CHRONIC OBSTRUCTIVE PULMONARY DISEASE

CHRONIC OBSTRUCTIVE PULMONARY DISEASE(COPD)

INTRODUCTION

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. Many people suffer from this disease for years and die prematurely from it or its complications. COPD is the fourth leading cause of death in the world, and further increases in its prevalence and mortality can be predicted in the coming decades.

 In United States approximately 14.2 million people have COPD.Since 1982, the patients diagnosed with COPD increased by 41.5%. Researchers estimate the prevalence of chronic airflow obstruction in the United States as 8-17% for men and 10-19% for women. The prevalence rates increased in women by 30% in the last decade.

Mortality/Morbidity

Absolute mortality rates for US patients aged 55-84 years (1985) were 200 per 100,000 males and 80 per 100,000 females. Internationally, a marked variation in overall mortality rates from COPD exists. The extremes are the more than 400 deaths per 100,000 males aged 65-74 years in Romania and the fewer than 100 deaths per 100,000 in Japan.

Sex

Researchers estimate that 4-6% of white male adults and 1-3% of white female adults have emphysema or COPD. Men have a higher mortality rate than women, but mortality due to COPD in women is expected to increase.

PATHOLOGY

Pathological changes characteristic of COPD are found in the proximal airways, peripheral airways, lung parenchyma,and pulmonary vasculature. The pathological changes include chronic inflammation, with increased numbers of specific inflammatory cell types in different parts of the lung, and structural changes resulting from repeated injury and repair. In general, the inflammatory and structural changes in the airways increase with disease severity and persist on smoking cessation.

Pathological Changes in COPD

Proximal airways (trachea, bronchi more 2 mm internal diameter)

Inflammatory cells: increasing of macrophages, CD8+ (cytotoxic)

T- lymphocytes, few neutrophils or eosinophils

Structural changes: Goblet cells, enlarged submucosal glands (both

leading to mucus hypersecretion), squamous metaplasia of epithelium

Peripheral airways (bronchioles less 2mm )

Inflammatory cells: Macrophages, T lymphocytes (CD8+ more than CD4+),

B lymphocytes, lymphoid follicles, fibroblasts, few neutrophils

or eosinophils

Structural changes: Airway wall thickening, peribronchial fibrosis, luminal

inflammatory exudate, airway narrowing (obstructive bronchiolitis)

Increased inflammatory response and exudate correlated with disease

severity

Lung parenchyma (respiratory bronchioles and alveoli)

Inflammatory cells: Macrophages, CD8+ T lymphocytes

Structural changes: Alveolar wall destruction, apoptosis of epithelial

and endothelial cells

• Centrilobular emphysema: dilatation and destruction of respiratory

bronchioles; most commonly seen in smokers

• Panacinar emphysema: destruction of alveolar sacs as well as respiratory

bronchioles; most commonly seen in alpha-1 antitrypsin deficiency

Pulmonary vasculature

Inflammatory cells: Macrophages, T lymphocytes

Structural changes: Thickening of intima, endothelial cell dysfunction,

smooth muscle pulmonary hypertension.

PATHOGENESIS

Inflammatory Cells

COPD is characterized by a specific pattern of inflammation involving neutrophils, macrophages, and lymphocytes. These cells release inflammatory mediators and interact with structural cells in the airways and lung parenchyma.

Inflammatory Mediators

The wide variety of inflammatory mediators that have been shown to be increased in COPD patients attract inflammatory cells from the circulation (chemotactic factors), amplify the inflammatory process (proinflammatory cytokines), and induce structural changes (growth factors).

Oxidative Stress

Oxidative stress may be an important amplifying mechanism in COPD. Biomarkers of oxidative stress (e.g., hydrogen peroxide, 8-isoprostane) are increased in the exhaled breath condensate, sputum, and systemic circulation of COPD patients. Oxidative stress is further increased in exacerbations. Oxidants are generated by cigarette smoke and other inhaled particulates, and released from activated inflammatory cells such as macrophages and neutrophils. There may also be a reduction in endogenous antioxidants in COPD patients. Oxidative stress has several adverse consequences in the lungs, including activation of inflammatory genes, inactivation of antiproteases, stimulation of mucus secretion, and stimulation of increased plasma exudation. Many of these adverse effects are mediated by peroxynitrite, which is formed via an interaction between superoxide anions and nitric oxide. In turn, the nitric oxide is generated by inducible nitric oxide synthase, which is expressed in the peripheral airways and lung parenchyma of COPD patients. Oxidative stress may also account for a reduction in histone deacetylase activity in lung tissue fromCOPD patients, which may lead to enhanced expression of inflammatory genes and also a reduction in the antiinflammatoryaction of glucocorticosteroids.

