Chronic Obstructive Pulmonary

Disease
 COPD

 defined as a disease state characterized by persistent respiratory symptoms and airflow

limitation that is not fully reversible (http://www.goldcopd.com/).
 COPD includes:
 Emphysema
 chronic bronchitis
 small airway disease
 classic definition of COPD requires the presence of chronic airflow obstruction, determined by
spirometry, that usually occurs in the setting of noxious environmental exposures—most
commonly cigarette smoking.
 COPD

 COPD is the third leading cause of death and affects >10 million persons in the United States.
 COPD is also a disease of increasing public health importance around the world.
 Estimates suggest that COPD will rise to the third most common cause of death worldwide by
2020.
PATHOGENESIS
 Pathogenesis of emphysema comprises a series of four interrelated
events:

 (1) Chronic exposure to cigarette smoke in genetically susceptible individuals

 (2) Inflammatory cells release proteinases
 (3) Structural cell death
 (4) Disordered repair of elastin and other extracellular matrix components
 INFLAMMATION AND EXTRACELLULAR MATRIX PROTEOLYSIS

 Elastin, the principal component of elastic fibers, is a highly stable component of the
extracellular matrix that is critical to the integrity of the lung.
 The elastase:antielastase hypothesis, postulated that the balance of elastin-degrading enzymes
and their inhibitors determines the susceptibility of the lung to destruction resulting in air space
enlargement.
 Oxidative stress is a key component of COPD pathobiology; the transcription factor NRF2, a
major regulator of oxidant-antioxidant balance, and SOD3, a potent antioxidant, have been
implicated in emphysema pathogenesis by animal models
 Cell Death

 Cigarette smoke oxidant-mediated structural cell death occurs via a variety of mechanisms
including excessive ceramide production and Rtp801 inhibition of mammalian target of
rapamycin (mTOR), leading to cell death as well as inflammation and proteolysis.
 Involvement of mTOR and other senescence markers has led to the concept that emphysema
resembles premature aging of the lung
 Ineffective Repair
 ability of the adult lung to replace lost smaller airways and microvasculature and to repair
damaged alveoli appears limited.
 Uptake of apoptotic cells by macrophages normally results in production of growth factors and
dampens inflammation, promoting lung repair.
 Cigarette smoke impairs macrophage uptake of apoptotic cells, limiting repair.
 It is unlikely that the intricate and dynamic process of septation that is responsible for
alveologenesis during lung development can be reinitiated in the adult human lung.
 PATHOLOGY

 Cigarette smoke exposure may affect the large airways, small airways (≤2 mm diameter), and
alveoli.
 Changes in large airways cause cough and sputum production, while changes in small airways and
alveoli are responsible for physiologic alterations.
 The early stages of COPD, based on the severity of airflow obstruction, appear to be primarily
associated with medium and small airway disease with the majority of Global Initiative for Chronic
Obstructive Lung Disease (GOLD) 1 and GOLD 2 subjects demonstrating little or no emphysema
 Advanced stages of COPD (GOLD 3 and 4) are typically characterized by extensive emphysema,
although there are a small number of subjects with very severe (GOLD 4) obstruction with virtually
no emphysema.
 The subjects at greatest risk of progression in COPD are those with both aggressive airway
disease and emphysema.
 Thus, finding emphysema (by chest CT) either early or late in the disease process suggests
enhanced risk for disease progression
 Pathology
LARGE AIRWAYS SMALL AIRWAYS LUNG PARENCHYMA
 Cigarette smoking often results in  The major site of increased resistance in most  Emphysema is characterized by
mucus gland enlargement and goblet individuals with COPD is in airways ≤2 mm destruction of gas-exchanging air spaces.
cell hyperplasia
diameter.  Their walls become perforated and later
 In response to cigarette smoking, goblet
cells not only increase in number but in
 Characteristic cellular changes include goblet obliterated with coalescence of the
extent through the bronchial tree. cell metaplasia, with these mucus-secreting delicate alveolar structure into large
cells replacing surfactant-secreting Club emphysematous air spaces.
 Bronchi also undergo squamous
cells.
metaplasia, predisposing to  Large numbers of macrophages
carcinogenesis and disrupting  Smooth-muscle hypertrophy may also be accumulate in respiratory bronchioles of
mucociliary clearance. present. essentially all smokers.
 Neutrophil influx has been associated Bronchoalveolar lavage fluid from such
 Reduced surfactant may increase surface 
with purulent sputum during respiratory individuals contains roughly five times as
tension at the air-tissue interface
tract infections.
many macrophages as lavage from
 Independent of its proteolytic activity,
 Respiratory bronchiolitis with mononuclear nonsmokers.
neutrophil elastase is among the most inflammatory cells collecting in distal airway
potent secretagogues identified. tissues may cause proteolytic destruction of  Neutrophils and T lymphocytes,
elastic fibers in the respiratory bronchioles particularly CD8+ cells, are also
and alveolar ducts increased in the alveolar space of
smokers.
 Narrowing and drop-out of small airways
precede the onset of emphysematous
destruction.
 Emphysema is classified into distinct pathologic types

