a. Objectives:
i.
ii.
iii.
iv.
v.
vi.
vii.
viii.
ix.
x.
List typical symptoms associated with COPD
Differentiate restrictive vs. obstructive lung disorders
Describe the typical CXR findings for COPD patients
Describe the spirometry findings of restrictive lung disease
Describe the spirometry findings of obstructive lung disease
Describe the factors associated with COPD prognosis
Describe the difference between Asthma and COPD
Describe the pathophysiology of Alpha1Antitrypsin deficiency and
Emphysema
Describe the most common medications used of Asthma and
COPD
Describe the diagnosis and treatment of Acute exacerbation of
COPD
USC Case # 5: COPD
Mrs. Elsie Melianos is a patient who is new to Rich Creek, where you are working as a student
with Dr. Brachenrich. Dr. Brachenrich says that it would be a huge help if you could go in first
and find out why Mrs.Melianos is here and do a basic History and Physical.
Before entering the examination room, you look over Mrs. Melianos’ new chart:
Age: 59 y.o.
CC: Shortness of breath
Vital signs: T = 98.9, P = 82 bpm, R = 20 per min, BP = 138/75
Before entering the room, you think about Mrs. Melianos’ chief complaint: Shortness of
breath. Develop a general differential diagnosis for shortness of breath.
The majority of etiologies of dyspnea fall into the categories of pulmonary
etiology, cardiac etiology, or a combination of the two. Other noncardiopulmonary causes are less common.
Pulmonary

Obstructive Lung Disorders
o Asthma
COPD
Upper Airway Obstruction
Restrictive Lung Disorders
o Intrinsic Pulmonary Pathology
 Interstitial fibrosis
 Pneumoconiosis
 Granulomatous disease
 Collagen Vascular disease
o Extrapulmonary causes
 Obesity
 Spine or chest wall deformities
Pneumonia
Pneumothorax
Pulmonary Embolism
Aspiration
ARDS
Hereditary Lung Disorders
o
o







Cardiac









Myocardial ischemia
o Recent or prior
CHF
o Right, Left, or Biventricular
Coronary Artery Disease
Valvular dysfunction
Left Ventricular Hypertrophy
Aysmmetric Septal Hypertrophy
Pericarditis
Arrhythmia
Cardiac Tamponade
Noncardiopulmonary



Metabolic
o Acidosis
Hematologic
o Anemia
Psychiatric
o Anxiety
o Panic disorders
o



Hyperventilation
Pain
Neuromuscular disorders
o MS
o Muscular Dystrophy
Otorhinolaryngeal disorders
o Nasal obstruction (polyps, septal deviation)
o Enlarged tonsils
o Supraglottic/subglottic airway stricture
You enter the examination room and see Mrs. Melianos sitting in a chair reading one of the office
magazines. You introduce yourself and then ask her, “What brings you in to the office today?”
Mrs. Melianos responds, “Well, I’ve been having a lot of shortness of breath recently. My son is
getting concerned and said that I should go see a doctor about it.”
You have already developed a broad differential diagnosis for Mrs. Melianos’ reported
shortness of breath. What questions might you ask her to help you narrow down the
differential?
You will want to obtain a better understanding of Mrs. Melianos’ dyspnea. Some questions to this
point include: (you would use shortness of breath because Mrs. Melianos doesn’t understand the
term dyspnea)







Under what conditions does the dyspnea occur?
o Do you have dyspnea with exertion? If so, how much activity do you have to do
before you develop dyspnea?
o Do you have dyspnea at rest?
When did the dyspnea start?
Since it developed, has it been getting better, worse, or remains unchanged?
Do you have difficulty with breathing when lying flat (orthopnea)?
Do you ever experience waking up from sleep and being short of breath (paroxysmal
nocturnal dyspnea)?
Do you ever notice any swelling of your feet or legs (edema)?
Do you experience back pain or chest pain with the dyspnea?
As well, Mrs. Melianos is a new patient and you have no past medical history, family history, or
social history for her. Some specific questions related to this that are pertinent to her chief
complaint include:






Have you been taking any medications, either prescribed or over-the-counter?
Have you ever smoked? If so how much and for how long?
What jobs have you held in the past?
o Did you ever have any jobs where you were exposed to dust, asbestos, or
chemicals?
Do you have any allergies?
In your family does anyone have asthma or other lung disorders?
Do you have any history of high blood pressure?

