STEP 7

1. What is the relation between the patient smoker and his job with his illness?

Fishman, Alfred P. 2008. Fishman’s Pulmonary Diseases and Disorders Fourth Edition.
McGraww Hill

Occupational Exposures
Increased respiratory symptoms and airflow obstruction have been suggested to
result from general exposure to dust and fumes at work. Several specific
occupational exposures, including coal mining, gold mining, and cotton textile dust,
have been suggested as risk factors for chronic airflow obstruction. Although
nonsmokers in these occupations developed some reductions in FEV1, the
importance of dust exposure as a risk factor for COPD, independent of cigarette
smoking, is not certain for most of these exposures. However, a recent study found
that coal mine dust exposure was a significant risk factor for emphysema in both
smokers and nonsmokers. In most cases, the magnitude of these occupational
exposures on COPD risk is likely substantially less important than the effect of
cigarette smoking.
Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition. 2012
Smoking is a particularly effective means of delivering nicotine to induce
psychoactive effects. When the drug is inhaled into the lungs its lipid solubility
allows it to be rapidly absorbed across the alveolar surface into the pulmonary
capillary blood. This results in a very rapid increase in nicotine levels in arterial
circulation. Consequently, at the level of receptors in the brain, nicotine
concentration rises very rapidly following inhalation of a cigarette.
Cigarette smoking is the major risk factor associated with the development
of chronic obstructive pulmonary disease. Emphysema likely develops from lung
damage, which can be a result of direct injury from oxidants in cigarette smoke, and
the action of oxidants released by inflammatory cells recruited into the lung as a
result of smoke exposure. Smoke-generated oxidants may also disrupt the anti-
protease protective mechanisms of the lung, creating a milieu more susceptible to
protease-induced damage. When damage induced by smoking is not balanced by
appropriate repair mechanisms, emphysema may result. In this context, cigarette
smoke may disrupt repair processes. Chronic bronchitis appears toresult fromsimilar
mechanisms in the airway. Inflammation induced by cigarette smoke appears
capable of stimulating both acute production of secretions and inducing long-term
anatomic changes in the airway. Changes such as goblet cell metaplasia may
predispose to a hypersecretory state. Others, such as peribronchial fibrosis, may
result in airflowobstruction. The development of autoimmune processes has been
suggested to contribute to disease that persists after smoking cessation. The
heterogeneity of clinical COPD likely results from varied host responses to the many
pathogenetic pathways initiated by cigarette smoke.
 Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition. 2012

Cigarette smoke contains many oxidant molecules, capable of inducing oxidative stress in
the lung. Oxidative stress has diverse effects, including the oxidative inactivation of
antiproteases in the lung as well as acetylation of specific histones in the chromatin of lung
cells and macrophages, allowing the expression of various pro-inflammatory genes. Histone
deacetylase activity is reduced in COPD, which in turn may result in an inability to control
the pro-inflammatory response in this condition. Pro-inflammatory gene expression
promotes cytokine production and release, contributing to further inflammatory cell
recruitment and activation.
ANDREOLI AND CARPENTER ’ S CECIL ESSENTIALS OF MEDICINE. 2010. Elsevier
 Fishman, Alfred P. 2008. Fishman’s Pulmonary Diseases and Disorders Fourth Edition.
McGraww Hill

2. What are the composition of cigarette?

Nikotin,
tar,
CO the one of the gas no smell was produce of the burn of carcoal substance,
thei gas is toxic, increase the blood bring the oxygen,
hydrogen cianida make evaporation,
NO,
alkaloid nicotin fo the taste of cigarrete

type of cigarrete:
1. White cigarrete: tar and nicotine lower, with filter
2. Kretek cigarrete: tar and nicotine middle, without filter
3. Cigar: high tar and nicotine
4. Electronic cigarrete;

Classification of smoker
 Mild: smoker can consume 1-10 cigarrete of a day
 Severe: 11-20 cigarrete a day
 More severe : >20 a day
 Intermiten smoker: from time to time
 Social smoker: when they go out

