Pulmonary (part 2) Flashcards
___ ___ is the most common lethal genetic disorder of white people
Cystic Fibrosis
Cystic fibrosis affects ____ people worldwide
70,000
In the U.S, there are ____ people with CF
30,000
Cystic fibrosis is an ___ ___ disorder
Autosomal recessive
CF is caused by a gene defect where there is a lack or a malfunction of _____ gene
CFTR
CFTR regulates the movement of ___ and ___ within cells in the airway
Cl- and HCO3
A mutation in CFTR gene causes…
-Defective Cl- and HCO3 secretion
-Enhanced Na+ reabsorption
The defects caused by CFTR mutation cause…
-Dehydrated secretions (not mobilized)
-Promoties bacterial infection
-Airways become colonized
Class I of CF (G542X) causes ____ ___ of CFTR
No synthesis
Class II of CF (F508del) causes ___ ___ of the CFTR gene, leading to an absense of functional protein at the cell membrane
Reduced trafficking
Class III of CF (G551D) causes ___ ___, so CFTR reaches the cell membrane, but becomes unstable
Reduced gating
Class IV CF (R117H) causes ___ ___, so CFTR reaches the cell membrane, but abnormal conformation of the pore leads to disrupted ion flow
Decreased conductance
Class V CF (A455E) causes ___ ___ of CFTR
Reduced synthesis
There are over ____ mutations of the CFTR gene, all with varying severity of disease
2000
If someone had an increased sweat ____, check for genotype and categorize to guide treatment
Chloride
In class I, there is…
No functional CFTR created
In class II, CFTR is created but ____ so it does not reach the surface
Misfolded
In classes III and IV, CFTR is created, but does not move through the ____ properly
Channel
In class V, there is inefficient ____, causing little or no CFTR production
Splicing
With minimal/no CFTR function, someone might experience…
-Chronic sinusitis
-Severe chronic infection
-Hepatobiliary disease
-CF-related diabetes
-GI: poor absorption of nutrients
-Male infertility
With partially effective CFTR function, someone might experience…
-Chronic sinusitis
-Chronic infection
-Normal hepatobiliary function
-Pancreatitis
-Normal or minimal problems
-Male infertility
The medial survival age for a child born with CCF in 2019 is ____ years
48
No other lung disease has seen such a dramatic ___ over time than CF
Improvement
What are we doing right for CF?
-CF centers: nationwide care model
-Newborn screening
-Family-clinician partnerships
-CF foundation- education and research
-High % participate in clinical trials
Since 2011, there have been ___ new drug targets for CFTR malfunction
3
____ is a potentiator drug that increases the time it takes for the CFTR channel to open
Ivacaftor (Kalydeco)
Ivacaftor (Kalydeco) has been shown to only be effective for CF class ___
III (G55ID)
Triple therapy includes ____ ____ and a ____; this has been effective for about 90% of patients for 6 or more years
2 correctors; potentiator
One example of a triple therapy is ____
Trikafta
Outcomes of Tricofta:
-Increased forced expiratory volume
-Decreased sweat chloride
-No dose-limiting side effects
The purpose of “vest” therapy is to ___ ___
Mobilize sputum
Vest therapy utilizes ___ ___ ___ ___ ___
High-frequency chest wall oscillation (HFCWO)
Vest therapy has shown to be highly effective in ____ ____
Secretion removal
We want to decrease ____ of the secretions in the lungs to reduce sputum-colonized bacteria
Viscosity
To control infection, ____ are recruited and release DNA filaments covered with neutrophil elastase (neutrophil extracellular traps)
Neutrophils
The goal is to kill bacteria over a ____ area
Wider
The problem is that ____ causes lung destruction and the process creates a low O2 environment
Elastase
The low O2 environment promotes growth of _____ _____ and biofilm; once this occurs, eradication is impossible
Pseudomonas. aeruginosa
Dornase (Pulmozyme) is a drug that can decrease sputum viscosity by…
-Breaking down neutrophil extracellular traps
-Decreasing viscosity of purulent sputum
-Making secretions easier to cough up
Dornase (Pulmozyme) is administered via ____ 1-2 times per day
Nebulizer
A ____ ____ trial was done to try and decrease viscosity
Hypertonic saline
The rationale for using hypertonic saline is that it may cause…
-Excessive sodium reabsorption would draw more moisture into the airways (water follows sodium)
Result of the hypertonic saline trial:
-Higher forced vital capacity, higher forced expiratory volume
-56% fewer pulmonary exacerbations
-Osmotic effect, H2O hydrates airways
It is also important to reduce ___ ___ for patients with CF
Bacterial load
How can we prevent between patient bacterial spread?
