Pathophysiology and Treatment of COPD - Kradjan Flashcards
What are the two guidelines for COPD?
Global Initiative for Chronic Obstructive Lung Disease
American Thoracic Society (ATS) and European Respiratory Society (ERS) joint guidelines
The guidelines are very similar
“A common preventable and treatable disease characterized by AIRFLOW limitation that is usually PROGRESSIVE and associated with an inflammatory response in the airways and lungs to noxious particles. Is not fully reversible”
COPD
What are the two major conditions associated with COPD?
Chronic bronchitis and emphysema. Asthma may be present, but is not included in COPD.
What is the airflow limitation in COPD caused by?
- Small airways disease and fibrosis
- Destruction of lung parenchyma (emphysema)
These seem to be caused by inflammation (systemic and pulmonary) that is a amplification of normal inflammatory response to noxious particles.
What percentage of people have COPD over 55?
2-10%. 4th leading cause of death after CAD (coronary artery disease), cancer, and stroke.
What is the concerning observation of a graph of the leading causes of death over the last 50 years?
The other causes of death seem to be in a downward trend, while COPD is on an upward trend (at least until 1998 when the graph stops)
Term: Presence of chronic productive cough for three months in each of two consecutive years in a patient in whom other causes of chronic cough (eg heart failure) have been excluded.
Chronic bronchitis
Looking at a small airway, how would it differ in chronic bronchitis vs. asthma?
In asthma the small airways would be constricted to just a portion of their normal size. In chronic bronchitis, there is fluid in the airways.
On a chest x-ray, how would emphysema present?
It would present as balloon shaped bullae. This impairs the gas exchange.
How does a patient with chronic bronchitis present usually?
Early: smoker’s cough, mucous production. Little functional problems early on (little SOB, exercise intolerance or change in PFT’s). (10-15 years of irritating but functional symptoms.
Moderate: SOB and exercise intolerance start to interfere with activities of normal living.
Moderate to severe: From here PFT’s decline. End stage is less than 50% of normal CO2 retention. Rales, bronchi, SOB with few steps. Recurrent infections.
What does emphysema do to the body?
- Destruction of alveolar walls, but without obvious fibrosis
- Abnormal permanent enlargement of the terminal airspaces (decreased air exchange location, less gas exchange).
- Air trapping (dead space)
- Loss of elastic recoil and structural support
- Obstruction and airway collapse during expiration
- Balloon shaped bullae on CXR
What is the pink puffer?
Sufferer of emphysema
How do you recognize a pink puffer?
- pursed lip breathing
- barrel chest
- less CO2 retention and hypoxia by breathing harder
- no mucus production
- bullae rupture, pneumothorax
- shortness of breath and decreased exercise capacity
What is the number one risk factor for COPD?
Smoking. 80-90% of cases linked to smoking.
50% of smokers have symptoms
What rate of decline in FEV1 is normal for non-smokers compared to smokers?
non-smokers: 25 mL/year
smokers: 50 mL/year
If you stop smoking, what happens to your FEV?
It doesn’t return to a non-smoker status, but it doesn’t decline as quickly.
What part do enzymes play in COPD?
The natural enzymes enhance lung tissue destruction.
- Elastases, proteases, cysteine proteinase, trypsin, matrix metaaloproteinases
What enzymes play a role in protecting the lungs?
elastase inhibitors, anti-proteases
How do people with a deficiency in alpha-1-antitrypsin present (an anti-protease)?
They do not have the mechanism to inhibit proteases, and so they develop emphysema symptoms by age 20 w/o smoking.
What is the mechanism for smoking?
Neutrophils and macrophages are attracted, and inhibitors are inactivated. Elastase is released.
How do COPD and asthma relate to each other?
They both have a chronic airway obstruction
Acute and chronic inflammation
Overproduction of some mucus glands (chronic bronchitis only)
Smooth muscle hypertrophy
How do asthma and COPD differ?
COPD
Lower airway disease
Greater role of neutrophils over eosinophils
IL-8 and type I helper CD8 T lymphocytes (instead of IL-5)
Oxidative stress
Fixed airway obstruction without reversibility (or limited at least)
Tissue destruction
What are the inflammatory mediators in asthma? COPD?
Eosinophils for asthma, neutrophils for COPD.
When is the usual age of onset in COPD?
40’s or later.
What are the symptoms of someone with COPD?
chronic cough w/ or w/o mucus production
Dyspnea (SOB perception)
Respiratory infection that is persistent
What is the dyspnea scale and what are the scores?
