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Obstructive Lung DiseaseMichael Alter, MD FCCP, FAASM

Department of Pulmonary/Critical Care/SleepHealthPartners Medical GroupAssistant Professor of Medicine

University of Minnesota Medical School

COPD

•Natural history•Pathophysiology•Diagnosis •Out‐patient management• In‐patient management

COPD

•Natural history•Pathophysiology•Diagnosis •Out‐patient management•In‐patient management

Case 1

•78 y.o. male•COPD•Current smoker•On no therapy•FEV1 70%•Can walk without any limitation, no respiratory symptoms

•SpO2 94% on RA

•Advair 250/50•Oxygen therapy•Albuterol prn•Spiriva•Prednisone burst•Daily Prednisone•Smoking cessation•Pulmonary Rehab

Case 2

•82 y.o. female•COPD•Former smoker•Daily cough and wheezing

•On Albuterol•FEV1 30%• Limited to ADLs•SpO2 87% on RA

•Advair 250/50•Prn Albuterol•Oxygen therapy•Spiriva•Prednisone burst•Daily Prednisone•Smoking cessation•Pulmonary Rehab

Case 3

•68 y.o. male•COPD•Former smoker•Daily cough and wheezing

•On Spiriva•FEV1 60%•Worsening SOB over last year

•SpO2 90% on RA


Burden of COPD

• Increasing Global Prevalence4th-leading cause of death worldwide12th-leading cause of disabilityBy 2020: 3rd-leading cause of death, 5th-leading cause of disabilityAnnual cost: $40 billion

Murray CJL, Lopez AD, Harvard University Press, 1996

COPD is a major public health problem in the US• 5% of adult population (1 in 20 adults)

• 16 to 20 million cases

• 4th leading cause of death: 112,000 deaths annually

• 2nd leading cause of disability

• In 2002 more women in US died of COPD then men

Burden of COPD

Michaud CM, et al. JAMA. 2002

Natural History of COPD

25 35 45 55 65Age (years)

4

3

2

1

0

Symptoms

Death

Nonsmoker

Averagesmoker

“Susceptible”smoker

FEV1(liters)

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

•Launched in 1997 • in collaboration with the NHLBI, NIH and the WHO

•committees of experts around the world

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

•Guidelines updated January 2015•Global strategy for the diagnosis, management, and prevention of COPD

•GOLD Website: www.goldcopd.org

GOLD Definition of COPD

2015 goldcopd.orgCOPD.com

“A common preventable and treatable disease, is characterized by airflow limitation that is usually

progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to

noxious particles or gases.”

Causes of COPD not caused by tobacco smoke•Not all patient’s with COPD smoke ~ 15%•Need to entertain COPD in non‐smokers if the shoe fits‐ cough, wheeze, SOB, dyspnea, hyperinflation on CXR

Risk Factors for COPD

GenesExposure to particlesTobacco smokeOccupational dusts, organic and

inorganic Indoor air pollution from heating

and cooking with biomass in poorly ventilated dwellings

Outdoor air pollution

Tager et al. Am Rev Resp Dis. 1988;

Causes of COPD not caused by tobacco smoke

Diagnosing COPD

•Spirometry required•FEV1/FVC < 0.70 AND FEV1< 0.80

•CT scan• If it shows emphysematous changes•Blebs does not = COPD

GOLD Number: Severity of Obstruction*

• In patients with FEV1/FVC < 0.70:

•GOLD 1: Mild FEV1 > 80% predicted •GOLD 2: Moderate 50% < FEV1 < 80% predicted•GOLD 3: Severe 30% < FEV1 < 50% predicted•GOLD 4: Very Severe FEV1 < 30% predicted

*Based on Post-Bronchodilator FEV1

GOLD 2015 goldcopd.org

Spirometry

Mortality based on GOLD Severity

Hurst JR, et al. N Engl J Med 2010Decramer M, et al. (UPLIFT)Lancet 2009Jenkins CR, et al. Respir Res 2009Goldcopd.org

COPD


Therapeutic Options: Key Points

Smoking cessation has the greatest capacity to influence the natural history of COPD.

