Interstitial Lung Disease Flashcards
What is the interstitium?
-Space between the capillary endothelial cells and alveolar epithelial cells
=Collagen
=Fibroblasts
=Dendritic cells
=Where gas transfer occurs so thin
What is ILD?
-Diseases in which there is inflammation and/or fibrosis primarily to the lung interstitium
Classification of ILDs
-Known causes
-Idiopathic
-Rare/miscellaneous
Types of ILD with known cause or association
-Inhaled dusts/ antigens/ fibres
-Iatrogenic
-Connective tissue disease associated
-Smoking-related
Examples of haled dusts/ antigens/ fibres
-Coal Worker’s Pneumonconiosis
-Asbestosis
-Silicosis
-Hypersensitivity pneumonitis due to birds, moulds, other exposures
Examples of iatrogenic ILD
-Drugs
-Radiation-induced
Examples of connective tissue disease associated
-Rheumatoid
-Systemic Sclerosis
-Other CTD
Examples of smoking related ILDs
-Respiratory-bronchiolitis ILD (RB-ILD)
-Desquamative interstitial pneumonia (DIP)
-Langerhans cell histiocytosis
Examples of idiopathic IDLs
-Sarcoidosis
-Idiopathic Usual Interstitial Pneumonia (UIP) = Idiopathic pulmonary fibrosis (IPF)
- Idiopathic non-specific interstitial pneumonia (NSIP)
-Cryptogenic organising pneumonia (COP)
-Idiopathic Acute Interstitial Pneumonia (AIP)
Examples of miscellaneous and rare ILDs
-Eosinophilic pneumonia
-Lymphangioleiomyamotosis
-Alveolar Proteinosis
-Lipoid pneumonia
-Lymphocytic Interstitial Pneumonia
Most common ILDs
-Sarcoidosis
-Idiopathic Usual Interstitial Pneumonia/ Idiopathic pulmonary fibrosis
General presentation of ILD
-Breathlessness
-Cough
-Incidental findings on CXR or CT
General investigations in ILD
-HRCT scan (high resolution)
-Lung biopsy
Drugs often associated with ILD
-Amiodarone
-Methotrexate
-Leflunamide
-‘Biologicals’ e.g. anti-TNF, Rituximab
-Nitrofurantoin
-Sulphasalazine (anti-inflammatory)
-Bleomycin
Drugs rarely associated with ILD
-Omeprazole
-Statins
-SSRI anti-depressants
ILD examination findings
-Clubbing (IPF, Asbestosis)
-Features of connective tissue disease (RhA, systemic sclerosis)
-Lung crepitations (mid and late respiratory)
CXR in ILD
-Bilateral diffuse infiltrates
=Nodular
=Reticular
=Reticulo-nodular
Pathogenesis of IPF
-Normal injury to alveolar epithelial cells and response
-IPF
=Aberrant repair process= overactive inflammatory response so overactive fibroblasts= transdifferentiate into myofibroblasts so lots of collagen deposition (fibroblastic foci)
=Type 2 alveolar epithelial cells hypertrophy with abnormal phenotype and can’t differentiate into Type 1
Histology of IPF
-Subpleural dominant disease
-Grossly distorted lung architecture
-Honeycomb fibrosis/ cysts
-Temporal and spatial heterogeneity (fibrotic lung and inflamed lung closely adjacent to normal lung)
-Fibroblastic foci
Epidemiology of IPF
-Occurs world-wide
-5-15 cases per 100,000 population
-4-5000 new cases per year in UK
-Lothian approx 90 new cases per year
-Median age at presentation approx 70 yr
-M:F 2:1
-Smokers: non-smokers 2:1
Symptoms in IPF
-Breathlessness 88%
-Dry cough 70% (bronchi stretches= irritable)
NOT
=Orthopnoea or PND
=Haemoptysis
=Wheeze
=Chest pains
Clinical signs in IPF
-Bibasal fine mid and late inspiratory (velcro) crepitations in 90%
-Clubbing 60%
Indication for CXR in primary care for IPF
-Aged 45 or older
-Persistent breathlessness
-With or without cough
-Bibasal chest crepitations
Spirometry in IPF
-Restrictive disease= reduced FEV1 and FVC therefore normal or raised FEV1/FVC ratio
-Early disease= normal spirometry
-With co-existing emphysema, spirometry may be normal or even obstructive (FEV1/FVC reduced)
-Change in FVC is the current ‘gold standard’ biomarker for IPF disease progression: >10% decline in FVC over 6-12 months predicts poorer prognosis
Lung volumes, gas transfer and walking tests in IPF
-Lung volumes are reduced in IPF
-TCO and KCO are reduced in IPF (the TCO tends to fall before the KCO)
-Patients with IPF (and others ILDs) tend to experience oxygen desaturation on exercise / walk tests
HRCT findings in IPF
-Reticular pattern which is made of intra-lobular lines
-Traction bronchiectasis / bronchiolectasis
-Honeycomb cyst formation
-These changes must be subpleural and basally dominant
1, First changes in phrenic angles
2. Shaggy hemidiaphragm and heart border
When is lung biopsy performed?
