Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by airflow limitation that is not fully

reversible. COPD includes emphysema, an anatomically defined condition characterized by destruction and enlargement of the lung
alveoli; chronic bronchitis, a clinically defined condition with chronic cough and phlegm; and small airways disease, a condition in
which small bronchioles are narrowed and Airways are less than 2 mm in diameter.

COPD is also a disease of increasing public health importance around the world. According to Philippine COPD Prevalence Study:
Philippine College of Chest Physicians Council on COPD 2007, It is the 7th leading cause of death in the Philippines and Affects 1.69
million Filipinos. Estimates suggest that COPD will rise from the sixth to the third most common cause of death worldwide by 2020.

Airflow limitation, the major physiologic change in COPD, can result from both small airway obstruction and emphysema. small
airways may become narrowed by cells (hyperplasia and accumulation), mucus, and fibrosis.

The dominant paradigm of the pathogenesis of emphysema comprises four interrelated events: (1) Chronic exposure to cigarette
smoke leads to inflammatory and immune cell recruitment within the terminal air spaces of the lung. (2) These inflammatory cells
release elastolytic and other proteinases that damage the extracellular matrix of the lung. (3) Structural cell death (endothelial and
epithelial cells) occurs directly through oxidant-induced cigarette smoke damage and senescence as well as indirectly via proteolytic
loss of matrix attachment. (4) Ineffective repair of elastin and other extracellular matrix components result in air space enlargement
that defines pulmonary emphysema.

THE ELASTASE:ANTIELASTASE HYPOTHESIS

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 proposed in the mid- 1960s states that the balance of elastin-degrading
enzymes and their inhibitors determines the susceptibility of the lung to destruction resulting in air space enlargement.

INFLAMMATION AND EXTRACELLULAR MATRIX PROTEOLYSIS

Upon exposure to oxidants from cigarette smoke, macrophages and epithelial cells become activated, producing proteinases and
chemokines that attract other inflammatory and immune cells. Matrix metalloproteinases and serine proteinases, most notably
neutrophil elastase, work together by degrading the inhibitor of the other, leading to lung destruction. Proteolytic cleavage products
of elastin also serve as a macrophage chemokine, fueling this destructive positive feedback loop

Autoimmune mechanisms may promote the progression of disease. Increased B cells and lymphoid follicles are present in patients,
particularly those with advanced disease. Antibodies have been found against elastin fragments as well; IgG autoantibodies with
avidity for pulmonary epithelium and the potential to mediate cytotoxicity have been detected

Concomitant cigarette smokeinduced loss of cilia in the airway epithelium and impaired macrophage phagocytosis predispose to
bacterial infection with neutrophilia.

Cell Death

Cigarette smoke oxidant-mediated structural cell death occurs via a variety of mechanisms including rt801 inhibition of mammalian
target of rapamycin (mTOR), leading to cell death as well as inflammation and proteolysis. Cigarette smoke impairs macrophage
uptake of apoptotic cells, limiting repair. Uptake of apoptotic cells by macrophages results in production of growth factors and
dampens inflammation, promoting lung repair.

PATHOLOGY

Cigarette smoke exposure may affect the large airways, small airways (2 mm diameter) (which is the major site of increased
resistance in most individuals with COPD), and alveoli. Changes in large airways cause cough and sputum (Cigarette smoking often
results in mucus gland enlargement and goblet cell hyperplasia, leading to cough and mucus production that define chronic
bronchitis) , while changes in small airways and alveoli are responsible for physiologic alterations. For the small airways, there would
be goblet cell metaplasia replacing surfactant-secreting Clara cells, smooth-muscle hypertrophy and reduced surfactant ; all of these
would cause the luminal narrowing. And for the lung parenchyma, there would be Destruction of gas-exchanging airspaces,
Perforation of walls or Obliteration with coalescence of small air spaces into abnormal and much larger spaces.
Emphysema is classified into distinct pathologic types. Centriacinar emphysema, the type most frequently associated with cigarette
smoking; 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 1 AT deficiency, which has a predilection for the lower lobes.

PATHOPHYSIOLOGY

Persistent reduction in forced expiratory flow rates is the most typical finding in COPD.

Airflow limitation, also known as airflow obstruction, is typically measured by spirometry. Key parameters obtained from spirometry
include the volume of air exhaled within the first second of the forced expiratory maneuver (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.