Protease-Antiprotease Imbalance

There is compelling evidence for an imbalance in the lungs of COPD patients between proteases that break down connective tissue components and antiproteases that protect against this. Several proteases, derived from inflammatory cells and epithelial cells, are increased in COPD patients. There is increasing evidence that they may interact with each other. Protease-mediated destruction of elastin, a major connective tissue component in lung parenchyma, is an important feature of emphysema and is likely to be irreversible.

PATHOPHYSIOLOGY

Airflow Limitation and Air Trapping

The extent of inflammation, fibrosis, and luminal exudates in small airways is correlated with the reduction in FEV1 and FEV1/FVC ratio, and probably with the accelerated decline in FEV1 characteristic of COPD4. This peripheral airway obstruction progressively traps air during expiration, resulting in hyperinflation. Although emphysema is more associated with gas exchange abnormalities than with reduced FEV1, it does contribute to air trapping during expiration. This is especially so as alveolar attachments to small airways are destroyed when the disease becomes more severe. Hyperinflation reduces inspiratory capacity such that functional residual capacity increases, particularly during exercise (when this abnormality is known as dynamic hyperinflation), and this results in dyspnea and limitation of exercise capacity. It is now thought that hyperinflation develops early in the disease and is the main mechanism for exertional dyspnea. Bronchodilators acting on peripheral airways reduce air trapping, thereby reducing lung volumes and improving symptoms and exercise capacity.

Gas Exchange Abnormalities

Gas exchange abnormalities result in hypoxemia and hypercapnia, and have several mechanisms in COPD. In general, gas transfer worsens as the disease progresses. The severity of emphysema correlates with arterial PO2 and other markers of ventilation-perfusion (VA/Q) imbalance. Peripheral airway obstruction also results inVA/Q imbalance, and combines with ventilatory muscle impaired function in severe disease to reduce ventilation, leading to carbon dioxide retention. The abnormalities in alveolar ventilation and a reduced pulmonary vascular bed further worsen the VA/Q abnormalities.

Mucus Hypersecretion

Mucus hypersecretion, resulting in a chronic productive cough, is a feature of chronic bronchitis and is not necessarily associated with airflow limitation. Conversely, not all patients with COPD have symptomatic mucus hypersecretion. When present, it is due to mucous metaplasia with increased numbers of goblet cells and enlarged submucosal glands in response to chronic airway irritation by cigarette smoke and other noxious agents. Several mediators and proteases stimulate mucus hypersecretion and many of them exert their effects through the activation of epidermal growth factor receptor (EGFR).

Pulmonary Hypertension

Mild to moderate pulmonary hypertension may develop late in the course of COPD and is due to hypoxic vasoconstriction of small pulmonary arteries, eventually resulting in structural changes that include intimal hyperplasia and later smooth muscle hypertrophy/hyperplasia17. There is an inflammatory response in vessels similar to that seen in the airways and evidence for endothelial cell dysfunction. The loss of the pulmonary capillary bed in emphysema may also contribute to increased pressure in the pulmonary circulation. Progressive pulmonary hypertension may lead to right ventricular hypertrophy and eventually to right-side cardiac failure (cor pulmonale).

Systemic features

It is increasingly recognized that COPD involves several systemic features, particularly in patients with severe disease, and that these have a major impact on survival and comorbid diseases. Cachexia is commonly seen in patients with severe COPD. There may be a loss of skeletal muscle mass and weakness as a result of increased apoptosis and/or muscle disuse. Patients with COPD also have increased likeliness of having osteoporosis, depression and chronic anemia. Increased concentrations of inflammatory mediators, including TNF- IL-6, and oxygen-derived free radicals,may mediate some of these systemic effects. There is an increase in the risk of cardiovascular diseases, which is correlated with an increase in C-reactive protein (CRP)

CLINICAL PRESENTATION

1.            RISK FACTORS

•             Genes

COPD is a polygenic disease and a classic example of gene-environment interaction. The genetic risk factor that is best documented is a severe hereditary deficiency of alpha-1 antitrypsin. A significant familial risk of airflow obstruction has been observed in smoking siblings of patien with severeCOPD, suggesting that genetic factors  could influence this susceptibility. Through genetic linkage analysis,several regions of the genome have been identified that likely contain COPD susceptibility genes, including chromosome.Genetic association studies have implicated a variety of genes in COPD pathogenesis, including transforming growth factor beta 1 (TGF-_1) microsomal epoxide hydrolase 1 (mEPHX1), and tumor necrosis factor alpha (TNF_). However, the results of these genetic association studies have been largely inconsistent, and functional genetic variants influencing the development of COPD (other than alpha-1 antitrypsin deficiency) have not been definitively identified.

