Obstructive Lung Diseases Flashcards
1
Q
Lab tests of obstructive lung disease
A
- Greatly decreased FEV1
- Decreased or normal FVC
- Decreased FEV1/FVC ratio ( < 0.7)
- Increased Residual Volume (RV)
- Increased Total Lung Capacity (TLC), due to increased residual volume
2
Q
Clinical Presentations of COPD - The Blue Bloater (Type B)
A
- Bronchitic” phenotype
- Long history of cough and sputum production
- Frequent exacerbations
- Less dyspnea
- Chronic hypoxemia
- Pulmonary hypertension
- Cor pulmonale – an alteration in the structure and function of the right ventricle (RV) of the heart caused by a primary disorder of the respiratory system
- Right-sided heart failure
- Normal habitus or obese
3
Q
Clinical Presentations of COPD - The Pink Puffer (Type A)
A
- “Emphysematous” phenotype
- Long history of exertional dyspnea
- Little sputum
- Infrequent exacerbations
- Hyperinflation
- Use of accessory muscle
- Pursed-lips breathing
- Normal oxygenation
- Thin; weight loss a problem
4
Q
Pathogenesis of Emphysema
A
- Smoke Induced Inflammation Drives Alveolar Destruction
- Synergistic with respiratory infections
- Neutrophilic inflammation
- Chemokines for neutrophils, e.g. interleukin-8
- Triggers an imbalance of proteases and antiproteases
- Steroid resistant
5
Q
mechanisms of airway obstruction in chronic bronchitis
A
- Intralumenal blockage (usually excessive secretions); lumen smaller
- Edema, inflammation, hypertrophy
6
Q
Lung Volumes in Asthma
A
- Typically no change in mild asthma
- Increased RV in more severe or acute disease (premature airway closure); See increase in residual volume as asthma severity increases
- FRC and TLC are usually normal, but, in more severe asthma, loss of lung elastic recoil may occur with increased TLC
7
Q
Asthma therapy as it related to the asthma cascade
A
8
Q
Asthma triggers
A
- Allergen exposure
- Viral infections
- Exercise
- Occupational exposure
- Medications
- Circadian variation (night time-sleep)
9
Q
Complications of COPD - Pulmonary Artery Hypertension
A
- predominately the result of alveolar hypoxia and resultant vasoconstriction other contributors:
- vascular bed obliteration (emphysema)
- increased blood viscosity (erythrocytosis) – thicker blood harder to get through capillaries
- compensatory right ventricular hypertrophy right ventricular failure (cor pumonale)
- peripheral edema
- jugular venous distention
- primary treatment is O2 supplementation
10
Q
Where is the obstruction?: smooth muscle hypertrophy
A
terminal bronchioles; asthma
11
Q
Airway Obstruction in Asthma
A
- Best defined by low FEV1/FVC,
- Can also have low PEFR, FEF 25-75)
- Obstruction is typically reversible (12% increase in FEV1 in response to inhaled bronchodilator = diagnostic); using albuterol to see if patient has asthma
- It is common to have normal lung function in between acute attacks
- Airway resistance is increased when obstruction is present
- Reversibility may not always result in normal lung function; can lose the reversibility over time
12
Q
Treatment of Asthma
A
Goals
- Control attacks
- Prevent attacks
- Restore normal lung function
Tools
- Medications
- Environmental control – removing triggering allergen
- Patient education
13
Q
potential protective factors of rural life
A
- Contact with animals
- Exposure to high levels of endotoxin (LPS)
- Activates innate immune responses (IL-10, IFN-γ)
- Early exposure to bacterial products – The “Microbiome” (being researched)
14
Q
Airway Remodeling in Asthma
A
- Structural airway changes in asthma include subepithelial fibrosis, increased smooth muscle mass, new vessel formation and mucus gland hyperplasia
