COPD Flashcards
What are the most common conditions comprising COPD?
Chronic bronchitis
Emphysema
What is COPD?
Chronic obstructive pulmonary disease
Characterised by airflow limitation which is not fully reversible.
This limitation is usually progressive and assoc. with abnormal inflammatory response of the lungs to noxious particles or gases
Is COPD curable?
No.
COPD can be prevented, but not cured. Treatment is symptomatic and preventing further exacerbations
What is the epidemiology of COPD?
15% of adults in NZ get COPD. This is increasing due to smoking at this point in time
COPD is the 4th leading cause of death in the world
How is chronic bronchitis classified?
“Blue bloater”
There is a chronic cough with copious sputum production for 3months in the last 2 years, irrreversible with a β2 agonist.
There is no allergic component involved.
Onset age often 46-65 years,
Patients often obese with high incidence of cigarette use
Chest diameter is increased- barrel chest (in severe disease)
There may be right ventricular failure (which can be shown by jugular venous distension)
CO2 retention is caused by decreased responsiveness of respiratory centre to prolonged hypoxemia and leads to cyanosis.
How is emphysema classified?
“Pink puffer”
There is an abnormal enlargement of the airspace distal to the terminal bronchioles accompanied by destruction of terminal bronchiole wall.
This leads to impaired ventilation due to loss of anatomical structure integrity of lung and destruction of alveolar sac.
Patients often have dysponea even at rest
Airway function is irreversible with a β2 agonist
There is minimal cough with a scanty sputum production
Patients are usually aged 55-75 , often with barrel chest due to overuse of accessory muscles of chest and neck to assist with breathing.
They Hyperventilate to compensate for hypoxia, leading to a Flushed appearance
What are the risk factors for COPD?
Smoking
Occupational exposure
Pollution
Genetic
Other (SEP, age, gender which are mostly linked to smoking)
How is smoking a risk factor for COPD?
Smoking is the #1 risk factor.
80-90% of COPD is linked to smoking
However NOT all smokers get COPD
How is occupational exposure a risk factor for COPD?
Patients working in coal mining, asbestos, grain handling, potter workers and farming are more likely to get COPD
How is pollution a risk factor for COPD?
Patients living in urban areas are more likely to get COPD due to inhalation of polluting gases e.g. From cars, factories etc.
How is genetic predisposition a risk factor for COPD?
Decreased α-1 antitrypsin increases the risk of COPD
Polymorphisms of SERPINA1 gene result in differences in α-1 antitrypsin production resulting in variant neutrophil elastase inhibition.
What does the SERPINA1 gene code for?
The SERPINA1 gene encodes the anti protease α-1 antitrypsin.
α-1 antitrypsin is higher in the white population and is produced by hepatocytes and mononuclear phagocytes.
It is a major inhibitor of neutrophil elastase which is capable of destroying components of the lung matrix.
M1 ala and M2 alleles have significantly lower elastase inhibitor capacity compared to M1val gene
What is the most common aetiology of COPD?
Most common aetiology is exposure to tobacco smoke although other chronic inhalation all exposures can also lead to COPD
What is the pathophysiology of COPD?
Inhalation of noxious particles and gases stimulate the activation of
- neutrophils
- macrophages
- CD8+ lymphocytes
These release a variety of chemical mediators (TNF-α, IL-8, LTB4)
These lead to widespread destructive changes in the airways, pulmonary vasculature and lung parenchyma
What are the results of the widespread destructive changes caused by TNF-α, IL-8 and LTB4?
Oxidative stress
Inhibition of α-1 antitrypsin activity
Mucous production
Vascular changes
What happens in oxidative stress?
Increased oxidants (generated by cigarette smoke) can react with and damage various proteins and lipids. This results in cell and tissue damage.
Oxidants also promote inflammation directly and exacerbate the protease-anti protease imbalance by inhibiting anti protease activity
What happens when the anti protease α-1 antitrypsin is inhibited?
