8.2 Bronchiectasis And Cystic Fibrosis Flashcards
How is cystic fibrosis inherited?
Autosomal Recessive
What causes cystic fibrosis?
mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Causes thickened secretions
What systems are most commonly affected in cystic fibrosis?
Respiratory Pancreas - malabsorption Liver - biliary cirrhosis Sweat glands (heat shock) Vas deferents (infertility)
What is needed to diagnose CF?
One or more of the characteristic phenotypic features
o Or a history of CF in a sibling
o Or a positive new-born screening test result
And
o An increased sweat chloride concentration
o (> 60 mmol/l) – SWEAT TEST
o Or identification of two CF mutations – genotyping
What is meconium?
Dark green faecal material that accumulates in the faecal intestine and is discharged at or near the time of birth
What is meconium ileum?
Intestinal obstruction by sticky secretions in the newborn with cystic fibrosis due to trypsin deficiency
How commonly does meconium ileum happen in newborns with CF?
15-20%
What are signs of meconium ileum?
Bilious vomiting, abdominal distension, delay in passing meconium
How might CF present?
Meconium ileum Intestinal malabsorption Recurrent chest infections Newborn screening Pseudomonas aeruginosa colonisation and infection Cf associated diabetes mellitus
How common is intestinal malabsorption in CF?
Over 90% of CF individuals have intestinal malabsorption. In most this is evident in infancy.
What is the main cause of intestinal malabsorption in patients with CF?
Severe deficiency of pancreatic enzymes
How might patients with milder CF present and why?
With atypical symptoms as CFTR is faulty rather than entirely misfunctioning.
History of ‘asthma’ but dont respond to typical asthma management
What are features of CF?
Chronic sinusitis Nasal polyps Abnormal sweat secretions Repeated LRTI/Bronchiectasis Pancreatic insufficiency/diabetes Finger clubbing Osteoporosis Male infertility Arthritis Steatorrhoea Liver disease/portal hypertension/gallstones Distal intestinal obstruction syndrome
What are common complications of CF?
Respiratory infections Low body weight Distal intestinal obstruction syndrome CF related diabetes Bronchiectasis
How are respiratory infections in a patient with CF treated?
o Needs aggressive therapy with lung physio and
antibiotics
o Patients often receive prophylactic antibiotics to maintain health
How is low body weight in patients with CF treated?
o needs careful monitoring
o If it is the consequence of pancreatic insufficiency give pancreatic enzyme replacement therapy
o high calorie intake and often extra supplements
o may need NG or PEG feeding – especially in children with severe disease
What is DIOS?
Distal intestinal obstruction syndrome is faecal obstruction in the ileo-caecum due to thick dehydrated faeces. Presents with palpable right iliac fossa mass
How is DIOS different to constipation?
DIOS vs. constipation – faecal obstruction in ileo-
caecum versus whole bowel
What causes DIOS in CF patients?
insufficient prescription of pancreatic enzymes or non-compliance, also salt deficiency / hot weather
How is DIOS diagnosed?
Symptoms of obstruction, palpable Right Iliac Fossa
Mass, Abdominal XR demonstrating faecal loading
at junction of small and large bowel
What lifestyle advice should be given to patients with CF?
o No smoking
o Avoid other CF patients
o Avoid friends / relatives with colds / infections
o Avoid Jacuzzis (pseudomonas)
o Clean and dry nebulisers thoroughly
o Avoid stables, compost or rotting vegetation – risk of aspergillus fumigatus inhalation
o Annual influenza immunisation
o Ensure strep pneumo vaccination up to date
o Sodium chloride tablets in hot weather / vigorous
exercise
What is bronchiectasis?
Bronchiectasis is the chronic, irreversible dilatation of
one or more bronchi. Abnormally enlarged bronchi.
Why are patients with bronchiectasis predisposed to recurrent or chronic bacterial infection?
As bronchi are deformed, their ciliary function is impaired, they exhibit poor mucus clearance, stagnant pools of mucus predisposes for respiratory tract infection.
What is the gold standard diagnostic test for bronchiectasis?
High resolution CT
What are the main causes of bronchiectasis?
Post infective Immune deficiency Genetic / mucociliary clearance defects Obstruction Toxic insult - gastric aspiration Idiopathic Allergic bronchopulmonary aspergillosis
What is whooping cough?
An acute infection of the tracheobronchial tree by bordetella pertussis. Symptoms are runny nose and a violent cough
What infections might result in bronchiectasis?
Whooping cough, TB
What immune deficiencies cause bronchiectasis?
Hypogammaglobinaemia
Alpha-1-antitrypsin deficiency
What are the genetic / mucociliary clearance defects that can cause bronchiectasis?
CF Primary ciliary dyskinesia Youngs syndrome Kartagener syndrome Yellow nail syndrome
What obstruction can cause bronchiectasis?
Foreign body, tumour, extrinsic lymph node.
What organisms commonly are seen in patients with Bronchiectasis?
Haemophilus influenzae Pseudomonas aeruginosa Moraxella catarrhalis Stenotrophomonas maltophilia Fungi – aspergillus, candida Non-tuberculous mycobacteria Less common - Staphylococcus aureus (think about CF)
How is bronchiectasis managed?
