Prof Dr Roslina Abdul Manap
Depatment of Medicine UKM Medical
Centre
Concept of restrictive lung disease:
„intrinsic‟/interstitial lung disease and
„extrinsic‟ lung disease
Typical lung function findings in restrictive
lung disease
Examples of extra-parenchymal lung disease
Examples of interstitial lung disease –IPF
Management/Prognosis
In restrictive lung disease, lung volumes are reduced because of:
1. Alteration in lung parenchyma.
2. Diseases of the pleura, chest wall or neuromuscular apparatus.
Hence, restrictive lung diseases may be divided
into the following groups:
Intrinsic lung diseases (diseases of the lung
parenchyma)
- „interstitial lung disease‟ (ILD)
- „diffuse parenchymal lung disease‟(DPLD)
Extrinsic disorders (extra-parenchymal
diseases)
Disorders of the chest wall, pleura and respiratory muscles cause lung restriction and impair ventilatory function.
These are grouped as:
Non-muscular diseases of the chest wall
Neuomuscular disorders
Examples: kyphosis, scoliosis, ankylosing spondylitis, morbid obesity, thoracoplasty, flail chest
Examples: Guillain-Barré syndromemultiple sclerosis, myasthenia gravis, amyotrophic lateral sclerosis
The thoracic cage and neuromuscular
structures are a part of the respiratory
system.
Any disease of these structures will cause
restrictive disease and ventilatory
dysfunction
Diseases of the pleura, thoracic cage,
decrease compliance of respiratory system.
There is reduction in lung volumes.
Secondarily, atelectasis occurs leading to
V/Q mismatch and hypoxaemia.
Pneumothorax - either primary or secondary.
Pleural effusion - acute or chronic.
Pleural thickening – longstanding pleural effusion results in fibrotic pleura which splints the lung and prevents its expansion.
Deformity of thoracic cage such as kyphoscoliosis and ankylosing spondylitis.
Scoliosis – lateral curvature of spine, kyphosis – posterior curvature.
Patients develop exertional dyspnea, rapid shallow breathing.
Hypoxemia, hypercapnia and cor-pulmonale supervene.
Pulmonary function tests show restrictive ventilatory defect with normal diffusion.
Cause of death is respiratory failure or intracurrent pulmonary infection.
Treatment is non-invasive or invasive chronic ventilation.
Diseases affecting muscles of respiration or their nerve supply.
Poliomyelitis, Guillain-Barre syndrome, ALS, myasthenia gravis, muscular dystrophies.
All these lead to dyspnoea and respiratory failure.
PFT‟s show reduced FVC, TLC and FEV1.
The progress of disease can be monitored by FVC and blood gases.
Maximal inspiratory and expiratory pressures are reduced.
Treatment is either treating the underlying cause or assisted ventilation.
Inflammation and/or scarring of lung
tissue (interstitial lung disease)
or
Filling of the air spaces with exudate
and debris
(pneumonitis/‟pneumonia‟)
These are classified further
according to aetiological factor
ILD
Known
Aetiology
Associated systemic
disease
Idiopathic
Pulmonary
Fibrosis
(Other
IIPs)
Occupational dusts
Drugs- amiodarone,
methotrexate,
sulfasalazine,
nitrofurantoin
Hypersensitivity
Pneumonitis
(organic)
Infection- TB
Sarcoid
RA
SLE
Sjogrens
UC
Idiopathic
Diffuse parenchymal disorders cause reduction in all
lung volumes.
This is produced by excessive elastic recoil of the
lungs.
Expiratory flows are reduced in proportion to lung
volumes.
Arterial hypoxemia is caused by ventilation/perfusion
mismatch.
Impaired diffusion of oxygen will cause exercise-
induced desaturation.
Hyperventilation at rest secondary to reflex
stimulation.
Physiologically restrictive lung diseases are
defined by reduced total lung capacity, vital
capacity and functional residual capacity, but
with preserved air flow
Spirometry reveals a restrictive pattern.
