Download Pulmonology - Dr. Roy

Pulmonary Medicine
Thomas Roy, MD
ETSU
Internal Medicine Board
Review
The Essentials
Pulmonary Functions
• Spirometry determines
patency of the tubes) :
• Diagnoses Obstructive
diseases
– Expiratory Flows
– Flow-Volume Loops
– Response to
Bronchodilators
– Response to
Bronchoprovocation
Expiratory Flows
• FEV1/FVC < 70% defines Obstruction
– FVC – the maximal amount of air that can be
forcibly exhaled
– FEV1 – the volume exhaled during the first second
of a forced vital capacity ( FVC)
Expiratory Flows
• The degree of obstruction can then be
determined by comparing the measured
FEV1 to the FEV1 predicted by age, Ht,
gender, ethnicity
• Normal: ratio = 0.8
• “Mild” “Moderate” “Severe”
• GOLD criteria (ATS, EU, BTS)
Pulmonary Functions
• Lung Volumes
determine the elasticity
of parenchyma
• Diseased parenchyma
is stiff
• Diagnoses restrictive
diseases
Restrictive Lung Disease
• Small lungs with increased stiffness from
parenchymal disease or scarring
• FEV1 and FVC are each decreased
• However, decreased proportionately so
FEV1/FVC ratio is preserved
Dynamic Lung Volumes
Obstructive
Restrictive
FVC
FEV1
FEV1/FVC
< 70%
FVC = Force Vital Capacity
FEV1 = Forced Expiratory Volume in 1 second
> 70%
Question
• A 16 year old male presents to your office with
complaints of wheezing on exertion.
• He has enjoyed good health except for a
prolonged bout with Guillian-Barre syndrome
when he was 12 years old.
• He has recently taken up cross-country running
and notes audible wheezing at the height of his
exertion.
• He has tried his friend's asthma inhaler after the
wheezing starts, but without much success.
Question
This patient would benefit most from:
(A) Using a B2 inhaler before starting his tennis match
(B) Using chromolyn sodium as prophylaxis for exercise–
induced asthma
(C) Having PFTs performed with a flow-volume loop
(D) Having a bronchoprovocation challenge test for asthma
(E) Having fluoroscopy of the diaphragm to document
residual paralysis
Question
(C) Having PFTs with a flow-volume loop
• All patients deserve PFTs to document
suspected asthma. A flow-volume loop will
provide additional information regarding the
upper airway that would help diagnose vocal
cord problems or benign adenomas as
alternate causes of wheezing. This patient
had a pattern consistent with a fixed upper
airway obstruction likely due to prior
intubation during his bout with GuillianBarre syndrome.
The Flow-Volume Loop
• Spirometry data presented in a different
fashion (flow is the first derivative of
volume/time)
• Plot volumes on the X axis and Flow on the
Y axis
• Note position of the Inspiratory and
Expiratory Loops
Pulmonary Function Test:
Spirometry
Flow (L/s)
Expiratory
Inspiratory
Volume Vs Time
FEV1
PEFR
FEF 25%
FEF 50%
FEF 75%
0
0
IRV
Vt
ERV
RV
FVC
FRC
TLC
Lung Volumes and Capacities
Expiratory Flow-Volume Loops
Pulmonary Function Test:
Flow (L/s)
Expiratory
Inspiratory
Intrathoracic / Extrathoracic Obstruction
FEF50
FIF50
FEF50 / FIF50
<1
Intrathoracic
>1
Extrathoracic
1
Fixed
Flow-Volume in UAO
• Dynamic Extrathoracic: obstruction on
inspiration:
– tracheomalacia
– vocal cord lesion
– Vocal Cord Dysfunction syndrome
Fixed Upper Airway Obstruction
• Both inspiratory
and expiratory loops
are flattened
– compressive tumors
– tracheal stenosis –
“prolonged intubation”
Response to Bronchodilators
• Use inhaled B2-agonist in obstruction to
check for response
• Significant response = Bronchial hyperreactivity (BHR)
• Improvement in FEV1 or FVC from
baseline by 12% and 200 cc
DLCO Determination
• Linear Diffusion of Carbon Monoxide (DLCO)
• A most important concept for this exam
• The measurement of the volume of gas
transferred across the alveolar-capillary
membrane per minute per mm of mercury
difference between the alveolus and capillary
blood
DLCO
• Pt exposed to a
known concentration
of CO for a known
time
• CO attaches to Hgb
• New concentration of
CO allows calculation
of transfer speed
Reduced DLCO
• A loss of effective
capillary surface and
interface, or
• Destruction and
thickening of the
alveolar-capillary
membrane
DLCO
• Decreased in:
– Pulmonary fibrosis/ILD
• thickened basement membrane
– Emphysema
• loss of alveoli & pulmonary capillaries
Pulmonary Hypertension
• loss of pulmonary capillaries
Diagnose pulmonary disease
Chronic
Bronchitis
Emphysema
↓
↓
↑
nl
TLC
nl
↑
↓
nl
DLCO
nl
↓
↓
↓
FEV1/FVC
Pulmonary
Fibrosis
Pulmonary
vascular
disease
Obstructive Lung Diseases
Obstructive Lung Disease
“C BABE”
•
•
•
•
•
Cystic Fibrosis
Bronchiectasis
Asthma
Bronchitis
Emphysema
Asthma
Asthma - essentials
The syndrome is characterized by:
• Episodic airflow obstruction that is reversible
• Bronchial hyperresponsiveness (BHR) to a
variety of stimuli
• Persistent lung inflammation, particularly in
the airways
• A multifactorial etiology
• A genetic predisposition
PFT Patterns
• Asthmatics often have normal PFTs
between attacks
• Diagnosis then requires a provocation test
– Usually methacholine challenge
– 20% fall in FEV1 with low dose metacholine
less than 8 mg/ml suggests BHR
Pulmonary Function Test:
Methacholine Challenge
Normal
FEV1 % control
100
80
60
PC20
Abnormal
40
0.1
50 100
500
1000
CUMULATIVE INHALATION UNITS (Methacholine)
PC20 : 8 mg/ml or 80 - 100 cumulative inhalation units
Pulmonary Function Tests
A normal methacholine challenge test
means it is:
NOT ASTHMA
Pathophysiology of Asthma
• Individual must have a
