Lecture 15- Bronchiectasis and Cystic fibrosis Flashcards
define bronchiectasis
- chronic IRREVERSIBLE dilatation of one or more bronchi- pathological condition can be caused by many diseases or be idiopathic-resulting in abnormally enlagred bronchi
deformed bronchi in bronchiectasis exhibit
poor mucous clearance
- predisposition to recurrent or chronic bacterial infections
aetiology of bronchiectasis
Variety of underlying causes, with a common underlying emchanism of chronic inflammation
chronic inflammation and bronchiectasis
- Inflammaiton causes destruction of elastic and muscular components of the bronchial wall and peribronchial fibrosis
- Used to primarily be caused by pertussis and TB
- Some part of the world still primary cause
- Ask where they grew up/ have been
- Underlying congenital conditions primary triggering cause in UK/ europe/ USA
radiological findings of bronchiectasis: CXR
- Usually abnormal
- May be normal in early disease
- Inadequate in diagnosis or quantification of bronchiectasis/ bronchial dilatation
- Classic abnormality: dilated bronchi with thickened walls (tram-track signs)
radiological findings of bronchiectasis: CT
gold standard
- Demonstrates bronchial dilation biggeer than the adjacent blood vessel, bronchial wall thickening
- signet ring sign
Gross pathologic lung specimen from a patient with bronchiectasis
notice te small pulmonary artery abutting the much larged dilated bronchus (arrow) both of which are seen on cross-section
bronchiectasis causative organisms
- H.influenza
- pseudomonas aeruginosa
- moraxella catarrhalis
- fungi- aspergillus, candidida
- Mycobacteria tuberculosis
- less common: S. aureus
bronchiectasis viscious cycle
bronchial dilation leads to mucus accumulation, impaired ciliary fucntion and increased risk of infection
infection leads to inflammation na dloss of bronchial elastic fibres and smooth muscle– more dilatation
Clinical symptoms (not very specific) of bronchiectasis
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-
Very common
- Chronic cough
- Daily mucopurulent sputum production- can vary in quantity, colour and consistency- can smell
-
Common
- Breathlessness on exertion
- Intermittent haemoptysis (coughing up blood)
- Nasal symptoms
- Chest pain
- Fatigue
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Less common
- Wheeze
Clinical signs of bronchiectasis
- Hypoxaemia in advanced case of bronchiectasis (pulse oximetry)
- Fever relativeky common
- Haemoptysis – 50% of pt-s usually mild
- Fine crackles (rales)
- High pitches inspiratory squeaks
- Rhonchi
- Sometimes can hear both crackles and wheezing- lung sounds from CF pts w/bronchiectasis
- Clubbing of digits
- Systemic signs- weight loss
causes of bronchiectasis
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Post infective
- Whooping cough (pertussis) and TB
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Immune deficiency
- Hypogammaglobulinemia
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Mucociliary clearance defects
- CF, primary ciliary dyskinesia, Youngs syndrome (triad of bronchiectasis, sinusitis and reduced fertility), Kartagener syndrome (triad of bronchiectasis, sinusitis and situs inversus)
- Alpha-1 antitrypsin deficiency
- Obstruction–> foreign body, tumour, extrinsic lymph node
- Toxic insult –>gastric aspiration (post lung transplant), inhalation of toxic chemicals/ gases
- Allergic bronchopulmonary aspergillosis
- Secondary immune deficiency’s- HIV, malignancy
- Rheumatoid arthritis
- Idiopathic
- Associations- IBD, yellow nail syndrome
Early diagnosis and treatment- ask yourself ‘does this pt have bronchiectasis’
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- Treatment of predisposing underlying disorders may slow disease progression
- History of asthma but new spirometry shows no reversibility with bronchodilator – enquire more about history and think about bronchiectasis
- History of COPD but diminished breath sounds, characterising COPD, but not found and different risk factors
- History of
- Severe chest infection earlier in life
- Lifelong chest infections? Genetic cause?