FVC is reduced, FEV1/FVC is increased.
All lung volumes – TLC, FRC, RV – are reduced
Restrictive defect
FVC is reduced
FEV1 is reduced in proportion or slightly less
FEV1:FVC ratio normal or raised
Diffuse interstitial lung disease (ILD) is a group of disorders that affect the connective tissue (interstitium) that forms the support structure of the alveoli of the lungs.
When affected by an interstitial lung disease, the tissue supporting the alveoli becomes inflamed and stiff, which makes it difficult for the alveoli to fully expand.
As interstitial disease progresses, the supporting tissue scars and thickens the alveolar walls, further decreasing lung function.
Synonyms: idiopathic pulmonary fibrosis, interstitial pneumonia, cryptogenic fibrosing alveolitis.
Pathology Thickening of interstitium.
Initially, infiltration with lymphocytes and plasma cells.
Later fibroblasts lay down thick collagen bundles.
These changes occur irregularly (heterogenously) within the lung.
Eventually alveolar architecture is destroyed – honeycomb lung
Unknown, may be immunological reaction.
Clinical Features
Uncommon disease, affects adults in late middle age.
Progressive exertional dyspnoea, later at rest.
Non-productive cough.
Physical examination shows finger clubbing, fine inspiratory crackles throughout both lungs.
Patient may develop respiratory failure terminally.
The disease progresses insidiously, median survival 4-6 years.
ILD
Known
Aetiology
Associated systemic
disease
Idiopathic
Pulmonary
Fibrosis
(Other
IIPs)
Occupational dusts
Drugs- amiodarone,
methotrexate,
sulfasalazine,
nitrofurantoin
Hypersensitivity
Pneumonitis
(organic)
Infection- TB
Sarcoid
RA
SLE
Sjogrens
UC
Idiopathic
CXR changes:
1. Reticulo-
nodular
shadowing
2. Loss of
volume
3. Widespread
/ bilateral
HRCT changes: bi-basal, peripheral reticulonodular opacities,
honeycombing, loss of lung architecture, traction
bronchiectasis. Peripheral and lower zone predominance.
Rarely GGO. Appearances on the HRCT may be sufficiently
characteristic to diagnose.
Unknown aetiology
Histology
„Usual Interstitial
Pneumonia‟
Patchy fibroblasts with collagen deposition
and cystic changes (honeycombing)
Arterial PaO2 and PaCO2 are reduced, pH normal.
On exercise PaO2 decreases dramatically.
Physiologic dead space and physiologic shunt and VQ mismatch are increased.
Diffuse impairment contributes to hypoxemia on exercise.
There is marked reduction in diffusing capacity due to thickening of blood gas barrier and VQ mismatch.
Diagnosis is often suggested by history, chest radiograph and high resolution CT scan of the lungs.
If old chest x-rays show classical disease, absence of other disease processes on history and no occupational or environmental exposure – clinical diagnosis can be made.
In other cases, a surgical lung biopsy is obtained.
Each patient is individually assessed.
Patients are treated if they have
symptoms or progressive dysfunction on
pulmonary function tests.
Ancillary therapies such as oxygen,
rehabilitation, psychosocial aspects are
helpful.
The recommendation against the use of the following agents for
the treatment of IPF is strong:
Anticoagulation (warfarin)
Imatinib, a selective tyrosine kinase inhibitor against
platelet-derived growth factor (PDGF) receptors
Combination prednisone, azathioprine, and N-acetylcysteine
Selective endothelin receptor antagonist (ambrisentan)
The recommendation for the use of the following agents for the
treatment of IPF is conditional:
Nintedanib, a tyrosine kinase inhibitor that targets multiple
tyrosine kinases, including vascular endothelial growth
factor, fibroblast growth factor, and PDGF receptors
Pirfenidone
The recommendation against the use of the following agents for
the treatment of IPF is conditional:
Phosphodiesterase-5 inhibitor (sildenafil)
Dual endothelin receptor antagonists (macitentan, bosentan)
“Best supportive care”
Symptom management- pulmonary rehab, oxygen therapy, opiates, PPIs, palliative care input
To date no therapy proven to improve survival
Weak recommendation for „NAP‟
Transplant list
Clinical trials recruitment
Poor prognosis and relentless course
Mean life expectancy for newly diagnosed
cases of between 2.9 and 5 years
Can be complicated by bronchogenic
carcinoma
Most patients die of respiratory failure (type 1)
A disease characterized by the presence of
granulomatous tissue.
