ABIM Board Review: Pulmonary Medicine. Overview Topics – Respiratory Infections – Airway Disease...

ABIM Board Review:ABIM Board Review:Pulmonary MedicinePulmonary Medicine

OverviewOverview

Topics– Respiratory Infections– Airway Disease– Restrictive Lung Diseases– Pulmonary Vascular Disease– Pleural Disease– Sleep– Potpourri

HintsHints

Stress certain topics– ASTHMA, TB, SARCOID, ILD’s,PFT’s

‘Things marked with these things are pearls to remember’

Disclaimer: A 3 year fellowship is difficult to condense into a 1 hour lecture…

Respiratory InfectionsRespiratory Infections

Community Acquired PNA (CAP)HealthCare Assocoiated PNA

– Hospital Acquired PNA (HAP)– Ventilator Associated PNA (VAP)– Nursing Home Associated PNA

TB

Types of PneumoniaTypes of Pneumonia

Community Acquired– Bacterial– Atypical

Hospital Acquired >72 hours after admission

Ventilator AssociatedAspiration Syndromes

Physical Signs of PneumoniaPhysical Signs of Pneumonia

Bronchial Breath soundsDullness to percussionEgophony

Community Acquired Community Acquired Pneumonia BugsPneumonia Bugs

Strep pneumoniae mycoplasma viral Chlamydia H. influenzae Staph aureus Legionella Anerobic?

Hospital Acquired PNA BugsHospital Acquired PNA Bugs

Gram negative entericsStaph aureus (MRSA)H. influenzaeStrep pneumonia

Indicators of Severe Indicators of Severe PneumoniaPneumonia

MultilobarAdvanced ageElevated BUNElevated Respiratory rateHigh or Low WBCHigh or Low Temp.Hypotension

AntibioticsAntibiotics

Outpatient younger than 60ATS

– Macrolide or TetracyclineIDSA

– Macrolide or Fluoroquinolone or Doxycycline – Alternative: Oral second-generation

cephalosporin or AugmentinE-mycin does not cover H. flu (COPD)

Antibiotics Cont.Antibiotics Cont.

Outpatient older than 60 or with co-morbid conditions

ATS– Second generation cephalosporin, Bactrim,

Augmentin with or without a macrolide IDSA

– Macrolide or Fluoroquinolone or Doxycycline – Alternative: Oral second-generation

cephalosporin or Augmentin


Inpatient Ward– ATS

Second or third generation cephalosporin or beta lactam/beta lactamase inhibitor with a macrolide

– IDSA Beta lactam with a macrolide or fluoroquinolone

alone


Inpatient Severe– ATS

Macrolide with antipseudomonal agent plus an aminoglycoside

– IDSA Cefotaxime, ceftriaxone, or Beta-lactam/ Beta-

lactamase inhibitor with macrolide or fluoroquinolone

Follow-Up CXRFollow-Up CXR

Fifty percent of pneumonias clear within 2 weeks and 75 percent clear with in 6 weeks

<5% of 20 year olds, 10-20% of 40 year olds, 30% of 60 year olds and 50% of 80 year olds will continue to have infiltrates at 12 weeks

Multilobar pneumonias are slower to resolve

Pneumovax Pneumovax

Persons older than the age of 50Persons with asplenia, high risk

environments, immunosuppression and chronic illness.

Give vaccine if status is unknownRepeat vaccination should be considered for

patients at high risk and those vaccinated before 65 if not given with in 5 years.

TBTB For Another Time…For Another Time…

Extra-Pulmonary Tuberculosis – Lungs> Kidneys> Bone> Brain

Mycobacterium Other Than Tuberculosis (MOTT) AKA Non-Tuberculous Mycobacteria (NTM)

AKAAKA

Phthisis- “wasting”; chronic pulmonary tuberculosis

“Consumption”“White Plague”

NomenclatureNomenclature

Phthisiology- the study of tuberculosis of the lungs

Converter- patient who has experienced an increase of > 10mm of induration in PPD test size within a two-year period, regardless of age.

Reactor- a non-converter patient with a positive skin test.

LTBI- latent tuberculosis infection. “Treatment of Latent Tuberculosis Infection” has replaced “preventative therapy” and “chemoprophylaxis”.

EpidemiologyEpidemiology

An estimated 1/3 of the world’s population is believed to be infected with M. Tuberculosis (roughly 2 billion people).

Because actual reporting is generally unreliable, several surrogate values have been used, including:– Average annual risk of MTB infection (ARTI)– Estimated incidence of smear positive MTB– Case Notifications– Estimated Case-Fatality rates.

Re-Emerging Scourge?Re-Emerging Scourge?

Although MTB experienced a resurgence in the mid-late 80’s, the incidence has actually continued to decline since 1993 and, as of 2005 was at an all-time low…

Location, Location, LocationLocation, Location, Location

In 1998 active TB reported in every state.Seven states (CA, FL, GA, IL, NJ, NY and

TX) accounted for 60% of all cases.40% of all cases in America’s 64 largest

cities.

A Disease of ImportA Disease of Import

Incidence of MTB among Foreign-born persons varies by country of origin:– Latin America (57% from Mexico)– Philippines– Vietnam– South Korea– China

HIV: TB’s Not-So Silent HIV: TB’s Not-So Silent PartnerPartner

HIV’s effect on cell-mediated immunity uniquely positions it as a dominant factor in susceptibility to MTB in SE Asia and Sub-Saharan Africa.

Rates of co-infection have increased as high as 45-fold between 1990 and 1994 (Thailand)

Where the Money is…Where the Money is…

Active MTB cases: 1990-1999– North America: 320,000– Sub-Saharan Africa: 15,000,000– Asia and the Sub-Continent:

55,000,000

High-Risk Groups: InfectionHigh-Risk Groups: Infection

HIV+ Foreign-born in endemic regions (4-6X) Children of foreign-born from endemic regions Homeless Veterans IV Drug users Congregate living- Nursing homes, prisons, etc.

High-Risk Groups: InfectionHigh-Risk Groups: Infectioncon’tcon’t

Close contacts of individuals known, or suspected, to have active MTB.

Health care workers (i.e. you)

High Risk Groups: DiseaseHigh Risk Groups: Disease

HIV+ (100X) Diabetes Mellitus (3X) Post-Gastrectomy or Intestinal Bypass Silicosis (30X) Certain Cancers- Leukemia, Lymphomas,

HEENT(16X) Pharmacologically Immunosuppressed

– Post-chemotherapy, DMARD, Steroids Post solid-organ transplant (20-74X)

Recent infection (within 2 years)

High-Risk Groups: Disease High-Risk Groups: Disease con’tcon’t

CXR consistent with prior disease without adequate treatment.

ESRD (10-25X)Chronic malabsorption syndromesLow Body Weight (<10% below ideal)

(2X)

Clinical PathogenesisClinical Pathogenesis

Although one organism per 12,000 cu ft has been shown to produce infection, only up to 1/3 of individuals in close contact with patient with active MTB develop infection.

Most infected aerosolized droplets are cleared by upper airway mechanisms.

Those less than 5 microns reach the alveolus, and are phagocytosed by macrophages (MTB infection).

Bacilli multiply at this primary site of infection and within 2 weeks are transported to lymphatics to establish secondary site.

Within 4 weeks delayed-type hypersensitivity develops leading to granuloma formation and subsequent decrease in bacterial burden.

However, sterilization rarely occurs, even though host displays acquired immunity, rapidly clearing subsequent exposures.

THEORETICALLY, as the host begins to control MTB through the primary response, the normally aerophilic bacilli downshifts into a non-replicating stage as surrounding oxygen tension drops.

This non-replicating, or latent, stage allows organisms to avoid the anti-microbial effects of MTB regimens.

The goal of treating latent tuberculosis infection (LTBI) is prolonged courses of therapy so effective drug levels are persistent for months as latent organisms reactivate, rendering themselves susceptible.

By the Numbers…By the Numbers…

Once infected with MTB 3-5% of immunocompetent hosts develop active disease within one year. A further 3-5% will develop active disease within their lifetime.

Said another way: Once primarily infected, lifetime risk of active MTB is 10%; half of those within the following year.

More NumbersMore Numbers

For immunosuppressed, risk of developing active MTB is 7-10% annually.

Diagnosis: SymptomsDiagnosis: Symptoms

Pulmonary– Prolonged productive cough– Hemoptysis– Chest pain

Systemic– Fevers/Chills– Drenching Night Sweats– Anorexia/Weight loss– Easy Fatigability

Diagnosis: H&PDiagnosis: H&P

After considering diagnosis of MTB (and putting a mask on you or patient), focus history on risk factors for MTB infection or disease (see previous) as well as past exposure and treatment history.

Don’t forget to perform adequate review of systems as only 73% of pulmonary MTB cases are exclusively pulmonary.

Diagnosis: The LaboratoryDiagnosis: The Laboratory

The gold standard for diagnosis, the sputum smear, is neither sensitive nor specific.– >10,000 organisms/ml are required for

detection, leaving the smear positive in only 50% of active MTB cases

– Any acid-fast bacilli present will cause the test to be positive.

