Cystic Fibrosis Flashcards
What kind of disease is CF and what causes it?
CF is an autosomal recessive disease
CF is caused by mutations of the the Cystic Fibrosis Transmembrane Conductance Regulator CFTR gene
How common is CF in Ireland and why is this the case?
Incidence of about 1 in 1,461 people
With 1 in 19 people being carriers of the condition
How common is CF in Ireland and why is this the case?
Incidence of about 1 in 1,461 people
With 1 in 19 people being carriers of the condition
CF is common in Ireland as CFTR gene mutations confer resstance against salmonella typhi which would have provided protection during the great famine, i.e. those with the CFTR mutation were more inclined to have survived the famine
How does CF affect a person?
CF affects the lungs, sinuses, pancreas, liver, bones, vas deferens etc etc
Its usually decline in lung function that kills the patient
Explain the pathophysiology of CF as a disease
Mutations in the CFTR gene affect mucocilliary transport by causing a depletion of airway surface flluid
The CFTR gene is responsible for normal sodium/chloride and fluid regulation in and out of epithelial cells, mutations in this gene result in a loss of airway surface fluid
CF patients build up a thick layer of mucous which then clogs smaller bronchioles etc
Organisms can become trapped in this mucous
Some organisms can produce proteins such as alginate which are really sticky
What are the main steps in CF as a disease process
CF gene mutation
Ion transport abnormailities
Altered airway environment
Inflammation + Infection
Tissue damage
*This cycle of tissue damage will ontinuously repeat
What are the main steps in CF as a disease process
CF gene mutation
Ion transport abnormailities
Altered airway environment
Inflammation + Infection
Tissue damage
*This cycle of tissue damage will ontinuously repeat
How exactly does CF affect the lung?
Structural damage
Bronchiectasis
Pulmonary insuffuciency
Respiratory failure
List the most commonly isolated organisms from a CF lung
(7)
Haemophilus Influenzae (non-capsulated)
Staphylococcus Aureus, MRSA and small colony variants
Pseudomonas Aeruginosa (non mucoid and mucoid)
Burkholderia Cepacia Complex (BCC)
Gram negative non-fermenters
Non-TB-Mycobacterium Species
Scedosporium species
List some gram negative non-fermenters you might isolate from a CF lung
(7)
Pseudomonas species (Non-PA)
Alkaligenes species
Chromobacter species
Stenotrophomonas species
Burkholderia gladioli
Pandorea species
Pedunculosis species
Give two examples of non-tb mycobacterium you could isolate from a CF lung
Mycobacterium abscessus
Mycobacterium cheloni
Talk about the range of organisms found in a CF lung
Huge range of organisms can be found
Haemophilus and staph often found in younger patients
Pseudomonas more in teenagers and up
Burkholderia in older patients
NLFs tend to be opportunistic bacteria -> majority are ubiquitous in nature
Unusual fungal infections can be seen in CF patients such as scedosporium
Infections tend to be polymicrobial
Talk about the range of organisms found in a CF lung
Huge range of organisms can be found
Haemophilus and staph often found in younger patients
Pseudomonas more in teenagers and up
Burkholderia in older patients
NLFs tend to be opportunistic bacteria -> majority are ubiquitous in nature
Unusual fungal infections can be seen in CF patients such as scedosporium
Infections tend to be polymicrobial
What are small colony variants?
These are variants of S. areus which originate by mutations in metabolic genes, these resul in auxotrophic bacterial subpopulations
These variants gro slowly and have many atypical characterics
These can be seen in CF lungs as they adapt to conditions within the CF lung
Can be difficult to isolate and identify -> auxotrophic
Talk about mucoid vs non-mucoid pseudomonas
Pseudomonas aeruinosa has two forms; mucoid and non-mucoid
P. auriginosa infections in CF patients start of as acute non-mucoid infections but conversion to mucoid PA results in long lasting (often life-long) chronic infection
The conversion from non-mucoid to mucoid affects the lilfe expectancy of a patient drastically -> chronic infections cannot be cleared, life long, no treatment, only immune suppression
Talk about the different microorganisms that can be isolated from CF patients of different age cohorts
H influenzae is more common in infancy
S. aureus is more common in younger patients and peaks in teens at about 17
MRSA is more common in young adults peaks at about 20
P. aeruginosa risk worsens with age and peaks at about 40
NLFs such as B cepacia, Stenotrophomons and Achromobacter stay realatively uncommon throughout life
Talk about the prevalence of microorganisms isolaed in CF patients as trends over time
The amount of S. aureus weve isolated since the 90s has been increasing
The amount of P. aeruginosa weve isolated since the 90s has been decreasing
MRSA isolations have been increasing
H. influenzae have staed relatively the same
Steno and achromobacter have increased
B. cepacia remained the same
*not entirely reflective as detection methods are a lot better now, less likely to miss an MRSA or an NLF nowadays compared to the 90s etc
Talk about Haemophilus Influenzae involvement in CF
A common commensal of the upper respiratory tract
A frequent coloniser of infants and children
Seen in 20% of CF children under 1
Seen in 32% of CF children between 2 and 5
May cause acute exacerbations in chronic conditions
Produces IgA1 proteases and can cause ciliostasis
Can decrease mmucociliary cleanance up to 10 fold in CF patients
What are the main virulence factors of Haemophilus influenzae and how do they affect CF
Produces IgA1 proteases which cleave peptide bonds in human IgA
Can cause ciliostasis -> cilia of the airways nolonger move -> prevents mucous from moving
What are the main virulence factors of Haemophilus influenzae and how do they affect CF
Produces IgA1 proteases which cleave peptide bonds in human IgA
Can cause ciliostasis -> cilia of the airways nolonger move -> prevents mucous from moving
Talk about Staph aureus involvement in CF
S. aureus is often the first isolate
Can be seen in up to 70% of CF isolates
More common in younger patients/teens etc
Concern with empyema (pus build-up) and lung abscesses
Role of slime and teichoic acid which play a role in adherence to respiratory epithelial cells
Talk about the S, aureus biofilm and why it is of concern?