- Recurrent chest infections? Immunodeficiency
- Recurrent sinus infections since childhoods? Ciliary dysfunction
- Sputum culture positive for common organisms such as
- Haemophilus or pseudomonas and atypical mycobacterium
- IBD, RA also associated with bronchiectasis
bronchiectasis is an
obstructive airway disease
reduced FEV1/FVC ratio <70% (late finding)
bronchiectasis pulmonary function tests
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Obstructive airways disease
- Reduced FEV1/FVC ratio of <70% (late finding)
- Full PFT may show elevation of Residual Volume/Total Lung Capacity ratio consistent with air trapping
- DLCO may be reduced in severe disease (when inflammation spread to alveolar)
differentiating between bronchiectasis and chronic bronchitis
Chronic bronchitis (mucous gland hyperplasia) is not the same as bronchiectasis (airway dilation, scarring).
Management of bronchiectasis
- Physio/airway clearance
- Daily airway clearance is essential for treatment success
- Sputum sampling- routine culture and non tuberculosis mycoplasma (NTM)
- Exclude immunodeficiency/treat identifiable causes
- Consider longer-term therapies at future visits
- Annual flu and routine vaccinations against Influenzaw and Streptococcus pneumoniae
- An established MDT is key
Acute exacerbation of bronchiectasis
A person with bronchiectasis with deterioration in 3 or more key symptoms for at least 48 hours
what is the most common identifiable cause of bronchiectasis in the western world
CF
life expectancy of someone with CF
- In 1950s median life expectancy was a few months
- In 1990s- late teens
- Today- 40 y/o
CF is an ……. …….. disroder
- Autosomal recessive disorder
- 1 in 2,500
- Most common within northern European ancestry
- Predominant mutation in those with CF is the
Phe508del – deletion of phenylalanine at position 508 of the polypeptide chain
where is the mutation found and what abnormal function does it lead to
- Caused by mutation of gene located on long arm chromosome 7 that leads to abnormal function of epithelial chloride channel- Cystic fibrosis transmembrane conductance regulation (CFTR)
CFTR mutation also causes disruption in epithelial function in other body organs
- Important comorbidities caused by epithelial cell dysfunction occur in the pancreases (malabsorption), liver (biliary cirrhosis), sweat glands (heat shock) and vas deferens (infertility)
CFTR is a
transmembrane protein that transports chloride and bicarbonate and also regulates the epithelial sodium channel (ENAC)
CFTR and Cl
CFTR enables Cl to be trnapsorted out of cells into airways- the transport of chloride helps control moevemnt of water
CFTR and Na
CFTR also regulates sodium reabsorption into cells
CFTR control of sodium and Cl plays a critical role in th
hydration of the mucous at the surface of the airway tract
defective ion transport mediated by CFTR reduces airway surface liquid hydration, which leads to thick and sticky mucous and impairs muco-ciliary clearance
how many mutations related to CTFR gene
2000
mutations ahev different effects on the
- manufactue of CFTR protein
- transportation of CFTR
- CFTR processing fucntion
- CFTR stability at the cell membrane
Most common mutation CFTR which causes CF
Phe508del CFTR protein of Chromosome 7
Phe508del CFTR protein mutation
- Causes:
- Defective intracellular processing and trafficking
- Decreased stability, which drastically reduces the quantity of CFTR protein at the apical surface of epithelial cells
- Also exhibits defective channel gating, which further limits anion transport
presentation of classic CF
- meconium ileus
- intestinal malabsorption
- recurrent chest infections
- new-born screening
- Meconium ileus
- In 15-20% of new-born CF infants the bowel is blocked by sticky secretions
- Signs of intestinal obstruction soon after birth with bilious vomiting, abdominal distension and delay in passing meconium
- Intestinal malabsorption
- 90% of CF individuals have intestinal malabsorption
- Severe deficiency of pancreatic enzymes secondary to blockage of exocrine glands
CF diagnosis
One or more characteristic phenotypic features
- Or a history of CF in a sibling
- Or a positive new-born screening test result
And
- An increased sweat chloride concentration >60mmol/l- sweat test- very salty
- Or identification of 2 CF mutations- genotyping- may need extended genotyping- not all mutations catalogues