Do you have any history of heart disease?
Some additional questions that may help elucidate an etiology are:






Have you been having any feelings of anxiety or panic?
Have you had any trauma to your chest recently?
Have you been experiencing any cough?
Have you been experiencing any episodes of wheezing?
Have you noticed any fevers, chills, or night sweats since the dyspnea began?
Have travelled anywhere recently
Mrs. Melianos answers all of your questions for you. She reports that she cannot tell you exactly
when her shortness of breath began, but she does know that three years ago she did not have
any problems with shortness of breath, unless she walked a long distance (>15 minutes of
walking). She reports that now she has difficulty when she walks to the corner grocery store,
which is one block from her house, but denies any dyspnea at rest. She does report, however,
that she has had a chronic cough and that occasionally she is able to cough up a colorless
sputum in the morning. She denies any episodes of orthopnea or paroxysmal nocturnal dyspnea,
as well as any edema, fever, chills, or night sweats.
When you question her about her past medical history, she reports that she is currently a
secretary at the local community college and has only ever worked as a housewife or a secretary.
She reports that she used to smoke. When you further question her, you find out that she began
smoking when she was around 15 years old and smoked ~1 ½ packs per day until she was 45
years old, at which point she stopped smoking and has not smoked since then. She denies ever
having any allergies. She currently takes one aspirin a day because she heard that “…it is
supposed to help my heart.” She reports that she is otherwise generally healthy and has no
conditions for which she sees doctors or for which she takes medications.
In what ways, if any, has this new information changed your differential diagnosis?
Pertinent positives from Mrs. Melianos’ history:



Progressively worsening dyspnea with exertion; onset appears insidious in nature
Chronic cough with sputum production
Positive history for 45 pack-years of cigarette smoking
Pertinent negatives:




No dyspnea at rest
No orthopnea or PND
No apparent occupational exposures
No history of other significant medical conditions
The information provided by Mrs. Melianos indicates a likely cardiopulmonary disease (dyspnea
on exertion), although not severe enough at this time to have dyspnea at rest. Her history of 45
pack years of smoking puts her at significant risk for chronic bronchitis, emphysema, or asthma,
and her chronic cough with sputum production supports a pulmonary etiology.
What are you going to look for on physical exam related to you differential?
To further elucidate and refine your differential, a good physical exam is critical. Listed below are
aspects of the physical exam, which may yield direct evidence of the etiology of the patient’s
dyspnea.
Components of Physical Exam
Associated Conditions
GENERAL
 What is the patient’s general
Assessment of the patient’s general
appearance?
condition can help in assessing if this is
 Do they appear to be in respiratory
a stable condition, or an acute
distress?
condition/exacerbation, which may
potentially require intubation or other
rapid measures.
HEENT
 Nasal polyps or septal deviation
Oropharyngeal/nasopharyngeal
obstruction
 Postnasal discharge
Allergies
 Expiratory pursing of lips
Increased expiratory effort
 Inspiratory nasal flaring
Lack of adequate air delivery/exchange
NECK
 JVD (Jugular venous distension)
CHF (Congestive heart failure)











Hepatojugular reflex
Bruits
Valvular dysfunction/atherosclerotic
carotid arteries
Use of accessory muscles
Increased work of breathing
THORAX
Increased AP (anteroposterior)
Significant respiratory compromise, as
diameter
in cystic fibrosis or emphysema
Evidence of trauma
Can result in a pneumothorax
Kyphosis or scoliosis
Spine deformities which can restrict
respiration
Tachypnea (>20 breaths per minute)
Many conditions, including anxiety,
hypoxemia, and pain
LUNGS – PERCUSSION
Hyperresonance
Hyperinflation of the lung; seen in
emphysema, pneumothorax, or asthma
Dullness/flatness
Atelectasis, pleural effusion,
pneumothorax, or asthma
LUNGS – AUSCULTATION
Crackles (Rales)
Disruption of air passing through the
lower respiratory tract, especially in the
small airways; often heard in
pulmonary edema and pneumonia
Rhonchi
Passage of air through an obstructed
airway; may be heard in asthma or
tracheobronchitis













