undressing

Adapted from VA and DoD guidelines Continued…



Adapted from VA and DoD guidelines

Variable Points on BODE Index

0 1 2 3

FEV1 (% predicted) ≥65 50-64 36-49 ≤35

Distance walked in 6 min, meters ≥350 250-349 150-249 ≤149

MMRC dyspnea scale score 0–1 2 3 4

Body mass index >21 ≤21

Points for each variable summed w/ possible range 0–10

Higher numbers worse prognosis


What other lab tests should clinicians order when evaluating COPD?No tests other than spirometry routinely recommended

Chest X-ray

CT scan

ECHO

α1-antitrypsin testing

Exercise testing

May show destruction pulmonary parenchyma in pts w/ emphysema May indicate possibility of cor pulmonale from pulmonary HTN

Use of vasodilators for pulm HTN in COPD off-label and of no proven benefit may not improve exercise tolerance or reduce PH, may worsen oxygenation

Consider measuring level in pts w/

• COPD onset < 40 years old

• Absence of recog’d risk factor (e.g., smoking, occupational dust exposure)

• Family Hx emphysema or α1-antitrypsin deficiency, bronchiectasis, liver disease, or panniculitis

May be useful in diff’l Dx of pts w/ dyspnea when unclear if symptom origin pulmonary or cardiac

May show flattened diaphragm and hyperlucency

Jennifer Wilson

rewrote question to shorten

Jennifer Wilson

from itc: "...with onset as early as thefifth decade of life..."Is this correct? or is it w/ earlier onset?


What other disorders should clinicians consider in patients with suspected COPD?

Any condition that produces airflow obstruction

Asthma Bronchiectasis Cystic fibrosis Bronchiolitis Upper airway obstruction (due to tumors of trachea, tracheal stenosis, tracheo-malacia, vocal cord dysfxn)

Less common Dx

Other pulmonary conditions that cause dyspnea (interstitial lung disease; pulmonary arterial HTN)

Chest wall disorders (kyphoscoliosis)

Cardiac causes (some may also coexist with COPD)


How should clinicians distinguish between COPD and asthma?

Pts w/asthma… Usually develop symptoms at

younger age

Less likely to be smokers

Experience symptoms intermittently, w/more variability (may be seen with monitoring daily peak flow)

Spirometric obstruction, cough, wheeze, and dyspnea common to both COPD and asthma

Pts w/COPD…Disease onset usually later

Chronic productive cough common

Dyspnea more persistent

Generally less consistent response to drugs (inhaled corticosteroids and bronchodilators)


Which smoking cessation interventions are most effective?

Urge all patients with COPD who smoke to quit and to enroll in a smoking cessation program

More structured smoking cessation programs effective in up to 30% of pts at 1y

Typically include: 2 or 3 longer advice sessions

Meds (e.g., nicotine prep’ns, bupropion, varenicline)

Stopping smoking reduces decline in pulm fxn & mortality

Multicenter RCT of intensive smoking cessation program including behavioral modif’n and nicotine gum vs. placebo: Over 5 yrs, mid-aged smokers in intervention group had slower rate of decline in FEV1 (34 mL/y) than those in placebo group (63 mL/y)

Follow-up: After 14.5y, all-cause mortality significantly lower in smoking cessation group than in usual care group (8.83 vs. 10.38/1000 person-yrs; P=0.03)



Assess disease severity before initiating treatment

Check FEV1 (note, however, that symptoms don’t necessarily correlate w/ FEV1)

Ask about baseline symptoms

Ask about nature and frequency of exacerbations

Use validated instruments for additional info

Modified Medical Research Council (MMRC) Dyspnea Severity Scale for Calculation of BODE Index


Step Tx for pts w/COPD*

*ATS/ERS guidelines



How should clinicians approach drug therapy? Overall Tx strategy includes smoking cessation, inhaled

meds, education, pulmonary rehabilitation & long-term oxygen Tx in hypoxemic pts

Cornerstone of pharmacotherapy inhaled meds (β2-agonists, anticholinergics, corticosteroids)

Tx goal: symptom relief, particularly dyspnea, prevention of exacerbations, improvement in long-term respiratory health status

Only smoking cessation convincingly reduces rate of decline in pulmonary fxn; only smoking cessation and long-term oxygen Tx decrease mortality

Dyspnea may respond to drug Tx at any level but most studies indicate effectiveness for symptomatic pts w/FEV1 <60% predicted


Inhaled short-acting β2-agonist (albuterol, levalbuterol, meta-proterenol, pirbuterol)

Dosage: 2 inhalations as needed, ≤12 inhalations/d Side effects: Sympathomimetic symptoms (e.g., tremor, tachycardia.Notes: Generally used as needed.