3. Why dispnea in patient continue in 1 week with plegn sputum?

Large Airway
Cigarette smoking often results in mucous gland enlargement and goblet cell
hyperplasia leading to cough and mucus production that define chronic
bronchitis, but these abnormalities are not related to airflow limitation. Goblet
cells not only increase in number but in extent through the bronchial tree.
Bronchi also undergo squamous metaplasia, predisposing to carcinogenesis and
disrupting mucociliary clearance. Although not as prominent as in asthma,
patients may have smooth-muscle hypertrophy and bronchial hyperreactivity
leading to airflow limitation. Neutrophil influx has been associated with purulent
sputum of upper respiratory tract infections. Independent of its proteolytic
activity, neutrophil elastase is among the most potent secretagogues
identified.
Small Airways
The major site of increased resistance in most individuals with COPD is in
airways ≤2 mm diameter. Characteristic cellular changes include goblet cell
metaplasia, with these mucus-secreting cells replacing surfactant-secreting Clara
cells. Infiltration of mononuclear phagocytes is also prominent. Smooth-muscle
hypertrophy may also be present. These abnormalities may cause luminal
narrowing by fibrosis, excess mucus, edema, and cellular infiltration. Reduced
surfactant may increase surface tension at the air-tissue interface, predisposing
to airway narrowing or collapse. Respiratory bronchiolitis with mononuclear
inflammatory cells collecting in distal airway tissues may cause proteolytic
destruction of elastic fibers in the respiratory bronchioles and alveolar ducts
where the fibers are concentrated as rings around alveolar entrances. Because
small airway patency is maintained by the surrounding lung parenchyma that
provides radial traction on bronchioles at points of attachment to alveolar septa,
loss of bronchiolar attachments as a result of extracellular matrix destruction
may cause airway distortion and narrowing in COPD.
Lung Parenchyma
Emphysema is characterized by destruction of gas-exchanging air spaces, i.e.,
the respiratory bronchioles, alveolar ducts, and alveoli. Their walls become
 perforated and later obliterated with coalescence of small distinct air spaces
into abnormal and much larger air spaces. Macrophages accumulate in
respiratory bronchioles of essentially all young smokers. Bronchoalveolar lavage
fluid from such individuals contains roughly five times as many macrophages as
lavage from nonsmokers. In smokers' lavage fluid, macrophages comprise >95%
of the total cell count, and neutrophils, nearly absent in nonsmokers' lavage,
account for 1–2% of the cells. T lymphocytes, particularly CD8+ cells, are also
increased in the alveolar space of smokers.
Emphysema is classified into distinct pathologic types, the most important being
centriacinar and panacinar. Centriacinar emphysema, the type most frequently
associated with cigarette smoking, is characterized by enlarged air spaces found
(initially) in association with respiratory bronchioles. Centriacinar emphysema is
usually most prominent in the upper lobes and superior segments of lower lobes
and is often quite focal. Panacinar emphysema refers to abnormally large air
spaces evenly distributed within and across acinar units. Panacinar emphysema
is usually observed in patients with 1AT deficiency, which has a predilection for
the lower lobes. Distinctions between centriacinar and panacinar emphysema
are interesting and may ultimately be shown to have different mechanisms of
pathogenesis. However, garden-variety smoking-related emphysema is usually
mixed, particularly in advanced cases, and these pathologic classifications are
not helpful in the care of patients with COPD.
Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition. 2012
4. Why is there barrel chest in physical examination?
Nikotin, neutrofil will arise  neutrofil enter alveolar in the alveolus, neutrofil
produce neutrofil elastase cause defec of 1 alfa anyitripsin(elastic recoil) 
dilatation, co will accumulate in lung  barrel chest  difficult to expiration

5. What are causes the retraction of chest muscle?

Sign of increase use of difficulty breathing, as breathing become difficult, area of
the chest where retraction can be seen increase
Classification:
Mild : cause the retraction of subcosta and sub sternal
Moderate: same area with mild but the is intercosta reaction
Severe: retraction same area with mild and the retaraction of the neck,
supraclavicular and suprasternal

6. Why is there pulse lips breathing in the physical examination?

 The patien to compensate for the lack of oxygen in the lung , pulse lips breathing
improve yhe air sack in the lung and ventilation then release trap air in the lung.
Decrease the work of breathing keep the air ways open for longer period.