Due to high-velocity air flow through a
narrowed airway; heard with reactive
airway disease (asthma),and acute and
chronic bronchitis
Stridor
Heard with a foreign body
CARDIOVASCULAR
Tachycardia
Present in many conditions, including
hypoxia, hyperthyroidism, and heart
failure
Abnormalities in rate or rhythm
May be due to atrial fibrillation
Displacement of PMI
Ventricular hypertrophy or dilatation
Murmurs
Valvular dysfunction
S3
CHF
Abnormalities in peripheral pulses
Peripheral arterial disease
ABDOMEN
Hepatomegaly
May be seen with CHF
EXTREMITIES
Edema
Right-sided heart failure
Cyanosis
Hypoxemia, poor peripheral perfusion
Clubbing
Fibrotic lung disease (cystic fibrosis) or
congenital heart disease resulting in
chronic cyanosis
PSYCHIATRIC
Tremulous, sweating, nervous
Potential anxiety disorder
Wheezes
For more information on this physical diagnosis of the respiratory system see:
Seidel, Henry M; Ball, Jane W; Dains, Joyce E; Benedict, G William. 2003. Mosby’s Guide to
Physical Examination. 5th Edition. Mosby, St. Louis. Chapter 12.
During your exam you find:







Normal head and neck exam
Lungs are clear to auscultation except for an occasional wheeze diffusely throughout.
The expiratory phase is slightly prolonged and there is tachypnea (20 breaths per
minute). There is no evidence of use of accessory muscles.
Cardiovascular exam is normal
Abdominal exam is normal
No edema, cyanosis, or clubbing of extremities
Normal neurologic exam
Positive chronic tissue texture changes and other TART findings in the T1-T5 area
What initial testing would you like to have for this patient?
While there are a number of different modalities that may yield information that is pertinent to your
differential diagnosis, there are some simple and relatively inexpensive diagnostic tools that can
be used, especially with the understanding that the most common causes of dyspnea are
cardiopulmonary in nature. An electrocardiogram, chest radiograph, and CBC (or finger-stick
hemoglobin) are all recommended as initial diagnostic tools. The results of these tests, in
combination with your history and physical exam may warrant further, and more specific, testing.
However, many of these should be considered as second-line tests. As well, please remember
that Mrs. Melianos will also likely need to have a number of health maintenance issues
addressed. While this is not the focus of this case, you would not be at fault to inquire about
recent immunizations, etc.
Test Results
You discuss
your ideas and
plans for Mrs.
Melianos with
Dr. Sampson
and your
preceptor
agrees with
you. You
schedule a
follow-up
appointment for
Mrs. Melianos
in 1 week and
arrange for her
to get a CBC,
EKG, and chest
X-ray (CXR) in
the attempt to
further elucidate
the etiology of
her dyspnea
(although you
think you
already have a
good idea of
what the
problem is!)
Three days
later your
preceptor
comes up to
you and says
that they have
received the
films from Mrs.
Melianos’ CXR,
however the
report seems to
have gone
missing. Your
preceptor asks
you to look at
the CXR and
give your
interpretation.
What is your interpretation of the AP chest X-ray?
Typical findings in a chest X-ray from a patient with COPD include:






Flattened diaphragms
Hyperinflated lungs
Thin appearing heart and mediastinum
Parenchymal bullae or suprapleural blebs in patients with emphysema
Increased AP diameter (on a lateral CXR)
Increased pulmonary vasculature
Mrs. Melianos EKG and CBC are normal. You and your preceptor discuss Mrs. Melianos clinical,
physical, and radiologic findings. You both agree that there is significant suspicion that Mrs.
Melianos has COPD.
Mrs. Melianos returns to the office for her scheduled follow-up appointment. She reports that she
continues to have dyspnea and occasional cough.
How are you going to explain COPD to Mrs. Melianos?
An example of an explanation that you might provide Mrs.Melianos is: from what you have told
me about your shortness of breath and cough, as well as what I observed from your physical
exam and from the results of your EKG, blood work, and chest X-ray, we feel that you may have
a condition known as COPD. Do you know anything about COPD?
COPD stands for chronic obstructive pulmonary disease and is most-likely a result of your
previous cigarette smoking. In your case it is likely that your lungs were irritated and damaged by
smoking cigarettes, and this has led to your lungs not working as well, thereby decreasing the
oxygen available to your body. This is why you feel short of breath when you try to do physical
activity. This is also likely the reason why you say you have to cough a lot, as the irritation from
the smoking has caused your lungs to produce more mucus than normal. I know that this is a lot
of information--what questions do you have for me?”
Remember that it is likely that your patients will have many questions and may not understand or
remember everything that you told them. It is important to remember to explain diseases and
disease processes to patients in terms that are understandable to them. Refer them to sources of
patient information that you have previously reviewed—it is better to send them to a source that
you know has good factual information then to have them out “surfing the net” finding information
that may not be 100% true.
Some good patient education web sites on COPD:
American Academy of Family Physicians. Chronic Obstructive Pulmonary Disease (COPD). July
2004. Available at http://familydoctor.org/706.xml
Pamet, Sharon MS; Lynm, Cassio MA; Glass, Richard M MD. JAMA patient page. Chronic
Obstructive Pulmonary Disease. JAMA. 290(17): 2362. November 5, 2003. Available at
http://jama.ama-assn.org/cgi/content/full/290/17/2362
Mrs. Melianos thanks you for taking time to explain COPD to her, however she wants to know
what the next step is going to be.
The information that you have obtained from your history-taking, the physical exam, and
diagnostic testing indicates that Mrs. Melianos has COPD. However, the diagnosis of COPD
requires pulmonary function testing (PFT), including spirometry. PFT is also important for the
management of COPD and other pulmonary diseases, as it is reproducible, quantitative, and
allows longitudinal monitoring.
For more information on pulmonary function testing see:
Evans, Scott E. MD; Scanlon, Paul D. MD Current Practice in Pulmonary Function Testing. Mayo
Clinic Proceedings. 78(6):758-763, June 2003.
At this point it would be a good idea to schedule a baseline Pulmonary Function Test, or Office
Spirometry to determine the degree of obstruction or restriction that she has, as well as to
determine if she improves with bronchodilators.
You send
Mrs.
Melianos for
spirometry
and tell her
to return for
a follow-up
visit in one
week, at
which point
you will
discuss the
results of her
pulmonary
function
testing with
her and
develop a
specific
management
plan.
It is one
week later
and you are
about to see
Mrs.
Melianos at
her follow-up
appointment.
Before going
in to see her,
you look at
her
spirometry
results.
Interpret the results of Mrs. Melianos’ PFT and explain how they support or refute your
diagnosis of COPD
Review of Spirometry:







Spirometry: measures the volume of air inhaled or exhaled as a function of time
Vital capacity (VC): amount (Volume) of air displaced by maximal inhalation or exhalation
Total lung capacity (TLC): Lung volume reached after maximal inspiration
Residual volume (RV): Volume of air remaining in lung after maximal expiration
Forced expiratory vital capacity (FEVC, FVC): Patient forcefully expels air from a point of
maximal inspiration until they reach maximal expiration
Forced inspiratory vital capacity (FIVC): Forced inhalation from RV to TLC.
FEV1: Forced expiratory volume in first second of the FVC maneuver

