Interstitial lung disease Flashcards
Sarcoidosis definition
Sarcoidosis is a multisystem inflammatory disease of unknown etiology that predominantly affects the lungs and intrathoracic lymph nodes with widespread non-necrotising granulomas
Presentation of sarcoidosis
- Approximately 5% of cases are asymptomatic and incidentally detected by CXR.
- If bilateral lymphadenopathy on CXR with no other symptoms- sarcoidosis
- Presentation depends on the extent and severity of the organ involved.
- Systemic symptoms occur in 45% of cases such as :
- Fever.
- anorexia
- Fatigue.
- Night sweats .
- Weight loss .
- Pulmonary, dyspnea on exertion, cough, chest pain, and hemoptysis (rare) occur in 50% of cases.
Diagnosis of sarcoidosis
Diagnosis on CXR! bilateral lymphadenopathy with no symptoms
dyspnea, cough, vague chest discomfort, and wheezing.
Chest radiographs in patients with sarcoidosis have been classified into four stages:
–stage 1, bilateral hilar lymphadenopathy without infiltration.
–stage 2, bilateral hilar lymphadenopathy with infiltration.
–stage 3, infiltration alone.
–stage 4, fibrotic bands, bullae, hilar retraction, bronchiectasis, and diaphragmatic tenting.
These so-called stages represent radiographic patterns and do not indicate disease chronicity or correlate with changes in pulmonary function
Sarcoidosis on pathology
Non necrotising granulomatous inflammation !!!
Diagnosis of exclusion
extrapulmonary mainfestations of sarcoidosis
SARCOID mnemonic
Skin – erythema nodosum
Arthritis esp. of feet, hands
Respiratory – bilateral hilar lymphadenopathy, pulmonary infiltrates
Cardiac – heart block, VT, heart failure
Ocular – anterior uveitis, can lead to blindness
Intracranial (brain) – chronic meningitis, seizures, neuropathy
Derangement of liver and renal function – hepatic granuloma (70% patients), hypercalcaemia (can lead to kidney stones and nephrocalcinosis)
Treatment of sarcoidosis
May not need any treatment
- steroids
- azothioprine, methotrecate
Prognosis of sarcoidosis
stage 1- 80% spontaneous remission
Stage 2 - 30% spontaneous remission
Pulmonary fibrosis defintion
Pulmonary fibrosis is a condition that causes lung scarring and stiffness. This keeps the body from getting enough oxygen. Increased scarring makes breathing difficult and affects the heart.
Lots of causes
NB Idiopathic pulmonary fibrosis (cxr) is the equivalent of the pathological condition Usual interstiital Pneumonitis- EXACTLY THE SAME
Causes of pulmonary fibrosis
1) Occupational & Environmental – Silicosis, Asbestosis, Hypersensitivity Pneumonitis
2) Drug Induced – Amiodarone, Nitrofurantoin, Methotrexate, Cocaine
3) Connective Tissue Diseases – Lupus, RA, Scleroderma
4) Primary Diseases – Sarcoidosis, LAM
5) Idiopathic (25%) – IPF, NSIP
6) Genetics
>200 CAUSES!
