Understanding Gastroesophageal Reflux Disease(GERD)

COPD: Causes, Symptoms, Diagnosis & Treatment

Chronic Obstructive Pulmonary Disease (COPD)

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

COPD is an infection state depicted through airflow limitation or restriction that isn't totally reversible. Airflow constraint is by and large both reformist and is connected with a bizarre inflammatory response of the lungs to poisonous particles or gases. It is also manifested by an extent of obsessive changes in the lung, extra aspiratory impacts, and comorbidities that may contribute to the seriousness of contamination in individual patients.

Hence, COPD ought to be viewed as an aspiratory sickness, however, these huge comorbidities should be considered in a complete symptomatic appraisal of seriousness and in deciding best and effective treatment.

OBSTRUCTIVE DISEASE

Obstructive diseases are characterized by limitation of airflow due to increased resistance caused by partial or complete obstruction at any level.

RESTRICTIVE DISEASE

Reduced expansion of lung parenchyma accompanied by decreased total lung capacity is referred to as restrictive disease.

COPD for the most part alludes to emphysema or chronic bronchitis. Emphysema is obsessively characterized and described by alveolar wall annihilation and airspace expansion. Chronic bronchitis is clinically characterized as a persistent hack or cough for at least 3 months for 2 continuous years. Its pathologic trademark includes aggravation and fibrosis of the little airways.

Mainly, much cross-over exists between these two conditions because both are brought about by cigarette smoking. It ought to likewise be called that small airway inflammation is a significant quality of COPD, which seems to connect with the more serious phases of the illness whether the patient has "ongoing bronchitis.

Asthma, the other significant infection element described via airflow limitation, can coincide in patients with COPD. In any case, the pattern of airway inflammation in asthma varies fundamentally from that which happens in COPD, and asthma isn't by and large thought-about part of the range of COPD.

The critical risk factor for developing COPD is cigarette smoking. People having COPD have a current or past history of cigarette smoking.

Inhalation of toxic specialists, for example, tobacco smoke, prompts the enactment of occupant insusceptible and parenchymal cells, which thus select extra incendiary cells from the foundational compartment into the lung. The specific components liable for the pathogenesis of COPD are not altogether clear, yet likely include actuation of the inborn and versatile safe framework, prompting persistent inflammation.

As COPD advances, extra foundational results can emerge, including cachexia, cardiovascular and skeletal muscle brokenness, osteoporosis, sorrow, and iron deficiency. Aspiratory restoration is prescribed to address these foundational indications.

The determination of COPD depends on the presence of hazard factors (normally including smoking), clinical side effects, and airflow impediment dependent on spirometric testing. By and large, COPD shows in the 6th decade of life (or later) with indications of hack, wheeze, or dyspnea on effort. The seriousness of illness depends on organizing models, which then, at that point guides treatment.

EPIDEMIOLOGY OF COPD

Chronic Obstructive Pulmonary Disease (COPD) kills multiple million individuals consistently, making it the fourth-biggest reason for death in the world. It has been assessed that by the year 2020, COPD will rank fifth in weight of illness and third as a reason for death. As per the World Health Organization, COPD kills a greater number of individuals than HIV-AIDS, Malaria and tuberculosis all set up in the southeast Asian area.

CAUSES OF COPD

REVERSIBLE CAUSES

1. Presence of mucus and inflammatory cells and mediators in bronchial secretions.       
2. Bronchial smooth muscle contraction in peripheral and central airways.
3. Dynamic hyperinflation during exercise.

IRREVERSIBLE CAUSES

1. Fibrosis & narrowing of airways.
2. Reduced elastic recoil with loss of alveolar surface area.
3. Destruction of alveolar support with reduced patency of small airways

The exact mechanisms responsible for the pathogenesis of COPD are not entirely clear, but likely involve activation of the innate and adaptive immune system leading to chronic inflammation. As a general rule, inhalation of toxic specialists, for example, tobacco smoke, prompts the initiation of inhabitant immune and parenchymal cells, which thus enroll extra incendiary cells from the foundational compartment into the occupant tissue and aviation route.

The activation and recruitment of immune cells are because largely mediated through the production and release of cytokines and chemokines. Recent proof likewise upholds a job for oxidant stress as an illness middle person. The results of an oxidant-rich environment incorporate the initiation of fiery qualities, inactivation of antiproteases, incitement of bodily fluid discharge, and expansions in plasma exudate.

When the local concentration of antiproteases becomes overwhelmed, proteases go unchecked and destroy the major connective tissue components in the lung, such as elastin, leading to the irreversible loss of alveoli. The classic example of this occurs in patients with α1-antitrypsin deficiency.