-Contact precautions
-Physical separation of patients
-Masks in health care settings
-Good hand hygiene
We can use ____ to reduce airway inflammation
Azithromycin
We can also use ___ ___ ___ if pseudomonas is present
Cyclic inhaled antibiotics
In patients with CF, we should also try to prevent ___ ___ and maintain fitness
Weight loss
Those with CF lack ____ ___, which may cause fat malabsorption and failure to thrive
GI enzymes
The median survival age in the USA is ___ years while it is ____ in Canada
40.6; 50.9
The difference between survival rates is due to…
-Earlier adoption of high-fat, high-calorie diet
-Difference in health care systems (private vs national health care)
The benefits of a lung transplant depend on…
-Lung function (clear advantage if forced expiratory volume < 40%)
-Age at transplant (better survival over age 30)
Asthma is very common and affects ___ million people including 5.5 million children
24.7
____ is defined as variable airflow limitation and airway hyperresponsiveness due to exaggerated contractile response of airways
Asthma
Asthma causes…
-Bronchoconstriction
-Airway inflammation
-Mucus secretion
There can be both ___ and ____ triggers of asthma
Allergic and non-allergic
Allergic triggers of asthma might be due to limited ____ exposure as a child or exposure to an allergen
Biodiversity
Non-allergic triggers of asthma might be due to…
-Exposure to an irritant (gas, chemical, dust)
-Exercise-induced
-Obesity related
Pathophysiology of allergic asthma:
-Initial allergen exposure
-Allergen-specific IgE antibodies synthesized and secreted
-IgE antibodies bind to high-affinity receptors on mast cells
-Allergen in inhaled, cross-links on mast cell surface
-Followed by mediator release
-Inflammatory cells (eosinophils) enter airway
Non-allergic asthma is caused by a _____ airway
Hyperreactive
With non-allergic asthma, a trigger can be…
-An irritant like gas, chemicals, or dush
-Decreased airway surface liquid (exercise, cold air)
Non-allergic asthma responds with _____
Bronchoconstriction
Prevalence of asthma has been ____
Increasing
It is thought that asthma is becoming more common because of exposure to less ____ as a child (AKA “Hygiene Hypothesis”)
Biodiversity
People who are predisposed to asthma favor ____ cytokines
Th2
What may predispose a child to asthma?
-No siblings
-No daycare
-No pets
-“clean home” lifestyle
-Antibiotic use
People who are not predisposed to asthma favor ___ cytokines
Th1
What would decrease risk of asthma for children?
-Older siblings
-Early day care
-Pets
-Farm life
In a study done in Europe, compared to those who lived in the city, adults who lived on a farm had…
-Less atopic (allergic) asthma
-Less bronchial hyper-responsiveness
-Less allergic rhinitis
In an RCT, a daily patch with 250 ug of peanut protein was given to children with peanut allergy and this allowed children to tolerate food peanuts at ___ ___ (35% tolerated a higher dose)
12 months
Because of this peanut allergy study, the FDA approved the drug ____, which allows peanut-allergic children to tolerate 1-2 peanuts per day without a reaction
Palforzia
The goal for asthma is “___ ___’
Well controlled
What are the first steps in treating asthma?
-Confirm asthma diagnosis
-Reduce trigger exposure
-Monitor level control
The Assessment of Symptoms Control for asthma a questionnaire that asks “in the past 4 weeks, have you had…
-Daytime symptoms > 2 x per week?
-Any night wakening due to asthma?
-Symptoms reliever > 2 x per week?
-Any activity limitations due to asthma?