α-1 antitrypsin inhibits several protease enzymes including neutrophil elastase. Inhibition of this antiprotease will allow increase neutrophil elastase activity. This can lead to damage of the alveolar wall (which comprises of elastin)
What happens in mucous production?
Inflammatory exudate present in the airways lead to an increased number and size of goblet cells and mucous glands.
Mucous secretion will increase, impairing ciliary motility.
The smooth muscle and connective tissues in airways will thicken.
Chronic inflammation results in scarring and fibrosis, limiting expiratory air flow, diffuse airway narrowing occurs (although this is more prominent in small peripheral airways)
What happens in the advanced stages of COPD?
Vasuclar changes occur. This includes
Thickening of pulmonary vessels leading to endothelial dysfunction of pulmonary arteries.
Structural changes increase pulmonary pressures - especially during exercise.
In severe COPD, secondary hypertension results in right sided heart failure due to hypoxia in poorly ventilated lungs, vasoconstrictor peptides produced by the inflammatory cells, and vascular remodelling.
What are the initial symptoms of COPD?
Chronic cough, sputum production
Patients may have these symptoms for several years before dysponea develops
How is COPD diagnosed?
Using the COPD-X framework.
C- confirm diagnosis O- optimise management P- prevent deterioration D- develop support and self management plan X- eXacerbation management
How can COPD be confirmed?
Patient history Physical examination Spirometry Exercise testing Arterial blood gas measurements
What sort of history would confirm a diagnosis of COPD?
History of chronic progressive symptoms Like cough Wheeze Breathlessness Sputum production
History of tobacco use
How would physical examination confirm a diagnosis of COPD?
Physical examination is not good for detecting mild to mod COPD
Common features: Hyperinflation of chest Reduced chest expansion Rales (crackling noises signalling oedema Ronchi (coarse rattling sound) Prolonged expiratory phase
How can spirometry confirm a diagnosis of COPD?
Where the forced expiratory flow in one second and the forced vital capacity ratio is less than 0.7
(The normal value is 0.8)
This is the best predictor of COPD
How can exercise testing confirm the diagnosis of COPD?
You can differentiate between breathlessness resulting from cardiac or respiratory disease.
How can arterial blood gas measurements confirm COPD diagnosis?
Oxygen saturation should be >92%
In respiratory failure, the partial pressure of oxygen is 50mmhg
Why are PEFR not adequate for diagnosis of COPD?
They have a low specificity and a high degree of effort dependence
How can treatment with a short acting β2 agonist confirm COPD diagnosis?
An improvement in FEV1 less than 12% after treatment with inhaled rapid acting bronchodilator is considered to be evidence if irreversible airflow obstrcution.
What are the treatment goals of COPD ?
Prevent disease progression Relieve symptoms Improve exercise tolerance Improve overall health status Prevent and treat exacerbations Prevent and treat complications Reduce morbidity and mortality
What are the short acting bronchodilators used to treat COPD?
Salbutamol 100-200μg up to qid for relief of breathlessness
Ipratropium bromide 2puff qid which can be titrated up to 24 puffs/day
How is ipratropium bromide different from salbutamol?
The duration of ipratropium bromide is longer and more effective than β agonists.
The peak effect occurs in 1.5-2 hours.
The duration of effect is 4-6 hours
Adverse reactions: dry mouth, nausea, occasional metallic taste
Poorly absorbed systemically so anticholinergic side effects are uncommon
What is the mechanism of action of ipratropium bromide?
Produce bronchodilation by competitive inhibition of cholinergic receptors in bronchial smooth muscle.
This blocks ACh reducing cGMP which would normally constrict bronchial smooth muscle.
Also helps reduce mucous secretions
What are the long acting bronchodilators used in COPD?
Salmeterol 50μg bd up to 100μg
Tirotropium bromide 1capsule od
What does salmeterol provide?
