Restrictive Lung Disease Flashcards
what is restrictive lung disease
Lung volumes are small and expansion of the lung is restricted
What are the types of restrictive lung disease
Intrinsic and extrinsic
What is intrinsic lung disease and give example
alterations to lung parenchyma.
interstitial lung disease (ILD)
What is extrinsic lung disease and give example
compress lungs or limit expansion
Pleural
Chest wall
Neuromuscular (decrease ability of respiratory muscles to inflate / deflate the lungs)
Define lung parenchyma
the alveolar regions of the lung
Name 4 components of the lung parenchyma
Alveolar type 1 epithelial cell
Alveolar type 2 epithelial cell
Fibroblasts
Alveolar macrophages
What do alveolar type 1 epithelial cells do
gas exchange surface (approx. 70m^2)
What do alveolar type 2 epithelial cells do
surfactant to reduce surface tension, stem cell for repair
What do fibroblasts do
produce extracellular matrix (ECM) e.g Collagen type 1
What do alveolar macrophages do
phagocytose foreign material, surfactant
What is interstitial space and its purpose
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
What are macrophages closely associated with
Lung epithelium
What do interstitial lung diseases involve
Inflammation or fibrosis in the interstitial space
What are the classifications of ILDs
Idiopathic - IPF, NSIP, DIP etc.
Autoimmune related - CTD associated (RA-ILD, SSc-ILD) etc.
Exposure related - Hypersensitivity pneumonitis (HP), drug-induced etc.
With cysts or airspace filling
Sarcoidosis
Others - Eosinophilic pneumonia etc
Key points in ILD history
Progressive breathlessness
Non-productive cough
Limitation in exercise tolerance
Symptoms of connective tissue disease?
Occupational and exposure history
Medication history (drug induced ILD. antibiotics, particularly nitrofurantoin.
immunosuppressant drugs, such as methotrexate)
Family history (up to 20% of idiopathic ILDs are familial)
Features of ILD in clinical examination
Low oxygen saturations (resting or exertion)
Fine bilateral inspiratory crackles
Digital clubbing
(+/- features of connective tissue disease – skin, joints, muscles)
ILD investigations
- Blood tests e.g. anti-nuclear antibody (ANA), rheumatoid factor (RhF), anti-citrullinated peptide (CCP)
- Pulmonary function tests
- 6-minute walk test (6MWT) – SpO2 ≤ 88% associated with increased risk of death
- High-resolution CT scan (HRCT) (Essential for ILD diagnosis)
Invasive testing: - Bronchoalveolar lavage (BAL)
- Surgical lung biopsy (2-4% mortality)
Lung physiology in ILD
Scarring makes the lung stiff - ↓ lung compliance
↓ Lung volumes (TLC, FRC, RV)
↓ FVC
↓ diffusing capacity of lung for carbon monoxide (DLCO)
↓ arterial PO2 – particularly with exercise
Normal or ↑ FEV1/ FVC ratio
How does HRCT work
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 functional lung unit identifiable on CT)
High vs low density substances on HRCT
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
HRCT patterns
Usual interstitial pneumonia
Non-specific interstitial pneumonia
Organising pneumonia
ILD management in early disease
Pharmacological therapy – immunosuppressive drugs, antifibrotics
Clinical trials
Patient education
Vaccination
Smoking cessation
Treatment of co-morbidities – gastroesophageal reflux, obstructive sleep apnoea, pulmonary hypertension
Pulmonary rehabilitation
ILD management in late disease
Supplemental oxygen
Lung transplantation
Palliative care – symptom management, end-of-life care
What is idiopathic pulmonary fibrosis (IPF)
Progressive, scarring lung disease of unknown cause
6,000 new cases diagnosed each year
1% of all deaths in UK
Incidence increases with age - most >60yrs
More common in men
Average decline in forced vital capacity (FVC) = 150 – 200mls / year