genetic predisposition
-plus• Challenge stimulus
– Allergen
– Infectious pathogen
– Environmental agent
-results in• Chronic Inflammation
• Airway reactivity
Asthma is Chronic Inflammation
• Once asthma begins
there is a perpetual
situation of chronic
inflammation
• An overt attack is a
signal that the underlying
inflammation has reached
a critical threshold and is
poorly controlled
Asthma is Chronic Inflammation
• The number of clinical events in a specific time
period and the PEFR are used to classify the
intensity of the asthmatic inflammation
– Days/week
– Nights/month
– Variation in daily PEFR
– Functional limitations
Peak Expiratory Flow
• PEF- part of the FEV1
• Normal 600-800 LPM
• Usually less than 20%
difference between
morning and night time
values
Asthma PEFR and FEV1
• Reasonable
correlation between
FEV1 and PEFR
• PEFR can be used in
clinical situations to
give an objective
measurement of
severity of airflow
obstruction
Peak Flow Meter
• Easily measured
• Inexpensive
• Exaggeration of the
normal diurnal
difference also
indicates increased
airway inflammation
EPR-3 Summary Report 2007
Expert Panel Report 3
Achieving and maintaining asthma control
requires 4 components of care:
• Assessment and monitoring
• Education for a partnership in care
• Control of environmental factors and
comorbid conditions that affect asthma
• Medications
Expert Panel Report 3
• Assess severity to initiate therapy
• Assess control to adjust therapy
– Assess impairment by rule of “2s”
– Assess risk to formulate action plan
Expert Panel Report 3
• Adding LABA to low-dose ICS reduces the
frequency of exacerbations to a greater
extent than doubling the dose of ICS
• LABA monotherapy has the potential risk
of rare life-threatening or fatal
exacerbations
Expert Panel Report 3
• Omalizumab is now recommended for
consideration for youths ≥12 years of age
who have allergies or for adults who
require step 5 or 6 care (severe asthma).
– Clinicians who administer omalizumab should
be prepared and equipped to identify and
treat anaphylaxis that may occur.
Expert Panel Report 3
• Assess patient adherence to medication,
inhaler technique, and environmental
control measures before making a step up
in therapy
Assess Risk
• Most patients have mildto-moderate asthma that
responds to inhaled
corticosteroids
• Severe asthma
represents approximately
10% of all subjects with
asthma
•
Classification of asthma severity in
patients who have severe asthma
exacerbations
Expert Panel Report 3
• Environmental control to reduce
exposures
• Consideration of subcutaneous
immunotherapy for patients who have
allergies and require care at steps 2 to 4
when there is a clear relationship between
symptoms and exposure to an allergen to
which the patient is sensitive.
Expert Panel Report 3
• Integrate asthma self-management
education into all aspects of asthma care
• Provide to all patients a written asthma
action plan that includes instructions for
both daily management and actions to
manage worsening asthma
Expert Panel Report 3
• Recommend influenza vaccination
• Consider pneumovax
Asthma/Special situations
• Occupational Asthma
• Constitutes 15% of all asthma
• Up to 30% of new-onset adult asthma
• One out of every 7 to 10 cases of adult asthma
is caused by workplace exposures.
Occupational Asthma
• New-onset asthma as an adult
• Symptoms worse at work or at night on
workdays
• Symptoms worse with specific exposures
• Improved symptoms on vacation, over
weekends, or other times away from work
• Presence of work-related rhinitis or
conjunctivitis
Occupational Asthma
• The most practical approach is to document
work-related changes in pulmonary function
• Serial peak flow recordings are most
frequently used and the most easily accessible
test
• The currently recommended method is for the
patient to record his or her peak flow at least
four times daily (on awakening, middle of work
shift or lunch, end of work shift, and before bed)
Question
Which of the following is the most frequent
cause of occupational asthma?
A) Toluene di-isocyante
B) Western cedar wood dust
C) Coffee leaves
D) Cotton fiber dust
E) Detergent enzymes
Asthma: Occupational Etiology
•
•
•
•
Isocyanates Cotton Dust Wood Dust –
Antibiotics –
Commonest
Byssinosis
Western Cedar
Manufacture
Reactive Airways Disease
Syndrome RADS
• Single massive irritant chemical exposure
• No prior hx of asthma or allergy
• Airways damaged by the exposure
• Patient is left with reactive airways for life
Asthma/Special situations
• Presentation : chronic cough
“cough variant asthma”
• Asthma one of main causes of
unexplained chronic cough
• Trial of albuterol
• Methacholine challenge
“Cough Variant Asthma”
• The most common causes of chronic cough are
asthma, postnasal drip syndrome (chronic
sinusitis-rhinitis), and gastroesophageal reflux
disease (GERD)
• The diagnosis of cough-variant asthma is
suggested by the presence of airway
hyperresponsiveness and confirmed when
cough resolves with asthma therapy
Asthma/Special situations
• Exercise induced bronchospasm (EIB)
• Asthma occurs during rest from exercise
– Diagnose EIB by a thermal challenge - either
exercise or hyperventilation or
– Provocation with cold or dry air
– Fall of FEV1 of 15% following exercise
Exercise induced bronchospasm
• Sensitivity to cold air is a clinical marker of
airway hyperresponsiveness that can also be
confirmed with a methacholine challenge test.