This is a systemic disease which involves
eyes, brain, heart, lungs, bones and kidneys,
skin, liver and spleen.
On pathology a non-caseating granuloma
composed of histiocytes, giant cells and
lymphocytes.
In advanced lung disease fibrotic changes are
seen.
Unknown, likely immunological basis.
Four stages are identified:
Stage 0: No obvious intrathoracic involvement
Stage 1: Bilateral hilar lymphadenopathy, often accompanied by arthritis, uveitis and erythema nodosum.
Stage 2: Pulmonary parenchyma is also involved, changes in mid and upper zones.
Stage 3: Pulmonary infiltrates and fibrosis without adenopathy.
Pulmonary Function
No impairment occurs in stages 0 and 1.
In stages 2 and 3 restrictive changes are
seen.
Treatment and Prognosis
85% of these patients improve
spontaneously, but 15% may develop
progressive fibrosis and respiratory failure.
Treatment is other observation, but in
symptomatic patients or deteriorating PFT‟s
– treatment recommended.
Prednisone 0.5- 1 mg/kg initially, then
tapered and continued for 6 months to 1-2
years.
Also known as extrinsic allergic alveolitis.
Hypersensitivity reaction in the lung occurs in response to inhaled organic dust.
Example is farmer‟s lung.
The exposure may be occupational or environmental.
The disease occurs from type III and type IV hypersensitivity reactions.
Farmer‟s lung is due to thermophilic actinomyces in mouldy hay.
Bird fancier‟s lung is caused by avian antigen.
Pathology
There is infiltration of alveolar walls with
lymphocytes, plasma cells and histiocytes.
There are loosely formed granulomas.
Fibrotic changes occur in advanced
disease.
The disease may occur in acute or chronic forms.
Acute HP
Dyspnea, fever, malaise and cough appear 4-6 hours after exposure.
These symptoms continue for 24-48 hours.
Physical examination shows fine crackles throughout the lungs.
These patients present with progressive dyspnea over a period of years.
Chest radiograph may be normal, but may show reticular nodular infiltration.
Patients present with progressive dyspnea.
Physical examination shows bilateral
inspiratory crackles.
Chest x-ray shows reticular nodular
infiltration and fibrosis predominantly in
upper lobes.
Pulmonary function tests – restrictive
pattern.
Gas exchange shows hypoxemia which
worsens on exercise.
Various drugs cause acute pulmonary reaction – proceeding to interstitial fibrosis.
These drugs are busulfan, nitrofurantoin, amiodarone, bleomycin.
High oxygen concentration – interstitial fibrosis.
Radiation exposure – acute pneumonitis – fibrosis.
Several collagen vascular diseases particularly systemic sclerosis and lupus and rheumatoid arthritis may lead to systemic sclerosis.
Dyspnoea is often severe.
A definite diagnosis requires surgical lung biopsy.
Treatment is corticosteroids plus cytotoxic therapy.
Concept of restrictive lung disease:
„intrinsic‟/interstitial lung disease and
„extrinsic‟ lung disease
Diffuse interstitial lung disease (ILD) is a
group of disorders that affect the connective
tissue (interstitium) that forms the support
structure of the alveoli of the lungs.
These are classified further according to
aetiological factor – idiopathic, „known‟,
systemic disease association
IPF is the prime example of idiopathic ILD