Interstitial Lung Diseases

Overview

Definition

• Interstitial lung disease (ILD) comprises a heterogeneous group of disorders that cause varying degrees of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of the lung interstitium, the space between the capillary endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology and the alveolar epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology.
• Clinically, affected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will show restrictive lung disease by pulmonary function studies.

Epidemiology

Idiopathic Idiopathic Dermatomyositis pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis, and ILD associated with connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology diseases are the most common types of ILD.

Classification

It is useful to categorize ILDs into those with and without a known cause.

Diagnosis

History

Physical examination

• End-inspiratory fine crackles in lung bases Bases Usually a hydroxide of lithium, sodium, potassium, rubidium or cesium, but also the carbonates of these metals, ammonia, and the amines. Acid-Base Balance (common finding, especially in IPF)
• Wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing is uncommon (may be found in HP, Churg-Strauss disease, sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis)
• Severe disease findings: cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination, digital clubbing Clubbing Cardiovascular Examination, cor pulmonale Cor Pulmonale Cor pulmonale is right ventricular (RV) dysfunction caused by lung disease that results in pulmonary artery hypertension. The most common cause of cor pulmonale is chronic obstructive pulmonary disease. Dyspnea is the usual presenting symptom. Cor Pulmonale

Laboratory studies

Autoantibody detection may help with the diagnosis of some CTDs.

Pulmonary function testing Pulmonary Function Testing Pulmonary Function Tests

• The diffusing capacity for carbon monoxide Carbon monoxide Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. Carbon Monoxide Poisoning ( DLCO DLCO Pulmonary Function Tests) shows reduction.
• Most show a restrictive pattern.

Imaging

• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests may be suggestive of a type of ILD:
  • Peripheral reticular pattern in lower lung zones and small cystic Cystic Fibrocystic Change spaces suggests IPF.
  • Central nodular pattern in mid-to-upper lung zones and hilar lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node enlargement suggests sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis.
• Chest computed tomography Chest Computed Tomography Hemothorax (CT):
  • Standard initial test
  • May confirm the diagnosis of IPF in the right setting and obviate the need for lung biopsy Lung Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
  • Better defines disease extent and features (e.g., honeycombing)
  • Helps exclude comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (e.g., pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax) or differential diagnosis (e.g., malignancy Malignancy Hemothorax)
  • Helps determine the best location for biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

Lung biopsy Lung Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

• Establishes the diagnosis
• Performed via fiberoptic bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia or surgery
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is not needed if:
  • High-resolution CT High-resolution CT Imaging of the Lungs and Pleura ( HRCT HRCT Pulmonary Function Tests) shows classic usual interstitial pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia and the patient has no systemic diseases suggestive of an another disorder.
  • Patient has minimal signs or symptoms and a stable/nonprogressive disease.
• Indicated in cases of comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus or rapidly progressive symptoms

Individual Forms

Idiopathic Idiopathic Dermatomyositis pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans

• Most common ILD of unknown cause
• Commonly diagnosed in 5th or 6th decade
• Affects men more than women
• Frequently associated with smoking
• 3–5-year survival rate is 50%.
• May be associated with acute exacerbations
• Lung HRCT HRCT Pulmonary Function Tests shows a pattern of UIP: subpleural reticular pattern with posterior-basal predominance with more advanced fibrotic features such as honeycombing and traction bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis.
• Histopathology shows a pattern of UIP: subpleural reticulation Subpleural reticulation Pulmonary Fibrosis, honeycombing, fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis, skipped lesions with preserved architecture (temporal and spatial heterogeneity).
• Treatment: physical therapy Physical Therapy Becker Muscular Dystrophy and supplemental oxygen Supplemental Oxygen Respiratory Failure, antifibrotic therapy ( pirfenidone Pirfenidone Pulmonary Fibrosis), and lung transplantation Lung transplantation The transference of either one or both of the lungs from one human or animal to another. Organ Transplantation if patient meets criteria

