Managing Chronic Obstructive Pulmonary Disease in the Longterm Care Setting

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Managing Chronic Obstructive Pulmonary Disease in
the Long-term Care Setting

• James R McCormick M.D., FCCP
• Professor and Head
• Pulmonary/Critical Care/Sleep Medicine
• University of Kentucky Medical Center

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Definition of COPD

• COPD is a preventable and treatable disease
  state characterized by airflow limitation that is
  not fully reversible. The airflow limitation is
  usually progressive and is associated with an
  abnormal inflammatory response of the lungs to
  noxious particles or gases, primarily caused by
  cigarette smoking.
• ERS/ATS COPD Guidelines 2005

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE

• Emphysema
• Chronic Bronchitis
• Diffuse Panbronchiolitis
• Chronic Asthma
• ATS Standards for the Diagnosis and Care of
  Patients with COPD Nov. 1995

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Chronic Obstructive Pulmonary Disease

• 10 million diagnosed patients
• 14 million potentially undiagnosed
• Worldwide 600,000,000 est. WHO
• 8 million office visits/yr
• 1.5 million ER visits/yr
• 726,000 hospitalizations/yr
• 119,000 deaths(2000)4th leading cause in US
• 18 billion annual cost

CDCPSurveillance Reports(SS6) MMWR 200251 AHCPR
1997
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Case 1

• A 77 year old recently widowed woman has just
  come into an assisted-living facility because she
  is having difficulty managing her affairs at
  home, has never driven, and prefers not to live
  with her daughter and her fourth husband.
• She has a history of adult-onset diabetes for
  which she takes glyburide and has taken an
  aspirin a day for several years for my heart.

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Case 1 (contd)

• She also has a history of asthma, diagnosed about
  10 years ago when she presented to an emergency
  room complaining of shortness of breath. She has
  had slowly progressive dyspnea with exertion for
  many years and now has difficulty climbing a
  flight of stairs or carrying laundry on level
  ground without slowing down or stopping to catch
  her breath.

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Case 1 (contd)

• She currently has a slight non-productive
  cough,usually in the mornings but had a chronic
  cough and sputum production when she smoked.
• Her weight is stable and she hasnt had fever or
  trouble sleeping. There is no history of heart
  disease, stroke or cancer. She had eczema as a
  child but there is no history of hay fever or
  allergies.

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Case 1 (contd)

• She smoked 2 packages of cigarettes daily for 40
  years but quit 12 years ago. She enjoys 2-3
  highballs in the evening.
• Her medications include albuterol inhaler (prn
  but generally used 4-5 times daily), Advair bid,
  theophylline 400 mg qd and oxygen prn. She also
  takes the ASA and glyburide.
• Her family history is remarkable in that her
  father died of lung cancer at age 57.
• She was a housewife who completed high school and
  raised her only daughter with her husband of 55
  years. He died last year of pneumonia.

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Case 1 (contd)

• On examination,she is a thin, pleasant woman with
  bright eyes who seems a bit anxious. She seems
  slightly breathless when speaking.
• Pulse is 77RR-22BP 112/70afebrile
• HEENT-corneal arcus
• Neck- trachea midlinecarotids normal no JVD at
  45 degrees elevation.

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Case 1 (contd)

• Chest-There is a slight dorsal kyphosis and
  hyperesonance by percussion with low diaphragms
  which dont move much between inspiration and
  expiration. Breath sounds are distant and the
  expiratory maneuver is prolonged. With forced
  exhalation, a faint wheeze is heard.
• Heart-The point of maximal impulse is felt near
  the xiphoid process of the sternum. Regular
  rhythm. Normal sounds.
• The rest of the examination is normal.

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Case 1 (contd)

• How would you define her pulmonary problem?
• Is she receiving appropriate treatment?
• What changes might you suggest to improve her
  symptoms?

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COPD

• The slowly progressive dyspnea, history of
  chronic cough and sputum,smoking history (gt 20
  pack years) and physical examination all support
  a diagnosis of advanced COPD in this woman.
• Although she had eczema as a child,there is no
  other history of allergic disease or of symptoms
  suggesting acute nor chronic asthma.

