eMedicine Specialties > Pulmonology > Interstitial Lung Diseases

Restrictive Lung Disease

Author: Lalit K Kanaparthi, MD, Senior Fellow, Department of Pulmonary Medicine, Lenox Hill Hospital
Coauthor(s): Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital; Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Contributor Information and Disclosures

Updated: Jul 27, 2009

Introduction

Background

Restrictive lung diseases are characterized by reduced lung volume, either because of an alteration in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus. In physiological terms, restrictive lung diseases are characterized by reduced total lung capacity (TLC), vital capacity, or resting lung volume. Accompanying characteristics are preserved airflow and normal airway resistance, which are measured as the functional residual capacity (FRC). If caused by parenchymal lung disease, restrictive lung disorders are accompanied by reduced gas transfer, which may be marked clinically by desaturation after exercise.

The many disorders that cause reduction or restriction of lung volumes may be divided into 2 groups based on anatomical structures.

The first is intrinsic lung diseases or diseases of the lung parenchyma. The diseases cause inflammation or scarring of the lung tissue (interstitial lung disease) or result in filling of the air spaces with exudate and debris (pneumonitis). These diseases can be characterized according to etiological factors. They include idiopathic fibrotic diseases, connective-tissue diseases, drug-induced lung disease, and primary diseases of the lungs (including sarcoidosis).

The second is extrinsic disorders or extraparenchymal diseases. The chest wall, pleura, and respiratory muscles are the components of the respiratory pump, and they need to function normally for effective ventilation. Diseases of these structures result in lung restriction, impaired ventilatory function, and respiratory failure (eg, nonmuscular diseases of the chest wall, neuromuscular disorders).

Pathophysiology

Air flows to and from the alveoli as lungs inflate and deflate during each respiratory cycle. Lung inflation is accomplished by a contraction of respiratory, diaphragmatic, and external intercostal muscles, whereas deflation is passive. FRC is the volume of air in the lungs when the respiratory muscles are fully relaxed and no airflow is present. The volume of FRC is determined by the balance of the inward elastic recoil of the lungs and the outward elastic recoil of the chest wall. Restrictive lung diseases are characterized by a reduction in FRC and other lung volumes because of pathology in lungs, pleura, or the structures of the thoracic cage.

The distensibility of the respiratory system is called compliance, the volume change produced by a change in the distending pressure. Lung compliance is independent of the thoracic cage, which is a semirigid container. The compliance of an intact respiratory system is an algebraic sum of the compliances of both of these structures; therefore, it is influenced by any disease of the lungs, pleura, or chest wall.

In cases of intrinsic lung disease, the physiological effects of diffuse parenchymal disorders reduce all lung volumes by the excessive elastic recoil of the lungs, in comparison to the outward recoil forces of the chest wall. Expiratory airflow is reduced in proportion to lung volume.

Arterial hypoxemia in these disorders is primarily caused by ventilation-perfusion mismatching, with further contribution from an intrapulmonary shunt. The diffusion of oxygen is impaired, which contributes a little towards hypoxemia at rest but is primarily the mechanism of exercise-induced desaturation.

Hyperventilation at rest and exercise is caused by the reflexes arising from the lungs and the need to maintain minute ventilation by reducing tidal volume and increasing respiratory frequency.

In cases of extrinsic disorders of the pleura and thoracic cage, the total compliance by the respiratory system is reduced, and, hence, lung volumes are reduced. As a result of atelectasis, gas distribution becomes nonuniform, resulting in ventilation-perfusion mismatch and hypoxemia. In kyphoscoliosis, lateral curvature, anteroposterior angulation, kyphosis, or several of these conditions are present. The Cobb angle, an angle formed by 2 limbs of a convex prime curvature of the spine, is an indication of the severity of disease. An angle greater than 100° is usually associated with respiratory failure.

Neuromuscular disorders affect an integral part of the respiratory system, a vital pump. The respiratory pump can be impaired at the level of the central nervous system, spinal cord, peripheral nervous system, neuromuscular junction, or respiratory muscle. The pattern of ventilatory impairment is highly dependent on the specific neuromuscular disease.

Frequency

United States

For intrinsic lung diseases, studies cite an overall prevalence of 3-6 cases per 100,000 persons, with a prevalence of idiopathic pulmonary fibrosis (IPF) of 27-29 cases per 100,000 persons. The prevalence for adults aged 35-44 years is 2.7 cases per 100,000 persons. Prevalence exceeded 175 cases per 100,000 persons among patients older than 75 years. Exposure to dust, metals, organic solvents, and agricultural employment is associated with increased risk.

