Interstitial Lung Diseases Flashcards
what is pulmonary Interstitium?
the space between the alveolar epithelium and endothelial basement membrane. Fibroblasts and connective tissue lie here. This is where gas exchange occurs.
is pulmonary Interstitium visible radiographically?
The pulmonary Interstitium is not normally visible radiographically (chest x ray/ CT scan).
It only becomes visible when there is disease present (i.e. oedema, fibrosis, tumour) which increases its volume & attenuation
what are the 3 subdivisions that the Interstitium is composed of?
double check if we need to know this?
Bronchovascular Region: surrounds bronchi, arteries, & veins from the lung root to the level of respiratory bronchiole.
Parenchymal region: situated below the alveolar & capillary basement membranes.
Subpleural Region: situated beneath the pleura & in the interlobular septae
what does gas exchange require?
Functioning alveoli (alveoli that allow for gas exchange)
Alveolar ventilation
Pulmonary circulation (blood circulating around alveoli)
what are the 3 things that impairment of gas exchange could come from?
- Impaired ventilation:
Central (due to impairment in nervous system)
Mechanical (swallowed something/blockage) - Impaired circulation: blockage of circulation around alveolus
- Abnormal alveoli structure: prevents gas exchange from happening.
when determining the effect of lung disease or pulmonary fibrosis, what is the main things that need to be measured?
what would you see in a spirometry of interstitial lung disease?
restrictive spirometry
due to effects of fibrosis in the interstitium and stiffness:
Low FVC
Normal/high FEV1/FVC
the other important measures are lung volumes:
there’s a reduction in TLC and RV
what is the difference between intrapulmonary and extrapulmonary restrictive spirometry
Intrapulmonary - effect the interstitium/ gas exchange
* Fibrosis
* Inflammation/Infection - pneumonia
* Sarcoidosis
* Atelectasis
- FVC, FEV1 decrease
- Ratio normal or raised
- Slope of curve increase
- TLC/RV decrease
- Diffusion decrease
Extrapulmonary
* Pleural cavity - pleural thickening (due to asbestos)
* Neuromuscular
* Chest wall
* Obesity - splinting of diaphragm
- FVC, FEV1 decrease
- Ratio normal
- Slope of curve normal or
decrease - TLC/RV decrease
- Diffusion normal
what is pulmonary fibrosis and when does it occur?
Pulmonary fibrosis: scarring of the Interstitium
Usually occurs after inflammation - formation of fibrous tissue (scaring).
As a result of pulmonary fibrosis the lungs become stiff –> increasing the work of breathing, and gas exchange across the alveoli is impaired.
what would the results of pulmonary fibrosis spirometry be?
You get restrictive spirometry:
Low FVC
Normal/high FEV1/FVC ratio
low RV
low TLC
DLCO is low
what is Interstitial lung disease (ILD)?
Interstitial lung disease (ILD): is an umbrella term for a whole range of diseases that causes fibrosis in the Interstitium.
what are the 8 types of interstitial lung disease?
- Cryptogenic fibrosing alveolitis (CFA):
- Cause unknown.
- Also known as idiopathic pulmonary fibrosis
- Usual interstitial pneumonitis - Non-specific interstitial pneumonitis
- RB-ILD (respiratory bronchiolitis associated interstitial lung disease)
- DIP (desquamative interstitial pneumonia)
- COP (cryptogenic organising pneumonia)
- LIP (Lymphoid interstitial pneumonia)
- Extrinsic ‘Allergic’ Alveolitis (EAA)
- Sarcoidosis
what is the aetiology of pulmonary fibrosis?
Pulmonary fibrosis can be widespread throughout the lungs or restricted to the upper or lower zones.
The causes vary…
how do you work out the cause of pulmonary fibrosis?
We can work out the cause of pulmonary fibrosis using the following:
Autoantibody screen - provides evidence for/against connective tissue disease
Drug history - to see if a drug has caused fibrosis
Take occupational and exposure history
what is the incidence rate of pulmonary fibrosis?
