Lecture 14 - Pathophysiology Of Interstitial Lung Disease Flashcards
1
Q
Restrictive lung disease
A
- reduced lung volume
- Pulmonary: interstitial lung disease
- Extrapulmonary: pleural disease, chest wall abnormality, neuromuscular disease
2
Q
Defining ILD
A
- lung disease characterised by damage to the interstitium of the lung by barying degrees of inflammation and fibrosis
- includes a diverse cluster of parenchymal lung diseases
3
Q
Interstitium
A
- space between epithelial and endothelial basement membranes
- space betweel alveoli and the capillary bed
4
Q
MEchanism of ILD
A
- depends on the cause of the ILD
- lung responds to damage by attempting to repair
- if known source not treated or removed then lung healing is delayed or prolonged
- if imperfect: permanent damage
5
Q
ILD of known cause or association
A
- Exposure: Occupation, envt, medication, drug, radiation, smoking
- systemic disease: CTD, IBD, sarcoidosis
- Genetic: Familial, HPS
6
Q
ILD of unkown cause
A
- IIP: IPF, NSIP, COP, LIP
- Specific pathology: LAM, PAP
7
Q
Why does the exact diagnosis matter?
A
- prognosis
- treatment
8
Q
Prgnosis and ILD
A
- IPF, fibrotic NSIP are bad
- cellular NSIP, sarcoidosis or drug induced have a better prognogis
- early diagnosis is important - no difference in survival of NSIP and IPF in patients with severe disease
9
Q
Impact of appropriate diagnosis on management
A
- IPF: antifibrotic drug, lung transplantation, clinical trials, supportive care
- non IPF ILD : corticosteroids and or immunosuppressive therapy. Lung transplant not possible
10
Q
5 key considerations in ILD
A
- does the patient have an ILD?
- is it idiopathic or are there systemic features?
- Is it IPF?
- how severe is the disease overall?
- what is the rate of disease progression?
11
Q
History for ILD
A
- exposure: smoking, medication, occupation, hypersensitivity triffers
- connective tissue symptoms (may be present in up to 20% of patients)
- GORD, dysphagia
- Sarcoid, vasculitic symptoms
12
Q
Physical examination
A
- 80% have fine crackles on inspiration
- inspiratory squeaks in primary bronchiolitis, HP
- Clubbing - more common in IPF, chronic HP, DIP, HCX, - rare in RB-ILD, CVD, sarcoid, COP or LIP
- pulmnonary hypertension
13
Q
Blood and Urine tests
A
- FBC, UEC, LFT, ESR, CRP, Ca/PO4
- CK, BNP, ACE
- autoimmune: ANA, ENA, dsDNA, RF, ANCA, antiCCP, anticentromere, myositis screen
- Immunoglobulins, TPMT
- Hypersensitivity screen - precipitins or antibodies
- specific serlogy
- Urine: MSU
- 24 hr Urine: protein/Ca
14
Q
Pulmonary function test
A
- not specific for diagnosis but useful to assess disease severity
RESTRICTIVE PICTURE
- TLC
15
Q
DLco and KCO
A
- DLco is the diffusing capacity. It is reduced in ILD
- KCO = DLco/VA
- KCO is relatiely preserves as both variables are decreased
- KCO is reduced when there is concomitant emphysema or pulmonary hypertension
16
Q
High Resolution CT chest
A
- Helpful in diagnosis of ILD
- highly specialised field
17
Q
Idiopathic pulmonary fibrosis pattern
A
= UIP pattern
- patchy - areas of normal lung
- thin walls at the base of the lung
- pattern is basal + peripheral
18
Q
- Non-specific intersticial pneumonitis
A
- grey fuzziness
- quite homogenous
19
Q
Respiratory bronchiolitis interstitial lung disease
A
- tiny nodules that are scattered
20
Q
Desqamative interstitial pneumonia
A
- grey fuzziness
- tiny little custs
- severe
21
Q
Lymphocytic interstitial pneumonia
A
- big thin wall cysts
- histology: plenty of infiltrated lymphocytes
22
Q
Bronchoscopy
A
- airways usually look normal
- BAL: lymphocytosis in sarcoid, hypersenstivity. Helps confirm diagnosis and exclude infection
- Transbronchial lung biopsy: neoplastic cells or sarcoid, cryobiopsy
- EBUS: combined nodaul aspirate and TBBx can increase the yield for sarcoidosis to 80% +
23
Q
Surgical lung biopsy
A
- only 10-20% undergo biopsy
- mortality in up to 2%
- complications in 5-10%
- diagnostic yield is 50-90%
24
Q
Surgical lung biopsy useful when
A
- non-classic HRCT appearance