Prolonged bronchodilation for at least 12 hours
Use for patients suffering 2 or more exacerbations
What does tirotropium bromide provide?
Protects against cholinergic bronchoconstriction for more than 24 hours
Onset of effect is within 30 min with peak effect in 3 hours
Inhibits cholinergic receptors in bronchial smooth muscle
Acts locally,
Most common compliant is a dry cough
What is the fev1 for mild COPD?
When fev1 is 60-80%
What is fev1 for moderate COPD ?
40%-59%
What is the fev1 for severe COPD ?
<40%
What is the suggested treatment for mild COPD?
Intermittent bronchodilator salbutamol 200μg or ipratropium bromide 49μg prn before exercise
What is the suggested treatment for moderate COPD?
Intermittent or regular bronchodilator like salbutamol 200-400μg qid or ipratropium bromide 40μg qid. Combination bronchodilators may be considered
What is the suggested treatment for severe COPD?
Regular combination bronchodilator like salbutamol 200-400μg qid and ipratropium bromide 40-80μg qid.
What is an oral bronchodilator that can be used for COPD?
Methylxanthines like theophylline.
What is theophylline?
250-500mg bd
This is not favoured due to its narrow therapeutic index and is not suitable with macrolides antibiotics .
It is a weak bronchodilator but will have additional actions in COPD by increasing respiratory drive, improved diaphragmatic function and improved cardiac output
Adverse reactions include nausea, vomiting, diarrhoea, headache, dizziness, tachycardia
What is the mechanism of action of theophylline?
It inhibits phosphodiesterase type 4 by increasing intracellular concentrations of cAMP which reduces smooth muscle contraction
What is an example of glucocorticoids used in COPD?
Prednisolone (20-50mg od for 2 weeks)
Does not reduce mortality or show a slow decline in lung function
But reduces frequency of exacerbations, hospitalisation and overall health status.
Is is helpful in mod to severe disease with fev1<50% predicted
May increase risk of pneumonia and osteoporosis
Adverse reactions include sore throat, oral candidiasis, skin bruising.
Severe adverse reactions include adrenal suppression
What are the benefits of combination therapies for COPD?
Combining bronchodilators with different mechanisms of action allows the lowest effective doses to be used
Helps reduce adverse effects from individual agents
Combination of both short and long acting β2 agonists with ipratropium has been shown to provide added symptomatic relief and improvements in pulmonary function.
What combination therapy is available for COPD ?
Combivent which contains salbutamol and ipratropium is availble as a MDI for chronic maintenance therapy of COPD
What are characteristics of patients at risk of COPD?
They have a score of 0
Chronic symptoms
Exposure to risk factors
Normal spirometry
Avoidance of risk factors by giving influenza vaccination and pneumococcal vaccine
What are the characteristics of patients with mild COPD?
They have a score of 1
Fev1/FVC ratio <70%
With or without symptoms.
As well as giving flu and pneumococcoal vaccine, can ADD a SABA when needed
What are the characteristics of patients with moderate COPD?
They have a score of 2
FEV1/FVC ratio <70%
FEV1 is between 50% and 80%
With or without symptoms
As well as vaccines and SABA prn, add treatment with 1 or more LABA and rehabilitation.
What are the characteristics of patients with Severe COPD?
They have a score of 3
FEV1:FVC ratio <70%
FEV1 between 30% and 50%
With or without symptoms
As well as vaccine, SABA prn, regular LABA and rehabilitation, an ICS is also added if there are repeated exacerbations
What are the characteristics of patients with Very severe COPD?
They have a core of 4
FEV1/FVC ratio < 30% or presence of chronic respiratory failure OR right heart failure
As well as vaccinations, SABA prn, regular LABA, rehabilitation and ICS treatment, Long term oxygen therapy is added and surgical treatments are considered
What are the non pharmacological interventions for COPD?
physical activity smoking cessation pulmonary rehabilitation Influenza and pneumococcal vaccinations Chest physiotherapy Nutrition
How does physical activity help COPD?
