Week 10 Flashcards
What is a forced vital capacity?
After slow maximal inspiration, exhalation as hard and long as possible, its total lung volume minus residual volume
What is FEV1.0/FVC ratio?
Measure of airflow obstruction
What does Hypoxia tend to result from?
V/Q mismatching
What is a normal FEV1.0/FVC ratio?
> 0.7
What is the FEV1.0/FVC ratio for obstructive lung disease?
< 0.7
List 4 common obstructive lung diseases?
- Asthma
- COPD
- Bronchiectasis
- Cystic fibrosis
Describe Asthma?
- Non-smoking related
- Allergic
- Younger patients
- Intermittent
- Non-progressive
- Eosinophil infiltration
- Diurnal variation
- Good corticosteroid & bronchodilator response
- Preserved FVC & TLCO
- Normal gas exchange
Descrive COPD?
- Smokers
- Non-allergic
- Over 50s
- Chronic
- Progressive
- Neutrophils
- No diurnal variation
- Poor corticosteroid & bronchodilator response
- Reduced FVC & TLCO
- Impaired gas exchange
What is the FEV1.0?
Forced expiratory volume after 1 second of maximal expiration
What is FVC?
Forced vital capacity, volume exchanged from maximum inhalation to maximum exhalation
How is FCV affected by obstructive lung disease?
May be reduced
How is FEV affected in obstructive lung disease?
Reduced
How is FRC affected in obstructive lung disease?
Increased
How is TLC affected in obstructive lung disease?
Increased
How is FCV affected in restrictive lung disease?
Decreased
How is FEV1 affected in restrictive lung disease?
May be decreased
How is FRC affected in restrictive lung disease?
Decreased
How is RV affected in restrictive lung disease?
Decreased
How is TLC affected in restrictive lung disease?
Decreased
How is asthma diagnosed clinically?
- Wheeze
- Breathlessness
- Chest tightness
- Cough
- Esp. if diurnal variation in symptoms & history of atopy
What are asthma symptoms in response to?
- Allergen
- Exercise
- Cold air
What are the 3 pathophysiological components of asthma?
- Airway narrowing/obstruction (Reversible)
- Airway hyper-responsiveness
- Airways inflammation (eosinophils)
What different pathological changes can occur in asthma?
Airway remodelling
- Smooth muscle hypertrophy & hyperplasia
- Thickened BM
- Oesematous submucosa
- Cellular infiltration
- Hyperplasia of mucous glands
- Desquamation of epithelium
- Mucous plug
- Neovascularisation
What are the 3 SIGN approved non-pharmacological intervention for asthma?
- Achieve & maintain a normal BMI if overweight
- Breathing exercise programmed
- Stop smoking
What makes a condition chronic?
Symptoms last more than 3 months in 2 consecutive years
What does the “pulmonary” part in COPD mean?
Disease affects both the airways & the lungs
What is COPD?
- Common, preventable & treatable
- Persistent airflow limitation
- Usually progressive & associated with enhanced chronic inflammatory response in airways & lung to noxious particles or gases
- Exacerbations & comorbidities contribute to overall severity
What are the 3 main causes of COPD?
- Mainly Tobacco smoking
- Indoor/outdoor pollution from biomass fuels
- a1 antitrypsin deficiency
What is the pathophysiology of COPD?
- Inflammation & fibrosis of the bronchial wall
- Hypertrophy of the submucosal glands & hyper secretion of mucous
- Loss of elastic, parenchymal lung fibres (emphysema)
What does a1-antitrypsin do?
Inhibits the release of elastase
What is Elastase?
An enzyme that digests elastin and can cause emphysema
Define and describe a “Pink Puffer” presentation of COPD?
- Person where emphysema is primary underlying pathology
- Pink, pursed lips
- Barrel chest due to air trapping
- Use of accessory muscles
- Decreased breath sounds
- Weight loss
Define and describe a “Blue Bloater” presentation of COPD?
- Person who suffers from recurring episodes of bronchitis
- Cyanosed
- Signs of right heart failure
- Skeletal muscle dysfunction
- CVS disease
- Depression
- Osteoporosis
What are the 5 grades of Breathlessness Assessment for COPD?
- Not troubled except on strenuous exercise
- Short of breath when hurrying on level / walking slight hill
- Walk slower, stops after a mile or so / stops after 15mins walking at own pace
- Stops for breath after walking ~100yds / after few mins on level
- Too breathless to leave house/undress
What is the main intervention for COPD?
STOP SMOKING!
What do we tend to give COPD & asthma patients?
LABA= Long-acting beta-agonists which are bronchodilator
What is the criteria for patients with domiciliary oxygen therapy?
- PaO2 <7.3 - 8kPa
- Must have stopped smoking
- Must be breathed for >15 hours/day to improve mortality
When is something/unit called a capacity and not a volume?
- When its a sum of more than one volume.
- Volume cannot be sub-divided!
What are the 3 Observational studies in EBM?
- Case control
- Cohort
- Cross Sectional studies
What are the 2 Experimental studies in EBM?
- Randomised trails
2. Non-randomised trails
What are the 3 examples of Reviews for EBM?
