Restrictive Lung Disease Flashcards
What is restrictive lung disease?
- Espansion of the lung is restricted by:
a) Intrinsic lung disease: - alterations to lung parenchyma [interstitial lung disease (ILD)]
b) Extrinsic disorders: - compress lungs or limit expansion:
1. Pleural
2. Chest wall
3. Neuromuscular (decrease ability of respiratory muscles to inflate / deflate the lungs)
[Lung volumes are small in restrictive lung disease]
What is meant by lung parenchyma? What are it’s cellular components?
“the alveolar regions of the lung”
CELLULAR COMPONENTS:
- Alveolar type 1 epithelial cell – gas exchange surface (approx. 70m2) [LINE ALVEOLAR REGION, THIN]
- Alveolar type 2 epithelial cell – surfactant to reduce surface tension, stem cell for repair [PREVENTS ALVEOLAR COLLAPSE]
- Fibroblasts – produce extracellular matrix (ECM) e.g Collagen type 1 [STRUCTURAL INTEGRITY & SIGNALLING]
- Alveolar macrophages – phagocytose foreign material, surfactant
What is Interstitial lung disease? What are the different types of ILD’s
“Inflammation or fibrosis in the interstitial space- space b/t alveolar epithelium and capillary epithelium”
- Idiopathic (a disease of unknown cause)
- Autoimmune related
- Exposure related
- With cysts or airspace filling
- Sarcoidosis
- Others (e.g. Eosiniophilic pneumonia)
(different types of restrictive lung diseases vary in prognosis)
What clinical presentations would you find in the history of Interstitial lung diseases?
- Progressive breathlessness
- Non-productive cough (dry)
- Limitation in exercise tolerance
- Symptoms of connective tissue disease (e.g, joint issues, rash, dry eyes/ mouth, etc)
- Occupational and exposure history (not just their current job)
- Medication history (drug induced ILD, http://www.pneumotox.com)
- Family history (up to 20% of idiopathic ILDs are familial)
What clinical presentations would you find in Interstitial lung diseases?
- Low oxygen saturations (resting or exertion) [Scarring of gas exchange surface]
- Fine bilateral inspiratory crackles
- Digital clubbing [swollen fingers and nails]
(+/- features of connective tissue disease – skin, joints, muscles)
What are the investigations in ILD?
- Blood tests e.g. anti-nuclear antibody (ANA), rheumatoid factor (RhF) [INDICATES RHEUMATOID A], anti-citrullinated peptide (CCP)
- Pulmonary function tests
- 6-minute walk test (6MWT) [see how far you can walk before complete oxygen saturation] – SpO2 ≤ 88% associated with increased risk of death
- High-resolution CT scan (HRCT) = pattern of disease
Invasive testing:
* Bronchoalveolar lavage (BAL) [flood lungs with saline & suck as much as possible out & study the sample under a microscope]
* Surgical lung biopsy (2-4% mortality)
Describe the lung pysiology in ILD
- Scarring makes the lung stiff - ↓ lung compliance
- ↓ Lung volumes (TLC, FRC, RV)
- ↓ FVC (forced vital capacity- indicates how bad the ILD is)
- ↓ diffusing capacity of lung for carbon monoxide (DLCO)
- ↓ arterial PO2 – particularly with exercise
- Normal or ↑ FEV1/ FVC ratio
How would you use a High-resolution CT (HRCT) – for ILD diagnosis
- 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 - density substances e.g. bone/ muscles absorb more x-rays and appear whiter
DENSE WHITE PATCHES CAN INDICATE PNEUMONIA AND ILD’s - Low - density substances e.g. air absorb few x-rays and appear darker
- Images viewed in axial, sagittal and coronal view
How would you manage the early stages of Interstitial lung disease ?
- Pharmacological therapy – immunosuppressive drugs (not suitable for every type of scarring), antifibrotics (prevent scarring)
- Clinical trials
- Patient education
- Vaccination
- Smoking cessation
- Treatment of co-morbidities – gastroesophageal reflux, obstructive sleep apnoea, pulmonary hypertension
- Pulmonary rehabilitation
How would you manage the late stages of Interstitial lung 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” (no cure currently- treatment attempts to slow it down)
- Incidence increases with age - most >60yrs
- More common in men
- Average decline in forced vital capacity (FVC) = 150 – 200mls / year
What are some features of the trajectory of idiopathic pulmonary fibrosis?