Inhaled short-acting anticholinergic (Ipratroplum)

Dosage: 2 inhalations qid increase as tolerated Side effects: Dry mouth, mydriasis on contact w/eye.Notes: Use as maintenance Tx. Don’t use w/tiotropium.

Inhaled long-acting anticholinergic (tiotropium)

Dosage: 18 μg/d Side effects: Dry mouth, mydriasis on contact w/eye. Notes: Use as maintenance Tx. Don’t use w/ipratropium.

Inhaled long-acting β2-agonist (salmeterol, formoterol, aformoterol )

Dosage: depends on agent used. Side effects: Sympathomimetic symptoms.Notes: Use as maintenance Tx. Overdosage can be fatal.

Oral theophylline (aminophylline:.generic and brand-name sustained and short-acting)

Dosage: Aim for serum levels betw 5 and 14 μg/mL Side effects: Tachycardia, nausea, vomiting, disturbed pulmonary fxn, insomnia. Overdose can be fatal. Notes: Use as maintenance Tx. Use intravenously in emergency dept. May improve respiratory muscle fxn.

Oral β2-agonists (albuterol, meta-proterenol, terbutaline)

Dosage: depends on agent usedSide effects: Sympathomimetic symptoms. Notes: Use as maintenance tx. Rarely used bc side effects.

What is the role of inhaled bronchodilators?


What is the role of inhaled bronchodilators?

Short-acting bronchodilators preferred for

Mild COPD, intermittent symptoms, rescue treatment (for breakthrough symptoms in pts on long-acting meds)

Begin treatment w/single bronchodilator No data avail to recommend one over another for initial use

Base choice on pt preference, potential side effects, cost

Educate pt on proper use (open-mouth technique not recom’d for hydrofluoroalkane propellant-driven or anticholinergic metered-dose inhalers)

Long-acting bronchodilator monotherapy reduces exacerbation frequency and improves overall resp health, but no sig reduction hospitalization or mortality

Step up to combination bronchodilator Tx if add’l symptomatic relief required

inhaled combination LABA + long-acting anticholinergic may improve FEV1 (unclear if better than monotherapy for dyspnea, exercise tolerance, exacerbations)


When should clinicians prescribe corticosteroids?

Inhaled corticosteroids Fluticasone Budesonide Triamcinolone

Dosage: Fluticasone, 880 μg/d; budesonide, 800 μg/d; triamcinolone, 1200 μg/d; all in divided doses. Side effects: Skin bruising, oral candidiasis, rarely adrenal suppression poss glaucoma, decreased bone density, diabetes, systemic HTN, cataracts.Notes: Can be used as maintenance Tx. In pts w/Hx frequent exacerbations, high doses best studied. Pulmonary fxn improved in 10%-20% of pts, but symptoms & exacerbations reduced in larger percent. No effect on decline in pulm fxn. Not approved by FDA for COPD.

Oral corticosteroidsPrednisone Prednisolone

Dosage: Varying doses Side effects: Skin bruising, adrenal suppression, glaucoma, osteoporosis Notes: Avoid use, if poss, in stable COPD. Pulm fxn improved in 10%-20% of pts. Reduce to lowest effective dose, including transition to inhaled corticosteroids, alt day oral corticosteroids, or both. IV or oral corticosteroids standard Tx & effective for acute exacerbations.


When should clinicians prescribe corticosteroids?

When pts w/mod/severe COPD (FEV1 <50% predicted) remain symptomatic or have repeated exacerbations while taking inhaled long-acting bronchodilators

Inhaled corticosteroids + LABA = improved pulmonary fxn and clinical outcomes > either agent alone

Inhaled corticosteroid + long-acting anticholinergic + LABA = improved QOL compared w/monotherapy w/ long-acting anticholinergic

FDA advised against using LABAs w/o concomitant admin of inhaled corticosteroids, due to safety concerns but recom’n didn’t apply to COPD

Reserve oral corticosteroids for limited periods to treat acute exacerbation avoid ongoing use in stable disease (limited benefits & high pot’l for side effects)


When should clinicians consider adding oral theophylline to inhaled drug therapy?

Start at low dose and titrate to effect aim for blood level 5-14 micrograms/mL

Monitor serum drug levels frequently narrow therapeutic window, multiple interactions w/ other meds, potential toxicity

Side effects common, esp nausea and tachyarrhythmia

Bronchodilator effects relatively modest

Discontinue if symptoms don’t improve after several wks

Do not use in treating acute exacerbations of COPD

When pt has refractory symptoms even if receiving inhaled bronchodilators and/or inhaled corticosteroids


What immunizations should clinicians administer?

