Lecture 14: Bronchiectasis and Cystic Fibrosis Flashcards
What is bronchiectasis?
Chronic irreversible dilatation of one or more of the bronchi
- can be caused by diseases or be idiopathic
- the deformed bronchi exhibit poor mucous clearance due to impaired cilia function: stagnant mucous pools so there is predisposition to recurrent/chronic bacterial infection
What causes chronchiectasis?
Variety of underlying causes with a common underlying mechanism of chronic inflammation
- inflammation causes destruction of the elastic and muscular components of bronchial wall and peribronchial fibrosis
- used be be primarily caused by pertussis (whooping cough) and TB
What are the radiological findings of bronchiectasis?
CXR- normal in early disease, non-specific abnormalities in later disease (dilated bronchi with thickened walls: tram track sign)
Gold standard: High resolution CT which demonstrates bronchial dilatation bigger than the adjacent blood vessel, bronchial wall thickening (you can see extend of damage across lung)
(signet ring sign: dilated bronchus and accompanying pulmonary artery are seen in cross section, in healthy lung bronchus is usually smaller than the artery)
What are the symptoms of bronchiectasis?
Very common
- chronic cough
- daily mucopurulent (mucus and pus) sputum production: vary in quantity, colour and consistency
Common
- breathlessness on exertion
- nasal symptoms
- chest pain
- fatigue
- intermittent haemoptysis
Less common
-wheeze
(not very specific symptoms)
What are the clinical signs of bronchiectasis?
- pulse oximetry may reveal hypoxaemia in advanced cases
- fever is common
- haemoptysis
- fine crackles/wheezing/high pitched inspiratory squeaks/rhonchi
- history of weight loss
- clubbing of digits
What are the main causes of bronchiectasis?
Post-infective: pertussis, TB
Immune deficiency: hypogammaglobulinaemia
Mucociliary clearance defects: cystic fibrosis, primary ciliary dyskinesia, Young’s syndrome, Kartagener syndrome
Alpha-1-antitrypsin deficiency
Obstruction: forgein body/tumour/extrinsic lymph node (compression so bronchus can’t be cleared leading to inflammation)
Toxic insult: gastric aspiration/inhalation of toxic chemicals/gases
Allergic bronchopulmonary aspergillosis
Secondary immune deficiency: HIV/malignancy
RA
Idiopathic
What organisms do we see in chronic infections caused by bronchiectasis?
- H.influenza
- Pseudomonas aeruginosa
- moraxella catarrhalis
- Strep.pneumoniae
- Stenotrophomonas maltophilia
- Fungi: candida, aspergillus
- Mycobacteria tuberculosis
- Nontuberculous mycobacteria (NTM)
Antibiotic use is difficult as they become resistant
What do you see in bronchiectasis PFT’s?
Obstructive airway disease: reduced FEV1 or reduced FEV1/FVC ratio
- elevation of RV/TLC ratio consistent with air trapping
- diffusing capacity for CO may be reduced in severe disease
How do you differentiate bronchiectasis from chronic bronchitis?
Chronic bronchitis -mucous gland hyperplasia, hypersecretion -due to tobacco, smoke, air pollutants -cough, sputum production Bronchoiectasis -airway dilatation -scarring -persistent/severe infections -cough, purulent sputum, fever
How do you manage bronchiectasis?
- physio/airway clearance (daily)
- sputum sampling
- exclude immunodeficiency/treat identifiable causes
- annual flu vaccinations
- long term therapies
How do we define acute exacerbation in bronchiectasis?
Deterioration in 3 or more key symptoms for at least 48 hours
- cough
- sputum volume +/- consistency
- sputum purulence (foul smelling)
- breathlessness +/- exercise intolerance
- fatigue
- haemoptysis
What is the most common cause for bronchiectasis in the western world?
Cystic fibrosis-autosomal recessive disorder
- Phe508del (deletion of phenylalanine at position 508 of polypeptide chain)
- caused by mutations of gene located on long arm of chromosome 7 leading to abnormal function of CFTR (epithelial chloride channel), has a key role in maintaining lung epithelial function
- dehydrated, viscous, site of chronic infection
What is the role of CFTR?
-transmembrane protein that transports chloride and bicarbonate and regulates ENAC
-enables Cl- to be transported out of cells into airways: helps to control movement of water
-also regulates sodium reabsorption into cells
Therefore CFTR plays critical role in hydration of mucous at surface of airway track
=defective ion transport mediated by CTFR reduces airway surface liquid hydration which leads to thick, sticky, mucous and impairs muco-ciliary clearance
What is the most common mutation to CFTR and its causes?
Phe508del CFTR protein mutation causes:
- defective intracellular processing and trafficking
- decreased stability (drastically reduces the quantity of CFTR protein at apical surface of epithelial cells)
- defective channel gating
How do you diagnose CF?
- history of CF in sibling
- positive newborn screening test result
- sweat test: increased sweat chloride conc
- extended genotyping
What are the main CF clinical presentations?
- Meconium ileus: bowel is blocked by sticky secretions, signs of intestina obstruction after birth- bilious vomiting, abdominal distension, delay in passing meconium
- Intestinal malabsorption: severe deficiency of pancreatic enzymes secondary to blockage of the exocrine glands (can eventually go on to have endocrine dysfunction causing diabetes mellitus)
- Recurrent chest infections
- Newborn screening
Can people develop CF later on in life?
Atypical later diagnosis of CF
- mutation associated with residual CFTR function (gene still works but not as well)
- recurrent sinus infection/infertility/allergic bronchopulmonary aspergillosis/recurrent pancreatitis
What are some complications of CF?
(any organs which have ducts lined by epithelial cells) Lungs -bronchiectasis -pneumothorax -ABPA -haemoptysis -resp failure Nasal/upper resp tract -chronic sinusitis -nasal polyposis Pancreas -diabetes mellitus -pancreatic insufficiency Gut -oesophageal reflux -intestinal obstruction Liver -chronic liver disease -portal hypertension Biliary tree -gallstones Heart -cardiac failure -arthritis -osteoporosis (malabsorption) Reproductive tract -infertility -congenital bilateral absence of vas deferens
What is the CF lifestyle advice?
- no smoking
- avoid other CF patients: different resistant infections
- avoid jacuzzis (pseudomonas colonisation here)
- avoid friends/relatives with colds/infection
- avoid stables/compost/rotting veg (aspergillus fumigatus inhalation)
- annual influenza immunisation
- vaccines
- sodium chloride tablets in hot weather/exercise
How do we maintain lung hygeine?
Saline clearance for mucous from lung
-chest physio also
Why is nutrition so important in CF?
Impaired nutritional status in CF
- pancreatic insufficiency
- chronic malabsorption
- chronic inflammation leading to increased energy expenditure
- increased energy requirements of breathing
- impaired taste, fatigue: anorexia
Nutritional therapy led to: (NG tube)
- improved pulmonary function parameters/spirometry
- improved respiratory muscle strength
- gains in exercise capacity
What are the 6 catagories of mutation in CF?
-no protein production
-protein made but never reaches cell membrane
-protein gets to membrane but doesn’t work as well
-protein made but only partially active
-protein expressed at gene level but substantial reduction in mRNA/protein synthesis
-protein gets to membrane but is partially unstable
=medications developed that target underlying disease mechanisms
Why has survival improved in CF patients?
Understanding the importance in:
- augmenting airway clearance 2-3x a day
- aggressively treat infection (without overtreating)
- correcting nutrition deficits
- new drug treatments
How do you cure CF?
Lung transplant
or heart and lung transplant
