biochiectasis and cystic fibrosis

Question 1

physical defences#

Answer 1

Humidification
• Particle expulsion (cough/ sneeze)
• Particle removal
– 90% 10µm particles removed in
nostril/nasopharynx
– 1-2 µm particles deposited in distal lung

Question 2

airway fluid defence

Answer 2

Mucus is gelatinous substance consisting
mainly of polysaccharides
• Relatively impermeable to water
• Secreted from goblet/ mucous glands
• Cilia contact with this gel layer and
coordinate to push the layer continually
upwards (mucociliary escalator)

Question 3

soluble factors?

Answer 3

Alpha 1 Antitrypsin: inhibits chymotrypsin and
trypsin
• Lysozyme/ Lactoferrin : bacteriocidal properties
• Defensins: bacteriocidal peptides
• Interferon: produced in response to viral infection
• Complement:
• Surfactant protein A: opsonises bacteria/particles

Question 4

cellular aspects

Answer 4

Bronchus associated lymphoid tissue
(BALT)
• Macrophages: predominant cell type
– Migrate from bloodstream
– Phagocytose particles (incl bacteria)

Question 5

bronchiectasis?

Answer 5

Chronic disease characterised by
irreversible dilatation of bronchi due to
bronchial wall damage resulting from
infection /inflammation

aetiology

Genetic : CYSTIC FIBROSIS (4%)
• Post Infective : (40%)
• Aspiration : (4%)
• Immune Deficiency : e.g. CVI (5%)
• ABPA : (7%)
• Ciliary Defect : PCD (3%)
• Connective Tissue Disease : (5%)
• Idiopathic (32%)

Question 6

ABPA

Answer 6

allergic bronchopulmonary aspergillosis

Question 7

syptoms

Answer 7

Cough
• Chronic copious sputum production
• Recurrent chest infections
• Haemoptysis
• Wheeze
• Shortness of breath
• Pleurisy
• Malaise, weight loss

Clubbed

• Cyanosis
• Hyperinflation
• Crackles
• Weight loss

Question 8

investigations

Answer 8

FBC, CRP, total IgG, then IgA, IgM, IgE and
IgG subclasses. Aspergillus IgG and IgE,
auto-antibodies and alpha-1 antitrypsin.
• Chest and sinus X-rays
• PFTs
• Sputum ~ smear and culture + AAFB
• HRCT
• Bronchoscopy

Sweat test,CF genotyping and semen
analysis
• Nasal MCC, nasal NO, CBF and EM
• Investigate associated conditions

Question 9

treatment?

Answer 9

Physiotherapy + regular exercise
• Bronchodilators + inhaled steroids
• Underlying causes ~ replace IgGs, steroids
for ABPA, treat UC Crohn’s etc
• Long-term inhaled antibiotics/oral
• Treat exacerbations aggressively
• Regular review
• Nutrition
• Surgical resection or transplant

Question 10

what is cystic fibrosis

Answer 10

Clinical syndrome described with:
– High sweat sodium and chloride
– Chronic bronchopulmonary sepsis
– Intestinal malabsorption due to pancreatic
exocrine insufficiency
• Descriptions date back several centuries in
western Europe

Question 11

genetics?

Answer 11

1 in 2500 live births
• Inheritance autosomal
recessive
• Carrier state in 5% of
normal population
• CF Gene identified in 1989
• Present on long arm of
Chromosome 7
• CFTR described 1992

Question 12

cf gene pic

Answer 12

Question 13

CFTR protein?

Answer 13

cystic fibrosis transmembrane conductance regulator protein

Protein sequence 1480 amino acids
• Functions as a chloride channel
• Present in exocrine cells
• Most common abnormality F508del
– 52% homozygous (Wales 43%)
– 36% heterozygous (Wales 40%)
– 12% no F508del

Question 14

diagnosis of CF?

