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.

Researchers estimate the prevalence of chronic airflow obstruction in the world as

4-6%.

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable

disease with some significant extrapulmonary effects that may contribute to the

severity in individual patients. Its pulmonary component is characterized by

airflow limitation that is not fully reversible. The airflow limitation is usually

progressive and associated with an abnormal inflammatory response

of the lung to noxious particles or gases. The chronic airflow limitation

characteristic of COPD is caused by a mixture of small airway disease (obstructive

bronchiolitis) and parenchymal destruction (emphysema), the relative contributions

of which vary from person to person.

Etiology

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.

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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. The

most dangerous combination is work in a harmful environment and smoking.

An infectious factor is considered the second, which joins later, when

special conditions appear – on a background of chronic cough with

expectoration , favourable to infecting of bronchial tree.

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.

Pathogeny

chronic inflammation of bronchial tubes, parenchyma and lungs

Oxidative Stress

Protease-Antiprotease Imbalance

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.

CLINICAL PRESENTATION

The characteristic symptoms of COPD are chronic and progressive dyspnea,

cough, and sputum production. Chronic cough and sputum production may precede

the development of airflow limitation by many years.

Cough. Chronic cough, often the first symptom of COPD, is often discounted by

the patient as an expected consequence of smoking and/or environmental

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exposures. Initially, the cough may be intermittent, but later is present

every day, often throughout the day. The chronic cough in COPD may be

unproductive. In some cases, significant airflow limitation may develop without

the presence of a cough..

Sputum production. COPD patients commonly raise small quantities of tenacious

sputum after coughing. Regular production of sputum for 3 or more months in 2

consecutive years (in the absence of any other conditions that may explain it) is the

epidemiological definition of chronic bronchitis).

Dyspnea. Dyspnea, the hallmark symptom of COPD, is the reason most patients

seek medical attention and is a major cause of disability and anxiety associated

with the disease. Typical COPD patients describe their dyspnea as a sense of

increased effort to breathe, heaviness,air hunger.

DIAGNOSTICS

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 diagnosis19.

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• 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.

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.

CLASSIFICATION

Stages of COPD

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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.

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Differential diagnostics

For differential diagnostics of COPD with other bronchopulmonary diseases use

bronchoscopy , if necessary – biopsy.

Testimonies to bronchoscopy :

1) suspicion on a neoplasty process ;

2) intrabronchia foreign body ;

3) congenital anomalies of the respiratory system, tuberculosis of bronchial

tubes and lymphatic glands ;

4) bronchiectasis, abscess of lungs;

5) hemoptysis, pulmonary bleeding;

6) bronchial asthma in combination with a bronchitis, pneumonia;

7) with the purpose of sanation of bronchial tubes.

Contra-indications:

1) stenocardia;

2) acute myocardial infarction ;

3) chronic decompensated pulmonary heart;

4) General severe condition of patient.

Bronchography is used for diagnostics of multiple bronchiectasis.

Main reason of late diagnostics of COPD is absence of possibility of timely

research of FVD.

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.

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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.

Inhaled bronchodilators

Drugs Dose (mcg) Duration of

action

short-acting beta-agonists:

salbutamol (Ventolinum),

Fenoterol(Berotek).

100

100

4-6

4-6

short-acting cholinergic antagonist:

Ipratropiya bromide (Ipravent) 20, 40 6-8

Combined drugs

(short-acting beta-agonists +

short-acting cholinergic antagonist:

Fenoterol + Ipratropiya bromide (berodual)

salbutamol + Ipratropiya bromide (combivent)

Long-acting inhaled β2-agonists

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Salmeterol (Serevent)

Formoterol (Zafiron)

25, 50

4, 12

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Long-acting cholinergic antagonist

Tiotropiya bromide (Spiriva) 18 24

Theophylline and its various salts are medium-potency bronchodilators with

questionable anti-inflammatory propertie.

