biochiectasis and cystic fibrosis Flashcards
physical defences#
Humidification
• Particle expulsion (cough/ sneeze)
• Particle removal
– 90% 10µm particles removed in
nostril/nasopharynx
– 1-2 µm particles deposited in distal lung
airway fluid defence
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)
soluble factors?
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
cellular aspects
Bronchus associated lymphoid tissue
(BALT)
• Macrophages: predominant cell type
– Migrate from bloodstream
– Phagocytose particles (incl bacteria)
bronchiectasis?
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%)
ABPA
allergic bronchopulmonary aspergillosis
syptoms
Cough
• Chronic copious sputum production
• Recurrent chest infections
• Haemoptysis
• Wheeze
• Shortness of breath
• Pleurisy
• Malaise, weight loss
Clubbed
- Cyanosis
- Hyperinflation
- Crackles
- Weight loss
investigations
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
treatment?
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
what is cystic fibrosis
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
genetics?
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
cf gene pic
CFTR protein?
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
diagnosis of CF?
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
how the channel dysfunction leads to the disease
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
pulmonary complications of CF?
- 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
cf infection?
Staphylococcus aureus, MRSA
• Haemophilus influenza
• Pseudomonas aeruginosa
• Burkholderia cepacia complex
• Atypical mycobacteria
• Aspergillus fumigatus, C.albicans, Scedosporium
apiospermum
• Viruses
ntimicrobial treatment
Staph aureus
– Oral flucloxacillin
• Haemophilus influenzae
– Oral augmentin/ amoxycillin
• Pseudomonas aeruginosa
– Oral Ciprofloxacin + nebulised antibiotics
prophylaxis
• 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
IV antibiotics?
• 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
treatment strat for CF lung disease?
• 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
increased mucociliary clearance
• 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.
resp failure in cf?
• Oxygen therapy
– Symptomatic benefit
• Non-invasive ventilation
– ? Expanding role
– Used successfully as bridge to transplantation
• Bilateral sequential Lung
atelectasis
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
complications
atelectasi
pneumothorax
haemoptusis
pneumothorax
Complicated
pneumothorax
common
• Intercostal tube
drainage usually
required
• Surgical liaison
essential – minimally
invasive options best
haemoptysis
• Minor haemoptysis common
• More important haemoptysis (>250ml/ 24 hrs)
occurs in 7% of adults
• Predispositions include infection, liver disease
and vitamin K deficiency
haemoptysis tratment?
• 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.
ABPA
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
treat ABPA?
• 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
sinus disease?
• Almost universal
• May be reservoir for
infection
• Nasal polyps common
• ENT liaison invaluable
non resp complications?
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
distal intestinal obstruction syndrome?
• Symptoms:
– Colicky abdominal
pain,
– nausea, vomiting,
– constipation
• AXR reveals faeces
and fluid levels
DIOS therapy?
• Surgical management associated with high mortality
• Medical management with:
– Movicol, oral +/- PR Gastrograffin, Kleenprep (or
Parvolex)
• Colonoscopy may be required rarely
cf diabetes mellitus?
• 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
cf liver disease?
• 5% CF deaths
• More common teenagers
• Intrahepatic obstruction and biliary stasis
• Common cirrhotic histology
• Treatment
– Ursodeoxycholic acid
– ?IFδ
– ?Colchicine
cf and bone mineral density
• 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
joint and skin cf
• Finger clubbing
• Hypertrophic pulmonary
osteoarthropathy
• CF arthropathy
• CF-associated vasculitis
cf and bronchiectasi
- 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
exclusion for lung transplant
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