Approx 50/ 100,000 (30,000+)/yr
* 8/ 100,000 ( 5,000/yr) Idiopathic Pulmonary Fibrosis (IPF)
* ~ 40% autoimmune rheumatic / connective tissue diseases (CT-ILDs)/ sarcoidosis
* ILD found in 10%-40% patient with Rheumatoid arthritis;
* 70-90% Systemic sclerosis
* ~ 40% idiopathic of which ~50% IPF
what are some clinical features of pulmonary fibrosis?
Symptoms (may not occur until disease is more advanced):
Dry cough (usually presents first)
Dyspnoea (shortness of breath)
Fine end inspiratory crepitations (crackling) at base of lungs
Usually occurs in middle age
Occurs in men > women
what are the signs of pulmonary fibrosis on a chest X ray?
what are the signs of pulmonary fibrosis on a CT scan?
how do you manage pulmonary fibrosis?
Management depends on cause, histology, severity and rapidity of progression.
Example:
UIP (usual interstitial pneumonia) 🡪 pirfenidone or nintendanib
Autoimmune disease 🡪 immunosuppression
Lung transplantation 🡪 if patient is becoming hypoxic because you can’t treat inflammation.
PFTs (pulmonary function test) are then used to monitor patients to see how they are responding to treatment.
Depends on cause, histology, severity & rapidity of
progression.
*IPF pirfenidone or nintendanib
*Progressive pulmonary fibrosis
nintendamib
* Autoimmune disease immunosuppression
* Transplantation
* Monitor using PFTs
Depends on type and cause!
* COP – corticosteroids
* Smoking-related ILD – respiratory bronchiolitis ILD (RB-ILD)
/desquamative interstitial pneumonia (DIP) – smoking
cessation
* Hypersensitivity pneumonitis – avoidance of causative
agent, corticosteroids
* CTD-ILD – immunosuppression – corticosteroids,
cyclophosphamide
* Sarcoidosis - corticosteroids
why may biopsies of the lung be required?
how are they performed?
Biopsies are required if:
It is not clearly UIP on a high-resolution CT scan.
No clear cause on antibody tests/history etc.
Biopsies can be performed using
Bronchoscopic washings (BAL) + transbronchial biopsy (collect cells)
Surgery (VATS): Wedge of lung taken out and sent to pathology.
what are the types of interstitial lung disease?
UIP = Usual interstitial pneumonitis
NSIP = non-specific interstitial pneumonitis
what is Usual interstitial pneumonitis?
UIP = Usual interstitial pneumonitis
Occurs in basal region of the lung
Presents in the peripheral/sub-pleural regions
Not much ground-glass change seen on CT (as it is an established fibrosis)
Honeycombing seen
Blood test will be negative for antibodies etc.
what is non-specific interstitial pneumonitis?
Anything non-specific (see a mix of fibrosis, honeycombing, +/- ground glass change, not mainly in lower zones) will be labelled as this.
Generally better prognosis than classical UIP
Causes: lots e.g. exposure to asbestos, autoimmune diseases etc.
explain the other 4 types of ILD?
- RB-ILD (respiratory bronchiolitis associated interstitial lung disease)
- DIP (desquamative interstitial pneumonia)
Both are:
- Smoking related
- Look for emphysema on CXR
- Treated with smoking cessation - COP (cryptogenic organising pneumonia)
- Has a more acute onset
- Responds well to steroids
- Present like pneumonias - LIP (Lymphoid interstitial pneumonia)
- Usually now called NSIP
- Associated with autoimmune causes
what are some rarer types of ILD?
Extrinsic ‘Allergic’ Alveolitis (EAA)
Granulomatous Lung Diseases
Sarcoidosis (Type of ILD)
what is Extrinsic ‘Allergic’ Alveolitis (EAA)?
