Pulmonary Board Review

2009

What we’re going to speed through1. Evaluation of symptoms: cough and dyspnea2. PFTs3. Asthma4. COPD5. Interstitial lung diseases6. Pneumoconioses7. Pleural disease8. Sleep9. Pulmonary embolism10. Mechanical ventilation

Respiratory symptoms: cough Cough

Chronic cough = duration > 3 weeks First: Make sure the patient is not on an ACE inhibitor Most common etiologies

Postnasal drip syndrome Asthma GERD

Others: Chronic bronchitis Bronchiectasis ACE inhibitor Post-infectious Eosinophilic bronchitis Endobronchial lesion

Respiratory symptoms: dyspnea Chronic dyspnea: lasting > 1 month

2/3 of patients with one of the following COPD Asthma ILD Cardiomyopathy

Others: neuromuscular disease, hyperventilation syndrome, GERD, pulmonary vascular disease

Work-up: History, PFTs, chest Xray Cardiopulmonary exercise testing

PFTs: Spirometry Approach

Is it a good test? reproducible, adequate exhalation time (at least 6 seconds), technician comments regarding patient effort and compliance

Is there obstruction? FEV1/FVC < 70% indicates obstructive disease. Severity of obstruction as follows:

I: Mild FEV1 > 80% predicted

II: Moderate FEV1 < 50-80% predicted III: Severe FEV1 < 30- 50% predicted

IV: Very Severe FEV1 < 30% predicted Is there restriction? FVC < 80% predicted indicates possible restrictive

disease Is there airway reactivity? Response to bronchodilator testing: > 12% or >

200mL

Lung volumes

Lung Volumes

0

20

40

60

80

100

120

nl COPD rest n-m obese

RV

FRC

TLC

PFTs: DLCO Decreased in:

Diseases that obliterate the alveolar-capillary interface: Emphysema Fibrotic lung disease Pulmonary vascular diseases

Diseases that increase the thickness of the interface: Fibrotic lung diseases Interstitial edema/alveolar edema

Anemia

PFTs: flow volume loops Useful in looking for

central airway obstruction

Flow volume volumes

Asthma 22 millions pts per year in U.S.

Overall increasing disease prevalence Decreasing number of asthma deaths Significant racial disparities in disease burden

Puerto Ricans African Americans

Asthma categories of severity 2007 NAEPP report

Intermittent Mild persistent Moderate persistent Severe persistent

Treatment recommendations based upon severity

Intermittent asthma: Symptoms ≤ 2 days per week Requirement for rescue albuterol ≤ 2 days per

week Nocturnal awakenings ≤ 2 times per month No limitations in ADLs Normal PFTs

RX: Intermittent albuterol

Mild persistent asthma Symptoms > 2 days per week or 3-4 nocturnal awakenings a month or Minor limitation in ADLs

AND Normal PFTs

RX: Step 2 low dose inhaled corticosteroids

Moderate persistent asthma Daily symptoms or > 1 nocturnal awakening per week or Moderate limitation in ADLs or FEV1 60-80%

Rx: step 3 in asthma treatment protocol Low dose inhaled corticosteroids + LABA Medium dose inhaled corticosteroid

Severe persistent symptoms Ongoing daily symptoms with significant exercise

limitation and frequent nocturnal awakenings

Rx: Step 4: High dose ICS + LABA Step 5: High dose ICS + LABA + systemic

corticosteroid therapy AND consider omalizumab

Asthma syndromes Cough variant asthma Aspirin-induced asthma or triad asthma Exercise induced asthma Occupational asthma Allergic bronchopulmonary aspergillosis

Occupational asthma 5 – 15% of all asthmatics Over 300 agents have been reported to cause OA Different prevalence for specific populations

OA may develop in 2.5% for hospital workers exposed to latex

2-40% millers and bakers 20% exposed to acid anhydrides 5% exposed to toluene diisocyanate (TDI)