The SputumThe Sputum

Early AM specimens on three consecutive days are ideal. Induced sputum with inhaled saline may be required in patients unable to provide adequate lower airway samples.

Alternatives– Bronchoscopy (choose wisely)– Early AM Gastric aspiration

SensitivitiesSensitivities

All initially positive MTB cultures must be tested for sensitivities to guide anti-microbiologic treatment and identify Multi-Drug Resistant-TB (MDRTB).

Sensitivities should be repeated if patient experiences clinical treatment failure or cultures remain positive despite two months of treatment.

Purified Protein DerivativePurified Protein Derivative

First recognized as potential tool for diagnosis by Sir Arthur Conan Doyle.

Later perfected by Mantoux. Though fairly accurate for diagnosing

infection (not disease), limited by false positive rate around 10% and false negative rates around 20-30% (higher in immunocompromised).

PPD con’tPPD con’t

A PPD may take up to 10 weeks to turn positive after initial infection.

The PPD is the only way to diagnose MTB infection prior to MTB disease.– Role of Interferon-Gamma…

The PPD ItselfThe PPD Itself

0.1 ml of PPD tuberculin containing 5 TU is injected intradermally on the inner surface of the forearm producing a 6-10 mm wheal.

A reading 48-72 hours from PPD placement should be obtained:– Positive readings may be obtained up to one

week after placement.– Failure to obtain reading within 72 hours

indicates need for repeat testing

More PPDMore PPD

The area of induration (not erythema) is measured in millimeters perpendicular to the long-axis of the forearm.

“Conversion”- defined as an increase of >10mm within a 2-year period.

A Positive PPDA Positive PPD

>5 mm– HIV+– Recent contacts of active MTB case– CXR consistent with healed MTB– Patients with organ transplants or

immunosuppression > 15mg/day of prednisone > 1 month

>10 mm– Recent arrivals (<5 years) from endemic regions.– IVDU– Residents/Employees of:

Prisons/jails Nursing home/shelters Hospitals, including mycobacterial labs

– High-Risk of Progressing to MTB disease– Children <4 yo

> 15mm– No known risk factors for MTB.

PPD: False PositivesPPD: False Positives

MOTTBCG vaccination

PPD: False NegativesPPD: False Negatives

Recent MTB infectionVery Young (< 6mos)Live-Virus vaccinationOverwhelming MTB diseaseHIV+ or other viral infectionImmunosuppressive Therapy

BCG BCG

Bottom line: prior vaccination with BCG should be ignored and the patient treated appropriately if the PPD is positive.

Boost Effect?Boost Effect?

Delayed-Type Hypersensitivity may fade over time, resulting in subsequent negative testing in those previously infected. This exposure to tuberculin may “re-awaken” sensitivity and lead to potential misinterpretation of future positive testing as a new infection.

Two-Step TestingTwo-Step Testing

This “Boost” phenomenon, and subsequent misinterpretation, may be sidestepped by performing two-step testing.

This entails a second test 1-3 weeks after the first with positive tests indicating past infection and treated appropriately

Who Not to TestWho Not to Test

Pregnant women without specific high-risk.Previously positive PPD patients should not

receive repeat testing (including yearly CXR’s); instead, these patients should be followed symptomatically.

Other TestingOther Testing

Some populations may require screening for active MTB disease which is more appropriately performed by CXR.– Prisoners– New accessions to congregate living– POW’s/Detainees

Targeted TestingTargeted Testing

Screening should be limited to previously described high-risk groups.

Prior to testing a follow-up plan for further testing and treatment must be considered:– “The decision to test is the decision to treat.”

The Chest RadiographThe Chest Radiograph

Though traditionally relied upon to assist in making diagnosis, HIV and other forms of immunosuppression have impacted its utility.– Old-school:

Primary: Middle or lower lung field infiltrates with ipsilateral lymphadenopathy.

Reactivation: Upper-lobe infiltrates and cavities in 98% of non-AIDS cases.

– Predilection for apical and posterior segments of upper lobe and superior segments of lower lobes

CXR con’tCXR con’t

– New: Up to 35% of AIDS patients with active MTB may have clear CXR; frequent findings include lymphadenopathy or effusion alone.

Old Granulomatous Disease Old Granulomatous Disease (OGD)(OGD)

Common radiographic term used to describe stigmata of prior infection, frequently MTB. – Implies dense, smaller nodules without or

without visible calcification or fibrotic scarring typically seen in the upper lobes.

– Bronchiectasis, volume loss or pleural scarring may accompany OGD.

Diagnosis: LabDiagnosis: Lab

Smear/Cultures– AFB+/MTB culture growth from sputum,

pleural fluid or pleural biopsy

Pathology– Demonstration of caseating granulomas in

pleural tissue.

Pleural Fluid Analysis

Diagnosis: LabDiagnosis: LabPleural FluidPleural Fluid

Exudative with higher total protein levels (esp.> 5.0g/dl) adding to specificity.

Lymphocyte pre-dominance (though early effusions may be neutrophil pre-dominant).

> 10% eosinophils virtually excludes MTB as diagnosis (unless prior thoracentesis or PTX).

Likewise, the presence of > 5% mesothelial cells makes MTB less likely (does not apply to HIV+ individuals).

Pleural Fluid: ADAPleural Fluid: ADA

Adenosine Deaminase levels may correspond directly with likelihood of MTB infection.– < 40 U/L- unlikely MTB– 40-70 U/L- questionable– > 70 U/L- likely MTB

Other clinical conditions (RA and empyema) may have elevated ADA levels, but should be easy to clinically differentiate.

TreatmentTreatment

Several different nuances to treatment modalities:– LTBI– Empiric (4 drug)– Therapeutic– MDRTB

Treatment of LTBITreatment of LTBI

Essential for any program aimed at reducing future spread of MTB.

MTB disease must be considered and ruled out prior to treating LTBI.

RegimensRegimens

Isoniazid (INH) aloneRifampin/Pyrazinamide (PZA)Rifampin aloneKnown exposure to MDRTB

INH aloneINH alone

Daily INH for 12 months reduces the risk of MTB disease by 90%.

6 months of therapy reduces risk by 70%. Two acceptable regimens:

– 300mg once daily– 15mg/kg twice weekly (DOT) (900mg max)

Though a 6 month regimen is acceptable, 9 months of therapy is considered optimal in both HIV+ and HIV- individuals.

Post-exposure to MDRTBPost-exposure to MDRTB

Regimens should consist of two drugs to which the organism has demonstrated susceptibility.– PZA– Ethambutol– Quinalone

MonitoringMonitoring

Though baseline laboratory testing is not indicated at the start of treatment for LTBI, baseline liver function tests should be obtained in those whose initial evaluation suggests a liver disorder, pregnant women, and HIV+ patients.

Though advancing age increases risk of hepatotoxicity, routine screening of LFT’s is not recommended in the elderly.

Monitoring con’tMonitoring con’t

Monthly evaluations should address:– Adherence to prescribed regimen.– Signs and Symptoms of active MTB disease.– Signs and Symptoms of hepatitis– Other potential side effects from individual

regimens.

Empiric (4-drug) TherapyEmpiric (4-drug) Therapy

Clinical Dogma– Adherence must be ensured.– Multiple drugs to which the organism is

susceptible must be used for prolonged periods.– Never add a single drug to a failing regimen.

PIRESPIRES

4-drug therapy should be administered for the initial 2 months of therapy; potential agents include:– Pyrazinamide (PZA)– Isoniazid (INH)– Rifampin (RIF)– Ethambutol (EMB)– Streptomycin (SM)

More PIRESMore PIRES

Each agent plays a special role in the initial 2-month course of therapy.– INH and RIF allow for short-course regimens

with high cure rates.– PZA has potent sterilizing ability allowing for

shortening from 9 to 6 mos– EMB (or SM) is added to prevent emergence

of further drug resistance if primary INH resistance is possible.

Continuation of TreatmentContinuation of Treatment

As culture and sensitivity data return, regimens may be tailored, recalling that at least two drugs must be used at all times.

Typical minimal length of therapy is six months:– “4 drugs for 2 months, followed by 2 drugs for 4

months”– If RIF is not used, 18 months of therapy is required.

INH therapy should be discontinued if:– LFT’s > 3X nl and Pt is symptomatic– LFT’s > 5X nl and Pt is asymptomatic

End of TherapyEnd of Therapy

A chest x-ray should be obtained to establish baseline for future examinations.

Sputum sample should be obtained at end of therapy to document cure.

MTB Treatment: PregnancyMTB Treatment: Pregnancy

The preferred initial treatment is INH, RIF and EMB.– SM has proven harmful fetal effects.– PZA’s effect are unknown

Since PZA is excluded treatment must continue for 9 months.

Multi-Drug Resistant TBMulti-Drug Resistant TB(MDRTB)(MDRTB)

Definition: MTB resistant to both INH and rifampin.