(DASA)
Well-controlled asthma will have ____ of the symptoms listed in the assessment of symptom control
0
Partially-controlled asthma will have __-__ of the symptoms listed in the assessment of symptom control
1-2
Uncontrolled asthma will have __-__ of the symptoms listed in the assessment of symptom control
3-4
A ____ ___ ____ provides objective measure of the extent of airflow compromise and can be used at home by patients (very inexpensive- $20)
Peak flow meter
The green zone of a peak flow meter would be ___-___% of the patient’s personal best
80-100
The yellow zone of a peak flow meter would be ___-___% of the patient’s personal best
50-80
The red zone of a peak flow meter would be <___% of the patient’s personal best
50
What are two types of inhalers?
-Pressurized (MDI): propelled by gas
-Dry powder (PDI): inhaled as powder
Steps for using a PDI (dry powder inhaler):
-Open so you can see the mouthpiece
-Load medication (click, twist, etc.)
-Gently breathe out
-Do not exhale into the device
-Seal lips around the mouthpiece
-Inhale rapidly and deeply
-Hold breath 10 seconds to deposit
-Remove from mouth and exhale
-If powder remains, repeat
-Wait 1 minute between puffs
Steps for using a MDI (pressurized inhaler):
-Remove the cap and hold the inhaler upright
-Shake the inhaler vigorously for 5 seconds
-Tilt your head back slightly and breathe out
-Place the inhaler in the mouth
-Press down as you inhale
-Breath in slowly
-Hold breath for 10 seconds to deposit
-Wait 1 minute between puffs
-Once a week, remove, rinse, and dry
Standard therapy for asthma:
-Inhaled corticosteriod (ICS)
-Long-acting beta agonist (LABA)
-Leukotriene receptor antagonist (LTRA)
Inhaled corticosteroids decrease ____ ____ (chronic)
Airway inflammation
Long-acting beta agonists stimulate b2 adrenergic receptors in order to…
-Increase cAMP
-Cause smooth muscles surrounding bronchi to relax
Leukotriene receptor antagonists block the action of ____, which are inflammatory chemicals that cause asthma on contact with allergen
Leukotrienes
What are three treatment options for well-controlled asthma?
- SMART (single maintenance and reliever therapy): dual inhaler inhaled corticosteroid/formoterol (LABA) for symptom relief; (has to be formoterol-> 5-minute action)
- Inhaled corticosteroid + short-acting beta agonist (2 inhalers) prn for symptom relief
- Inhaled corticosteroid bid + short acting beta agonist prn
There is commonly poor adherence to treatment option #___ (inhaled corticosteroid bidaily plus short-acting beta agonist prn)
3
Overuse of ___ ___ ___ ____ can be deadly and is a major risk factor for increased emergency room visits and mortality
Short-acting beta agonists
Mean age for somone who dies from asthma is ___ years
32
What gender and race have higher incidence of deaths from asthma?
-Males
-African Americans
___% of asthma deaths are due to using or overusing short-acting beta agonists
91
Standard therapy for treating poorly-controlled asthma:
- Inhaled corticosteroids (ICS)
- Add long-acting beta-agonist (LABA)
- Add leukotriene receptor agonists (LTRA)
- Increase inhaled corticosteroid dose
- Check eosinophil level (may need biologic therapy)
Severe asthma is ___ ___
Therapy resistant
With severe asthma, there is increased levels of ___ and ___
IgE and eosinophils
Severe asthma is sometimes called “____ ___”
Eosinophilic asthma
What medication options can be used for severe asthma?
-IL-4
-IL-5
-IL-13
What are three treatment options for well-controlled severe asthma?
-Inhaled corticosteroid and formoterol (SMART)
-Inhaled corticosteroid prn and short-acting beta agonist prn
-Inhaled corticosteroid bid and short-acting beta agonist prn
What are treatment options for poorly controlled severe asthma?
-Inhaled corticosteroid
-Long-acting beta-agonists
-Leukotriene receptor antagonist
-If eosinophil level is high: Anti IgE or Anti IL-5, Anti IL-4, Anti IL-13
What are some environmental risk factors for COPD?
-Cigarette smoke
-Air pollution
-Biomass fuels
What are some genetic risk factors for COPD?