 Centrilobular emphysema, the type most frequently associated with cigarette smoking, is
characterized by enlarged air spaces found (initially) in association with respiratory bronchioles.
Centrilobular emphysema is usually most prominent in the upper lobes and superior segments
of lower lobes and is often quite focal.
 Panlobular emphysema refers to abnormally large air spaces evenly distributed within and
across acinar units. Panlobular emphysema is commonly observed in patients with α1AT
deficiency, which has a predilection for the lower lobes.
 Paraseptal emphysema occurs in 10–15% of cases and is distributed along the pleural margins
with relative sparing of the lung core or central regions. It is commonly associated with
significant airway inflammation and with centrilobular emphysema.
 PATHOPHYSIOLOGY
Persistent reduction in forced expiratory flow rates is the most typical finding in COPD. Increases
in the residual volume and the residual volume/total lung capacity ratio, non-uniform distribution
of ventilation, and ventilation-perfusion mismatching also occur.

 AIRFLOW OBSTRUCTION
 HYPERINFLATION
 GAS EXCHANGE – non uniform ventilation and ventilation – perfusion mismatch
 RISK FACTORS
 CIGARETTE SMOKING
 AIRWAY RESPONSIVENESS AND COPD
 RESPIRATORY INFECTIONS
 OCCUPATIONAL EXPOSURES
 AMBIENT AIR POLLUTION
 PASSIVE, OR SECOND-HAND, SMOKING EXPOSURE
 GENETIC CONSIDERATIONS

 α1Antitrypsin Deficiency
 Other Genetic Risk Factors
 Clinical Presentation
History
 three most common symptoms in COPD are cough, sputum production, and exertional
dyspnea
 Many patients have such symptoms for months or years before seeking medical attention
 The development of exertional dyspnea, often described as increased effort to breathe,
heaviness, air hunger, or gasping, can be insidious. It is best elicited by a careful history focused
on typical physical activities and how the patient’s ability to perform them has changed.
 In the most advanced stages, patients are breathless doing simple activities of daily living.
 Accompanying worsening airflow obstruction is an increased frequency of exacerbations.
Patients may also develop resting hypoxemia and require institution of supplemental oxygen.
 PHYSICAL FINDINGS
 prolonged expiratory phase and may include expiratory wheezing. In addition, signs of hyperinflation include a
barrel chest and enlarged lung volumes with poor diaphragmatic excursion as assessed by percussion
 use of accessory muscles of respiration, sitting in the characteristic “tripod” position to facilitate the actions of the
sternocleidomastoid, scalene, and intercostal muscles. Patients may develop cyanosis, visible in the lips and nail
beds.
 Advanced disease may be accompanied by cachexia, with significant weight loss, bitemporal wasting, and diffuse
loss of subcutaneous adipose tissue
 Some patients with advanced disease have paradoxical inward movement of the rib cage with inspiration
(Hoover’s sign), the result of alteration of the vector of diaphragmatic contraction on the rib cage as a result of
chronic hyperinflation.
 Signs of overt right heart failure, termed cor pulmonale, are relatively infrequent since the advent of supplemental
oxygen therapy.
 Clubbing of the digits is not a sign of COPD
 LABORATORY FINDINGS

