TzxÇwt · – Prospective audit - Criteria m onitored antibiotics/clinical indications (eg...
Transcript of TzxÇwt · – Prospective audit - Criteria m onitored antibiotics/clinical indications (eg...
TzxÇwt7:30-8:00am BREAKFAST/Registration/Exhibit
8:00-8:10am Introduction and Welcome Andrew Martin, MD Chair, Pulmonary Medicine; Director, Institute for Sleep Medicine Deborah Heart and Lung Center
8:10-9:00 am ABX Stewardship: Antibiotic Management Keith Kaye, MD
Professor of Medicine, Corporate Medical Director, Hospital Epidemiology and Antimicrobial Stewardship Detroit Medical Center and Wayne State University
9:00-9:50am Sleep Medicine and Investigation into the Capacity for Sleep- Inspired Insights Michael Nolledo, MD
Pulmonary and Critical Care Medicine Deborah Heart and Lung Center
9:50-10:10am BREAK/Exhibit
10:10-11:00am Pulmonary Manifestations of Scleroderma Vivien Hsu, MD
Scleroderma Program Rheumatology and Connective Tissue Research Robert Wood Johnson University Hospital
11:00-12:00pm Surgical Treatments for Obstructive Pulmonary Disease Arthur Ng, MD
Thoracic and Cardiac Surgery Deborah Heart and Lung Center
12:00-12:50pm LUNCHEON/Exhibit
12:50-1:40pm Clinical Update on Pulmonary Testing Andrew Martin, MD Chair, Pulmonary Medicine; Director, Institute for Sleep Medicine
Deborah Heart and Lung Center
1:40-2:30pm Case Presentations
We would like to thank our Vendors for their continued support of educational programs and making 2010 an Incredible Success!
Honoraria Grant
"Restoring quality of life through interventional solutions"
Exhibitor Grant:
“The Sixth Annual ElectroMechanical Therapy Symposium”. Presented by Deborah Heart and Lung Center
“Ablation Therapy, Top to Bottom”
Antimicrobial Stewardship
Keith S. Kaye, MD, MPHProfessor of Medicine
Corporate Director, Infection Prevention, Hospital Epidemiology and Antimicrobial Stewardship
Detroit Medical Center and Wayne State University
Overview
• Key components and structure of an effective team
• Structure of stewardship programs
• Why is antibiotic stewardship important?– Making the business case
• Successfully implementing stewardship programs
Why Participate in Stewardship
• The primary goal of stewardship is to…Optimize clinical outcomes while minimizing
unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms, and emergence of resistance.
• Secondary goals…Reduce healthcare costs without adversely
impacting quality of care.Dellit TH et al. Clin Infect Dis 2007;44:159-77
Data Support Antimicrobial Stewardship
• 36 published studies on effect of antimicrobial stewardship
– 26/36 (72%) included a pharmacistO l 7/36 (19%) i l d d i bi l i– Only 7/36 (19%) included microbiologist
• Cost: 27 of 29 demonstrated a reduction• Resistance: 22 studies with positive effects on
multiple organisms/drugs including C. diff • Adverse Effects: 1 of 2 demonstrated improvement
Patel D et al. Expert Review of Anti-Infective Therapy 2008
Key Members of the Team• Two major components: a) expertise and leadership and b)
key stakeholders/major users/local leaders• Experts and Hospital Leadership
– Infectious Diseases physician(s) (compensated)– ID Pharmacist (compensated)– Microbiology– Administration (support, agree with metrics and goals)
I f i– Informatics support• Key stakeholders/major users/local leaders
– Critical Care– Emergency Medicine– Infection Control– Nursing – Clinical pharmacy– Hospitalists– P and T
Establish (and Understand) Data Streams
• The worst thing in the world is to have no data
• The second worst thing is to have data that d ’you don’t use
Measures of prescribing
• Antibiotic use, by unit/service unit– DDDs, antibiotic days,
• Clinical indications– Reason why antibiotic is being prescribed
• Rates of resistant pathogens C difficile• Rates of resistant pathogens, C. difficile• Process
– Pre-operative prophylaxis (agents, timing, duration)
– CAP, HAP therapy (agents, combinations)• Cost
Outcomes: what metrics should be focused on?
• Be careful what you pick– Antimicrobial resistance: multi-factorial causes
• Quality of care– Adherence to evidence-based guidelines– Antibiotic duration– Mortality, duration of hospitalization might be hard to directly
related to antibiotics– Process: appropriateness of treatment in important clinical
scenarios• Cost
– Should NEVER be primary goal– Often impossible to decrease cost– Cost-related goals might be to contain, limit cost increases
Be Careful What you Choose . . .
• Most important mechanisms of spread of pathogens and antimicrobial resistance is via hands of healthcare workers
Antimicrobial Stewardship Styles
• Formulary restriction and preauthorization– “Big Stick” – formal, rigidly enforced antibiotic approval;
many antibiotics require approval
• Prospective audit with intervention and feedback– “Feedback of data, epidemiologic approach” – routinely
feed back data to prescribers regarding appropriateness of use, bulk usage, antimicrobial resistance organisms/C. difficile, and trends/benchmarking of data
• Many programs use a combined approach with some restriction, some feedback of data
Big Stick/Pre-authorization• “Up front” – before the train leaves the station
– Formulary restrictions/pre-authorization for specific antibiotics
• Other less rigid “up front” options– Prospective audit - Criteria monitored antibiotics/clinical
indications (eg follow-up/monitoring by ID-Pharmacists– Guidelines and clinical pathways – can be very effective ifGuidelines and clinical pathways can be very effective if
local leadership is vested in success (eg VAP pathway in an ICU)
• Pros: stop overuse before it starts; potential for tight control
• Cons: Labor intensive; culture in some hospitals will limit up-front control; difficult to convince providers to limit empiric broad spectrum coverage in acutely ill patients
Audit with Feedback • Abx stewardship targets “downstream” opportunities
– - at the first (or second) toll booth– De-escalation: modifying broad-spectrum empiric therapy
on day 2 , 3 or 4– Shorten durations of therapy for common hospital
infections in certain populations (eg 7 day therapy for VAP; using CPIS score; surgical prophylaxis)*; g ; g p p y )
– IV to PO – often “low-hanging” fruit remains• Pros – focus on modifying therapy once data returns,
after “empiric” phase; avoid conflicts regarding broad empiric therapy in acutely ill patients
• Cons – durations can get lost in the shuffle in complex patients; if patients are doing well providers sometimes resistant to change
* ATS/IDSA guidelines, AJRCC, 2005; Dunbar, CID, 2003; Singh,
Many Stewardship Programs Utilize Both Up Front and Downstream Processes
• 24/7 pager for key, restricted agents– Broad spectrum, toxic and/or expensive– Often, “first dose free”
• Feedback, follow-up for key agents or key units
Modifying empiric therapy
• “Empiric therapy”: treatment prescribed before culture data, other testing available
• In most cases, empiric therapy should be narrowed at day 3-4 or earlier– If cultures are negative, narrow regimen– If cultures are positive, usually can focus regimenp , y g
• Often, empiric antibiotics are continued due to inertia, complicated clinical picture
• Need automated reminders at day 3-4 for multi-antimicrobial antibiotic regimens – aggressive efforts to decrease number, duration of antibiotics
• Success might be stopping one agent out of 3, or limiting durations to 7 days instead of 14
Optimal antimicrobial prescribing: one approach
• Broad spectrum therapy for empiric treatment of suspected invasive nosocomial infection
• Rapid de-escalation by day 3-4 • When possible, short durations of in-hospital
antibiotics for selected populationsa t b ot cs o se ected popu at o s• Avoid anti-pseudomonal agents when possible (eg
type 1 carbapenam)• “Hit hard, de-escalate, get out”
Supplemental Elements to a Stewardship Program
• Education – eg Antibiotic rounds in the ICU• Guidelines and clinical pathways• Antimicrobial cycling• Antimicrobial order forms• Antimicrobial order forms• Combination therapy• Streamlining and de-escalation of therapy• Dose optimization• Parenteral to oral conversion
Clinical Pathways and Guidelines: Antimicrobial Stewardship Program in a Surgical ICU
• Rationale for implementation:1. Standardization of treatment for nosocomial
pneumonia2. Desired improvement in bacterial resistance rates3. Elimination of unnecessary antibiotic use3. Elimination of unnecessary antibiotic use
• Protocol’s key features:1. Stepwise approach to diagnose pneumonia2. Antibiotic rotation to decrease resistance3. Defined duration of antibiotic therapy
• Compromising to maximize efficacy– Antimicrobial cycling
Suspect Pneumonia Clinically
Focal or Localized Infiltrate on CXR
Check: WBC, ABG, CXR
Mini-BAL Bronchoscopy Brush Biopsy
START:
Core Antibiotic on
START:
Core Antibiotic on
No Yes
Monthly Rotation:
Ceftazidime
Piperacillin/tazobactam
Pneumonia algorithm
Core Antibiotic onmonthly rotation +
Second Anti-Pseudomonal
Antibiotic +
Vancomycin
Penicillin Allergy:
Vancomycin +
Aztreonam +
Ciprofloxacin
Follow-up culture results in 48-72 hours. If 104 or greater CFU then patient likely has a pneumonia.