•             Inhalational Exposures

Because individuals may be exposed to a variety of different types of inhaled particles over their lifetime, it is helpful to think in terms of the total burden of inhaled particles. Each type of particle, depending on its size and composition, may contribute a different weight to the risk, and the total risk will depend on the integral of the inhaled exposures Of the many inhalational exposures that may be encountered over a lifetime, only tobacco smoke and occupational dusts and chemicals(vapors, irritants, and fumes) are known to cause COPD on their own. Tobacco smoke and occupational exposures also appear to act additively to increase the risk of developing COPD. However this may reflect an inadequate data base from populations who are exposed to other risk factors, such as heavy exposures to indoor air pollution from poorly vented biomass cooking and heating.

•             Tobacco Smoke:

Cigarette smoking is by far the most commonly encountered risk factor for COPD. Cigarette smokers have a higher prevalence of respiratory symptoms and lung function abnormalities, a greater annual rate of decline in FEV1, and a greater COPD mortality rate than nonsmokers. Pipe and cigar smokers have greater COPD morbidity and mortality rates than nonsmokers, although their rates are lower than those for cigarette smokers. Other types of tobacco smoking popular in various countries are also risk factors for COPD. although their risk relative to cigarette smoking has not been reported. The risk for COPD in smokers is dose-related. Age at starting to smoke, total pack-years smoked, and current smoking status are predictive of COPD mortality. Not all smokers develop clinically significant COPD, which suggests that genetic factors must modify each individual’s risk.

•             Occupational Dusts and Chemicals:

Occupational exposures are an underappreciated risk factor for COPD. These exposures include organic and inorganic dusts and chemical agents and fumes. An analysis of the large US population-based NHANES III survey of almost 10,000 adults aged 30-75 years, which included lung function tests, estimated the fraction of COPD attributable to work

was 19.2% overall, and 31.1% among never smokers16.These estimates are consistent with a statement published by the American Thoracic Society that concluded that occupational exposures account for 10-20% of either symptoms or functional impairment consistent with COPD.

•             Indoor Air Pollution:

Wood, animal dung, crop residues,and coal, typically burned in open fires or poorly functioning stoves, may lead to very high levels of indoor air pollution.The evidence that indoor pollution from biomass cooking and heating in poorly ventilated dwellings is an important risk factor for COPD (especially among women in developing countries) continues to grow, with case-control studies and other robustly designed studies now available.

•             Outdoor Air Pollution:

High levels of urban air pollutionare harmful to individuals with existing heart or lung disease.The role of outdoor air pollution in causing COPD is unclear,but appears to be small when compared with that of cigarette smoking. It has also been difficult to assess the effects of single pollutants in long-term exposure to atmospheric pollution. However, air pollution from fossil fuel combustion,primarily from motor vehicle emissions in cities, is associated with decrements of respiratory function. The relative effects of short-term, high-peak exposures and long-term,low-level exposures is a question yet to be resolved.

2.            Assessment of Symptoms

Although exceptions occur, the general patterns of symptom development in COPD is well established. The main symptoms of patients in

Stage I: Mild COPD are chronic cough and sputum production. These symptoms can be present for many years before the development of airflow limitation and are often ignored or discounted by patients and attributed to aging or lack of conditioning. As airflow limitation worsens in

Stage II: Moderate COPD, patients often experience dyspnea, which may interfere with their daily activities1. Typically, this is the stage at which they seek medical attention and may be diagnosed with COPD. However, some patients do not experience cough, sputum production, or dyspnea and do not come to medical attention until their airflow limitation becomes more severe or their lung function is worsened acutely by a respiratory tract infection.

