COPD Flashcards
what is COPD?
Chronic: progressive and long lasting
Obstructive: narrowing of airways that causes airflow limitation
Pulmonary: small airways and/or alveoli destruction
Disease: multicomponent illness with extra-pulmonary effects
Characterised by airflow limitation that is NOT fully reversible.
Progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases.
What is the airflow limitations of COPD caused by?
Airflow limitation is caused by a mixture of small airway disease and parenchymal destruction: chronic bronchitis and emphysema.
what are the risk factors of COPD?
Smoking (~80% of COPD) Enviromental pollution Genetic factor Occupational exposure Frequent infections of the airways
Age > 35
Socio-economical deprivation
Poor diet
symptoms of COPD?
Progressive and exertional breathlessness (dyspnea)
Chronic cough
Sputum production
Wheezing and chest tightness
Frequent winter bronchitis
Upper respiratory infection (purulent sputum)
Pulmonary hypertension
what are the symptoms in severe COPD?
In severe COPD: Weight loss, anorexia Asymptomatic rib fractures Ankle swelling Depression, anxiety
A diagnosis of COPD should be considered in:
A diagnosis of COPD should be considered in:
patients over the age of 35
who have a risk factor (generally smoking)
who present with exertional breathlessness, chronic cough, regular sputum production, frequent winter ‘bronchitis’ or wheeze. [2004]
The presence of airflow obstruction should be confirmed by performing post-bronchodilator spirometry.
COPD pathophysiology : emphysema?
what is emphysema and its causes?
Emphysema: persistent inflammation destroys alveoli at the end of small airways.
Permanent enlargement of the air spaces distal to the terminal bronchiole accompanied by destruction of their walls.
Destruction of the parenchyma decreases the area for gas exchange and lung elasticity
Hypertrophy of capillaries reduces ability to absorb oxygen and may increase blood pressure.
The alveoli have a good blood supply and the oxygen from the air that a person breathes in is transferred into their bloodstream from the alveoli. If the alveoli are damaged (as in emphysema), this oxygen transfer becomes affected. Thus, it is harder to absorb oxygen
Lungs less able to contract and expel air on breathing out
Since the lungs are damaged, the amount of oxygen that goes to the blood is reduced. This produces high blood pressure in the blood vessels from the heart to the lungs, and makes it even more difficult for the heart to pump much-needed blood to the rest of the body. This lung disease can also cause the body to produce more red blood cells, which can make the blood thicker and harder to pump. The COPD and hypertension working together forces the person to breathe faster in order to take in more oxygen
Pulmonary hypertension in COPD patients is caused by the loss of alveolar structure, remodeling of the pulmonary vessels by chronic hypoxia and inflammation, decreases in the levels of endothelial vasodilators such as nitric oxide, and vasospasm caused by factors such as endothelin-1
COPD pathophysiology : chronic bronchitis and bronchilitis?
what is chronic bronchitis and its causes?
Chronic bronchitis and Bronchiolitis: Inflammation of central airways (trachea/bronchi) and smaller airways (bronchioles)
Hypertrophy and hyperplasia occur to the mucus-secreting glands and smooth muscle in smaller airways
Small airways become obstructed by intraluminal mucus, mucosal oedema and airways wall fibrosis.
The obstruction and the mucus increase resistance to airflow and cause chronic viral and bacterial colonisation in the retained mucus.
what is the pathogenesis of COPD
1) Inflammatory cells and mediators
Chronic Inflammation
(neutrophils produces proteinase and leukotrines
macrophages produces cytokines and chemokines
2) Oxidative stress
Reactive oxygen and nitrogen species
(causes oxidation of lipids, proteins and DNA
increase in transcription of pro-imflammatory proteins
increase in protease activations
decrease in antiprotease
aptosis)
Imbalance between oxidant and antioxidant damage to intracellular matrix oxidation of biological molecules cell destruction
Acetylation of histone due to impairment of histone deacetylase
Oxidative stress casues Alveolar epithelial injury and remodeling of extracellular matrix
3) Protease-antiprotease imbalance
a1-antitrypsin deficit
A1AT helps to balance the protease enzymes in the lungs and stop lung damage.
Its main function is to protect the lungs from damage caused by other types of proteins called enzymes.
Alpha-1 antitrypsin (A1AT) deficiency is an inherited genetic condition (a condition that can be passed on from your parents through your genes). It can lead to lung and, in some people, liver damage
In COPD there is an increase production/activity of proteineses or there is reduction of activity/production of antiproteinases alfa1-antitrypsin.
deficit increase risk of COPD maybe COPD inactivate alpha1 anti-proteinase
what are the clinical differences between asthma and COPD
smokers/ ex - smokers = nearly ALL COPD
symptoms under 35 - Rare in COPD
chronic productive cough - common in COPD
Breathlessness - persistent and progressive in COPD
night time waking up with breathlessness - common in asthma
day to day variability in symptoms - asthma
The severity of COPD - FEV1 %
> 80 = mild
50-79 = moderate
30-49 = severe
less than 30 = very severe
what are the aims of managing stable COPD?