7. Why the doctor consider smoking eventhough he has stop smoking more than 5
years?
If the patient smoking, the coplication after years
Because his work
Smoke control the body

8. How the interpretation from spirometer examination?

Bope, Edward T.. CONN’S CURRENT THERAPY 2013. Elsevier

9. What are the differential diagnosis and diagnosis of the scenario?

Differential Diagnosis
Several diseases can manifest with symptoms and signs of COPD. Asthma and
COPD have similar symptoms and signs. Asthma usually has an early onset as
opposed to COPD, which rarely occurs before the fourth decade. The presence
of allergy history, family history, and the absence of smoking history favors the
diagnosis of asthma. Spirometry can show complete reversibility in asthma, and
partial reversibility is usually observed in COPD. Another lung disease that can
mimic COPD is bronchiectasis. Dyspnea may be a presenting symptom in
diseases other than COPD in the elderly population; these include congestive
heart failure and coronary insufficiency.
Bope, Edward T.. CONN’S CURRENT THERAPY 2013. Elsevier
 Fishman, Alfred P. 2008. Fishman’s Pulmonary Diseases and Disorders Fourth
Edition. McGraww Hill

10. What are the etiology of this scenario?

Cigarette smoking is by far the most common cause of COPD; however, other
factors such as inhalation of cooking fire smoke, air pollution, occupational
exposures to dust and fumes, and infections contribute to the occurrence,
severity, and progression of the disease. Although cigarette smoking is the most
common cause, it is important to note that only 20% of smokers are thought to
develop clinically significant COPD (although many more may experience some
loss of lung function). This finding suggests that COPD results from a
susceptibility to environmental factors (e.g., tobacco) as a result of a genetic
predisposition. A genetic predisposition is also implied by the documentation of
familial clusters of COPD. The only genetic disorder thus far definitively linked to
COPD is α1-antitrypsin deficiency, which accounts for less than 1% of all cases.
The deficient enzyme, α1-antitrypsin, an acute-phase reactant, is produced
primarily in the liver, from which it travels to the lung, where it deactivates
 elastases released by inflammatory cells that are capable of degrading
connective tissue matrices. In doing so, α1-antitrypsin prevents the uncontrolled
degradation of elastin in the lung parenchyma and protects against the
development of emphysema. Patients who develop emphysema at a young age
(<40 years) should be evaluated for this condition whether or not they smoke.
Polymorphisms in various other candidate genes that may be relevant to
susceptibility to COPD are under investigation.
ANDREOLI AND CARPENTER ’ S CECIL ESSENTIALS OF MEDICINE. 2010. Elsevier
11. How is the patogenesis of the scenario?
Airflow Obstruction
Airflow limitation, also known as airflow obstruction, is typically determined by
spirometry, which involves forced expiratory maneuvers after the subject has
inhaled to total lung capacity. Key parameters obtained from spirometry include
FEV1 and the total volume of air exhaled during the entire spirometric maneuver
[forced vital capacity (FVC)]. Patients with airflow obstruction related to COPD
have a chronically reduced ratio of FEV1/FVC. In contrast to asthma, the reduced
FEV1 in COPD seldom shows large responses to inhaled bronchodilators,
although improvements up to 15% are common. Asthma patients can also
develop chronic (not fully reversible) airflow obstruction.
Airflow during forced exhalation is the result of the balance between the elastic
recoil of the lungs promoting flow and the resistance of the airways limiting
flow. In normal lungs, as well as in lungs affected by COPD, maximal expiratory
flow diminishes as the lungs empty because the lung parenchyma provides
progressively less elastic recoil and because the cross-sectional area of the
airways falls, raising the resistance to airflow. The decrease in flow coincident
with decreased lung volume is readily apparent on the expiratory limb of a flow-
volume curve. In the early stages of COPD, the abnormality in airflow is only
evident at lung volumes at or below the functional residual capacity (closer to
residual volume), appearing as a scooped-out lower part of the descending limb
of the flow-volume curve. In more advanced disease the entire curve has
decreased expiratory flow compared to normal.
Hyperinflation
Lung volumes are also routinely assessed in pulmonary function testing. In COPD