Always treated with daily DOT therapy.XDRTB not likely to be tested…

MDR TB Cases, 1993 - 1998

MDRTB: High-Risk GroupsMDRTB: High-Risk Groups

Prior treatment with MTB drugs.Contacts with known carriers of MDRTBForeign-born persons from MDRTB

endemic regionsRemains smear or culture positive despite 2

months of treatmentReceived inadequate therapy for > 2 weeksCavitary Disease

Public HealthPublic Health

Assume infectiousness in persons known, or suspected to have pulmonary or laryngeal MTB if they are:– Coughing or are “smear-positive” and– Not receiving therapy, just started therapy or

have a poor response to therapy.

Mask on you or them and ISOLATE.

Public health con’tPublic health con’t

Patients with drug-susceptible MTB disease are no longer considered infectious if they meet all of the following:– On adequate therapy.– Have experienced a clinical response to

therapy.– Three consecutive negative sputum smears

from three different days.

Home IsolationHome Isolation

Isolation is not required to occur in a hospital. In fact, an estimated 60% of all costs spent in the US treating MTB are due to hospitalization.

Must ensure that others in the home are not at high risk for developing MTB disease and that simple precautions (physical isolation, surgical masks, etc) are followed until non-infectivity can be assured.

Directly-Observed Therapy Directly-Observed Therapy (DOT)(DOT)

Health Care Worker watches patient swallow each and every dose of MTB meds

Considered for patients with:– Concerns for non-adherence.– Intermittent dosing regimen.– Household member on DOT for active MTB

disease.

Airway DiseaseAirway Disease

AsthmaCOPDBronchiectasis

– CF– ABPA

DefinitionDefinition

Asthma is an inflammatory disorder manifested by a clinical syndrome of episodic dyspnea, wheeze, and cough with reversible airflow obstruction and bronchial hyper-responsiveness.

Initial Assessment andInitial Assessment and Diagnosis of Asthma Diagnosis of Asthma

Determine that:Determine that:– Patient has history or presence of episodic Patient has history or presence of episodic

symptoms of airflow obstructionsymptoms of airflow obstruction

– Airflow obstruction is at least partially Airflow obstruction is at least partially

reversiblereversible

– Alternative diagnoses are excludedAlternative diagnoses are excluded

Initial Assessment andInitial Assessment andDiagnosis of Asthma Diagnosis of Asthma (continued)(continued)

Is airflow obstruction at least partiallyIs airflow obstruction at least partiallyreversible?reversible? Use spirometry to establish airflow obstruction:Use spirometry to establish airflow obstruction:

– FEVFEV11 < 80% predicted; < 80% predicted;

– FEVFEV11/FVC <65% or below the lower limit of normal/FVC <65% or below the lower limit of normal

Use spirometry to establish reversibility:Use spirometry to establish reversibility:– FEVFEV11 increases increases >>12% and at least 200 mL after using a short-12% and at least 200 mL after using a short-

acting inhaled betaacting inhaled beta22-agonist-agonist

Bronchoprovocation TestingBronchoprovocation Testing

Methacholine ChallengeExercise Induced Bronchospasm

Increased sensitivityDecreased specificityVery high negative predictive value

Methacholine ChallengeMethacholine Challenge

Increasing doses of methacholine given by inhalation

Repeated spirometry performed Decrement of FEV1 by 20% is diagnostic of

bronchial hyper-reactivity at dose < 4 mg/ml.– 4-16 mg/ml is considered by most to be borderline– Clinical interpretation in requires correlation with

symptoms.

Classification of Asthma Severity: Clinical Features Before Treatment

Monitoring SymptomsMonitoring Symptoms

Symptom history should be based onSymptom history should be based ona short (2 to 4 weeks) recall perioda short (2 to 4 weeks) recall period

Symptom history should include:Symptom history should include:

– Daytime asthma symptomsDaytime asthma symptoms

– Nocturnal wakening as a result ofNocturnal wakening as a result ofasthma symptomsasthma symptoms

– Exercise-induced symptomsExercise-induced symptoms

– ExacerbationsExacerbations

Monitoring Lung Function: Monitoring Lung Function: SpirometrySpirometry

Spirometry is recommended:Spirometry is recommended:

– At initial assessmentAt initial assessment

– After treatment has stabilized symptoms After treatment has stabilized symptoms

– At least every 1 to 2 yearsAt least every 1 to 2 years

Monitoring Lung Function: Monitoring Lung Function: Peak Flow Monitoring Peak Flow Monitoring (continued)(continued)

Patients should:Patients should: Measure peak flow on waking before taking Measure peak flow on waking before taking

a bronchodilatora bronchodilator

Use personal bestUse personal best

Be aware that a peak flow <80% of personal best indicates Be aware that a peak flow <80% of personal best indicates a need for additional medicationa need for additional medication

Use the same peak flow meter over timeUse the same peak flow meter over time

Monitoring PharmacotherapyMonitoring Pharmacotherapy

Monitor:Monitor:

– Patient adherence to regimenPatient adherence to regimen

– Inhaler techniqueInhaler technique

– Frequency of inhaled short-actingFrequency of inhaled short-actingbetabeta22-agonist use-agonist use

– Frequency of oral corticosteroid “burst” therapyFrequency of oral corticosteroid “burst” therapy

– Side effects of medicationsSide effects of medications

Control of Factors Control of Factors

Contributing to Asthma SeverityContributing to Asthma Severity

Assess exposure and sensitivity to:Assess exposure and sensitivity to: Inhalant allergensInhalant allergens Occupational exposuresOccupational exposures Irritants:Irritants:

Indoor air (including tobacco smoke)Indoor air (including tobacco smoke) Air pollutionAir pollution

Control Other Factors That Control Other Factors That Can Influence Asthma SeverityCan Influence Asthma Severity

RhinitisRhinitis– Intranasal corticosteroids are most effectiveIntranasal corticosteroids are most effective

SinusitisSinusitis– Promote drainage; antibiotics for complicating Promote drainage; antibiotics for complicating

acute bacterial infectionacute bacterial infection Gastroesophageal refluxGastroesophageal reflux

– Medications; no food before bedtime; elevate Medications; no food before bedtime; elevate head of bedhead of bed

Influenza vaccine annuallyInfluenza vaccine annually

Overview ofOverview ofAsthma MedicationsAsthma Medications

Daily: Long-Term ControlDaily: Long-Term Control– Corticosteroids (inhaled and systemic)Corticosteroids (inhaled and systemic)– Cromolyn/nedocromilCromolyn/nedocromil– Long-acting betaLong-acting beta22-agonists-agonists

– MethylxanthinesMethylxanthines– Leukotriene modifiersLeukotriene modifiers

Overview of Overview of Asthma Medications Asthma Medications (continued)(continued)

As-needed: Quick ReliefAs-needed: Quick Relief– Short-acting betaShort-acting beta22-agonists-agonists

– AnticholinergicsAnticholinergics– Systemic corticosteroidsSystemic corticosteroids

Inhaled CorticosteroidsInhaled Corticosteroids

Most effective long-term-control therapy Most effective long-term-control therapy for persistent asthmafor persistent asthma

Small risk for adverse events at Small risk for adverse events at recommended dosagerecommended dosage

Reduce potential for adverse events by:Reduce potential for adverse events by:– Using spacer and rinsing mouthUsing spacer and rinsing mouth– Using lowest dose possibleUsing lowest dose possible– Using in combination with long-acting Using in combination with long-acting

betabeta22-agonists-agonists– Monitoring growth in childrenMonitoring growth in children

Inhaled CorticosteroidsInhaled Corticosteroids(continued)(continued)

Benefit of daily use:Benefit of daily use:– Fewer symptomsFewer symptoms– Fewer severe exacerbationsFewer severe exacerbations– Reduced use of quick-relief medicineReduced use of quick-relief medicine– Improved lung functionImproved lung function– Reduced airway inflammationReduced airway inflammation

Long-Acting BetaLong-Acting Beta22-Agonists-Agonists

Not a substitute for anti-inflammatory therapyNot a substitute for anti-inflammatory therapy

Not appropriate for monotherapyNot appropriate for monotherapy

Beneficial when added to inhaled corticosteroidsBeneficial when added to inhaled corticosteroids

Not for acute symptoms or exacerbationsNot for acute symptoms or exacerbations

Short-Acting BetaShort-Acting Beta22-Agonists-Agonists

Most effective medication for relief of Most effective medication for relief of

acute bronchospasmacute bronchospasm More than one canister per month suggests More than one canister per month suggests

inadequate asthma controlinadequate asthma control Regularly scheduled use is not generally Regularly scheduled use is not generally

recommendedrecommended

Leukotriene ModifiersLeukotriene Modifiers

MechanismsMechanisms– 5-LO inhibitors5-LO inhibitors– Cysteinyl leukotriene receptor antagonistsCysteinyl leukotriene receptor antagonists

IndicationsIndications– Long-term-control therapy in mildLong-term-control therapy in mild

persistent asthmapersistent asthma Improve lung functionImprove lung function Prevent need for short-acting betaPrevent need for short-acting beta22-agonists-agonists Prevent exacerbationsPrevent exacerbations

– Further experience and research neededFurther experience and research needed– Do not replace inhaled corticosteroidsDo not replace inhaled corticosteroids– Not for monotherapyNot for monotherapy

Stepwise Approach to Stepwise Approach to Therapy: Gaining ControlTherapy: Gaining Control

STEP 4STEP 4Severe PersistentSevere Persistent

STEP 3STEP 3Moderate Moderate PersistentPersistent

STEP 2STEP 2Mild PersistentMild Persistent

STEP 1STEP 1Mild IntermittentMild Intermittent

11 22

1. Start high and 1. Start high and step down. step down.

2. Start at initial2. Start at initiallevel of severity; level of severity;

gradually step gradually step up.up.