 The hallmark of COPD is airflow obstruction. Pulmonary function testing shows airflow obstruction with a
reduction in FEV1 and FEV1/FVC
 With worsening disease severity, lung volumes may increase, resulting in an increase in total lung capacity,
functional residual capacity, and residual volume
 In patients with emphysema, the diffusing capacity may be reduced, reflecting the lung parenchymal
destruction characteristic of the disease.
 The degree of airflow obstruction is an important prognostic factor in COPD and is the basis for the GOLD
spirometric severity classification
 Arterial blood gases and oximetry may demonstrate resting or exertional hypoxemia.
 Radiographic studies may assist in the classification of the type of COPD.
 Recent guidelines have suggested testing for α1AT deficiency in all subjects with COPD or asthma with
chronic airflow obstruction
 TREATMENT
STABLE PHASE COPD
 The two main goals of therapy are to provide symptomatic relief (reduce respiratory symptoms,
improve exercise tolerance, improve health status) and reduce future risk (prevent disease
progression, prevent and treat exacerbations, and reduce mortality).
 Response to therapy should be assessed, and decisions should be made whether or not to
continue or alter treatment.
 Only three interventions—smoking cessation, oxygen therapy in chronically hypoxemic
patients, and lung volume reduction surgery (LVRS) in selected patients with emphysema—
have been demonstrated to improve survival of patients with COPD.
mMRC
CAT
 PHARMACOTHERAPY

 Smoking Cessation
 Bronchodilators
 Anticholinergic Muscarinic Antagonists
 Beta Agonists
 Combinations of Beta Agonist — Muscarinic Antagonist
 Inhaled Corticosteroids
 PHARMACOTHERAPY
 Oral Glucocorticoids
 Theophylline
 PDE4 Inhibitors
 Antibiotics
 Oxygen
 `α1AT Augmentation Therapy
 NONPHARMACOLOGIC THERAPIES

 Pulmonary Rehabilitation

 Lung Volume Reduction Surgery

 Lung Transplantation
 EXACERBATIONS OF COPD

 Exacerbations are episodic acute worsening of respiratory symptoms, including increased

dyspnea, cough, wheezing, and/ or change in the amount and character of sputum.
 They may or may not be accompanied by other signs of illness, including fever, myalgias, and
sore throat.
 The strongest single predictor of exacerbations is a history of a previous exacerbation.
 The frequency of exacerbations increases as airflow obstruction worsens; patients with severe
(FEV1 <50% predicted) or very severe airflow obstruction (FEV1 <30% predicted) on average
have 1–3 episodes per year
Precipitating Causes and Strategies to Reduce Frequency of Exacerbations

 A variety of stimuli may result in the final common pathway of airway inflammation and
increased respiratory symptoms that are characteristic of COPD exacerbations.
 Studies suggest that acquiring a new strain of bacteria is associated with increased near-term
risk of exacerbation and that bacterial infection/superinfection is involved in >50% of
exacerbations.
 Viral respiratory infections are present in approximately one-third of COPD exacerbations.
 In a significant minority of instances (20–35%), no specific precipitant can be identified.
 Patient Assessment

 Patients with severe underlying COPD, who are in moderate or severe distress, or those with focal findings
should have a chest x-ray or chest CT scan
 Patients with advanced COPD, a history of hypercarbia, mental status changes (confusion, sleepiness), or
those in significant distress should have an arterial blood-gas measurement. The presence of hypercarbia,
defined as a Pco2 >45 mmHg, has important implications
 The presence of hypercarbia, defined as a Pco2 >45 mmHg, has important implications for treatment
 In contrast to its utility in the management of exacerbations of asthma, measurement of pulmonary function
has not been demonstrated to be helpful in the diagnosis or management of exacerbations of COPD.
 The need for inpatient treatment of exacerbations is suggested by the presence of respiratory acidosis and
hypercarbia, new or worsening hypoxemia, severe underlying disease and those whose living situation is
not conducive to careful observation and the delivery of prescribed treatment
 TREATMENT OF ACUTE EXACERBATIONS

