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Year 2 - BRS > 5.16 - Restrictive lung diseases > Flashcards

5.16 - Restrictive lung diseases Flashcards

1
Q

What are lung volumes like in restrictive lung disease?

A

Lung volumes are small - expansion is restricted

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2
Q

What are the two types of restrictive lung disease?

A
  • intrinsic lung disease - alterations to lung parenchyma e.g. interstitial lung disease (ILD)
  • extrinsic disorders - compress lungs or limit expansion
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3
Q

What are the different structures that can cause extrinsic disorders? (3)

A
  • pleural
  • chest wall
  • neuromuscular (decrease ability of respiratory muscles to inflate/deflate the lungs)
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4
Q

What is the lung parenchyma?

A

The alveolar regions of the lung

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5
Q

What are the important cellular components of the lung parenchyma? (4)

A
  • alveolar type 1 epithelial cell
  • alveolar type 2 epithelial cell
  • fibroblasts
  • alveolar macrophages
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6
Q

What is the function of alveolar type 1 cells?

A

Gas exchange surface (approx. 70cm2)

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7
Q

What is the function of alveolar type 2 cells? (2)

A

Surfactant to reduce surface tension, stem cells for repair

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8
Q

What is the function of fibroblasts?

A

Produce extracellular matrix (ECM) e.g. collagen type 1

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9
Q

What is the function of alveolar macrophages? (2)

A

Phagocytose foreign material, surfactant

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10
Q

What is the interstitial space?

A
  • space between alveolar epithelium and capillary epithelium
  • contains lymphatic vessels, occasional fibroblasts and ECM
  • structural support to lung
  • very thin (few micrometres thick) to facilitate gas exchange
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11
Q

What are alveolar macrophages closely associated with?

A

The lung epithelium

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12
Q

What is found in interstitial lung diseases?

A

Inflammation or fibrosis in the interstitial space (ILD = umbrella term for disorders causing fibrosis and scarring of lungs, over 200 ILDs recognised)

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13
Q

What can we use to classify interstitial lung disease?

A

ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002, 2013)

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14
Q

How can interstitial lung disease be classified? (6)

A
  • idiopathic - IPF (idiopathic pulmonary fibrosis), NSIP, DIP
  • autoimmune-related - CTD associated (connective tissue disease associated) e.g. RA-ILD, SSc-ILD
  • exposure related - hypersensitivity pneumonitis (HP), drug-induced
  • with cysts or airspace filling
  • sarcoidosis
  • others - eosinophilic pneumonia etc
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15
Q

What kinds of interstitial lung disease (ILD) have better/worse prognoses?

A
  • DIP/RBILD/cellular NSIP - 100% survival
  • fibrotic NSIP ~ 30% survival
  • UIP (usual interstitial pneumonia) - almost 0% survival, bad prognosis
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16
Q

How does interstitial lung disease present? (4)

A
  • progressive breathlessness
  • non-productive cough (dry)
  • limitation in exercise tolerance
  • symptoms of connective tissue disease
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17
Q

What do you ask about when taking a history for interstitial lung disease? (3)

A
  • occupational and exposure history
  • medication history (drug-induced ILD)
  • family history (up to 20% idiopathic ILDs are familial)
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18
Q

What would you find on clinical examination of someone with interstitial lung disease? (4)

A
  • low oxygen saturations (resting or exertion)
  • fine bilateral inspiratory crackles
  • digital clubbing
  • +/- features of connective tissue disease - skin, joints, muscle
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19
Q

What investigations can be done to diagnose ILD? (5)

A
  • blood tests e.g. anti-nuclear antibody (ANA), rheumatoid factor (RF), anti-citrullinated protein (CCP)
  • pulmonary function tests
  • 6-minute walk test (6MWT) - SpO2<88% associated with increased risk of death
  • high-resolution CT scan (HRCT) - essential to diagnosis
  • invasive testing: bronchoalveolar lavage (BAL), surgical lung biopsy (2-4% mortality)
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20
Q

What is the pathophysiology of interstitial lung disease (ILD)?