- Disease is progressive- patients can go through exacerbations
- Acute exacerbations of IPF (AE-IPF)
- Occur in 5-15% of patients
- Median survival 3-4 months
- In-hospital mortality ~50% - Patients never recover to original baseline after each exacerbation
Describe the mechanism of idiopathic pulmonary fibrosis
- Either:
-Genetic susceptibility (MUC5B, DSP)
-Environmental triggers (smoke, viruses, pollutants, dusts)
- Cellular ageing
cause injury to alveolar epithelium - Fibroblasts are recruited= aberrant fibroblast activity
- Leads to excess accumulation of ECM= scarring
- Leads to remodelling & honeycomb cyst formation (makes the lungs less efficient
Describe the Histopathology of IPF (idiopathic pulmonary fibrosis)
- Microscopic honeycomb cysts
- Airspaces replaced by scar tissue
- Fibroblastic foci= proliferating fibroblasts/ myofibroblasts (it is an active disease)
what are the characteristic features of IPF (idiopathic pulmonary fibrosis) on CT scan?
- Lungs shrink
- Subpleural honeycombing
- Traction bronchiectasis (airways ‘tugged apart’ by scar tissue in lungs)
What affect does immunosuppression have on idiopathic pulmonary fibrosis?
Immunosuppression is harmful in IPF
PANTHER-IPF trial (Randomized, double-blind, placebo-controlled trial)
- Combination treatment with steroids + immunosuppressants given to subjects
- increased risk of death and hospitalisation
- Led to a change in the conventional treatment for IPF
How is idiopathic pulmonary fibrosis treated?
Antifibrotics (slow disease progression in IPF but do not cure)
- Drugs target fibrotic pathways (e.g. Galectin- 3 inhibitor, Anti-IL-13)
What is hypersensitivity pneumonitis (HP)?
ILD caused by immune- mediated response in susceptible and sensitised individuals to inhaled environmental antigens
(Involves small airways and parenchyma)
How can you classify hypersentivity pneumonitis?
a) Acute HP - Intermittent, high-level exposure – abrupt symptom onset, flu-like syndrome 4-12 hrs after exposure
b) Chronic HP - Long-term, low-level exposure
* Nonfibrotic (purely inflammatory)
* Fibrotic – associated with higher mortality
Describe the mechanism for hypersensitivity pneumonitis
- 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 (switch from innate inflammatory response to adaptive)- possibly triggered by second hit? e.g. viral infection
What are some example of environmental antigens that could trigger HP?
- Moldy hay and straw
- Parrots
- Wind instruments (poorly cleaned)
- Outdoor hot tubs
- birds
- rats
How would you attempt to diagnose HP?
- Detailed exposure history – antigen not identified in ~50%
- Inspiratory ‘squeaks’ on auscultation - caused by the coexisting bronchiolitis
- Specific circulating IgG antibodies (serum precipitins) to potential antigens [indicates exposure not disease]
- HRCT
- Bronchoalveolar lavage (BAL) lymphocyte count >30%
How would you treat HP?
- 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)
What is Systemic sclerosis (SSc) ?
“SSc is an autoimmune connective tissue disease characterised by immune dysregulation and progressive fibrosis that affects skin, with variable internal organ involvement”
- Affects young, middle-aged women
- Slow indolent course vs. rapid progression
- Male, older age, smoker, >20% extent on HRCT, FVC <70% =worse survival
What are clinical features of systemic sclerosis?
- Sclerodactyly (thickening/ tightening of skin on the fingers)
- Abnormal nailfold capillaroscopy
- Digital ulcer (ulcers on the nails)
- Raynaud’s (causes some areas of the body — such as fingers and toes — to feel numb from reduced blood circulation)
- Telangiectasias (small, widened blood vessels on the skin, e.g. on the face)
How can you classify SSc?
Can be classified based on skin involvement -
a) limited cutaneous SSc
(Pulmonary hypertension more common)
b) diffuse cutaneous SSc
(ILD more common)
What autoantibodies cause SSc?
- Anti-centromere
- Anti-Scl-70 - associated with increased with ILD
Describe the pathogenesis of SSc-ILD
- Autoantibodies=
- Tissue injury (genetic predisposition, oxidative stress, environmental stimuli, etc)
- Vascular injury (tissue hypoxia & ineffective angiogenesis)
- Autoimmunity also leads to release of IL-6= Fibrocytes recuirted & fibroblasts are activated
- Myofibroblasts express aSMA and produce collagen
=Sclerosis (hardening of tissue)
What are the HRCT patterns in SSc-ILD?
HRCT (high resolution CT scan)
Non-specific interstitial pneumonia (NSIP) pattern is the most common pattern
How would you manage SSc?
- 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)