Annual flu vaccination: significantly reduces exacerbations

Pneumococcal vaccination: admin once to adults 19-64 y who smoke or who have COPD; admin again after age 65 if previous vaccination given >5 y earlier

If pt not vaccinated before age 65, then one-time pneumococcal vaccination recommended


What criteria are used to define a COPD acute exacerbations?

Criteria and Classification of Acute COPD Exacerbation

Major criteria

• Increase in sputum volume

• Increase in sputum purulence (generally yellow or green)

• Worsening dyspnea

Additional criteria

• Upper respiratory infection in past 5 d

• Fever of no apparent cause

• Increase in wheezing and cough

• Increase in respiratory rate or heart rate 20% above baseline

Mild exacerbation = 1 major criterion plus ≥1 add’l criteria

Moderate exacerbation = 2 major criteria

Severe exacerbation = all 3 major criteria(Adapted from Anthonisen NR, et al. Ann Intern Med. 1987; 106:196-204. [PMID: 3492164])


How should clinicians manage acute exacerbations?

Inciting factor for exacerbation typically unknown bacterial or viral infection or inhaled irritants

Treatment should be guided by:

Severity of exacerbation (if pneumonia suspected, obtain chest X-ray to confirm)

Degree of impaired pulmonary function

History of exacerbations

Response to previous treatment should guide therapy

Prompt recognition Possible adjustment bronchodilator and steroid Tx Initiation antibiotics Assessment of need for hospitalization



Antibiotics: esp in pts w/purulent sputum

Improve peak flow, reduce mortality and treatment failure

β-lactam/β-lactamase inhib, extended-spectrum macrolide, 2nd- or 3rd-generation cephalosporin, or fluoroquinolone: for mod/severe exacerbation

Tetracycline or trimethoprim-sulfa-methoxazole: for mild exacerbations

Prophylactic Abx may prevent future exacerbation requires better data before recommended; danger of resistance

Oral corticosteroids: for mod/erate severe acute exacerbation

Dose not well-defined: 30-60 mg/d for ≤2 wks typical; longer course increases risk for adverse effects

Appears to reduce treatment failures



PPIs may prevent exacerbations in older patients

Mucolytics may help prevent in pts w/ chronic bronchitis (effect seems absent in pts using inhaled corticosteroids)

If outpatient mgmt of exacerbation inadequate hospitalize pt for poss intubation + mechanical ventilation

Frequency of exacerbation in past year predicts frequency of exacerbation in following year (overall 43% sensitivity, 87% specificity)

Best predictor of future exacerbations: ≥2 in past yr (also baseline FEV1 <50% predicted, Hx GERD heartburn)



Indications for hospital assessment or admission

Marked increase in intensity of symptoms (e.g., sudden development of resting dyspnea)

Severe underlying COPD

Onset new physical signs (e.g., cyanosis, periph edema)

Failure of exacerbation to respond to initial medical mgmt

Significant comorbid conditions

Frequent exacerbations

Newly occurring arrhythmias

Diagnostic uncertainty

Older age

Insufficient home support


When should clinicians recommend pulmonary rehabilitation?

Patients most likely to benefit:

Impaired QOL from COPD

Breathlessness & anxiety limiting activity

Willing to undertake intensive edu’n and exercise program

Pulmonary rehab = multidisciplinary program Exercise training Education Psychological and nutritional counseling

Components beneficial individually but comprehensive, integrated appear most effective HC team provides pulmonary rehab thru structured program to groups of pts w/COPD

For all symptomatic pts w/ COPD part of overall trmt plan as drug trmt optimized

Benefits

Improved exercise ability

Improved health-related QOL

Reduced dyspnea

Reduced future hospital admissions

Reduced mortality

Patients with severe COPD require program lasting ≥6 mos to achieve benefit

Patients w/ mild-to-moderate COPD could benefit from shorter program


What other adjunctive measures should clinicians consider?

Relaxation techniques to reduce anxiety due to shortness of breath

Pursed-lip breathing and diaphragmatic breathing to reduce shortness of breath

Nutritional interventions to achieve ideal body weight and improve performance of daily activities and exercise

Chest physiotherapy, percussion and vibration, and postural drainage to enhance sputum clearance and alleviate shortness of breath Limited usefulness w/o excessive sputum prod’n and

inadequate bronchial clearance

Adjunctive therapies commonly used but little evidence supports effectiveness


When should clinicians prescribe oxygen therapy?

