Interstitial Lung Diseases

Dr David CL Lam
Department of Medicine
Nov, 2021
 OBJECTIVES

• Describe clinical features of interstitial

lung disease (ILD)
• Diagnostic approach for ILD and
differential diagnosis
• Management of ILD

• Health problems of dust exposure in

construction sites and industries
• Compensation for occupational lung
diseases

1. Inhaled substances
Inorganic
• Silicosis
• Asbestosis
• Berylliosis
Organic
• Hypersensitivity pneumonitis
2. Drug induced
• Antibiotics
• Chemotherapeutic drugs
• Immune-checkpoint inhibitor
• Antiarrhythmic agents
• Statins
3. Connective tissue disease
• Systemic sclerosis
• Polymyositis
• Dermatomyositis
• Rheumatoid arthritis
Different types of
interstitial lung diseases
4. Infection
• Atypical pneumonia
• Pneumocystis pneumonia (PCP)
• Tuberculosis
• Chlamydia trachomatis
• Respiratory Syncytial Virus
5. Idiopathic
• Sarcoidosis
• Idiopathic pulmonary fibrosis
• Hamman-Rich syndrome
• Anti-synthetase Syndrome
6. Malignancy
• Lymphangitis carcinomatosis
7. Radiation
 IDIOPATHIC PULMONARY FIBROSIS

Idiopathic pulmonary fibrosis (IPF) is a chronic and

ultimately fatal disease characterized by a
progressive decline in lung function.

The term pulmonary fibrosis means scarring of lung

tissue and is the cause of worsening dyspnoea.

Fibrosis is usually associated with a poor prognosis.

The term 'idiopathic' is used because the cause of

pulmonary fibrosis is still unknown.
Thorax 1998;53:469-476 doi:10.1136/thx.53.6.469
 The pulmonary interstitium is the microscopic space
between the alveolar epithelium and capillary
endothelium and is crucial for gas exchange.

Abnormal fibrosis
and thickening

Dempsey O J et al. BMJ 2010;340:bmj.c2843

 HEALTHY LUNG FIBROTIC LUNG

Dempsey O J et al. BMJ 2010;340:bmj.c2843

Arrows indicate pulmonary interstitium in (left) healthy lung and (right) pulmonary fibrosis.
• Increase in interstitial tissue causing loss
of lung compliance
• Physiological restrictive deficit
• Alveolar-capillary interface is the key site
of injury and pathogenesis
• Acute and chronic disease processes
• Many, many different causes / patterns!

Thin elastin-rich connective component

containing capillary blood vessels
Early stage acute pathology is an alveolitis
(injury with inflammatory cell infiltration)

Late stages characterised by fibrosis

Clinical effects due to hypoxia (respiratory

failure), pulmonary hypertension, cor
pulmonale and cardiac failure;

Thin elastin-rich connective component

containing capillary blood vessels
 Idiopathic Pulmonary Fibrosis (IPF) or
Usual Interstitial Pneumonia (UIP).

• Progressive interstitial fibrosis of unknown cause.

• Variable association with inflammation.

• Associated with clubbing.

• Pathological process centred on fibrosis at the subpleural and basal

segments.

• Terminal lung structures replaced by dilated spaces surrounded by

fibrous walls. Reduced compliance and DLCO.
Examples of drugs that can cause interstitial lung disease / pulmonary fibrosis

Anti-cancer drugs
• bleomycin, busulfan, chlorambucil, melphalan, methotrexate, mitomycin C, tyrosine kinase
inhibitors (gefitinib, erlotinib)
• Immune checkpoint inhibitors

Cardiac drugs
• amiodarone, angiotensin converting enzyme inhibitors, aspirin, atenolol, statins

Antibiotics
• cephalosporin, minocycline, nitrofurantoin, quinine, sulfasalazine

Illicit drugs
• cocaine, heroin, intravenous talc, methadone

Miscellaneous
• high flow oxygen, inhalation or aspiration of fat-containing substances (drugs containing mineral
oils, certain laxatives, petroleum jelly), paraquat, radiotherapy
 Although the cause of IPF is unknown, several risk factors have been
suggested