• The methacholine challenge test has a negative
predictive value of nearly 100% in the context of
cough; this test is extremely useful in ruling out
asthma
EIB
• Inhaled β2-agonists will prevent EIB for more
than 80% of patients
• A warm-up period before exercise may reduce
the degree of EIB
• A mask or scarf over the mouth may attenuate
cold-induced EIB
• Daily chromolyn, nedocromil, Leukotriene
inhibitors
Asthma/Special situations
Allergic Bronchopulmonary Aspergillosis
(ABPA)
• ABPA involves growth of the fungus within
mucus plugs in asthma patients
• Usually presents as refractory asthma
responding only to oral corticosteroids with
recurrent pulmonary infiltrates
ABPA Profile
• Asthma
• Elevated total IgE level >417 IU (1000
ng/mL)
• Eosinophilia > 5%
• Positive immediate skin test (prick
test)**
• Central bronchiectasis
ABPA
• Treatment is prednisone, initially 0.5 mg
per kilogram with gradual tapering
• Azole antifungal agents as adjunctive
therapy may also be helpful
• End-stage ABPA often involves lung
fibrosis if untreated
Question
Mary has moderate persistent asthma and a
positive pregnancy test. You would expect
her asthma symptoms to:
A) Get better
B) Get worse
C) Stay the same
Asthma and Pregnancy
• The most common medical condition to
complicate pregnancy
• 1/3 better, 1/3 same, 1/3 worse
• Episodes requiring emergency department
visits or hospitalization have been reported
in 9–11% of pregnant women managed by
asthma specialists
Asthma and Pregnancy
Poorly managed asthma during pregnancy
is associated with a higher risk of:
• preterm delivery
• low birth weight
• complications such as preeclampsia
Asthma and Pregnancy
• The principles of management of asthma
during pregnancy are not different from
those recommended for nonpregnant
women
• Asthma attack carries more risk to fetus
than use of asthma medications
• A 20-year-old woman has episodic wheezing and
dyspnea without cough or sputum production.
• Between episodes, examination and pulmonary function
testing, including methacholine challenge, have been
normal. She is otherwise healthy and takes no
medications.
• She has inspiratory and expiratory wheezing. She is
afebrile with pulse rate of 100/min, respiration rate of
24/min; oxygen saturation on ambient air is 96%.
• After receiving albuterol and intravenous corticosteroids,
she continues to wheeze and appears in moderate
respiratory distress.
• Oxygen saturation on ambient air remains at 96%.
Chest radiograph shows decreased lung volumes.
Asthma
Which of the following is the most appropriate management
for this patient?
A) Chest CT scan
B) Intravenous aminophylline
C) Intravenous azithromycin
D) Intravenous terbutaline
E) Laryngoscopy
Vocal cord dysfunction (VCD)
• This patient likely has vocal cord dysfunction
(VCD)
• Difficult to differentiate from asthma
• Affected patients do not respond to the usual
asthma therapy, oxygenation is not affected,
and inspiratory wheezes are prominent (not
expected in mild to moderate asthma)
VCD
• Laryngoscopy, when done while the patient is
symptomatic, can reveal characteristic
adduction of the vocal cords during
inspiration
• Characteristic Flow-Volume loop
Chronic Obstructive Lung
Diseases
Which one of the following statements
regarding COPD is not true?
A) It is the only leading cause of death with an
increasing prevalence
B) The prevalence of COPD in adults is estimated
at 4–10%
C) 15% of COPD patients have never smoked
D) There is a direct relationship between packyears of smoking and functional impairment
E) Most COPD mortality is due to acute-on-chronic
respiratory failure
Answer
E. Acute-on-chronic respiratory failure is the
cause of death in about 38% of patients.
Heart failure, pulmonary infection,
pulmonary embolism, cardiac arrhythmia,
lung cancer, and other malignancies are
responsible for the majority of deaths
COPD
• A preventable and treatable disease
characterized by airflow limitation that is:
– Not fully reversible
– Slowly progressive over time
– Punctuated by acute episodes of clinical
deterioration
• Associated with an abnormal
inflammatory response of the lung to
noxious particles or gases
COPD
• The overall prevalence of COPD in adults
is estimated at 4–10%
• Estimated to affect 24 million Americans,
half of whom have conditions that remain
undiagnosed
• 120,000 deaths annually in USA
COPD
• Cigarette smoking is the most important
risk factor
• Accounts for 80% to 90% of the risk
• About 15–30% of smokers develop
COPD
Asymptomatic smokers
– Health assessment- “know your flow”– FEV1-Decrease 30mL/ yr is normal
– 50-80 ml/yr in susceptible smokers COPD
COPD
• Approximately 15% of COPD may be
attributable to workplace exposures
– agricultural dust (farming)
– occupational exposure to inorganic dust
– occupational exposure to irritant gases, fumes
or vapors
COPD
• COPD should be suspected in persons
presenting with cough, dyspnea, or
increased sputum production, especially
those with a history of smoking
• GOLD Stage 0 – At risk
Gold Staging Criteria
Pharmacotherapy
Gross N. J. Mayo Clin Proc. 2008;83:1241-1250
© 2008 Mayo Foundation for Medical Education and Research
Theophylline
• A methylxanthine (theophylline) could be
used in addition to these treatments or as
an alternative in patients intolerant of β2agonist adverse effects
• Mechanism for improvement is not solely
bronchodilation from phosphodiesterase
inhibition
Theophylline
• The doses currently recommended
(approximately 300 mg once daily at
bedtime or 200 mg every 12 hours) are
unlikely to carry a risk of toxicity.
• Monitoring blood levels at low dosages
(plasma concentrations of 5-10 mg/L) is
not necessary.
Question
• 56 y/o male with hypertrophic cardiomyopathy and peptic ulcer has taken
theophylline for his COPD with good
results. His theophylline level consistently
runs 12-13 mcg/dl. His new doctor has
taken him off his metoprolol and cimetidine
– but his pulmonary meds stay the same.
Question
You would expect his pulmonary symptoms
to:
A) Stay the same
B) Get better
C) Get worse
Theophylline
Decreases level
• Rifampin
• Dilantin
• Phenobarbital
• Carbamazepine
• Smoking
Increases level
• Acyclovir
• Cimetidine*
• Macrolides
• Fluoroquinolones
• Propranolol*
• Allopurinol
• Zafirlukast
Theophylline
• Theophylline use may decrease serum
levels of:
– Lithium
– Phenytoin
COPD
COPD
• None of the existing medications for
COPD have yet been shown prospectively
to modify the long-term decline in lung
function
• Pharmacotherapy is used to decrease
symptoms and reduce complications such
as acute exacerbations
Question
Which one of the following statements about
smoking cessation is not true?