AIMS
Prevent and control symptoms
Reduce the frequency and severity of exacerbations
Improve general health status and exercise tolerance
what are non- pharmacological management for COPD?
- offer treatment and support to stop smoking
- offer influenza and pneumococcal vaccination
- offer pulmonary rehab
- self management plans
- optimise treatment for comorbidities
Rationale:
Reduce the frequency and severity of exacerbations
Improve general health
when should inhaled therapy be used in COPD?
- if non-pharmacological treatment was offered
- inhaled therapy is needed to help breathlessness and exercise limitations
-they have been trained to use the inhaler with good technique
: offer SABA or SAMA
what is the mechanism of b2 Adrenoceptor Agonists
Mechanism of action
Activate b2AR in airway smooth muscle
Cause airway smooth muscle relaxation by cAMP-dependent (and independent?) mechanism
β-agonist binds to β2-AR, activating adenyl cyclase through Gαs, leading to an increase in cAMP levels. The surge in cAMP in turn activates PKA which phosphorylates myosin light chain kinase to inhibit contraction. PKA also activates K+channels, inducing membrane hyperpolarization which counteracts electrical excitation leading to contraction.
Moreover, cAMP inhibits Ca2+ release from intracellular store
All of which aid relaxation of the airway smooth muscle
what is the role of muscarinic receptor in the lungs
M1:
M1 receptors may mediate bronchodilation, by the release of a relaxing agent from respiratory epithelia or pulmonary nerves
what is the role of muscarinic receptor in the lungs
M2:
M2 autoreceptors, on post-ganglionic cholinergic nerves: provide negative feedback to reduce acetylcholine release
what is the role of muscarinic receptor in the lungs
M3:
M3 on airway smooth muscle cells and glands: mediate bronchoconstriction and mucus secretion
what is the mechanism of action of Inhaled Anticholinergics Drugs
Mechanism of action
Block muscarinic acetylcholine receptors (M3) to cause bronchodilation and reduce mucus secretion
what is an example of Short-acting antimuscarinic drugs
Ipratropium Bromide (SAMA) Onset after 20 minutes peak effect within 30-60 minutes, and duration of action3 to 6 hours
what is an example of Short-acting antimuscarinic drugs
Long-acting antimuscarinic drugs
Tiotropium Bromide (LAMA)
Onset of action 30 minutes, peak effect within 3 to 4 hours, and 24-hour duration of action
what are the side effects of Inhaled anticholinergics drugs
Common: dry mouth; arrhythmias;cough;dizziness;headache;nausea
Uncommon: Constipation; dysphonia; glaucoma; palpitations; skin reactions; stomatitis; urinary disorders; vision blurred
what are the side effects of tiotropium
Caution
Tiotropium: arrhythmia,heart failure,myocardial infarction
when is the Use of inhaled combination therapies used
if
the person is limited by symptoms or has excerbation despite treatment
no asthmatic features or features suggesting steroid responsiveness : Offer LABA or LAMA
asthmatic features or features suggesting steroid responsiveness : Consider LABA and ICS
The last step is
LABA + LAMA and ICS
If no improvement revert to LABA And LAMA
what are further treatment option
Oral corticosteroid maintenance therapy NOT normally recommended
Mucolytic drug therapy
Considered in patients with a chronic cough productive of sputum
Long-acting phosphodiesterase-4 inhibitor
Theophylline: after a trial of inhaled combination therapy in patients unable to use inhaled therapy
Roflumilast
Maintenance use of oral corticosteroid therapy in COPD is not normally recommended.
Mucolytic drug therapy should be considered in patients with a chronic cough productive of sputum.
Theophylline should only be used after a trial of short-acting bronchodilators and long-acting bronchodilators, or in patients who are unable to use inhaled therapy, as there is a need to monitor plasma levels and interactions.
Roflumilast, as an add-on to bronchodilator therapy, is recommended as an option for treating severe chronic obstructive pulmonary disease in adults with chronic bronchitis
Oral inhibitor of phosphodiesterase-4 Example Mechanism Use Side effect
Roflumilast (Daxas)
Mechanism of action:
Selective inhibition of the PDE4 isoenzyme in lung cells
Unclear mechanism of action
Use:
Oral add-on to bronchodilator therapy, for severe COPD associated with chronic bronchitis and prevention of exacerbations
Side Effects:
Common: diarrhoea, weight loss and nausea
Increase in psychiatric adverse reactions
what is exacerbation
Exacerbation= A sustained acute-onset worsening of the person’s symptoms from their usual stable state, which
goes beyond their normal day-to-day variations
Worsening breathlessness, cough, increased sputum production and change in sputum colour
Corticosteroids and COPD
Little clinical benefit in COPD!
Reduce but DO NOT suppress lung inflammation and secretion of inflammatory proteins!
Reduce incidence of exacerbations BUT give higher incidence of pneumonia (immune suppression)
DO NOT reduce mortality or progression of disease but reduce requirement for systemic glucocorticoids and hospitalisation rate.
Licenced in UK only in combiantion with LABA!
What is the summary of the treatment plan for COPD
- non-pharmacological
- SABA or SAMA
- LABA and LAMA or LABA and ICS (combined)
- LABA + LAMA + ICS
