CF and Bronchiectasis Flashcards
CF definition
AR
Over 2000 mutations and most common deltaF508 90% on long arm C7
Reduce function and quantity of protein
90% one copy and 50% 2
Clinical presentation CF
Baby
Hypo atresia
Meconium ileus
Distal ideal obstruction
Failure to thrive
Undernutrition
Adolescent
Adult
Recurrent LRTI
Sinus disease
Oozospermia
Pancreatitis
Malabsorption
Complications CF
Nasal polyp
Sinus disease
Underweight
Meconium ileus
85% Pancreatic insufficiency then ADEK deficiency w creon.
Distal ileal obstruction - cp rif mass, avoid surgery if able
10% CLD due to biliary disease PBC or fibrosis vessels liver. Causes portal htn. Mx nutrition w usda
Pancreatitis
GORD
30% DM less dis, mx insulin
Colorectal cancer 8-10x and present younger. Colonoscopy 5y
OP so vit D and Ca
Puberty may need hormones
Male infertility
Dx CF
Infant
Blood immunoreactive trypsin screening
Or
2x Sweat test less than 30 normal, 30-59 int, more than 60 Dx — int or Dx genetic
Or
At least 2 mutations significant disease
Or
Clinical manifestation with negative sweat and genetic test
Epidemiology CF
1 in 2500 birth rate
1/25 carrier
90% delF508
Prognosis CF
46 men
41 female
Pathophysiology CF
Healthy apical chloride channel
Chloride out of cell and Na follows
Mucus well hydrated
Airway defect
Na and CL not in airway so no water
Mucus concentrated so cilia blocked
Bicarbonate affects innate airway
Sweat gland
Citrus healthy pumps chloride back into cell
Defect more chloride in sweat
Management CF
Airway clearance
Not for chest wall oscillation
- postural drainage, breath and cough assist, flutter, percussion ventilation
NIV to help
Bronchodilator Saba
Copd and asthma as per protocol
Mucoactive
DNAse reduces exacerbation and increases fev1
Hyperactive saline reduces exacerbation
Mannitol increases FEV1
Pulmonary infection
Staph aureus - fluclox
MRSA - Rifampicin or linezolid or neb/iv vanc
Pseud - iv ceftaz or mero or taz or aztreonam then 3m colistin
Burkholdeira is GN resistant- iv ceftaz/ taz/ mero/ tobramycin/aztreonam
HiB - CoA or doxy or iv cef
NTM
Aspergillus depending on presentation. ABPA pred then itra. Invasive iv voriconazole
Stenotropomonas - 4 weeks septin
PTX
1% incidence
Risk older men
Mx no TALC and surgery early vats w sealant for BPF+ refer tx
Gene modulators
Haemoptysis
Mx small stop ac/txa/ vit k/ blood tx and correct coagulopathy and abx for all
Major CTA and embolise —> I&V with double lumen tube and isolate affected side
Nutrition
Dietitian - high calorie, creon, adek
CT in CF
Upper zone bronchial dilation with non tapering airways 1cm from pleural surface
Mucus plugging
Bronchial dilation with formation bronchocele
Small airway
Cystic airway
CF acute exacerbation mx
Presentation
Sputum thicker
Increased volume
Fever
Chest pain
Ix
Fev1 falls 10%
Bloods in bc
Sputum afb and mcs and fungal culture
Total Ige or asp Ige+IgG or bdg or galactomanan
ABG
Cxr and CT
Mx
IVF and iv Abx empiric
BM
Nutrition with CREON
Chest PT
Hypertonic and DNAse
Lung transplant CF
Chronic Resp failure with pH less than 7.3
Hypoxia on LTOT
Itu admission
FEV1 less than 30%
Ptx or Haemoptysis
<20 rapid fall 20% in a year
Double lung transplant
10y survival
Contraindications Tx in CF
Contraindications
Burkholdeira
MB abscessus
S cedospirium
I&V
Relative
BMI less than 17
CF gene modulators
Types
1 defect protein synthesis Tezacaftor
2 defect protein trafficking
3 keeps channel open IVACAFTOR
4 defect ion transport
5 defect splicing
6 increase turnover
————————————-
No protein no targets
Misfolded then Kaftrio w IVACAFTOR and tezacaftor and elexacaftor
Over 3 and 2 copies deletion
Increased FEV1 and reduce exacerbation
Kaldeydeco is IVACAFTOR
Reduced volume protein in one of 9 mutations significant disease.