Core Antibiotic onmonthly rotation +
Second Anti-Pseudomonal
Antibiotic +
Vancomycin
YesYes
Imipenem
If no MRSA, STOP Vancomycin
Adjust antibiotics as indicated according to culture and sensitivity data
If no Pseudomonas, STOP second anti-Pseudomonal agent
Consult ID if ICU or primary team feel second agent is needed for longer
than empiric period
Stop antibiotics if pneumonia ruled out
Pneumonia algorithm
Stop antibiotics at 14 days or per ID
recommendations
Patient is immunocompetent, WBC has normalized, no fevers, and weaning successfully or extubated
Adjust antibiotics as indicated according to culture and sensitivity data
Stop antibiotics at 8 days
YesNo
Impact on ResistanceOrganism-
antibioticSICU MICU
Pseudomonas aeruginosa
2002%Sensitive(#isolates)
2004%Sensitive(#isolates)
p-value* 2002%Sensitive(#isolates)
2004%Sensitive(#isolates)
p-value*
Ceftazidime 67 (64) 92 (42) 0.002 64 (28) 56 (40) 0.444
Imipenem 80 (64) 75 (42) 0.399 57 (28) 38 (40) 0.110
Piperacillin 78 (64) 92 (42) 0.043 64 (28) 60 (40) 0.917
Gentamicin 60 (64) 75 (42) 0.109 67 (28) 63 (40) 0.649
Ciprofloxacin 71 (64) 75 (42) 0.516 50 (28) 28 (40) 0.058
Bennett KM et al. J Trauma 2007;63:307-11
Information Technology and Computer-based Surveillance
• Health care information technology in the form of electronic medical records, CPOE, and clinical decision support can improve antimicrobial decisions through the incorporation of data on patient-specific microbiology cultures and susceptibilities, organ function, drug-drug interactions, allergies and costallergies and cost.
• Computer-based surveillance can facilitate good stewardship by more efficient targeting of antimicrobial interventions, tracking of antimicrobial resistance patterns and identification of nosocomial infections and adverse events.
1. Commercially available programs2. Partnering with infection control
Dellit TH et al. Clin Infect Dis 2007;44:159-77
An Example: Incorporating Reason for Antibiotic Use into the Ordering Process
• All new antibiotic orders required an indication for use.
• Indications were grouped into 2 categories as follows:– prophylaxis – treatment
• Indication is included as a required field at the time of order entry by all prescribers.
Pre-Defined Indications
Prophylaxis Indications• Surgical- Pre-op• Surgical- Post-op• Non-surgical prophylaxis
Treatment indications:1. Bloodstream 2. Bone and joint 3. Central nervous system4. Diabetic foot5 E i i h f b ilNon surgical prophylaxis 5. Empiric therapy– febrile
neutropenia6. Empiric therapy-unclear source7. Intraabdominal8. Pneumonia– community-acquired9. Pneumonia– Other10. Skin/soft tissue 11. Urinary tract12. Other (followed by prompting for
free-text response)
Program Validation: Results
• Overall, performance of clinical indication tools was good• Only 17/156 (11%) orders were discordant
• Areas for improvement:• Education regarding use of “other” fieldEducation regarding use of other field• Encouraging use of pre-defined indication options• Capture missing indications ordered as part of order-sets
• Future clinical uses:• Targeting problem orders at the time of order entry• Lifting initial restrictions on antimicrobial agents
Examples of Questionable Indications:
• Ertapenem– “Post-operative prophylaxis”
• Moxifloxacin– “UTI”
• Vancomycin, piperacillin/tazobactam, imipenem– “prophylaxis”
Indications for Use- Piperacillin/tazobactam
Urinary Tract Infections
Making the Business Case for Antimicrobial Stewardship
• Quality of care
• Core measures/regulatory issues
• Reimbursement (lack of) for healthcare associated infections
• Antimicrobial resistance
• Cost
Published Cost Estimates for HAI
Anderson, ICHE, 2008
Additional Costs of Multi-Drug Resistant Organisms (MDROs)
Clostridium difficile (C. diff) ~ $5,000/episode
MRSA Infection ~ $5,000/episode
ESBL ~ $10,000/episode
Acinetobacter ~ $20,000/episode
Dubberke, et al, CID, 2008; Cosgrove et al, ICHE, 2005; Schwaber, et al, AAC, 2006; Lee et al, ICHE 2006; Cosgrove, Arch Int Med, 2002; Wilson et al, AJIC, 2004
Hospital A Cost Saving Estimates: HAIInfection type
Number of annual infections
Cost per infection ($)
Total cost($)
Infections prevented (n)and cost Savings with 10% reduction ($)
CA- BSI 42 23,400 982,800 N=4.2; 98,280
VAP 13 25,000 325,000 N=1.3; 32,500
CA-UTI 1* 750 750
ResistantOrganisms
110 1,295,000 N=11; 129,500
Total 2,603,550 260,355
*ICU only
Hospital A Cost Saving Estimates: Antibiotics
Cost savings with 10% reduction ($)
2008 antibiotic purchases ($)
1,646,000 164,600
Hospital A Cost Saving Estimates: Antibiotics and HAI
Cost savings with 10% reduction ($)
2008 antibiotic purchases ($)
1,646,000 164,600purchases ($)
Infection Costs 2,603,550 260,355
Total infection and antibiotic costs
4,249,550 424,955
Keys for successful implementation of antibiotic interventions
• Antibiotic committee: multi-disciplinary committee of MDs, PharmDs, nursing, microbiogy– Data manager, programmer
• Surveillance in place for antimicrobial utilization
• Work with infection control, ID, intensivists to identify key issues in antimicrobial resistance
Keys for Implementation (2)
• New policies: get buy in of key clinical leaders for new programs, policies– Encourage key users/leaders to participate in development
• Identify issues for local leadership to manage– Local ownership is critical
• Routine reporting and feedback of data to providers, administrators
• Support clinical pharmacists “in the trenches”
Keys for implementation (3)• Automate as much data as possible
– Infection Control Antibiotic Relational Database (ICARD)
Quality Management• Support reporting mandates• Evaluate root cause• Identify and monitor patient safety /
IC programs
Infection Prevention• Relieve administrative burden• Prioritize workflow
ICARDR l Ti
ADTSystem
LaboratorySystem
Source of data
Combining Data from Disparate Sources …
… to Provide Real-time Alerts and Analytics …
… for Management and Clinical Staff
What is ICARD
• Prioritize workflow• Increase prevention activities
Pharmacists• Establish and monitor antimicrobial
stewardship programs• Increase quality and quantity of
interventions
Administration• Support patient safety campaigns• Monitor reimbursement
implications• On-going performance monitoring
Real-TimeDatabase
Analytic Engine
AnalyticDatabase
yLIS
PharmacySystem
PIS
Surgery System
SIS
RadiologySystem
RIS
Keys for implementation (4)• Frequent, clear communication with clinicians,
administrators
– Clearly identify goals and challenges
• Document interactions/feedback
• Avoid big stick, when possible
• Process changes: formulary
Limitations
• Resources• Time• Bad habits, poor compliance by healthcare
workers (HCWs)• Changing epidemiology of healthcare
– Role of “healthcare-associated infections”– Pathogens (eg CA-MRSA)– Medical practice (invasive procedures in
outpatient settings)– Formulary budgets, restrictions
Tips for success
• Write annual report– Describe successes, challenges– Demonstrate instances of prevention
• Make business case for support, resources
• Establish data stream, feedback data frequently to providers, administrators
• Communication and collaboration with infection control
Tips for success (2)
• Gain support of key thought/clinical leaders• When possible, delegate oversight, policing to
local levels– Can occasionally monitor through data audits,
point prevalence studypoint prevalence study• For non-compliant untouchable “icons” at
institutions make appropriate “higher ups” aware of persistent problems, lack of compliance
Tips for success (3)
• Low hanging fruit: goals that all can agree on– IV to PO– Alerts for inappropriate combinations: double anaerobic,
double -lactams– Focus on process: obtaining cultures at beginning of
therapy, avoiding single-set blood culturestherapy, avoiding single set blood cultures
• Synergize goals with regulatory needs, ongoing efforts
• Pilot projects: can roll out intervention in compliant unit with strong leadership before going hospital-wide
• Present to Board of Trustees, Hospital presidents routinely
Looking to the future . . ..