- Expert opinion
- Systematic review
- Meta-analysis
What are case studies?
Report written from patient file and history taking on particularly interesting/rare patient
What is a case series?
Case studies of multiple patients
What are the advantages of a Case study, series or report?
- Quick & cheap
- Rapid publication
- Early indicators of problems
- Can help detect new drug side effects and potential uses (adverse/beneficial)
What are the disadvantages of a Case study, series or report?
- Statistically weak
- No control group
- Very small numbers of patients
- Cases may not be generalisable to wider population
What is a Cross Sectional Survey?
Observational study that analyses data collected from a population, or a representative subset, at a specific point in time
What are the advantages of a cross sectional survey?
- Cheap & simple
- Ethically safe
- Useful for planning purposes
What are the disadvantages of a cross sectional survey?
- Cause & effect?
- Volunteer bias
- Unequal distribution of confounders
What is a confounder?
- Uncontrolled extraneous variables
- ie. Smokers tend to have smaller babies than non-smokers
What is a spurious association?
- When 2+ events/variables are not causally related to each other, yet it may be wrongly inferred that they are
- ie. is ultrasound harmful to fetus?
What is the aim of case control studies?
Epidemiologically working out underlying cause for health problems by looking at consistent differences between patients and controls
What are the advantages of a Case control study?
- Simultaneously look at multiple risk factors
- Good for studying rare conditions or diseases
- Useful as initial studies to establish an association
What are the disadvantages of case control study?
- Retrospective study which relies on patient recall to determine exposure (recall bias) or patient records
- Confounders
- Selection of control group is difficult
What is a Cohort Study?
Take a group of interest and comparison/control group, follow both over time and compare outcomes
What are the advantages of a Cohort Study?
- Ethically safe
- Subjects can be matched
- Can show cause precedes the effect
- Easier & cheaper than RCT
What are the disadvantages of a Cohort Study?
- High drop out rate
- Exposure may be linked to hidden confounder
- Blinding is difficult
- Outcome of interest may take a long time to occur
What is a randomized control trial?
Group of patients are randomly allocated treatment or control intervention, and are followed up and compared
What does “Single blind” mean?
Subjects did not know which treatment they were receiving
What does “Double Blind” mean?
Neither subjects or investigators aware of which treatment subjects receives
What does “Crossover” mean?
Each subject received both the intervention and control treatment (randomly) often separated by a washout period
What does “Placebo controlled” mean?
Control subjects receive placebo (inactive pill, sham operation)
What are the advantages of a RCT?
- Unbiased
- Clearly identified populations
- Randomised helps statistical analysis
- More likely to be “blinded”
What are the disadvantaged of a RCT?
- Expensive
- Volunteer bias (population may not be representative)
- Ethical issues if treatment group are seen to respond badly or better than expected
What does parallel group comparison involve in RCTs?
Each group receives a different treatment simultaneously and you compare the groups
What does paired (matched) comparison in RCTs involve?
Subjects are matched to balance out confounders such as age and sex, and differences are analysed between subject pairs
What is the meaning of within subject comparison in RCTs?
Subjects assessed before and after an intervention, within subject changes
What are the 5 problems associated with RCTs?
- Impossible- in very rare diseases number of patients too limited
- Unnecessary- when there are already good treatments
- Stopping trials early- interim analyses stops trials early
- Resources- cost of RCTs substantial money, time, energy
- Generalisability- specific types of patients for relatively short periods of time
What are the 6 points in the Bradford hill criteria for establishing cause and effect?
- Strength of association
- Dose-response relationship
- Temporality
- Consistency
- Biological plausibility
- Reversibility
What is an expert (narrative) review?
Review written by an expert in the field (secondary research)if
What are the advantages of an expert (narrative) review?
- Comprehensive survey
- Answer a specific question
What is the disadvantage of an expert (narrative) review?
Expert bias
What is a Systematic Review?
- Attempts to identify, appraise and synthesise all empirical evidence that meets pre-specified eligibly criteria to answer a given research question.
- Aimed to minimise bias
Why are systematic reviews viewed as the “gold standard”?
Avoidance and/or minimisation of bias
what are the advantages of systematic reviews?
- Comprehensive analysis of all the best primary evidence using explicit and reproducible methodology
- Results can be combined and statistically analyzed as if they were one study
- Considered an evidence based resource and the best guide to practice
- Less costly to review studies than to initiate a new study
What are disadvantages of systematic reviews?
- Results often disagree
- Publication bias
- Very time consuming
What is meta analysis?
Combines qualitative & quantitative study data from several selected studies to develop a single conclusion that has greater statistical power
- establish statistical significance with studies that have conflicting results
- develop a more accurate estimate of effect magnitude
- provide a more complex analysis of harms, safety data and benefits
- examine subgroups with individual numbers that are not statistically significant
What are the advantages of meta analyses?
- Greater statistical power
- Greater ability to extrapolate to the general population
- Considered an evidence based resource
What are the disadvantages of meta analyses?
- Results often disagree
- Heterogeneity of study populations
- Very time consuming
- Requires advanced statistical techniques
What is the definition of an Allergy?