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Symptomatic Treatment of Patients with COPD

• Anticholinergics
• B2-agonists
• Combined therapy
• Long-acting inhaled ß2-agonists
• Oral ß2-agonists
• Corticosteroids
• Oxygen
• Narcotics

ATS Standards AJRCCM 1995 Nov. Pt 2 CHEST
1995, May Suppl NHLB Workshop JAMA 1997
277246. GOLD NHLB/WHO Guideline 2007
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Formoterol vs Theophylline in COPD

Mean FEV1 values measured predose (time point 0)
and over 12 h following the morning dose of study
medications at 3 months (top) and 12 months
(bottom) of the treatment period (Intent-to-treat
population). At each time point postdose, a
difference in mean FEV1 of 120 mL between
treatment groups was considered to be clinically
relevant. Rossi,et al Chest 20021211058
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Muscarinic Receptors and Control of Airway Smooth
MuscleFryer and Jacoby AJRCCM 1998158S154
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Tiotropium A Long-Acting Muscarinic Antagonist
for COPD

• Quaternary ammonium muscarinic receptor
  antagonist
• Binds to M1,M2,M3 receptors but dissociates from
  M1 and M3 100 times more slowly than ipratropium
• Protects against methacholine challenge for gt 72
  hrs
• Slower in onset of action (35 vs 15 min)
• Prolonged duration of action gt 24 hrs

Barnes PB CHEST 200011763S
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Tiotropium A New Quaternary Ammonium Muscarinic
Antagonist Bronchodilator

• Improves lung function,symptoms and reduced
  exacerbations when compared to placebo
  Eur Respir
  J 200219217
• Imroves dyspnea,exacerbations,HRQL and lung
  function when compared to ipratropium
• Eur Respir J 200219209
• Improves lung function, dyspnea, HRQL and time to
  exacerbation compared with salmeterol
  Thorax 200358399
• 2 one-year studies 1 six-month study

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A 6-Month, Placebo-Controlled Study Comparing
Lung Function and Health Status Changes in COPD
Patients Treated With Tiotropium or Salmeterol
CHEST 200212247

• 623 patients in 39 centers in 12 countries
• Age gt 40 years Smoked gt 10 pack-years
• FEV1 lt 60 and FEV1/FVC lt 70
• Stable, no other serious disease which could
  influence the outcome of the study
• No asthma, atopy or eosinophil count gt600
• No O2

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Tiotropium vs Salmeterol vs PlaceboCHEST
200212247

• Mean FVC before and after administration of
  tiotropium, salmeterol, and placebo on days 1,
  15, and 169 of treatment. p lt 0.001 for
  tiotropium vs placebo on all test days
  posttreatment p lt 0.05 for tiotropium vs
  salmeterol on all test days except day 1 and - 1
  h and - 10 min on day 15.

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Tiotropium and Exercise Tolerance
2 Studies with Tiotropium and Exercise ODonnell
et al1 Maltais et al2
Patients Moderate to severe COPD Measured
Exercise endurance time and lung volumes Method
Cycle ergometry
1ODonnell et al. Eur Resp J 2004. 2Maltais et
al. Chest 2005.
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Exercise Trial (Maltais et al)Change in
Endurance Time
Tiotropium (n 131)
Placebo (n 117)


Change in Median Exercise Duration (seconds)
105 sec
100 sec
Days
plt0.001
Median baseline exercise endurance time 434
seconds Testing on day 0 was following the first
dose of study drug The clinical significance of
this increase in exercise endurance time is
unknown
Maltais et al. Chest 2005 Data on file,
Boehringer Ingelheim Pharmaceuticals, Inc. Trial
205.223 Please see Full Prescribing
Information
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Case 2

• A 67 year old right-handed man was admitted to a
  nursing home following a stroke which has left
  him with a left hemiparesis. He has progressed in
  his physical therapy to the point where he can
  move about independently using a rolling walker.
• He has no cough but appears to the staff to be
  dyspneic when walking the hallways and coming
  into the dining area.

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Case 2

• He has not seen a physician in more than 20 years
  until this illness but has hypertension (now
  treated). He has never smoked and doesnt drink
  alcohol.
• He is unmarried and has lived alone since his
  parents died.

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Case 2

• On physical examination he is a thin man with an
  obvious left-sided weakness including a mild left
  facial palsy. His vital signs are normal except
  for a respiratory rate of 24 when moving to the
  bed from a chair. There is evidence of use of
  accessory muscles of respiration. He has a
  barrel chest with hyperesonance by
  percussion,prolonged expiration and distant
  breath sounds. The heart can be palpated at the
  xiphoid process. The rest of the exam is normal.

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How shall we treat him?
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Case 2

• Does this man have chronic obstructive pulmonary
  disease?
• Can his symptoms be attributed to this disorder?
• If so, what is a reasonable approach to therapy?