• Fewer and fewer antibiotics for gram-negative pathogens
• More and more regulation• Antibiotic Stewardship will become “required” at all
j h i lmajor hospitals• Dedicated funding for Antibiotic Stewardship
Programs• Antibiotic utilization and appropriateness of
prescribing measures in pay for performance, “balanced score card”
1
Sleep Inspired Insights
Michael S. Nolledo, MDMedical DirectorInstitute for Sleep Medicine at DHLC
Objectives
Background and historical perspective regarding sleep and learning in humans.
Discuss the latest data on improved learning with sleep with particular emphasis on:
Simple tasksMemory consolidationInference and Insight
“What could not be repeated at first is readily put together on the following day; and the very time which is generally thought to cause forgetfulness is found to strengthen memory”
- Quintilian, commenting on the benefits of sleep (1st century AD)
2
What Dreams May Come?
“I awoke, turned on the light, and jotted down a few notes on a tiny slip of thin paper. Then I fell asleep again. It occurred to me at six o’clock in the morning that during the night I had written down something most important. The next night at three o’clock, the idea returned. It was the design of an experiment to determine whether or not the hypothesis of chemical neurotransmission that I had uttered 17 years ago was correct. I got up immediately, went to the laboratory, and performed a simple experiment on a frog heart according to the nocturnal design.” Otto Loewi, Easter Sunday 1921
Otto Loewi’s Dream
3
Behavioral States in Humans (Hobson, Nature 2005)
Sleep Architecture (Stickgold, Nature 2005)
Dependence on REM Sleep of Overnight Improvement of a Perceptual Skill (Karni et al. Science 1994)
6 young adults (3M and 3F aged 17-22 y.o.) with normal vision and no history of neurological or chronic illness.Task was to distinguish a target texture that differed only in orientation from a background texture.Testing was done before and after an interval (either normal sleep or sleep disrupted at a particular stage).
4
Test of Perceptual Skill (Karni et al. Science 1994)
Sleep Stage Deprivation Results (Karni et al. Science 1994)
Study Results (Karni et al. Science 1994)
5
Visual Texture Discrimination (Stickgold et al. Nat Neurosci 2000)
Motor Sequence Task (Walker et al. Neuron 2002)
fMRI Patterns in Motor Sequence Task (Walker et al. Neuroscience 2005)
6
Motor Adaptation Task (Huber et al. Nature 2004)
Correlation of Brain Measures and Sleep Dependent Learning (Stickgold Nature 2005)
Need to see the Big Picture
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The Big Picture
What about more complex tasks?
Conventional wisdom dictates that conscious thought leads to good decisions and satisfactory choices.
Unconventional wisdom dictates that choice and indeed insight can be gained by “sleeping on it”
Human relational memory requires time and sleep (Ellenbogen et al. PNAS 2007)
56 participants learned “five premise pairs”
An embedded hierarchy existed within the pairs which was unknown to the participants
8
Embedded Hierarchy (Ellenbogen et al. PNAS 2007)
Human relational memory requires time and sleep (Ellenbogen et al. PNAS 2007)
Interference Pairs (Ellenbogen et al. PNAS 2007)
9
Results 1 (Ellenbogen et al. PNAS 2007)
Results 2 (Ellenbogen et al. PNAS 2007)
Conclusion (Ellenbogen et al. PNAS 2007)
Sleep appears to facilitate distant inferential judgments, a benefit that may operate below the level of conscious awareness.
10
Posttraining increases in REM sleep intensity implicate REM sleep in memory processing(Smith et al. Learn Mem 2004)
18 participants (6 each in low, medium and high IQ groups) were trained in the tower of hanoitask after a baseline night of sleep.
Patients then slept and number of REMs were counted both during the baseline night of sleep and the night following training.
Tower of Hanoi task
Number of REMs (Smith et al. Learn Mem 2004)
11
Tower of Hanoi task performance (Smith et al. Learn Mem 2004)
Sleep Inspires Insight (Wagner et al. Nature 2004)
22 participants tested using a modified number reduction task
Tested before and after an 8 hour interval:Nocturnal sleepNocturnal wakefulnessDaytime wakefulness
Task and Experimental design (Wagner et al. Nature 2004)
12
Results (Wagner et al. Nature 2004)
Conclusion (Wagner et al. Nature 2004)
Sleep acts on newly acquired mental representations of a task and insight into hidden task structures is facilitated.
What about Naps? (Walker et al. AAAS 2010)
39 healthy young adults were divided into 2 groups – nap and no-nap.
12NN – participants were subjected to a rigorous fact based memory test.
2PM – nap group took a 90 minute siesta and the no-nap group stayed awake.
6PM – both groups were retested.
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Nap Results (Walker et al. AAAS 2010)
The road may be long and winding…
The path may even be dark…
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But if you sleep on it, the light will shine and you’ll figure it out!
Dr. Vivien HsuDirector, UMDNJ Scleroderma Program
New Brunswick, NJOctober 2010
Financial disclosure:
Gilead expert consultant (<$10,000) in 2010
Summary
Review of clinical manifestationsReview of current treatment modalities forReview of current treatment modalities forpulmonary complicationsRecommendations guidelines for minimum standard of care
No diagnostic test for sclerodermaPathogenesis is unknownprominent features of disease reflect characteristic pathophysiologic triad of autoimmunity inflammation vascularpathophysiologic triad of autoimmunity, inflammation, vasculardamage & fibrosisaffects 1 in 4000 adults in USA; 120,000 casesfemale predominancemore frequent in African Americans than CaucasionsHas the highest case fatality among CTD with a 10 year survival of 55%
Face
Upper arm
Anteriorchest
Upper arm
Abdomen
Uninvolved
Mild thickeningModerate thickening
Severe thickening
0123
Clinical Assessment of Skin Thickening (modified RSS)
Forearm
Hand
Fingers
Thigh
Leg
Foot
Forearm
Hand
Fingers
Thigh
Leg
Foot
LimitedLimited DiffuseDiffuse
• Diffuse cutaneous• Limited cutaneous• Sine scleroderma• undifferentiated connective tissue disease (UCTD)• overlap or mixed connective tissue disease (MCTD) • Myositis (dermato and polymyositis)
• Localized (morphea)
Scleroderma spectrum organ involvementClinical manifestations related to fibrotic and vascular
disease:
HHeartLungGI tractKidney Skin digital ischemia; contractures of
oral structures making intubation difficult
Limited cutaneous SScInsidious onset Raynaud & skin changes often overlooked for yearsGERD common
% h i20 30% have anti centromereMost common lethal complication is pulmonary hypertension (PH) occurs many years after dz onsetRisk increases with time
Skin Thickness in Scleroderma
Diffuse cutaneous SScTypically have skin progression of trunk and proximal extremitiesThe faster the pace of skin disease, the higher likelihood of organ involvement esp within 5 yrs oflikelihood of organ involvement, esp. within 5 yrs ofdisease onsetSkin disease plateaus after 2 4 yrs then regressesScleroderma antibody (SCl70) common in 20 30%Nucleolar pattern ANA present in 10 20% patients
Diffuse scleroderma:Pulmonary fibrosis is common (>70%)Renal crisis still occurs in 10 20%Cardiac involvement common often subclinicalGI involvement common: both GERD and lowerGI involvement common: both GERD and lowerintestinal disease due to fibrotic complications
Despite distinction of complications with both types of SSc—there is considerable overlapCommon to see both PH and interstitial lung disease (ILD) in the same patient.
Immune cell activation and localization
TGFß
IL-4PDGF
IL 1Endothelin
IL-13
Accumulation of interstitial matrix
TGFßIL-1
Masson Trichrome stain of a digital artery from a patient
with diffuse sclerodermaNormal artery
Figure 1 Survival of patients with systemic sclerosis between 1972 and 2002.
Copyright ©2007 BMJ Publishing Group Ltd.
Steen, V. D et al. Ann Rheum Dis 2007;66:940-944
Figure 2 Changes in causes of systemic sclerosis-related deaths between 1972 and 2001. GI, gastrointestinal; PAH, pulmonary arterial hypertension; PF, pulmonary fibrosis; SRC,
scleroderma renal crisis.
Copyright ©2007 BMJ Publishing Group Ltd.
Steen, V. D et al. Ann Rheum Dis 2007;66:940-944
SCLERODERMA LUNG DISEASE
ALVEOLITISINTERSTITIAL FIBROSISRECURRENT ASPIRATIONPULMONARY VASCULOPATHYPULMONARY VASCULOPATHY
The major clinical issue is defining the relative contribution of each process and choosing appropriate therapy
SSc Pulmonary complicationsFatigue, respiratory symptoms often nonspecificDyspnea on exertion or rest; cough, fatiguePE: inspiratory fine crackles at bases may be absent, prominent P2 signs of right sided heart failureprominent P2, signs of right sided heart failure
Key tests: Pulmonary function test with DLCO Presence of ILD causes reduced lung volumes or restrictive lung disease: < %FVC and <%TLCHigh Resolution chest CT (1mm cuts /no dye) prone position
Interstitial Lung DiseaseOccurs in both: limited (23%) vs diffuse SSC (>40%)Prevalence 20 90% depending on method of dxPFT: restrictive patternHigh Resolution chest CT: ILD found in 90 100%Increased mortality; loss of lung volume in first 2 yrsDeath occur in second 5 yrs : Severe involvement: FVC <55% and DLCO<40%
High resolution CT of lung in patient with early SSc. Note Scattered “ground glass” appearance of bibasilar alveolitis
Scleroderma Lung Study INEJM 2006;354(25):2655 2666
81 CYC 81 PLAC
1W
6, 9 and/or 12 mo f/u not available
6, 9 and/or 12 mo f/u available
6, 9 and/or 12 mo f/u available
6, 9 and/or 12 mo f/u not available
5W
162Randomized
B.