Environmental factors Infection

A large number of studies
Cigarette smoking have examined this, but
Strongly associated with IPF findings are not conclusive
Especially in those
with a smoking Gastroesophageal reflux
history of (GER) disease
> 20 pack-years Proposed cause of repeated
microinjury

Genetic factors
Environmental pollutants
Associated with an increased risk of IPF Familial pulmonary fibrosis
Exposure to metal and wood dusts, farming, raising birds, accounts for < 5% of total
hairdressing, stone cutting/polishing, and exposure to livestock, population with IPF
vegetables or animal dust
 Clinical features of ILD

1. Dyspnoea exacerbated by exertion

2. Cough, often persistent and sometimes severe;
3. Fatigue
4. Tachypnoea which is often laboured
5. Loss of appetite and weight loss
6. Chest pain
7. Fever
8. Central cyanosis
9. Cor pulmonale (right ventricle heart disease)
10. Respiratory insufficiency and failure
 SIGNS AND SYMPTOMS

1. Age usually over 50 years

2. Dry, non-productive cough on exertion
3. Progressive exertional dyspnoea (shortness of
breath with exercise)
4. Dry, inspiratory bibasilar "velcro-like" crackles on
auscultation
5. Clubbing of fingers
6. Abnormal pulmonary function test results, with
evidence of restriction and impaired gas
exchange
Initial assessment of patients with suspected interstitial
lung disease.
• Investigation is tailored towards the symptoms and signs.

• Most patients have blood testing, chest x-ray, pulmonary

function testing, and high resolution CT thorax.

• HRCT thorax is the best mode of investigation to diagnose

interstitial lung disease.

• Diagnosis based on lung biopsy is only required if the clinical

history and imaging are not clearly suggestive of a specific
diagnosis or malignancy cannot otherwise be ruled out.

• DLCO will be decreased in these patients.

 Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis
and Management*

Usual interstitial Pneumonia Pattern

• Does not equate to diagnosis of IPF

• IPF only if known causes of ILD (e.g., environmental
exposure, connective tissue disease, and drug
toxicity )are excluded
• Collagen vascular / Connective tissue diseases
• Asbestosis
• Chronic hypersensitivity pneumonitis
* Raghu et al, AJRCCM :183;788-824,2011
 Usual Interstitial Pneumonia (UIP) and
Idiopathic Pulmonary Fibrosis :
:
• Potential Pitfalls in Making a diagnosis
of IPF
• Exclusion of ‘known/environmental causes’
• Exclusion of collagen vascular diseases
• HRCT SCAN techniques
• Local expertise in ILD ?
• Multidisciplinary discussions ?
 UIP pattern vs NSIP
pattern

HRCT diagnostic criteria for UIP

pattern HRCT features of NSIP:
1. More ground glass opacity
1.Subpleural, basal predominance
2. Reticulation usually comes
2.Reticular abnormality
with a peribronchovascular
3.Honeycombing with or without
traction bronchiectasis
distribution
3. Less honeycomb changes and
4.Absence of features considered to
be inconsistent with UIP pattern traction bronchiectasis
• Regular follow-up lung function tests (FVC, TLC, DLco, Kco)
provide valuable information on disease progression.

• Flexible Bronchoscopy ± BAL ± Transbronchial Biopsy (TBBx)

• Thoracoscopic VATS Biopsy – more invasive but more reliable

and generates far more tissue.

• 6MWT, and exercise tolerance assessments provide functional

status.

• Breathlessness scores are valuable to help grade and assess

patient symptoms.

• Multi-disciplinary approach including physiotherapists,

pulmonary rehab, and occupational therapists.
Spirometry is suggestive, but not diagnostic, of
restrictive lung physiology

Normal Obstructive pattern Restrictive pattern

• ILD is not a single disease, but encompasses many different
pathological processes. Hence treatment is different for each
disease.
• If a specific occupational exposure cause is found, the person
should avoid that environment.

• If a drug cause is suspected, that drug should be discontinued.

