COPD

Question 1

Chronic obstructive pulmonary disease, or COPD

Answer 1

A common preventable and treatable lung disease. It is characterised by persistent airflow limitation that is usually progressive. COPD is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases especially cigarette smoke. Exacerbations and comorbidities (additional diseases that coexist) contribute to the overall severity in individual patients.

Question 2

symptoms of COPD

Answer 2

Reduction in the size of a patient’s airways (chronic obstructive bronchitis)

Degradation of the airway wall (emphysema)

Question 3

COPD increasing?

Answer 3

Unlike many other diseases, COPD is on the increase 1965. CVD stands for cardiovascular disease.

Question 4

When should the diagnosis of COPD be considered?

Answer 4

If the patient has dyspnea (difficult or labored breathing or shortness of breath), chronic cough or sputum production and a history of exposure to risk factors for the disease (such as smoking).

Question 5

Why is Spirometry important for COPD?

Answer 5

It is required to make the diagnosis, which measures how much air a patient can breathe out in one forced breath.

Question 6

How is spirometry done?

Answer 6

Spirometry is a method of assessing lung function by measuring the volume of air that the patient can expel from the lungs after a maximal inspiration. The indices derived from this forced exhaled maneuver have become the most accurate and reliable way of supporting a diagnosis of COPD.

When these values are compared with predicted normal values determined on the basis of age, height, sex, and ethnicity, a measure of the severity of airway obstruction can be determined. It is on these values that COPD guidelines around the world base the assessment of mild, moderate, and severe disease levels.

Question 7

FVC

Answer 7

Forced Vital Capacity – the total volume of air that the patient can forcibly exhale in one breath.

Question 8

FEV1

Answer 8

Forced Expiratory Volume in One Second – the volume of air that the patient is able to exhale in the first second of forced expiration.

Question 9

FEV1 /FVC

Answer 9

The ratio of FEV1 to FVC expressed as a fraction (previously this was expressed as a percentage).

Values of FEV1 and FVC are measured in liters and are also expressed as a percentage of the predicted values for that individual.

Question 10

The ratio of FEV1/FVC is normally between?

Answer 10

0.7 and 0.8. Values below 0.7 are a marker of airway obstruction, except in older adults where values 0.65–0.7 may be normal. Predicted values are calculated from thousands of normal people and vary with sex, height, age, and ethnicity.

Question 11

Tiffeneau-Pinelli index:

Answer 11

Tiffeneau-Pinelli index = FEV1FVC
= FEV1%
An FEV1FVC
< 0.70 confirms the presence of persistent airflow limitation and thus of COPD.

FEV1% predicted (also known as mean FEV1) is the patient’s FEV1% divided by the average FEV1% for the patient’s demographic.

Question 12

Asthmas v COPD, onset?

Answer 12

Asthmas- Childhood
COPD- midlife

Question 13

Asthmas v COPD, usual etiology?

Answer 13

Asthmas- immunological stimuli, family history
COPD- risk factors such as cigarette smoke

Question 14

Asthmas v COPD, course?

Answer 14

Asthmas- intermediate and variable
COPD- chronic and progressive

Question 15

Asthmas v COPD, airflow limitation?

Answer 15

Asthmas- largely reversible
COPD- partially reversible

Question 16

Asthmas v COPD, clinical features?

Answer 16

Asthmas- wheeze, chest tightness, cough
COPD- cough, sputum

Question 17

Asthmas v COPD, inflammatory mediator?

Answer 17

Asthmas- eosinophils
COPD- neutrophils

Question 18

COPD in lungs

Answer 18

Fibrosis: Damaged and scarred lung tissue.
Alveolar disruption: Disrupting the ability of the alveolar to stretch when inhaling and shrink when exhaling.
Neutrophils, T lymphocytes and epithelium cells are all elevated in COPD patients

Question 19

How do COPD therapies work? 2 main types?

Answer 19

They do not act upon the biological mechanism directly, but treat the symptoms. The two main therapies, bronchodilators and steroids relax the smooth muscle of the airways and reduce inflammation respectively.

Question 20

How are Anti-inflammatory drugs best used?

Answer 20

They are often used in combination with bronchodilators for best effect.

Question 21

There are two classes of drugs that act as bronchodilators:

Answer 21

Beta2 agonists and cholinergic antagonists.

Question 22

How are bronchodilators prescribed?

Answer 22

The choice of treatment depends on the availability of medications and each patient’s individual response in terms of symptom relief and side effects.

The principal bronchodilator treatments are beta2-agonists, cholinergic antagonists, theophylline or combination therapy.

Question 23

What bronchodilators do COPD patients bests respond to?

Answer 23

cholinergic antagonists.

Question 24

How do bronchodilators, Beta2 agonists work?

Answer 24

They bind to the β2 adrenergic receptor; a protein that spans cell membranes. The endogenous ligand of β2 adrenergic receptors is adrenaline or epinephrine. Note how similar salbutamol is to the endogenous ligand.

β2 adrenergic receptors are involved in the dilation of smooth muscle, including bronchial passages. Thus a synthetic drug such as salbutamol can amplify the function of β2 adrenergic receptors causing airways to increase.