OA with a latency period: specific antigens identified, mostly HMW antigens although some LMW antigens as well IgE mediated: usually HMV antigen with a median latency

period of ~ 5 years. Atopy is a risk factor Non-IgE mediated: usually LMW antigens with a median

latency period of 2 years. Atopy is not a risk factor

OA without a latency period: 1) nonspecific irritant-induced asthma or 2) reactive airways dysfunction syndrome

COPD 6th leading cause of death worldwide Underdiagnosed GOLD: stages of severity

Based of spirometry Stage 0: normal spirometry but symptoms present Stage I: Mild ratio < 70% but FEV1 > 80% Stage II: Moderate

IIa FEV1 50-80% IIb FEV1 30-50%

Stage III: Severe

Adapted from Fletcher et al. BMJ. 1977;1:1645-1648.

FE

VF

EV

11 (%

) R

elat

ive

to A

ge

25 (

%)

Rel

ativ

e to

Ag

e 25

Death

Disability

Age (years)5050 7575252500

Symptoms

00

2020

6060

100100

8080

4040

Healthy

COPD

Rehabilitationat 45 (mild COPD)

Exercise Performance Over Time

Rehabilitationat 65 (severe COPD)

COPD risk factors Tobacco:

15-20% 1ppd smokers develop COPD 25% 2ppf smokers develop COPD

Genetic factors: Alpha1-antitrypsin deficiency Gender: Males more at risk than females Bronchial hyperresponsiveness Atopy and asthma Childhood illnesses Prematurity

COPD Treatment:

Smoking cessation Oxygen therapy Medical therapy Pulmonary rehabilitation LVRS

Transplantation

*Four-step algorithm for the implementation of inhaled treatment; *Four-step algorithm for the implementation of inhaled treatment; ††Pathway on left is recommended; pathway on right side is a Pathway on left is recommended; pathway on right side is a valid alternative; valid alternative; ‡‡Defined as need for rescue medication on more than 2 occasions per week; Defined as need for rescue medication on more than 2 occasions per week; §§A short-acting bronchodilator A short-acting bronchodilator can be used for rescue. Low-dose methylxanthines can be prescribed if the response to inhaled bronchodilator therapy is can be used for rescue. Low-dose methylxanthines can be prescribed if the response to inhaled bronchodilator therapy is insufficient; insufficient; ¶¶ Defined as 2 or more exacerbations per year. Defined as 2 or more exacerbations per year.Cooper et al. Cooper et al. BMJBMJ. 2005;330;640-644. (B). 2005;330;640-644. (B)

Inhaled TherapyInhaled Therapy

0000

IIII

IIIIIIII Salmeterol or formoterol +Salmeterol or formoterol +ipratropium, salbutamol, ipratropium, salbutamol,

or combinationor combination

Salmeterol or formoterol +Salmeterol or formoterol +ipratropium, salbutamol, ipratropium, salbutamol,

or combinationor combination

*Tiotropium +*Tiotropium +albuterolalbuterol

*Tiotropium +*Tiotropium +albuterolalbuterol

IIIIIIIIIIII

Salmeterol or Formoterol +Salmeterol or Formoterol +Tiotropium§Tiotropium§

Salmeterol or Formoterol +Salmeterol or Formoterol +Tiotropium§Tiotropium§

*Tiotropium +*Tiotropium +salmeterol or formoterol§salmeterol or formoterol§

*Tiotropium +*Tiotropium +salmeterol or formoterol§salmeterol or formoterol§

IVIVIVIV

*Tiotropium + salmeterol or formoterol *Tiotropium + salmeterol or formoterol + inhaled corticosteroid+ inhaled corticosteroid§§

*Tiotropium + salmeterol or formoterol *Tiotropium + salmeterol or formoterol + inhaled corticosteroid+ inhaled corticosteroid§§

Clinical Algorithm for the Treatment of COPDClinical Algorithm for the Treatment of COPDNonpharmacologic Nonpharmacologic

TherapyTherapy

Smoking cessationSmoking cessationAvoidance of exposureAvoidance of exposure

Smoking cessationSmoking cessationAvoidance of exposureAvoidance of exposure

VaccinationVaccination(influenza, pneumococcal)(influenza, pneumococcal)