A) It is the only intervention able to reduce the
progression of COPD
B) It is essential for optimal effects of supplemental
oxygen
C) 10 years after quitting lung cancer risk matches the
normal population
D) Nicotine reduction therapy increases success
E) The largest improvements in lung function and
symptoms occur within the first year
Smoking cessation
• The most important (and cost-effective)
intervention
• The only intervention able to reduce the
progression of COPD
– patients who quit smoking experience less
respiratory symptoms and hyperresponsiveness than those who continue to
smoke
Smoking cessation
• The largest improvements in lung function and
symptoms occur within the first year after
cessation
• The rate of decline in lung function is slower
among persons who quit smoking
• 10 years after quitting: The lung cancer death
rate is about half that of a continuing smoker's
Smoking cessation
• With good smoking cessation programs, 20 to 40
percent of participants are able to quit for at least one
year.
• Brief clinical interventions by health care providers
can increase the chances of successful cessation, as
can counseling and behavioral cessation therapies.
• The use of a pharmaceutical product in concert with
counseling doubles a person's chances of success
Flu Vaccine
• Immunization against influenza in COPD is
associated with:
– A 52% reduction in hospitalizations for all
episodes of influenza and pneumonia
– A 70% reduction in deaths from all causes
– A significant cost savings
Pneumococcal Vaccine
• The role in COPD is less clear.
• Although pneumococcal vaccine has
shown to reduce mortality and
hospitalization in the general older
population, data for its effectiveness in
patients who have COPD are sparse
Question
Most insurance companies are willing to pay for
pulmonary rehab programs because:
A) Rehab pts have fewer hospitalizations
B) PFTs usually improve by more than 15%
C) Improvement in ABGs is typical
D) All cause mortality is decreased
E) None of the above
Pulmonary rehabilitation
• All patients with COPD benefit from
exercise training programs (pulmonary
rehabilitation)
• Reduces dyspnea, anxiety and
depression, improves exercise capacity
and quality of life
• May reduce hospitalizations
Pulmonary rehabilitation
• Does not change Pulmonary function
measurements
• Does not change ABGs
• Does not decrease mortality
Oxygen
• Long-term oxygen administration (>15 h
per day) has been shown to improve
survival in patients with chronic respiratory
failure
• It is the only therapy that increases their
life span
Chronic O2 use in COPD
• Criteria for chronic (continuous) O2 use:
• Resting PaO2 < 55 or O2 sat < 88%
• PaO2 < 59 mmHg or Sat 89% with evidence of
cor pulmonale or erythrocytosis (hct > 55%)
• Patients who qualify as above should be on
oxygen 24 hours a day
Chronic O2 use in COPD
• Some patients desaturate with exercise
or while sleeping
• Survival benefit is unproven
• If prescribe supplemental O2 in the
hospital you should re-evaluate the
continued need after 2 months
– Rule of 21
Surgery
• In addition, lung volume reduction surgery
or lung transplant may be considered in
selected patients
Question
• A 36-year-old woman has had increasing
dyspnea for 8 years. She has no cough or
increased sputum production. On physical
examination there is hyperresonance to
percussion in the bases. A chest radiograph
reveals increased lung volumes with flattening of
the diaphragmatic leaves bilaterally. Which of
the following laboratory findings is she most
likely to have?
Question
A) Positive metacholine challenge test
B) Increased sweat chloride
C) Decreased alpha-1-antitrypsin
D) Elevated serum iron stores
E) Decreased ceruloplasmin
Emphysema
• Emphysema is the permanent enlargement of
the airspace distal to the terminal bronchioles
with destruction of the alveolar septa
• Destruction is due to imbalance between
proteases and antiproteases
– Increased protease activity
• proteolytic elastase from neutrophils (tobacco
smoke)
– Decreased antiprotease
• Alpha-1-antitrypsin deficiency
COPD
• 3-5% of COPD is genetic
• Due to a severe hereditary deficiency of
alpha1-antitrypsin
• Most common in Caucasians
– 96% of AAT deficiency patients have a
ZZ genotype
COPD
• GOLD recommends α1-antitrypsin
screening in white patients who develop
COPD before the age of 45 years or in
those with a strong family history of COPD
Alpha-1-antitrypsin deficiency
Panacinar alpha-1-antitrypsin deficiency
• 3%-5% of emphysema from alpha-1 deficiency
• Smoking exacerbates emphysema formation in
A1A deficiency
• Alpha-1-antitrypsin deficiency: bullae in the
lung bases rather than apices
• Onset in late 30’s rather than late 40’s
Question
• A 23 year old female patient presents with
dyspnea and persistent cough that is often
productive. Chest radiograph suggests
areas of bronchiectasis and her sputum
culture grows Burkholderia cepacia. Which
of the following laboratory findings is she
most likely to have?
Question
A) Positive metacholine challenge test
B) Increased sweat chloride
C) Decreased alpha-1-antitrypsin
D) Elevated serum adenosine deaminase
E) Decreased serum hyaluronic acid
Cystic fibrosis
• About 1,000 new cases each year
• 70% are diagnosed by age 2
• Sweat chloride > 60 mMol
– Genetic screening CFTR F508
• 4% are not diagnosed until older than 18 yrs
– typical age at adult diagnosis 26yrs
Cystic fibrosis
• 40% of the CF patient population is age 18
or older
• Expected median survival of childhood CF
is now 38 yrs
Cystic Fibrosis
• Chronic unexplained pulmonary symptoms
– Less severe than childhood form
– Often misdiagnosed
• Usually infected
– Pseudomonas, especially mucoid strains
– Staph spec.
– Burkholderia cepacia
• Sweat chloride > 60 mMol
– Genetic screening CFTR F508
Cystic Fibrosis
Complications
– Bronchiectasis
– Hemoptysis
– Pneumothorax
– Infections
• ABPA
• Mycobacterium avium intracellulare
Cystic Fibrosis
• Usually treated in specialized centers
– Inhaled DNase for improving mucociliary
clearance.