Answer 14

family history

• Evidence of altered epithelial ion transport:
– Sweat test / nasal potential differences
• Sweat Na and Cl > 70 mmol/l
• DNA analysis may be useful but N/N does not
exclude diagnosis

• Diagnosis suggested by other
features:
– Respiratory symptoms in 51%
– Failure to thrive/malnutrition in 43%
– Steatorrhoea/abnormal stools in 35%
– DIOS (MIE) in 20%
– Family history in 17%
– Infertility

Question 15

how the channel dysfunction leads to the disease

Answer 15

Thickened secretions from exocrine cells leads to:
– Increased mucus viscosity in airways
– Failure of secretion of pancreatic digestive enzymes
– Intrahepatic bile duct obstruction
– Dehydration of small and large gut
– Infertility

Question 16

pulmonary complications of CF?

Answer 16

• Bronchiectasis- infective exacerbation
• Increased airway responsiveness
• Sinus disease
• Collapse/atelectasis
• Haemoptysis
• Pneumothorax
• ABPA, aspergilloma
• Lung abscess
• Atypical mycobacteria infection
• Cor pulmonale, respiratory failure
• Complications of lung tx

Question 17

cf infection?

Answer 17

Staphylococcus aureus, MRSA
• Haemophilus influenza
• Pseudomonas aeruginosa
• Burkholderia cepacia complex
• Atypical mycobacteria
• Aspergillus fumigatus, C.albicans, Scedosporium
apiospermum
• Viruses

Question 18

ntimicrobial treatment

Answer 18

Staph aureus
– Oral flucloxacillin
• Haemophilus influenzae
– Oral augmentin/ amoxycillin
• Pseudomonas aeruginosa
– Oral Ciprofloxacin + nebulised antibiotics

Question 19

prophylaxis

Answer 19

• Staph aureus
– Oral flucloxacillin, tetracycline, ? gentamicin nebs
• Pseudomonas aeruginosa
– nebulised colomycin, tobramycin (TOBI)
• Burkholderia cepacia complex
– Nebulised ceftazidime, Taurolidine 2%
• Stenotrophomonas maltophilia
– Oral co-trimoxazole, minocycline

Question 20

IV antibiotics?

Answer 20

• IV antibiotic therapy
– Severe infection / failure to respond to orals
– Combination therapy
• Beta-lactam + aminoglycoside
• High doses / prolonged courses
• May use long-term venous access devices
• Home vs. hospital administered IVs
– 1
st
dose in hospital, even if prior use

Question 21

treatment strat for CF lung disease?

Answer 21

• Maximise airway clearance
– Chest physiotherapy
– Mucolytic therapy in some subjects e.g. rhDNase
(pulmozyme)
– 5% Hypertonic Saline
• Regular sputum analysis in all patients
– First pseudomonal isolates treated aggressively
– Continuous antibiotic therapy if colonisation occurs –
oral or nebulised antibiotics
• Aggressive antibiotic therapy to cover intercurrent illnesses

Question 22

increased mucociliary clearance

Answer 22

• Thick sputum is consequence of bronchial sepsis
• Bronchi and bronchioles obstructed by thick,
tenacious secretions
• DNA from degraded neutrophils in sputum
contribute to increased viscosity.

Question 23

resp failure in cf?

Answer 23

• Oxygen therapy
– Symptomatic benefit
• Non-invasive ventilation
– ? Expanding role
– Used successfully as bridge to transplantation
• Bilateral sequential Lung

Question 24

atelectasis

Answer 24

block in air duct (bronchi/ioles/alvioli) and part of lung collapses

caused by :

foreign body

ressure from chest tumour

trapped sputum or mucus

• Atelectasis may
involve entire lobe
• May be associated
with ABPA
• Rx with antibiotics
and physiotherapy
• Occasionally, steroids,
lavage +/- DNase

Question 25

complications

Answer 25

atelectasi

pneumothorax

haemoptusis

Question 26

pneumothorax

Answer 26

Complicated
pneumothorax
common
• Intercostal tube
drainage usually
required
• Surgical liaison
essential – minimally
invasive options best

Question 27

haemoptysis

Answer 27

• Minor haemoptysis common
• More important haemoptysis (>250ml/ 24 hrs)
occurs in 7% of adults
• Predispositions include infection, liver disease
and vitamin K deficiency

Question 28

haemoptysis tratment?

Answer 28

• Initially supportive
– Volume replacement, correction of coagulation
– Treat infection, continue physiotherapy
– Vasopressin useful with continued bleeding
• Bronchial artery embolisation if continued
haemoptysis – poor outcome with surgery
• Favourable outcome with ITU support if
required, including ventilation.