A
  • scarring makes the lung stiff and reduces lung compliance
  • reduced lung volumes (TLC, FRC, RV)
  • reduced FVC
  • reduced diffusing capacity of lung for carbon monoxide (DLCO)
  • reduced arterial pO2 - particularly with exercise
  • normal or increased FEV1/FVC ratio
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21
Q

What is essential for ILD diagnosis?

A

High-resolution CT (HRCT)

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22
Q

How does HRCT work?

A
  • CT uses X-rays to obtain cross-sectional images
  • rotating X-ray source and detectors spin around the patient gathering data
  • HRCT - thin slices and high-frequency reconstruction - gives good resolution at level of secondary pulmonary lobule (smallest functioning lung unit identifiable on CT)
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23
Q

How do high and low density substances differ in X-rays?

A
  • high-density substances e.g. bone absorb more X-rays and appear whiter
  • low-density substances e.g. air absorb few X-rays and appear darker
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24
Q

What three planes are images viewed in?

A
  • axial (perpendicular to long axis of body)
  • coronal (parallel to long axis of body)
  • sagittal
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25
Q

What HRCT pattern is seen in usual interstitial pneumonia (UIP)?

A

Honeycomb changes - bottom and edges of lungs (found in IPF etc)

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26
Q

What HRCT pattern is seen in organising pneumonia?

A

Ground-glass change and areas of inflammation

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27
Q

Why is multidisciplinary diagnosis important in ILD?

A

Integration of clinical, radiological +/- pathological information is needed to make a diagnosis

28
Q

Which members of the MDT are involved in diagnosis and managing ILD? (7)

A
  • physiotherapist and occupational therapist
  • clinical nurse specialist
  • radiologist
  • pulmonologist
  • respiratory physiologist
  • pathologist
  • rheumatologist
29
Q

How is ILD managed in early stages? (7)

A
  • pharmacological therapy - immunosuppressive drugs, antifibrotics
  • clinical trials
  • patient education
  • vaccination
  • smoking cessation
  • treatment of comorbidities - gastroesophageal reflux, obstructive sleep apnoea, pulmonary hypertension
  • pulmonary rehabilitation
30
Q

How is ILD managed in late/end stages? (3)

A
  • supplemental oxygen
  • lung transplantation
  • palliative care - symptom management, end-of-life care
31
Q

What is idiopathic pulmonary fibrosis? (IPF)

A
  • progressive, scarring lung disease of unknown cause
  • average decline in forced vital capacity (FVC) = 150-200mls per year
32
Q

What is the epidemiology of idiopathic pulmonary fibrosis like?

A
  • 6000 new cases diagnosed each year
  • 1% of all deaths in the UK
  • incidence increases with age - most >60 years
  • more common in men
33
Q

What is the clinical trajectory like in IPF like?

A
  • variable clinical trajectory - not everyone affected in the same way
  • differences in sub-clinical period, pre-diagnosis period and post-diagnosis period
  • differences in onset of disease, onset of symptoms, diagnosis and death
34
Q

What are acute exacerbations of IPF?

A
  • occur in 5-15% of patients
  • median survival 3-4 months
  • in-hospital mortality ~50%
35
Q

What kind of prognosis is IPF associated with?

A

IPF associated with a poor prognosis - median untreated survival 3-5 years

36
Q

What are the proposed predisposing factors for IPF? (3)

A
  • genetic susceptibility - MUC5B, DSP
  • environmental triggers - smoke, viruses, pollutants, dusts
  • cellular ageing - telomere attrition (short telomeres), senescence
37
Q

What is the proposed mechanism of IPF?

A
  1. injury
  2. alveolar epithelial cell dysfunction
  3. profibrotic macrophages
  4. aberrant fibroblast activity
  5. excess accumulation of ECM –> thickens interstitium and makes it harder to get air in and out of alveoli
  6. alveolar remodelling and honeycomb cyst formation (reduced gas exchange)
38
Q

What is IPF initiated by?