54 CYC completed (73 evaluable) 55 PLAC completed (72 evaluable*)
3W1W
2W / 2D7W
2F / 4W
1F / 4W
Start
3 mos
6 mos
9 mos
2W2W
1F
2D / 2F / 5W
1W
2F / 4W
80
76
65
59
76
72
70
61
Scleroderma Lung Study ICYC PLACEBO
re Im
prov
ed
Moderate
Major
Frequency 5 10152025 5 10 15 20 25
Scor
e W
orse
ned
Scor
30 30
No change
Mild
Moderate
Major
Mild
SLS 1 (other domains)Favored improvement in treated group:
mean %FVC=2.48 between 2 groupsHAQ Disability indexSF 36: 2 domains: vitality & health transitiondyspnea total skin scores
No improvement in cough
Treatment of SSc ILD with CTX vs Placebo after one year:
At the end of treatment, FIB was significantly worse in the placebo treatment group than in the CYC treatment group (p = 0.014). Furthermore, differences in the 12 month change in FIB between the CYC andin the 12 month change in FIB between the CYC andplacebo groups correlated significantly with other outcome measures, including the 12 month changes in FVC (p < 0.05), total lung capacity (p < 0.05), and dyspnea (p < 0.001) scores. However, no differences were noted between the two groups with respect to changes in either GGOs or HCs. Goldin J et al. Chest 2009;136:1333 1340
Representative paired images from a patient in the placebo arm whose FIB was visually scored as being worse over time (A, baseline; B, 12-month follow-up) and a patient in the CYC
arm whose serial scans were scored as not worse (C, baseline; D, 12-month follow-up).
Goldin J et al. Chest 2009;136:1333-1340
©2009 by American College of Chest Physicians
Effects of 1 year treatment of cyclophosphamide at 2 years in Scleroderma Lung StudyTashkin et al, Am J Resp Crit Care Med,176:1026 1034, 2007
BAL concordance with HRCT in dyspneic patients with scleroderma Clements et al, A&R 2004
18 subjects with SSc and dyspnea had BAL, 15 also had chest HRCT
9/18 had alveolitis (>3%neu or >2%eos) in both middle & lower lobes by BAL
alveolitis found in only 4 subjects in one segment of lung ( usually lower); thus BAL of middle lobes alone underestimates presence of activelower); thus BAL of middle lobes alone underestimates presence of activealveolitis
HRCT found excellent correlation between ground glass in middle lobes predicting alveolitis but missed infections. Poor correlation in lower lobes
BAL & culture should include >2 lung sites to diagnose alveolitis.HRCT needs careful interpretation of middle lobes to increase concordance with BAL
BAL and response to CTX in SSc ILDTo evaluate whether lavage cellularity identifies dictinct subsets of disease and/or predicts CTX responsiveness
201 patients lavaged; 71.6% had abnormal cellularity; these had more severe lung function, GG and fibrosis in RML;
Despite these relationships, multivariate analyses found the presence orp p y pabsence of abnormal cell differential was NOT an independent predictor ofdisease progression or response to CTX
The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response*
*Strange et al: Am J Resp Crit Care 2008 Jan; 177(1):91 98
Novel (antifibrotic agents) for SSc ILDAblation of TGFBeta pathways via tyrosine kinase inhibition: case reports suggesting benefit:
Imatinib: graft vs. host ( 3 4)pulmonary hypertension (1 Freyhaus et al)p y yp ( y )pulmonary fibrosis (1 Sabnani et al)preclinical studies or animal models of fibrosis (>4)
refractory diffuse scleroderma (2)
Dasatinib: phase 2 trial underway in early diffuse SSc
Mycophenolate vs. cyclophosphamide (SLS 2) Others: Antibody to interferon, TGF B, CTGF, CD 19, IL 13,MCP 1, PDGF, cellular therapy (stem cell transplantation)….
Monitoring of ILD:Yearly PFT with DLCO remains standard referenceSerial CT scan changes:
Early ILD: septal or subpleural lines; d l b i iblground glass may be irreversible
As fibrotic lung progresses, honeycombing or traction bronchiectasis;
No effective agent found to alter disease course
HematoxylinHematoxylin and eosin stain of lung from patient with fatal interstitial lung disease. and eosin stain of lung from patient with fatal interstitial lung disease. There is interstitial fibrosis, persistent interstitial inflammation, and striking There is interstitial fibrosis, persistent interstitial inflammation, and striking intimalintimalhyperplasia of a pulmonary arteriolehyperplasia of a pulmonary arteriole..
Pulmonary HTN screening
Pulmonary hypertension (PH) can be suggested by echo but must be confirmed by right heart cath.
PFT show diminished %DLCO disproportionately toPFT show diminished %DLCO disproportionately to%FVC (ie: FVC/DLCO >1.6)echo/doppler >50 mm Hg6 minute walk test (measure oxygen saturation, distance; dyspnea index)
Right heart catheterization (mean PA, CO, CI, PCW)
Scleroderma related PAHSSc related PH leading cause of death Defined as mean PA>25 mmHg (nl PCW) and PVR >3 Wood unitsIf d PAH RV h h RVIf untreated PAH causes RV hypertrophy, RV pressureoverload, dilation and death due to RV failure
Integrity of RV function rather than degree of vascular disease that determines symptoms and mortality
PAH classification Dana Point 2009
WHO Group I: increased PVR due to vascular remodeling and occlusion of pulmonary arteries: SScPAH is in this groupWHO Group II: PH due to left sided heart disease:WHO Group II: PH due to left sided heart disease:including diastolic dysfunction. WHO Group III: due to lung disease (ILD) and chronic hypoxiaWHO Group IV: chronic thromboembolic dzWHO Group V: unclear etiology/miscellaneous
PAH therapy: THERAPY: based on pathophysiology: concept that endothelial cell dysfunction leading to imbalance between endothelial derived vasoactive substances and abnormal smooth muscle tone and proliferation
Despite improving functional and quality of life SSc PAHDespite improving functional and quality of life, SSc PAHstill have poorer outcome than those with idiopathic PAH
SSc PAH therapy chosen from 3 currently approved classes of vasodilators: PG, PDE 5 inhibitors and ET blockers
LV dysfunction, diastolic dysfunction frequently recognized as a cause of dyspnea
MacGregor et Al; Rheumatology 2001:40 (4): 453
Challenges in ICU management of SSc
Tamponade echo/RHC short trial of steroid, needle drain/window
RHF RHC for dx IV prostacyclin, diuretics, oxygen, inotropes
Flare of ILD HRCT, nl PCW lung bx lung transplantation; treat CHF/infections; no role for steroid
Renal crisis triad present short acting ACE oral captopril, enalapriluntil DBP <80 and SBP <120; continue ACE if dialysis occur for 6 12 months later
Digital ischemia angiogram IV prostacyclin; digital block
Bowel obstruction CT Abd decompress with NGT/rectal tube; TPN; prokinetic agents
Farber et al: J intensive Care Med: June 2010 (10):1 12
Scleroderma spectrum patient evaluation (suggestions):
HISTORYRecent onset Raynaud in subject >30 yrs ageHistory of digital ulcers/ presence of digital pitsAchy joint or muscle pain
h f b hShortness of breathPersistent GERD
EXAMSkin thickening handsBasilar dry rales on lung exam, prominent P2 Labs: hemoglobin, creat, urinalysis, CPK/aldolase, Serologies (ANA, RF, anti centromere, scleroderma or Scl70)
GUIDELINES for : performance of minimal standards of care
PFT: Spirometry with DLCO & echo/doppler study
Repeat PFT annually for 5 years (if disease onset < 5yrs) because this detects decline in lung function due to progressive ILD this would define treatment for the patient.