Stage III: Severe COPD: symptoms of cough and sputum production typically continue, dyspnea worsens, and additional symptoms heralding complications (such as respiratory failure, right heart failure, weight loss, and arterial hypoxemia) may develop. It is important to note that, since COPD may be diagnosed at any stage, any of the symptoms described below may be present in a patient presenting for the first time.

Additional features in severe disease.

Weight loss and anorexia are common problems in advanced COPD. They are prognostically important13 and can also be a sign of other diseases (e.g., tuberculosis, bronchial tumors), and therefore should always be investigated. Cough syncope occurs due to rapid increases in intrathoracic pressure

during attacks of coughing. Coughing spells may also cause rib fractures, which are sometimes asymptomatic. Ankle swelling may be the only symptomatic pointer to the development of cor pulmonale. Finally, psychiatric morbidity, especially symptoms of depression and/or anxiety, is common in advanced COPD and merits specific enquiry in the clinical history.

3.Investigations

Medical History

A detailed medical history of a new patient known or thought to have COPD should assess:

Physical Examination

Though an important part of patient care, a physical examination is rarely diagnostic in COPD. Physical signs of airflow limitation are usually not present until significant impairment of lung function has occurred and their detection has a relatively low sensitivity and specificity.A number of physical signs may be present in COPD, but their absence does not exclude the diagnosis.

Inspection.

• Central cyanosis, or bluish discoloration of the mucosal membranes, may be present but is difficult to detect in artificial light and in many racial groups.

• Common chest wall abnormalities, which reflect the pulmonary hyperinflation seen in COPD, include relatively horizontal ribs, “barrel-shaped” chest, and protruding abdomen.

• Resting respiratory rate is often increased to more than 20 breaths per minute and breathing can be relatively shallow.

• Ankle or lower leg edema can be a sign of right heart failure.

Palpation and percussion.

• These are often unhelpful in COPD.

• Detection of the heart apex beat may be difficult due to pulmonary            hyperinflation.

• Hyperinflation also leads to downward displacement of the liver and an increase in the ability to palpate this organ without it being enlarged.

Auscultation.

• Patients with COPD often have reduced breath sounds, but this finding is not sufficiently characteristic to make the diagnosis.

• The presence of wheezing during quiet breathing is a useful pointer to airflow limitation. However, wheezing heard only after forced expiration has not been validated as a diagnostic test for COPD.

• Inspiratory crackles occur in some COPD patients but are of little help diagnostically.

• Heart sounds are best heard over the xiphoid area.

OTHER CRITARIA

This is usually clinical (GOLD criteria). There is a history of breathlessness and sputum production in a lifetime smoker. In the absence of a history of cigarette smoking a working diagnosis of asthma is usual unless there is a family history of lung disease suggestive of a deficiency of α1-antitrypsin inhibitor. The patient may have signs of hyperinflation and typical pursed lip respiration. No individual clinical feature is diagnostic. Emphysema is often incorrectly diagnosed on signs of overinflation of the lungs (e.g. loss of liver dullness on percussion), but this may occur with other diseases such as asthma. Furthermore, centri-acinar emphysema may be present without signs of overinflation. Some elderly men (without emphysema) develop a barrel-shaped chest as a result of osteoporosis of the spine, and a consequent decrease in height.

Lung function tests

show evidence of airflow limitation. The ratio of the FEV1 to the FVC is reduced and the PEFR is low. In many patients the airflow limitation is reversible to some extent (usually a change in FEV1 of < 15%), and the distinction between asthma and COPD can be difficult. Lung volumes may be normal or increased, and the gas transfer coefficient of carbon monoxide is low when significant emphysema is present.

Chest X-ray

is often normal, even when the disease is advanced. The classic features are the presence of bullae, severe overinflation of the lungs with low, flattened diaphragms, and a large retrosternal air space on the lateral film. There may also be a deficiency of blood vessels in the periphery of the lung fields compared with relatively easily visible proximal vessels.

Haemoglobin level and PCV

can be elevated as a result of persistent hypoxaemia (secondary polycythaemia,

Blood gases

are often normal. In the advanced case there is evidence of hypoxaemia and hypercapnia.

Sputum examination

is unnecessary in the ordinary case as Strep. pneumoniae or H. influenzae are the only common organisms to produce acute exacerbations. Occasionally Moraxella catarrhalis may cause infective exacerbations.

Electrocardiogram.

In advanced cor pulmonale the P wave is taller (P pulmonale) and there may be right bundle branch block (RSR' complex) and the changes of right ventricular hypertrophy.