 Bronchodilators

 Antibiotics

 Oxygen

 Mechanical Ventilatory Support

Thank you
Quiz
1. A 25 year old smoker with a 10 pack year history of smoking should be given what counsel to
prevent development of COPD?
A. Use albuterol as needed to prevent symptoms
B. Use ipratropium as needed to prevent symptoms
C. Need for an influenza vaccination
D. Smoking cessation information
E. All of the above
2. A 65 year old man, who comes to the clinic today for his annual visit. He complains that he
walks slower than his friends with same age. While reviewing his records you discover he has had
5 COPD exacerbations requiring hospitalization since his last visit a year ago. The most recent
event occurred two months ago. Spirometry reveals a FEV1 of 29%. How should you classify this
patient's COPD?
A. Group A
B. Group B
C. Group C
D. Group D
3. All of the following are risk factors for COPD EXACERBATION EXCEPT:
A. Diabetes
B. Heart Failure
C. Nonproductive cough
D. Advanced age
E. Recent antibiotic therapy
4. Which of the following organisms is least likely to have an influence on a COPD exacerbation
in someone with a long COPD history and multiple exacerbations?
A. Pseudomonas
B. MSSA
C. H. influenza
D. M. catarrhalis
E. Mycoplasma pneumoniae
5. All of the following are true regarding pathology in COPD, except.
a. Cigarette smoking often results in mucus gland enlargement and goblet cell hyperplasia
b. The major site of increased resistance in most individuals with COPD is in airways <5mm
diameter
c. Narrowing and drop-out of small airways precede the onset of emphysematous destruction
d. None of these
6. Which of the ff pathologic types of emphysema is usually most prominent in the upper lobes
and superior segments of lower lobes?
a. Centrilobular
b. Panlobular
c. Paraseptal
d. All of the above
7. Which of the following is the current definitive test for establishing presence of emphysema?
a. Chest xray
b. Chest CT scan
c. Chest MRI
d. Spirometry
8. What is the hallmark of COPD?
a. Ariflow obstruction
b. Airway hyperresponsiveness
c. Antitrypsin deficiency
d. Ventilation perfusion mismatch
 9. this drug has been demonstrated to reduce exacerbation frequency in patients with severe
COPD, chronic bronchitis, and a prior history of exacerbations; its effects on airflow
obstruction and symptoms are modest.
a. Prednisone
b. ICS
c. Salbumtaol + ipratropium
d. Roflumilast
10. Which of the following is/are not candidates for lung volume reduction surgery?
a. FEV1 <20%
b. Upper lobe predominant emphysema
c. Low post rehab exercise capacity
d. None of the above
11. Following hospitalization for COPD, what is the percentage of patients that are re-hospitalized?
a. 5%
b. 10%
c. 15%
d. 20%
12. True regarding treatment of acute exacerbation in COPD, except.
a. Typically patients are treated with inhaled B agonists and muscarinic antagonists
b. Patients with moderate or severe exacerbations are usually treated with antibiotics even in the
absence of data implicating a specific pathogen
c. Current recommendations suggest 30–40 mg of oral prednisolone or its equivalent typically
for a period of 5–10 days in outpatients.
d. No exception
13. Based on the recommended pharmacologic treatment for stable COPD. What is the preferred
treatment for patients with history of not more than 1 admission per year and with dyspnea when
walking about 100 yards.
a. SABA
b. LAMA+LABA
c. LAMA
d. LAMA+LABA+ICS
 14. Which of the following has/have been demonstrated to improve survival of patients with
COPD?
a. smoking cessation
b. oxygen therapy
c. lung volume reduction surgery (LVRS)
d. All of the above
 15. Which of the following is characterized as paradoxical inward movement of the rib cage
with inspiration, the result of alteration of the vector of diaphragmatic contraction on the rib
cage as a result of chronic hyperinflation?
a. Tripod sign
b. Hoover sign
c. Diaphragmatic paradox
d. Litten sign