HYPERINFLATION

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 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 must
generate greater tension (t) to develop the transpulmonary pressure (p) required to produce tidal breathing. Also, because the
thoracic cage is distended beyond its normal resting volume, Increased work of breathing by inspiratory muscles Must occur to
overcome the resistance of the thoracic cage

GAS EXCHANGE

The partial pressure of oxygen in arterial blood 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 is decreased to ~50% of predicted. An elevation of arterial level of carbondioxide
(Paco2 ) is not expected until the FEV1 is <25% of predicted and even then may not occur. Also at FEV1 <25%, Pulmonary
hypertension severe enough to cause cor pulmonale and right ventricular failure due to COPD.

Nonuniform ventilation and ventilation-perfusion mismatching are characteristic of COPD, reflecting the heterogeneous nature of
the disease process within the airways and lung parenchyma.

CIGARETTE SMOKING By 1964, the Advisory Committee to the Surgeon General of the United States had concluded that cigarette
smoking was a major risk factor for mortality from chronic bronchitis and emphysema. The dose-response relationship between
reduced pulmonary function and cigarette smoking intensity accounts for the higher prevalence rates of COPD with increasing age.
The effects of cigarette smoking on pulmonary function appear to depend on the intensity of smoking exposure, the timing of
smoking exposure during growth, and the baseline lung function of the individual

AIRWAY RESPONSIVENESS. The considerable overlap between persons with asthma and those with COPD in airway responsiveness,
airflow obstruction, and pulmonary symptoms led to the formulation of the Dutch hypothesis. This suggests that asthma, chronic
bronchitis, and emphysema are variations of the same basic disease, which is modulated by environmental and genetic factors to
produce these pathologically distinct entities. The alternative British hypothesis contends that asthma and COPD are fundamentally
different diseases: Asthma is viewed as largely an 1703 allergic phenomenon, whereas COPD results from smoking-related
inflammation and damage.

RESPI INFECTIONS. the association of both adult and childhood respiratory infections with the development and progression of
COPD remains to be proven
Occupational exposures: coal mining, gold mining, cadmium exposure, cotton textile dust. the magnitude of these occupational
exposures on COPD risk is likely substantially less important than the effect of cigarette smoking.

Some investigators have reported increased respiratory symptoms in those living in urban compared to rural areas and Prolonged
exposure to smoke produced by biomass combustion. However, ambient air pollution is a much less important risk factor for COPD
than cigarette smoking.

PASSIVE, OR SECOND-HAND, SMOKING EXPOSURE Exposure of children to maternal smoking results in significantly reduced lung
growth. The importance of this risk factor in the development of the severe pulmonary function reductions in COPD remains
uncertain.

Severe 1 AT deficiency is a proven genetic risk factor for COPD. Many variants of the protease inhibitor (PI or SERPINA1) locus that
encodes 1 AT have been described. The common M allele is associated with normal 1 AT levels. The S allele, associated with
slightly reduced 1 AT levels, and the Z allele, associated with markedly reduced 1 AT levels. only approximately 1% of COPD
patients are found to have severe 1 AT deficiency as a contributing cause of COPD. PiZ individuals often develop early-onset COPD.

CLINICAL PRESENTATION

The three most common symptoms in COPD are cough, sputum production, and exertional dyspnea.

PHYSICAL FINDINGS In the early stages of COPD, patients usually have an entirely normal physical examination. In patients with
more severe disease, the physical examination is notable for a prolonged expiratory phase and may include expiratory wheezing. In
addition, signs of hyperinflation include a barrel chestm enlarged lung volumes with poor diaphragmatic excursion, exhibit use of
accessory muscles of respiration, sitting in the characteristic tripod position to facilitate the actions of the sternocleidomastoid,
scalene, and intercostal muscles.

Traditionally: emphysema (pink puffers) chronic bronchitis (blue bloaters): current evidence demonstrates that most patients have
elements of both bronchitis and emphysema and that the physical examination does not reliably differentiate the two entities.

Advanced disease may be accompanied by cachexia, with significant weight loss, bitemporal wasting, and diffuse loss of
subcutaneous adipose tissue. This syndrome has been associated with both inadequate oral intake and elevated levels of
inflammatory cytokines (TNF-). Some patients with advanced disease have paradoxical inward movement of the rib cage with
inspiration (Hoovers sign), the result of alteration of the vector of diaphragmatic contraction on the rib cage as a result of chronic
hyperinflation.