0-4, with 4 being too breathless to leave the house or when undressing.
What are the three ways of assessing air outflow? How are each measured? What is the average of each?
- Peak flow (in L/min). Average is 500 L/min
- FEV1 (in L). Average is 4-4.5L
- FVC ( in L). Average is 4.5-5L
When a postbronchodilator reading is taken and gives a FEV1/FVC ratio of 0.7, what can that mean?
That there is possibly the presence of COPD, especially if indicators are present.
How is therapeutic success monitored in COPD patients?
Through subjective improvement rather than objective measurements (such as PFTs).
How do the stages in COPD compare to the stages in asthma?
COPD has: ATS and GOLD.
ATS: at risk, groups A-D
GOLD: Stages 1-5
Asthma has steps that address the intermittent, mild persistent, moderate persistent, and severe persistent stages.
What is the most important therapy goal for COPD?
To stop smoking! This should help increase quality of life, prevent acute exacerbations, maximize functional ability, etc.
At what point should bronchodilators start to be used in COPD?
If symptomatic and FEV1 is less than 60% of predicted.
In COPD, what would you prescribe for those in Group A?
A SABA (as needed for intermittent symptoms)
In COPD, what would you prescribe for those in Group B?
Add a LABA or LAMA (scheduled rather than as needed)
In COPD, what would you prescribe for those in Group C?
Add a second LABA, or use corticosteroids (especially if multiple exacerbations.
In COPD, what would you prescribe for those in Group D?
Use all used in previous steps, but add oxygen therapy, phosphodiesterase 4 inhibitor, or surgery.
In COPD, what would you prescribe for those at risk?
Get flu shot, stop smoking
Are leukotriene modifiers more useful in asthma or COPD?
Asthma
How long does it take to assess a response to a COPD drug?
4-8 weeks, especially with LAACs.
When evaluating if a medication works, is it better to use improvement from a single dose response or data from cumulative responses?
Cumulative after 1-4 weeks.
Which anticholinergic is indicated for both COPD and asthma?
Tiotropium (Spiriva)
What anticholinergics are out there for COPD?
Tiotropium
Aclindinium
Umeclidinium
Glycopyrrolate
What does acetylcholine have to do with constricted airways?
ACh modulates the basal tone in airways. In COPD, ACh causes a greater constriction than normal. Anticholinergics are used to target this ACh.
Which receptors provide inhibitory feedback to reduce ACh release from cholinergic nerve endings?
M2 receptors.
Which receptors line the airway smooth muscle cells mucus glands?
M3 receptors.
Which receptors enhance cholinergic neurotransmission?
M1 receptors
Which receptors would the ideal anticholinergic drug hit?
M1 & M3 receptors.
What would happen if the M2 receptors were also blocked?
There would be an increase in ACh release, because the negative feedback loop would be turned off.
What receptors do ipratropium hit?
Non-selectively inhibits M1, M2, M3
What receptors do tiotropium hit?
M1 and M3 (may also bind M2, but rapidly dissociates)
Compare salmeterol and tiotropium:
Equally effective in symptom improvement, but better FEV1 improvement with tiotropium.
What receptors do alidinium hit?
Equal affinity for all 5.
What did the UPLIFT data from a trial show?
That there was not an increased risk for stroke and cardiovascular events related to the tiotropium handihaler.
What are the LABA agents in COPD?
Salmeterol (both) Formoterol (both) Indacaterol Olodaterol Vilanterol
Which LABA has the fastest onset? Which of the following has 24 hours dosing?
Formoterol has the fastest onset. Tiotropium has 24 hour dosing.
Which medications can be combined with steroids in the same inhaler? LABAs or LAMAs?
LABAs
In COPD, which may have the better outcome with combinations (not in same inhaler)? LABA w/ steroid or LABA w/ LAMA?
LAMA w/ LABA. It may have an additive effect on improving pulmonary function, and may avoid needing to use a higher dose or either agent.
What LABA/LAMA combo products are there?
Olaterol plus tiotropium
Vilanterol plus umeclidinium
Indacaterol plus glycopyrrolate
When do steroids seem to work best in COPD? What combo products are out there for COPD that have steroids?
When there is an asthma component.
Advair, Symbicort, Breo Ellipta, Dulera
What type of medication is Roflumilast?
A phosphodiesterase inhibitor
How does azithromycin help COPD patients?
Daily use decreases acute exacerbations by 27%. Hearing loss also problem.
What do beta blockers do in COPD?
May reduce mortality and risk of exacerbations in patient with COPD.