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Improvement in Resting IC and Hyperinflation with
Tiotropium in COPD

• 4 week trial in 81 patients with severe COPD
• Same inclusion criteria as before except
• FEV1 gt 30 and lt 65 predicted
• TGV gt 120 predicted
• Mean FEV1 lt50 predicted
• Mean FEV1/FVC lt 50
• Mean TGV gt170 predicted

Celli B CHEST 20031241743
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Improvement in Resting IC and Hyperinflation with
Tiotropium in COPD

• Changes in IC over 3 h following 4 weeks of
  treatment with tiotropium or placebo.
• CHEST 20031241743

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Improvement in Resting IC and Hyperinflation with
Tiotropium in COPD

• Changes in TGV (Total Lung Capacity) over 3 h
  following 4 weeks of treatment with tiotropium or
  placebo.
• CHEST 20031241743

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Case 3

• An 81 year old man has mild dementia and very
  severe COPD (FEV1 27 predicted). He has been a
  resident of your nursing home for 2 years. He has
  chronic dyspnea on exertion (bathing, dressing,
  walking to meals) and a chronic cough productive
  of scant amounts of white sputum. He sleeps well
  with a low dose of olanzapine and has no
  behavioral issues..as long as he can smoke a few
  cigarettes each day.

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Case 3

• Three days ago,he began experiencing increased
  cough, productive of a few teaspoonfuls of yellow
  sputum, and significantly more dyspnea, even at
  rest. He has also been found waking up at night
  to use his albuterol inhaler.
• His routine medications include ipratropium
  inhaler,2 puffs qid and prn albuterol.

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Case 3

• You learn that he has had two or three such
  episodes each year since becoming a resident at
  the nursing home.

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Case 3

• On physical examination, he is a thin,
  tired-appearing man in obvious respiratory
  distress. He is afebrile but his pulse is 111 and
  his respiratory rate is 28. He is using accessory
  muscles, has an increased antero-posterior
  diameter of his chest, hyperesonance by
  percussion and prolonged expiration with
  wheezing. The rest of the examination is
  unremarkable.

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Case 3

• Is this an acute exacerbation of COPD?
• What is an appropriate treatment approach?
• How can future episodes be prevented?

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Prevention of Exacerbations of COPD with
Tiotropium, a Once-Daily Inhaled Anticholinergic
BronchodilatorAnn Int Med 2005143317

• 26 VA Medical Centers
• 1829 patients enrolled age gt 40 99 males
• All smokers gt 10 pack-years
• COPD FEV1 lt60 predicted (mean 35) FEV1/FVC lt
  70 (mean 48)
• Stable for at least 30 days lt 20 mg prednisone
• No asthma, MI within 6 months, serious
  arrhythmia, hospitalization within 1 year,
  moderate renal impairment, severe BPH,
  narrow-angle glaucoma, malignancy under treatment

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Prevention of Exacerbations of COPD with
Tiotropium, a Once-Daily Inhaled Anticholinergic
BronchodilatorAnn Int Med 2005143317

• Randomized, double-blind, placebo- controlled
  trial of tiotropium once daily vs placebo for 6
  months.
• Outcomes prevention of exacerbation or
  hospitalization for exacerbation of COPD
• No other anticholinergics permitted
• All other agents allowed 38 long-acting
  beta-agonists 60 inhaled steroids 14
  theophylline

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Definition of an Exacerbation Ann Int Med
2005143317

• Increase or new-onset of cough, sputum, wheezing,
  dyspnea or chest tightness lasting for at least 3
  days and
• Requiring treatment with antibiotics or systemic
  steroids and/or hospitalization for the
  exacerbation

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Risk Indexes for Exacerbations and
Hospitalizations Due to COPDCHEST 200713120

• Reviewed data from prior clinical trial of
  tiotropium (1829 patients)
• 6 month follow-up data used
• How to predict an exacerbation?
• Age
• Cough
• FEV1
• Duration of COPD
• Treatments for prior exacerbations in last 1 year
• Hospitalizations in last 1 year

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Prevention of Exacerbations of COPD with
Tiotropium, a Once-Daily Inhaled Anticholinergic
BronchodilatorAnn Int Med 2005143317
14 reduction
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What about inhaled steroids for COPD?

• Does their chronic use help?

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Highland Ann Int Med 2003
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Asthma vs COPD

• In asthma, a sensitizing agent leads to chronic
  airway inflammation with CD4 T-lymphocytes which
  favors eosinophil recruitment, activation and
  prolonged survival.
• In COPD, the lower airway inflammatory response
  consists of neutrophils and macrophages
  predominantly.