Pharmacotherapy and nicotine replacement reliably increase long-term smoking abstinence rates.

All COPD patients benefit from regular physical activity and should repeatedly be encouraged to remain active.

Prevention of COPD ProgressionSmoking Cessation

Years of follow-up

MeanFEV1 (L)

0 1 5432

2.9

2.8

2.7

2.6

2.5

2.4

Sustained quitters

Continuing smokers

Anthionsen, et al. JAMA 1994;272:1497

Prevention of COPD Progression:Smoking Cessation

•Only therapy proven to slow the decline in lung function

•Reduces all cause mortality by 27%

•Difficult to achieve• long-term abstinence rates can be as high as 25% in patients with

early COPD

Anthonisen NR, Ann Intern Med. 2005Anthonisen NR, Ann Intern Med. 2005

Natural History of COPD

25 35 45 55 65Age (years)

4

3

2

1

0

Symptoms

Death

Nonsmoker

Averagesmoker

“Susceptible”smoker

FEV1(liters)

Quitters

Smoking Cessation

•Nicotine replacement therapy & counseling• 25% sustained quit rate

• Bupropion (Zyban™) & counseling• 25 to 29% sustained quit rate

•Varenicline (Chantix) & counseling• 43% sustained quit rate

•When I ask all successful quitters how they quit• →Cold turkey

160

120

80

40

0Influenza 1 Influenza 3Influenza 2Interim 1 Interim 2

Period

Vaccinated

Unvaccinated

Nichol, et al. Ann Intern Med 1999; 130: 397

Prevention of COPD ExacerbationsInfluenza Vaccination

Respiratory hospitalizations/1000 patient-years

•Influenza vaccines can reduce serious illness

• Not 100% effective

• The odds are in their favor to vaccinate

•Pneumococcal vaccine recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV1 < 40% predicted

• No effect on morbidity, mortality, exacerbation rate

• Reduced pneumonia

Therapeutic Options: Other Pharmacologic Treatments

Therapeutic Options: COPD Medications

Beta2-agonists

Short-acting beta2-agonists- e.g Albuterol

Long-acting beta2-agonists – e.g. Salmeterol, Formoterol

Anticholinergics

Short-acting anticholinergics- e.g. Ipratropium

Long-acting anticholinergics – e.g. Tiotroprium

Combination short-acting beta2-agonists + anticholinergic in one inhaler – e.g. Combivent ™Methylxanthines

Inhaled corticosteroids – anything that ends in –sone, -lone, etc

Combination long-acting beta2-agonists + corticosteroids in one inhaler- .e.g Advair ™ (Serevent/Fluticasone), Symbicort ™Systemic corticosteroids

Phosphodiesterase-4 inhibitorsMacrolide antibiotics

Treatment options

•COPD is a disease of airflow obstruction•Obstruction stems from mucus production, airway narrowing, bronchospasm, smooth muscle contraction

•Treatment is aimed at ↓ mucus produc on, ↓inflamma on, ↓ bronchospasm,↓ smooth muscle contraction

•Steroids (↓inflamma on and mucus produc on) and Bronchodilators (↓smooth muscle contrac on, ↓airway narrowing)

Treatment options

•COPD is a disease of airflow obstruction• Obstruction stems from mucus production, airway narrowing, bronchospasm, smooth muscle contraction

• Treatment is aimed at ↓ mucus produc on, ↓inflamma on, ↓ bronchospasm,↓ smooth muscle contrac on

•Steroids (↓inflamma on and mucus produc on) and Bronchodilators (↓smooth muscle contrac on, ↓airway narrowing)