A
  • alveolar epithelial injury
  • denuded alveolar epithelium seen by electron microscopy
  • targeted injury to AECIIs (alveolar epithelial type 2 cells) in mouse model - increased collagen deposition
  • re-epithelialisation disturbed in IPF
39
Q

What is the histopathology of IPF like?

A
  • usual interstitial pneumonia (UIP) pattern
  • microscopic honeycomb cyst
  • fibroblastic foci = proliferating fibroblasts/myofibroblasts - active disease
  • spatial and temporal heterogeneity
40
Q

What are the characteristic features of IPF on a CT scan?

A
  • subpleural honeycombing (at edges)
  • traction bronchiectasis (widened bronchi due to pulling by damaged lungs)
  • basal predominance
  • textbook finding on CT: bilateral interstitial shadowing (typically small, irregular, peripheral opacities - ground-glass, later progressing to honeycombing)
41
Q

Is immunosuppression used for IPF?

A

Immunosuppression is harmful in IPF

42
Q

What did the PANTHER-IPF trial show with regard to immunosuppression?

A
  • immunosuppression is harmful in IPF
  • randomised, double-blind, placebo-controlled trial
  • combination treatment with prednisolone + azathioprine + N-acetylcysteine –> increased risk of death and hospitalisation
  • led to a change in the conventional treatment for IPF
43
Q

How can antifibrotics be used in IPF?

A

Antifibrotics slow disease progression in IPF but do not cure

Nintedanib: tyrosine kinase inhibitor
Pirfenidone: pyridine compound

44
Q

How can clinical trials be used to treat IPF?

A

Different clinical trials/drugs target different parts of the fibrotic pathways - alveolar space, epithelium, mesenchyme, endothelium, vascular space

45
Q

What is hypersensitivity pneumonitis (HP)?

A
  • ILD caused by immune-mediated response in susceptible and sensitised individuals to inhaled environmental antigens
  • genetic and host factors may explain why only few exposed individuals get HP
  • involves small airways and parenchyma
46
Q

How can hypersensitivity pneumonitis (HP) be classified?

A
  • acute HP: intermittent, high-level exposure
    • abrupt symptom onset, flu-like syndrome 4-12h after exposure
  • chronic HP: long-term, low-level exposure
    • nonfibrotic - purely inflammatory
    • fibrotic - associated with higher mortality
47
Q

What is an example of acute HP? (4)

A
  • going on holiday and contacting animal faeces
  • rat faeces
  • bird droppings
  • hot tubs/metals/foods
48
Q

What is the epidemiology of hypersensitivity pneumonitis (HP)? (6)

A
  • rare: incidence in UK ~1 per 100k
  • mean age onset 50-60 years
  • M = F
  • less frequent in smokers
  • worldwide prevalence varies due to differences in antigen exposure, agricultural, industrial practices etc
  • 3-fold increased risk of death compared to general population
49
Q

What is hypersensitivity pneumonitis driven by?

A
  • HP driven by immunological dysregulation
  • antigen exposure and processing by the innate immune system
  • inflammatory response mediated by T-helper cells and antigen-specific immunoglobulin (Ig) G antibodies
  • accumulation of lymphocytes and formation of granulomas
50
Q

What triggers hypersensitivity pneumonitis?

A

Environmental allergens: bacteria, mycobacteria, fungi, animal proteins, plant proteins, enzymes, chemicals, metals

51
Q

How do you do a diagnostic work-up of hypersensitivity pneumonitis? (5)

A
  • detailed exposure history - antigen not identified in ~50%
  • inspiratory ‘squeaks’ on auscultation - caused by coexisting bronchiolitis
  • specific circulating IgG antibodies (serum precipitins) to potential antigens
  • HRCT (ground-glass changes, air-trapping)
  • bronchoalveolar lavage (BAL) lymphocyte count >30%
52
Q

What HRCT changes are seen in hypersensitivity pneumonitis? (5)

A
  • centrilobular ground-glass nodule (bronchiolocentric inflammation)
  • air-trapping (narrowing of small airways)
  • ground glass (interstitial inflammation)
  • mosaic attenuation pattern
  • three-density pattern
53
Q

How is hypersensitivity pneumonitis treated? (4)

A
  • complete antigen removal/avoidance is crucial
  • corticosteroids often used
  • immunosuppressants e.g. mycophenolate mofetil (MML) and azathioprine used but poor evidence base
  • progressive, fibrotic HP - Nintedanib (antifibrotic)
54
Q

What is systemic sclerosis associated (SSc) ILD?