Forced expiratory flow (25%-75%) (FEF25-75): the mean expiratory flow rate in the
middle half of the FVC assessment
Mrs. Melianos’ spirometry results indicate that she has obstructive lung disease. Obstructive lung
disease includes asthma, COPD, and upper airway obstruction. It is characterized on spirometry
by a decrease in FEV1 which is greater than the decrease measured in FVC, hence an overall
decreased FEV1/FVC. The Global Initiative for Chronic Obstructive Lung Disease (GOLD)
defines COPD as having a FEV1 of less than 80% predicted normal value and a FEV1:FVC ratio
of less than 0.7.
Restrictive lung disease is characterized by an overall decrease in total lung capacity (TLC).
Restrictive lung disease can be due to (1) paraenchymal disease such as interstitial fibrosis or
collagen vascular disease, or (2) extraparenchymal etiologies such as obesity or chest wall/spinal
deformities. On spirometry, restrictive lung disease is defined as a FVC < 80%, often with a near
equivalent decline in FVC and FEV1. The FEV1/FVC ratio is normal, or may even be increased,
with the FEV1/FVC ratio being >0.7 in pure restrictive lung disease.
The table below summarizes the typical spirometry result obtained in obstructive and restrictive
lung disease.
Obstructive Lung Disease
Restrictive Lung Disease
FEV1
Decreased
(<80%)
Decreased
FVC
Decreased
FEV1/FVC
Decreased (<0.7)
Decreased
(<80%)
Normal (> 0.7) or
Increased
For a review of spirometry see:
Gross, Thomas. Interpretation of Pulmonary Function Tests: Spirometry. University of Iowa
Virtual Hospital. June 2002. Available at
http://www.vh.org/adult/provider/internalmedicine/Spirometry/SpirometryHome
How would you stage the severity of Mrs. Melianos’ COPD?
There are a number of staging criteria that can be used to determine the severity
of COPD, some of which use only results from spirometry, specifically FEV1, as
that is a good reflection of the severity of obstruction. However, it has been
recommended by the Global Initiative for Chronic Obstructive Lung Disease
(GOLD) that you use not only results from spirometric evaluation, but combine
these with patient symptoms to determine severity. In Mrs. Melianos’ case her
FEV1 and symptoms place her in Stage II (moderate disease).
Severity of airflow limitation in COPD (based on
postbronchodilator FEV1)
In patients with FEV1/FVC <0.7:
GOLD 1
Mild
FEV1 ≥80 percent predicted
GOLD 2
Moderate
50 percent ≤FEV1 <80 percent predicted
GOLD 3
Severe
30 percent ≤FEV1 <50 percent predicted
GOLD 4
Very severe
FEV1 <30 percent predicted
FEV1: forced expiratory volume in one second; FVC: forced vital capacity; respiratory failure:
arterial partial pressure of oxygen (PaO2) less than 60 mmHg (8 kPa) with or without arterial
partial pressure of CO2 (PaCO2) greater than 50 mmHg (6.7 kPa) while breathing ambient air
at sea level.
From the Global Strategy for the Diagnosis, Management and Prevention of COPD 2013, Global
Initiative for Chronic Obstructive Lung Disease (GOLD), www.goldcopd.org.
COPD Foundation system — The COPD Foundation has introduced a staging system that
includes seven severity domains, each of which has therapeutic implications (figure 6) [8,37].
These domains are based upon assessment of spirometry, regular symptoms, number of
exacerbations in the past year, oxygenation, emphysema on computed tomography scan,
presence of chronic bronchitis, and comorbidities. Within these domains, the COPD Foundation
uses five spirometric grades:
●SG 0: Normal spirometry
●SG 1: Mild, postbronchodilator FEV1/FVC ratio <0.7, FEV1 ≥60 percent predicted
●SG 2: Moderate, postbronchodilator FEV1/FVC ratio <0.7, 30 percent ≤FEV1 <60 percent
predicted
●SG 3: Severe, postbronchodilator FEV1/FVC ratio <0.7, FEV1 <30 percent predicted
●SG U: Undefined, postbronchodilator FEV1/FVC ratio >0.7, FEV1 <80 percent predicted
An advantage of this staging system is that it simplifies the interpretation of spirometry; any
spirometric finding results in a classification, which is not the case in GOLD.
Table 6:
COPD Foundation guide to assessment of COPD severity
COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in one second;
FVC: forced vital capacity; SG: spirometry grade; PaO2: arterial tension of oxygen; CT:
computed tomography.
Reprinted with permission from the COPD Foundation. Slight modifications were made.
(Thomashow B, Crapo J, Yawn B, et al. The COPD Foundation Pocket Consultant Guide.
Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. 2014; 1(1): 8387). Copyright © 2014 Informa Plc.
Why do you think Mrs. Melianos is experiencing dyspnea now and not five years ago?
Often there is significant compromise of lung function before patients begin to
experience symptoms such as dyspnea. It has been postulated that symptoms often do not
begin until after FEV1 reaches approximately 50% of predicted normal value. This is one
reason why it has been recommended that patients greater than 40 years-old with a 10
pack-year history have spirometry performed as a screening method, even if they are
asymptomatic.
Now that you have a complete picture of Mrs. Melianos’ disease, what pharmacological
