Restrictive Lung Disease / Interstitial Lung Disease

Question 1

compare and contrast the pathophysiology of interstitial lung disease with COPD

Answer 1

interstitial lung disease = restrictive in nature, predominantly a disease of the interstitium leading to fibrosis

• leads to reduced gas transfer due to fibrosis of interstitium
• dry cough with crackles

COPD = obstructive in nature, predominantly a disease of the alveoli and architecture of alveoli

• leads to reduced gas transfer due to loss of alveolar surface area
• wet cough with crackles, wheeze

Question 2

inorganic and organic dust exposure can lead to…?

Answer 2

pneumoconiosis- pathology dependent on the amount of dust retained, size/shape of particles/solubility and toxicity/additional irritants (smoke etc)

Question 3

how does coal workers pneumoconiosis present?

Answer 3

History: coal worker

examination: dyspnoea
investigations: small black fibrotic nodules in UPPER LOBE

Question 4

what does coal worker’s pneumoconiosis progress into?

Answer 4

progressive massive fibrosis

• large 2-10cm nodules which often cavitate - these patients develop increasing hypoxemia, pulmonary hypertension and cor-pulmonale

Question 5

what is silicosis?

Answer 5

silica associated pneumonitis

• generally a slow progressing pneumoconiosis
• silica activates the macrphages and stimulates a release of cytokines = fibrosis
• calcifies the edge of lymph nodes
• effects the upper lobes
• often get “egg shell” calcification in lymph nodes
• incresaed susceptibility to TB

Question 6

what is asbestosis?

Answer 6

restrictive disease

pathology goes as follows

1) pleural plaques - indicate exposure NOT illness
2) asbestosis - fibrotic lung disease usually LOWER LOBES diagnosed by seeing iron-laden asbestosis bodies
3) bronchial carcinoma - most common form of cancer associated with asbestos AND cigarretes (synergistic effect)
4) mesothelioma - pleural malignancy- associated solely with asbestosis but still less common than bronchial carcinoma

Question 7

what is hypersensitivity pneumonitis?

Answer 7

immunologically medicated dust disease - reaction to dusts, spores, fungi, animal proteins

ex) bird fancier’s lung, farmers lung,

Immune mediated as shown by

• increased T lymphs. cytokinds
• specific serum antibodies
• complement and Ig demonstrable (type 3 reaction)
• granulomas

Question 8

what makes hypersensitivity pneumonitis different to asthma?

Answer 8

asthma -= type 2 hypersensitivity - acute immediate onset upon exposure to antigen

allergic pneumonitis= type 3 hypersensitivity - acute onset 4-6 hours post exposure to antigen - no wheeze and no eosinophilia

Question 9

what is the pathology of hypersensitivity pneumonitis?

Answer 9

1. interstitial chronic inflammation
2. non-caseating small granulomas
3. fibrosis - more chronic cases

Question 10

what is sarcoidosis?

Answer 10

non-caseating granulomatous disease of uknown etiology

• relatively uncommon
• usually presents in young adults and may be picked up by chance
• may present acutely as fever, malaise, weight loss, lymphadenopathy and painful red skin nodules
• respiratory symptoms may be minimal
• often presents with lung symptoms: progressive SOB and cough

Question 11

what is the pathology of sarcoidosis?

Answer 11

it is an exaggerated cellular immune response skewing towards the CD4+ Th1 lymphocytes- macrophage activation and the formation of granulomas with serum hypergammaglobulinemia

Question 12

what would microscopy show in sarcoidosis?

Answer 12

well formed non-caseating granulomas with inclusion of giant cells

• calcified schaumann bodies and star-shaped asteroid bodies are seen typically

Question 13

what is idiopathic pulmonary fibrosis?

Answer 13

pulmonary fibrosis from unknown origin - may reflect repeated acute alveolitis - fibroblast proliferration

linked to smoking and genetics

reflects acute alveolitis

skewed towards fibroblast proliferation so steroids are less useful

Question 14

how does idiopathic pulmonary fibrosis present?

Answer 14

progressive SOB and relentless respiratory failure

• CXR lower zone opacities
• restrictive pulmonary function tests
• crackles
• decreased chest expansion
• finger clubbing

Question 15

what are the subtypes of idiopathic pulmonary fibrosis?

Answer 15

a) usual interstitial pneumonitis - ‘cobblestoned lungs’ or ‘honeycomb fibrosis’ - regional variation with subpleural fibrosis - poor prognosis
b) non-specific interstitial pneumonitis - younger patients with more exagerated inflammation- less temporal variability and better prognosis
c) desqaumative interstitial pneumonitis - young smokers - numerous intraalveolar macrophages with minimal fibrosis - respond well to steroids
d) cryptogenic organizing pneumonia - no interstitial fibrosis/honeycomb change- get intra-alveolar granulation tissue- often recover spontaneoulsly

Question 16

what connective tissue disorders are associated with pulmonary fibrosis?

Answer 16

rheumatoid arthritis, radiation and drug reactions

Question 17

what signs on chest Xray indicate interstitial lung diease?

Answer 17

bilateral nodules/fibrosis particularly effecting the

lower zones of the chest = RA, asbestosis, connective tissue disorders, idiopathic Interstitial lung disease, other drugs

upper zones of chest = sarcoid, coal workers pneumoconiosis, hypersensitvity pneumonitis, ankylosing spondylitis, radiation, TB

Question 18

the ‘signet ring sign’ on Xray is a sign of what?

Answer 18

Bronchiectasis

Question 19

how would usual interstitial pneumonitis present on CT?

Answer 19

remember this is worst prognosis condition in idiopathic interstitial lung disease - also the most common

• looks very similar on CT to asbestosis and result of rheumatoid arthritis - the presence of pleural plaques (asbestosis) or diffuse pleural thickening helps distinguish asbestosis from UIP
• patients with chronic hypersensitivity peumonitis or with end-stage sarcoid may develop a similar CT patter to UIP

Question 20

what is the most powerful predictor of mortality in usual interstitial pneumonitis?

Answer 20

6MWT - desaturation <88% on exercise = powerful predictor of mortality

Question 21

what complications are associated with UIP?

Answer 21

• pneumothorax
• lung cancer 10x fold increase incidence in UIP population
• pulmonary emboli
• left ventricular dysfunction

Question 22

what sort of treatments do we use for UIP?

Answer 22

anti-fibrotic therapy (perfinidone)

tyrosine kinase inhibitor - for TKs which mediate elaboration of fibrogenic growth factors VEGF etc. (nintedanib)

prevention of GORD/microaspiration - shown to slow disease progression - with PPI

lung transplant

Question 23

what does UIP look like on CT?

Answer 23

intralobular septal thickeing

honeycomb cysts

wide bronchus - all the way to edge with uneven edge appearance

Question 24

what does non-specific intesrtitial pneumonitis show on CT?

Answer 24

diffuse homongenous crushed glass appearance without honeycombing

Question 25

what can cause non-specific interstitial pneumonitis?

Answer 25

rheumatoid arthritis (remember can present before joint symptoms)

collagen vascular disease

hypersensitivity pneumonitis

drug reaction

Question 26

what might we find on imaginge cryptogenic organizing pneumonia?

Answer 26

pattern of organized blobs of peripheral consolidation dispersed throughout the lungs (unilateral or bilater)

Question 27

how does cryptogenic organized pneumonitis present?

Answer 27

presents similar to pneumonia

unresolving consolidation (non-infective)

cough, DOE, crackles, bronchial breathing

Question 28

how do we treat cryptogenic organized pneumonitis?

Answer 28

CCS - treated for 1 year to prevent relapse

treat associated airflow obstruction