GUIDELINES for : performance of minimal standards of care
Echo/doppler if PASP >50 mmHg (or TR velocity >3.5 mm/sec)RHC within 3 months because this is the definitive test for diagnosing PHfor diagnosing PHIf SSc and NYHA/WHO functional class 2 4, then treatment initiated within 3 months of RHC because this improves morbidity and mortality
Surgical Treatment of Surgical Treatment of COPDCOPD
11
10/9/201010/9/2010Dr. Arthur NgDr. Arthur Ng
Deborah Heart and Lung CenterDeborah Heart and Lung CenterDepartment of SurgeryDepartment of Surgery
COPDCOPD
The Global Initiative for Chronic The Global Initiative for Chronic Obstructive Lung Disease (GOLD) works Obstructive Lung Disease (GOLD) works with health care professionals and public with health care professionals and public health officials around the world to raise health officials around the world to raise awareness of Chronic Obstructive awareness of Chronic Obstructive Pulmonary Disease (COPD) and to Pulmonary Disease (COPD) and to improve prevention and treatment of this improve prevention and treatment of this
GOLD ObjectivesGOLD ObjectivesRecommend effective COPD management Recommend effective COPD management and prevention strategies for use in all and prevention strategies for use in all countries.countries.Increase awareness of the medical Increase awareness of the medical community, public health officials and the community, public health officials and the general public that COPD is a public general public that COPD is a public h l h blh l h bl
22
p pp plung disease.lung disease.Through the development of evidenceThrough the development of evidence--based guidelines for COPD management, based guidelines for COPD management, and events such as the annual celebration and events such as the annual celebration of World COPD Day, GOLD is working to of World COPD Day, GOLD is working to improve the lives of people with COPD in improve the lives of people with COPD in every corner of the globe.every corner of the globe.GOLD was launched in 1997 in GOLD was launched in 1997 in collaboration with the National Heart, collaboration with the National Heart, Lung, and Blood Institute, National Lung, and Blood Institute, National Institutes of Health, USA, and the World Institutes of Health, USA, and the World Health Organization.Health Organization.
health problem.health problem.Decrease morbidity and mortality from Decrease morbidity and mortality from COPD through implementation and COPD through implementation and evaluation of effective programs for evaluation of effective programs for diagnosis and management.diagnosis and management.Promote study into reasons for increasing Promote study into reasons for increasing prevalence of COPD including prevalence of COPD including relationship with environmentrelationship with environmentImplement effective programs to prevent Implement effective programs to prevent COPD.COPD.
COPDCOPD
33
COPDCOPD
16 million people in US currently diagnosed with 16 million people in US currently diagnosed with COPDCOPDAdditional 14 million people in US still Additional 14 million people in US still not not or under or under diagnosed with COPDdiagnosed with COPD
44
ggCOPD is the fourth leading cause of death in the US COPD is the fourth leading cause of death in the US accounting for 125,000 deaths/year. It is the only accounting for 125,000 deaths/year. It is the only major disease with an increasing death rate and it is major disease with an increasing death rate and it is projected to become the third leading cause of death projected to become the third leading cause of death by the year 2020by the year 2020
COPDCOPD
The total estimated cost of COPD in the US in 2002 The total estimated cost of COPD in the US in 2002 was $32.1 billionwas $32.1 billion
$18 billion in direct cost$18 billion in direct cost$14.1 billion in indirect cost$14.1 billion in indirect cost
55
$14.1 billion in indirect cost$14.1 billion in indirect costCOPD accounted for 1.5 million ED visits and COPD accounted for 1.5 million ED visits and 726,000 hospitalizations in 2000726,000 hospitalizations in 2000
COPDCOPD
66
COPDCOPD
DiagnosisDiagnosisSymptomsSymptoms
Chronic coughChronic coughDyspneaDyspnea
77
Inhalation exposureInhalation exposureSmokingSmokingOccupational dust/chemicalsOccupational dust/chemicals
SpirometrySpirometryFEVI <80%FEVI <80%FEVI/FVC <0.7FEVI/FVC <0.7
COPDCOPD
88
COPDCOPD
99
COPDCOPD
1010
COPDCOPD
1111
1212
1313
Centrilobular EmphysemaCentrilobular Emphysema
1414
1515
1616
1717
Treatment of Stable Chronic COPDTreatment of Stable Chronic COPDBronchodilatorsBronchodilators
Short acting bronchodilatorsShort acting bronchodilatorsB antagonistB antagonistAnticholinergicAnticholinergicCombinationCombination
Long acting bronchodilatorsLong acting bronchodilators
Supplemental TherapySupplemental TherapyOxygenOxygen
Smoking cessationSmoking cessationSecretion clearanceSecretion clearanceVaccinationVaccinationRehabilitationRehabilitation
1818
g gg gB antagonistB antagonistAnticholinergicAnticholinergicCombinationCombination
Inhaled glucocorticoidsInhaled glucocorticoidsTheophyllineTheophyllineRarely used medicationsRarely used medications
Systemic glucocorticoidsSystemic glucocorticoidsAntibiotic therapyAntibiotic therapy
RehabilitationRehabilitationPatient educationPatient educationNutritionNutrition
SurgerySurgeryBullectomyBullectomyLVRSLVRSLung transplantLung transplant
COPDCOPD
1919
Bullectomy LVRS
Surgery for COPDSurgery for COPD
2020Lung Transplant
LVRS/BullectomyLVRS/Bullectomy
RationaleRationale
Reduce size mismatching between hyperinflated lungs Reduce size mismatching between hyperinflated lungs
and the chest cavityand the chest cavity
2121
and the chest cavityand the chest cavity
Restore normal diaphragm dooming and functionRestore normal diaphragm dooming and function
Surgery for COPDSurgery for COPD
BullectomyBullectomyExcision of one or more localized bullae from one Excision of one or more localized bullae from one or both hemithoracesor both hemithoraces
LVRSLVRS
2222
LVRSLVRSSeries of wedge resections to 20Series of wedge resections to 20--35% of each lung: 35% of each lung: Targeting the most diseased portionsTargeting the most diseased portions
BullectomyBullectomy
BullaeBullae
Indications for resectionIndications for resection
2323
Single on few localized bullaeSingle on few localized bullae
Bullae > 30%Bullae > 30%--50% hemithorax50% hemithorax
Atelectasis of adjacent nonAtelectasis of adjacent non--emphysematous lungemphysematous lung
COPDCOPD
2424
National Emphysema Treatment Trial Group (NETT)National Emphysema Treatment Trial Group (NETT)
COPDCOPD
2525
ATS 2006ATS 2006
COPDCOPD
NETT Trial DesignNETT Trial Design
1218 Patients with Advanced Emphysema6-10 wks mandatory pulmonary rehab (multi-center)
2626
LVRS Medical Therapy
Primary end points: Primary end points: 1) Mortality1) Mortality2) Maximum exercise capacity at 24 months2) Maximum exercise capacity at 24 months
NETT TrialNETT Trial
2727
NETT TrialNETT Trial
Patient CharacteristicsPatient CharacteristicsGOLD Stage IV (FEVI < 30%)GOLD Stage IV (FEVI < 30%)BODE Score ~ 5BODE Score ~ 5E pected mean s r i al 2E pected mean s r i al 2 5 ears5 ears
2828
Expected mean survival 2Expected mean survival 2--5 years5 years
NETT TrialNETT Trial
1218
140 A (high risk)
1078 (non-high risk)
2929
538 surgery 540 medical
NETT Trial ResultsNETT Trial Results
Mortality (Non High Risk)Mortality (Non High Risk)
LVRSLVRS MedicalMedical
3030
90 days90 days 5.2%5.2% 1.5%1.5%
2 years2 years 115/538 (21%)115/538 (21%) 130/540 (24%)130/540 (24%)
NETT Trial ResultsNETT Trial Results
Increased Exercise Capacity (10W)Increased Exercise Capacity (10W)
LVRSLVRS MedicalMedical
3131
16%16% 3%3%
NETT Trial ResultsNETT Trial Results
SubSub--Group AnalysisGroup AnalysisAA
High risk =140High risk =140FEV1 < 20 % di t dFEV1 < 20 % di t d andand
3232
FEV1 < 20 % predictedFEV1 < 20 % predicted andandDLCO < 20 % or homogenous emphysemaDLCO < 20 % or homogenous emphysema30 day surgical mortality 29% (20/70)30 day surgical mortality 29% (20/70)
NETT Trial ResultsNETT Trial ResultsSub Group AnalysisSub Group Analysis
BB (24%)(24%)Upper lobe emphysemaUpper lobe emphysemaLowLow exercise capacityexercise capacity
Mortality Mortality
CC(34%)(34%)Upper lobe emphysemaUpper lobe emphysemaHighHigh exercise capacityexercise capacity
±± MortalityMortality
3333
yyExercise capacityExercise capacity
yy Exercise capacity Exercise capacity
DD(12%)(12%)Non upper lobe emphysemaNon upper lobe emphysemaLowLow exercise capacityexercise capacity