Reduces COPD admissions and mortality
How does smoking cessation help COPD?
Most effective strategy to reduce risk of developing COPD
The only intervention proven to affect long term decline in FEV1 and slow the progression of COPD (this difference is shown 10 years post cessation)
How doe pulmonary rehabilitation help COPD?
This includes exercise training along with smoking cessation, breathing exercises, psychosocial support and health education about COPD
How do the influenza and penmococcal vaccinations help COPD?
Annual vaccination with the inactivated IM influenza vaccine is recommended.
- shown to reduce exacerbations, hospitalisations and death
One dose of the polyvalent penumococcal vaccine is indicated for patients at any age with COPD, and revaccination is recommended for patients > 65 years
- less conclusive evidence but recommended by guidelines
How do chest physiotherapy help with COPD?
This assists sputum removal and improves lung ventilation.
Using SABA prior to treatment may help
How does nutrition help with COPD?
Excessive weight will increase the work of breathing and predisposes to sleep apnoea. Low weight on the other hand, indicates poor survival so diet should be adjusted accordingly.
How can we prevent deterioration of COPD?
Smoking cessation
Recommending annual influenza vaccination
recommending pneumococcal vaccination and revaccination every 5&10 years
Consider long term home oxygen therapy
reduce risk factors
Why is smoking cessation used to prevent deterioation of COPD?
Buproprion amfebutamone inhibitions nueronal NA and Dopamine uptake reducing the tobacco withdrawal symptoms by increasing CNS dopamine levels however should not be used in patients with
bulimia, anorexia, bipolar disorder, severe hepatic cirrhosis, or those taking MAO inhibitors.
Side effects: dry mouth, insomnia, headache, dizziness, allergic reactions, taste disorders, seizuires
Why are supports and a self management plan for COPD developed
Checks for psychosocial problems and can suggest supportive strategies
Refer for pulmonary rehabilitation therefore reducing career strain and increases patient knowledge
Refer to a respiratory physician who can clarify diagnosis, consider other therapies, and long term home oxygen therapy as well as facilitate pulmonary rehabilitation
Refer to hospital if inadequate response to ambulatory management
What are some other situations where you would refer a COPD patient to hospital?
inability to walk between rooms,
inability to eat or sleep due to dysponea,
altered mental status suggestive of hypercapnia,
cannot manage at home or
has a high risk of comorbidity conditions
How are COPD exacerbations managed?
Treat with bronchodilators Antibiotics Oxygen Corticosteroids Aminophylline, IV fluids
What is a COPD exacerbation?
Defined as an event in the natural course of the disease which is characterised by a change in the patients baseline dysponea, cough and/or sputum which is beyond normal day to day variations.
Sudden worsening of symptoms- SOB, sputum production, lasting several days and is acute in onset
What are the common causes of exacerbations?
Infection Air pollution Smoking Lack of pulmonary rehabilitation programme Improper use of inhaler Poor adherence to drug therapy programme
What is the FEV1 of a severe exacerbation?
Less than 1L or <40% predicted
How do bronchodilators treat COPD exacerbations?
Nebulised β2 agonist like salbutamol (2.5-5.0mg) and a nebulised anticholinergic like ipratropium bromide (500μg)
How are antibiotics used to treat COPD exacerbations?
These are shown to be effective against the development of purulent sputum (containing pus)
What is the first line therapy antibiotic for COPD exacerbation?
Aminopenicillin or a macrolides with activity against haemophilus influenzae
What are the common organisms for acute exacerbation of COPD?
Haemophilus influenza,
Amophilus influenzae,
Streptococcus penumonia
What are other antibiotics which can treat the common organisms causing COPD exacerbations causing infection?
Amoxicillin
Clarithromycin
Roxithromycin
Which antibiotics should NOT be used to treat COPD exacerbations causing infection?