Idiopathic pulmonary fibrosis definition
a specific form of chronic fibrosing interstitial pneumonia of unknown aetiology
limited to the lung
Key clinical features of idiopathic pulmonary fibrosis
Age of onset > 50,
male > female
Progressive breathlessness, productive cough, cyanosis
Respiratory failure, cor pulmonale, pulmonary hypertension
Fine bilateral end-inspiratory crackles
Finger clubbing (2/3)
usually a h/o cigarette smoking
Relevant points on clinical history of IPF
Occupation
Environment
Past medical history
Drugs
Travel
Smoking
Diagnosis of idiopathic pulmonary fibrosis
Lung Function Tests
- Restrictive defect
- FEV1 to FVC ratio normal to high (both values reduced)
- CO gas transfer reduced
Arterial Blood Gases - Type 1 Respiratory Failure
- caused by a combination of alveolar capillary block (loss of capillary volume) and V/Q mismatch
- PaCO2 normal or low owing to hyperventilation
Radiology
- changes predominantly at lung bases
- CXR -
- ground glass changes*→ irregular reticulonodular shadowing → honeycombing
- High resolution CT Chest
- 3 biopsys from three different lobes of lung
- subpleural reticular abnormalities
- honeycombing - thick-walled cysts 0.5 - 2 cm in diameter in respiratory and terminal bronchioles
- traction bronchiectasis
- *ground glass changes (usually an HRCT comment) - hazy areas of increased attenuation in the lung with preserved bronchial and vascular markings, caused by alveolar wall inflammation or thickening and/or partial air-space filling
Macroscopic features of idiopathic pulmonary fibrosis
pleural surfaces of the lung are “cobblestoned”
fibrotic areas of lung - firm rubbery and white
disease mainly basal and subpleural, with thickening of the interlobular septae
Histology of IPF
patchy interstitial fibrosis, varies in intensity and age (temporal heterogeneity)
fibroblastic foci in early fibrosis - areas of fibroblastic/myofibrobalastic proliferation - become less cellular as disease progresses and collagen deposited
Pathogenesis of IPF
- “repeated cycles” of epithelial activation/injury by some unidentified agent
- abnormal activation of epithelial cells lead to a dysregulated repair process
- inflammatory pathways also promote fibrosis
- induction of a Th2 type T cell response seen
- Abnormal epithelial repair at site of injury/inflammation leads to the formation of the fibroblastic foci
Cell types involved in IPF
- eosinophils, mast cells, macrophages and lymphocytes
- release cytokines such as IL-4, IL-1, TNFα and IFNγ
- damaged epithelial cells
- activated to release growth factors - TGFβ1, FGF, IGF1, PDGF
- type 1 pneumocytes are reduced
- injured cells produce TGFβ1 which promotes the transformation of fibroblasts to myofibroblasts
- fail to develop from type 2 pneumocytes add to the deveopment of dysfunctional alveolar epithelium
- reduced levels of calveolin 1, an anti-fibrotic molecule produced by these cells
- fibroblasts/myofibroblasts
- myofibroblasts secrete excessive amounts of extracellular matrix proteins, mainly collagens
Other molecules which may be invovled
- Matrix metalloproteinases (MMPs)
- Molecules produced by activation of the coagulation cascade
Genetic factors associated with IPF
No genetic factors consistently associated with sporadic cases of IPF
MUC5B gene polymorphisms is associated with familial cases of IPF
Management of IPF
Steroids and immunosuppressants are not routinely recommended for treatment of IPF
- Steroids not effective in most cases
- Azathioprine may worsen prognosis when used with prednisolone
No longer advised to give the “triple therapy”of steroids+azathioprine+N-acetylcysteine
N-acetyl cysteine
- does not improve survival or slow lung function decline
- is a mucolytic, so might be tried if a patient has cough or sputum, as has little toxicity
Pirfenidone
recently approved for use in IPF (patients with FVC 50 - 80 % predicted)
antifibrotic and anti-inflammatory effects; slows lung function decline
mechanism of action unclear but likely to suppress fibroblast proliferation, so reducing the production of fibrosis-associated proteins and cytokines
Nintedanib
- intracellular inhibitor of multiple tyrosine kinases
- slows lung function decline in recent trial. (Not yet approved for use in UK)
Long term oxygen therapy
Diuretics for fluid retention if develop cor-pulmonale
Antibiotics to treat infection
Lung transplantation in younger patients (age < 65)
Prognosis of IPF
3-5 years from time of diagnosis
Upper lobe pulmonary fibrosis causes
Sarcoidosis
TB
Pnemonoconiosos
ABPA
Lower lobe fibrosis causes
Bronchiectasis
Asbestosis
extrinsic allergic alveolitis definition
IgG mediated type III and IV hypersensitivity reaction to inhaled particles causes pneumonitis
Causes of EAA
Farmers lung: thermophillic actinomyces in mouldy hay
Bird fanciers lung : seen in keepers of pigeons and budgerigars. Due to keratin in faeces and feather bloom
Mal workers lung: aspergillus calcatus
Mushroom workers lung: thermophilic actinomyces
Clinical features
- fever, cough, breathlessness 4-9 hours after exposure. No wheeze. settles in 48 hours
- chronic disease - dypsnoea in strain, sputum production, fatigue, anorexia, weight loss
Investigations of EAA
CXR
- normal
- nodular shadows
- hazy infiltrate
Spirometry
- irreversible fibrosis and restrictive spirometry
Serum precipitants
No eosinophillia
Bronchoalveolar lavage or transbronchial biopsy
Treatment of EAA
Avoidance of precipitant and steroids in acute illness