Question 29

ABPA

Answer 29

allergic bronchopulmonary aspergillosis

• Allergic response to
fungal antigens
• Associated with
cough, wheeze,
sputum production
• Diagnostic criteria:
– SPT to aspergillus
– Wheeze, sputum
– CXR infiltrates
– Blood eosinophilia
– Raised total IgE
– Raised spec. IgE
– Precipitins
– Aspergillus in sputum

Question 30

treat ABPA?

Answer 30

• Treatment:
– Oral corticosteroids
– Long course may be
required
– May be some role for
Itraconazole
• Relapsing/remitting
course
• Balance effects of
treatment and ABPA
• Remains a challenge

Question 31

sinus disease?

Answer 31

• Almost universal
• May be reservoir for
infection
• Nasal polyps common
• ENT liaison invaluable

Question 32

non resp complications?

Answer 32

GIT
• Rectal prolapse (~20% under 5yrs)
• Intersussception
• DIOS (MIE) (9-26% adults)
• Cirrhosis, PHT
• Gall stones, biliary stricture
• Pancreatitis
• Malabsorption
• GORD

OTHER
• Salt loss
• Diabetes
• Osteoporosis
• CF arthropathy
• Vasculitis
• Male subfertility
• Renal stones
• Malignancy
• Treatment related
• Fibrosing colonopathy

Question 33

distal intestinal obstruction syndrome?

Answer 33

• Symptoms:
– Colicky abdominal
pain,
– nausea, vomiting,
– constipation

• AXR reveals faeces
and fluid levels

Question 34

DIOS therapy?

Answer 34

• Surgical management associated with high mortality
• Medical management with:
– Movicol, oral +/- PR Gastrograffin, Kleenprep (or
Parvolex)
• Colonoscopy may be required rarely

Question 35

cf diabetes mellitus?

Answer 35

• More than 30% of all CF patients affected
• Prevalence increases with age
• CFRDM associated with more “severe” CFTR
mutation classification
• Association between DM and low FEV1
and BMI

CFRDM combination of insulin resistance and
reduced insulin secretion
• Dietary control impossible
• May be subgroup of patients who can be
adequately managed with oral Rx
• Insulin therapy indicated where persisting clinical
instability, weight loss or elevated HbA1c

Question 36

cf liver disease?

Answer 36

• 5% CF deaths
• More common teenagers
• Intrahepatic obstruction and biliary stasis
• Common cirrhotic histology
• Treatment
– Ursodeoxycholic acid
– ?IFδ
– ?Colchicine

Question 37

cf and bone mineral density

Answer 37

• Osteoporosis-related fractures in 1%
• Risk factors include:
– Delayed puberty, malnutrition, malabsorption Vit D
deficiency, DM, steroids, infection
• Surveillance of benefit with appropriate Vit D, calcium &
bisphosphonate supplementation
• Benefits of drug therapy unclear

Question 38

joint and skin cf

Answer 38

• Finger clubbing
• Hypertrophic pulmonary
osteoarthropathy
• CF arthropathy
• CF-associated vasculitis

Question 39

cf and bronchiectasi

Answer 39

• FEV1 < 30% predicted
• Rapidly declining FEV1
• Frequent hospital admission
• Massive haemoptysis
• PaO2 < 7.3kPa (55mmHg)
• PaCO2 > 6.7kPa (50 mmHg)
• Young female patients who deteriorate rapidly
• absence of Burkholderia Cenocepacia

Question 40

exclusion for lung transplant

Answer 40

Presence of major organ dysfunction
Acutely ill or unstable clinical status (especially active infection)
Active neoplasia
Unacceptable nutritional status (BMI <19 or >25)
Drug alcohol abuse (including tobacco)
HIV, Hepatitis B or C infection

Cachexia
Osteoporosis
Severe musculoskeletal disease
High dose steroid treatment (>10mg prednisolone / day)
Absence of Burkholderia cenocepacia
Colonisation with fungi, or atypical mycobacterium, MRSA,
pan resistant pseudomonas
Unsatisfactory psychological profile and social support