there is often "air trapping" (increased residual volume and increased ratio of
residual volume to total lung capacity) and progressive hyperinflation (increased
total lung capacity) late in the disease. Hyperinflation of the thorax during tidal
breathing preserves maximum expiratory airflow, because as lung volume
increases, elastic recoil pressure increases, and airways enlarge so that airway
resistance decreases.
Despite compensating for airway obstruction, hyperinflation can push the
diaphragm into a flattened position with a number of adverse effects. First, by
decreasing the zone of apposition between the diaphragm and the abdominal
wall, positive abdominal pressure during inspiration is not applied as effectively
to the chest wall, hindering rib cage movement and impairing inspiration.
Second, because the muscle fibers of the flattened diaphragm are shorter than
those of a more normally curved diaphragm, they are less capable of generating
inspiratory pressures than normal. Third, the flattened diaphragm (with
increased radius of curvature, r) must generate greater tension (t) to develop
the transpulmonary pressure (p) required to produce tidal breathing. This
follows from Laplace's law, p = 2t/r. Also, because the thoracic cage is distended
beyond its normal resting volume, during tidal breathing the inspiratory muscles
must do work to overcome the resistance of the thoracic cage to further
inflation instead of gaining the normal assistance from the chest wall recoiling
outward toward its resting volume.
Gas Exchange
Although there is considerable variability in the relationships between the FEV1
and other physiologic abnormalities in COPD, certain generalizations may be
made. The PaO2 usually remains near normal until the FEV1 is decreased to
~50% of predicted, and even much lower FEV1 values can be associated with a
normal PaO2, at least at rest. An elevation of arterial level of carbon dioxide
(PaCO2) is not expected until the FEV1 is <25% of predicted and even then may
not occur. Pulmonary hypertension severe enough to cause cor pulmonale and
right ventricular failure due to COPD typically occurs in individuals who have
marked decreases in FEV1 (<25% of predicted) and chronic hypoxemia (PaO2
<55 mmHg); however, recent evidence suggests that some patients will develop
significant pulmonary hypertension independent of COPD severity (Chap. 250).
Nonuniform ventilation and ventilation-perfusion mismatching are characteristic
of COPD, reflecting the heterogeneous nature of the disease process within the
airways and lung parenchyma. Physiologic studies are consistent with multiple
parenchymal compartments having different rates of ventilation due to regional
differences in compliance and airway resistance. Ventilation-perfusion
mismatching accounts for essentially all of the reduction in PaO2 that occurs in
COPD; shunting is minimal. This finding explains the effectiveness of modest
elevations of inspired oxygen in treating hypoxemia due to COPD and therefore
the need to consider problems other than COPD when hypoxemia is difficult to
correct with modest levels of supplemental oxygen in the patient with COPD.
Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition. 2012

Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition. 2012

 12. What are the clinical manifestation of this scenario?
Clinical Manifestations
COPD is a slowly progressive disease that ultimately causes severe limitation of
physical activity, deterioration of quality of life, and ultimately premature death.
COPD commonly occurs in patients who are 40 years of age and older. In most
instances, the smoking history is very prominent (>20 pack-years). Cough and
sputum production (chronic bronchitis) are present in the majority of patients.
Early in the disease, symptoms may be subtle, and many patients relate them to
the aging process. Fatigue and activity limitation are very common. Dyspnea on
exertion is common, although many patients limit their activity and might not
report dyspnea until late in the disease. Dyspnea is usually progressive and leads
to exercise intolerance. The course of COPD is often complicated with repeated
exacerbations, which are the first presenting symptoms in some cases. Several
extrapulmonary morbidities can complicate its course, including cardiac disease,
depression, osteoporosis, and muscle wasting. Several clinical phenotypes for
COPD that can have therapeutic implications have been described, although
these need to be further explored.
Bope, Edward T.. CONN’S CURRENT THERAPY 2013. Elsevier
13. What are the risk factor of this scenario?