Trimethroprim sulfamathoxole should not be used due to increased pneumococcal resistance,
Erythromycin is inactive against H. Influenzae
When should antibiotics be given in a COPD exacerbation caused by infection?
Initiated within 24 hours of symptoms to prevent unnecessary hospitalisation. Antibiotics generally continued for at least 7-10 days
What is the aim of oxygen therapy?
Improve oxygen delivery to cells and improve hypoxia
What are the two types of oxygen therapy?
Intermittent therapy: to increase mobility and capacity for exercise. Most beneficial in emphysema patients
Long term oxygen therapy: to be administered for at least 15 hours/day and shown to improve survival in patients with severe COPD
What are the criteria for prescribing long term oxygen therapy?
If kPa is below 7.3
Or if kPa is between 7.3-8.0 and patient has polycythemia, nocturnal hypoventilation or pulmonary hypertension
How are corticosteroids used to treat COPD exacerbations?
Prednisolone (25-37.5mg/day) if patient meets following criteria:
Patient already taken oral steroids
Previous documented response to oral steroids
Obstruction fails to response to an increase in bronchodilator dosage
First presentation of airflow obstruction
What are the effects of long term corticosteroid use?
Osteoporosis
Why is aminophylline used in COPD exacerbations?
It causes bronchodilation through the same mechanisms of action as theophylline, which inhibits the phosphodiesterase type 4 by increasing intracellular cAMP concentrations reducing smooth muscle contraction.
Improves respiratory drive, diaphragmatic function and cardiac output in COPD but adverse reactions include nausea, vomiting, diarrhoea, headache, dizziness and tachycardia
How do IV fluids help treat COPD exacerbations?
Dehydration can be a problem due to hyperventilation, pyrexia, and inability to eat or drink
What sort of monitoring is required in COPD?
Monitor arterial blood gases and oxygen saturation in severe exacerbations
Patient adheence to therapeutic regimen,
side effects,
potential drug interactions
Subjective measures of quality of life
White blood count,
Vital signs
Chest X-ray
Changes in frequency of dyspnoea
Sputum volume and Sputum purulence to be assessed at onset and throughout exacerbation.
Although corticosteroids are used in COPD, why are they limited as opposed to their use in asthma?
In COPD the inflammation is different. Their efficacy can be measured by testing PEF measurements, symptom frequency, exercise tolerance after a 2 week trial of oral prednisone 30mg OD.
How do the exacerbations of asthma compare with the exacerbations of COPD?
Asthma: characterised by recurrent wheezing, shortness of breath, chest tightness, cough. Identifiable triggers: allergens, cold air, exercise.
COPD: commonly respiratory tract infections
What are the major differences in immune cells present in asthma compared with COPD?
Asthma: eosinophils, SMALL increase in macrophages, increased CD4+ TH2 lymphocytes, activation of mast cells
COPD: neutrophils, LARGE increase in macrophages, increase in CD8+ T lymphocytes
What are the differences in immune mediators in asthma compared to in COPD?
Asthma: LTD4, IL-4, IL-5 plus many others
COPD: LTB4, IL-8, TNFα
What are the differences in the molecular consequences of asthma compared to COPD?
Both asthma and COPD result in mucous metaplasia and glandular enlargement
In addition to this,
Asthma: fragile epithelium, thickening of basement membrane,
COPD: squamous metaplasia of epithelium, parenchymal destruction,
What are the differences in the response to treatment of asthma compared with COPD?
Asthma: glucocorticosteroids inhibit inflammation
COPD: glucocorticosteroids have variable effect
What are the general and main differences of asthma compared with COPD?
Asthma: early onset in life, symptoms vary from day to day, symptoms at night/early morning, Allergy, rhinitis and/or eczema also present Family history Largely reversible airflow limitation
COPD: Onset in midlife Symptoms slowly progressive Long smoking history Dyspnoea during exercise Largely irreversible airflow limitation
