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

7

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.

13

Nap Results (Walker et al. AAAS 2010)

The road may be long and winding…

The path may even be dark…

14

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?