Restrictive Lung Disease Flashcards by Elizabeth Akeju

What is restrictive lung disease?

Lung volumes are small, expansion is limited by
- Alterations to lung parenchyma - intrinsic disorders, e.g. ILD
- Compression/limited expansion of the lungs (pleural, chest wall, neuromuscular) - extrinsic disorders

How well did you know this?

Not at all

Perfectly

What is the lung parenchyma?

Alveolar regions of the lung

How well did you know this?

Not at all

Perfectly

What the different cellular components of the lung parenchyma and what are their functions?

Alveolar type 1 epithelial cell - gas exchange surface
Alveolar type 2 epithelial cell - surfactant to reduce surface tension; stem cell for repair
Fibroblasts - produce extra cellular matrix e.g. collagen type 1; also plays a role in cell signalling
Alveolar macrophages - phagocytose foreign material; surfactant

How well did you know this?

Not at all

Perfectly

What is the interstitial space and what is its function?

Space between alveolar epithelium and capillary endothelium
Contains lymphatic vessels, occasional fibroblasts and ECM
Provides structural support to lung
Very thin (few micrometers thick) to facilitate gas exchange

How well did you know this?

Not at all

Perfectly

What are interstitial lung diseases characterised by?

Inflammation or fibrosis in the interstitial space

How well did you know this?

Not at all

Perfectly

What are the different categories of interstitial lung diseases?

Idiopathic
Autoimmune-related
Exposure related, e.g. hypersensitivity pneumonitis
With cysts or airspace filling
Sarcoidosis
Others e.g. eosinophilic pneumonia

How well did you know this?

Not at all

Perfectly

Different patterns of fibrosis influence survival. True or false?

True

How well did you know this?

Not at all

Perfectly

What may be present in a history suggestive of ILD?

Progressive breathlessness
Non-productive cough
Limitation in exercise tolerance
Symptoms of connective tissue disease (joint problems, rashes, dry eyes/mouth)
Occupational and exposure history
Medication history (drug induced ILD)
Family history (up to 20% idiopathic ILDs are familial)

How well did you know this?

Not at all

Perfectly

What may you find on clinical examination of someone with suspected ILD?

Low oxygen saturations (resting or exertion)
Fine bilateral inspirations crackles
Digital clubbing
(+/- features of connective tissue disease)

How well did you know this?

Not at all

Perfectly

What are some investigations used in ILD?

Blood tests - anti-nuclear antibody (ANA), rheumatoid factor (RhF), anti-citrullinated peptide (CCP)
Pulmonary function tests
6-minute walk test (6MWT)
High resolution CT scan (HRCT)
Invasive testing: bronchoalveolar lavage (BAL) and surgical lung biopsy

How well did you know this?

Not at all

Perfectly

Why is a high-resolution CT scan useful in ILD diagnosis?

Can allow you to see the pattern of fibrosis - useful for distinguishing between disease types

How well did you know this?

Not at all

Perfectly

What oxygen saturation is associated with an increased risk of death in the 6MWT?

SpO2 </= 88%

How well did you know this?

Not at all

Perfectly

Describe the lung physiology in ILD

Scarring makes lungs stiff - reduced 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

How well did you know this?

Not at all

Perfectly

What type of ILD does this image show and what are the features of disease?

Usual interstitial pneumonia
Honeycomb cysts - advanced fibrosis

How well did you know this?

Not at all

Perfectly

What does this image show and what are the features of disease?

Non-specific interstitial pneumonia
Greyer areas - ground glass (hazy) opacifications

How well did you know this?

Not at all

Perfectly

What is show in this image and what are the features of disease?

Organising pneumonia
Consolidation (dense, white area)

How well did you know this?

Not at all

Perfectly

Which HCP may be involved in a diagnosis of ILD?

Integration of clinical, radiological +/- pathological information:
- Pulmonologist
- Radiologist
- Respiratory physiologist
- Rheumatologist
- Clinical nurse specialist
- Physiotherapist/occupational therapist

How well did you know this?

Not at all

Perfectly

What are the general principles of ILD management in early disease?

Pharmacological therapy - immunosuppressive drugs, antifibrotics
Clinical trials
Patient education
Vaccination
Smoking cessation
Treatment of co-morbidities - reflux, obstructive sleep apnoea, pulmonary hypertension
Pulmonary rehabilitation

How well did you know this?

Not at all

Perfectly

What are the general principles of ILD management in late disease?

Supplemental oxygen
Lung transplantation
Palliative care - symptom management, end-of-life care

What is idiopathic pulmonary fibrosis?