±± MortalityMortality±± Exercise capacityExercise capacity
EE (18%)(18%)Non upper lobe emphysemaNon upper lobe emphysemaHighHigh exercise capacityexercise capacity
±± MortalityMortality±± Exercise capacityExercise capacity
Surgical OutcomesSurgical Outcomes
3434
Surgical OutcomesSurgical Outcomes
3535
Potential Indications and Contraindications for LVRSPotential Indications and Contraindications for LVRS
Parameter Indications Contraindications
Clinical Age < 75 years Age 75 years
Ex-smoker (>6 months) Current Smoker
Clinical picture consistent with emphysema Surgical constraints (eg. Previous thoracic procedures, pleurodesis, chest wall deformity)
Dyspnea despite maximal medical treatment and pulmonary rehabilitation
Pulmonary hypertension (PA systolic >45 mmHg, Pa mean >35 mmHg)
Comorbid illness Clinically significant bronchiectasis
Clinically significant coronary heart disease
3636
Heart failure with an ejection fraction < 45%
Uncontrolled hypertension
Obesity
Physiology FEV1 after bronchodilator < 45% predicted FEVI 20% predicted with either DLCO 20% or homogeneous emphysema
Hyperinflation (TLC > 100% predicted, RV > 150%) PaO2 45 mmHg on room air
Post rehabilitation 6-minute walk distance > 140 meters
Low post rehabilitation maximal achieved cycle ergometry watts
Imaging Chest radiograph - hyperinflation Homogeneous emphysema with FEV1 20% predicted
HRCT confirming severe emphysema, ideally with upper lobe predominance Significant pleural or interstitial changes on HRCT
Non upper lobe predominant emphysema and high post rehabilitation maximal achieved cycle ergometry watts
Bronchoscopic Lung Volume ReductionBronchoscopic Lung Volume Reduction
3737
Lung TransplantLung TransplantRecipient Selection/GuidelinesRecipient Selection/Guidelines
Appropriate ageAppropriate ageSingle lung transplant ~ 65 yearsSingle lung transplant ~ 65 yearsDouble lung transplant ~ 60 yearsDouble lung transplant ~ 60 years
Clinical and physiologic severityClinical and physiologic severityI ff i il bl di lI ff i il bl di l
3838
Ineffective or unavailable medical treatmentIneffective or unavailable medical treatmentLimited life expectancy due to lung diseaseLimited life expectancy due to lung diseaseAcceptable nutritional status, 80%Acceptable nutritional status, 80%--120% of ideal body 120% of ideal body weightweightSatisfactory psychosocial profile and support systemSatisfactory psychosocial profile and support systemAdequate financial source for the procedure and Adequate financial source for the procedure and postoperative carepostoperative care
Lung TransplantLung Transplant
Recipient Selection/GuidelinesRecipient Selection/GuidelinesContraindicationsContraindications
Uncontrolled/untreatable infectionsUncontrolled/untreatable infectionsHIV, hepatitis B or C HIV, hepatitis B or C
Malignancy within 2 yearsMalignancy within 2 years
3939
Malignancy within 2 yearsMalignancy within 2 yearsSignificant coronary artery disease or heart failureSignificant coronary artery disease or heart failureChest wall/spinal deformityChest wall/spinal deformityCurrent smokerCurrent smokerUnresolved psychosocial problems/medical noncomplianceUnresolved psychosocial problems/medical noncompliance
Drug or alcohol additionDrug or alcohol additionAbsence of reliable support systemAbsence of reliable support system
Lung TransplantationLung Transplantation
COPD is the most common indication for COPD is the most common indication for lung transplantationlung transplantationAnnual world lung transplant volume Annual world lung transplant volume 18001800 2200/year2200/year
4040
18001800--2200/year2200/yearMedian survival for all adult recipients is Median survival for all adult recipients is 5 years but BLT have better median 5 years but BLT have better median survival than SLT (5.9 vs 4.4 yrs.)survival than SLT (5.9 vs 4.4 yrs.)Growing trend favors BLT over SLTGrowing trend favors BLT over SLT
Surgical OutcomesSurgical Outcomes
4141
Surgical OutcomesSurgical Outcomes
4242
PULMONARY FUNCTION PULMONARY FUNCTION TESTINGTESTING
Andrew Martin, MDAndrew Martin, MDChair, Pulmonary DepartmentChair, Pulmonary Department
Deborah Heart and Lung CenterDeborah Heart and Lung Center
DisclosuresDisclosures
•• No financial disclosuresNo financial disclosures•• No off label use of medications or devices No off label use of medications or devices
will be discussedwill be discussedwill be discussed.will be discussed.
General Uses For Standard General Uses For Standard Pulmonary Function TestsPulmonary Function Tests
•• Evaluation of patients with breathing Evaluation of patients with breathing difficultiesdifficulties
•• Following the course of established lungFollowing the course of established lungg gg gdiseasedisease
•• Assessment for pulmonary resectionAssessment for pulmonary resection•• Assessment for disabilityAssessment for disability•• Detection of subclinical lung disease in Detection of subclinical lung disease in
smokerssmokers
Major PFT ParametersMajor PFT Parameters•• Total lung capacity (TLC) Total lung capacity (TLC) –– total gas volume in total gas volume in
lungs at full inspirationlungs at full inspiration•• Vital capacity (VC) Vital capacity (VC) –– total gas exhaled from full total gas exhaled from full
inspiration to full expiration, slow (SVC) or inspiration to full expiration, slow (SVC) or p p , ( )p p , ( )forced (FVC)forced (FVC)
•• Forced expiratory volume in one second (FEV1) Forced expiratory volume in one second (FEV1) ––amount exhaled in first second of a forced vital amount exhaled in first second of a forced vital capacity maneuver.capacity maneuver.
•• Functional residual capacity (FRC) Functional residual capacity (FRC) –– amount of amount of gas in lungs at end expiration at restgas in lungs at end expiration at rest
Major PFT ParametersMajor PFT Parameters
•• Residual volume (RV) Residual volume (RV) –– amount of gas amount of gas remaining in lungs after full expirationremaining in lungs after full expiration
•• FEV1/VCFEV1/VC –– ratio of FEV1 to vital capacityratio of FEV1 to vital capacityFEV1/VCFEV1/VC ratio of FEV1 to vital capacityratio of FEV1 to vital capacity
lum
e
FEV
FORCED EXPIRATION MANEUVERFORCED EXPIRATION MANEUVER
FVC
0 1 2 3 Time (seconds)
Vo
FEV1 FVC
Calculation Of Lung VolumesCalculation Of Lung VolumesTLC=FRC+IC
IC IRVVC
FRC
RV=FRC-ERV
ERV
TV
Measurement Of FRCMeasurement Of FRCDilution TechniquesDilution Techniques
C1V1 = C2V2
FRC = V2-V1
Measurement Of FRCMeasurement Of FRCDilution TechniquesDilution Techniques
Effect Of BullaeEffect Of BullaeFRC = V2-V1
C2 falsely high
V2= C1V1C2
C2 falsely highso V2 falsely low
andFRC falsely low
Measurement Of FRCMeasurement Of FRCDilution TechniquesDilution Techniques
Effect Of LeakEffect Of Leak
FRC = V2-V1
C2 falsely low
V2= C1V1C2
C2 falsely lowso V2 falsely high
andFRC falsely high
Measurement of FRCMeasurement of FRCBody PlethysmographyBody Plethysmography
MouthPressure
BoxPressure
Boyle’s Law
P1V1=P2V2
Pressure
Measurement of FRCMeasurement of FRC
•• Helium dilutionHelium dilution–– Measures communicating lung unitsMeasures communicating lung units–– May miss severely obstructed units and bullaeMay miss severely obstructed units and bullaeMay miss severely obstructed units and bullaeMay miss severely obstructed units and bullae
•• PlethysmographyPlethysmography–– Measures total thoracic gas volumeMeasures total thoracic gas volume–– May include nonMay include non--functioning unitsfunctioning units
Flow(L/sec)
RV
Expiration
Flow Volume LoopsFlow Volume LoopsNormalNormal
Volume (L)
RV
TLCInspiration
Steps In The Interpretation Of Steps In The Interpretation Of PFT’sPFT’s
•• Normal or abnormal?Normal or abnormal?•• Restrictive or obstructive?Restrictive or obstructive?•• Response to bronchodilatorsResponse to bronchodilators•• Response to bronchodilatorsResponse to bronchodilators•• Diffusion abnormalitiesDiffusion abnormalities•• Associated featuresAssociated features
–– Air TrappingAir Trapping–– Signs of muscle weaknessSigns of muscle weakness
Normal Or AbnormalNormal Or Abnormal
•• Based on TLC, SVC, RV, FVC, FEVBased on TLC, SVC, RV, FVC, FEV11,,FEVFEV11 /FVC, Diffusing capacity/FVC, Diffusing capacity
•• Other parametersOther parameters -- PEFR FEFPEFR FEF2525 7575 areareOther parametersOther parameters PEFR, FEFPEFR, FEF2525--7575 arearesuggestive but not diagnostic by suggestive but not diagnostic by themselves.themselves.
•• Mouth pressures Mouth pressures -- PIPImaxmax, PE, PEmaxmax to check for to check for muscle weaknessmuscle weakness
Restrictive Or Obstructive?Restrictive Or Obstructive?