Periodically evaluate pts w/ mod-to-severe COPD to determine if supplemental oxygen needed

Criteria for Initiation of Long-Term Oxygen Therapy

Room air PaO2 ≤55 mm Hg or between 55 and 60 mm Hg w/ cor pulmonale; signs of tissue hypoxia (e.g., polycythemia); or SaO2 ≤88% or 89% w/ signs of tissue hypoxia, OR

Nocturnal hypoxemia w/ SaO2 ≤88% (use oxygen only at night), OR

Exercise hypoxemia w/ PaO2 ≤55 mm Hg or SaO2 ≤88% (use oxygen only with exertion)



PaO2 measurement after 30mins breathing room air most accurate clinical standard for initiating Tx

Use pulse oximetry (sensor that measures Hgb oxygenation)

To qualify pts for long-term oxygen Tx

To adjust oxygen flow rates after initial Dx, over time

To allow pts to self-adjust rate of oxygen flow w/ Inexpensive pulse oximeters (instruct pt in use, keeping SaO2 above and near 90%)

For pts titrating oxygen flow at different altitudes



Long-term home oxygen Tx: improves survival in select group of pts w/ + severe hypoxemia

Doesn’t improve survival in pts w/ mild-to-mod hypoxemia or w/ only arterial desaturation at night

Unclear if nocturnal oxygen in pts w/o daytime hypoxemia benefits mortality, health-related QOL, or daytime fxn

When long-term oxygen Tx indicated

Use ≥15h/d, ideally 24h/d

Follow-up w/in 3 mos initially yearly thereafter

In pts who don’t qualify for continuous Tx

Use to reduce dyspnea during exercise (in those w/ exertional desaturation)

Use during sleep (in those who desaturate at night)


When should clinicians refer patients to a pulmonologist?

When to Consider Referral to a Pulmonary Specialist* Disease onset before 40 years of age

Frequent exacerbations (≥2/yr) despite adequate treatment

Rapidly progressive course of disease (decline in FEV1, progressive dyspnea, decreased exercise tolerance, unintentional weight loss)

Severe COPD (FEV1 <50% predicted) despite optimal treatment

Need for oxygen therapy Onset of comorbid cond’n (osteoporosis, HF, bronchiectasis, lung CA) Diagnostic uncertainty (e.g., coexisting COPD and asthma) Symptoms disproportionate to severity of airflow obstruction

Confirmed or suspected α1-antitrypsin deficiency

Patient requests a second opinion Possible candidate for lung transplant or lung-volume reduction surgery Very severe disease and requires elective surgery that may impair respiratory function *Adapted &modified from ATS/ER and VA/DoD guidelines.


When should clinicians consider surgical therapies?

Lung volume-reduction surgery

Improves exercise capacity, lung fxn, dyspnea, QOL doesn’t improve survival vs. medical Tx alone

May improve survival for subgroup w/upper lobe emphysema and low exercise capacity

Consider if pulmonary rehab completed and patient meets the following criteria:

• Evidence of bilateral emphysema on CT scan• Postbronchodilator TLC > 150% predicted and RV > 100% predicted • Max FEV1 ≤45% predicted; and • Room air PaCO2 ≤60 mm Hg and PaO2 ≥45 mm Hg

Unlikely benefit + high risk if FEV1 ≤20% predicted + either homogeneous emphysema on CT scan or CO-diffusing capacity ≤ 20% predicted


When should clinicians consider surgical therapies? Lung transplantation

Improves pulmonary function, exercise capacity, QOL, and possibly survival

Consider if pt BODE index 7-10 and ≥1 of following: • Hx hospitalization for exacerbation associated w/acute hypercapnia (PCO2 >50 mm Hg)• Pulm HTN, cor pulmonale, or both despite O2 Tx• FEV1 <20% predicted + either CO-diffusing capacity <20% predicted or homogeneous distribution of emphysema

Survival single lung transplantation for pts w/COPD ≈83% at 1y; 60% at 3y; 43% at 5y (double-lung transplant survival similar/ slightly higher)

Chronic allograft rejection prevalence as high as 50%-70% among survivors (at 5 yrs after transplant)


What do professional organizations recommend with regard to prevention, screening, diagnosis, and treatment?

4 guidelines provide comprehensive approach to Dx and management of COPD (all drawing from variety of sources: RCTs; cohort and case-control studies; public policy org recommendations; expert opinion)

Global Initiative for Chronic Obstructive Lung Disease, updated 2009 American College of Physicians / American Thoracic Society/ European Respiratory Society, updated 2011 VA and DoD, updated 2007 National Institute of Clinical Excellence, updated 2010


What measures do stakeholders use to evaluate the quality of care for patients with COPD?

Centers for Medicare & Medicaid Services 2010 Physicians Quality Reporting Initiative

Percentage of patients ≥18y w/ Dx of COPD who had:

Spirometry evaluation documented

FEV1/ FVC ratio <0.70, and symptoms such as dyspnea, cough, sputum, or wheezing who were prescribed inhaled bronchodilator

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