Treatment strategies

•Maintenance therapy•Generally long acting medications

•Rescue therapy•Generally short acting•Used for exacerbations or before activity

• Avoidance of risk factors

- smoking cessation

- reduction of indoor pollution

- reduction of occupational exposure

• Influenza vaccination

Manage Stable COPD: All COPD Patients

Bronchodilator central to symptomatic management

prescribed as-needed or regular basis to prevent or reduce symptoms

Principal bronchodilator: beta2-agonists and anticholinergics or combo therapy

Choice of treatment depends on availability of medications and each patient’s individual response in terms of symptom relief and side effects

Therapeutic Options: Bronchodilators

Long-acting inhaled bronchodilators (LABA)

convenient and more effective for symptom relief than short-acting bronchodilators

reduce exacerbations and related hospitalizations and improve symptoms and health status.

Cognitive function and ability to properly use inhaler therapy should be assessed regularly

Therapeutic Options: Bronchodilators

Wilt T, Niewoehner DE, Kim C, et al. AHRQ Report 05-E017-2, 2005

Prevention of ExacerbationsLong-acting Inhaled Beta Agonists

Relative Risk (95% CI) of Exacerbation

Favors LABA Favors Placebo

0.2 10.5 2 5

Mahler 2002BrusascoCalverley 1CelliChapmanRennardVan NoordMahler 1999Boyd

Subtotal

Calverley 2AalbersRossiWadboDahlSzafranski

Subtotal

Total 0.82 (0.76 - 0.90)

0.84 (0.74 - 0.97)

0.81 (0.73 - 0.90)

Salmeterol

Formoterol

LABA

Hospitalizations for COPDEffect of Long Acting Anticholinergic

Barr RG, et al. The Cochrane Database of Systematic Reviews 2005, Issue 2.

Tiotropium vs placeboBrusasco 2003Casaburi 2002Niewoehner 2005

Subtotal

Tiotropium vs ipratropiumVincken 2002

Subtotal

Tiotropium vs salmeterolBrusasco 2003

Subtotal

0.1 1 2 5 100.50.2Odds ratio (95% CI)

Favors tiotropium Favors comparator

0.65 ( 0.50, 0.85 )

0.59 ( 0.32, 1.09 )

0.59 ( 0.29, 1.23 )

LAMA

Regular treatment with inhaled corticosteroids (ICS) improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1< 60% predicted.

Associated with an increased risk of pneumonia

Withdrawal may lead to exacerbations in some patients

Therapeutic Options: Inhaled Corticosteroids

Wilt T, Niewoehner DE, Kim C, et al. AHRQ Report 05-E017-2, 2005

Prevention of ExacerbationsInhaled Corticosteroids

Relative Risk (95% CI) of Exacerbation0.2 10.5 2 5

BurgeCalverley 03Mahler 02van der ValkPaggiaro

Subtotal

BourbeauCalverly 04SzafranskiVestbo

Subtotal

Fluticasone

Budesonide

WeirSubtotal

Total

Beclomethasone0.64 (0.41 - 1.00)

0.78 (0.66 - 0.91)

0.81 (0.68 - 0.95)

0.78 (0.70 - 0.88)

Favors ICS Favors Placebo

Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-to-risk ratio.

Therapeutic Options: Systemic Corticosteroids

inhaled corticosteroid + long-acting beta2-agonist

more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD.

Combination therapy is associated with an increased risk of pneumonia

Addition of a long-acting beta2-agonist/inhaled glucocorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits

Therapeutic Options: Combination Therapy

Severe and very severe COPD (GOLD 3 and 4) + history of exacerbations and chronic bronchitis

Phospodiesterase-4 inhibitor (PDE-4), roflumilast (Daliresp™)

Reduces exacerbations treated with oral glucocorticosteroids

I have no patients taking this

Therapeutic Options: Phosphodiesterase-4 Inhibitors

Relieve symptoms Improve exercise tolerance Improve health status

Prevent disease progression Prevent and treat exacerbations Reduce mortality

Reducesymptoms

Reducerisk

Manage Stable COPD: Goals of Therapy

Manage Stable COPD: Pharmacologic Therapy(Medications in each box are mentioned in alphabetical order, and therefore not

necessarily in order of preference.)