Although the traditional idea of disease pathogenesis focuses on smoking-related lung injury, more recent hypotheses suggest that another important component of disease pathogenesis may involve inadequate lung repair. For sure, there is proof that ordinary lung homeostatic systems are modified in COPD. This may involve inadequate production of growth factors as well as altered regulation of apoptosis, or programmed cell death.

RISK FACTORS OF COPD

1.    ENVIRONMENTAL FACTORS

• Cigarette smoke (The risk of COPD increases with increasing consumption of cigarettes but it is also large inter-individual variation in susceptibility)
•   Biomass solid fuel fires
•   Occupational dust & chemicals
• Outdoor & indoor air pollution (Death rates are higher in urban areas than in rural areas. Indoor air contamination from consuming biomass fuel is likewise involved as a danger factor especially in immature spaces of the world.
• Socioeconomic status (COPD is more common in people with low socioeconomic status)
• Infections
• Age (The risk of ventilator impairment increases with increasing age)
• Gender (COPD is more common in males due to higher incidence of smoking)

2.    Host factors

• Α1-antitrypsin deficiency (Α1-antitrypsin deficiency is the strongest genetic factor accounting for about 1-2% of COPD cases.
• Airway hyperresponsiveness & allergy
• Low birth weight
• Lung growth
• Childhood illness

PATHOPHYSIOLOGY OF COPD

These are certain physiological abnormalities that occur in COPD, 

1. Mucus hypersecretion and ciliary dysfunction
2. Airflow limitation and hyperinflation
3. Gas exchange abnormalities
4. Systemic effects
5. Pulmonary hypertension

MUCUS HYPERSECRETION AND CILIARY DYSFUNCTION

Broadened mucus glands cause hypersecretion of mucus and the squamous metaplasia of epithelial cells brings about ciliary brokenness. These are ordinarily the principal physiological anomalies in COPD. Typically, cilia and mucus in the bronchi secure against breathed in aggravations, which are caught and expectorated. The diligent aggravation brought about by cigarettes and other smoke causes a misrepresentation in the reaction of these protective mechanisms and prompts irritation of the little bronchioles (bronchiolitis) and alveoli (alveolitis).

Tobacco smoke likewise restrains mucociliary clearance, which causes a further development of bodily fluid in the lungs. Thus, macrophages and neutrophils penetrate the epithelium and trigger a level of epithelial annihilation. This, along with an expansion of mucus-producing cells, prompts the stopping of more modest bronchioles and alveoli with mucus and particulate matter. This exorbitant mucus production causes distension of the alveoli and loss of their gas trade work. Discharge and contaminated bodily fluid gather, prompting intermittent or ongoing viral and bacterial diseases. The essential microorganism is usu-partner viral yet bacterial disease regularly follows. Normal bacterial microorganisms incorporate Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae.

Bronchiectasis is a neurotic change in the lungs where the bronchi become for all time widened. It isn't unexpected after early assaults of intense bronchitis during which mucus both plugs and stretches the bronchial walls. In extreme contaminations, the bronchioles and alveoli can turn out to be for all time harmed and don't get back to their typical size and shape. The deficiency of muscle tone and loss of cilia can add to COPD because bodily fluid tends to collect in the widened bronchi.

AIRFLOW LIMITATION AND HYPERINFLATION

Irritation, fibrosis, aviation route exudate, and narrowing (aviation route rebuilding) of the more modest directing aviation routes are the primary site of expiratory wind current limit in COPD (estimated by (spirometry). Reformist damaging development of the respiratory bronchioles, alveolar pipes, and alveolar sacs called Emphysema. Loss of accessible gas trade surfaces and loss of flexible force in the little aviation routes, peripheral aviation route breakdown, especially during the lapse. Expanded thoracic gas volume and excessive inflation of the lungs cause diminished respiratory limit which causes dyspnea and decline practice limit.

GAS EXCHANGE ABNORMALITIES

Terminal bronchioles (alveolar pipes and sacs) are significant locales where gas trade happens. Ruinous loss of alveolar dividers and growth of terminal airspace prompts blood vessel hypoxemia (decreases O2) with or without hypercarbia (increases CO2). This outcome in unusual dissemination of ventilation and perfusion inside the lungs and make the abnormal gaseous exchange.

PULMONARY HYPERTENSION

Persistent irritation and edema cause thickening of the bronchiole and alveolar dividers and blockage and impediment of the aviation routes. Alveolar distension and obliteration cause twisting of the veins that are firmly connected with the alveoli which cause the increment in pulse in the aspiratory flow Reduction in gas dispersion across the alveolar epithelium causes hypoxemia (V/Q). Because of ongoing vasoconstriction, there is a constant expansion in circulatory strain.