Question 25

How do bronchodilators, Cholinergic antagonists work?

Answer 25

They work via an entirely different mechanism to how Beta2 agonists work. They block the binding of acetylcholine to nerve transmitters. The charged ammonium ion means that acetylcholine cannot penetrate the blood-brain barrier. It is found in the central nervous system (brain) and the peripheral nervous system (non brain) but cannot cross between the two.

Acetylcholine is also through to interact with the muscarinic receptors. The muscarinic receptor M3, is known to be involved with the dilation of smooth muscle.

Question 26

Salmeterol

Answer 26

Long-acting inhaled bronchodilators, such as salmeterol are convenient and more effective for symptom relief than short-acting bronchodilators.

Long-acting inhaled bronchodilators reduce exacerbations and related hospitalisations and improve symptoms and health status.

Combining bronchodilators of different pharmacological classes may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

Question 27

Short-acting vs. Long-acting Beta2 Agonists

Answer 27

Short-acting beta2 agonists, such as salbutamol and terbutaline, have a rapid onset of action and provide quick relief of bronchoconstriction symptoms. These medications typically have a duration of action of about 4-6 hours.

On the other hand, long-acting beta2 agonists, such as salmeterol, formoterol, and indacaterol, provide sustained bronchodilation with a duration of action that can range from 12 to 24 hours or more. LABAs are used as maintenance therapy in patients with asthma and COPD to provide consistent symptom control and reduce the risk of exacerbations.

Question 28

The logD value

Answer 28

Of a drug is an indicator of its lipophilicity, which influences its absorption, distribution, metabolism, and excretion.

Question 29

For of beta2 agonists, a higher logD value =

Answer 29

It translates to a longer duration of action. This longer duration of action can be attributed to the increased affinity of the drug for the lipid-rich environment of the cell membrane, which facilitates its slow release and prolonged activity at the receptor site.

Question 30

bronchodilators: Salmeterol, LABA v SABA, Log D ?

Answer 30

It has a higher logD value compared to the SABAs salbutamol and terbutaline.

Question 31

Treatment Recommendations Based on LogD Values: For patients requiring rapid relief from acute bronchoconstriction?

Answer 31

Short-acting beta2 agonists with lower logD values are recommended, as they provide quick onset of action and short duration of effect. These medications can be used on an as-needed basis for symptom relief.

Question 32

Treatment Recommendations Based on LogD Values: For patients with persistent symptoms or frequent exacerbations?

Answer 32

Long-acting beta2 agonists with higher logD values are more suitable as maintenance therapy. The extended duration of action provided by LABAs leads to sustained bronchodilation, which can help improve symptom control and reduce the frequency of exacerbations. LABAs should not be used as monotherapy in asthma patients and should be combined with inhaled corticosteroids for optimal asthma control.

Question 33

Corticosteroids

Answer 33

Corticosteroids are a class of anti-inflammatory medications that act on the glucocorticoid receptor (GR), a nuclear receptor found in various cell types throughout the body, including immune cells and airway epithelial cells.

Question 34

What is the main anti-inflammatory for treating COPD?

Answer 34

Corticosteroids, with regular treatment with inhaled corticosteroids (ICS) improves symptoms, lung function, and quality of life and reduces the frequency of exacerbations for COPD patients with an FEV1 < 60% predicted. However, inhaled corticosteroid therapy is associated with an increased risk of pneumonia. Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients.

Question 35

Anti-inflammatory, Transrepression MOA :

Answer 35

When corticosteroids enter the cell, they bind to the glucocorticoid receptor, causing a conformational change that releases chaperone proteins and exposes the DNA-binding domain of the receptor. The corticosteroid-receptor complex then translocates to the nucleus, where it can interact with specific DNA sequences called glucocorticoid response elements (GREs) or negatively interfere with other transcription factors, such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). This process, called transrepression, results in the suppression of pro-inflammatory gene expression and a reduction in the production of inflammatory mediators, such as cytokines, chemokines, and adhesion molecules

Question 36

Anti-inflammatory, Transactivation MOA:

Answer 36

The corticosteroid-receptor complex can also bind to GREs and positively regulate the expression of anti-inflammatory and immunosuppressive genes, such as those encoding annexin A1, mitogen-activated protein kinase (MAPK) phosphatase-1, and interleukin-10. This process, called transactivation, further contributes to the anti-inflammatory effects of corticosteroids.

Question 37

What is the usual combination therapy for COPD?

Answer 37

Corticosteroids and beta2 agonists

Question 38

In 2017 the Global Initiative for Chronic Obstructive Lung Disease (GOLD) produced a report on the future treatment of COPD. Its findings were clear:

Answer 38

Stopping patients smoking is paramount. However, even if exposure to noxious agents stops, the disease may still progress.

Question 39

How are COPD patients clinicians are now focussing on personalised medicine?

Answer 39

They are working out the best combination of bronchodilators and/or anti inflammatories to best manage the condition. For this, clinicians ideally need biomarkers to help guide them towards the biological mechanisms that are dominant in the patient’s disease. Research in this area is in its infancy. However it demonstrates that finding new drugs is not always the answer. Understanding the disease better can results in optimal use of the pharmaceuticals already developed.