• In North America, the prevalence of sarcoidosis is 10-40 cases per 100,000 persons.
• The incidence of chronic interstitial lung diseases in persons with collagen-vascular diseases is variable, but it is increasing for most diseases.
• Kyphoscoliosis is a common extrinsic disorder. It is associated with an incidence of mild deformities amounting to 1 case per 1000 persons, with severe deformity occurring in 1 case per 10,000 persons.
• Other nonmuscular and neuromuscular disorders are rare, but their incidence and prevalence are not well known.

International

In Sweden, the prevalence rate for sarcoidosis is 64 cases per 100,000 persons. In Japan, the prevalence rate of sarcoidosis is 10-40 cases per 100,000 persons. The prevalence of sarcoidosis is difficult to determine, and tuberculosis is common.

The worldwide prevalence of fibrotic lung diseases is difficult to determine because studies have not been performed.

Mortality/Morbidity

The mortality and morbidity from various causes of restrictive lung disease is dependent on the underlying case of the disease process.

The median survival time for patients with IPF is less than 3 years. Factors that predict poor outcome include older age, male sex, severe dyspnea, history of cigarette smoking, severe loss of lung function, appearance and severity of fibrosis on radiologic studies, lack of response to therapy, and prominent fibroblastic foci on histopathologic evaluation.

Race

Although a familial variant of IPF exists, a genetic predisposition is not documented. US prevalence of sarcoidosis is estimated to be 10-17 times higher among African Americans compared to white Americans.

Sex

Lymphangioleiomyomatosis (LAM) and lung involvement in tuberous sclerosis occur exclusively in premenopausal women. Men are more likely to have pneumoconiosis because of occupational exposure, IPF, and collagen-vascular diseases (eg, rheumatoid lung). Worldwide, sarcoidosis is slightly more common in women.

Age

IPF is rare in children. Some intrinsic lung diseases present in patients aged 20-40 years. These include sarcoidosis, collagen-vascular–associated diseases, and histiocytosis X. Most patients with IPF are older than 50 years.

Clinical

History

The initial evaluation of patients should consist of a complete history, including a total review of past systemic conditions. A careful history of occupation, travel, habits, hobbies, exposures, and HIV risk factors is critical to help identify any etiologic agent.

• Duration of illness
  • Acute disorders last days to weeks and include acute interstitial pneumonitis, eosinophilic pneumonia, and diffuse alveolar hemorrhage.
  • Hypersensitivity pneumonitis and bronchiolitis obliterans-organizing pneumonia (BOOP) may manifest as acute, subacute, or chronic disease.
  • Subacute disorders lasting weeks to months include sarcoidosis, drug-induced interstitial lung disease, alveolar hemorrhage syndrome, BOOP, and connective-tissue diseases.
  • Chronic cases lasting months to years include idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pulmonary histiocytosis X.
• Smoking history: Pulmonary histiocytosis X, desquamative interstitial pneumonitis, IPF, and respiratory bronchiolitis occur with increased frequency among persons who smoke or those who previously smoked.
• Prior medication use
  • A detailed history of previously used medications is needed to exclude the possibility of drug-induced lung disease. These commonly used drugs are nitrofurantoin, amiodarone, gold, chemotherapeutic agents, procainamide, and hydralazine.
  • Radiation may also cause pneumonitis and fibrosis.
• Family history: Familial associations include IPF, sarcoidosis, and LAM.
• Occupational history
  • Seek a strict chronological listing of the patient's lifelong employment, including specific duties and known exposures.
  • Inhaled inorganic dust from substances (eg, silica, asbestos, beryllium, hard metals, cobalt) can cause pneumoconiosis.
  • Inhaled organic dust may cause hypersensitivity and pneumonitis.
• Environmental exposure: A review of the domestic and work environment of the patient and spouse is invaluable.
• Symptoms of intrinsic diseases
  • Progressive exertional dyspnea is the predominant symptom. Grading the level of dyspnea is useful as a method to gauge the severity of the disease and to follow its course.
  • A dry cough is common and may be a disturbing sign. A productive cough is an unusual sign in most patients with diffuse parenchymal lung disorders.
  • Hemoptysis or grossly bloody sputum occurs in patients with diffuse alveolar hemorrhage syndromes and vasculitis.
  • Wheezing is an uncommon manifestation but can occur in patients with lymphangitic carcinomatosis, chronic eosinophilic pneumonia, and respiratory bronchiolitis.
  • Chest pain is uncommon in most instances of the disease, but pleuritic chest pain can occur in patients with rheumatoid arthritis, systemic lupus erythematosus, and some drug-induced disorders.
• Symptoms of extrinsic disorders
  • Nonmuscular diseases of the chest wall affect patients with kyphoscoliosis. Patients younger than 35 years tend to be asymptomatic, whereas middle-aged patients develop dyspnea, decreased exercise tolerance, and respiratory infections.
  • The cause of respiratory failure is often multifactorial and is secondary to spinal deformity, muscle weakness, disordered ventilatory control, sleep disordered breathing, and airway disease.
  • Neuromuscular disorders occur as the respiratory muscle weakness progresses. Patients develop dyspnea upon exertion, followed by dyspnea at rest, and their condition ultimately advances to respiratory failure.
  • Patients with neuromuscular diseases develop significant respiratory muscle weakness and may demonstrate fatigue, dyspnea, impaired control of secretions, and recurrent lower respiratory tract infections. In these patients, the central drive is not decreased.¹ Acute and chronic respiratory failure, pulmonary hypertension, and cor pulmonale eventually ensue.