VaccinationVaccination(influenza, pneumococcal)(influenza, pneumococcal)

Pulmonary rehabilitationPulmonary rehabilitation(Exercise prescription)(Exercise prescription)

Pulmonary rehabilitationPulmonary rehabilitation(Exercise prescription)(Exercise prescription)

Supplemental oxygenSupplemental oxygenLung volume reduction surgeryLung volume reduction surgery

Lung transplantationLung transplantation

Supplemental oxygenSupplemental oxygenLung volume reduction surgeryLung volume reduction surgery

Lung transplantationLung transplantation

*Short-acting bronchodilator as needed*Short-acting bronchodilator as needed(for example, ipratropium, salbutamol, or combination)(for example, ipratropium, salbutamol, or combination)

*Short-acting bronchodilator as needed*Short-acting bronchodilator as needed(for example, ipratropium, salbutamol, or combination)(for example, ipratropium, salbutamol, or combination)

GOLD StageGOLD Stage(approximate)(approximate)

ClinicalClinicalstagestage

At riskAt risk

IntermittentIntermittentsymptomssymptoms

PersistentPersistentsymptomssymptoms‡‡

FrequentFrequentexacerbationsexacerbations¶¶

Respiratory failureRespiratory failure

††

Interstitial lung diseases orDiffuse parenchymal lung disease DPLD of known cause:

Drugs Connective tissue disease Occupational lung disease

Granulomatous disease Sarcoidosis Hypersensitivity pneumonitis

Idiopathic interstitial pneumonia (IIP) Idiopathic pulmonary fibrosis (i.e., usual interstitial pneumonia) Others

Non-specific interstitial pneumonia Desquamative interstitial pneumonia Respiratory bronchiolitis interstitial lung disease Cryptogenic organizing pneumonia Acute interstitial pneumonia (Hamman Rich syndrome) Lymphocytic interstitial pneumonia

Misc Lymphangioleiomyomatosis Histiocyotsis X Pulmonary alveolar proteinosis

DPLD Chest Xray can be normal in

10-15% patients with diffuse lung disease 30% patients with bronchiectasis 60% patients with emphysema

High resolution chest CT Sensitivity of 90% and specificity approaching 100% Can provide a confident diagnosis in ~50% cases; ~93% of these cases

are ultimately proven correct Findings usually seen in DPLD

Ground glass opacity Findings consistent with fibrosis

Interlobular and intralobular septal thickening Honeycombing

HRCT findings: linear and reticular opacities Intralobular interstitial thickening

“fine reticular pattern” with lines of opacity separated by a few mmm Fine lacy or netlike appearance When seen in fibrosis, often seen in conjunction with dilated bronchioles

(“bronchiolectasis”) DDX:

IPF Chronic hypersensitivity pneumonitis Pneumoconioses ILD: NSIP, DIP Lymphangitis carcinomatosis Pulmonary edema Pulmonary hemorrhage Pneumonia Alveolar proteinosis

Figure 3-24

DPLD General approach:

Timeline Smoking history Occupational history Environmental and toxin exposures Drug history Extrapulmonary symptoms and manifestations

Sarcoidosis CTD

Testing PFTs HRCT CTD serologies Assess for exertional hypoxemia

Diagnosis PFTs Bronchoscopy

BAL limited utility Looks for eosinophilia (> 10%) Lymphocytosis Mast cells

Biopsy limited utility Helps if high pre-test probability of sarcoidosis, HP, LIP,

lymphangitic carcinomatosis Dismal if you are thinking UIP or NSIP

IPF Older age, M > F Histopath: UIP

Fibroblastic foci Temporally heterogeneous Minimal inflammation Lots of collagen deposition

Predominantly subpleural and basilar Similar findings in abestosis, rheumatoid lung disease Progressive disease with a median survival 2-3 years

from diagnosis

NSIP Path: temporally uniform with interstital

inflammation Rad: ground glass with areas of fibrosis

Often also seen with CTD such as scleroderma

DIP/RBILD Path:

Pigmented macrophages Peribronchiolar inflammation

Rad: Patchy ground glass Intralobular septal thickening Mosaic pattern

DPLD: Hypersensitivity pneumonitis Disease of varying intensity and manifestation caused by the

immunologic response to inhaled antigen, usually organic Hundreds of antigens have been described. Occupations

with highest frequency of HP: Farmers “Farmer’s lung” Poultry workers “Poultry worker’s lung,” “Bird breeder’s lung,”

“Bird fancier’s lung” Animal workers Grain processing “Grain handler’s lung” Textiles Lumber

Also described with inhalation of contaminated water “Humidifier lung,” “Air conditioner lung,” “Hot tub lung”

Subacute HP

Mostly mid to upper lung zones

Chronic HP

HP: Treatment and prognosis Treatment

Remove the inciting antigen from the environment or remove the patient from the environment

Corticosteroids for severe cases

Prognosis Acute and subacute disease have excellent

outlooks Chronic can progress to end stage fibrosis

Y. Rosen, M.D. Atlas of Granulomatous Diseases

Sarcoidosis: Four stages

Sarcoidosis in the lungs: Stage I Only the lymph nodes

are enlarged Pulmonary function is

intact 55-90% pts with Stage

I sarcoidosis resolve spontaneously

Sarcoidosis: Stage II Lymph nodes

enlarged Inflammation

in the lung Lung function

is impaired 40-70% pts

resolve spontaneously

Sarcoidosis: Stage III Lymph nodes are not

enlarged Only 10-20% resolve

spontaneously

Sarcoidosis 90% with lung

involvement 75% liver 20% skin 20% eyes 25% spleen 10% MSK 5% heart 5%

Pneumoconioses Silicosis CWP Asbestosis Talcosis Berylliosis

Silicosis: Exposure Mining Quarrying Tunneling Stone cutters Sandblasting Glass manufacturing Foundry work

Enameling Quartz crystal

manufacturing Rubber industry

Silicosis: clinical presentations

Chronic silicosis Accelerated silicosis Progressive massive fibrosis Acute silicosis

Chronic silicosis Usually 10-30 years after initial exposure. Can become radiographically apparent

even after removal of exposure Ranges from asymptomatic with normal

PFTs to very very symptomatic with restrictive spirometry and low DLCO

Chronic silicosis: CXR findings Simple silicosis is the

earliest finding of chronic silicosis

Nodules usually 1-3 mm

Chronic silicosis: CXR findings As disease

progresses, nodules increase in number and coalesce to form larger lesions

Chronic silicosis: CXR findings Eggshell calcification

Progressive massive fibrosis (PMF)

Occurs in a minority of pts with chronic silicosis

More likely to occur in pts with accelerated silicosis

PFTs abnormalities: mixed obstructive/restriction, air trapping

PMF: CXR findings The nodules coalesce

into conglomerate masses

Calcified lymph nodes “eggshell calcification”

Coal worker’s pneumoconiosis AKA, black lung disease or anthrasilicosis Rate and quantity of dust accumulation

most important factor in pathogenesis of CWP

Clinical presentations similar to silicosis: 1. Simple

2. Chronic

3. PMF

Asbestos-related lung diseases Pleural plaques Benign asbestos related pleural effusion Asbestosis Mesothelioma

Asbestos: Pleural plaques Usually first identified > 20 years after initial

exposure Occur in 50% persons exposed to asbestos Parietal pleura adjacent to ribs, particularly

along 6th-9th ribs and along diaphragm Calcifications on CXR in 20% and on chest

CT in 50%

Asbestos: Pleural plaques

Benign asbestos pleural effusion Most common pleuropulmonary manifestation within the first

20 years of exposure… but can present <1 post-exposure to >50 years after first exposure

Typical presentation: acute pleuritic CP, fever, other systemic sx but can be insidious

Can resolve spontaneously Pleural fluid analysis: exudative, serosanguinous,

predominance of eosinophils, cytology with atypical macs, occasionally positive for RF

