Interstitial Lung Disease

Definition
Interstitial lung diseases (ILDs) represent > 200 separate diseases of known and unknown causes. All involve the parenchyma of the lung: the alveoli, alveolar epithelium, capillary endothelium, and the spaces between these structures, as well as the perivascular and lymphatic tissues. These disorders are classified together because of similar clinical, roentgenographic, physiologic, or pathologic manifestations. They are often associated with considerable morbidity and mortality. See also Interstitial Lung Disease Associated with Collagen Vascular Disorders.

Epidemiology
Incidence of ILD o 2631 cases per 100,000 persons per year Prevalence of ILD o 80.9 per 100,000 men o 67.2 per 100,000 women o Recent work with CT scanning indicates that the prevalence may be significantly higher than the rates cited above. Estimated relative frequency of ILDs o Idiopathic interstitial pneumonias: 40% Idiopathic pulmonary fibrosis (IPF): 55% Nonspecific interstitial pneumonia: 25% Respiratory bronchiolitisILD and desquamative interstitial pneumonia: 15% Cryptogenic organizing pneumonia: 3% Acute interstitial pneumonia: < 1% o Occupational and environmental: 26% o Sarcoidosis: 10% o Connective tissue diseases: 9% o Drug and radiation: 1% o Pulmonary hemorrhage syndromes: < 1% o Other: 13% Age o Most patients with sarcoidosis, ILDs associated with connective tissue disease (CTD), lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis (PLCH), and inherited forms of ILD (familial IPF, Gauchers disease, or HermanskyPudlak syndrome) present between 20 and 40 years of age.

Most patients with IPF are > 50 years of age.

Sex Lymphangioleiomyomatosis and pulmonary involvement in tuberous sclerosis occur exclusively in premenopausal women. o ILD in HermanskyPudlak syndrome (an inherited form of oculocutaneous albinism) and in the CTDs is more common in women. An exception is ILD in rheumatoid arthritis, which is more common in men. o Because of occupational exposures, pneumoconioses occur more frequently in men.
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Risk Factors

Family history of ILD Smoking Occupational or environmental exposures

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Etiology
General

Inorganic dust Organic dust o Various fumes or gases Existing CTD Exposure to parasites through travel HIV infection

ILDs are nonmalignant disorders and are not caused by identified infectious agents. The precise pathways leading from injury to fibrosis are unknown. Each ILD may have an acute phase and a chronic phase. Among ILDs of known cause, the largest group comprises occupational and environmental exposures. ILD is classified into 2 groups on the basis of the major underlying histopathology. o Predominantly inflammation and fibrosis o Predominantly granulomatous reaction in interstitial or vascular areas Each group can be further subdivided according to whether the cause is known or unknown.

Alveolitis, interstitial inflammation, and fibrosis

Known cause

Asbestos

Fumes, gases Drugs: antibiotics, amiodarone, gold, and chemotherapeutic agents Radiation Aspiration pneumonia Residual of adult respiratory distress syndrome

Unknown cause
Idiopathic interstitial pneumonias o IPF, also known as usual interstitial pneumonia (UIP) o Desquamative interstitial pneumonia (DIP) o Respiratory bronchiolitis-associated ILD o Acute interstitial pneumonia (AIP), also known as diffuse alveolar damage o Cryptogenic organizing pneumonia (COP) (bronchiolitis obliterans with organizing pneumonia [BOOP]) o Nonspecific interstitial pneumonia (NSIP) CTDs o Systemic lupus erythematosus (SLE) o Rheumatoid arthritis o Ankylosing spondylitis o Systemic sclerosis o Sjgrens syndrome o Polymyositis and dermatomyositis Pulmonary hemorrhage syndromes o Goodpastures syndrome o Idiopathic pulmonary hemosiderosis o Isolated pulmonary capillaritis Pulmonary alveolar proteinosis Lymphocytic infiltrative disorders o Lymphocytic interstitial pneumonitis associated with CTD Eosinophilic pneumonias Lymphangioleiomyomatosis Amyloidosis Inherited diseases o Tuberous sclerosis o Neurofibromatosis o NiemannPick disease o Gaucher disease o HermanskyPudlak syndrome GI or liver diseases o Crohns disease o Primary biliary cirrhosis o Chronic active hepatitis

o Ulcerative colitis Graft-versus-host disease Bone marrow transplantation Solid-organ transplantation

Granulomatous reaction Known cause o Hypersensitivity pneumonitis (organic dusts) o Inorganic dusts Beryllium Silica Unknown cause o Sarcoidosis o Langerhans cell granulomatosis (eosinophilic granuloma of the lung) o Granulomatous vasculitides Wegeners granulomatosis Allergic granulomatosis of Churg-Strauss o Bronchocentric granulomatosis o Lymphomatoid granulomatosis