- Remodeling can cause airway obstruction, lack of reversibility, disease progression and morbidity
- Smooth muscle hypertrophy and hyperplasia
- Submucosal gland hypertrophy → causes mucous plugging
- Basement membrane fibrosis/thickening → as a result of collagen deposition
- ↑ vascularity
- Inflammatory infiltration → most commonly eosinophils
15
Q
The Asthmatic Inflammatory Cascade
A
- Inflammatory Stimuli
- Cell Activation/Mediator Release
- Bronchial epithelial cells + dendritic cells
- T-cells
- Eosinophils
- Mast cells
- Asthmatic Inlammation
- Smooth muscle hypertrophy, bronchial hyperresponsiveness
- Clinical asthma
16
Q
Dose-Response Curves of Methacholine Challenge: healthy vs. asthma
A
- No change in normal person
- Look at “PC 20”: provocative concentration producing 20% fall in FEV1
17
Q
Eicosanoids in Asthma
A
- = 20 carbon, polyunsaturated fatty acids
- Most commonly derived from phospholipase-A2 activity on membrane phospholipids producing arachadonic acids
- Several subfamilies: prostaglandins, thromboxanes, leukotrienes, lipoxins, resolvins and eoxins
- PGD2 and cysteinyl-leukotrienes contribute to bronchoconstriction
- Enzymatic modification of cyclo-oxyganase by aspirin, NSAIDS
- Receptor antagonism by fevipiprant and montelukast respectively
18
Q
Where is the obstruction?: incomplete formation or degradation of cartilage rings, floppy airways
A
tracheomalacia or bronchomalacia (trachea or bronchi)
19
Q
examples of things that can lead to COPD
A
asthma, cystic fibrosis, bronchiectasis
20
Q
Diffusion impairment in emphysema
A
- Decreased alveolar surface area
- Decreased elastic recoil
- Increased alveolar gas volume
- Fewer capillaries
21
Q
histology of chronic bronchitis
A
- huge expansion of submucosal gland layer in patient with chronic bronchitis vs. a normal patient
22
Q
Emphysema
A
- destructive process of elastic fibers involving lung parenchyma defined anatomically
- Hard to diagnose clinically; need histology or CT scan
- destruction of alveolar walls and loss of associated capillaries
- enlargement of airspaces distal to terminal bronchioles
- universally present in advanced COPD
23
Q
Where is the obstruction?: mucous hypersecretion (often irreversible), bronchiectasis
A
chronic bronchitis
24
Q
COPD Commonly subdivided into
A
chronic bronchitis and emphysema
25
Q
Histamine in Asthma
A
- Derived from the a.a. histadine by decarboxylation
- Made primarily by mast cells and basophils
- 4 receptors, broad distribution including CNS
- H1 receptor activation leads to bronchoconstriction, vasodilation, edema, and itching
- Antagonized by several over the counter products:
- diphenhydramine, loratidine, fexofenidine, and cetirizine
26
Q
The 4 major discrete sub-categories of obstructive lung diseases are:
A
- Chronic bronchitis
- Emphysema
- Asthma
- Bronchiectasis
27
Q
Eosinophils in asthma
A
- Release of cytokines and chemokines leading to increased inflammation
- Growth factors –> airway remodeling
- Leukotriene’s –> bronchial obstruction
- Granule proteins –> airway hyperresponsiveness and epithelial injury
28
Q
Asthma Epidemiology
A
- Affects at least 5 % of the US population
- More common during childhood; Possible to outgrow it; can develop in adulthood
- Allergy is a key risk factor
- Incidence increased over the past 3-4 decades
- More than 4,000 deaths per year despite availability of effective therapy
29
Q
Define obstructive lung disease
A
- inspiration is normal, but airway obstruction causes impairment of expiration (expiration is prolonged). This can result in air being trapped in the lungs and hyperinflation of the lungs chronically.