The hallmark of COPD is airflow obstruction (discussed above). Pulmonary function testing shows airflow obstruction with a
reduction in FEV1 and FEV1 /FVC (Chap. 306e). 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. More recently it has been shown that a multifactorial index incorporating airflow obstruction, exercise performance,
dyspnea, and body mass index is a better predictor of mortality rate than pulmonary function alone.

Arterial blood gases and oximetry may demonstrate resting or exertional hypoxemia. An elevated hematocrit suggests the presence
of chronic hypoxemia, as does the presence of signs of right ventricular hypertrophy. Recent guidelines have suggested testing for
1 AT deficiency in all subjects with COPD or asthma with chronic airflow obstruction.

Chest x-ray: Obvious bullae, paucity of parenchymal markings, or hyperlucency suggests the presence of emphysema.

Computed tomography (CT) scan is the current definitive test for establishing the presence or absence of emphysema in living
subjects. From a practical perspective, the CT scan currently does little to influence therapy of COPD except in individuals
considering surgical therapy for their disease) and as screening for lung cancer.

Spirometry - gold standard for diagnosis & assessment of COPD because most reproducible, standardized & objective way of
measuring airflow limitation. Where there is no access to spirometry, the diagnosis of COPD could be suspected on the basis of
history, symptoms and physical signs.
Only three interventionssmoking cessation, oxygen therapy in chronically hypoxemic patients, and lung volume reduction surgery
in selected patients with emphysemahave been demonstrated to influence the natural history of patients with COPD. There is
currently suggestive, but not definitive, evidence that the use of inhaled glucocorticoids may alter mortality rate (but not lung
function). All other current therapies are directed at improving symptoms and decreasing the frequency and severity of
exacerbations

SMOKING CESSATION

all patients with COPD should be strongly urged to quit smoking and educated about the benefits of quitting

bronchodilators are used for symptomatic benefit in patients with COPD. The inhaled route is preferred for medication delivery
because the incidence of side effects is lower than that seen with the use of parenteral medication delivery.

Anticholinergic. Ipratropium bromide improves symptoms and produces acute improvement in FEV1 . Tiotropium, a long-acting
anticholinergic, has been shown to improve symptoms and reduce exacerbations.

Beta Agonists These provide symptomatic benefit. The main side effects are tremor and tachycardia. Long-acting inhaled agonists,
such as salmeterol or formoterol, have benefits comparable to ipratropium bromide. Their use is more convenient than short-acting
agents. The addition of a agonist to inhaled anticholinergic therapy has been demonstrated to provide incremental benefit.

INHALED GLUCOCORTICOIDS reduce exacerbation frequency by ~25%

Theophylline produces modest improvements in expiratory flow rates and vital capacity and a slight improvement in arterial oxygen
and carbon dioxide levels in patients with moderate to severe COPD. Nausea is a common side effect. Monitoring of blood
theophylline levels is typically required to minimize toxicity. The selective phosphodiesterase 4 (PDE4) inhibitor roflumilast has been
demonstrated to reduce exacerbation frequency in COPD patients with chronic bronchitis and a prior history of exacerbations

Antibiotics As outlined below, there are strong data implicating bacterial infection as a precipitant of a substantial portion of
exacerbations. a randomized clinical trial of azithromycin, chosen for both its anti-inflammatory and antimicrobial properties,
demonstrated a reduced exacerbation frequency and longer time to first exacerbation

Supplemental O2 is the only pharmacologic therapy demonstrated to unequivocally decrease mortality rates in patients with COPD.

Patients with COPD should receive the influenza vaccine annually. Polyvalent pneumococcal vaccine is also recommended, although
proof of efficacy in this patient population is not definitive.

Pulmonary Rehabilitation This refers to a treatment program that incorporates education and cardiovascular conditioning. In COPD,
pulmonary rehabilitation has been demonstrated to improve health-related quality of life, dyspnea, and exercise capacity. It has also
been shown to reduce rates of hospitalization over a 6- to 12-month period

Lung Volume Reduction Surgery (LVRS) The National Emphysema Treatment trial demonstrated that LVRS offers both a mortality
benefit and a symptomatic benefit in certain patients with emphysema. Patients with upper lobepredominant emphysema and a
low post-rehabilitation exercise capacity are most likely to benefit from LVRS.

Lung Transplantation - COPD is currently the second leading indication for lung transplantation. Current recommendations are that
candidates for lung transplantation should have severe disability despite maximal medical therapy and be free of comorbid
conditions such as liver, renal, or cardiac disease.