Indicators of PoorIndicators of PoorAsthma ControlAsthma Control

Step up therapy if patient:Step up therapy if patient:

– Awakens at night with symptomsAwakens at night with symptoms

– Has an urgent care visitHas an urgent care visit

– Has increased need for short-acting Has increased need for short-acting inhaled betainhaled beta22-agonists-agonists

– Uses more than one canister of short-acting Uses more than one canister of short-acting betabeta22-agonist in 1 month-agonist in 1 month

Indicators of PoorIndicators of Poor Asthma Control Asthma Control (continued)(continued)

Before increasing medications, check:Before increasing medications, check:

– Inhaler techniqueInhaler technique

– Adherence to prescribed regimenAdherence to prescribed regimen

– Environmental changesEnvironmental changes

– Also consider alternative diagnosesAlso consider alternative diagnoses

Managing Exercise-Induced Managing Exercise-Induced Bronchospasm (EIB)Bronchospasm (EIB)

Anticipate EIB in all patientsAnticipate EIB in all patients Teachers and coaches need to be notifiedTeachers and coaches need to be notified DiagnosisDiagnosis

– History of cough, shortness of breath, chest pain or History of cough, shortness of breath, chest pain or tightness, wheezing, or endurance problemstightness, wheezing, or endurance problemsduring exerciseduring exercise

– Conduct exercise challenge Conduct exercise challenge OROR have patient have patientundertake task that provoked the symptomsundertake task that provoked the symptoms

– 15% decrease in PEF or FEV15% decrease in PEF or FEV11 is compatible with EIB is compatible with EIB

Managing Exercise-Induced Managing Exercise-Induced Bronchospasm (EIB) Bronchospasm (EIB) (continued)(continued)

Management StrategiesManagement Strategies– Short-acting inhaled betaShort-acting inhaled beta22-agonists used shortly -agonists used shortly

before exercise last 2 to 3 hoursbefore exercise last 2 to 3 hours– Salmeterol may prevent EIB for 10 to 12 hoursSalmeterol may prevent EIB for 10 to 12 hours– Cromolyn and nedcromil are also acceptableCromolyn and nedcromil are also acceptable– A lengthy warmup period before exercise may A lengthy warmup period before exercise may

preclude medications for patients who can preclude medications for patients who can tolerate ittolerate it

– Long-term-control therapy, if appropriateLong-term-control therapy, if appropriate

Management of Management of Asthma ExacerbationsAsthma Exacerbations

Inhaled betaInhaled beta22-agonist to provide prompt -agonist to provide prompt

relief of airflow obstructionrelief of airflow obstruction

Systemic corticosteroids to suppress and Systemic corticosteroids to suppress and reverse airway inflammationreverse airway inflammation

– For moderate-to-severe exacerbations, orFor moderate-to-severe exacerbations, or

– For patients who fail to respond promptly and For patients who fail to respond promptly and completely to an inhaled betacompletely to an inhaled beta22-agonist -agonist

Risk Factors for Risk Factors for Death From AsthmaDeath From Asthma

Past history of sudden severe exacerbationsPast history of sudden severe exacerbations Prior intubation or admission to ICUPrior intubation or admission to ICU

for asthmafor asthma Two or more hospitalizations for asthmaTwo or more hospitalizations for asthma

in the past yearin the past year Three or more ED visits for asthmaThree or more ED visits for asthma

in the past yearin the past year

Risk Factors for Risk Factors for Death From Asthma Death From Asthma (continued)(continued)

Hospitalization or an ED visit for asthmaHospitalization or an ED visit for asthmain the past monthin the past month

Use of >2 canisters per month of inhaled Use of >2 canisters per month of inhaled short-acting betashort-acting beta22-agonist-agonist

Current use of systemic corticosteroidsCurrent use of systemic corticosteroidsor recent withdrawal from systemic or recent withdrawal from systemic corticosteroidscorticosteroids


Difficulty perceiving airflow obstructionDifficulty perceiving airflow obstructionor its severityor its severity

Co-morbidity, as from cardiovascular Co-morbidity, as from cardiovascular diseases or chronic obstructive pulmonary diseases or chronic obstructive pulmonary diseasedisease

Serious psychiatric disease or psychosocial Serious psychiatric disease or psychosocial problemsproblems


Low socioeconomic status andLow socioeconomic status andurban residenceurban residence

Illicit drug useIllicit drug use

Sensitivity to Sensitivity to AlternariaAlternaria

Aspirin Sensitive AsthmaAspirin Sensitive Asthma

Sampter’s Triad– Asthma– ASA sensitivity– Nasal polyps

Difficult to controlProbable role for leukotriene modifiersRole for ASA desensitization

Difficult to Control AsthmaDifficult to Control Asthma

Consider alternative or complicating diagnoses– Rhinitis, Sinusitis, GERD– Allergic Bronchopulmonary Aspergillosis– Churg-Strauss Vasculitis– Vocal Cord Dysfunction– Non-pulmonary Disorders

COPD- EpidemiologyCOPD- Epidemiology

Rising Mortality rates now place COPD 4th in US Tobacco use responsible for 85-90% of cases

– Alpha-1 AT def < 1%

~20% of smokers develop COPD– ~20% of COPDer’s develop CO2 retention

FEV1 < 0.75L Mortality– 1 year = 30%– 10 year = 95%

COPDCOPD

Emphysema– Centrilobular

Tobacco Related

– Panacinar Alpha-1 AT def

Chronic Bronchitis– ‘Two tablespoons of sputum daily for three

months of any 2 year period’

Emphysema- DxEmphysema- Dx

Suspected in patients with sig tobacco exposure and sx’s– Dx: SPIROMETRY!

DLCO reduction with emphysema vice CBImaging reveals bullous lung disease

– Only severe disease on CXR

Emphysema- DxEmphysema- Dx

Alpha1- AT def- Suspect in patients with sx’s and age < 50.– May have no tobacco exposure, but smoking

will accelerate sx presentation– May have family hx of lung or liver

involvement– ‘Basilar Predominance to Bullous lung disease’

Emphysema- TxEmphysema- Tx

‘Tobacco Cessation and Oxygen’ Symptom relief

– Bronchodilators– Anti-inflammatories– Methylxanthines– Oral steroids as tx of last resort

Pulmonary Rehabilitation Surgery

– Bullectomy- Bullae > 1/3 hemithorax– LVRS- Upper lobe predom with low exercise cap– Transplant-

Emphysema- TxEmphysema- TxAcute ExacerbationsAcute Exacerbations

Pt’s with 2/3 ‘Winnipeg Criteria’ deserve Abx– Increased SOB– Increased Sputum volume– Sputum purulence

Trump card = HospitalizationAny abx will do…

‘‘Indications for OIndications for O22’’

Resting Sp02 < 88%Resting Pa02 < 55mmHgResting Pa02 56 to 59 mmHg if

– Cor pulmonale (including peripheral edema)– Polycythemia

Remember to re-eval for O2 requirements ~4-6 weeks after acute exacerbation.