30
Q
The Role of Respiratory Infections in Asthma
A
- Infections in early childhood like RSV and HRV can lead to wheezing illnesses that combine with possibly present genetic factors that can all result in asthma OR resolution
- Exacerbation – viruses can exacerbate condition in children who already have asthma
- Thought that some infections contribute to a chronic state of asthma (adult with asthma)
31
Q
Three mechanisms of lower airway obstruction (lower as in location, NOT decreased)
A
- Mucous
- Airway Wall thickening or bronchoconstriction
- Decreased tethering – elastic fibers lost, airway floppy
32
Q
Chronic Obstructive Pulmonary Disease (COPD)
A
- a chronic condition characterized by: respiratory symptoms (cough; exertional dyspnea) and airflow obstruction (reduced FEV1/FVC) that is not reversible (chronic airflow obstruction)
- the vast majority of cases are the result of smoking
- COPD is an umbrella term
33
Q
Chronic Bronchitis
A
- “smoker’s cough”, diagnosed by history defined clinically as chronic sputum production
- cough and sputum daily for 3 months in two successive years; can have periods of getting better/worse
34
Q
COPD - Physical Examination
A
- may be normal
- “barrel chest”
- hyperresonant percussion and low diaphragm
- diminished breath sounds
- prolonged expiratory phase
- Rhonchi (coarse rattling), wheeze
- lower extremity edema, cyanosis, cachexia
- Tend to not eat big meals because they make it hard to breath when they do
35
Q
Where is the obstruction?: destruction of elastic fibers
A
emphysema in respiratory zones; decreased tethering, floppy airways, and not reversible
36
Q
COPD - Symptoms
A
- persistent and progressive dyspnea
- chronic productive cough
- transient periods of sputum discoloration
- wheezing
- lower extremity edema (cor pulmonale)
- orthopnea
- Hemoptysis – the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs
37
Q
COPD - Radiographic Changes
A
- may be minimal
- hyperlucency- decrease in peripheral vascular lung markings
- hyperinflation
- low, flattened diaphragm
- increase in retrosternal air space
- narrow, vertical cardiac silhouette
- bullous disease
- enlargement of pulmonary arteries (PA hypertension)
38
Q
cross-section and photomicrographs of lung with emphysema
A
Cross-section: Lung with emphysema has pockets of empty spaces in the lungs; like the holes in swiss cheese
Photomicrographs – much smaller surface area and total of alveoli
39
Q
Emphysema X-Ray
A
- Flattened diaphragm & Shortened Muscle fiber length
- Leads to weakness
- Darker than usual
40
Q
Complications of COPD: Exacerbations
A
- Episodes associated with increased symptoms
- Increased cough & sputum production
- Increased purulence (discoloration) of sputum
- Increased dyspnea
- 50% or more associated with bacterial or viral infections
- Unclear cause for those without infection – pollutants, dust, fumes
- Rx includes antibiotics and systemic steroids
41
Q
qualifications of hypoxemia
A
- PaO2 < 55mmHg (Sat <88% or
- PaO2 < 60mmHg plus evidence of end-organ dysfunction:
- Right heart failure
- P-pulmonale on ECG
- Erythrocytosis (HCT>55%)
42
Q
COPD - Pulmonary Function Tests
A
- invariably low FEV1/FVC ratio and FEV1
- FVC may be normal, reduced in advanced cases lung volumes
- normal or ↑ TLC (hyperinflation)
- normal or ↑ FRC
- normal or ↑ RV (gas trapping)
- Diffusion Capacity (DLCO)- typically reduced blood gases may show hypoxemia and hypercapnia
43
Q
Airway inflammation in Asthma
A
- Almost universal in asthma
- Leukocyte infiltration
- Cell activation
- Damage to airway epithelium
- Exposed, or denuded , basement membrane
- Increased mucus secretions (to help cover exposed basement membrane)
- May lead to airway remodeling
44
Q
COPD - Medical Management
A
- prevention