S. aureus can produce a multilayered biofilm embedded within a glycocalyx or slime layer, the solid components is primarily composed of teichoic acids
Talk about the MRSA and its incidence in CF
Both CA and HA MRSA are seen in CF patients
Talk about Pseudomonas and its role in CF
PA is the most prevalent respiratory bacterial pathogen
Higher prevalence in adults
Isolated i about 50% of cf patients
Infection associated with significant morbidity
Mucoid vs non-mucoid
Epidemic strains
Talk about mucoid P. auriginosa
PA can change from non-mucoid to mucoid
PA forms biofilm -> organism will downregulate their metabolism inside this biofilm
Biofilm allows organism to tolerate both the immune response and antimicrobials
Talk about epidemic strains of PA
There have been certain transmissable strains of PA such as ‘midlands’, ‘liverpool’ and ‘australia’
These have been associated with CF to CF spread of PA
What actually causes tissue damage in CF
Inflammatory response
+lots of virulence factors from infection
+ Cytokines
Talk about the evolution of PA infection in CF patients as theey age?
First positive isolate, antibiotic treatment, second isolate clear, infection treated, only an intermittent infection
Older patient, third isolate positive, antibiotic treatment, repeated positive isolates, chronic infection, not treated
Talk about the evolution of PA infection in CF patients as theey age?
First positive isolate, antibiotic treatment, second isolate clear, infection treated, only an intermittent infection
Older patient, third isolate positive, antibiotic treatment, repeated positive isolates, chronic infection, not treated
Comment on the microbiome diversity of a CF lung as disease progresses
Usually very diverse early on, usually even find weird NLFs or fungi etc
As disease progresses pseudomonas becomes more and more dominant until it takes over
How are PA infections classified?
At least 4 cultures in the last 12 months required:
> 50% positive = chronic infection
<= 50% positive = intermittent infection
Never positive = free of PA
When is a CF patienet most likely to have mucoid PA
In general PA is more common in older people
Non mucoid strains are more commonly seen in young people
Mucoid strains are more commonly seen in older patients
What two organisms have ‘transmissible strains’ to be concerned about
Pseudomonas and Burkholderia
How is pseudomonas infections treated?
In newborns -> avoidance/prevention and antibiotic prophylaxis
In young -> treatment of early infections to eradicate pseudomonas
In older -> chronic infection -> immune suppression
Talk about Burkholderia Cepacia Complex and its role in CF
Ubiqitous -> found in nature -> opportunistic -> non pathogenic in healthy humans
Can cause long term colonisation without affecting lung function
Can cause chronic infection associated with slowly declining lung function
Can cause acute fulminant lung infection leading to death in weeks/months -> necrotising pneumonia/cepacia syndrome
Just under 3% of CF patients are infected
What are some of the clinical implication of B. cepacia infection?
Deteriorating lung function
More pulmonary exacerbations/hospital admissions
More IV antibiotics
Reduced life expectancy
Hospital segregation
Social isolation
Implications for transplantation
Name a Burkholderia epidemic strain
ET12 -> often seen in outbreaks but doesnt always case outbreaks
Talk about stenotrophomonas maltophilia in CF
S. maltophilia was initially classed as a pseudomonas but molecular methods allowed for the classing as a steno
Found in soil -> mostly community acquired
Tends to be transient and recurrent
Peakas in teens and young adults