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The Effects of Inhaled Corticosteroids in
COPDAlsaeedi A,et al Am J Med 200211359
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Combined Salmeterol and Fluticasone in the
Treatment of COPD

• TRial of inhaled steroids ANd long-acting ß-2
  agonists study group (TRISTAN)
• 196 hospitals/25 countries
• COPD,no O2, no response to inhaled
  bronchodilator,50 current smokers
• 1465 pts randomized1009 completed the trial
• Placebo vs. Salmeterol 50ug bid vs. Fluticasone
  500ug bid vs. both active agents

Lancet 2003361449
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Combined Salmeterol and Fluticasone in the
Treatment of COPD
Lancet 2003361449
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Combined Salmeterol and Fluticasone in the
Treatment of COPD

• Each active treatment improved FEV1 , symptoms,
  HRQL and reduced rescue medication and frequency
  of exacerbations (which were few,even in the
  placebo group).
• Combination therapy was superior in improving
  post-bronchodilator FEV1 , HRQL and daily
  symptoms in patients with no initial response to
  an inhaled ß-agonist.

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Combined Salmeterol and Fluticasone in the
Treatment of COPD
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Combined Salmeterol and Fluticasone in the
Treatment of COPD

• Improvements in FEV1 and FVC were small (
  about 150 ml) compared to placebo.
• The changes in breathlessness and in nocturnal
  awakenings were statistically significant but
  miniscule0.12 points on a 4 point scale for
  breathlessness and 2 less nocturnal awakenings
  every 3 weeks.
• Overall health status was better in the
  combination group at studys end compared to
  itself.

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Inhaled Corticosteroids and Mortality in
COPDCHEST 2006 130640 (Sept)

• In people gt 65 years of age, inhaled steroids
  were associated with a 25 reduction in mortality
  between 90 and 365 days after hospital discharge,
  .. Inhaled steroids were associated with an even
  larger mortality reduction in people aged 35 to
  64 years.
• Therapy with ICSs reduced mortality in COPD
  patients the effect was particularly notable for
  cardiovascular death and was short term in that
  it was dependent on recent exposure.
• The risk of death in the period 90-365 days after
  discharge from hospital for COPD exacerbation was
  greatest for those on bronchodilators alone.

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Risk of death (total and cause-specific) after 90
days in patients gt 65 years of age who were
segregated by treatment within 90 days of
discharge from hospital
Macie, C. et al. Chest 2006130640-646
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Systematic ReviewClinical Outcomes in COPD
ß-Agonist Use Compared with Anticholinergics and
Inhaled SteroidsClin Rev Allergy Immunol
200631219

• Salpeter and Buckley, Stanford
• Pooled results from randomized, controlled trials
• Anticholinergics and inhaled corticosteroids
  reduce exacerbations over time.
• Conclusion ß-Agonists increase respiratory
  deaths in COPD, possibly as a result of poorer
  disease control.

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Salmeterol and Fluticasone and Survival in COPD
(TORCH Trial)NEJM 2007356 775

• An ambitious, 3 year study of more than 6000
  patients with moderately severe COPD from 42
  countries and 444 centers to determine if Advair
  500 reduced mortality compared to placebo,
  Serevent or Flovent.
• Moderately severe COPD. Good stratification and
  statistical design
• No long-acting bronchodilators or inhaled
  steroids allowed outside of the study drugs.
• 40 drop out rate

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Salmeterol and Fluticasone and Survival in COPD
(TORCH Trial)NEJM 2007356 775

• The combination therapy improved lung function
  and quality of life, reduced exacerbations and
  hospitalizations compared to placebo. It was
  superior than either of the other active agents.
• Inhaled steroid therapy was associated with a
  significant increased risk of pneumonia.
• There was no effect on mortality.

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Salmeterol and Fluticasone and Survival in COPD
(TORCH Trial)NEJM 2007356 775
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FEV1 Over One Year (vs Ipratropium)
Vincken W et al. Eur Respir J (2002)
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Effect of Tio with/without Formoterol in COPDvan
Noord JA, et al CHEST 2006 129509
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Tiotropium in Combination with Placebo,
Salmeterol or Fluticasone-Salmeterol for
Treatment of COPD A Randomized TrialAnn Int Med
2007 February 19 epub

• Canadian study1 year 27 sites 449 patients
  with mod-severe COPD (age 67FEV1 38 pred)
• 40 of those assigned to Tiotropium or
  Tiotropium-Salmeterol dropped out.
• No differences in percent experiencing an
  exacerbation ( 60)
• The Tiotropium-Fluticasone group had better lung
  functional improvement and suffered less
  hospitalizations.

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Side-Effects of High-Dose Inhaled Steroids

• Cost
• Oral thrush
• Dysphonia
• Skin bruising
• Osteoporosis ?
• Fractures ?
• Adrenal suppression ?
• Pneumonia???

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