Caused by inhalation of organic particles
Farmer’s lung (inhalation of hay fungi)
Bird fancier’s lung (bird proteins),
Mushroom worker’s lung (various fungi)
Cause found when taking a history (occupation, pets etc)
You get an antibody formation (‘precipitins’) & T cell sensitisation –> leads to type III/IV hypersensitivity lung damage
what are the 2 types of Extrinsic ‘Allergic’ Alveolitis (EAA)?
symptoms of each one?
Acute (confused with asthma or bronchitis)
Symptoms (4-hr post exposure):
- Dry cough
- Hypoxia
- Fevers,
- Myalgia
Removing exposure to organic particle –> substantial improvement 1-2d, complete recovery 7-10 d
Chronic (continuous exposure to particles) (may be confused w/ CFA)
Symptoms:
- progressive dyspnoea
- irreversible lung damage
- Treat with steroids or removing irritant
The presentation sub-acute (acute/chronic) is determined by?
The presentation (acute/chronic) is determined by type of exposure:
Pigeon breeder cleaning coop out:
Short and intense exposure => acute EAA
Parrot Owner
Long and low-grade exposure => chronic EAA = fibrosis
Diagnosis of EAA
how do you diagnose EAA?
- Identification of potential antigen
- Characteristic clinical & Radiological findings:
- CXR & High-resolution CT –> Upper lobe fibrosis
- Blood test –> +ve avian/aspergillus precipitins, N IgE (antigens)
what is the treatment for EAA?
antigen avoidance - may get better with just this.
Steroids (anti-inflammatory)
Treatment Results (removal of parrot)
Image 1: lots of ground glass change
Image 2: no more ground glass changes.
what is Granulomatous Lung Diseases and what is it caused by?
Granulomatous lung disease: a broad group of infectious and non-infectious conditions characterised by the formation of granulomas.
Can be caused by:
Bugs
* TB
* Fungi (Histoplasmosis/ Blastomycosis/Coccidiodomycosis)
Inflammatory
* Sarcoidosis
* Extrinsic Allergic Alveolitis
Vasculitic
* Churg-Strauss
* Wegener’s - Granulomatosis with polyangiitis
* Polyartetitis nodosa
what is Sarcoidosis and what is its presentation?
Multisystem disease
Unknown cause
Presentation:
Non-caseating (non-necrotising) granulomas
More common in Afro-Caribbean (x3)
treatment for Sarcoidosis?
Rule of third’s:
1/3 get better without treatment
1/3 require short term course of steroids
1/3 some will require longer term treatment
what is pulmonary sarcoidosis and what is its presentation?
sarcoidosis in the lung
Presentation
Bilateral Hilar lymphadenopathy (blue circle)
Fibrosis (not in this image)
Infiltrates
Pulmonary infiltrate: is a substance denser than air, such as pus, blood, or protein, which lingers within the parenchyma of the lungs
Symptoms: Lofgren’s syndrome
symptoms of pulmonary sarcoidosis?
Symptoms: Lofgren’s syndrome
Bilateral Hilar lymphadenopathy
Erythema nodos (redness occurs in shins)
Polyarthralgia (pain and swelling in joints)
85% of patients will resolve spontaneously
what are the symptoms of Sarcoidosis outside the lung (extrapulmonary disease)?
effect heart, eyes, skin, neuro, liver
how do you investigate for Sarcoidosis?
Full lung function test
High resolution CT scan
ECG - conductance defects may be observed
what is the treatment of Sarcoidosis?
Steroids
Other steroid sparing immune suppressants
Other newer anti-inflammatory mAB
what is Vasculitis?
examples?
diagnosis?
an autoimmune disease
It causes inflammation of BVs - may obstruct and/or bleed
Often multisystemic, commonly effect kidneys
Examples:
Wegner’s granulomatosis
Goodpasture’s disease
Diagnosis:
Immunology
Kidney, Renal and Lung biopsies
what are the symptoms of a pulmonary haemorrhage?
Symptoms:
Dyspnoea
Haemoptysis (coughing up blood)
Looks opaque on CXR
PFTs show high gas transfer (contamination of blood in lungs),
Visualise via bronchoscopy
Fibrosis may occur due to healing
what is Wegener’s Disease?