Emphysema- TxEmphysema- TxAcute ExacerbationsAcute Exacerbations

Steroids– Oral = IV (equivalent to 40-60mg prednisone)– Rapidly tapered over 2 weeks

Aggressive BD tx’s

‘‘Bronchiectasis’ DefinedBronchiectasis’ Defined

Bronchial dilatation frequently associated with:– Bronchial wall thickening– Fluid retention within the bronchi– Chronic inflammation/infection

Can be localized or diffuse

BronchiectasisBronchiectasis

Restrictive Lung DiseasesRestrictive Lung Diseases

Pleural DiseaseAlveolar DiseasesInterstitial DiseasesNeuromuscular DiseasesThoracic Cage Diseases

Parenchymal DiseaseParenchymal Disease

Interstitial Lung Disease– Idiopathic Interstitial PNA’s– Sarcoidosis– Collagen Vascular Disorders– Eosinophilic Lung Diseases

Alveolar Lung Disease– Pulmonary Edema Syndromes – Pulmonary Alveolar Proteinosis

NomenclatureNomenclature

Pneumonia vs PneumonitisAlphabet Soups

– COP, BOOP, BO, BOS, OB, CB

Name Game– That was then, this is now…

Disease’s Clinical name vs Histologic name

New NamesNew Names

Hypersensitivity Pneumonitis – Extrinsic Allergic Alveolitis (EAA)

Eosinophilic Granuloma or Histiocytosis X – Langerhan’s Cell Histiocytosis (LCH)

Idiopathic Bronchiolitis Obliterans Organizing Pneumonia– Cryptogenic Organizing Pneumonia (COP)

An Alphabet Soup of New An Alphabet Soup of New NamesNames

Idiopathic Interstitial Pneumonias (IIP’s)– Idiopathic Pulmonary Fibrosis (IPF)– Non-Specific Interstitial Pneumonia (NSIP)– Desquamative Interstitial Pneumonia (DIP)– Respiratory Bronchiolitis Interstitial Lung

Disease (RBILD)– Cryptogenic Organizing Pneumonia (COP)– Acute Interstitial Pneumonia (AIP)

Clinical Name vsClinical Name vsHistologic NameHistologic Name

Same entity may be referred to by different names by different specialists or in different circumstances.– Idiopathic Pulmonary Fibrosis -Clinical

Usual Interstitial Pneumonia (UIP)- Histologic

Blood,Pus, Water…Blood,Pus, Water…

BloodMineralWaterCellsProteins

BloodBlood

Diffuse Alveolar Hemorrhage Syndromes Hemosiderosis

MineralsMinerals

Calcium– Pulmonary Alveolar Microlithiasis– Metastatic Calcinosis

Pneumoconioses– Asbestos– Silicosis– Talc– Coal Worker’s Pneumoconiosis

WaterWater

Cardiogenic Pulmonary EdemaARDSRadiation Toxicity

CellsCells

Lymphocytes– LIP, most Collagen Vascular Dz assoc. ILD

Eosinophils– Eosinophilic Pneumonias, ABPA, CSS

Multi-Nucleated Giant Cells (Granuloma)– Sarcoid/Berylliosis, EAA

Histiocytes– Langerhan’s Cell Histiocytosis

Malignant– Lymphangitic CA, BAC

ProteinProtein

AmyloidosisGaucher’s DiseasePulmonary Alveolar Proteinosis

When to Think “Interstitial When to Think “Interstitial Lung Disease?”Lung Disease?”

Dyspnea evaluation– +/- Hypoxemia

Chronic Cough Refractory “CHF” Abnormal radiograph

– Exceptions: Stage 0/1 Sarcoid, EAA, DIP/RBILD

Abnormal PFT’s– Isolated DLCO defect


Previously felt to occur in 5 per 100,000Recently estimated to occur in 31.5 per

100,000 males in US (by death certificate diagnosis of ILD).– 26.1/100,000 females

Most common ILD is “Idiopathic Pulmonary Fibrosis” accounting for up to 45% of ILD diagnoses.

Epidemiology Con’tEpidemiology Con’t

Accounts for approx. 100,000 hospital admissions annually in US.

Represents approx. 15% of office visits to pulmonologists.

Expanding populations of patients at risk for ILD ( AIDS, post-chemotherapy, etc.) is likely to lead to higher incidence of these diseases.

Idiopathic Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis

Prevalence: 13–20/100,000 in US (approximately 35,000-55,000 cases)

Onset: Usually between 50 and 70 yr Clinical presentation

– Progressive dyspnea on exertion– Paroxysmal cough, usually nonproductive– Abnormal breath sounds on chest auscultation – Abnormal chest x-ray or HRCT– Restrictive pulmonary physiology with reduced lung

volumes and DLCO and widened AaPO2

Coultas DB et al. Am J Respir Crit Care Med. 1994;150:967.ATS/ERS. Am J Respir Crit Care Med. 2000;161:646.

DIAGNOSIS OF IPFDIAGNOSIS OF IPF Major criteria

– Exclusion of other known causes of ILD– Abnormal pulmonary function studies– Bibasilar reticular abnormalities on HRCT scan– No histologic or cytologic features on transbronchial lung

biopsy or BAL analysis supporting another diagnosis Minor criteria

– Age >50 yr– Insidious onset of otherwise unexplained exertional dyspnea– Duration of illness 3 mo– Bibasilar, dry (“Velcro”) inspiratory crackles

SarcoidosisSarcoidosis “Sarcoidosis is a multi-system disorder of

unknown cause…” characterized by “…histological evidence of noncaseating epithelioid cell granulomas. Granulomas of known causes and local sarcoid reactions must be excluded.” ATS Statement on Sarcoidosis. AJRCCM 1999.

First described in 1877 by Hutchinson Boeck coined the term “sarkoid” in 1899 Organs that may be involved:

– Lung, skin, eyes, liver, spleen, lymph nodes, salivary glands, heart, nervous system, muscles, bones, kidneys, joints, stomach

Epidemiology Epidemiology

Most commonly affects < 40 years old Slightly higher disease rates in women Swedes, Danes, and US AA’s highest prevalence

rates– Lifetime risk US white: .85%, US black: 2.4%

Significant variability in disease presentation and severity among different groups– More severe disease in AA’s, caucasians with asx disease– EN in Europeans– Cardiac and ocular more common in Japan

SkinSkin Approx 20% of patients Most common subacute finding => maculopapular

eruption– Nares, lips, eyelids, neck, previous trauma (‘scars and tatoos’)

Erythema Nodosum– Hallmark of acute sarcoidosis– Red, raised, tender nodules on anterior legs– Adjacent joints may be painful, swollen– Lasts 6-8wks and rarely recurs– ‘Lofgren’s syndrome – fever, arthralgia, EN, bilat hilar LAN’

Lupus pernio– Marker of chronic sarcoidosis– Indurated plaques located on cheeks, lips, nose, ears– Prolonged course with rare spontaneous remission

Erythema nodosumErythema nodosum Lupus Lupus perniopernio

PulmonaryPulmonary

>90% of patients1/3-1/2 describe dyspnea, dry cough, vague

chest tightness<20% with “crackles”, clubbing is rareRare findings – effusion, chylothorax, PTX,

cavitary lesions, calcified LAN5 stages based on CXR findings

– Stage 0 – no intrathoracic findings

Stage 1Stage 1 Bilateral hilar adenopathy – 50% of patients 60-80% spontaneous remission

Stage 2Stage 2 Bilateral hilar adenopathy with parenchymal

infiltrate – 25% of patients 50-60% spontaneous remission

Stage 3Stage 3 Parenchymal infiltrate without hilar LAN <30% spontaneous remission

Stage 4Stage 4 Advanced fibrosis

– Honey-combing, hilar retraction, bullae, cysts, emphysema

Diagnostic evaluationDiagnostic evaluation

Diagnosis:– Compatible clinical picture– Compatible histology– Exclusion of other causes

Goals of work-up:1 – histologic confirmation

2 – assess extent and severity of organ involvement

3 – assess disease stability and whether will progress

4 – determine if therapy will benefit patient

Diagnostic evaluationDiagnostic evaluation

Biopsy– Lymph node– Skin lesions– Bronchoscopy

40- 90+% yield

– Mediastinoscopy– VATS– Open lung bx

Natural historyNatural history Highly variable and influenced by race and genetic factors

– 4-7% present with serious extrapulm involvement Spontaneous remission in 2/3

– >85% within 2yrs– If remission or stabilization, 2-8% relapse

Chronic or progressive in 10-30%– Failure to remit in 24 mos

Mortality 1-5% Poor prognostic indicators

- Lupus pernio - chronic high Ca- AA race - nephrocalcinosis- age onset >40 - chronic uveitis- neurosarcoid - cardiac involvement- progressive pulm dz - cystic bone lesions- nasal mucosal involvement

TreatmentTreatment

Controversial and unclear– Large number of spont remissions or benign

clinical course Stg 1 – 60-80%, 2 – 50-60%, 3 – 30%

– No good method to assess activity– Variability in presentation and course not

amenable to developing guidelines– Cause is unknown, no specific tx

TreatmentTreatment

Steroids first line therapyTopical therapy

– Uveitis, skin, cough

Systemic therapy– Definite indications- heart, neuro, ocular not

responding, hyperCa

Treatment of pulmonary Treatment of pulmonary sarcoidsarcoid

Observation– Asx or mild sx stage 1, 2, 3– Eval q6mth stage 1, q3mth stage 2, 3– Tx if worsening sx’s, deteriorating lung fxn, progressive xray

findings Treatment

– .5 – 1mg/kg for 4-6 wks– If response, taper by 5-10mg every 4-8wks to maintenance of 5-

10mg/d– If no response after 3mths then taper off steroids– Total duration of therapy 12mths then taper off– Relapse rate high – 60-90%

SurveillanceSurveillance

If no treatment, most intense in first 2 yrs then annual

If treated, most intense in first 3 yrs after discontinuation of therapy then “at least annually”

