Airway & Lung Diseases Flashcards
Asthma stats
affects ~10% population (39.5 million ppl)
- higher in blacks
- higher in females
- higher in children
Pathophysiology of Asthma
-chronic inflammatory disease involving episodes of REVERSIBLE airway obstruction (reversibility distinguishes asthma from COPD)
Asthma characterized by:
A) Chronically inflamed airways
B) Airway Hyperreactivity
C) Airway Smooth Muscle Hypertrophy
D) IgE-Mediated Immune Response
A) Chronically Inflamed Airways
- epithelial damage
- mucosal edema
- inflammatory cell infiltration (eosnophils, lymphocytes, neutrophils)
- mediator release
Mediator Release
- PGs : bronchoconstriction
- Leukotrienes C4/D4 : bronchoconstriction, airway hyperreactivity
- Platelet Activating Factor: airway hyperreactivity
- Histamine: no role
- Adenosine: bronchoconstriction, mast cell activation -Cytokines: IL5-eosinophil recruitment, IL4-IgE production
- Tryptase: airway inflammation (PAR2: protease activated receptors)
What evidence could you provide that argues against histamine or PGs being important mediators of asthma?
Antihistamine and COX-inhibitors do not help in asthma!
B) Airway Hyperreactivity
-increased responsiveness to a variety of stimuli (bronchoconstrictors, irritants, exercise)
C) Airway smooth muscle hypertrophy
-increase bronchial reactivity
D) IgE mediated immune response
- mast cells have an important role in asthma
- continual exposure to antigen
- inflamed airways
- increased airway reactivity
Hygiene hypothesis
in early life, decreased exposure to infections + increased antibiotic use + decreased exposure to noxious pulmonary stimuli causes a change in immune system development
- decreased Th1 response (infection fighting)
- increased Th2 response (allergic diseases, asthma)
Bronchoconstriction precipitated by variety of stimuli:
A) Environmental (house dust mite, animal dander, tobacco smoke, air pollutants, ozone)
B) Occupational (grain dust, red cedar)
C) Drugs (propanolol, aspirin)
D) Exercise
Reducing exposure–>less asthmatic episodes
Asthmatic episodes divided into:
A) Early response
B) Late Response
Early Response
bronchoconstriction occurring immediately after exposure
Late Response
bronchoconstriction occurring hours after exposure
- hyperreactivity lasts for several weeks
- may relate to release of mediators from infiltrating inflammatory cells and the time it takes for them to infiltrate
Asthmatic episodes exacerbated by:
- viral respiratory infection
- rhinitis
- sinusitis
- cigarette smoke
- pollution
- gastroesophageal reflux
Clinical features of Asthma
- wheezing, chest tightness
- non-productive cough
- episodic airflow obstruction
- increased airway reactivity to non-specific stimuli
Episodic airflow obstruction
A) During remission: PFTs may be normal
B) During partial remission: no clinical signs, but may see decreased pulmonary function from peak flow meter (bronchoconstriction without knowing it, flow meter can detect the bronchoconstriction without them knowing it is present)
Diagnosis
PFTs (pulmonary function test):
- decreased expiratory flow rate, FEV-1, FVC
- increased residual volume, FRV
- decreased ability to exhale, causes increased residual volume
Diagnosis
2) Bronchial provocation tests:
- airway hyperreactivity correlates with severity of asthma
- PFTs performed before and after admin. of incrementally-increased conc. of bronchoconstrictor aerosol (e.g. methacholine)
- the more hyperreactive your airways are, the more likely you are to have bronchoconstriction
COPD epidemiology
-affects ~6% of population of industrialized countries -15 million people in USA diagnosed in 2011
COPD prevalence
- whites,black>hispanic
- women>men
- older>younger
- Smoker>non-Smoker, and former smoker>non-smoker
- less education>more education
–unemployed>employed
COPD stats
-3rd leading cause of death in US -2nd leading cause of disability -# of death declining, but declining more in men than in women -$43 billion cost of COPD–> significant impact on healthcare
COPD Pathophys.