Sweat test
An increased sweat chloride concentration >60mmol/l- sweat test- very salty
- hypertonic sweat dye to dysfunctional NaCl absorption due to defect in CTFR
(in normal sweat gland NaCl we be reasborbed along the duct)
CF is usualyl identified
following new-born screening or during first few year
Late diagnosis
- People diagnosed after 20 yrs of age usually have a mutation associated with residual CFTR function
- Or heterozygous CFTR mutations: one severe and one mild
- Increasingly recognised that some variants of CF may present in adults- atypical CF
when to consider atypical CF (late diagnosis)
- Consider In cases of recurrent ‘idiopathic pancreatitis”, recurrent sinusitis and lung infections, allergic bronchopulmonary aspergillosis (IgE hypersensitivity reaction aspergillus species)
CF complications
anywhere lined with epithelial cells
- lungs
- nasal/upper resp tract
- pancreas
- gut
- liver
- biliary tree
- heart
- reproductive tract
lung conditions associated with VF
- bronchiectasis
- pneumothroax
- ABPA
- haemoptysis
- resp failure
Nasal/ upper resp tract conditions associated with CF
- chronic sinusitis
- nasal polyposis
Pancreatic conditions associated with CF
- DM
- pancreatic insufficiency
GI conditions associated with CF
- distal intestinal obsturction syndrome (DIOS)
- oesophageal reflux/ oesophagitis
liver conditions associated with CF
- chronic liver disease
- portal hypertension
biliary tree conditions associated with CF
gallstones
heart conditions associated with CF
- cardiac failure
joints and bone conditions associated with CF
- arthritis
- osteoporosis
reproductive tract conditions associated with CF
- male infertility
- congenital bilateral abscence of vas derences (CBAVD)
CF lifestyle advice
- No smoking
- Avoid other CF pts
- Risk of infection and sharing pseudomonas resistance to Abx
- Avoid friends/relatives with colds/infections
- Avoid Jacuzzis (pseudomonas)
- Clean and dry nebulisers thoroughly
- Avid stables, compost or rotting vegetation- risk of aspergillus fumigatus inhalation
- Annual influenza immunisation
- Pneumococcal vaccine
- Sodium chloride tablets in hot weather/ vigorous exercise
CF management os
complex- lead by CF spceiclialist centres/ MDTS
- holistic/ multisystem focus
- up to dat epneumococcal and hameophilus influenza vaccinations and annual influenza
- key is maintaining lung health (chest physio, infection management)
- optical nutiritonal state- pancreatic status, vitamin status, weight/ BMI
though that inhaling salt water is good??
think australian surfing story
role of nutrition in CF
- earliest amnifestation of disease related to GI and nutritional derangmeent
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factors which contirbite to impaired nutritional status and cystic fibrosis
- pancreatic insufficiency
- chronic malabsorption
- chronic inflammation leading to increased energy expenditure
- increased energy requirements of breathing
- suboptimal nutrient intake related to impaired taste (sinuses), fatigue , inflammatory mediated anorexia
nutritional status plays an important role in
progession of pulmonary diseasee- better nutritional status- better lung function (improve FEV1)
CFTR can be divided into 6 classes according to their effects on protein function
- no protein production
- protein made but never gets to cell membrane
- protein gets to cell membrane but doesnt work at all
- protein made but only partially active
- protein expressed at gene level but substantial reduction in mRNA or protein, or both, synthesis
- protien gets to membrane but partially unstable
Cystic fibrosis survival
Tremendous improvement in life expectancy have been achieved by understanding the importance of
- Airway clearance 2-3 x day
- Aggressively treating infections
- Correcting nutrition deficits
- New drug treatments targeting underlying molecular defect
bronchiectasis key concept
pathological condition characterised by irreversibly dilated bornchi with associated mucous accumulation, impared muco-ciliary function, inflammation, recurrent infections
- Mucociliary clearance defects
- CF
- primary ciliary dyskinesia
- Youngs syndrome
- Kartagener syndrome
Youngs syndrome
triad of bronchiectasis, sinusitis and reduced fertility
Kartagener syndrome
triad of bronchiectasis, sinusitis and situs inversus