- atypical presentation
- clinically fit for surgery
- always biopsy two distant sites
- changes diagnosis in 50-70% of non-IPF cases, but rarely in classic IPF
25
Other tests in ILD
- 6 min walk test: distance + oxyen desaturation
26
Three pillars of treating ILD
- Disease specific therapy: pharmacological treatments, pulmonary rehab, management of comorbidities
- symptom based management: dyspnoea, cough
- Patient education: support groups, participation in care
27
Disease centered management targets for IPF therapy
- prevent AEC apoptosis
- block TGF-b production/activation
- prevent fibrocyte recruitment
- inhibit fibroblast activation
- Prevent EMT
- prevent injury
- block TGFb activity
- prevent telomere shortening
28
Pirfenidone
- novel antifibrotic
- inhibits TGF-b induced collagen synthesis
- blocks the mitogenic effect of PDGF and TGF-b on lung fibroblasts
- reduces lung fibrosis in animal models
- reduces mortality and IPF related deaths
- reduces any serios adverse event
- increase adverse events leading to treatment discontinusation (GIT side effects and skin side effects)
29
Nintedanib in IPF
- intracellular tyrosine kinase inhibitor
- PDGF, FGF, and VEGF receptor blocker
- inhibits belomycin-induced lung fibrosis in rat
- decreased rate of decline in FVC by 50%
- decrease acute exacerbation
- non-significant decrese in QOL
- non-significant decrease in Mortality
- moe adverse events than placebo, as well as more drug-related AE
- more adverse events leading to discontinuation
- no difference in severe AE and fatal AE
30
Main adverse event with Nintadenadib
- Diarrhoea
- mostly mild or moderate intensity
- premature discontinuation in
31
Pulmonary rehabilitation
- short term gain in 6Min Walking distance and Quality of life
- more effective in early disease
32
IPF is associated with a number of comorbidities
- Pulmonary hypertension
- cardiovascular disease
- GORD reflux
- Sleep disorders
- psychiatric disorder (depression/anxiety) - almost universal
33
Symptom management: Dyspnoea
- Dyspnoea is so multifactorial. Can also lead to muscle weakness from deconditioning, depression and anxiety
- management: regularly assess and educate, refer for pulmonary rehab early and often, evaluate for comorbidities
34
Cough
- common feature
- often sign that leads to investigations and diagnosis
- often more troubling feature
- impact greatly on QOL
- consider antitussives including codein
35
Fourth pillar: transplantation
- even for those in early stage of disease
| - work up allows for listing once patient deteriorates
36
Hypersensitivity pneumonitis`
- immune reaction to inhaled antigens
- two hit hypothesis
- present with: sudden SOB, chest pain, fevers, chills, cough, malaise
- in chronic HP patients may have symptoms that are very mild and do not present for months or years after exposure
37
Hypersensitivity pneumonitis - treatment
- need to remove exposure to particular antigen
| - medications - corticosteroid treatment used to suppress immune response
38
Idiopathic pulmonary fibrosis
- specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause
- most common idiopathic interstitial pneumonia
- pulmonary manifestation only
- specific radiologic and histopathological features
39
IPF presentation
- progressive breathlessness
- mild cough, perhaps worsening at the time of diagnosis - trigger for investigation
- decreased exercise tolerance
- long asymptomatic period
- more common in men
- age of onset >50
- survival 3-5 years from diagnosis
40
Radiology and pathology of OPF
- very specific radiologic picture
- commonly agreed upon criteria by expert groups associated with ATS.ERS
- most prominent radiological feature are honeycomb cysts
- clinical-pathological-radiological concencus diagnosis
- lung biopsy not required for diagnosis
41
Pathogenesis of IPF
- poorly understood
- previously thought to be inflammatory process leading to fibrosis
- may be suscpeitble individual
- aberrant healing response
- repetitive alveolar injury
- laying down of collagen and the ECM