For maintenance therapy, long-acting theophylline compounds are available and

are usually given once or twice daily. Single-dose administration in the evening

reduces nocturnal symptoms and helps keep the patient complaint-free during the

day. They are now considered second-line therapy, and as such they are rarely used

in acute situations and infrequently in chronic ones.

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

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Antibiotics

In patients with COPD, chronic infection or colonization of the lower

airways is common from Streptococcus pneumoniae, Haemophilus influenzae, and

Moraxella catarrhalis.

Empiric antimicrobial therapy must be comprehensive and should cover all

likely pathogens in the context of the clinical setting. The goal of antibiotic therapy

in COPD is not to eliminate organisms but to treat acute exacerbations.

Exacerbations are indicated by increased sputum purulence and volume and the

development of dyspnea along with other features, including fever, leukocytosis, or

infiltrate on a chest radiograph.

The first-line treatment choices include amoxicillin, or cefaclor.

Second-line antibiotic regimens are the more expensive antibiotics, including

azithromycin, clarithromycin, and fluoroquinolones.

The use of antibiotics in patients with COPD is supported by the results of a meta-

analysis showing that patients who received oral antibiotic therapy had a small, but

clinically significant, improvement in peak expiratory flow rate and a more rapid

resolution of symptoms. Patients who benefitted most were those whose

exacerbations were characterized by at least 2 of the following: increases in

dyspnea, sputum production, and sputum purulence.

Mucolytic agents

These agents reduce sputum viscosity and improve secretion clearance. Viscous

lung secretions in patients with COPD consist of mucous-derived glycoproteins

and leukocyte-derived DNA.

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The oral agent N-acetylcysteine has antioxidant and mucokinetic properties and is

used to treat patients with COPD. However, the efficacy of mucolytic agents in the

treatment of COPD is debatable.

Complications

Respiratory failure is a syndrome in which the respiratory system fails in one

or both of its gas exchange functions: oxygenation and carbon dioxide elimination.

In practice, respiratory failure is defined as a PaO2 value of less than 60 mm Hg

while breathing air or a PaCO2 of more than 50 mm Hg. Furthermore, respiratory

failure may be acute or chronic. While acute respiratory failure is characterized by

life-threatening derangements in arterial blood gases and acid-base status, the

manifestations of chronic respiratory failure are less dramatic and may not be as

readily apparent.

The cause of respiratory failure often is evident after a careful history and

physical examination.

o Cardiogenic pulmonary edema usually develops in the context of a

history of left ventricular dysfunction or valvular heart disease.

o A history of previous cardiac disease, recent symptoms of chest pain,

paroxysmal nocturnal dyspnea, and orthopnea suggest cardiogenic

pulmonary edema.

o Noncardiogenic edema (eg, acute respiratory distress syndrome

[ARDS]) occurs in typical clinical contexts such as sepsis, trauma,

aspiration, pneumonia, pancreatitis, drug toxicity, and multiple

transfusions.

Classification of RF is based on clinical features:

RF has three degrees of severity:

- I degree - patient feels appearance of shortbreathing during the usual

physical exercises (the level of such exercises is individual for every patient and

depends on physical development);

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- II degree -shortbreathing appears during the insignificant physical

exercises (for example, at walking on an plane surface);

- III degree -shortbreathing is observed in a state of rest.

Pulmonary rehabilitation

o Many patients with COPD are unable to enjoy life to the fullest

because of shortness of breath, physical limitations, and inactivity.

o Pulmonary rehabilitation encompasses an array of therapeutic

modalities designed to improve the patient's quality of life by

decreasing airflow limitation, preventing secondary medical

complications, and alleviating respiratory symptoms.

o The 3 major goals of the comprehensive management of COPD are

the following:

1. Lessen airflow limitation

2. Prevent and treat secondary medical complications (eg,

hypoxemia, infection)

3. Decrease respiratory symptoms and improve quality of life

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