Pulmonary Edema SyndromesPulmonary Edema Syndromes

Cardiogenic– High-Output Failure– Low-Output Failure

Systolic Dysfunction Diastolic Dysfunction

Noncardiogenic– Pulmonary– Non-pulmonary

Pulmonary EtiologiesPulmonary Etiologies

PNAAspirationAcute Interstitial Pneumonia (Hamman-

Rich)Acute Eosinophilic PneumoniaDiffuse Alveolar Hemorrhage Syndrome

Non-Pulmonary EtiologiesNon-Pulmonary Etiologies

‘Surgical’– Burns– Trauma– Surgical SIRS

Re-perfusion PE Negative Pressure PE Narcotic-Related PE General Anesthesia PE

‘Medical’– MICU

TRALI Pancreatitis Sepsis Neurogenic

– Emboli Fat Amniotic Air

– Other HAPE SIPE Drugs

Fat EmboliFat Emboli

Patients: – ‘Post-Trauma, esp. long bone fracture’– Sickle Cell patients, exp post-partum

Signs– Central Nervous System– Renal Failure– Acute Lung Injury– Petechiae

Eosinophilic Lung DiseasesEosinophilic Lung Diseases

Pulmonary Infiltrates w/Eosinophilia (PIE)– Primary

Acute vs. Chronic Eosinophilic PNA Simple Pulmonary Eosinophilia (Loeffler’s) Idiopathic Hypereosinophilic Syndrome

– Secondary ILD’s ‘Asthma syndromes’ Malignancies Infections Drugs

Acute vs. Chronic Eosinophilic Acute vs. Chronic Eosinophilic PNAPNA

Acute– Presents acutely like

PNA/ARDS – CXR mimics

PNA/ARDS– Peripheral Eosinophilia

rare; High count on BAL

– Prompt, lasting response to steroids

Chronic– Presents subacutely

with Mild Hypoxemia– CXR- ‘Photographic

negative of CHF’– Peripheral Eosinophilia

common; High count on BAL

– Prompt response to steroids, but recurrence common

Simple Pulmonary Simple Pulmonary Eosinophilia (Loeffler’s)Eosinophilia (Loeffler’s)

Migratory Pulmonary InfiltratesEosinophiliaCause:

– Ascaris Lumbricoides

ILD’sILD’s

SarcoidosisLangerhans Cell HistiocytosisIdiopathic Pulmonary FibrosisCollagen Vascular DiseasesBronchioloitis Obliterans Organizing

Pneumonia (BOOP/COP)

‘‘Asthma syndromes’Asthma syndromes’

Allergic Angiitis & GranulomatosisAllergic Bronchopulmonary MycosisAllergic Reaction

Allergic Angiitis & Allergic Angiitis & GranulomatosisGranulomatosis

AKA Churg-Strauss Syndrome– Diagnostic Criteria (4/6)

Migratory Pulmonary Infiltrates (‘fleeting’) Eosinophilia (>10%) Peripheral Neuropathy Sinus disease Asthma Biopsy findings

– Extravascular eosinophils– Granuloamtous Angiitis– Extravascular Necrotizing Granulomas

Allergic Bronchopulmonary Allergic Bronchopulmonary MycosisMycosis

Diagnostic Criteria– Asthma– + skin test to fungus– + IgG precipitins– + IgE precipitins– Elevated IgE– Central BTX– Eosinophilia with CXR

ASO’s

‘Central or Proximal Bronchiectasis’

‘Coughs up brown, plugs’

‘Finger-in-gloves-’ X-ray

MalignanciesMalignancies

NHLNSCLCALeukemias

InfectionsInfections

ParasitesPCPMycobacteriaFungal

– Especially Cocci

Other ILD’sOther ILD’s

Wegener’s– ‘ELK’– ‘c-ANCA’

Goodpasture’s– Bleeding Kidneys and lungs– ‘Anti-GBM ab’

Langerhans Cell Histiocytosis– ‘Young, male smokers with recurrent PTX’

LAM– ‘Young, female non-smokers with recurrent PTX’

‘‘Drugs and Lung Disease’Drugs and Lung Disease’

ARA-c = ARDSBleomycin = ARDS/Fibrosis worsened with

oxygen exposureAmiodarone = Pulm fibrosis, typically

dose-dependantHydralazine/Procainamide = SLE-likeCrack-lung = hemorrhage, ARDS, vaculitis

Pulmonary Vascular DiseasePulmonary Vascular Disease

Venous Thromboembolic Disease (VTE)– DVT– PE– CTEPH

Pulmonary Hypertension (PH)

DVTDVT

EtiologiesDiagnosisTreatment

DVT: EtiologiesDVT: Etiologies

TraumaRecent SurgeryMedical ImmobilityMedications- e.g. OCP’sMedical conditions- Behcet’s, IBD, SCD,

CA, Nephrotic synHypercoaguable States

Hypercoaguable StatesHypercoaguable States

APC resistance (Factor V Leiden)APLSProtein C defProtein S defAT III defHomocystenemiaProthrombin Gene mutation

DiagnosisDiagnosis

Duplex compression U/S– Role of serial testing in low-risk setting

VenographyCT

TreatmentTreatment

Anticoagulation– UFH vs LMWH

Look for HIT/HAT

– Warfarin

Vena Caval FilterStockings

Total IncidenceTotal Incidence630,000630,000

11%11%Death withinDeath within1 hr1 hr67,00067,000

89%89%SurvivalSurvival> 1 hr> 1 hr563,000563,000

29%29%Diagnosis made,Diagnosis made,therapy institutedtherapy instituted163,000163,000

71% 71% Diagnosis notDiagnosis notmademade400,000400,000

8%8%Death Death 13,00013,000

92%92%SurvivalSurvival150,000150,000

30%30%DeathDeath120,000120,000

70%70%SurvivalSurvival280,000280,000

Pathophysiology of Acute PEPathophysiology of Acute PE Related to reduction in cross-sectional area of Related to reduction in cross-sectional area of

pulmonary vasculaturepulmonary vasculature increase in PVR=> impedance of RV ejection of increase in PVR=> impedance of RV ejection of blood blood

=> decreased filling of LV=> decreased filling of LV

Predicting the Severity of Pulmonary EmbolismPredicting the Severity of Pulmonary EmbolismPE SeverityPE Severity PA PA PA meanPA mean RA meanRA mean CICI

obstructionobstruction pressurepressure pressurepressureMildMild <50 <50 <20 <20 <10 <10 >2.5>2.5Mod or SubmassiveMod or Submassive 50-75 50-75 25-40 25-40 <10 <10 >2.5>2.5MassiveMassive >75 >75 40-45 40-45 >10 >10 <2.5<2.5

Acute PE (cont.)Acute PE (cont.) Thrombolysis or embolectomy Thrombolysis or embolectomy

massive PE with hemodynamic instability or massive PE with hemodynamic instability or refractory hypoxemiarefractory hypoxemia

Heparin/Lovenox Heparin/Lovenox Oral anticoagulationOral anticoagulation IVC filter IVC filter

patients with contraindication to anticoagulationpatients with contraindication to anticoagulation recurrent embolism despite anticoagulationrecurrent embolism despite anticoagulation unable to tolerate further emboliunable to tolerate further emboli

Pulmonary Hypertension Pulmonary Hypertension Symptoms and SignsSymptoms and Signs

Dyspnea on exertion in a young femaleFatigue Shortness of Breath and Chronic Hypoxia About 10% of primary and >50% of

secondary P-HTN patients have Raynaud's phenomenon

Symptoms and SignsSymptoms and Signs

Chest pain– Secondary to RV ischemia in the face of RV

hypertrophy and increased sys and dias pressures

Syncope– Usually exertional or post exertional implies a

severely restricted CO with deminished cerebral blood flow

Symptoms and SignsSymptoms and Signs

Symptoms of right sided heart failure – Peripheral edema and hepatic congestion

(abdominal pain)

– Distended neck veins and fluid retention

– Ineffective filling of Left ventricle, with resultant hypotension

The Demise in Pulmonary The Demise in Pulmonary HypertensionHypertension

Progressive RV failure leads to dyspnea, hypoxemia, and progressive decrease in CO

This leads to death from RV failure or fatal dysrhythmias

Arterial hypoxemia and acidosis predispose to fatal dysrhythmias

The Demise in Primary The Demise in Primary Pulmonary HypertensionPulmonary Hypertension

Common causes of death include:– Brady and tachy dysrhythmias– PE– Massive pulmonary hemorrhage– Sudden RV ischemia / infarction

DiagnosisDiagnosis

Clinical Definition Presence of pulmonary HTN: mean PA

pressure >25mm Hg at rest (or 30mm in exercise) – Normal pulmonary capillary wedge pressure

(PCWP) – Absence of secondary etiology (for primary P-

HTN)

DiagnosisDiagnosis

Evaluate for secondary etiology – Echocardiography – Ventilation-Perfusion (V/Q) Scanning– Pulmonary Angiography– Autoantibody serologies – Pulmonary Function Testing – Note that many patients with primary P-HTN

have low titer autoantibodies

DiagnosisDiagnosis

CXR: Evidence of pulmonary hypertension– Prominent main pulmonary artery– Enlarged hilar and pulmonary vessels– Enlarged R heart structures– 6-10% of patients have a normal CXR

