Restrictive Lung Disease Flashcards
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
What is the lung parenchyma?
Alveolar regions of the lung
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
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
What are interstitial lung diseases characterised by?
Inflammation or fibrosis in the interstitial space
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
Different patterns of fibrosis influence survival. True or false?
True
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)
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)
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
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
What oxygen saturation is associated with an increased risk of death in the 6MWT?
SpO2 </= 88%
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
What type of ILD does this image show and what are the features of disease?
Usual interstitial pneumonia
Honeycomb cysts - advanced fibrosis
What does this image show and what are the features of disease?
Non-specific interstitial pneumonia
Greyer areas - ground glass (hazy) opacifications
What is show in this image and what are the features of disease?
Organising pneumonia
Consolidation (dense, white area)
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
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
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