A

SSc is an autoimmune connective tissue disease characterised by immune dysregulation and progressive fibrosis that affects skin, with variable internal organ involvement

55
Q

What is the epidemiology of systemic sclerosis associated ILD like?

A
  • rare: 10-50 cases per 1million per year
  • affects young, middle-aged women
  • ILD develops in 30-40% and is most common cause of death - 10-year mortality of 40%
  • slow indolent course vs rapid progression
56
Q

What factors can worsen survival in SSc-associated ILD? (5)

A
  • male
  • older age
  • smoker
  • > 20% extent on HRCT
  • FVC<70%
57
Q

What are the clinical features of systemic sclerosis (SSc)? (5)

A
  • sclerodactyly
  • Raynaud’s
  • telangiectasias
  • abnormal nailfold capillaroscopy
  • digital ulcer
58
Q

What is CREST syndrome (SSc)?

A
  • Calcinosis (white calcium deposits in skin)
  • Raynaud’s phenomenon (spasm of blood vessels in response to cold/stress)
  • Esophageal dysfunction (acid reflux and decreased oesophagus motility)
  • Sclerodactyly (thickening and tightening of the skin on the fingers and hands)
  • Telangiectasias (dilation of capillaries causing red marks on surfaces of skin)
59
Q

How can SSc be classified based on skin involvement? (2)

A
  • limited cutaneous SSc - pulmonary hypertension more common
  • diffuse cutaneous SSc - ILD more common
60
Q

High levels of what antibodies can indicate SSc? (2)

A
  • anti-centromere (limited cutaneous)
  • anti-Scl-70 (diffuse cutaneous, associated with increased ILD)
61
Q

What is the pathogenesis of SSc-ILD?

A
  • tissue injury, vascular injury and autoimmunity trigger fibrosis
  • fibrosis: fibrocytes recruited and resident fibroblasts activated, myofibroblasts express alphaSMA and produce collagen –> ECM deposition
  • this triggers inflammation (Treg, Th17, Th2 –> IL4, IL5, IL13)
62
Q

What can trigger tissue injury in SSc-ILD? (4)

A
  • genetic predisposition
  • gastro-oesophageal reflux
  • oxidative stress
  • environmental stimuli:
    • organic solvents
    • silica
    • viruses
63
Q

What can trigger vascular injury in SSc-ILD? (3)

A
  • endothelial cell injury
  • tissue hypoxia
  • ineffective angiogenesis
64
Q

What are HRCT patterns in SSc-ILD?

A

Non-specific interstitial pneumonia (NSIP) pattern is the most common pattern (can also get UIP pattern)

65
Q

How is SSc-ILD managed?

A
  • determined by disease extent on HRCT and lung function trajectory (monitor every 3-6 months)
  • corticosteroid use is controversial and risk of renal crisis with high doses (>10mg/day)
  • immunosuppressives - cyclophosphamide, mycophenolate mofetil (MMF)
  • progressive fibrotic phenotype - Nintedanib (antifibrotic)
66
Q

Summary slide on restrictive lung disease.

A
  • interstitial lung disease (ILD) is an important cause of restrictive lung disease
    • characterised by inflammation or fibrosis in the interstitium which causes impaired gas exchange
    • pathogenesis, disease trajectory and treatment varies according to type of ILD
    • most common type is IPF which is associated with poor prognosis
  • other causes of restrictive lung disease include extrinsic disorders which compress lungs or limit expansion
    • diseases of pleura, chest wall and neuromuscular disease

Year 2 - BRS (84 decks)

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