– Inhaled tobramycin as maintenance
therapy
– Transplant: bilat, +/- heart — 50% 3 yr
survival
Interstitial Lung Diseases
Interstitial Lung Disease
• A diverse group of
disorders that affect
the supporting or
architectural tissue
of the lung,
especially structural
portions
of the alveolar walls
Interstitial Lung Disease
• If alveolitis is not
addressed then
chronic insult
results in
irreversible
healing by either
fibrosis or
granuloma
formation
Interstitial Lung Disease
• The parenchymal
healing involves the
deposition of
abnormal collagen
and fibrosis
• The lung becomes
“stiffer” and its
expansion is
“restricted”
Interstitial Lung Disease
•
•
•
•
Exertional dyspnea or cough
Diffuse radiographic disease on CXR
Restrictive pulmonary function
Abnormal gas exchange
parameters (DLCO)
• Abnormal high resolution CT of chest
Late Symptoms
•
•
•
•
Gradual progressive hypoxemia at rest
Dry, nonproductive cough
Pulmonary hypertension
Weight loss, malaise and fatigue may be
noted
• Fever is rare and should suggest another
dx
Physical Examination
• Crackles/dry rales (velcro) in 80%
– Most prevalent in the bases
• Clubbing present in 25-50%
• Cor pulmonale with accentuated P2 in late
phase
• Peripheral edema due to cor pulmonale
HRCT
• The diagnostic
sensitivity of
HRCT for ILD is
94% compared
with 80% for
chest
radiography
HRCT
• Ground glass opacity on HRCT scans
predicts the response to treatment and
increased survival compared with patients
in whom the predominant HRCT
abnormality is a reticular pattern
– Ground glass opacity = alveolitis
– >25% suggests treatment may be helpful
ILD
• The combined information from clinical,
laboratory and HRCT findings allows a
correct diagnosis to be made in the
majority of patients with ILD
• Most will not need open lung biopsy
Occupational/Environmental
Inhalation Exposure
• Organic material – hypersensitivity
pneumonitis
– Granulomatous nodules
– Lymphocyte driven
• Inorganic material – pneumoconiosis
– Fibrotic nodules
– PMN driven
Hypersensitivity Pneumonitis
• An immune reaction (granulomatous)
localized to the lung caused by
inhalation of organic antigens following
a period of sensitization
• Acute - cough, fever, dyspnea, fleeting
infiltrates (usual stimulus = birds)
• Chronic- may progress to chronic
irreversible state (ILD)
Acute Hypersensitivity Pneumonitis
• History of recurrent ‘pneumonias’
• Temporal relation to organic trigger
• Serum precipitins are nonspecific and
represent exposure, not necessarily disease.
• No eosinophilia (distinguish from eosinophilic
pneumonia)
– Type III and Type IV reactions
Acute HP
Hypersensitivity Pneumonitis
Farmer's lung
Moldy hay
Micropolyspora faeni
Bagassosis
Moldy sugar cane
Thermoactinomyces
sacchari
Grain handler's
lung
Humidifier/airconditioner lung
Bird breeder's lung
Moldy grain
Thermoactinomyces
vulgaris
Contaminated
heated water
Pigeons,
parakeets
Cotton fiber
T vulgaris
Byssinosis
Avian or animal
proteins
Gram negative
endotoxin
Hypersensitivity Pneumonitis
• Mainstay of treatment is antigen
avoidance
• Steroids for severe attacks
HP natural history - untreated
Question
• A 66-year-old man has had increasing dyspnea
for about a year. He is a smoker. He is retired
from the construction business. There are
some crackles in both lungs. A chest radiograph
reveals diffuse interstitial lung disease with
indistinct diaphragms and a shaggy heart
border. Pulmonary function studies reveal a low
FVC and a normal FEV1/FVC ratio. These
findings are most likely to suggest prior
exposure to which of the following environmental
agents?
Question
A) Berrylium
B) Silcates
C) Asbestos fibers
D) Iron particles
E) Cotton fibers
Inorganic Dusts - Asbestosis
CXR pattern is highly suggestive
• Pulmonary fibrosis (reticular opacities)
concentrated at the bases of the lungs
• Shaggy heart border
• May have associated:
– Pleural thickening or plaques
– Calcification of plaques and/or diaphragm
Asbestos Exposure
• Parenchymal
fibrosis
• Concentrated
at bases
• Shaggy heart
border
Asbestos Exposure
• Pleural plaques
• Calcification in
diaphragm
Inorganic Dusts - Asbestosis
• Asbestosis is the pulmonary parenchymal
fibrosis and impairment caused by prolonged
exposure to asbestos
• Classic features of ILD
• Significant exposure > 10 years
• Long latency period 20-30 years
Asbestos - Pleural Plaques
• Benign, midthoracic pleural plaques
and thickening
• May or may not have asbestosis
•
• Also seen on diaphragm
• Can calcify
• Do not become mesotheliomas
• Do not signicantly impair PFTs
• 20-year latency
Asbestos exposure
• Independent risk factor for bronchogenic
carcinoma
• Smoking + asbestos exposure multiplies
risk
• Squamous and adenocarcinoma
Asbestos exposure
• Malignant mesothelioma - rare but 80% have
asbestos exposure
• Requires less exposure but longer latency
• Incidence unaffected by smoking
• Can occur in the pleura or the peritoneal cavity
• No current effective therapy
• Mortality within 12 months from onset of
symptoms
ILD - Silicosis
• Stone masons, quarry
worker’s, grinder’s,
foundry workers
• Characteristic CXR
– Upper lobe distribution of
fibrosis
– Egg shell calcification in
hila (10%)
Silicosis
• Silica exposure markedly increases the risk of
developing active tuberculosis and other
mycobacterial disease.