Fishman, Alfred P. 2008. Fishman’s Pulmonary Diseases and Disorders Fourth Edition.
McGraww Hill
14. What are treatments for this diagnosis?
a. a1-Proteinase inhibitor (Prolastin, Aralast)
- a1-Proteinase inhibitor is used to treat emphysema caused by a deficiency
in a1-proteinase, a peptide that inhibits elastase. In patients with the
deficiency, elastase destroys lungparenchyma.
- This agent is administered by weekly IV injection to treat patients
homozygous for this deficiency.
Rosenfeld, Gary. 2010. BRS Pharmacology Fifth Edition. Lippincott Williams
Wilkins
b. Nonpharmacologic Interventions
- Vaccination
Reducing further damage to lung tissue is a main goal of therapy in any
chronic lung disease. With that in mind, yearly influenza vaccination (killed
[Fluzone, Fluarix] or live inactive [FluMist] viruses) can reduce more-severe
forms of influenza and acute exacerbations of COPD (by 60%).
Pneumococcal vaccination (Pneumovax 23) reduces invasive pneumococcal
disease and is recommended in COPD patients with more-severe lung
disease (FEV1 < 40%) and elderly patients.
- Smoking Cessation
Smoking cessation is the single most effective and cost-effective
intervention to reduce the progression of COPD and should be attempted in
 all patients. Unfortunately, even with the best intervention strategies, less
than a third of smokers become sustained quitters. Once patients develop
demonstrable airflow obstruction, their symptoms and airway inflammation
can persist even after smoking cessation. Several effective therapies for
tobacco dependence are available and should be considered in patients
interested in quitting smoking. These include behavioral techniques, support
groups, and pharmacotherapy (Table 2) including nicotine supplements,
bupropion (Zyban), and nicotine-receptor partial agonists like varenicline
(Chantix).
- Exercise and Pulmonary Rehabilitation
Pulmonary rehabilitation is currently recommended to be considered in the
management of patients with moderate or worse COPD. Pulmonary
rehabilitation is an individualized multidisciplinary program that aims to
optimize patients’ performance and self-control. The program includes
upper and lower body and breathing exercises; nutritional, psychological,
and behavioral interventions; and education. Pulmonary rehabilitation
produces significant improvement in respiratory symptoms, exercise
capacity, quality of life, and health care utilization.
- Surgical Therapies
Lung volume reduction surgery (LVERS) includes resection of severely
emphysematous areas of the lungs. The procedure can be performed
through thoracoscopy or median sternotomy. In the National Emphysema
Treatment Trial (NETT), LVRS improved spirometry, lung volumes, exercise
tolerance, dyspnea, and quality of life. Subjects with upper lobe disease and
low baseline exercise capacity had improved longevity when compared to
optimal medical therapy. In contrast, NETT showed that patients with very
advanced COPD including FEV1 of 20% or less, diffusing capacity of 20% or
less, or diffuse emphysema had shorter longevity with LVRS. LVRS can help
COPD patients with severe lung disease as long as it is performed in centers
with experience in this type of surgery. COPD patients with giant bulla (>1/3
hemithorax) might benefit from bullectomy with improvement in symptoms
(dyspnea), lung function, oxygenation and ventilation, exercise capacity, and
quality of life. In selected patients with advanced COPD, lung transplant can
improve pulmonary function, exercise capacity, and quality of life.
 Bope, Edward T.. CONN’S CURRENT THERAPY 2013. Elsevier

Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition. 2012

Fishman, Alfred P. 2008. Fishman’s Pulmonary Diseases and Disorders Fourth Edition.
McGraww Hill