DiagnosisDiagnosis

EKG– May show right axis deviation– RVH– R Heart strain pattern– Peaked P waves in lead II– Findings do not correlate with the severity of

disease

DiagnosisDiagnosis

Echocardiography– Elevated pulmonary pressures– May reveal RA and RV enlargement– May reveal a normal to decreased LV chamber

size– Loss of normal septal curvature and decreased

LV filling may reflect disease severity

TreatmentTreatment

Overview of Vasodilator Therapy In general, response to acute vasodilator

administration predicts chronic response Chronic prostacyclin may be beneficial in absence

of acute response Diltiazem combined with oxygen may have

synergistic chronic effects Invasive monitoring a must during acute infusions

in patients

TreatmentTreatment

Other Therapies – Oxygen - usually improves function, acts as vasodilator

– Digoxin - may be useful in setting of atrial fibrillation, improved inotropy

– Note that diltiazem may also reduce ventricular response in atrial fibrillation

– Lung (± heart) transplantation may be only other treatment at present

TreatmentTreatment

Anticoagulation– Patients with PPH are at increased risk for

intrapulmonary thrombosis and thromboembolism due to:

Sluggish pulmonary blood flow Dilated right heart chambers Venous stasis Sedentary lifestyle Increased risk of atrial fibrillation

InternshipInternship

Pleural DiseasePleural Disease

Pleural Effusions– Transudates– Exudates

Pneumothorax (PTX)

‘‘Light’s Criteria’Light’s Criteria’

Any one of the following qualifies the effusion as exudative:– Protein P/S > 0.5– LDH P/S > 0.6– Pleural LDH > 200 or > 2/3 upper limits of

serum normal

TransudatesTransudates

‘-Oses’– Nephrosis- Nephrotic syn– Cirrhosis– Cardiosis- Pulmonary Venous HTN (CHF)

Other– Hypo-Thyroid, PE, ATX, pericardial disease,

trapped lung, urinothorax, SVC syn

ExudatesExudates

Parapneumonic EffusionsMalignancyChylothorax

Lymphocyte Predominant Lymphocyte Predominant ExudatesExudates

Chylothorax Rheumatoid Yellow Nail Sarcoid TB Acute Rejection Lymphoma Post CABG

Eosinophilic ExudatesEosinophilic Exudates

Air Benign Asbestos Pleural Effusion (BAPE) Cancer, esp lymphomas Drugs Embolism Fungus Granulomatous Disease Hemothorax Infection (Parasite, TB?)

Parapneumonic EffusionsParapneumonic Effusions

Predictors for Poor Outcomes (i.e. should be drained)– Low Glucose– Low pH– + gram stain– + culture– Complicated appearance (i.e. loculated) on CT

or US

MalignancyMalignancy

Usually proven with cytologyPoor prognostic indicator

– IIIb disease– Average life expectancy ~ 6 mos

Low pH implies poor response to pleurodesis

ChylothoraxChylothorax

‘Milky Appearance’Triglycerides > 110 or chylomicrons on

lipid analysisDDx- post-trauma > tumor > idiopathicHigh cholesterol implicates ‘pseudochylous

effusion’Do NOT drain repeatedly- leads to

immunocompromise and malnutrition

PneumothoraxPneumothorax

Spontaneous Secondary

– Traumatic– COPD– CF– TB– Diffuse Parenchymal Lung Disease

PTX: TreatmentPTX: Treatment

ASX PTX < 15% of hemithorax = observe>15% = simple aspiration

– Failure of aspiration will require tube thoracostomy.

– BPF’s may require large bore tube.

A 2nd spontaneous PTX deserves pleurodesis

SleepSleep

Sleep-Disordered Breathing– OSA– Central Apneas

NarcolepsyInsomnia

OSAOSA

Incidence- ~3% of all Americans, mostly undiagnosed.

Signs/Sx’s- Excessive daytime somnolence, morning headaches, HTN, caffeine dependence, snoring, witnessed apneas

AHI > 5 arousals/hour

OSA: TreatmentOSA: Treatment

CPAPOral appliancesSurgery

Central ApneasCentral Apneas

‘Cheynes-Stokes is associated with CHF.’

NarcolepsyNarcolepsy

EDSCataplexy- sudden loss of tone in weight-

bearing muscles.Hypnagogic Hallucinations- visual/auditory

hallucinations occuring as patient falls asleep.

Sleep Paralysis- total paralysis while falling asleep or waking up.

Narcolepsy: DxNarcolepsy: Dx

Multiple Sleep Latency Test- demonstrates sleep onset in < 5 minutes and two episodes of Rapid Onset REM sleep.

Narcolepsy: TxNarcolepsy: Tx

Avoid excessive sleep deprivation.Stimulants

– Amphetamines– Modafinil

PotpourriPotpourri

Lung TransplantLung CancerPerioperative Lung EvalPFT’sHemoptysis

Lung TransplantLung Transplant

Lung Transplant may be considered for end-stage Lung Disease.– Post-Transplant Survival

1 month- 88% 1 year- 72% 3 year- 56% 5 year- 43%

Lung Cancer Lung Cancer EpidemiologyEpidemiology

Estimated in 2004, 174,000 Americans will be diagnosed

In 2003, approximately 157,200 deaths due to lung cancer

Leading cause of cancer death in both men and women in U.S.

Causes more deaths than colon, breast, and prostate combined

5 year survival for all patients newly diagnosed is 15% (colon – 61%, breast – 86%, prostate – 96%)

EpidemiologyEpidemiologyRare disease beginning 20th century; sharp rise in

1930’s; by mid-century leading cancer death in men

Rise in women followed in 1960’s to present when is now leading cancer death

Similar rates among African-American and white women, but 50% more frequent among AA males

More common in developed countries


Histologic subtype has shifted with adenocarcinoma replacing squamous cell as most common

Median survival untreated metastatic non-small cell 4-5 months (8 mths with state-of-the-art treatment)

5 year survival for potentially resectable disease:– IA – 67%– IB – 57%– IIA – 55%– IIB – 39%– IIIA – 23%

Cigarette SmokingCigarette Smoking Leading cause of lung cancer and accounts for

approximately 90% of cases in U.S.– Leading cause of preventable death (1 out of 5 deaths)– ½ of regular smokers die prematurely of tobacco-related disease

First scientific report associating cigarette smoking with increased risk of premature death in 1938

Doll and Hill in 1950 demonstrated clear epidemiologic evidence linking smoking and lung cancer

Compared to never smokers, 20 fold increase in risk

Cigarette SmokingCigarette Smoking

Risk increases with duration and number of cigarettes per day– Models show duration of smoking even stronger risk

than number per day– Those starting younger, most likely to develop cancer

and to do so at younger age Risk decreased in those who quit compare to those

who continue– As period of abstinence increases, risk decreases– Never returns to level of risk of never smokers

Occupational/EnvironmentalOccupational/Environmental Lung cancer attributed to occupational exposure

approximately 9-15% Asbestos

– Approximately 7 fold increased risk – Acts synergistically with cigarettes to increase to 16 fold– Dose dependent and fiber dependent

Radon– Formed from breakdown of uranium– Found in soil, groundwater, rock – can accumulate in homes

Ionizing radiation Approx 1-2% attributed to atmospheric pollution

HistologyHistology Adenocarcinoma

– Neoplastic gland formation or intracytoplasmic mucin– Peripheral in 75% of cases

Squamous cell– Proximal tracheobronchial tree 60-80% of cases– Can demonstrate central necrosis with cavitation

Small cell– Neuroendocrine features– Commonly proximal airways with involvement of hilum and mediastinum

Large cell– Diagnosis of exclusion– Commonly peripheral

Signs/Symptoms Due to Signs/Symptoms Due to Intrathoracic SpreadIntrathoracic Spread Due to lymphatic spread or direct extension Nerve involvement

– Recurrent laryngeal, phrenic, Pancoast tumor, Horner’s syndrome

Chest wall and pleura Vascular invasion

– SVC syndrome Visceral invasion

– Esophagus, heart and pericardium

Paraneoplastic SyndromesParaneoplastic Syndromes

Occur in approximately 10% of patientsUnrelated to size of tumorCan sometimes precede the diagnosis of the

tumorCan mark the recurrence of malignancy

Paraneoplastic SyndromesParaneoplastic SyndromesEndocrineSIADH

Hypercalcemia

Gynecomastia

Hypercalcitonemia

Elevated LH, FSH

Hypoglycemia

Hyperthyroidism

Carcinoid

NeurologicSubacute Sensory Neurop

Mononeuritis multiplex

Intestinal Pseudo-obstruct

Lambert-Eaton Syndrome

Encephalomyelitis

Necrotising myelopathy

Cancer-asstd retinopathy

SkeletalHOA

Clubbing

RenalGlomerulonephritis

Nephrotic Syndrome

MetabolicLactic acidosis

Hypouricemia

SystemicAnorexia

Cachexia

Fever

Coll/VascDermatomyositis

Polymyositis

Vasculitis

SLE

SkinE. Gyratum repens

E. Multiforme

Tylosis

Erythroderma

Exfoliative dermatitis

Acanthosis nigricans

Sweet Syndrome

Pruritis, urticaria

Hypertrichosis languinosa

HemeAnemia

Leukocytosis

Eosinophilia

Leukemoid rxn

Thrombocytosis

Thrombocytopenic purpura

CoagulationThrombophlebitis

DIC

Evaluating suitability for Evaluating suitability for surgerysurgery FEV1 most commonly used parameter If FEV1 > 2L for pneumonectomy or >1.5L for lobectomy, no

further eval (low risk) If suitable FEV1, but suspect ILD or patient with excessive

