prof dr roslina abdul manap depatment of medicine ukm ...diseases affecting muscles of respiration...

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