Echocardiogram –

performed to assess cardiac function.

α1-Antitrypsin levels.

The normal range is 2-4 g/L.

Measurement of Airflow Limitation (Spirometry)1

Spirometry should be undertaken in all patients who may have COPD. It is needed to make a confident diagnosis of COPD and to exclude other diagnoses that may present with similar symptoms. Spirometry should measure the volume of air forcibly exhaled from the point of maximal inspiration (forced vital capacity, FVC) and the volume of air exhaled during the first second of this maneuver (forced expiratory volume in one second, FEV1), and the ratio of these two measurements (FEV1/FVC) should be calculated. Spirometry measurements are evaluated by comparison with reference values based on age, height, sex, and race (use appropriate reference values).

Additional Investigations

For patients diagnosed with Stage II: Moderate COPD and beyond, the following additional investigations may be considered.

Bronchodilator reversibility testing.

Despite earlier hopes, neither bronchodilator nor oral glucocorticosteroid reversibility testing predicts disease progression, whether judged by decline in FEV1, deterioration of health status,or frequency of exacerbations in patients with a clinical diagnosis of COPD and abnormal spirometry. Small changes in FEV1 (e.g., < 400 ml) after administration of a bronchodilator do not reliably predict the patient’s response to treatment (e.g., change in exercise capacity). Minor variations in initial airway caliber can lead to different classification of reversibility status depending on the day of testing, and the lower the pre-bronchodilator FEV1, the greater the chance of a patient being classified as reversible even when the 200 ml volume criterion is included.

Differential Diagnosis

In some patients with chronic asthma, a clear distinction from COPD is not possible using current imaging and physiological testing techniques, and it is assumed that asthma and COPD coexist in these patients. In these cases, current management is similar to that of asthma. Other potential diagnoses are usually easier to distinguish from COPD.

Figure 5.1-7. Differential Diagnosis of COPD

Diagnosis                                Suggestive Features

COPD                                      Onset in mid-life.

                                                 Symptoms slowly progressive.

                                                 Long history of tobacco smoking.

                                                 Dyspnea during exercise.

                                                 Largely irreversible airflow limitation.

Asthma                                    Onset early in life (often childhood).

                                                 Symptoms vary from day to day.

                                                 Symptoms at night/early morning.

                                                Allergy, rhinitis, and/or eczema also present.

                                                 Family history of asthma.

                                                 Largely reversible airflow limitation.

Congestive Heart Failure        Fine basilar crackles on auscultation.

                                                Chest X-ray shows dilated heart,

                                                 pulmonary edema.

                                                Pulmonary function tests indicate

                                                volume restriction, not airflow limitation.

Bronchiectasis                         Large volumes of purulent sputum.

                                                Commonly associated with bacterial infection.

                                                Coarse crackles/clubbing on auscultation.

                                                Chest X-ray/CT shows bronchial dilation,

                                                 bronchial wall thickening.

Tuberculosis                           Onset all ages

                                                Chest X-ray shows lung infiltrate.

                                                Microbiological confirmation.

                                                High local prevalence of tuberculosis.

Obliterative Bronchiolitis       Onset in younger age, nonsmokers.

                                                May have history of rheumatoid arthritis or

                                                fume exposure.

                                                CT on expiration shows hypodense areas.

Diffuse Panbronchiolitis         Most patients are male and nonsmokers.

                                                Almost all have chronic sinusitis.

                                                Chest X-ray and HRCT show diffuse small

                                                Centrilobular nodular opacities and

                                                hyperinflation.

Stages of COPD

The impact of COPD on an individual patient depends not just on the degree of airflow limitation, but also on the severity of symptoms (especially breathlessness and decreased exercise capacity). There is only an imperfect relationship between the degree of airflow limitation and the presence of symptoms. Spirometric staging,therefore, is a pragmatic approach aimed at practical implementation and should only be regarded as an educational tool and a general indication to the initial approach to management.

Stage I: Mild COPD - Characterized by mild airflow limitation (FEV1/FVC < 0.70; FEV1 ≥80% predicted).Symptoms of chronic cough and sputum production may be present, but not always. At this stage, the individual is usually unaware that his or her lung function is abnormal.

