COPD Flashcards
What can COPD lead to?
May led to pulmonary hypertension, cynosis, hypoxia, right heart failure.
What is the defining criteria for COPD?
Progressive airflow limitation that is not fully reversible.
(Associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily cigarette smoke)
What does COPD include?
Chronic bronichitis: productive cough present over years. Excessive sputum production.
Emphysema: alveolar wall destruction, irreversible enlargement of the terminal air spaces.
Who is a blue bloater?
Chronic bronchitis. overweight, cyanotic, elevated hemoglobin, peripheral edema, rhonchi and wheezing.
Who is a pink puffer?
Emphysema: permanent enlargement and destruction or airspaces distal to the terminal bronchiole.
Older and thin, severe dyspnea, quiet chest, X-ray: hyperinflation with flattened diaphragms.
Risk factors for COPD:
Tobacco Smoke Urban pollution Industrial pollution Textile dust Biomass fuels
How does COPD progress?
Stage I: Asymptomatic
Stage II: Progressive dyspnoea
Stage III: Systemic disease, comorbidities.
Stage IV: respiratory failure, death.
How does the sputum differ between COPD and Asthma patients?
COPD: Neutrophil-rich sputum
Asthma: Eosinophilic rich.
Marked-hyper-responsiveness is associated with
Ashtma. Limited = COPD.
Reduced airflow which is very variable and has a diurnal variation is associated with:
Asthma. No variation = COPD.
Lymphocytes found in COPD are predominantly of what type?
TH1 and TC1
Lymphocytes found in Asthma are predominantly:
TH2
What is the Dutch hypothesis?
Asthma + Chronic bronchitis + Emphysema all overlap.
A: reversible airflow limitation
B: fixed obstruction, persistent sputum.
E: destruction of alveolar septa.
Neutrophil-rich sputum is associated with:
COPD
Fibrosis that is ______ is found in COPD.
Peribronchiolar,
Subepithelial is Asthma.
Eosinophilic sputum is associated with:
Asthma
How does excessive airway mucus occur in COPD?
Increased production: inflammatory cells, oxidative stress, viral infection, bacterial infection.
Reduced elimination: poor ciliary clearance, airway occlusion, reduced PEF, resp muscle weakness.
What are the three main mechanisms of airflow reduction in COPD?
Occlusion of airways by mucus.
Thickened airway walls
Loss of elasticity due to emphysema.
Leukocyte infiltration in COPD takes the form of:
Macrophages and CD8+ T cells.
Neutrophils in infection.
Chemoattractants found in COPD include:
IL-8 and LTB4
What are the consequences of the inflammation in COPD?
Epithelial damage: decreased ciliary cell function, increased mucus secretion from goblet cells.
Mucus cell hyperplasia - more cells, increased bronchial permeability –> airway oedema and protein exudation.
What is a cough?
Motor reflex in response to sensing chemicals, particulates and airway excessive mucus.
How can a cough be suppressed?
High dose opioids are effective,
OTC limited efficacy.
Most of the soothing benefit is from the sugar causing increased salivation.
What is emphysema?
Permanent enlargement of airspaces distal to the terminal bronchiole: destruction of the alveolar walls.
“Proteinase-antiproteinase hypothesis”
Decreased levels of what are seen in some emphysema patients?
Decreased serum alpha 1 antitrypsin.
IL-8 and LTB4
Chemoattractants
Lung elastases such as____, _____ and ______ are derived from neutrophils and macrophages.
Cathepsins,
Proteinase 3
Gelatinase
They degrade elastin, basement membrane and connective tissue.
Increased levels after smoking.
Strongly implicated in emphysema.
Why can a lack of liver produced a1 anti-trypsin be a problem?
a1 anti-trypsin is an elastase inhibitor.
High levels of elastase = emphysema.
TIMPS
Tissue inhibitors of metalloproteinase.
Elastase is produced by:
Neutrophils, macrophages.
Metallo-proteinases are produced by:
Monocytes, neutrophils.
Increased levels of which cytokines are found in COPD sputum compared with smoking or non-smoking controls?
IL-8
TNF
TNF increases mucin secretion, and elastase production.
Why can high levels of TNF cause emphysema?
TNF increases mucin secretion, and elastase production.
What do macrophages release that can cause fibrosis?
Fibroblast growth factors.
TGFB and EGF.
What is Aclidinium?
Muscarinic antagonist with a fast M2 off time.
DPI
Why are bronchodilators not of much use in COPD?
Bronchoconstriction is not a major cause of airway obstruction.
Why is tiotropium of pharmacokinetic advantage?
M3 selective agent, less effect on M2 so negative feedback is preserved and ACh release is suppressed.
What actions does ACh have when bound to:
a) M3
b) M2
M3 = bronchoconstrictive actions M2 = negative feedback, preventing its own release
What can occur if M2 ACh release negative feedback is inhibited by non-selective muscarinic agents such as ipratropium?
Non-specific muscarinic antagonists block both M2 and M3 so remove negative feedback via blocking M2 and thus sufficient ACh can be released as to overcome the M3 block.
Neurokinin antagonists and agents inhibiting sensory fibre activation are showing some efficacy in preventing what?
Mucus secretion in COPD.
Hypersecretion is associated with decline in FEV1 and hospitalisation.
Are corticosteroids of use in COPD treatment?
Some benefit of IV for acute exacerbations.
Limited evidence of benefit from inhaled steroids for maintenance.
Rofulimast is what?
PDE IV selective phosphodiesterase inhibitor.
PDE IV is present in leukocytes.
inhibitors prevent chemotaxis, granule release etc.
TNFa release prevented.
PDE III and IV inhibition leads to what?
Bronchodilation.
Bacterial infections caused by: _________ or _________ can be found in to ___ of stable COPD patients.
H.influenzae
S. Pneumoniae
50%
Viral infection in COPD is associated with acute exacerbation of symptoms and is predominantly caused by _______. __________. ________ and ________
Rhinovirus
Influenza
Parainfluenza
Coronavirus
Which antibiotic apparently has beneficial actions unrelated to antibiotic activity such as alveolar protection in smoke injury?
Clarithromycin, macrolide.
________ may be useful as a novel therapy in COPD. Normally used in the treatment of osteoporosis.
Alondronate
Inhaled bisphosphonates.
Inhibit experimental emphysema.
What effect do statins have on COPD management?
No benefits shown on lung function in randomised prospective trials.
What is N-acetyl cysteine?
Breaks disulphide bonds in mucin, Mucolytics.
DNAse (Dornase Alpha)
No evidence on mucus removal in COPD but beneficial in asthma,
Why do bronchodilators work well in COPD?
The occlusion is not due to bronchoconstriction but due to tissue remodeling and secretion.
Why are anti-inflammatory glucocorticoids not useful in COPD usually?
Oxidative stress results in decreased steroid sensitivity - impaired glucocorticoid receptor function.
Neutrophil apoptosis is inhibited by glucocorticoids.
What role does HAT play in gene expression?
Histone acetyltransferase acetylates histones:
unpacks chromatin and allows RNA polymerase binding to DNA.
Co-operates and amplifies NFKB action.
What role does HDAC play in gene expression?
Histone Deacetylase (HDAC) represses inflammatory gene expression.
Theophylline has what effect on HDAC?
Promotes its activity hence repressing gene expression.