TLC FVC FEV1 FEV1/FVC
Ob i N l N l N lObstruction Normal or Normal or
Restriction Normal or
Normalor
Response To BronchodilatorsResponse To Bronchodilators
12 % Increase In FVC or FEV12 % Increase In FVC or FEV11
andand
Absolute Increase > 200ccAbsolute Increase > 200cc
Other FindingsOther Findings
•• Air Trapping Air Trapping -- increased TLC, RV, and increased TLC, RV, and RV/TLCRV/TLC
•• HyperinflationHyperinflation -- same as above differentsame as above differentHyperinflationHyperinflation same as above, differentsame as above, differentmechanismmechanism
•• Muscle weakness Muscle weakness -- decreased mouth decreased mouth pressures (PIpressures (PImaxmax, PE, PEmaxmax), decreased MVV, ), decreased MVV, decreasing tidal volumes during MVVdecreasing tidal volumes during MVV
Obstructive Lung DiseasesObstructive Lung Diseases
•• Asthma and related disordersAsthma and related disorders•• Emphysema and chronic bronchitisEmphysema and chronic bronchitis•• BronchiectasisBronchiectasis•• BronchiectasisBronchiectasis•• Cystic FibrosisCystic Fibrosis•• Obliterative bronchiolitisObliterative bronchiolitis•• Rarely sarcoidosis or BOOPRarely sarcoidosis or BOOP
Obstructive Lung DiseasesObstructive Lung DiseasesPatternsPatterns
•• Asthma Asthma -- Different degrees of obstruction, Different degrees of obstruction, air trapping, bronchodilator response, air trapping, bronchodilator response, normal when asymptomaticnormal when asymptomaticy py p
•• Emphysema Emphysema -- Severe obstruction, Severe obstruction, hyperinflation, low DlCOhyperinflation, low DlCO
•• Chronic Bronchitis Chronic Bronchitis -- Mild obstruction, no Mild obstruction, no hyperinflation, normal DlCO hyperinflation, normal DlCO
Restrictive Lung DiseasesRestrictive Lung Diseases
•• Pulmonary fibrosisPulmonary fibrosis•• SarcoidosisSarcoidosis•• Bronchiolitis obliterans Bronchiolitis obliterans
•• CHFCHF•• Hypersensitivity Hypersensitivity
pneumonitispneumonitisorganizing pneumoniaorganizing pneumonia
•• Histiocytosis X Histiocytosis X (Eosinophilic(EosinophilicGranuloma)Granuloma)
•• Pulmonary alveolar Pulmonary alveolar proteinosisproteinosis
•• LymphangioleiomyomatosisLymphangioleiomyomatosis
•• KyphoscoliosisKyphoscoliosis•• Lung resectionLung resection•• PneumoniaPneumonia
Diffusing CapacityDiffusing Capacity
•• Why carbon monoxide?Why carbon monoxide?•• Diffusion vs. perfusion limitationDiffusion vs. perfusion limitation
Seconds
O2%Sat
.75
100
40.25
Capillary Transit
Diffusing CapacityDiffusing Capacity
•• Measures the ability of Measures the ability of the entire alveolar the entire alveolar membrane to effect membrane to effect diff i fdiff i f
111diffusion of gases.diffusion of gases.
•• Is dependent on Is dependent on alveolar capillary alveolar capillary blood volume.blood volume.
CML VDD
Dl = total lung diffusion Dm= membrane diffusion
x Vc = blood phase diffusion
Bronchoprovocation TestingBronchoprovocation Testing
•• Tests for decreased FEV1 following various Tests for decreased FEV1 following various stimuli : methacholine, exercise, cold air, stimuli : methacholine, exercise, cold air, occupational irritants.occupational irritants.pp
•• Methacholine challenge test most common Methacholine challenge test most common --very sensitive, not extremely specificvery sensitive, not extremely specific
•• PCPC2020 -- concentration of drug that causes a concentration of drug that causes a 20% fall in FEV20% fall in FEV11 from baselinefrom baseline
Diagnostic Value of PCDiagnostic Value of PC20201
0.9
0.8
0.7
0.6
0 5
prob
abili
ty
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0.5
0.4
0.3
0.2
0.1
0
Pre-test probability
Post
-test
(ATS 2000)
Characterization of Bronchial Characterization of Bronchial ResponsivenessResponsiveness
(ATS 2000)(ATS 2000)
PC20(mg/ml) Interpretation>16 Normal
4.0-16 Borderline BHR
1.0-4.0 Mild BHR (positive test)
<1.0 Moderate to severe BHR
Flow Volume LoopsFlow Volume LoopsNormalNormal
RV
Expiration
Flow(L/sec)
RV
TLCInspiration
Volume (L)
Restrictive Lung DiseaseRestrictive Lung DiseaseFlow
(L/sec)
Volume (L)
Obstructive Airway DiseaseObstructive Airway DiseaseFlow
(L/sec)
Post-treatment
“Scooping” is present.
Volume (L)
Flows preferentially affected at low lung
volumes
Variable Extrathoracic Variable Extrathoracic ObstructionObstruction
Flow(L/sec)
Volume (L)
Upper airway collapses during
inspiration.
Variable IntrathoracicVariable IntrathoracicObstructionObstruction
Flow(L/sec) Intrathoracic airways collapse
during expiration
Volume (L)
Flows preferentially affected at high lung
volumes
Fixed ObstructionFixed Obstruction
Flow(L/sec) Flows affected during both
inspiration and expiration
Volume (L)
Impulse Oscillometry?Impulse Oscillometry?•• Some Patients Cannot Perform Spirometry Some Patients Cannot Perform Spirometry
(effort, language, age, cooperation etc)(effort, language, age, cooperation etc)•• Some Patients Cannot Perform Spiro Some Patients Cannot Perform Spiro
Properly (ATS/ERS Recommendations)Properly (ATS/ERS Recommendations)p y ( )p y ( )•• Spirometry May Not Be Sensitive Enough Spirometry May Not Be Sensitive Enough
to Detect Response to Bronchodilatorto Detect Response to Bronchodilator•• Distinguish Proximal from Distal Distinguish Proximal from Distal
ObstructionObstruction•• Challenge Testing and Numerous FV LoopsChallenge Testing and Numerous FV Loops
IOSIOS-- The Basic Operational The Basic Operational ConceptsConcepts
•• The subject The subject breathes quietlybreathes quietly onondevice consisting of a device consisting of a pneumotach and a loudspeakerpneumotach and a loudspeaker
•• The loudspeaker sends pressure The loudspeaker sends pressure i l d d th ii l d d th iimpulses up and down the airwayimpulses up and down the airwayat A rate of 5 times per sec (5 at A rate of 5 times per sec (5 hertz) while subject hertz) while subject breathes breathes quietly (20quietly (20--30 sec)30 sec)
•• These impulses interact with the These impulses interact with the lung structures and then are lung structures and then are reflected back to the device for reflected back to the device for analysisanalysis
HertzHertz (Hz) = 1 Cycle/Second(Hz) = 1 Cycle/Second
•• The pressure impulses contain various The pressure impulses contain various frequencies (5frequencies (5--20 hz) that the computer filters 20 hz) that the computer filters and analyzesand analyzes
•• Smaller frequency (5 hz) can penetrate toSmaller frequency (5 hz) can penetrate to
(Not a Rental Car)
•• Smaller frequency (5 hz) can penetrate toSmaller frequency (5 hz) can penetrate tosmaller airways, so it gives information about smaller airways, so it gives information about the whole respiratory systemthe whole respiratory system
•• Higher frequency (20hz) cannot penetrate as Higher frequency (20hz) cannot penetrate as far; it gives information about proximal, larger far; it gives information about proximal, larger airwaysairways
•• Normal lungNormal lung--–– No frequency No frequency
dependence of dependence of resistanceresistance
•• COPD subjectCOPD subject--–– R5 > R20R5 > R20–– Frequency Frequency
dependence of dependence of resistanceresistance
Indications For Exercise TestingIndications For Exercise Testing
•• Diagnosis of exercise induced asthmaDiagnosis of exercise induced asthma•• Definition of the cause for exertional Definition of the cause for exertional
dyspnea (cardiac vs pulmonary)dyspnea (cardiac vs pulmonary)dyspnea (cardiac vs. pulmonary)dyspnea (cardiac vs. pulmonary)•• Assessment for disabilityAssessment for disability•• Assessment for home oxygen therapyAssessment for home oxygen therapy•• Assessment for pulmonary resectionAssessment for pulmonary resection
6 Minute Walk Test6 Minute Walk Test
•• Record distance walked with maximal effort Record distance walked with maximal effort in 6 minutes and oxygen saturation at in 6 minutes and oxygen saturation at minute intervals.minute intervals.