Stage II: Moderate COPD - Characterized by worsening airflow limitation (FEV1/FVC < 0.70; 50% ≤FEV1 < 80% predicted), with shortness of breath typically developing on exertion and cough and sputum production sometimes also present. This is the stage at which patients typically seek medical attention because of chronic respiratory symptoms or an exacerbation of their disease.

Stage III: Severe COPD - Characterized by further worsening of airflow limitation (FEV1/FVC < 0.70; 30% ≤FEV1 < 50% predicted), greater shortness of breath,reduced exercise capacity, fatigue, and repeated exacerbations that almost always have an impact on patients’ quality of life.

Stage IV: Very Severe COPD - Characterized by severe airflow limitation (FEV1/FVC < 0.70; FEV1 < 30% predicted or FEV1 < 50% predicted plus the presence of chronic respiratory failure). Respiratory failure is defined as an arterial partial pressure of O2 (PaO2) less than 8.0 kPa (60 mm Hg), with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) whilebreathing air at sea level. Respiratory failure may alsolead to effects on the heart such as cor pulmonale (right heart failure). Clinical signs of cor pulmonale include elevation of the jugular venous pressure and pitting ankleedema. Patients may have Stage IV: Very Severe COPD even if the FEV1 is > 30% predicted, whenever these complications are present. At this stage, quality of life is very appreciably impaired and exacerba-tions may be life threatening.

PHARMACOLOGIC TREATMENT

Pharmacologic therapy is used to prevent and control symptoms, reduce the frequency and severity of exacerbations, improve health status, and improve exercise tolerance.

Drug Category: Bronchodilators

These agents act to decrease muscle tone in both small and large airways in the lungs, thereby increasing ventilation. Category includes subcutaneous medications, beta-andrenergics, methylxanthines, and anticholinergics. Bronchodilator medications are central to symptom management in COPD.

Inhaled therapy is preferred. The choice between _2-agonist, anticholinergic,

theophylline, or combination therapy depends on availability and individual response in terms of symptom relief and side effects. Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms. Long-acting inhaled bronchodilators are more effective and convenient. Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

B2-agonists. The principal action of _2-agonists is to relax airway smooth muscle by stimulating _2-adrenergic receptors, which increases cyclic AMP and produces functional antagonism to bronchoconstriction. Oral therapy

is slower in onset and has more side effects than inhaled treatment..

Anticholinergics. The most important effect of anticholinergic medications, such as ipratropium, oxitropium and tiotropium bromide, in COPD patients appears to be blockage of acetylcholine’s effect on M3 receptors.

Drug Category: Corticosteroids  

A recent meta-analysis of 16 controlled trials in stable COPD found that approximately 10% of patients respond to these drugs. The responders should be identified carefully. An increase in FEV1 >20% is used as surrogate marker for steroid response. In acute exacerbation, steroids improve symptoms and lung functions. Inhaled steroids have fewer adverse effects compared to oral agents. Although effective, these agents improve expiratory flows less effectively than oral preparations, even at high doses. These agents may be beneficial in slowing rate of progression in a subset of patients with COPD who have rapid decline.

ANTIBIOTICS

Patients with COPD are frequently colonized with potential respiratory pathogens and it is often difficult to identify conclusively a specific species of bacteria responsible for a particular clinical event. Bacteria frequently implicated in COPD exacerbations include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In addition, Mycoplasma pneumoniae or Chlamydia pneumoniae are found in 5 to 10% of exacerbations. The choice of antibiotic should be based on local patterns of antibiotic susceptibility of the above pathogens, as well as the patient's clinical condition. Most practitioners treat patients with moderate or severe exacerbations with antibiotics, even in the absence of data implicating a specific pathogen.

Prognosis

•             The predictors of mortality are aging, continued smoking, accelerated decline in FEV1, moderate-to-severe airflow obstruction, poor bronchodilator response, severe hypoxemia, the presence of hypercapnia, development of cor pulmonale, and overall poor functional capacity.

•             The mortality rate is 24% in patients admitted to the ICU with an acute exacerbation; this doubles for patients aged 65 years or older. FEV1 is a reliable predictor of mortality from COPD. The mortality rate for patients who have an FEV1 of less than 0.75 L/s is 30% at 1 year and 95% at 10 years.

•             The American Thoracic Society (ATS) has recommended the clinical staging of COPD severity according to lung function. Stage I is FEV1 of equal or more than 50% of the predicted value. Stage II is FEV1 35-49% of the predicted value, and stage III is FEV1 less than 35% of the predicted value.