Non-specific interstitial pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia

• May be idiopathic Idiopathic Dermatomyositis or commonly associated with CTDs
• Commonly diagnosed in non-smoking women in their 5th decade
• 5-year survival rate is 80%.
• Lung HRCT HRCT Pulmonary Function Tests shows diffuse and symmetric subpleural ground-glass and reticular opacities; traction bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis may be seen; honeycombing and peribronchial thickening is uncommon.
• Histopathology shows uniform interstitial inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans without honeycombing.
• Treatment: physical therapy Physical Therapy Becker Muscular Dystrophy, supplemental oxygen Supplemental Oxygen Respiratory Failure, steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, immunosuppressive therapy, and lung transplantation Lung transplantation The transference of either one or both of the lungs from one human or animal to another. Organ Transplantation if patient meets criteria

Cryptogenic organizing pneumonia Cryptogenic organizing pneumonia An interstitial lung disease of unknown etiology, occurring between 21-80 years of age. It is characterized by a dramatic onset of a ‘pneumonia-like’ illness with cough, fever, malaise, fatigue, and weight loss. Pathological features include prominent interstitial inflammation without collagen fibrosis, diffuse fibroblastic foci, and no microscopic honeycomb change. There is excessive proliferation of granulation tissue within small airways and alveolar ducts. Bronchiolitis Obliterans

• May be idiopathic Idiopathic Dermatomyositis or secondary to polymyositis Polymyositis Polymyositis (PM) is an autoimmune inflammatory myopathy caused by T cell-mediated muscle injury. The etiology of PM is unclear, but there are several genetic and environmental associations. Polymyositis is most common in middle-aged women and rarely affects children. Polymyositis, medications, or malignancy Malignancy Hemothorax
• Commonly diagnosed in 6th or 7th decade
• Lung HRCT HRCT Pulmonary Function Tests shows migratory, patchy, subpleural consolidations and ground-glass opacities with or without a rim of subpleural sparing known as the halo sign Halo sign Aspergillus/Aspergillosis (characteristic).
• Treatment: steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and immunosuppressives

Smoking-related ILD

• Occurs in heavy smokers in the 5th or 6th decade
• Honeycombing is typically absent
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma confirms diagnosis
• Treatment includes smoking cessation and immunosuppressive therapy

Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disease–associated ILD and granulomatous ILD

Complications

• Acute exacerbations of IIPs:
  • Accelerated phase Accelerated phase The phase of chronic myeloid leukemia following the chronic phase, where there are increased systemic symptoms, worsening cytopenias, and refractory leukocytosis. Chronic Myeloid Leukemia of lung injury in a patient with an underlying ILD
  • Acute onset (< 30 days) of respiratory distress and hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome more severe than what was previously experienced by the underlying ILD and not explained by other causes (e.g., pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR))
  • Most commonly described in IPF
  • Lung HRCT HRCT Pulmonary Function Tests shows a change in the pattern previously observed due to the underlying ILD with patchy bilateral ground-glass opacities and consolidation Consolidation Pulmonary Function Tests in dependent regions.
  • Histopathology shows diffuse alveolar damage.
  • Treatment is supportive as no proven therapy exists; lung transplantation Lung transplantation The transference of either one or both of the lungs from one human or animal to another. Organ Transplantation may provide cure.
  • Mortality Mortality All deaths reported in a given population. Measures of Health Status rate > 85%
• Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
• Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
• Ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
• Thromboembolic disease
• Lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer

Differential Diagnosis

• Cardiovascular disease (e.g., heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR))
• Diffuse infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., pneumocystis pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia)
• Malignancy Malignancy Hemothorax (e.g., bronchoalveolar cell carcinoma):
  • Note that ILDs such as COP may occur secondary to dermatomyositis Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. Paraneoplastic Syndromes and malignancy Malignancy Hemothorax; however, lung malignancies such as bronchoalveolar cell carcinoma can mimic the symptoms and signs of ILD.