Restrictive Lung Disease Flashcards
Lung volume in restrictive disease
Smaller
what can lung expansion be restricted by?
intrinsic e.g. interstitial lung disease (alterations to lung parenchyma)
extrinsic disorders → compress lungs/limit expansion → pleural, chest wall, neuromuscular(decrease ability of lungs to inflate or deflate)
what are the components of lung parenchyma?
alveolar type I epithelial cell, type II, fibroblasts, alveolar macrophages
what are the roles of the two epithelial cell types
type 1 = gas exchange surface
type 2 = produce surfactant → reduce surface tension, stem cells for repair
what are the roles of the other parenchyma components?
fibroblasts → ECM production eg collagen type 1
macrophages → phagocytosis of foreign material, surfactant
- space between alveolar epithelium and capillary endothelium
what is the interstitial space?
space between alveolar epithelium and capillary endothelium
Contains lymphatic vessels, occasional fibroblasts and ECM
Structural support to lung
Very thin (few micrometers thick) to facilitate gas exchange
What does the interstitial space contain and role
lymphatic vessels, sometimes fibroblasts and ECM
structural support for lung, thin to facilitate gas exchange
different categories of interstitial lung disease?
idiopathic-IPF,NSIP,DIP
autoimmune-CTD,SSC
exposure related-hypersensitivty pneumnia,drug induced
with cysts or airspace filling
sarcoidosis
others-eosinophilic,pnemonia
typical clinical presentation of ILD
non-productive cough, progressive breathlessness, less exercise tolerance, relevant drug/family/exposure and occupational history,symptoms of connective tissue disease
Possible examination findings
low o2 sats, fine bilateral inspiratory crackles, digital clubbing (possible features and symptoms of connective tissue disease)
relevant ILD investigations?
- blood testsantinuclear antibody, anti-citrullinated peptide antibody (anti-CCP), rheumatoid factor
- invasive testingbronchoalveolar lavagesurgical lung biopsy (2-4% mortality)
pulmonary function tests, 6-minute walk test, high-resolution CT scan
6 minute walk test consideration?
o2 sats under 88% = increased risk of death
normal FEV1/FVC ratio?
approx 80% or more
Ratio in restrictive lung disease
Approx 80% or more
ILD → changes in lung physiology?
scarring = stiffness, reduced compliance
reduced FVC and lung volume (TLC,FRC,RV)
less diffusing capacity for carbon monoxide
less arterial PO2 esp with exercise
HRCT interpretation
dense = white (e.g. bone)
low density = dark (e.g. air)
HRCT pattern → different kinds?
usual interstitial pneumonia (honey comb type and cysts in X ray), non-specific interstitial pneumonia (inflammatory ground glass), organising pneumonia
general principles of ILD management by early/late disease?
early → pharmacological therapy e.g. antifibrotics & immunosuppressants, smoking cessation, comorbidity treatment,vaccination,pulmonary rehab
late → supplemental o2, lung transplant,palliative care
Idiopathic pulmonary fibrosis
progressive scarring lung disease with unknown cause
- more common in old people and in men
Aetiology of pulmonary fibrosis
More common in old ppl and men >60
Characteristics of IPF
poor prognosis
variable clinical course → rate of FVC decline different (150-200ml a year)
acute exacerbations possible → high mortality
Median untreated survival is 3-5 yrs
Predisposing factors of IPF
genetic susceptibility (MUC5B airway mucin ,DSP), environmental triggers,(smoke,viruses,pollutants dusts),cellular aging (telomere attrition and senescence as can’t deal with environmental insults)
Mechanism of IPF
alveolar injury, possibly in combination with altered microbiome → aberrant fibrotic activity, ECM accumulation, remodelling, honeycomb cyst formation
alveolar epithelium injury-in a study on mice AECIIS were injured and response saw increased collagen deposition thus re epithelization disturbed in ipf
characteristic features of IPF?
- histological?microscopic honeycomb cysts, fibroblast foci (proliferating fibroblasts/myofibroblasts in active disease)
Spatial heterogeneity is uneven fibrotic changes across the lungs. Temporal is variation in stages of fibrosis in lung tissue. - CT scan?subpleural honeycombing, basal predominance,traction bronchiectasis
treatment options of IPF
immunosuppressants harmful
Prednisolone and azathioprine and n acetylcysteine caused increased risk of death
antifibrotics can slow disease course but not cure. Eg nintedanib a tyrosine kinase inhibitor or pirfenidone a pyridine compound
- what is hypersensitivity pneumonitis?
ILD in susceptible and sensitised people → immune mediated response to inhaled environmental antigens
Involves small airways and parenchyma
Genetic and host factors explain why only a few ppl get
Classifications of hypersensitivity pneumonia
acute → intermittent, high-level exposure, abrupt symptom onset. Flu like syndrome 4-12 hours after exposure
chronic → long-term, low-level exposure. Non fibrotic (purely inflammatory) and fibrotic which is associated with higher mortality
Chronic subclasses of hp
non-fibrotic (purely inflammatory)
fibrotic (higher mortality)
Epidemiology of HP
equal between M and F, smokers = less common, most common onset = 50s,rare,3x more likely to die
HP pathophysiology?
antigen exposure → inflammatory response (mostly T-helper cells and IgG)
→ accumulation of lymphocytes, granuloma formation
Ie mould exposure and genetic risk and viral infection triggers
elements of HP diagnosis?
exposure history to identify antigen
circulating IgG to potential antigens
inspiratory squeaks bc coexisting bronchiolitis
HRCT patterns e.g. ground glass appearance
bronchoalveolar lavage → lymphocyte count above 30%
I’m bronchiocentric inflammation you see centrilobar ground glass nodules or mosaic attenuation pattern
In narrowing of small airways you see air trapping and three density pattern
In interstitial you see ground glass
how is HP treated?
complete antigen removal or avoidance (common: birds, hay, hot tubs)
corticosteroids
potentially immunosuppressants (eg azathioprine and mycophenolate mofetil but poor evidence based), antifibrotics for progressive fibrotic type (nintedanib)
What kind of disease is systemic sclerosis
autoimmune connective tissue disease → immune dysregulation and progressive fibrosis affecting skin and possibly internal organs including ILD
Typical epidemiology of systemic sclerosis
tends to affect younger middle aged women
ILD develops in 30-40%, main cause of mortality
older males who smoke ,>20% on HRCT,FVC<70%= worse survival rates
clinical features of SSc?
sclerodactyly (localised skin thickening causing claw shape in hands), digital ulcer, raynaud’s, telangiectasia (widening of small blood vessels)
Classifications of ssc
based on skin involvement
→ limited cutaneous SSc (pulmonary hypertension more common), diffuse cutaneous SSc (ILD more common)
Lung manifestations in each type of ssc
limited → pulmonary hypertension
diffuse → interstitial lung disease
pathogenesis of SSc-ILD?
tissue injury/vascular injury + autoimmunity = cycle of fibrosis and inflammation in lung tissue
most common HRCT pattern in ssc-ild
non-specific interstitial pneumonia = most common
how to determine the best SSc-ILD management?
determined by disease extent, lung function trajectory monitor every 3-6months
management options of ssc
corticosteroids (renal crises risk with high doses) >10mg
immunosuppressants-cyclophosphamide and mycophenolate mofetil
progressive fibrotic phenotype → antifibrotic e.g. nintedanib (anti fibrotic)
Autoantibodies associated with SSC
Anti centromere
Anti scl-70 associated with increased ILD