– 3x risk of general population
• Screen patients with silicosis for tuberculosis
• All patients with a positive test result (>10 mm of
induration) should receive INH prophylaxis
ILD - Connective Tissue Diseases
All connective tissue diseases can result in
pulmonary fibrosis and ILD
•
•
•
•
•
Rheumatoid arthritis
SLE
Scleroderma*
Sjogren’s (lymphocytic interstitial pneumonitis)
Dematomyositis/polymyositis
Scleroderma Lung
• Diffuse pulmonary fibrosis in 80%
• Pulmonary involvement more severe in
– Diffuse systemic slerosis
– Less so in the CREST variant
• Pulmonary hypertension*
Scleroderma
• A subset of patients develop rapidly
progressive ILD during the first 2 years of
their disease
• Spirometry and diffusion testing should be
mandatory at the time of diagnosis
• should have annual lung function testing
early in disease
Scleroderma
• Patients with declining DLCO or DLCO
<50% predicted should have transthoracic
echocardiography performed
• Long-term warfarin therapy should be
prescribed in patients with CTDassociated pulmonary artery hypertension
CTD - associated ILD
• For the majority of CTD-ILD, the
recommended initial treatment is oral
prednisolone at an initial dose of 0.5–1
mg/kg
• The exception of systemic sclerosis (SSc)
Scleroderma - ILD
• Recommended treatment, if required, is
with low-dose oral steroids (10 mg/day)
and/or cyclophosphamide
• High-dose corticosteroid treatment (daily
prednisolone dose >10 mg) should be
avoided if at all possible because of the
risk of renal crisis
Question
• A 24 y/o African American male applies for
work in the steel mill. He has a negative
health history and a normal review of
systems. A routine CXR is performed and
you are asked to review it.
Question
The patient should be advised to:
A) Submit 3 sputums for cytology
B) Submit 3 sputums for AFB
C) Get HRCT of the chest
D) Start glucocorticosteroids
E) Start work on Monday
Sarcoidosis - Stage I
• Typical exam presentation is a young
asymptomatic patient with incidental finding of
bilateral hilar adenopathy on CXR done for
another reason
• If patient is asymptomatic with large hilar nodes,
lymphoma is not likely
• Bronchoscopy with biopsy if you’re asked to
prove it
Sarcoidosis
• Excluding patients with stage I disease,
sarcoidosis is the second most common
interstitial lung disease
• The incidence of sarcoidosis appears to
be higher in Scandinavian countries and in
Afro-Caribbean people, and also
marginally higher in women
Sarcoidosis
• USA data suggest that females and AfroCaribbean people have an increased
morbidity and mortality
• Presentation varies from asymptomatic
(33%) to systemic disease
Sarcoidosis
• Increased ACE levels (80%)
– Does not establish a diagnosis; serum levels
increased in 5% of normal patients
– Is helpful in monitoring disease
• Noncaseating granulomas are not diagnostic of
sarcoid
• Diagnosis of exclusion
Sarcoidosis
• Diagnosis: Bronchoscopy with
transbronchial or bronchial wall biopsies
• EBUS is alsoexcellent for diagnosis
• Look for noncaseating granuloma*
– Exclude other granulomatous diseases:
berylliosis, hypersensitivity pneumonitis,
mycobacterial or fungal
Sarcoidosis
• Lofgren’s syndrome:
– Fever, arthralgias, erythema nodosum
– Usually means quick remission
• Heerfordt’s syndrome:
– Salivary gland involvement, uveoparotid fever
Sarcoidosis
• No consensus on many aspects of
treatment
• Remember spontaneous remission is
expected in most Stage I and Stage II
patients
– 75% recover without treatment
– 10-20% progress to further stages
Sarcoidosis
• Corticosteroids are used :
– Progressive or severely symptomatic
– Uveitis
– Neurosarcoidosis
– Cardiac or spleen involvement
– Hypercalcemia, hypercalciuria
(Methotrexate is an alternative)
ILD - Drugs and Poisons
• Chemotherapy medications
• Antibiotics
• Radiation therapy
Question
Which of the following agents is least likely
to cause ILD with chronic use?
A. Nitrofurantoin
B. Beta blockers
C. Calcium channel blockers
D. Amiodarone
E. Bleomycin
Drugs
• Nitrofurantoin
• Methotrexate
•
•
•
•
Bleomycin
Mitomycin C
Amiodarone*
Beta blockers
Idiopathic Pulmonary Fibrosis
• IPF accounts for 40-50% of ILD but
remains a diagnosis of exclusion
• Unidentified autoimmune trigger
• Age 40-70, equal gender involvement
• No extrapulmonary manifestations
(except clubbing)
IPF – Diagnosis HRCT
• Diagnosis can be made 90% of time by
trained radiologists
– Patchy, peripheral, subpleural, bibasilar
reticular pattern with ground glass opacities
– Traction bronchiectasis and bronchiolectasis
+/- subpleural honeycombing may be present
IPF - Lung Biopsy
• Via open thoracotomy or VATS
– Is specifically helpful if atypical radiologic
findings are present
– Rarely establishes etiology of ILD
• Transbronchial biopsy, TBB
– may be helpful in dx other disease that
mimics IPF but not for IPF itself
IPF - Disease Course
• Progresses in a relentless and insidious
manner
• Spontaneous remissions do not occur
• Mean survival from time of dx is 2-4 years
with a 5 year survival of 30-50%.
IPF - Treatment
• No pharmacologic therapy proven to be
beneficial
– Corticosteroids
– Azathioprine
– Cyclophosphamide
– MTX or chlorambucil
– Interferon gamma
Pleural Effusions
Question
Which one of the following observations does not
apply to pleural effusion?