• Some idiopathic and connective tissue-based causes of ILD
(associated with systemic sclerosis) may be treated with newer
targeted kinase like Nintedanib.

• Systemic glucocorticosteroid is no longer recommended as the

first line management, especially in IPF with UIP pattern;
though systemic steroid can still be used in acute exacerbation
• Some patients respond to immunosuppressant treatment.

• Patients with hypoxaemia may be given supplemental oxygen

(in the form of either ambulatory O2 or LTOT therapy).
NINTEDANIB (FORMERLY BIBF-1120)

• VEGF and multiple angiokinase inhibitor

• Small molecule like Pirfenidone
• VEGFR, FGFR, and PDGFR inhibitor
• Developed as a anti-vascular anti-cancer therapy
• In clinical trials, nintedanib showed a reduction
in the rate of decline in lung function. One
study demonstrated a longer time to first
exacerbation.
• Lung transplantation to replace the damaged lung
tissue is the most effective treatment, but is
associated with severe risks of its own.
Sildenafil in advanced IPF

• 10mg QDS dose

• Not achieved primary endpoint

• Improved QaLY / breathlessness scores (SGRQ)

• More studies required
• Early treatment of pulmonary hypertension
 SUPPORTIVE CARE

• Supplemental Oxygen
• Patient Education
• Pulmonary rehabilitation
• Vaccination – influenza and
pneumococcal polysaccharide
vaccines
• Palliative Care
Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)

• Chronic inflammatory disease.

• Small Airways
• Interstitial involvement
• Occasional granulomas

• Allergic origins – type III / type IV hypersensitivity

• Thermophilic bacteria = Farmer’s Lung

• Avian proteins = Bird / Pigeon Fancier’s Lung
• Fungi = Malt Worker’s Lung

• Precipitins / antibodies often detectable in serum samples.

• Unusual cases come to biopsy.
Hypersensitivity pneumonitis resulting from
dust exposure

Dempsey O J et al. BMJ 2010;340:bmj.c2843

 Chronic Interstitial Lung Diseases

• Idiopathic pulmonary fibrosis (IPF) or Usual Interstitial Pneumonia

(UIP)

• Sarcoidosis

• Hypersensitivity Pneumonitis (or Extrinsic Allergic Alveolitis)

• Pneumoconiosis

• Connective tissue diseases

 Pneumoconiosis

• Lung disease caused by mineral dust exposure e.g., asbestosis, coal

worker’s lung, silicosis.

• Disease severity depends on .. ..

i) Particle size (1-5µm)

ii) Reactivity of particles
iii) Clearance of particles
iv) Host response

• Asbestos (a silicate) – serpentine (curved) fibres relatively safe /

straight (amphibole) fibres highly dangerous to man.
 SILICOSIS

Silicosis (miner's phthisis, grinder's asthma,

potter's rot etc.) is a form of occupational
lung disease.

It is caused by inhalation of crystalline silica

dust, and is marked by inflammation and
scarring in the form of nodular lesions in the
upper lobes of the lungs.

It is a type of pneumoconiosis.
Occupational risk factors
• Stone mining and cutting
• Pneumatic drill worker
• Caisson worker
• Jade polisher and gemstone cutter
• Ceramic workers
• Other manual labourer in construction sites
 Clinical features of silicosis

1. Dyspnoea exacerbated by exertion

2. Cough, often persistent and sometimes severe;
3. Fatigue
4. Tachypnoea which is often laboured
5. Loss of appetite and weight loss
6. Chest pain
 SIGNS AND SYMPTOMS

1. Age usually over 50 years

2. Dry, non-productive cough on exertion
3. Progressive exertional dyspnoea (shortness of
breath with exercise)
4. Dry, inspiratory bibasilar "velcro-like" crackles on
auscultation
5. Clubbing of fingers
6. Abnormal pulmonary function test results, with
evidence of restriction and impaired gas
exchange
SILICOSIS
 SILICOSIS