Physical

• Intrinsic disorders
  • The physical examination in patients with intrinsic lung disorders may yield distinguishing physical findings.
  • Those with chest wall disorders show obvious massive obesity and an abnormal configuration of the thoracic cage (eg, kyphoscoliosis, ankylosing spondylitis).
  • Velcro crackles are common in most patients with interstitial lung disorders.
  • Inspiratory squeaks or scattered, late, inspiratory high-pitched rhonchi are frequently heard in patients with bronchiolitis.
  • Cyanosis at rest is uncommon in persons with interstitial lung diseases, and this is usually a late manifestation of advanced disease.
  • Digital clubbing is common in those with idiopathic pulmonary fibrosis (IPF) and is rare in others (eg, those with sarcoidosis or hypersensitivity pneumonitis).

• • Extrapulmonary findings, including erythema nodosum, suggest sarcoidosis. A maculopapular rash can occur in those with connective-tissue diseases, or it may be drug-induced. Raynaud phenomenon may be present in patients with connective-tissue diseases, and telangiectasia is present in those with scleroderma. Peripheral lymphadenopathy, salivary gland enlargement, and hepatosplenomegaly are signs of systemic sarcoidosis. Uveitis may be observed in those with sarcoidosis and ankylosing spondylitis.
  • Cor pulmonale occurs in the late stages of pulmonary fibrosis or advanced kyphoscoliosis. Pulmonary hypertension and cor pulmonale become evident when signs include a loud P2, right-sided precordial lift, and right-sided gallop.
• Extrinsic disorders
  • By their very nature, severe kyphoscoliosis and massive obesity are easily recognizable. The pleural disorders are associated with decreased tactile fremitus, dullness upon percussion, and decreased intensity of breath sounds.
  • In cases of neuromuscular diseases, the physical examination findings may indicate accessory muscles usage, rapid shallow breathing, paradoxical breathing, and other features of systemic involvement.

Causes

• Intrinsic lung diseases
  • Collagen-vascular diseases, including scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis, are a cause of restrictive lung disease.
  • Other causes may include drugs and other treatments (eg, nitrofurantoin, amiodarone, gold, phenytoin [Dilantin], bleomycin, bischloroethylnitrosourea [BCNU or carmustine], cyclophosphamide, methotrexate, radiation). Also see Drug-Induced Pulmonary Toxicity.
  • Causes related to primary or unclassified diseases may include sarcoidosis, pulmonary histiocytosis X, LAM, pulmonary vasculitis, alveolar proteinosis, eosinophilic pneumonia, and BOOP.
  • Inorganic dust exposure (eg, silicosis, asbestosis, talc, pneumoconiosis, berylliosis, hard metal fibrosis, coal worker's pneumoconiosis) may cause restrictive lung disease.
  • Organic dust exposure (eg, farmer's lung, bird fancier's lung, bagassosis, and mushroom worker lung, which all cause hypersensitivity pneumonitis) is another cause.
• Idiopathic fibrotic disorders: These may include acute interstitial pneumonia, idiopathic pulmonary fibrosis (IPF) (usually interstitial pneumonitis), lymphocytic interstitial pneumonitis, desquamative interstitial pneumonitis, and nonspecific interstitial pneumonitis.
• Extrinsic disorders
  • Nonmuscular diseases of the chest wall, in which kyphosis can be idiopathic or secondary, may cause restrictive lung disease. The most common cause of secondary kyphoscoliosis is neuromuscular disease (eg, polio, muscular dystrophy). Fibrothorax, massive pleural effusion, morbid obesity, ankylosing spondylitis, and thoracoplasty are other causes.
  • Neuromuscular diseases manifest as respiratory muscle weakness and are due to myopathy or myositis, quadriplegia, or phrenic neuropathy from infectious or metabolic causes.

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