Chronic Obstructive Pulmonary Disease (COPD) Causes, Symptoms And Treatment

According to the World Health Organization, chronic obstructive pulmonary disease is characterized by airflow limitation that is not fully reversible. Airflow limitation is usually both progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. These noxious particles or gases cause the release of inflammatory mediators. Obstructive disease is manifested by limitation of airflow due to increased resistance caused by partial or complete obstruction at any level. Chronic obstructive pulmonary disease (COPD) is the 4th largest cause of death in the world. It kills more than 3 million people every year. It will rank fifth in the burden of disease & third as a cause of death. According to the World Health Organization, it kills more people as compared to HIV-AIDS, malaria and tuberculosis. Males are at higher risk for developing COPD as compared to females. The risk of COPD increases with increasing age. Smoking also increases the chance for the development of COPD. People with α1-antitrypsin deficiency, airway hyper responsiveness & allergy, lung growth and low birth weight are at higher risk for developing COPD.

Causes

The airflow limitation reported in COPD can be either reversible or irreversible.  The reversible airflow limitation is caused by the following factors,

• Due to the presence of mucus and inflammatory cells and mediators in bronchial secretions
• The contraction of bronchial smooth muscle in peripheral and central airways
• Due to the dynamic hyperinflation during exercise

The irreversible airflow limitation is caused by the following factors,

• Due to the destruction of alveolar support
• Due to fibrosis & narrowing of airways
• As a result of reduced elastic recoil with loss of alveolar surface area

Chronic inflammation is caused by the activation of the innate and adaptive immune system. When you inhale noxious agents (cigarette smoke), it leads to the activation of resident immune and parenchymal cells. This activation will recruit additional inflammatory cells from the systemic compartment into the resident tissue and airway. The activation and recruitment of immune cells causes the increased production and release of inflammatory mediators and cytokines such as leukotriene B4, interleukin-8 and tumor necrosis factor-α (TNF-α). The actions of these inflammatory mediators damage the lungs and leads to the development of COPD. Proteinase antiproteinase imbalance is a genetic factor responsible for the development of emphysema in alpha-1 antitrypsin deficient individuals. While in chronic obstructive pulmonary disease, proteases enzyme is increased and antiproteases is decreased. Antiproteinase is alpha-1 antitrypsin that inhibits lung damage. Uncontrolled proteinase reduction causes the destruction of alveolar space and results in airspace enlargement. The inflammatory, immune and epithelial cells of the airways generate increased amounts of reactive oxygen. Due to this reactive oxygen and inhaled oxidants, the oxidative stress is generated which causes cellular dysfunction and damage to the lung.

Symptoms

The clinical presentation of chronic obstructive pulmonary disease particularly in severe disease depends on whether,

• Bronchitis
• Emphysema

Bronchitis

In case of bronchitis, the following symptoms are reported,

• Cyanosis (bluish discoloration of skin)
• Crackles (pop opening of small airways and alveoli)
• Wheezing
• Hypercapnia (increase the level of CO2 in blood)
• Hypoxemia (increase the level of O2 in blood)
• Prolong expiration
• Excessive mucus production
• Chronic productive cough
• Dyspnea

Emphysema

In case of emphysema, the following symptoms are reported,

• Pink skin
• Pursed lips breathing
• Accessory muscle use
• Cachectic appearance due to anorexia, increase the work of breathing
• Hyperinflation/barrel chest
• Decrease the breath sound
• Dyspnea(shortness of breath)
• Minimal cough
• Mucous production is scanty and mucoid
• Tachypnea (abnormal rapid breathing)
• Digital clubbing
• Thin in appearance

Treatment:

The aim of treatment in COPD is to relieve the patient from the symptoms. The standard treatment plan of COPD may include the following medications,

1. Bronchodilators

• β2-Agonist

• Anticholinergics

• Methylxanthines

2. Anti-inflammatory Agents:

•  Corticosteroids

3. Antibiotics

4.Alpha Antitrypsin Augmentation Therapy

Bronchodilators

Bronchodilators are used to dilate the bronchioles of the lungs.

β2-Agonist

β2-agonists produce bronchodilation by relaxing bronchial smooth muscles. They activate the adenylyl cyclase enzyme that catalyzes the formation of cAMP (cyclic adenosine monophosphate). cAMP is a smooth muscle relaxant (bronchodilator). Also more than 1mg dose of β2-Agonist cannot increase its effectiveness. There are two types of β2-agonist, short acting and long acting. The short acting β2 agonists include albuterol, metaproterenol, terbutaline, fenoterol, isoprenaline and procaterol. Formoterol, salmeterol, bambuterol and clenbuterol are long acting β2 agonists.

Anticholinergics

The cholinergic stimulation increases the activity of guanylyl cyclase. Guanylyl cyclase is the enzyme that is responsible for the formation of cyclic guanosine 3’,5’ monophosphate (cGMP). cGMP causes bronchoconstriction. Anticholinergic drugs inhibit cGMP in lungs and inhibit bronchoconstriction. The anticholinergic medicines used are aclidinium, tiotropium and ipratropium.

Methylxanthines

Methylxanthines is a non-specific phosphodiesterase inhibitor. Phosphodiesterase is the enzyme that catalyzes the breakdown of cAMP. So phosphodiesterases inhibitors inhibit the breakdown of cAMP and increase the level of cAMP in the body. They also act as antagonists for prostaglandins (PGE₂ are the PG’s that cause the inflammation in the COPD so antagonists reverse their action). They are also adenosine receptor blocker. Adenosine is the bronchoconstrictor that decreases the overnight decline in FEV (Forced Expiratory Volume) and decreases early morning symptoms. Theophylline and aminophylline are the most commonly used methylxanthines.

Anti-inflammatory drugs (corticosteroids)

Corticosteroids are used to reduce the inflammation due to chronic obstructive pulmonary disease. They can also improve FEV 1 (Forced Expiratory Volume), exercise improvement and dyspnea. They inhibit inflammation through histone deacetylase (HDAC) enzymes that switch off activated inflammatory genes. They are always used in combination with beta agonists or other bronchodilators. The most commonly prescribed corticosteroids are methylprednisolone and budesonide.

Antibiotics

The most commonly prescribed antibiotics are doxycycline, ampicillin, amoxicillin and cotrimoxazole. Antibiotics are recommended when sputum production and sputum purulence and dyspnea increases.

Alpha 1-antitrypsin augmentation therapy

Alpha-1 antitrypsin is a glycoprotein produced by Liver. Its main function is to balance the action of neutrophil-protease enzymes in the lungs. Neutrophils are the cells that are responsible for the inflammation in the COPD. Alpha-1 antitrypsin is protease inhibitor. The normal level of alpha-1 antitrypsin is 100-150mg/dl. If this level falls below 80mg/dl then it needs augmentation therapy. IV-Augmentation therapy is for the individuals with AAT deficiency and moderate airflow obstruction (FEV ı 35-60%). Three preparations of alpha-1 antitrypsin augmentation therapy are available. All preparations have the same dosage of 60 mg/kg/wk.