Patient First choice Second choice Alternative Choices

ASAMA prn

orSABA prn

LAMA or

LABA or

SABA and SAMA

Theophylline

BLAMA

orLABA

LAMA and LABA SABA and/or SAMATheophylline

C

ICS + LABAor

LAMA LAMA and LABAPDE4-inh.

SABA and/or SAMATheophylline

D

ICS + LABAor

LAMA

ICS and LAMA orICS + LABA and LAMA or

ICS+LABA and PDE4-inh. orLAMA and LABA or

LAMA and PDE4-inh.

CarbocysteineSABA and/or SAMA

Theophyllineazithromycin


•Maintenance therapy•Think through what you are treating:•SOB just with ac vity: → prn Albuterol•Use Albuterol more than BID → LABA or LAMA (Fomoterol, Incruse™)

•Night me symptoms → LABA or LAMA•Chronic Cough → LACS•Moderate to Severe COPD → LABA/LACS and/or LAMA (Symbicort™)


•Maintenance therapy•Rescue therapy for exacerbations

•Continue maintenance therapy•Short acting beta agonists scheduled

• Nebulizer more beneficial then MDI

•Prednisone 40 mg p.o. for 5 days• I’d avoid medrol dose packs


•Anti‐biotics• moderate or severe exacerbation of COPD

• having at least two of these three symptoms • ↑ dyspnea, ↑ sputum volume, or ↑sputum purulence

• No anti‐biotics• Mild‐ having only one of these three symptoms and not requiring hospitalization

•Haemophilus influenzae,Moraxella catarrhalis, and Streptococcus pneumoniae

COPD ExacerbationsAntibiotic Therapy

Ram FSF, et al. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD004403.

Alonso 1992

Anthonisen 1987

Elmes 1965

Jorgensen 1992

Pines 1968

Pines 1972

Total

Favors placeboFavors antibiotic

RR (95% CI) of Treatment Failure

0.67 (0.56 -0.80)

0.1 1 2 5 100.50.2

COPD


Inpatient treatment strategies

•When to hospitalize:•Acute or acute‐on‐chronic respiratory acidosis• Inadequate response to outpatient/ER management•↑ intensity of symptoms over baseline •Severe underlying COPD (eg, [FEV1] ≤50% of predicted)

•Older age• Insufficient home support•History of frequent exacerbations•Comorbidities

Inpatient treatment strategies

• Strategy focus similar to Outpatient management• Reduce inflammation: Steroids• Reduce bronchospasm: Nebulized Beta‐agonist• Oxygen therapy• Non‐invasive ventilation (Bi‐PAP) for respiratory acidosis• Mechanical ventilation for respiratory acidosis that does not respond to Bi‐PAP

• Target normal pH, not normal PaCO2

• Antibiotics

All COPD patients benefit from exercise training programs with improvements in exercise tolerance and symptoms of dyspnea and fatigue.

Although an effective pulmonary rehabilitation program is 6 weeks, the longer the program continues, the more effective the results.

If exercise training is maintained at home the patient's health status remains above pre-rehabilitation levels.

Therapeutic Options: Rehabilitation

Rehabilitation Therapy for COPDExercise Capacity

McGavin,1977Cockcroft, 1981Booker, 1984Jones, 1985Lake, 1990Simpson, 1992Weiner, 1992Goldstein, 1994Wijkstra, 1994Guell, 1995Strijbos, 1995

Overall effect

Favors control Favors treatment

Effect size (SD units)-2 -1 0 1 2 3 4

Lacasse, et al. Lancet 1996;348:1115

00

44

88

1212

1616

2020

PlaceboPlacebo RehabilitationRehabilitation0

4

8

12

16

20

Placebo Rehabilitation00

5050

100100

150150

200200

250250

ControlControl RehabilitationRehabilitation0

50

100

150

200

250

Control RehabilitationBaselineBaseline 6 weeks6 weeks 1 year1 year

Walking distance (m)Walking distance (m)Quality of life (CRQ score)Quality of life (CRQ score)

Efficacy of Pulmonary Rehabilitation in COPD

Griffiths et al. Lancet. 2000;355:362-368.

Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival in patients with severe, resting hypoxemia.

Ventilatory Support: Combination of noninvasive ventilation (NIV) with long-term oxygen therapy may be of some use in a selected subset of patients, particularly in those with pronounced daytime hypercapnia.

Therapeutic Options: Other Treatments

Long-term Oxygen for COPD

1.0

0

0.8

0.6

0.4

0.2

6 12 18 3630240Months on study

O2 - 18 hours/day

O2 - 12 hours/day

P = 0.01

Nocturnal Oxygen Therapy Trial GroupAnn Intern Med 1980;93:391Nocturnal Oxygen Therapy Trial GroupAnn Intern Med 1980;93:391

Pro

porti

on s

urvi

ving

P = 0.04

1.01.0

0.80.8

0.60.6

0.40.4

0.20.2

0000 1212 2424 3636 4848 6060

Months on study

O2 - 15 hours/day

No O2

Pro

porti

on s

urvi

ving

Medical Research Council Working PartyLancet 1981;1:681Medical Research Council Working PartyLancet 1981;1:681

Indications for Oxygen use

•SpO2 < 88% or PaO2 < 55 mmHg•SpO2 < 89% or PaO2 56‐59 mmHg

•Edema suggesting CHF•Pulmonary HTN or cor pulmonale•Hct > 56%

•If SpO2 > 88% → Exercise tes ng•Any other values will not be covered

•Mucoactive agents

•Methylxanthines

•Mechanical techniques to augment sputum clearance

•Have not been shown to confer benefit for patients with a COPD exacerbation

•It does not mean there is no place in their use

Therapeutic Options: Other Treatments without documented benefits

Case 1

• 78 y.o. male• COPD• Current smoker• On no therapy• FEV1 70%• Can walk without any limitation, no respiratory symptoms

• SpO2 94% on RA

• Advair 250/50• Oxygen therapy• Albuterol prn• Spiriva• Prednisone burst• Daily Prednisone• Smoking cessation• Pulmonary Rehab

Case 1

•78 y.o. male•COPD•Current smoker•On no therapy•FEV1 70%•Can walk without any limitation, no respiratory symptoms

•SpO2 94% on RA

•Advair 250/50•Oxygen therapy•Albuterol prn•Spiriva•Prednisone burst•Daily Prednisone•Smoking cessation•Pulmonary Rehab

Case 2

• 82 y.o. female• COPD• Former smoker• Daily cough and wheezing• On Albuterol• FEV1 30%• Limited to ADLs• SpO2 87% on RA

• Advair 250/50• Prn Albuterol • Oxygen therapy• Spiriva• Prednisone burst• Daily Prednisone• Smoking cessation• Pulmonary Rehab

Case 2

•82 y.o. female•COPD•Former smoker•Daily cough and wheezing

•On Albuterol•FEV1 30%• Limited to ADLs•SpO2 87% on RA


Case 3

•68 y.o. male•COPD•Former smoker•Daily cough and wheezing

•On Spiriva•FEV1 60%•Worsening SOB over last year

•SpO2 90% on RA


• 4th-leading cause of death worldwide• Not all patient’s with COPD smoke ~ 15%• Spirometry required: FEV1/FVC < 0.70 AND FEV1< 0.80• Patients with very Severe COPD FEV1 < 30% have 24% 3 year mortality• Smoking Cessation is key• Goal of treatment is to address the underlying cause

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