Restrictive Lung Disease

Question 1

Lung volume in restrictive disease

Answer 1

Smaller

Question 2

what can lung expansion be restricted by?

Answer 2

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)

Question 3

what are the components of lung parenchyma?

Answer 3

alveolar type I epithelial cell, type II, fibroblasts, alveolar macrophages

Question 4

what are the roles of the two epithelial cell types

Answer 4

type 1 = gas exchange surface

type 2 = produce surfactant → reduce surface tension, stem cells for repair

Question 5

what are the roles of the other parenchyma components?

Answer 5

fibroblasts → ECM production eg collagen type 1

macrophages → phagocytosis of foreign material, surfactant

• space between alveolar epithelium and capillary endothelium

Question 6

what is the interstitial space?

Answer 6

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

Question 7

What does the interstitial space contain and role

Answer 7

lymphatic vessels, sometimes fibroblasts and ECM

structural support for lung, thin to facilitate gas exchange

Question 8

different categories of interstitial lung disease?

Answer 8

idiopathic-IPF,NSIP,DIP
autoimmune-CTD,SSC
exposure related-hypersensitivty pneumnia,drug induced
with cysts or airspace filling
sarcoidosis
others-eosinophilic,pnemonia

Question 9

typical clinical presentation of ILD

Answer 9

non-productive cough, progressive breathlessness, less exercise tolerance, relevant drug/family/exposure and occupational history,symptoms of connective tissue disease

Question 10

Possible examination findings

Answer 10

low o2 sats, fine bilateral inspiratory crackles, digital clubbing (possible features and symptoms of connective tissue disease)

Question 11

relevant ILD investigations?

Answer 11

• 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

Question 12

6 minute walk test consideration?

Answer 12

o2 sats under 88% = increased risk of death

Question 13

normal FEV1/FVC ratio?

Answer 13

approx 80% or more

Question 14

Ratio in restrictive lung disease

Answer 14

Approx 80% or more

Question 15

ILD → changes in lung physiology?

Answer 15

scarring = stiffness, reduced compliance

reduced FVC and lung volume (TLC,FRC,RV)

less diffusing capacity for carbon monoxide

less arterial PO2 esp with exercise

Question 16

HRCT interpretation

Answer 16

dense = white (e.g. bone)

low density = dark (e.g. air)

Question 17

HRCT pattern → different kinds?

Answer 17

usual interstitial pneumonia (honey comb type and cysts in X ray), non-specific interstitial pneumonia (inflammatory ground glass), organising pneumonia

Question 18

general principles of ILD management by early/late disease?

Answer 18

early → pharmacological therapy e.g. antifibrotics & immunosuppressants, smoking cessation, comorbidity treatment,vaccination,pulmonary rehab

late → supplemental o2, lung transplant,palliative care

Question 19

Idiopathic pulmonary fibrosis

Answer 19

progressive scarring lung disease with unknown cause

• more common in old people and in men

Question 20

Aetiology of pulmonary fibrosis

Answer 20

More common in old ppl and men >60

Question 21

Characteristics of IPF

Answer 21

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

Question 22

Predisposing factors of IPF

Answer 22

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)

Question 23

Mechanism of IPF

Answer 23

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

Question 24

characteristic features of IPF?

Answer 24

• 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

Question 25

treatment options of IPF

Answer 25

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

Question 26

- what is hypersensitivity pneumonitis?

Answer 26

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

Question 27

Classifications of hypersensitivity pneumonia

Answer 27

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

Question 28

Chronic subclasses of hp

Answer 28

non-fibrotic (purely inflammatory) fibrotic (higher mortality)

Question 29

Epidemiology of HP

Answer 29

equal between M and F, smokers = less common, most common onset = 50s,rare,3x more likely to die

Question 30

HP pathophysiology?

Answer 30

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

Question 31

elements of HP diagnosis?

Answer 31

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

Question 32

how is HP treated?

Answer 32

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)

Question 33

What kind of disease is systemic sclerosis

Answer 33

autoimmune connective tissue disease → immune dysregulation and progressive fibrosis affecting skin and possibly internal organs including ILD

Question 34

Typical epidemiology of systemic sclerosis

Answer 34

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

Question 35

clinical features of SSc?

Answer 35

sclerodactyly (localised skin thickening causing claw shape in hands), digital ulcer, raynaud’s, telangiectasia (widening of small blood vessels)

Question 36

Classifications of ssc

Answer 36

based on skin involvement → limited cutaneous SSc (pulmonary hypertension more common), diffuse cutaneous SSc (ILD more common)

Question 37

Lung manifestations in each type of ssc

Answer 37

limited → pulmonary hypertension diffuse → interstitial lung disease

Question 38

pathogenesis of SSc-ILD?

Answer 38

tissue injury/vascular injury + autoimmunity = cycle of fibrosis and inflammation in lung tissue

Question 39

most common HRCT pattern in ssc-ild

Answer 39

non-specific interstitial pneumonia = most common

Question 40

how to determine the best SSc-ILD management?

Answer 40

determined by disease extent, lung function trajectory monitor every 3-6months

Question 41

management options of ssc

Answer 41

corticosteroids (renal crises risk with high doses) >10mg immunosuppressants-cyclophosphamide and mycophenolate mofetil progressive fibrotic phenotype → antifibrotic e.g. nintedanib (anti fibrotic)

Question 42

Autoantibodies associated with SSC

Answer 42

Anti centromere Anti scl-70 associated with increased ILD