Mainly effects upper airway
- Caused by granulomas which then bleed
- Cause sinusitis (inflammation of paranasal sinuses)
- Causes Saddle nose
Lungs
- Cause Haemorrhage
- Causes cavity formation
- May be mistaken for atypical pneumonias/TB
what is the mortality and morbidity rate of ILD?
High morbidity and mortality
* Median survival 3 years
* 1 in 5 survive > 5 years
statistics worse than lung and oesophageal cancer at 5 years
When should you suspect ILD?
History consistent with the diagnosis
* Shortness of breath on exertion
* Chronic cough
* History of CTD
* History of exposure to precipitating factor – history is KEY!
what are the causes of pulmonary fibrosis?
- IPF
- CTD – RA/ Scleroderma/ Ank Spond
- Sarcoidosis
- TB
- Drugs – Amiodarone/ Nitrofurantoin
- Radiotherapy
- Recurrent aspiration
- Occupational exposure
(asbestos, metalwork,
smoke, dusts) - Pets (birds)
- Hobbies (composting)
Upper Lobe – S-CHAARTS
* Sillicosis/Sarcoidosis
* Coal worker’s pneumoconiosis
* Histiocytosis
* Ankylosing spondylitis
* Allergic bronchopulmonary aspergillosis
* Radiation
* Tuberculosis
* Smoking
Lower Lobe - RASID
* Rheumatoid arthritis
* Asbestosis
* Scleroderma
* Idiopathic Pulmonary Fibrosis
* Drugs: busulphan, bleomycin, nitrofurantoin, hydralazine,
methotrexate, amiodarone
Traction Bronchiectasis
* Traction bronchiectasis – where the fibrosis has pulled the airways apart
but airways themselves normal
Distribution is key to diagnosis
IPF apical – basal gradient – bases worst.
* HP – upper zones worst
* Sarcoidosis – small nodules perilymphatic – upper & mid-zone
predominance
Is it really idiopathic?
- RhF, anti-CCP
- ANA
- ANCA
- ENA
- Fungal precipitins
- Avian precipitins
- History, History, HISTORY
NB lung disease may
manifest before other
signs/symptoms in CTD
Other investigations
* Bronchoalveolar lavage
* Transbronchial biopsy
* EBUS-guided LN biopsy
* VATS-lung biopsy
What do you need to make a diagnosis?
Idiopathic Pulmonary Fibrosis
- Chronic, progressive, fibrosing interstitial pneumonia of unknown
cause - UIP – histological pattern
- Honeycombing on CT
Treatments for IPF - antifibrotics
* Pirfenidone
* 5-Methyl-1-phenylpyridin-2-one
* Inhibits TGF-β stimulated collagen synthesis
* Decreases extracellular matrix
* Inhibits fibroblast proliferation
Treatments for IPF
* Nintedanib
* BIBF 1120
* Intracellular tyrosine kinase inhibitor
NICE-Pirfenidone
* FVC 50% – 80% predicted
* Treatment stopped if evidence of disease progression – 10% decline
in FVC over 12 months
NICE - Nintedanib
* FVC 50% – 80% predicted
* Discount
* Treatment stopped if evidence of disease progression – 10% decline
in FVC over 12 months
Hot of the press
Progressive pulmonary fibrosis – Nintendanib
INBUILD Trial – reduces FVC decline irrespective of underlying ILD
Don’t forget the basics!
* Pulmonary rehabilitation
* Oxygen
* Support groups
* Smoking cessation
* Palliative Care
HP
* Diagnosis
* Identification of a potential antigen
* Characteristic clinical & radiological findings
* CXR and HRCT UL fibrosis
* Blood +ve avian/aspergillus precipitins, N IgE
* Treatment
* Antigen avoidance may get better with just this
* Steroids
Granulomatosis with polyangiitis
* Upper airway
* Granulomas bleeding
* Sinusitis
* Saddle nose septal destruction
* Lungs
* Haemorrhage
* Cavities
ANCA +ve