- smoking cessation
- immunizations
- bronchodilatation
- anticholinergics
- beta agonists
- suppression of inflammation (corticosteroids)
- treatment of hypoxemia
- exacerbation management
- pulmonary rehabilitation
45
Q
bronchioles in emphysema
A
- collapsible
- Loss in recoil pressure (reduced radial traction)
- As lung volume gets smaller we can actually collapse the airways
46
Q
Mast cells in asthma
A
- Produce IgG that interact with antigen
- When interacted with antigen, releases:
- Histamine, prostaglandins, leukotrienes
- Cytokines IL-4, IL-13, IL-5, TNF-alpha, GM-CSF
- Growth factors, VEGF, bFGF – important for angiogenesis
- Metalloproteinases
47
Q
Confirming the Diagnosis of Asthma
A
- Pulmonary function
- Airflow limitation (low FEV1/FVC)
- Increased airway resistance
- Reversible with inhaled beta agonists
- Hyperresponsivness (methacholine)
- Laboratory
- Increased eosinophils (sputum, blood)
- IgE sensitivity (positive skin test or increased blood levels of total IgE)
- Additional tests may be necessary to rule out other conditions
48
Q
COPD - Diagnosis
A
- Spirometry demonstrating airflow obstruction that persists after inhaled bronchodilator
- FEV1/FVC < 0.70
- chronic respiratory symptoms
49
Q
Chest X-Ray in Severe Emphysema
A
- Large, hyperlucent lungs
- Absence of vascular markings in periphery
- Increased retrosternal air space
- Flattened diaphragms
50
Q
Airway hyperresponsiveness (twitchy airways) in Asthma
A
- Increased airway obstruction in response to bronchoconstricting agents
- Almost all asthma patients have airway hyper- responsiveness
- Is seen in other conditions (hay fever, smoking, bronchitis, influenza…etc) but, its most severe in asthma
- Can be induced by several agents in lab/clinic (methacholine, cold air, exercise)
51
Q
Causes of Airway Narrowing
A
- Contraction of airway smooth muscle
- Cellular debris and mucous in the airway lumen
- Edema of airway wall
- Airway remodeling
- Hypertrophy / hyperplasia of airway smooth muscle
- Subepithelial fibrosis
52
Q
The Hygiene Hypothesis
A
- Exposure to infections (Th1), microbes, animals via day care, older siblings, and farms allows for immune tolerance to be built; more healthy
- Child that experiences sterile environment with few infections more likely to have weak immunity and thus can develop allergies and asthma (Th2)
53
Q
Respiratory Broncholitis
A
- earliest pathologic abnormality in smokers structural changes in the bronchioles
- inflammation
- goblet cell metaplasia
- smooth muscle hypertrophy
- fibrosis and narrowing
- apparent site of obstruction in mild COPD thought to precede the development of emphysema
54
Q
COPD Pathogenesis
A
- cigarette smoking is by far the leading cause epidemiologic evidence
- smoking raises risk of death from COPD 20-30X
- COPD develops in 15% of smokers verses 2% nonsmokers
- autopsy evidence of advanced emphysema correlates with dose
- 0% nonsmokers
- 12% < 1 pack/day
- 20% > 1 pack/day
55
Q
structural changes in airways in chronic bronchitis
A
- inflammation (more neutrophilic than eosinophilic)
- metaplasia of the epithelium
- expansion of mucous glands
56
Q
What is Asthma?
A
- Asthma is an obstructive lung disease characterized by hyperreactivity of the airways that causes REVERSIBLE obstruction, and chronic inflammation
- Episodic triad of symptoms: wheeze, cough, and dyspnea
- Reversible airway obstruction and hyper-reactivity
- Cellular inflammation: eosinophils, mast cells, lymphocytes, PMNs
- Repetitive airway injury and basement membrane thickening
- smooth muscle hypertrophy; mucous hypersecretion
- Multiple phenotypes, > 30 genes, gene-by-environment interactions
Characterized by:
- Airway obstruction, often reversible
- Hyperresponsiveness
- Inflammation
- Mucous production
