Restrictive Lung Diseases Flashcards
What is restrictive lung disease?
Lung volumes are small
Expansion of the lung restricted by……
Intrinsic lung disease -
—alterations to lung parenchyma interstitial lung disease (ILD)
Extrinsic disorders -
compress lungs or limit expansion
—Pleural
—Chest wall
—-Neuromuscular (decrease ability of respiratory muscles to inflate / deflate the lungs
What are the important cellular components of the lung parenchyma?
Lung parenchyma = the alveolar regions of the lung
Alveolar type 1 epithelial cell – gas exchange surface (approx. 70m2)
Alveolar type 2 epithelial cell – surfactant to reduce surface tension, stem cell for repair
Fibroblasts – produce extracellular matrix (ECM) e.g Collagen type 1
Alveolar macrophages – phagocytose foreign material, surfactant
What is the interstitial space?
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 does interstitial lung disease involve?
Inflammation or fibrosis in the interstitial space
What are the types of interstitial lung diseases?
Idiopathic
Auto-immune related
Exposure related
With cysts or airspaces filling
Sarcoidosis
Others e.g. eosinophilic pneumonia
What is the clinical presentation in terms of history for ILD?
Progressive breathlessness
Non-productive cough
Limitation in exercise tolerance
Symptoms of connective tissue disease?
Occupational and exposure history
Medication history (drug induced ILD, http://www.pneumotox.com)
Family history (up to 20% of idiopathic ILDs are familial)
What is the clinical presentation in terms of clinical examination in ILD?
Low oxygen saturations (resting or exertion)
Fine bilateral inspiratory crackles
Digital clubbing
(+/- features of connective tissue disease – skin, joints, muscles)
What are the investigations for ILD?
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)
Invasive testing:
—–Bronchoalveolar lavage (BAL)
—–Surgical lung biopsy (2-4% mortality)
Explain the 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
Look at patterns of forced expiration**
How does a High-resolution CT (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 - 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
Look at HRCT patterns in pneumonia**
Who in the MDT is involved in diagnosis?
Integration of clinical, radiological +/- pathological information to make a diagnosis
Radiologist
Clinical nurse specialist
Physiotherapist/occupational therapist
Pulmonologist
Respiratory physiologist
Pathologist
Rheumatologist
What are the variables evaluated during an MDT?
Clinical information
Environmental exposures
Biology and autoimmunity
Familial history / genetic information
PFT
CT
Serological testing
Biopsy
Bronchoscopy / BAL
Longitudinal ILD evolution
What are general principles of ILD management in terms of 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
What are general principles of ILD management in terms of 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
What is the prognosis of IPF?
Median untreated survival 3 - 5 years
What are the proposed mechanisms of IPF
Predisposing factors
Genetic susceptibility
-MUC5B, DSP
Environmental triggers
-smoke, viruses, pollutants, dusts
Cellular ageing
-telomere attrition, senescence
What is IPF initiated by?
Alveolar epithelial injury
Denuded alveolar epithelium seen by electron microscopy
Targeted injury to AECIIs in mouse model – ↑ collagen deposition
Re-epithelialization disturbed in IPF
Look at the histopathology of IPF**
Microscopic honeycomb cyst
Fibroblastic foci
What are the characteristic features of IPF on CT scan?**
Axial plane - subpleural honeycombing
-traction bronchiectasis
Coronal plane- basal predominance
What is harmful in IPF?
Immunosuppression
What do antifibrotics do in IPF?
Slows disease progression but do not cure
e.g. nintedanib - tyrosine kinase inhibitor
-pirfenidone - a pyridine compound
What do drugs target in fibrotic pathways in clinical trials***
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 few exposed individuals get HP
-Involves small airways and parenchyma
What is acute HP?
Intermittent, high-level exposure – abrupt symptom onset, flu-like syndrome 4-12 hrs after exposure
What is chronic HP?
Long-term, low-level exposure
Nonfibrotic (purely inflammatory)
Fibrotic – associated with higher mortality
What is the mean onset age for HP?
Does smoking increases frequency?
50-60yrs
Yes
How is 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
Explain the diagnostic work up of 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
What is the treatment of 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 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
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
What are the clinical features of SSc?
Classified based on skin involvement -
limited cutaneous SSc
(Pulmonary hypertension more common)
or
diffuse cutaneous SSc
(ILD more common)
Autoantibodies –
—Anti-centromere
—Anti-Scl-70 - associated with increased with ILD
Explain further using images what the clinical features of SSc are? ***
Sclerodactyly
Raynaud’s
Telengectasias
Abnormal nailfold capillaroscopy
Digital ulcer
Explain the pathogenesis of ILD?***
Tissue injury
Vascular injury
Autoimmunity
Inflammation
Fibrosis
What are HRCT patterns in SSc-ILD?**
Non-specific interstitial pneumonia (NSIP) pattern is the most common pattern
What is the management of SSc-ILD?
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