•• Simple and easy to administerSimple and easy to administer•• Upper limit of distance one can walk Upper limit of distance one can walk
without running.without running.•• Used for evaluation of exercise tolerance Used for evaluation of exercise tolerance
and exercise induced hypoxemia.and exercise induced hypoxemia.
CardioCardio--pulmonary Metabolic pulmonary Metabolic Exercise TestingExercise Testing
•• Graded, symptom limited exercise testGraded, symptom limited exercise test•• Provides precise information on maximal Provides precise information on maximal
oxygen uptake physiology of exerciseoxygen uptake physiology of exerciseoxygen uptake, physiology of exerciseoxygen uptake, physiology of exerciselimitation, and estimation of anaerobic limitation, and estimation of anaerobic threshold.threshold.
Steps In Interpreting Metabolic Steps In Interpreting Metabolic Exercise TestsExercise Tests
•• Normal or Abnormal?Normal or Abnormal?–– Usually based on VO2Usually based on VO2maxmax or Workor Workmaxmax
–– Anaerobic threshold also usedAnaerobic threshold also usedAnaerobic threshold also usedAnaerobic threshold also used–– Dead space to tidal volume ratioDead space to tidal volume ratio–– Oxygen desaturationOxygen desaturation
•• Is the limitation cardiac or pulmonary?Is the limitation cardiac or pulmonary?•• PostPost--exercise bronchospasmexercise bronchospasm
Metabolic Exercise TestsMetabolic Exercise TestsPatternsPatterns
•• Pulmonary limitationPulmonary limitation–– no metabolic acidosisno metabolic acidosis–– VeVe > 80% of MVV> 80% of MVVVeVemaxmax 80% of MVV80% of MVV
•• Cardiac limitationCardiac limitation–– metabolic acidosismetabolic acidosis–– low VO2 maxlow VO2 max–– crossing of anaerobic thresholdcrossing of anaerobic threshold
Metabolic Exercise TestsMetabolic Exercise TestsPatternsPatterns
•• Pulmonary hypertensionPulmonary hypertension–– cardiac limitationcardiac limitation–– increase in Vd/Vtincrease in Vd/Vtincrease in Vd/Vtincrease in Vd/Vt
•• COPDCOPD–– increase in Vd/Vtincrease in Vd/Vt–– increase in PCOincrease in PCO22
Pulmonary Function TestsFEV1 > 2.0 liters?DLCO > 60% Predicted?
Q tit ti P f i S i
YES
YES
Evaluation For Pneumonectomy
Quantitative Perfusion ScanningPredicted Post-Op FEV1 > 0.8 liters?Predicted DLCO > 60% Predicted?
Metabolic Exercise TestMaximum VO2 > 20 ml/kg/min?
OPERATE
YES
The Arterial Blood GasThe Arterial Blood Gas
•• Measured ValuesMeasured Values–– pHpH–– PCOPCO22
100%
O2 Saturation
–– POPO22
–– Oxygen SaturationOxygen Saturation
•• Calculated ValuesCalculated Values–– Plasma BicarbonatePlasma Bicarbonate
50%
P50PO2
The AThe A--a Gradienta Gradient
P(AP(A--a)Oa)O22 -- PAOPAO22--PaOPaO22
RFIOFIOPACOPIOPAO 2
22221
At Rest On Room AirAt Rest On Room Air
R
8.0150 2
2PACOPAO
Normally 15 Torr
The Five Causes Of HypoxemiaThe Five Causes Of Hypoxemia
•• HypoventilationHypoventilation
•• VentilationVentilation--Perfusion MismatchPerfusion Mismatch
•• ShuntShunt
•• Diffusion AbnormalityDiffusion Abnormality
•• Low Inspired POLow Inspired PO22
Differentiation Of HypoxemiaDifferentiation Of Hypoxemia
Cause Effect On P(A-a)O2 Effect Of 100%FIO2
Hypoventilation No Change Corrected
Ventilation-perfusionImbalance
Increased Corrected
Right-to-left Shunt Increased No Correction
DiffusionAbnormality
No Change OrIncreased
Corrected
Low Inspired PO2 No Change Corrected
Steps In Interpreting Blood GasesSteps In Interpreting Blood Gases•• Presence or absence of acidemia or alkalemiaPresence or absence of acidemia or alkalemia•• Presence or absence of acidosis or alkalosisPresence or absence of acidosis or alkalosis•• If there is an acidIf there is an acid--base disorder is it:base disorder is it:
i b li ?i b li ?–– respiratory or metabolic?respiratory or metabolic?–– acute or chronic?acute or chronic?
•• Presence or absence of HypoxemiaPresence or absence of Hypoxemia•• AlveolarAlveolar--arterial POarterial PO22 DifferenceDifference
(A(A--a gradient)a gradient)
Blood Gases Vs. Diffusing CapacityBlood Gases Vs. Diffusing CapacityThe ParadoxThe Paradox
•• Emphysema Emphysema –– resting arterial blood gases resting arterial blood gases relatively well preserved until late in the relatively well preserved until late in the disease while diffusing capacity falls early.disease while diffusing capacity falls early.g p y yg p y y
•• Chronic bronchitis Chronic bronchitis –– resting arterial blood resting arterial blood gases show hypoxemia and hypercapnea gases show hypoxemia and hypercapnea early while diffusing capacity is well early while diffusing capacity is well preserved.preserved.
Blood Gases Vs. Diffusing CapacityBlood Gases Vs. Diffusing CapacityThe AnswerThe Answer
•• In emphysema membrane area is reduced In emphysema membrane area is reduced but V/Q ratios are preserved so resting but V/Q ratios are preserved so resting ABG’s are preserved but DlCO suffers.ABG’s are preserved but DlCO suffers.pp
•• In chronic bronchitis membrane area is In chronic bronchitis membrane area is normal but V/Q ratios are abnormal so normal but V/Q ratios are abnormal so resting ABG’s suffer but DlCO is resting ABG’s suffer but DlCO is preserved.preserved.
Case 1Case 1AA 6565 yearyear oldold malemale isis 44 hourshours postpost--opop fromfrom 33 vesselvessel coronarycoronary arteryarterybypassbypass surgerysurgery.. HeHe isis receivingreceiving continuouscontinuous dripsdrips ofof sodiumsodiumnitroprussidenitroprusside forfor hypertensionhypertension andand diltiazemdiltiazem forfor suprasupra--ventricularventriculartachycardiatachycardia.. ArterialArterial POPO22 onon 3535%% FIOFIO22 isis 5656 andand risesrises toto 6565 onon 100100%%FIOFIO22.. ChestChest XX--rayray revealsreveals leftleft lowerlower lobelobe atelectasisatelectasis..
Case 2Case 2AA 2626 yearyear oldold femalefemale atat 3535 weeksweeks gestationgestation presentspresents withwith aa severesevereasthmaasthma attackattack.. PulsePulse oximeteroximeter onon roomroom airair readsreads 8080%%.. AfterAfter severalseveralalbuterolalbuterol treatmentstreatments sheshe isis wearingwearing aa 100100%% nonnon--rebreatherrebreather maskmask andandisis obtundedobtunded.. PulsePulse oximeteroximeter readsreads 9898%% saturationsaturation.. ArterialArterial bloodbloodgasesgases readread asas followsfollows::
pH 6.9 / PCOpH 6.9 / PCO22 85 / PO85 / PO22 310310Case 3Case 3AA 2525 yearyear oldold malemale isis notednoted toto havehave aa lowlow pulsepulse oximeteroximeter readingreading ononroomroom airair inin thethe recoveryrecovery roomroom followingfollowing upperupper airwayairway surgerysurgery..ArterialArterial bloodblood gasesgases readread asas followsfollows::
pH 7.1 / PCOpH 7.1 / PCO22 72 / PO2 5072 / PO2 50
A 35 year old female has a cough, waking her up 3-4 nights a week in the early morning hours. Also finds herself coughing after jogging.
Value(liters)
% Predicted
FVC 4.46 102%FEV1 3 73 103%FEV1 3.73 103%FEV1/FVC 0.84
What is the interpretation of this spirometry?
What is the likely diagnosis?
What is the next diagnostic test?
A 66 year old male smoker has shortness of breath with minimal exertion. He also complains of audible wheezing.
Value(liters)
% Predicted
FVC 3.13 68%FEV1 0.81 23%FEV1/FVC 0.26TLC 7.28 103%RV 1.67 139%RV 1.67 139%RV/TLC 0.58 168%
What is the interpretation?
Bronchodilator Response
Pre(liters)
Post(liters)
% Increase
FVC 3.13 3.19 2%
FEV1 0.81 0.95 19%
A 71 year old male former asbestos worker complains of progressive dyspnea for 2 years. He is a lifelong non-smoker with no history of asthma.
Value (liters)
% Predicted
FVC 3.11 74% FEV1 2.42 75% FEV1/FVC 0.78 TLC 4.56 68%C .56 68%RV 1.34 55%
What is the interpretation?
What is the likely diagnosis?