therapeutic options should you consider in treating her COPD when it is stable (i.e. not an
acute exacerbation)?
There are a number of pharmacological options for the treatment of COPD.
Unfortunately, nothing has been shown to cure the disease, but rather the principle of
treatment is to decrease the symptoms of COPD and/or decrease the complications
secondary to COPD.
BRONCHODILATORS: The mainstays of pharmacological treatment of COPD are the
bronchodilators, which are effective in COPD symptom management by increasing
airflow and decreasing hyperinflation in the COPD patient. This results in a decrease in
the symptoms of COPD, as well as decreasing the number of exacerbations and
improving the quality of life for patients with COPD. Despite the evident subjective
improvement of patients with COPD on bronchodilators, there are not always objective
improvements (i.e. improvement in spirometry results) while on bronchodilators.
The table below outlines the four major categories of bronchodilators based upon
mechanism of action and duration.
Category
Short-acting B2-adrenergicreceptor agonists
Short-acting cholinergicreceptor antagonists
Long-acting B2-adrenergicreceptor agonists
Long-acting cholinergicreceptor antagonists
Example
albuterol
Duration
4-6 hours
Ipratropium (Atrovent)
4-6 hours
formoterol (Foradil),
salmeterol (Serevent)
tiotropium (Spiriva)
8-12 hours
>24 hours
At time of diagnosis, patients with COPD should be started on a bronchodilator (either
short- or long-acting, and of either mechanism of action). If a patient fails single
bronchodilator therapy, an additional bronchodilator of the other class should be added.
For patients with COPD, a short-acting bronchodilator for acute relief of symptoms may
also be useful.
METHYLXANTHINES: If patients fail combined bronchodilator therapy, the addition of
theophylline or aminophylline can be considered, as these have been shown to provide
additional improvement in lung function and symptoms. However, the use of
methylxanthines should be closely monitored, as they are potential toxic with significant
side effects. Not in vogue as much due to the potential side effects.
INHALED CORTICOSTEROIDS: Inhaled corticosteroids have not been shown to
substantially modify airway inflammation in COPD, as assessed by spirometry, however,
they do decrease symptoms, decrease the frequency of exacerbations, and increase
general health status. As such, there does appear to be clinical benefit independent of
measured FEV1 response, and it has been postulated that this is because inhaled
corticosteroids both decrease the level of hyperinflation and result in a decreased number
of exacerbations. They are recommended for COPD patients with moderate to severe
airflow limitation who demonstrate no improvement of symptoms, no change in
physiologic findings, and no decrease in the frequency of exacerbations despite
maximization of bronchodilator therapy.
SYSTEMIC CORTICOSTEROIDS: Systemic corticosteroids should not be used for
routine management of stable COPD, but rather may be used for acute exacerbations.
For one suggested treatment algorithm, see:
Sutherland, E. Rand; Cherniack, Reuben M. Current Concepts: Management of Chronic
Obstructive Pulmonary Disease. New England Journal of Medicine. 350(26):2689-2697,
June 24, 2004.
What are other potential (nonpharmacologic) therapeutic options might you consider
in the treatment of COPD?
SMOKING CESSATION: The most important recommendation that could be made is
that the patient stops smoking if the patient still does. It has been shown that patients who
stop smoking and maintain abstinence have a 50% decrease in the rate of lung function
decline. As Osteopathic Physicians, prevention or health maintenance is paramount for
the patient.
PATIENT EDUCATION: As always, patient education is important and necessary to
helping patients learn to cope and understand their disease.
PULMONARY REHABILITATION: Other options for the treatment of COPD include
pulmonary rehabilitation, especially for patients who have significant dyspnea with
exertion. This can include exercises and physical training, and is often more effective if
coupled with patient education.
OXYGEN: For treatment of hypoxemia, patients can be prescribed supplemental oxygen,
which has been shown to improve the long-term course of COPD. Supplemental oxygen
is recommended for patients with resting PaO2 < 55 mmHg or with an O2 saturation of
88% or less.
SURGERY: Surgical options may also be available for patients with severe disease. For
patients with severe emphysematous disease, lobar reduction surgery may be of use.
Lung-volume-reducing surgery may be used for hyperinflation and removal of large
bullae, which can compress areas of functional lung. Lung transplantation may also be an
option for patients who would otherwise die within 1-2 years.
OSTEOPATHIC MANIPULATIVE THERAPY: OMT can increase her range of motion
of the rib cage along with regulating the sympathetic/parasympathic tone. Reference to
Foundations for Osteopathic Medicine 2nd edition Pages 512-513, 1147
You go in to see Mrs. Melianos. When you walk in to the examination room Mrs. Melianos