A) After work-up, 20% remain unexplained
B) The cause of effusion is below the diaphragm 20% of
the time
C) CHF causes unilateral left effusion only 20% of the time
D) Transudates are misclassified as exudates 20% of the
time
E) Without ultrasound marking, about 20% of
thoracenteses result in PTX
Diagnostic Thoracentesis
• Done to establish general nature of the
fluid
– Transudative vs. Exudative
• Performed on approximately 50 cc of fluid
• Key markers are the pleural/serum ratios
of LDH and protein
Transudative Pleural Effusion
• A transudate is present if none of the
following is present:
– pleural/serum protein > 0.5
– pleural/serum LDH > 0.6
– Absolute LDH value > 2/3 normal value for
serum, usually > 200 IU
Separating Transudates
from Exudates
• Examining only LDH and protein initially is a
potential savings
• If a transudate the work up can be stopped
without further testing and expense
• Save the other tubes to send for other tests
only if exudative
Transudative Effusions
• If a pleural fluid is a transudate then it can
be attributed to an imbalance of
hydrostatic forces
• No further investigative procedures
need to be done
Transudative Effusions
• The most common causes are:
– CHF (500,000/yr)
– Cirrhosis (50,000/yr)
– Nephrosis
– Hypoalbuminemia
Exudative Pleural Effusion
• An exudate is suggested if one of the
following is present:
– pleural/serum protein > 0.5
– pleural/serum LDH > 0.6
– Absolute LDH value > 2/3 normal value for
serum, usually > 200 IU
– Correct classification 80% of the time
Exudative Pleural Effusion
• 20% of the time a transudate may look like
an exudate by LDH or protein criteria
• If a transudate then:
– Pleural cholesterol less than 45
– Pleural fluid/serum albumin ratio > 1.2
Exudative Effusions
• The most common causes are:
– Bacterial pneumonia (300,000/yr)
– Malignancy (200,000/yr)
– Pulmonary embolism (75,000/yr)
– Tuberculosis
Parapneumonic Effusion
• The most common exudative pleural
effusion in the USA is associated with
bacterial pneumonia
• An analysis of the fluid is required to
determine if antibiotic therapy will be
sufficient or if the fluid needs to be drained
Parapneumonic effusion
• Considered uncomplicated when:
– There is no pus in the pleural space
– Organisms are not present on Gram’s stain or
culture
– pH >7.2
• Antibiotics alone will do the job
Parapneumonic Effusion
• Considered to be complicated when:
– There is pus in the pleural space
– Organisms are present on Gram’s stain or
culture
– pH < 7.20
• Space needs to be drained
Malignant Effusion
• Generally large > 50% hemithorax
• Quick to reaccumulate
• Generally lymphocytic WBC’s
• Often bloody
– 3 “T’s” = tumor, trauma, thromboembolism
Exudative Effusions: Cytology
• 1st sample 60% yield
• Three separate samples = 90% yield
• Yield not significantly increased by blind
needle biopsy!
– Cope
– Abrams
Tuberculous Effusion
• AFB recovered in only 10%, but yield can
be increased with up to 3 taps
• Culture for AFB is positive in 65%
• Pleural biopsy and culture together identify
85%
• Blind pleural biopsy may be helpful
Tuberculous Effusion
• Adenosine deaminase levels may be
helpful
– Levels > 50 U/L 94% sensitive & 90% specific
– Levels < 45 U/L 100% sensitive and specific
for nontuberculous etiology
• Mesothelial cells are rarely present
Undiagnosed Effusions
• Pleural fluid studies yield Dx in 80% cases
• Undiagnosed exudative pleural fluids
should have:
– Repeated thoracentesis (up to 3 taps)
– Bronchoscopy if there is cough or other CXR
changes
– Consideration of Pulmonary embolism
– Pleural biopsy if considering TB
Pulmonary Vascular Diseases
Diagnose pulmonary disease
Chronic
Bronchitis
Emphysema
↓
↓
↑
nl
TLC
nl
↑
↓
nl
DLCO
nl
↓
↓
↓
FEV1/FVC
Pulmonary
Fibrosis
Pulmonary
vascular
disease
Pulmonary Vascular Disease
• Suggested when pulmonary
symptoms occur with “normal”
appearing CXR
• Pulmonary Hypertension
• Pulmonary Embolism
Pulmonary Hypertension:
Diagnosis
• Physical: Loud 2nd heart sound (P2),
tricuspid regurg, RV heave
• EKG: Right Axis Deviation
• CXR: Prominent PA’s and Hilar vessels
Pulmonary Hypertension
Echocardiogram:
• First test
• Estimates PA pressures, RV
function
• Can identify a R to L shunt
• Identifies any cardiac causes
Pulmonary Hypertension
• Mean Pulmonary Artery Pressure
– > 25 mm Hg at rest
– > 30 mm Hg during exercise
• Symptoms present when > 45 mm Hg
Primary Pulmonary Hypertension
•
•
•
•
•
Predominantly in young women
Ages 20-40 years
Unknown cause
Rare - 500-1000 new cases/yr USA
Exertional dyspnea, fatigue, syncope and
chest pain
• Sporadic or Familial
Primary Pulmonary Hypertension
Right Heart Catheterization:
•
•
•
•
Increased RA and right side pressures.