Y oral, lung and extrapulomonary, efficacy via sweat
X small proportion pts
Alyftrek is vanzacafter/tezac/deut
Corrector
Opens channel
3 rare mutations
Improves lung function and reduced chloride in sweat
Trikafta elex/ tez/ Iva
Corrector
At least one delF508
Symkevi — tezacaftor corrector and ivacaftor potentiator
2 x deletions
Increase fev1
Orkambi - lumacaftor corrector or ivacaftor potentiator
2x deletions
Slows decline lung function
Bronchiectasis definition
Irreversible airway dilation one or more bronchi
Due to chronic airway inflammation
500 per 100,000
More common females
Pathophysiology Bronchiectasis
Insult due to host immune response/ free radical/ neutrophil elastase/ IR or neovascularisation
Damage airway so colonisation so more inflammation
Damage mc escalator so can’t clear infection
Mucosal oedema
Obstructed secretions and volume loss
Aetiology Bronchiectasis
Commonest unknown 40% then infection then Copd then immune def then asthma
Congenital
CVID or x linked agamma or goodpastures
Cf or pcd or A1AT or ABPA or youngs
Structural Mounier-Kuhn
William Campbell - bronchial cartilage deficiency
Acquired
Asthma or Copd
Aspiration or gord or foreign body/LN/tumour
Chronic sinus with PND
HIV or CLL or nephrotic syndrome
Infection eg pertussis or NTM
IBD
CTD
Yellow nail - effusion, bre, sinusitis, yellow nail
Toxic gases
50% idiopathic
Bronchiectasis ix
Cxr and HRCT
Lung function obstruction
Sputum mcs/afbx3 and fungal culture
Bloods inc immunoglobulin/total IgE/ IgG to aspergillus/ RAST to aspergillus/ cftr gene/ vasculitis screen/ ciliary test pcd/ protein electrophoresis/ A1AT and HIv serology
Legionella and pneumococcal ag
Bronch localised disease
VF for aspiration
Aetiology
Sweat test or cf genotyping
Mucus ciliary video microscopy
TEM
PCD genotyping
Management Bronchiectasis
Treat cause eg asthma or Copd
- CF DNAse
- CVID Igg replacement
- ABPA pred and itra
- hiatus hernia ppi and pro kinetic
- IBD inhaled corticosteroid
Physiotherapy cycling or gravity or insufflation or gord sit up or autogenic drain or chest wall oscillation or percussion oscillation — sputum moved on expiration
Mucolytic with hypertonic saline and carbocisteine
Micro
Pseud eradicate
Nutrition
Vaccination
Surgical resection vs Tx
Pseud non CF Bronchiectasis
Gram negative
Need to eradicate on first presentation
S1
Treat cause
Airway clearance
Vaccine
ABC exac
S2 then 2 or less
Pt and Mucolytic
S3 3 or more exac
Severe iv Abx then neb colistin 3m w po azithro
Mild neb 3m then po azithro
No mo or not pseud then po azithro
Stage 4/5 - 5 or more exacerbations
Iv Abx 3m
Surveillance CX Bronchiectasis
Echo for PH
CT
LTOT or NIV as per guidelines
Lung tx and Bronchiectasis
Less than 65 and FEV1 less than 30%
Urgent
Ptx
Haemoptysis
ICU
O2 dependent or Raised co2
Management exacerbation BrE inc pseud erad
Mild
Po Abx for 10-14 days
MRSA IV eradication
Moderate or severe
2 weeks of Abx and 2 days after clearance
Pseud
Mild po cipro for 14d
Severe iv taz and gent for 14d then 3m neb colistin/po azithro
Macrolides
Pre
Sputum rule out NTM
QTC less than 450
Lft at 0m/1m/6m
Hearing
Side effect
GI deranged lft
Hearing loss
Long qtc
CVD
Indication
Copd with 3 or more exac and optimised and non smoker
Asthma 50-70/ 800mcg steroid/ more than 1 exac
Bre 3 or more exac
BO
Radiological types Bronchiectasis
Cylindrical signet ring
Varicose alternating dilated and constriction
Cystic tram track
PCD
AR
0.3%
Nasal NO low
Bronchiectasis middle lobe
Chronic rhinitis
Recurrent OM
Neonatal Resp symptoms
55% situs inversus
Infertility
Bronchiectasis mx specialist
3 or more exacerbations.
Pseud or NTM or MRSA
Long term tx
Declining lung function
Vasculitis or ABPA or Pcd or cf
Bronchiectasis severity index
Age older
BMI lower
FEV1 lower
Hospital admissions
Exactly more than 3
MRC
Pseud colonisation
Radiology 3 or more cystic change
Grade
More than 9 severe
Moderate 4-8
Mild 0-4
Indications CF ix
Staph aureus
Malabsorption
Male primary infertility
UL BrE
Childhood steatorrhoea
Ix 2x sweat and genetic analysis
CF MO by age
Baby staph and HIB
Adolescent pseud and capcasia
Adult pseud and capacia
Pseud in CF
Well
oral cipro or iv plus inhaled colistin then oral with nebs
Unwell
Iv and inhaled anti pseud
Then oral and inhaled
Nebs
Colistin
Alternative aztreonam or neb tobramycin
Chronic pseud always treated neb colomycin or neb tobramycin
CX
Decline lung function
Increase exacerbation
Mortality predictor
Burkholdeira
Accelerated decline fev1
Increased mortality
Capacia syndrome
Fever
Consolidation
Sepsis
Death
Gene modulator cf effect
Function IVACAFTOR
Quantity tezacaftor or elexacaftor or lumacaftor
Haemoptysis in CF
5-16% mortality
4% massive
Bleeding from bronchial in 90% and only Carries 1% CO but increases hypoxia
Massive over 100ml over days or 250ml one go
Mild pt and DNase. Stop hypertonic saline
Severe stop all, txa, abx, bleeding side down, Terli and bronchial artery emb
Bronchial artery emb side effects
Chest pain
Exacerbation
Infarct
Stroke
Pneumothorax cf
3%
Mucus plug so bronchial obstruction so air trap and alveoli burst
14% mortality
Drain no talc. Refer vats and tx
CT Bronchiectasis
Dilation bronchi
Ba more than 1
Lack tapering
Airway in 1cm costal pleural surface or touch mediastinal pleural
Other
Bronchial wall thickening
Mucous impaction
Mosaicism
Long term ag
Avoid crcl less than 30
Hearing loss
Challenge test
PR in BrE
MRC more than equal to 2
Bre surgery
Localised
Not controlled medical tx
Anatomy and cause BrE
Upper lobe CF
Upper lobe ABPA
Middle lobe - lady Windermere NTM
Lowe - A1AT or Pcd or aspiration
Complications Bronchiectasis
Infection inc abscess or empyema
Haemoptysis
Ptx
Respiratory failure
Amyloid
CV disease