introduces you to her son, Nicholas. You explain to Mrs. Melianos the results from her spirometry
evaluation and you ask her if she has any questions. She says that she has been reading on the
Internet that COPD usually occurs in people who have smoked cigarettes, but that there is a
genetic form of COPD as well, and she wonders if this could be why she has COPD, especially
since she not longer smokes.
What “genetic disease” she is talking about?
1-antitrypsin (AAT) deficiency is one of the less common causes of emphysema. It is
due to a recessive genetic disorder where there is a deficiency of 1-antitrypsin (AAT),
which is a protease inhibitor. Almost all people who have complete deficiency of this
protein will develop emphysema. AAT deficiency is responsible for less than 5% of all
cases of emphysema in the United States. This corresponds to ~100,000 Americans with
the disease, however it is estimated that there are ~25 million American who are carriers
of the gene. In the U.S. AAT deficiency is typically seen in people of Northern European
descent. AAT deficiency-related emphysema typically manifests as dyspnea. with
decreased exercise tolerance in the 4th decade of life. As such, AAT deficiency-related
emphysema should be suspected in dyspnea patients who are less than 45 years old
without other COPD risk factors. Treatment options for  AAT deficiency-related
emphysema are currently limited. There is the option for life-long replacement of  AAT.
As well, if diagnosed in children, there is the possibility for a liver transplant, as  AAT
is produced by the liver.
You explain to Mrs. Melianos about 1-antitrypsin deficiency, and indicate that, given the lack of
family history, her age at presentation, and her history of smoking, it isn’t 1-antitrypsin
deficiency. Mrs. Melianos is relieved, however she tells you that she also read that exposure to
second-hand smoke puts you at increased risk of developing COPD, and Mrs.Melianos says that
she often smoked around Nicholas. She says that they didn’t know what they know now about
how bad cigarette smoking is to our health.
Discuss the relationship between cigarette smoking, second-hand smoke, and COPD.
What is the relationship between smoking cessation and COPD mortality?
Cigarette smoking is a significant risk factor for the development of COPD. It is currently
estimated that 80-90% of COPD cases and deaths are attributable to cigarette smoking.
Although cigarette smoking is the most significant risk factor, there are other risk factors
for the development of COPD include air pollution, second-hand smoke, recurrent
respiratory tract infections, a family history of COPD, AAT deficiency, and domestic or
occupational pollutants.
As previously discussed, smoking cessation is the single greatest intervention to decrease
the rate of COPD progression. For patients who continue to smoke after diagnosis of
COPD, they will likely continue to have an accelerated decline in FEV1 over time.
For further information on smoking cessation in COPD see:
Pride, N B Smoking cessation: effects on symptoms, spirometry and future trends in
COPD. Thorax. 56 Supplement II:ii7-ii10, September 1, 2001.
You decide to initially start Mrs. Melianos on tiotropium bromide (Spiriva) DPI (dry-powder
inhaler) 1 inhalation daily and albuterol sulfate MDI (metered-dose inhaler) 2 puffs as needed for
acute symptoms up to every four hours. You also perform OMT on Mrs. Melianos since you
found thoracic and rib dysfunctions on exam. She seems happy with her treatment plan. You
send her home with a follow-up appointment scheduled in 2-3 weeks for more OMT and to see
how she is doing on her Rx.
Dr. Sampson comments that he is noticing more and more women being diagnosed with COPD
and asks you if you wouldn’t mind doing a little research on the epidemiology of COPD.
The incidence of COPD in the U.S. is reported at between 11 and 14 million people, and believed
to affect ~20% of the adults in the U.S. COPD is currently the 4th leading cause of death in the
U.S., resulting in the mortality of 120,000 Americans in 2002. Additionally, COPD is predicted to
be the third leading cause of death by 2020. Despite the wide prevalence of COPD diagnosed in
the adult population, it is estimated that 24 million adults have evidence of impaired lung function,
indicating an under-diagnosis of COPD in the U.S. currently.
While COPD used to be more prevalent in males, since 2000 the number of deaths attributed to
COPD has been greater in females than in males. When adjusted for age, the COPD death rate
for females has increased from 20.1 to 56.7 per 100,000 population from 1980 to 2000,
respectively. It is hypothesized that the incidence of COPD was delayed for women because
popularity of smoking in women occurred ~20 years after the popularity for men. Therefore it is
only now that we are seeing the true effects of smoking in women (i.e. COPD), whereas 20 years
ago the effects were evident in men. As well, the prevalence of self-reported COPD has been
shown to be greater in females than males and greater in whites than blacks.
For more information on the prevalence of COPD, see:
National Heart, Lung, and Blood Institute. Chronic Obstructive Pulmonary Disease: Data Fact
Sheet. March 2003. Available at http://www.nhlbi.nih.gov/health/public/lung/other/copd_fact.pdf.
What would you say to the other medical student about COPD versus emphysema versus
chronic bronchitis?
Chronic obstructive pulmonary disease (COPD) is a term used to describe a physiologic situation
where there is progressive airflow obstruction which is irreversible. There are two major diseases
which fall under the heading of COPD, chronic (obstructive) bronchitis and emphysema, which
frequently co-exist, thereby defining a patient as solely one or the other is often futile. There is
some debate about the inclusion of asthma, however the airflow obstruction experienced in
asthma is reversible with administration of a bronchodilator, unlike the irreversible nature of
COPD.
Chronic bronchitis is defined as excessive cough with sputum production for at least three months
in at least two consecutive years. The excessive cough is attributable to increased mucus
production secondary to inflammation of the lining of the bronchial tubes. The increased volume
of mucus also leads to improper clearing of the bronchial tubes, which results in an increased risk
of bacterial infections and airway obstruction.
In emphysema, lung damage results in alveoli not being able to stretch and recoil, as they have
become stiff. This results in air being trapped in the alveoli, which then impedes O2/CO2
exchange. Patients with emphysema often report chronic cough, dyspnea, and limited exercise
tolerance.
Six months later you are doing your Internal Medicine rotation with Dr. Parish and you see that
Mrs. Melianos is on your service! In morning report you hear that she was admitted for “COPD
Exacerbation”.
What is COPD Exacerbation?
COPD exacerbations are temporary worsening of the patient’s obstructive symptoms. During an
exacerbation there is often an increase in baseline sputum production and dyspnea, and sputum
typically becomes more purulent in nature. Exacerbations are typically linked to acute infections,
but they can also be triggered by certain weather conditions, allergens, pollutants, heart failure,
and noncompliance. Exacerbations can often require hospitalization for patients with COPD
because there can be a rapid decline in function, resulting in significant respiratory distress.
Bacterial infections are implicated in 70 to 75% of exacerbations. The most common infectious
causes of COPD exacerbations are Streptococcus pneumoniae, Haemophilus influenzae, and
Moraxella catarrhalis. Pseudomonas species are associated with more severe exacerbations,
which are more likely to occur in patients with severe disease and frequent exacerbations.
For additional information, refer to the case on pneumonia and see:
Hunter, Melissa H. MD; King, Dana E. MD. COPD: Management of Acute Exacerbations and
Chronic Stable Disease. American Family Physician. 64(4): 603-612. August 15, 2001. Available
at http://www.aafp.org/afp/20010815/603.html.
What additional health maintenance issues should Mrs. Melianos be aware of in the future
to potentially help prevent further exacerbations?
Although there is little evidence that there is a direct benefit of vaccinating people with COPD, it is
currently standard practice to recommend pneumococcal and annual influenza vaccinations, in
the attempt to decrease disease-specific and general mortality.
What is cor pulmonale and how is it related to COPD?
Cor pulmonale refers to pathologic changes in the right ventricle due to a primary respiratory
disorder. There are a number of potential etiologies of cor pulmonale, however it is estimated that
COPD is responsible for greater than 50% of the cases of chronic cor pulmonale. Pulmonary
hypertension is often viewed as the link between the primary respiratory disorder and the
subsequent development of right ventricular hypertrophy and eventually right-sided heart failure.
What factors for any patient with COPD are going to indicate an increased risk of
mortality?
The strongest predictors of mortality are (1) older age, and (2) progressive decline of FEV1 with
serial testing. The decline of FEV1 is most associated with continued cigarette smoking.
Other factors associated with a less favorable prognosis (increased rate of mortality):








FEV1 < 750 cc (<50% of predicted value)
Lower diffusion capacity
Hypoxia with PaO2 < 55 mmHg
Continued tobacco use
Hypercapnia with PaCO2 > 45 mmHg
Right-sided heart failure (cor pulmonale)
Malnutrition
Resting tachycardia
What are the gross pathologic changes expected in a COPD lung? (This one was for
Dr. Santo and Dr. Dudley)
Shown below images of an emphysematous lung, as compared to a normal lung. In the
emphysematous lung there are large dilated airspaces (bullae) which are evident throughout the
lung. In chronic bronchitis there is often evidence of mucus plugging.
Cross-section of emphysematous lung.
Emphysematous bullae.
Normal Lung.
Images courtesy of Department of Pathology, Penn State College of Medicine,
Pennsylvania.(home of Joe Paterno and the Orange Bowl Champ Nittany Lions)
Readings: Rakel’s Textbook of Family Medicine: pp243 - 251