Increased pulmonary vascular resistance
PADP usually > 20 mm Hg
Mean PAP > 25 mm Hg at rest
• PCWP is normal
• There can be no co-existent cardiopulmonary
disease for accurate diagnosis
Primary Pulmonary Hypertension
• Trial of vasodilators only during right heart
cath since hemodynamic collapse can occur
• Responders first get Calcium Channel
Blockers (25%)
– the primary treatment modality, and titration to
high doses appears to slow the progression of
the disease
Primary Pulmonary Hypertension
• Non repsonders to CCB:
– Prostacyclin by IV infusion pump
• Concerns are complications and tachyphylaxis
– Bosentan - an oral endothelin
receptor antagonist
• Concerns are hepatic insufficiency
Monitor LFT’s monthly
– Sildenafil (?) and others
• Heart-lung transplantation
Secondary Pulmonary Hypertension
•
•
•
•
•
•
•
Chronic hypoxemia
Silent recurrent PE
Sickle cell disease
Atrial Septal Defect
Left ventricular failure, mitral stenosis
IV drug use
Obstructive sleep apnea*
Sleep Disordered Breathing
Sleep Disordered Breathing
• Snoring, apnea, restlessness sleep, daytime
somnolence, cognitive impairment
• Apnea is cessation of airflow for at least ten
seconds
• Sleep apnea syndrome: >10 apneic spells an
hour during sleep study
Polysomnography
Sleep Apnea
• Obstructive - continued respiratory effort
during the absence of airflow
• Central - absence of effort and airflow
Types of Apnea
OSA
• More than 15-20/hr
requires treatment
• Treatment of OSA:
– Weight loss for mild
– Nasal CPAP or BiPAP
for moderate/severe
Treatment of OSA
• Weight loss
• Avoid sedatives, ETOH
• Nasal CPAP/BiPAP- splints the pharynx
• Severe: tracheostomy
• Uvulopalatopharyngoplasty eliminates
snoring but only 50% effective
at relieving sleep apnea
Central Sleep Apnea
• Disruption in central ventilatory drive or
neuromuscular control of respiratory
muscles
• Treatment: acidification with
acetazolamide, supplemental O2, CPAP
Narcolepsy
•
•
•
•
Severe daytime hypersomnolence
Cataplexy
Sleep paralysis
Hallucinations when drowsy
• Polysomnography and Multiple Sleep Latency
Test (MSLT) checks hyper-somnolence and
frequency of rapid eye movement (REM)
• Treat: stimulants and REM suppression by
tricyclic antidepressants and selective
serotonin reuptake inhibitors
Restless Leg Syndrome
•
•
•
•
Paresthesias that improve with movement
Worse in the evening and at night
Can cause insomnia
Associated with periodic limb movement
disorder - contraction of the anterior tibialis
muscle during sleep
• Treat: dopaminergic agonists/narcotics
Lung Cancer
Epidemiology of Lung Cancer
• #2 in men, #3 in women
• Leading cause of death from cancer in
both men and women in the United
States
Lung Cancer
• Smoking  risk 20-40 fold
• Asbestos exposure  risk 4 fold
• Together  risk 80 fold
• Silicosis  risk 1.3 fold
• Idiopathic pulmonary fibrosis  risk
• Uranium exposure  risk of SCC
• Radon, formaldehyde, nickel exposure may
increase risk
• Genetics
Lung Cancer
• Only 5% are asymptomatic
• Cough is most frequent symptom
• Dyspnea
• Hemoptysis (35-50%)*
• Obstructive pneumonitis*
The Solitary Pulmonary Nodule
• Nodule in middle to lateral 1/3
of the lung surrounded by normal tissue
• 35% are malignant
Solitary Pulmonary Nodule
• Tumor until proven otherwise
– Do not get sidetracked by PPD, serology, or
remote history
• Can watch only if:
1. There is no growth in 2 years when
compared to an old film
2. There is patterned calcification in the lesion
Solitary Pulmonary Nodule
The rumor is tumor
Tissue is the issue
Heal with steel
When in doubt, cut it out
Solitary Pulmonary Nodule
• CT scan assures that lesion is solitary and
helps define if calcium is present in lesion
• FOB not helpful if lesion is < 3 cm in size
• PET scan may predict cancer probability
– Its role is not yet determined
• FNA (??) or Surgery
Lung Cancer - TNM staging*
• KNOW WHO IS OPERABLE
• Stage IIIa and under are operable
• KNOW WHO IS INOPERABLE
T4 = direct invasion of mediastinum/vasculature
N3 = contralateral mediastinum or hilar lymph nodes or
any scalene or supraclavicular nodes
M1= distal mets
A Change in Strategy
National Lung Screening Trial
• Reduced lung-cancer mortality with lowdose computed tomographic screening. N
Engl J Med. 2011 Aug 4;365(5):395-409.
• Low-dose spiral CT annually x 3 years
NLST
• The recommendations are that CT screening
should be offered to smokers and former
smokers, aged 55-74, with more than 30
pack years of smoking
• CT screening is not recommended for
individuals with fewer than 30 pack years of
smoking, younger than 55 or older than 74,
with severe comorbidities that would preclude
potentially curative treatment or limit life
expectancy.
Question
• A 50-year-old woman has had a cough with production
of sputum for the past month. She is afebrile with
decreased breath sounds at the right lung base. A chest
radiograph reveals an area of consolidation in the right
lower lobe with air bronchograms. She is given antibiotic
therapy, but when seen 2 months later the radiographic
picture has not improved, and her cough continues. She
states that her sputum is clear but has a “bad” taste to it.
• Which of the following is the most likely diagnosis?
Question
A) Histoplasmosis pneumonia
B) Tuberculosis
C) Blastomycosis pneumonia
D) Bronchoalveolar cell carcinoma
E) Obstructive pneumonia from squamous
cell carcinoma
Bronchoalveolar carcinoma
•
•
•
•
•
Subclass of adenocarcinoma
1/3 never smokers
2:1 ratio of women to men
represents only 2% to 3% of all NSCLCs
May mimic pneumonia in appearance
– Persistent pneumonia
• Bronchorrhea is typically seen
– Frothy sputum
– Salty taste (K+)
Bronchoalveolar carcinoma
•
•
Inclined to stay within the lung and is
less likely to spread to other organs
Has a better overall survival when
matched stage for stage with other
NSCLCs
Superior Sulcus Tumor
Pancoast’s tumor
– Presents with shoulder pain
• May show you a shoulder film
– May have Horner’s syndrome
– Most commonly squamous cell (52%)
– Is usually operable
– MRI is used to evaluate brachial plexus and
plan surgery
Paraneoplastic Syndromes
• Primary lung tumors cause most
paraneoplastic syndromes
• Paraneoplastic syndrome does not
indicate metastatic spread
• Paraneoplastic syndrome does not
indicate unresectability
Paraneoplastic Syndromes
•
•
•
•
SIADH
Cushing’s syndrome
Eaton-Lambert
Hypercalcemia
Small cell*
Small cell
Small cell
Squamous cell*
•
•
•
•
Hyperprolactinemia
HPO/Clubbing
Murantic endocarditis
Cerebellar ataxia
Large cell
Adenocarcinoma*
Adenocarcinoma
Squamous cell