- An altered capacity of the body to react to a foreign substance
- Disease following a response by the immune system to an otherwise innocuous antigen
Describe Type I Hypersensitivity reaction?
- EXAMPLE: Allergy, Asthma
- IgE
- Soluble antigen
- Effector mechanism is Mast cell activation
Describe Type II Hypersensitivity reaction?
- EXAMPLE: Chronic Urticaria, Drugs
- IgG
- Antigen is cell/matrix associated or a cell surface receptor
- Effector mechanism is Complement, FcR+ cells or Ab alters signalling
Describe Type III Hypersensitivity reaction?
- EXAMPLE: Arthus reaction
- IgG
- Soluble antigen
- Effector mechanism is Complement, phagocytes
Describe Type IV Hypersensitivity reaction?
- Th1 cells- soluble antigen, macrophage activation. EXAMPLE: contact dermatitis tuberculin reaction
- Th2 cells- soluble antigen, eosinophil activation. EXAMPLE: chronic asthma & allergic rhinitis
- CTL- cell-associated antigen, cytotoxicity.
EXAMPLE: contact dermatitis
When does an allergy occur?
- When IgE triggers Mast cell degranulation
- Always occurs on secondary exposure to an allergen never 1st!!!
Where is IgE produced?
By plasma B cells in lymph nodes OR locally at site of inflammation
Why has IgE got a low serum concentration?
Located mostly in tissue, bound to Mast cell surface
What route of antigens favours IgE antibody production?
Transmucosal at low doses
Which T cell phenotype favors IgE responses?
CD4+ T cells of the Th2 phenotype
What interleukin do CD4+ Th2 cells produce?
IL4
What do CD8 cytotoxic cells produce?
- IFNγ, TNFα
- Target cell lysis
What do CD4 Th1 cells produce?
- IFNγ, GM-CSP, TNFα
- Macrophage activation
What do CD4 Th2 cells produce?
- IL4, IL5
- B cell activation
What is the only type of inhaled allergen which can induce T cell responses?
Proteins
What are normally enzymatically active allergens?
Often proteases
What does low dose inhaled allergens favour?
IL4 producing CD4 T cells
What is a feature of small size inhaled allergens?
Can diffuse out of particle
What is a feature of high soluble inhaled allergens?
Elutes readily from particle
What is a feature of a stable inhaled allergen?
Can survive desiccation (extreme dryness)
What is the major allergen in faeces of house dust mites?
What can this allergen do?
- Der p 1
- Can cleave tight junctions between epithelial cells in airway, thus enhancing access
How is Der p 1 allergen taken up in the body?
Taken up by Dendritic cells, presented to T cells, which become Th2, and cause B cells to secrete IgE
What is the 2 most important factors in what symptoms occur due to an allergen?
- Location of antigen
2. Distribution of antigen
What other use might IgE have?
Defence against parasites
Describe Allergic Asthma?
- Bronchial constriction
- Increased secretion of fluid and mucus, trapping inhaled air
- Chronic inflammation may occur due to continued presence of Th2 T cells, eosinophils, neutrophils
- Chronic asthma driven originally by specific antigen, then results in hyperreactive airway to other irritants
Describe a skin allergy?
- Rash
- Wheal & Flare 1st appearing in few mins, result of vasodilation after Mast Cell degranulation, localised redness
- ~6hrs more diffuse oedema at site due to influx of lymphocytes & other leukocytes, attracted by chemokines
What 2 main symptoms does ingested allergens lead to?
- Activation of GI Mast cells result in transepithelial fluid loss & smooth muscle contraction (diarrhea, vomiting)
- Enters bloodstream, generalised rash, Urticaria, (hives)
What can happen in severe cases of food allergy ie. nuts & shellfish?
Life threatening generalised anaphylaxis & cardiovascular collapse
What is the main chemical mediators of allergic responses?
Mast cell granules contain inflammatory mediators, lipids, toxic mediators, cytokines & enzymes
What do lipid prostaglandins do during an allergic response?
Increase vascular permeability & body temp
What does lipid Platelet activating Factor do during an allergic response?
Increase adhesion between endothelium & neutrophils
What do Leukotrienes do during an allergic response?
Attract & activate neutrophils, increase vascular permeability
What does Toxic mediator Histamine do during an allergic response?
Increase vascular permeability and promotes movement of fluid from the vasculature by constricting vascular smooth muscle
What does Toxic mediator Heparin do during an allergic response?
Inhibits coagulation
What do Cytokines IL-4, IL-13 do during an allergic response?
Amplify Th2 response
What do Cytokines IL-3, IL5, GM-CSF do during an allergic response?
Promote eosinophil activation and production
What do Cytokines TNF-α do during an allergic response?
- Pro-inflammatory
- Activates endothelium
What to Chemokine MIP-1α do during an allergic response?
Attracts macrophages & neutrophils
Name 4 enzymes which have a role in the bodies allergic response?
- Tryptase
- Chymase
- Cathepsin G
- Carbopeptidase
What are the 2 main types of treatment currently used for allergy?
- Desensitisation
2. Blockage of effector pathways