Progressive massive fibrosis

Upper lobe fibrocalcification, mediastinal lymph node enlargement with ‘eggshell’ calcification
Occupational risk for asbestosis and
malignant pleural mesothelioma
• Handling of asbestos products that has been
incorporated into construction work, even commercial
or household products
Construction works: demolition of
fireproof coatings or
bricks, or pipes
(including shipyard
workers and some
seamens)
Commercial/household: demolition work,
insulation wall layers
with broken asbestos
bricks in floorings and
roofings
Asbestosis
Diffuse
interstitial
fibrosis

Develops
after
prolonged or
heavy
exposure
 Pathogenesis
• Chronic
inflammation
• Fibroblasts
proliferate in
interstitium;
Fibrosis
• Bronchiolar epi.
extend to line
airspaces
 Pathogenesis – End stage disease

◼ Acini “simplified”,
become cystic spaces
◼ Bronchiolar epithelium
grows into cystic
spaces
◼ Honeycomb lung
Pathological Features

• Interstitial
fibrosis
• Obliteration of
some air spaces
• Cystic dilatation
of others
• Chronic inflam.
Cells – not
always present
Asbestosis bodies (extracted from human lung tissue).
Association of asbestos bodies in the context of
pulmonary fibrosis (asbestosis).
Pleural shadows on CXR
Pleural plaques in asbestosis
• Silicosis and asbestosis are irreversible conditions with
no cure.
• Treatment currently focuses on alleviating symptoms
and preventing complications.

• Stopping further exposure to silica and other lung

irritants, including tobacco smoking.

• Cough suppressants.
• Antibiotics for bacterial lung infection.
• TB prophylaxis for those with positive tuberculin skin
test or IGRA blood test.
• Prolonged anti-tuberculosis (multi-drug regimen) for
those with active TB.

• Both silica and asbestos are WHO Type I carcinogens

 Pneumoconiosis Compensation Fund Board (Hong Kong)
No. of Assessed New Cases
600

500 Pneumoconiosis Medical Board

Shau Kei Wan Chest Clinic

400

300

200 Total : 4774

100

0
What is Pneumoconiosis?
(Cap 360, Part I, Sect 2)

• fibrosis of the lungs to dust of free silica or dust containing free silica, whether
or not such disease is accompanied by tuberculosis of the lungs, or any other
disease of the pulmonary or respiratory organs caused by exposure to such
dust;

or

• fibrosis of the lungs due to dust of asbestosis or dust containing asbestos,

whether or not such disease is accompanied by tuberculosis of the lungs, or
any other disease caused by exposure to such dust

What is Mesothelioma?

(Cap 360, Part I, Sect 2)

• a primary malignant neoplasm of the mesothelial tissue due to dust of

asbestos or dust containing asbestos, whether or not such disease is
accompanied by tuberculosis of the lungs or by any other disease caused by
exposure to such dust
 Lung function impairment stratified
Entitlement to compensation by FVC measurement
Compensation shall be payable to:

• any person suffering from pneumoconiosis or mesothelioma (or both), in

respect of any incapacity resulting from the above disease or diseases and any
pain, suffering and loss of amenities arising from the above disease or diseases

• for a person suffering from pneumoconiosis (whether or not he is also

suffering from mesothelioma), compensation in respect of his pneumoconiosis
shall be payable only where the date of diagnosis of his pneumoconiosis
occurs on or after 1 January 1981

• for a person suffering from mesothelioma (whether or not he is also suffering

from pneumoconiosis), compensation in respect of his mesothelioma shall be
payable only where the date of diagnosis of his mesothelioma occurs on or
after 18 April 2008 AND

• a person resident in Hong Kong for 5 years or more at the date of the
notification of the claim, or resident in Hong Kong for less than 5 years at such
date if he contracted pneumoconiosis or mesothelioma (or both) in Hong Kong
 OBJECTIVES

• Describe clinical features of interstitial

lung diseases (ILD)
• Diagnostic approach for ILD and
differential diagnosis
• Management of ILD

• Health problems of dust exposure in

construction sites and industries
• Compensation for occupational lung
diseases
Thank you
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