-Possible UIP pattern
=Consider risk vs benefit
=2% risk of death
Risk of surgical lung biopsy in suspected IPF
-Risk depends on patients co-morbidities
-Overall 30-day mortality around 1-2% and morbidity 10%
-Risk is higher in older patients with more extensive fibrosis disease on CT and poorer lung function
Prognosis in IPF
-Idiopathic pulmonary fibrosis (IPF) progressive disease with a median survival of 3 to 5 years following diagnosis
-Only 20% survive longer than 5 years
-IPF shortens life expectancy by around 7-9 years
-IPF has a lower survival rate than many cancers
2 drugs to slow rate of decline in IPF
-Pirfenidone
-Nintedanib
=Slows rate of decline in FVC by 50%
Mechanism of action of Nintedanib
Inhibitor of multiple tyrosine-kinases
-Inhibit growth factors in lung
Side effects and tolerability of Pirfenidone
-Nausea
-Moderate rash/ photosensitivity
-Dyspepsia
-Weight loss
-20% discontinuation
Side effects and tolerability of Nintedanib
-Nausea
-Diarrhoea
-Dyspepsia
-20% discontinuation
Non-pharmacological treatment of IPF
-Smoking cessation
-Treat co-existing acid reflux symptoms (? micro aspiration of gastric contents)
-Ambulatory and domiciliary oxygen
-Pulmonary rehabilitation – proven and cost effective in IPF
-Lung transplantation – only suitable for younger patients without comorbidities
What is Sarcoidosis?
Systemic disease of unknown aetiology characterised by the presence of non-caseating granulomas
Epidemiology of sarcoidosis
-Peak at 25-35 and 50-60
-Does not show in elderly
-More common in temperate climates
Organ-specific symptoms of sarcoidosis
-Skin – rash of various types
-Eyes - iritis
-Joints – arthralgia
-Neurological – facial nerve palsy
-Liver –cirrhosis
Systemic general symptoms of sarcoidosis
-Fatigue
-Symptoms of hypercalcaemia (polyuria, polydypsia, renal stones, constipation, confusion)
-Enlarged lymph nodes
-Night sweats
Pulmonary symptoms of sarcoidosis
-Cough- almost always dry (granulomas affecting bronchi)
-Breathlessness
Examination findings of sarcoidosis
-May be evidence of systemic disease (skin, eyes, splenomegaly, palpable lymphadenopathy)
-Chest examination is often normal in sarcoidosis.
-Crackles are infrequent - even with extensive abnormalities are present on CXR
Staging in pulmonary sarcoidosis
-Based on CXR appearance
- Bilateral Hilar Lymphadenopathy (BHL) with normal lung parenchyma, erythema nodosum
- BHL with lung infiltrates
- Lung infiltrates without hilar node enlargement on CXR
Pulmonary function tests in sarcoidosis
-Will be normal in stage 1 disease or mild stage 2 or 3 disease
-Usually, a restrictive defect with more extensive stage 2 or 3 disease
-Occasionally an obstructive defect is seen with sarcoidosis, implying endobronchial disease
Blood tests in sarcoidosis
-Be aware that sarcoidosis is a cause of hypercalcaemia
-Serum angiotensin converting enzyme (SACE) may be raised in sarcoidosis. This test is not specific for sarcoidosis but is sometimes used to monitor disease activity
Skin tests in sarcoidosis
-Patients with sarcoidosis exhibit ‘anergy’ characterised by a blunted T-cell response
-This can be demonstrated using the tuberculin skin test – it is usually negative in patients with sarcoidosis
Diagnostic biopsy in sarcoidosis
-Stage 1 sarcoidosis with erythema nodosum often does not need histological proof
-A confident diagnosis of Stage 2 or 3 sarcoidosis may require a biopsy
-Biopsy the easiest site e.g. skin, lymph nodes if enlarged
-In the lung, a transbronchial biopsy will be positive in 80% of cases
-Sometimes a surgical lung biopsy is needed
When to treat pulmonary sarcoidosis
-Stage 1 sarcoidosis spontaneously remits in 60% of patients within 1-2 years, so hardly ever warrants treatment
-Stage 2 and 3 sarcoidosis can spontaneously remit, or does not progress, in 20-40% of cases, so should only be treated if there is evidence of active progressive lung disease or chest symptoms
-Failure to treat progressive stage 2 or 3 sarcoidosis can lead to permanent lung scarring with irreversible loss of function (sometimes called stage 4 disease)
Treatment of pulmonary sarcoidosis
-Corticosteroids are the standard treatment for sarcoidosis
-No randomised controlled trials have been performed in pulmonary sarcoidosis
-Over 50 years of observational data shows that corticosteroids can be associated with resolving CXR appearances and improved lung function tests and symptoms
5 phases of steroid therapy in pulmonary sarcoidosis
- Initial control 2-4 weeks 40mg prednisolone
- Taper 2-4 months down from 40 to 5mg prednisolone
- Maintenance 3-9 months at 5mg prednisolone
- Taper by 1mg/month
- Observation period
-If relapse, restart steroids
-Total period typically 18-24 months