-Low lung function in early adulthood (forced expiratory volume < 80%)
-AAT deficiency
An AAT deficiency causes greater lung tissue ____
Breakdown
Treatment for AAT deficiency includes…
-Infusion
-Lung transplant
Pathology of COPD:
-Irritants release free radicals
-This inactivates anti-proteases which increases tissue breakdown
-Neutrophils are then recruited (differs from asthma) and they release elastase which increases tissue breakdown
COPD also causes systemic ____
Inflammation
What are the symptoms of COPD?
-Lung hyperinflation
-Accelerated loss of forced expiratory volume as well as FEV1/FVC
-Systemic impact (skeletal muscle dysfunction)
With COPD, there is expiratory flow limitation which results in progressive increase in ___-___ ___ ___ above its resting value
End-expiratory lung volume
COPD is diganosed with an FEV1/FVC < ____%
70%
The severity of COPD is determined by decreases in ____
FEV1
What are possible impacts on lung function with COPD?
-Rapid decline of FEV1
-Slow decline of FEV1
-No decline of FEV1
What are possible areas of the lung involved with COPD?
-Upper lobe
-Lower lobe
-Upper and lower lobe
What are possible response to therapy with COPD?
-Frequent or few exacerbations
-Variable symptom burden
Medication for COPD is based on what three things?
-Phenotype
-Endotype
-Precision medicine
The use of ____ ___ for treatment of COPD depends on the area of the lung involved
Bronchial valves
High-resolution computed tomography is used to determine if someone meets criteria for bronchial valves; what are the criteria?
- > 40% destruction of target lobe
- > 90% intact fissure between target and ipsilateral lobes
-No vessels cross adjacent lobe
Using a ____, a valve is inserted into the airway so allow air to flow out, but not in
Bronchoscope
The bronchoscope progressively ____ the lobe and allows for more functional lung expansion
Deflates
Bronchial valves can ____ forced expiratory volume and ____ dyspnea
Increase; decrease
COPD patients may have elevated levels of blood ____
Eosinophils
People with COPD also have inflammation driven by ____ and/or ____
Neutrophils; eosinophils
Standard therapy for COPD:
-Short-acting inhaler (rapid onset, 4-6 hours)
-Long-acting bronchodilator (12-24 hours)
Examples of short-acting inhalers:
-Short-acting beta agonists (SABA): albuterol
-Short-acting antimuscarinic (SAMA): Ipratropium
Short-acting beta agonists stimulate b2 adrenergic receptors and increase ____ and decrease ____
cAMP; BC (bronchiole constriction)
Short-acting antimuscarinic targets muscarinic receptor to decrease ___ ___
Bronchiole constriction
Long-acting beta-agonists and long-acting antimuscarinic operate on with the ___ ___ same short-acting
Same mechanism
The new recommendation for those with COPD is a 2 drug regimen made up of ____ and ____
LABA and LAMA
The two drug regimen for COPD has been shown to…
-Have better symptom control
-Reduces hospitalizes 11%
-Reduced exacerbation risk 17%
-Less dyspnea, improves HRQoL
-However, more costly
The IMPACT trial looked at the outcome of 3 drug therapy (LABA, LAMA, ICS); this study showed that three-drug therapy ____ exacerbations but ____ rates of pneumonia
Decreased; increased
Who does best on a 3 drug regimen?
- > 1 exacerbation/year
-Eosinophils > 150 cells per uL (2-3%)
Primary risk reduction for COPD is ___ ___
Smoking cessation
All COPD patients benefit from regular ___ ___ and should repeatedly be encouraged to remain active
Physical activity
Why is exercise so difficult for someone with COPD?
-Air trapping (increased end-expiratory lung volume)
-Dynamic hyperinflation (can’t fully exhale)
-Ventilatory limitation (exercise stop secondary to dyspnea)
-Muscle deconditioning
The goal of pulmonary rehab is to promote ____ through self-management skills, exercise training, and reducing dyspnea
Activity
COPD is the most common indication for ___ ___
Lung transplant
Survival time with a lung transplant is about ___ years and it is difficult to judge the best time to do it
6
Average survival time of someone with CF who had a transplant is ____ years
9.9