The ongoing low oxygen levels cause polycythemia a condition wherein red platelets expansions in the body because of its increment underway to repay the low degree of oxygen so expansion in blood viscosity. Supported aspiratory hypertension causes thickening of the dividers of the pneumonic arterioles and pneumonic redesigning and right ventricular pressing factor inside the heart. PH makes more diligently for the heart to siphon blood to the lungs. If this high pressing factor proceeds, it puts a strain on the right half of the heart. That strain can cause right ventricular hypertrophy, expansion, and reformist right ventricular disappointment (cor pulmonale).

SYSTEMIC IMPACTS

Foundational irritation and skeletal muscle squandering can happen in COPD which cutoff practice limit and deteriorate forecast. Osteoporosis, misery, normocytic normochromic sickliness are potential sequelae, just as the expanded danger of cardiovascular illness-related with raised degrees of C-receptive protein.

SYMPTOMS OF COPD

COPD is a progressive disorder that passes through a potentially asymptomatic mild phase, moderate phase than the severe disease. The traditional description of COPD symptoms particularly in severe disease depends on whether,

1. Bronchitis
2. Emphysema

BRONCHITIS (BLUE BLOATER)

SIGNS

• Cyanosis (blue discoloration of the skin)
• Crackles (pop opening of small airways and Alveoli)
• Wheeze (narrowing or obstruction of airways)
• Prolong expiration if obstructive
• Obese

SYMPTOMS

• Excess mucous production
• Chronic productive cough
• Mild Dyspnea
• Hypercapnia (increase the level of CO2 in the blood)
• Hypoxemia (increase the level of O2 in the blood)

EMPHYSEMA (PINK PUFFER)

SIGNS

• 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
• Diaphragmatic excursion

SYMPTOMS

• Dyspnea (shortness of breath)
• Minimal cough
• Mucous production is scanty and mucoid
• Tachypnea (abnormally rapid breathing)

DIAGNOSIS & PATIENT ASSESSMENT FOR COPD

The suspected diagnosis of COPD should be based on the patient’s clinical symptoms or history of exposure to risk factors. It is important to distinguish COPD from asthma and other lung obstructive disorders because treatment and prognosis differ. Differentiating factors include the age of onset, smoking history, triggers, occupational history, and degree of reversibility measured by pre and post-bronchodilator spirometry.

PHYSICAL EXAMINATION

On physical examination, patients with early COPD may not exhibit any changes. Later findings vary with severity;

Early stages: normal or may show only prolonged expiration or wheeze on forced exhalation.

Increased severity: Hyperinflation, increased breath sound, wheeze, crackle at lung bases, distant heart sound.

End-stage: Adopt a position to relieve dyspnea, as leaning forward with arms outstretched and weight supported on the palms or elbows.

LABORATORY EXAMINATION

Various tests will be performed if a person has COPD including:

1. Sputum test
2. Pulmonary function test
3. Blood test
4. Imaging techniques

SPUTUM EXAMINATION

Sample of sputum is analyzed in the laboratories especially if the patient has a productive cough. To analyze whether a bacterial infection is present. The culture of sputum during COPD is as follows

• Streptococcus pneumoni
• Haemophilus influenza
• Moraxella catarrhalis
• Pseudomonas aeruginosa

PULMONARY FUNCTION TEST

A pulmonary function test is performed to detect and assess the severity of lung diseases. It is also helpful in following the progress of lung disease.

These include;

1. SPIROMETRY TESTING
2. PEAK FLOW MEASUREMENT
3. PULSE OXIMETRY TEST

SPIROMETRY TESTING

Spirometry is a gold standard measurement in assessing and monitoring obstructive lung disease. It measures the total volume of air that is inhaled or exhaled. During spirometry, a full breath is taken, followed by a forceful exhalation of all the air that can be exhaled (forced vital capacity FVC).  FEV1 is the volume of air that can be expired within the first second of an FVC maneuver.

A decrease in FEV1/FVC ratio indicates airflow obstruction. A value of less than 0.70 indicates airflow limitations and thus COPD. The disease severity is best assessed by examining the FEV1 as a percent of predicted. Then the value of FEV1 less than 70% predicted will show obstructive lungs disorder.

PEAK EXPIRATORY FLOW MEASUREMENT

The peak flow meter is used to determine peak expiratory flow rate (person's maximum speed of expiration). In case of acute COPD attack:

• 50-75% - moderate exacerbation
• 33-33% - acute severe
• <33% - life-threatening

PULSE OXIMETRY

Pulse oximetry is done in patients with advanced disease or with evidence of right ventricular pressure overload. It indirectly monitors the oxygen saturation of a patient's blood and changes in blood volume in the skin, producing a photoplethysmogram. Although a decrease in pulse oximetry (normal >97%) is common in COPD, values of 88% or less are consistent with chronic respiratory failures and qualify the patient for supplemental oxygen.