Acute exacerbations of IPF (AE-IPF)
Occur in 5-15% of patients
Median survival 3-4 months
In-hospital mortality ~50%
Median untreated IPF survival
3-5 years
IPF predisposing factors
Genetic susceptibility
-MUC5B, DSP
Environmental triggers
-smoke, viruses, pollutants, dusts
Cellular ageing
-telomere attrition, senescence
IPF mechanisms
- Altered microbiome
- Injury
- Alveolar epithelial cell dsyfunction and aberrant fibroblast activity
- Excess ECM accumulation
- Remodelling and honeycomb cyst formation
What medication is harmful in IPF
immunosuppression
IPF treatment
Antifibrotics - they slow down but don’t cure
Nintedanib - tyrosine kinase inhibitor
Pirfenidone – a pyridine compound
Drugs targeting fibrotic pathways in clinical trials
Galectin-3 inhibitor - TD139 combats injury
Cell based therapies targets epithelial cells
What is hypersensitivity pneumonitis (HP)
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
HP classifications
Acute HP - Intermittent, high-level exposure – abrupt symptom onset, flu-like syndrome 4-12 hrs after exposure
Chronic HP - Long-term, low-level exposure
Nonfibrotic (purely inflammatory)
Fibrotic – associated with higher mortality
HP epidemiology
Rare - incidence in UK ~ 1 per 100,000
Mean age onset 50 – 60 yrs
M = F
Less frequent in smokers
Worldwide prevalence varies due to differences in antigen exposure, agricultural, industrial practices etc.
3- fold ↑ risk of death compared to general population
HP pathophysiology
Driven by immunological dsyregulation
- Antigen exposure and processing by the innate immune system
- Inflammatory response mediated by T-helper cells and antigen-specific IgG antibodies
- Accumulation of lymphocytes and formation of granulomas
HP environmental antigens
Mouldy hay and straw
Humidifiers
Outdoor hot tubs
Birds (also feather pillows)
Rats
Paint/varnish
Diagnosing HP
Detailed exposure history – antigen not identified in ~50%1
Inspiratory ‘squeaks’ on auscultation - caused by the coexisting bronchiolitis
Specific circulating IgG antibodies (serum precipitins) to potential antigens
HRCT
Bronchoalveolar lavage (BAL) lymphocyte count >30%2
HP treatment
Complete antigen removal / avoidance is crucial
Corticosteroids often used
Immunosuppressants e.g. mycophenolate mofetil (MMF) and azathioprine used but poor evidence base
Progressive, fibrotic HP – Nintedanib (antifibrotic)1
What is systemic sclerosis associated (SSc) - ILD
SSc is an autoimmune connective tissue disease characterised by immune dysregulation and progressive fibrosis that affects skin, with variable internal organ involvement
Rare - 10 – 50 cases per 1,000,000 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
Male, older age, smoker, >20% extent on HRCT, FVC <70% worse survival
Types of SSc
limited cutaneous SSc
(Pulmonary hypertension more common)
or
diffuse cutaneous SSc
(ILD more common)
What is CREST
Associated with limited cutaneous SSc
Calcinosis - Ca deposits in skin
Raynaud’s
Esophageal dysfunction (acid reflux, decreased motility)
Sclerodactyly - thickening and tightening of skin on fingers and hands
Telangiectasias - dilated capillaries causing red marks on skin
Other clinical features of SSc
Abnormal nailfold capillaroscopy
Digital ulcer
SSc autoantibodies
Anti-centromere (more limited)
Anti-scl-70 (more diffuse)
Diffuse vs limited SSc
Limited = distal skin involvement.
Diffuse = Trunk outwards skin involvement
Pathogenesis of SSc-ILD
Tissue injury (genetic predisposition, oxidative stress)
Vascular injury
Autoimmunity
Fibrosis
Inflammation
HRCT patterns in SSc-ILD
Non-specific interstitial pneumonia (NSIP) pattern is the most common pattern
SSc-ILD management
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)1
Progressive fibrotic phenotype– Nintedanib (antifibrotic)2