DOE, can use DLCO (more testing if <60%) If patient does not meet above, then testing to evaluate post-op

FEV1 and DLCO– Post-op predicted FEV1 or DLCO <40% indicates high risk

Can use exercise testing to further assist – VO2 max >20ml/kg/min – low risk– VO2 max <15ml/kg/min – increased risk of perioperative complications– <10ml/kg/min – very high risk

Perioperative Lung EvalPerioperative Lung Eval Effects of Surgery Effects of Surgery

Lung volumesDiaphragm functionGas exchangeControl of breathingLung defense mechanisms

Lung VolumesLung Volumes

Dependent on site of surgeryRestrictiveReduction in vital capacity (VC) and

functional residual capacity (FRC) up to 70 and 50 percent respectively

FRC and CCFRC and CC

FRC = lung volume at end of normal expiration

CC = lung volume at which small airways in bases begin to close during expiration because of reduction in airway radial traction

Normally FRC > CC and airways remain open throughout tidal breath

DiaphragmDiaphragm

Temporary dysfunction following thoracic or upper abdominal surgery

Gas ExchangeGas Exchange

Arterial hypoxemia– First phase: initially post-op secondary to

residual anesthesia, shunting, V/Q mismatch– Second phase: CC > FRC

Control of BreathingControl of Breathing

Anesthetic agents inhibit respiratory drive and reduce ventilatory response to hypercapnia, hypoxia, and acidemia

Narcotics decrease sighs and may precipitate OSA

J Gen Intern Med, 1995.

Pulmonary ComplicationsPulmonary Complications

Incidence 5-90 percent 528 patients underwent elective abdominal

surgery Pulmonary complications >> cardiac

complications Pulmonary complications associated with longer

hospitalization Healthy non-obese, non-smoker < 1 percent

Pulmonary ComplicationsPulmonary Complications

AtelectasisInfection (tracheobronchitis and

pneumonia)Prolonged mechanical ventilation or

respiratory failureExacerbation of underlying pulmonary

diseaseThromboembolic disease

Pre-operative Risk FactorsPre-operative Risk Factors

Chronic lung disease Smoking General health Age Obesity Antecedent respiratory infection Obstructive sleep apnea

AsthmaAsthma

If under good control, minimal complicationsTracheal intubation can initiate bronchospasmConsider regional anesthesia in severe asthmaConsider stress dose steroidsTreat acute bronchospasmDelay surgery if necessary

Mayo Clin Proc 1989.

SmokingSmoking

200 consecutive CABG patients stratified by smoking history

Significant reduction in complications if patient stops at least 8 weeks prior to surgery1

Stop 12-18 hours pre-op to allow for sufficient carboxyHB clearance

Evidence for decreased HR, BP, and cathecholamine levels within 60 minutes after smoking

Ann Intern Med 1986.

ObesityObesity

Common false assumption10 series of gastric bypass surgery found no

increased incidence of pneumonia or atelectasis

Meta-analysis of 6 studies (4526 patients) demonstrated equal rate of complications in obese and non-obese

Post-operative Risk FactorsPost-operative Risk Factors

Inadequate post-operative analgesiaImmobilization

Inadequate post-operative Inadequate post-operative analgesiaanalgesia

Pain inhibits coughing and deep breathingPain discourages mobilityHesitancy to report painAnxiety of prescribing narcotics

ImmobilizationImmobilization

FRC decreases 500-1000cc when moving from upright to supine position

Increased risk of thromboembolic disease Ambulation is associated with clearance of

secretions

Pulmonary Function TestsPulmonary Function Tests

Not indicated for routine pre-operative screening

Indications:– Persistent cough or unexplained dyspnea– Hx of chronic lung disease– Hx of smoking– Planned lung resection

Incentive spirometerIncentive spirometer

Non-invasiveInexpensiveDecreased atelectasisDecreased hospital stay

PFT’s PFT’s IndicationsIndications

Detect presence or absence of lung dysfunction suggested by history, physical or presence of other abnormal tests.

Quantify severity of known lung disease. Assess change in function over time or effect of

therapy. Assess effects of environmental or occupational

exposure. Pre-surgical evaluation. Assess impairment or disability

Normal Flow-Volume LoopNormal Flow-Volume Loop

Obstructive Flow-Volume Obstructive Flow-Volume LoopLoop

Obstructive FVLObstructive FVL

Restrictive Flow-Volume LoopRestrictive Flow-Volume Loop

Restrictive FVLRestrictive FVL

‘‘Fixed Airway Obstruction’Fixed Airway Obstruction’

‘‘Dynamic Extrathoracic Airway Dynamic Extrathoracic Airway Obstruction’Obstruction’

‘‘Dynamic Intrathoracic Airway Dynamic Intrathoracic Airway Obstruction’Obstruction’

Determining “Normal”Determining “Normal”FlowsFlows

The use of “80% of predicted” as a cutoff between normal and abnormal is arbitrary.– Extremes of age and height are frequently

mislabeled– Lower limits of normal for flows

(e.g. ‘FEF25-75’) is closer to 50%.

Determining “Normal”Determining “Normal”FEVFEV11/FVC Ratio/FVC Ratio

This ratio is inversely related to age and height; therefore, use of a fixed ratio (i.e. 80%) will result in increased labeling of impairment in older patients.

Athletes and workers in demanding occupations frequently have disproportionately high FVC compared to FEV1.

Definition of An Obstructive Definition of An Obstructive DefectDefect

A disproportionate reduction of maximal airflow from the lung with respect to the maximal volume that can be displaced from the lung.– Low FEV1/ FVC.

‘‘Significant BD Response’Significant BD Response’

Many different definitions looking at different flows, volumes or ratios.

ATS:– Increase in FVC or FEV1 of 12% from baseline

AND

- an absolute increase of 200ml.

Definition of a Restrictive Definition of a Restrictive DefectDefect

One may infer the presence of a restrictive defect when VC is reduced and FEV1/FVC is preserved, but…– A restrictive defect is physiologically defined

by a reduction in TLC.

If a contradiction between TLC and VC arises, defining restriction should be based on TLC.

When to Obtain Lung When to Obtain Lung VolumesVolumes

To confirm and help stage the severity of disease suspected by spirometry.

To provide evidence of lung dysfunction not clearly evident from spirometric tests.

To trend the course of a disease or response to therapy.

Lung Volumes in Restrictive Lung Volumes in Restrictive Lung DiseaseLung Disease

Since Restrictive Lung Diseases are defined by a decrease in VC and TLC, measurements of lung volumes are most helpful in detecting, confirming and staging restrictive lung defects.

Lung Volumes may suggest the physiologic type of disease from the pattern of lung volume alterations.

Restrictive Lung Disease:Restrictive Lung Disease:Differential DiagnosisDifferential Diagnosis

Pleural- EffusionAlveolar- PAP, PNAInterstitial- ILD’s, IPFNeuromuscular- Thoracic Wall- Kyphoscoliosis, AS

Low DLCO:Low DLCO:Differential DiagnosisDifferential Diagnosis

Obstructive Lung Disease- COPD, CFInterstitial Lung Disease- Pulmonary Vascular Disease- Pulm HTN,

Venous Thromboembolic Disease

Cardiovascular Disease- Pulm EdemaAnemia

Elevated DLCO:Elevated DLCO:Differential DiagnosisDifferential Diagnosis

PolycythemiaAlveolar HemorrhageAsthmaIncreased Pulmonary Blood Flow

– Left Right Intracardiac shunt– Exercise– Mild CHF

HemoptysisHemoptysis

DDx:– Bronchitis– Lung Cancer– Idiopathic– Bronchiectasis– TB


‘Massive Hemoptysis’ = > 100-150mlRequires Emergent imaging and

bronchoscopy because:– Mortality due to asphyxiation > exsanguination


Tx:– Hemodynamic management– Reverse coagulopathies– Triage the DDx– Consider FOB, IR, Surgical intervention– ‘Bleeding side down if hemoptysis persists’

ABIM Board Review: Pulmonary Medicine. Overview Topics – Respiratory Infections – Airway Disease...

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