Rounded atelectasis and/or diffuse pleural thickening may be sequelae

Rounded atelectasis

Asbestos: Mesothelioma Annual incidence 1:1,000,000/year Incidence peaking now b/c of inadequate

control measures in 60s and 70s Any level of exposure may be a risk factor Usually presents 20-40 years after

exposure

Asbestosis Presents > 30 years after initial exposure Requires long term, heavy exposure Criteria for diagnosis:

1. History of asbestos exposure

2. Dyspnea

3. Basilar crackles in two or more locations

4. Reduced lung volumes

5. Radiographic abnormalities

Talc related diseases Talcosilicosis: caused talc mined with a high

silica content Talcoasbestosis: crystalline talc contaminated by

asbestos fibers Talcosis: inhalated of pure talc leading to

bronchitis IV talc injection: from cutting heroin with talc

formation of granulomas within the pulmonary vasculature pulmonary hypertension

Berylliosis Think aerospace, automotive, computer,

ceramics, and nuclear industries Clinical manifestations:

Acute disease due to direct irritant effects: rhinitis, pharyngitis, tracheobronchitis, chemical pneumonitis

Chronic disease: Think sarcoidosis except we have an etiology. Dx: finding beryllium somewhere or lymphocyte transformation test.

Diagnostic evaluation of pleural effusion Thoracentesis

Helpful in 75% cases Can be therapeutic as well

Routine labs: LDH, total protein, glucose, pH, gram stain and

culture, cytology, cell count and differential Additional labs that may be helpful

Albumin, cholesterol, triglycerides, amylase, adenosine deaminase, AFB

Pleural fluid analysis: Light’s criteria

Pleural fluid protein/serum protein > 0.5 Pleural fluid LDH / serum LDH > 0.6 Pleural fluid LDH > 2/3 upper limits of

normal for serum LDH

*Very accurate at identifying exudates (~98%) but less accurate with transudates

Pleural fluid analysis: Other pleural chemistries to help differentiate exudate from transudate

Cholesterol Absolute pleural fluid cholesterol > 45- 60mg/dL

Pleural fluid albumin gradient < 1.2 g/dL Bilirubin: pleural fluid bilirubin/serum

bilirubin > 0.6

Pleural fluid analysis: Cell count and differential Neutrophils

Typical of acute inflammatory process Eosinophils > 10%

air, blood most common etiologies. Other:

Parapneumonic #1, malignancy, tuberculosis, BAPE, drugs (dantrolene, bromocriptine,

nitrofurantoin), parasites, Churg-Strauss Lymphocytes > 50%

malignancy, tuberculosis or s/p CABG Mesothelial cells:

Uncommon in tuberculous effusions. Major exception: AIDS

Pleural fluid analysis: cell count Red blood cells

Blood-tinged fluid typically 5000 to 10000 RBC/mm3

Grossly bloody: 100000 RBC mm3 Trauma Malignancy Pulmonary embolism Infection

Hemothorax: pleural fluid hct to blood hct > 50%

Pleural fluid analysis: Glucose Glucose < 60mg/dL suggestive of the following

disorders Parapneumonic effusion:

the lower the glucose, the more complicated the effusion Malignant effusion:

15-25% pts with malignant effusion have low pleural glucose levels. The lower the glucose, the higher the tumor burden

Rheumatoid disease: majority of pts with rheumatoid effusion (78%) have pleural

glucose < 30mg/dL Tuberculous effusion Rare: Paragonimiasis, hemothorax, Churg-Strauss, lupus

Pleural fluid analysis: amylase Elevated levels suggestive of 1 of 3 dx

Pancreatitis: often higher than serum levels**Pseudocyst communication: amylase > 1000U/L

Esophageal rupture Malignant effusions: amylase level elevated in

10%

Pleural fluid analysis: LDH Serial LDHs can be helpful:

Increasing levels: worsening process Decreasing levels: resolving process LDH isoenzymes:

Mostly LDH-4 and LDH-5 If predominance LDH-1, the increase is due to

blood

Pleural fluid analysis: pH pH < 7.2:

Parapneuymonic effusion Esophageal rupture Rheumatoid pleuritis Tuberculous pleuritis Malignant pleural disease Hemothorax Systemic acidosis Paragonimiasis Lupus pleuritis Urinothorax

Reasons for caution Often not measured

correctly: must be measured using a blood gas machine

Must be collected anaerobically in a heparinized syringe

Lidocaine may falsely lower the pH

Pleural fluid analysis: other ADA level > 50 U/L in pts without empyema or

rheumatoid arthritis is virtually diagnostic of a tuberculous effsuion

Interferon-gamma level > 3.7 U/mL also quite good at distinguishing tuberculous effusions

RF: Pleural fluid titer > 1:320 strongly suggestive of rheumatoid effusion

ANA: tends to correlate with serum ANA

Pleural fluid analysis: lipid studies

Triglycerides > 110 mg/dL diagnostic of chylothorax

Triglycerides 50-110mg/dL equivocal Triglycerides < 50: not a chylothorax

Pleural fluid analysis: lipid studies

Triglycerides > 110 mg/dL diagnostic of chylothorax

Triglycerides 50-110mg/dL equivocal Triglycerides < 50: not a chylothorax

Parapneumonic effusions and empyemas

Pleural fluid characteristics associated with need for pleural fluid drainage Pus in the pleural space Positive gram stain or culture Glucose < 40 pH < 7.0 LDH > 3 x the ULN Loculated pleural fluid

ACCP recommendations Class I: Small < 10mm on decubitus film

No thoracentesis needed Class II: Typical parapneumonic effusion

More than 10mm on decubitus film needs sampling Pleural fluid characteristics:

Glucose > 40 pH > 7.2 LDH < 3x ULN

Treatment: antibiotics alone Class III: Borderline complicated

pH 7.0 -7.2 or LDH > 3x ULN Normal glucose Negative pleural micro Treatment: Antibiotics plus serial thoracenteses

Class IV through VII: Complicated pH < 7.0 or glucose < 40 or pleural fluid micro positive tube thoracostomy

Sleep disordered breathing Obstructive sleep apnea

RFs Obesity Facial soft tissue abnormalities Smoking! Nasal congestion DM

Mild AHI 5-15 Sedentary daytime sleepiness Sats > 90% more than 95% of time during sleep

Moderate: AHI 15-30 Daytime sleepiness requiring behavioral changes

Severe: > 30 disabling daytime sleepiness and signs of cardiopulmonary failure Nocturnal sats < 90% more than 20% of the time

Sleep disordered breathing Outcomes:

3-6x risk of all cause mortality Associated with: HTN, PH, MI, CVA, arrythrmias Treatment is associated with decreased mortality

Treatment: Weight Alcohol and drug avoidance NIPPV for

AHI > 5 and clinical sequelae (sleepiness, mood disorder, cardiovascular disease)

AHI > 15 without symptoms Oral appliances Surgery (UPPP)

Obesity hypoventilation syndrome Definition

Awake alveolar hypoventilation (pCO2 > 45) Obesity (BMI > 35) No other cause of hypoventilation

Usually seen with OSA Cor pulmonale

Outcomes: High mortality

Obesity hypoventilation Treatment

OSA present: Trial of CPAP is appropriate Transition to BiPap if volume cycled positive

airway pressure if symptoms persist or persistent daytime hypercapnia

Treatment of acute respiratory failure: BiPAP or VCPAP

Pulmonary embolism Mortality 30% without apporpriate treatment Mortality decreases to 2-8% with

appropriate diagnosis and treatement Increased risk of death

RV dysfunction Elevated BNP Elevated troponin

Copyright restrictions may apply.

Writing Group for the Christopher Study Investigators, JAMA 2006;295:172-179.

Clinical Decision Rule*

Treatment Anticoagulation IVC filter Thrombolysis

Mechanical ventilation Complications of invasive mechanical

ventilation Recognize PEEP related hypotension Appropriate ventilator management for

ARDS

Whew!