IMAGING

It is done in the patients when the cause is unclear and during acute exacerbation to exclude complicating processes (such as pneumonia, pneumothorax, and heart failure). It includes;

• Chest X-Ray
• Computed Tomography

CHEST X-RAY

No apparent changes are reported in the early stages of COPD. Thickened and increased lungs markings, hyperinflation, flattened diaphragm, and evidence of pulmonary arterial hypertension with enlarged pulmonary arteries is reported.

COMPUTED TOMOGRAPHY

It is done for severe COPD if the conditions worsen. It identifies individuals with predominantly upper lobe disease who may be candidates for lung volume reduction surgery.

TREATMENT OF COPD

The objective of therapy is to relieve the patient from the symptoms of COPD. The effective treatment of COPD consist of the following drugs,

1. Bronchodilators (β2-agonist drugs, Anticholinergic drugs, & 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-agonist drugs produce bronchodilation by relaxing bronchial smooth muscles. They activate the enzyme, adenylyl cyclase that catalyzes the formation of cyclic adenosine monophosphate (cAMP). Cyclic adenosine monophosphate is a smooth muscle relaxant (Broncho dilation).

The most common adverse effects of beta-2 agonists are tachycardia (Contractility ↑), hypokalemia, angina (↑H.R), cardiac arrhythmias, and tremors. 

Β2-agonist is contraindicated in patients with diabetes mellitus, hyperthyroidism, and glaucoma (All the β2-Agonist dilates the pupil and increases the intraocular pressure).

Tobacco smoking can reduce the beneficial effects of β2- agonists. Β2- Agonists with corticosteroids OR theophylline increase the risk of Cardiac arrest.

Commonly used short-acting Β2-agonist drugs are albuterol, levalbuterol, and pirbuterol and long-acting Β2-agonist drugs are salmeterol and formoterol.

ANTICHOLINERGIC DRUGS

The Parasympathetic NS plays a primary role in controlling broncho-motor tone in COPD. The cholinergic stimulation increases the activity of guanylate cyclase. Guanyl 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 the lungs and inhibit bronchoconstriction.

The common adverse effects of anticholinergic drugs are bitter taste, blurred Vision, angina due to increase contractility of the heart, and constipation because of decreased body secretions.

They are contraindicated in patients with glaucoma, urinary retention due to decrease body secretions, and hypersensitivity reactions. Ipratropium and albuterol combination give rise to acute angle-closure glaucoma.

Commonly prescribed anticholinergic drugs for the treatment of COPD are aclidinium, glycopyrronium, ipratropium, tiotropium, and umeclidinium.

METHYLXANTHINE

Methylxanthine acts as a non-specific phosphodiesterase inhibitor. Phosphodiesterase is the enzyme that catalyzes the breakdown of cAMP. So, phosphodiesterase inhibitors inhibit the cAMP breakdown and increase the cAMP level in the body.

It also acts as an antagonist for prostaglandins. PGE₂ is the PG’s that causes the inflammation in the COPD so antagonists reverse their action.

It decreases the overnight decline in FEV and decreases early morning symptoms. Commonly used drugs are theophylline and aminophylline. The commonly reported adverse effects are insomnia, restlessness, irritability, and tachycardia.   

ANTI-INFLAMMATORY AGENTS

CORTICOSTEROIDS

Oral corticosteroids improve FEV 1 (Forced Expiratory Volume), exercise improvement, and dyspnea. It inhibits inflammation through histone deacetylase (HDAC) enzymes that switched off activated inflammatory genes. Regular treatment with corticosteroids decreased the number of exacerbations and improves health status. However, Corticosteroids do not slow the long-term decline in pulmonary function. Commonly used corticosteroids are methylprednisolone and budesonide. The commonly reported side effects of corticosteroids are myopathy, ecchymosis, and dysphonia. They are contraindications in patients with osteoporosis, and glaucoma.

ANTIBIOTICS

Antibiotics are prescribed when sputum production, sputum Purulence, and dyspnea increase. The most commonly used antibiotics are doxycycline, ampicillin, amoxicillin, and cotrimoxazole. Commonly reported adverse effects are teeth aplasia of enamel with doxycycline, thrombocytopenia, and stevens-johnson syndrome.

ALPHA 1-ANTITRYPSIN AUGMENTATION THERAPY

Alpha-1 antitrypsin is a glycoprotein produced by the Liver. Its main function is to balance the action of neutrophil-protease enzymes in the lungs. AAT is a Protease inhibitor. Neutrophils are the cells that are responsible for the inflammation in COPD. The normal vevel of AAT is 100-150mg/dl. If the level is less than 80mg/dl, then the patient needs therapy. IV-Augmentation therapy is for individuals with AAT deficiency and moderate airflow obstruction. (FEV ı 35-60%). There are three preparations of alpha 1-antitrypsin augmentation therapy are available. All preparations have the same dosage of 60 mg/kg/week. Weekly transfusion of pooled human AAT that maintains the plasma level of the enzyme. 

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