Progressive, scarring lung disease or unknown cause
Average decline in FVC = 150-200mls/year

What is the epidemiology of IPF?

6,000 new cases diagnosed each year
1% of UK deaths
Incidence increases with age - most >60yrs
More common in men

How common are acute exacerbations of IPF and what is the median survival?

Occur in 5-15% of patients
Median survival -> 3-4 months
In-hospital mortality ~50%

What is the median untreated survival of IPF?

3-5 years

What factors may predispose to IPF?

Genetic susceptibility
- MUC5B (airway mucin gene), DSP
Environmental triggers
- Smoke, viruses, pollutants, dust
Cellular ageing
- Telomere attrition, senescence

What is the proposed mechanism of IPF?

Injury to epithelium (type 1 alveolar cells) Injured cells die and release profibrotic factors which recruit fibroblasts Fibroblasts lay down scar tissue - limits/prevents gas exchange Remodelling of lung tissue - honeycomb cyst formation

Describe the meaning of spatial and temporal heterogeneity in the histopathology of IPF

Classic feature of usual interstitial pneumonia Areas of normal lung tissue juxtaposed with areas of diseased lung tissue

Label this image

These scans are characteristic of which condition?

Idiopathic pulmonary fibrosis

Immunosuppressants slow the progression of IPF. True or false?

False, actually harmful - increased risk of death and hospitalisation

What drugs are used to manage IPF?

Antifibrotics: - Nintedanib - tyrosine kinase inhibitor - Pirfenidone - a pyridine compound

Does antifibrotics treat IPF?

No, slow disease progression - not a cure

What is hypersensitivity pneumonitis?

ILD caused by immune-mediated response in susceptible and sensitised individuals to inhaled environmental antigens Genetic and host factors may explain why only a few exposed individuals get HP Involves small airways and parenchyma

How is hypersensitivity pneumonitis classified?

Acute HP - Intermittent, high level exposure - Abrupt symptom onset - Flu-like syndrome 4-12 hours after exposure Chronic HP - Long-term, low-level exposure - Nonfibrotic (purely inflammatory) - Fibrotic - increased risk of mortality

Describe HP epidemiology

Rare - incidence 1/100,000 (UK) Mean age onset 50-60 years M=F Less frequent in smokers 3-fold increased risk of death compared to general population

Describe the pathophysiology of HP

Antigen exposure and processing by the innate immune system Inflammatory response mediated by T-helper cells and antigen-specific immunoglobulin (IgG) antibodies (formation of immune complexes) Accumulation of lymphocytes and formation of granulomas

What are the key diagnostic elements in HP?

Detailed exposure history - antigen not identified in ~50% of cases Inspiratory ‘squeaks’ on auscultation (caused by existing bronchiolitis) Specific circulating IgG antibodies to potential antigens HRCT Bronchoalveolar lavage - lymphocyte count >30%

How is HP treated?

Complete antigen removal/avoidance Corticosteroids Immunosuppressants e.g. mycophenolate mofetil (MMF) and azathioprine (poor evidence base) Progressive, fibrotic HP - Nintedanib

What is systemic sclerosis associated (SSc) ILD?

SSc - autoimmune connective tissue disease characterised by immune dysregulation and progressive fibrosis that affects skin with variable organ involvement ILD develops in 30-40% of cases - most common cause of death Slow indolent course vs rapid progression (track lung function)

What is the epidemiology of SSc?

10-50/1,000,000 Affects young, middle-aged women

What factors may worsen prognosis of SSc ILD?

Male Older age Smoker >20% extent on HRCT FVC <70%

What are the two main types of SSc and how are they classified?

Classified based on skin involvement: - Limited cutaneous SSc (up to elbow) - pulmonary hypertension more common - Diffuse cutaneous SSc (more generalised, e.g. face involvement) - ILD more common

Label these features. What condition are they characteristic of?

Systemic sclerosis

What autoantibodies are associated with SSc?

Anti-centromere Anti-Scl-70 - increased risk of ILD

Describe the pathogenesis of SSc-ILD

Tissue injury -> vascular injury -> autoimmunity -> fibrosis -> inflammation-> more fibrosis

What type of ILD pattern is show in these HRCTs and what condition are they associated with?

Non-specific interstitial pneumonia (NSIP) Most common SSc-ILD pattern

How is SSc-ILD managed?

Determined by disease extent on HRCT and lung function trajectory (monitored every 3-6 months) Corticosteroids - controversial, risk of renal crisis (high doses) Immunosuppressants- cyclophosphamide, mycophenolate mofetil (MMF) Progressive fibrotic phenotype - Nintedanib Typically not suitable for lung transplant due to oesophageal dysmotility and reflux