-COPD is a common preventable and treatable disease characterized by persistent airflow limitation that is USUALLY PROGRESSIVE and assoc. w/ enhanced chronic inflammatory response in airways and the lung to noxious particles or gases
=syndrome of progressive, NON-REVERSIBLE airflow limitation caused by chronic inflammation of the small airways and alveoli
COPD pathophys. con’t
- umbrella term that encompasses chronic bronchitis, emphysema, and small airway diseases (asthma affects central airways more)
- Primary cause is the EXPOSURE TO PARTICLES, e.g. TOBACCO SMOKE
COPD features
A) Chronically inflamed Airways
B) Imbalance between Protease and Anti-Protease Activity
C) Airway Remodeling
D) Pulmonary Vascular Changes
A) Chronically Inflamed Airways
- inflammatory cell infiltration of the (small) airways and alveoli (macrophages, lymphocytes, neutrophils)
- mucus hypersecretion
- decreaed ciliary motility
- mediator release
B) Imbalance Between Protease and Anti-Protease Activity
- Imbalance in favor of proteolysis –> remodeling –> emphysema
- Proteolytic activity correlates with disease severity
C) Airway Remodeling
- bronchiolar scar tissue development
- airway narrowing/fixed airway obstruction
- airflow limitation NOT FULLY REVERSIBLE (vs. asthma)
- emphysema
- centrilobular (respiratory bronchiole destrcution)
- panlobular (respiratory bronchioles and alveolar ducts/sacs destruction)
- decreased tethering of airways
- decreased gas exchange
D) Pulmonary Vascular Changes
- endothelial cell dysfunction (changes gas exchange)
- inflammatory cell infiltration of vessel wall (changes gas exchange)
- smooth muscle hypertrophy (changes flow)
Pathophysiological Consequences
- mucus hypersecretion + ciliary dysfunction –> increased cough & sputum
- airway narrowing + peripheral airway destruction–> expiratory flow limitation (irreversible)
- inflammatory cell infiltration + mucus hypersecretion–> expiratory flow limitation (reversible)
- peripheral airway remodeling –> impaired elastic recoil –> increased lung volume (gas gets trapped in lungs)
- airway obstruction + pulmonary vascular changes –> hypoxia/hypercapnia
Based on pathophys. consequences, what would happen to FEV-1 and residual volume in a patient with moderate COPD?
* Residual volume increases * FEV decreases
Risk Factors
A) Noxious Particles/gases * tobacco smoke * environmental particulates * occupational dusts & chemicals
B) Genetic * AAT-deficiency (genetically predisposed to emphysema) (important inhibitor of neutrophil elastase and serine proteases)
C) Older age >40yrs
D) Poor socioeconomic status
E) Lower Respiratory Tract infections
F) Low Birth weight * poor nutrition of fetus, small lungs, start life w/ reduced lung function
Pathogenesis
1) Inhaled Noxious stimulus
* epithelial cell damage
* alveolar macrophage activation cytokine release fibroblast activation (–>fibrosis)
* mac, neutrophil recruitment
Pathogenesis
2) Macrophage & Neutrophil Activation
* ROS/Protease release
* CD8- cell recruitment
* Tissue damage/remodeling–>emphysema
* goblet cell hyperplasia–> mucus
Macrophages and neutrophils in COPD pts (i) have reduced capacity to phagocytize bacteria and (ii) are less responsive to the effects of corticosteroids.
Bacteria in the airways are trapped in the mucus, have a lot of mucus and have less ability to clear the mucus, the inflammatory cells have less capacity to phagocytize bacteria, and steroids have less capacity in their anti-inflammatory effects in patients with COPD as opposed to asthma patients
Co-morbities
* lung cancer
* cardiovascular disease
* depression
* skeletal muscle wasting
* osteoporosis
Clinical features
* Persistent Dyspnea
* Chronic Cough
* Sputum Production
* Wheezing/Chest Tightness
Diagnosis
Suspect COPD in a pt > 40 if:
* persistent or progessive dyspnea (difficult gas exchange)
* chronic cough
* chronic sputum production
* history of exposure to risk factors (smoking)
* family history of COPD
Diagnosis
spirometry (PFT) required to validate clinical diagnosis of COPD
Spirometry diagnosis
* decreased expiratory flow rate, FEV-1, FVC, FEV-1/FVC
* increased residual volume, FRC
What are the differences in the causes of decreased FEV-1 in COPD vs asthma? (hint think about causes of flow limitation)
- Drop in FEV-1 in asthma is due to bronchoconstriction
- Drop in FEV-1 in COPD is due to REMODELING plus bronchoconstriction (COPD pt’s FEV will not look like a normal pt’s FEV b/c there is remodeling and thus not fully reversible, over time, the non-bronchodilator sensitive component will get worse and FEV will decrease more over time)