Treat underlying cause
Physiotherapy to help mucus clearance
Antibiotics according to sputum cultures
Aggressive management of disease progression
Supportive - flu vaccine, strep pneumoniae vaccine, bronchodilators
Pulmonary Rehab – MRC Dyspnoea Score >3
What is the aetiology of bronchiectasis?
Chronic inflammation -> destruction of elastic and muscular components of the bronchial wall and peribronchial fibrosis
What is another name for pertussis?
Whooping cough
What important question should be asked when suspecting bronchiectasis?
Travel history / where they have previously lived / childhood infections
TB and pertussis still common in some countries
What is the main cause of bronchiectasis in th UK
Underlying congenital conditions
How might a CXR look in bronchiectasis?
May appear normal in early disease. Progress to show:
Dilated bronchi with thickened walls
What will a CT of bronchiectasis look like?
Bronchial dilation - bigger than the accompanying pulmonary artery
Bronchial wall thickening and scarring
Signet ring sign
How is a CT scan used in bronchiectasis?
Diagnosis
Assess disease severity
Extent of lung involvement
What is tram track sign?
A sign of bronchiectasis on an X-ray - thick walled dilated bronchi
What is signet ring sign?
A sign of bronchiectasis on a CT scan
Dilated bronchus and accompanying pulmonary artery branch seen in cross section. Bronchus is dilated and appears wider than artery
What are the clinical symptoms of bronchiectasis?
Chronic cough Daily mucopurulent sputum production Halitosis Breathlessness on exertion Intermittent haemoptysis Nasal symptoms Chest pain Fatigue Wheeze
What are the clinical signs of bronchiectasis?
Pulse oximetry may reveal hypoxaemia Fever Haemoptysis Fine crackles/ High pitched inspirations squeaks /Rhonchi/ Crackles and wheezing (loud lungs) Weight loss Clubbing in digits
What conditions does alpha-1-antitrypsin deficiency contribute to?
Bronchiectasis and emphysema
Loss of protein that protects against enzymes that break the elastic fibres in the lung
What might bronchiectasis be misdiagnosed for?
Asthma
COPD
How is bronchiectasis diagnosed?
High resolution CT
Sputum cultus testing positive for haemophilus, pseudomonas or atypical mycobacterium - unlikely to be COPD
History of chest infection
Why is smoking history important to ask about to differentiate between COPD and Bronchiectasis?
Little history of smoking = bronchiectasis
What might a spirometry test of a patient with bronchiectasis show?
Obstructive air ways disease FEV1/FVC of less than 70%
Elevation of RV/TLC due to air trapping behind pus obstruction
DLCO reduced in severe disease
How is bronchiectasis differentiated from chronic bronchitis?
chronic bronchitis = smoking, white little sputum, cough, no fevers/haemoptysis, loss of lung sounds although may have some expiratory wheezing. Pathology is mucous gland over secretion/hyperplasia and airway remodelling.
Bronchiectasis = persistent severe infections, haemoptysis, fevers, thick purulent foul smelling sputum, halitosis, rhonchi and inspiratory squeaks pathology due to loss of smooth muscle and elastic fibres lining bronchi. Dilated deformed bronchi, ciliary dysfunction, stagnant mucous.
How do we define exacerbation in bronchiectasis?
Deterioration in 3 or more key symptoms for at least 48 hours: Cough Sputum volume or consistency Sputum purulent even Breathlessness / exercise tolerance Fatigue Haemoptysis
What is the predominant mutation in CF?
Mutation in Phe508del - deletion of phenylalanine at position 508 of the polypeptide chain.
Where is the gene for cystic fibrosis transmembrane conductance regulator located?
On the long arm of chromosome 7
What is the function of CFTR?
Is an epithelium transmembrane protein that transports chloride and bicarbonate. CFTR also regulates the epithelial sodium channel and therefore movement of sodium into cells.
CFTR enables chloride to be transported out of cells into airways, controlling the water movement.
What does a Phe508del CFTR protein mutation lead to?
defective intracellular processing and trafficking
decreased stability
defective channel gating
How might CF present in a patient diagnosed after the age of 20?
usually have a mutation associated with residual CFTR function
Or heterozygous CFTR mutations – one severe + one mild
What factors contribute to the impaired nutritional status of patients with CF?
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
Why should the nutritional status of a CF patient be a primary concern?
- Earliest manifestations of disease related to GI and nutritional derangement
- nutritional status plays an important role in the progression of the pulmonary disease – better nutritional status associated with better lung function. Appears to be related to preservation of muscle mass
- Suggestion that nutritional therapy supports lung growth and development
Why are the 6 classes of CFTR mutations?
- No protein production,
- Protein made but never gets to the cell membrane,
- Protein gets to the membrane but doesn’t work at all
- Protein made but only partially active
- Protein expressed at gene level but substantial reduction in mRNA or protein, or both, synthesis
- Protein gets to membrane but partially unstable
What is the only ‘cure’ for CF?
Lung transplant
What is the median life expectancy for a person with CF?
38 years