Associated Conditions
Allergy Pneumonia Infection o Parasitic o HIV o Tuberculosis o Echinococcosis o Histoplasmosis o Coccidioidomycosis o Nocardiosis CTDs o SLE o Rheumatoid arthritis o Ankylosing spondylitis o Systemic sclerosis o Sjgrens syndrome o Polymyositis and dermatomyositis GI and liver diseases o Crohns disease o Primary biliary cirrhosis o Chronic active hepatitis o Ulcerative colitis Vasculitis Graft-versus-host disease

Symptoms & Signs

Symptoms o Progressive exertional dyspnea: common, and most characteristic o Nonproductive cough o Hemoptysis o Wheezing o Chest pain o Sudden worsening of dyspnea, especially if associated with acute chest pain, may indicate spontaneous pneumothorax. o Fatigue o Weight loss Signs o Tachypnea o Bibasilar end-inspiratory dry crackles Common in ILD associated with inflammation, but less likely in the granulomatous lung diseases o Scattered late inspiratory high-pitched rhonchi (inspiratory squeaks) in patients with bronchiolitis o Advanced disease Signs and symptoms of pulmonary hypertension and cor pulmonale Cyanosis of the digits Clubbing of the digits Extrapulmonary signs and symptoms may accompany specific diagnoses. o Erythema nodosum, rash, uveitis, and conjunctivitis (e.g., in sarcoidosis and Behets syndrome) o Salivary gland enlargement (e.g., with Sjgrens syndrome and sarcoidosis) o Adenopathy and hepatosplenomegaly (e.g., with amyloidosis and sarcoidosis o Arthritis (e.g., connective tissue diseases, sarcoidosis, Behets syndrome, ankylosing spondylitis) o Weakness (e.g., polymyositis) o Neurologic findings (e.g., sarcoidosis)

Amyloidosis Emphysema Pneumothorax Chylous pleural effusion Lymphoma Sarcoidosis

Differential Diagnosis

IPF/UIP The most common form of idiopathic interstitial pneumonia Most patients with IPF are > 50 years. Biopsy is essential to confirm diagnosis; surgical biopsy is usually required.

DIP Rare but distinct clinical and pathologic entity found exclusively in cigarette smokers Peak incidence in fourth and fifth decades Biopsy confirms the diagnosis.

AIP (HammanRich syndrome) Rare, fulminant form of lung injury Diagnosis requires idiopathic syndrome of adult respiratory distress syndrome and lung biopsy confirmation of diffuse alveolar damage. Most patients are > 40 years of age. Onset is usually abrupt in previously healthy persons with a prodromal illness, generally lasting 714 days before presentation.

NSIP Subgroup of the idiopathic interstitial pneumonias that can be distinguished clinically and pathologically from UIP, DIP, AIP, and BOOP Presentation similar to IPF but usually at a younger age, often associated with a febrile illness

ILD associated with CTDs Progressive systemic sclerosis o Clinical evidence of ILD is present in ~50% of patients. o Pathologic evidence in 75% Rheumatoid arthritis o ILD more common in men o In up to 20% of cases SLE o Chronic progressive ILD is uncommon.

Polymyositis and dermatomyositis

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10% of cases Clinical features similar to those of IPF o Occurs more commonly in a subgroup of patients with an antiJo-1 antibody Sjgrens syndrome o Lung biopsy frequently required to establish precise pulmonary diagnosis Drug-induced ILD Many classes of drugs may induce diffuse ILD. Onset may be abrupt and fulminant or insidious, extending over weeks to months. Detailed medication history is needed, including overthe-counter medications, oily nose drops, or petroleum products (mineral oil). o Drug may have been taken for several years before a reaction develops (e.g., amiodarone). o Lung disease may occur weeks to years after drug has been discontinued (e.g., carmustine). Extent and severity of disease are usually dose related.

COP (idiopathic BOOP)

Onset is usually in the fifth and sixth decades. May present like a flulike illness

Eosinophilic pneumonia Eosinophilic pulmonary infiltrates and, commonly, peripheral blood eosinophilia

Pulmonary alveolar proteinosis Not strictly an ILD, but resembles and is therefore considered with these conditions Characterized by the accumulation of lipoproteinaceous material in the distal air spaces Little or no lung inflammation, and preservation of the underlying lung architecture Typical age at presentation is 3050 years; men predominate.

Clinical presentation is usually insidious and manifested by progressive exertional dyspnea, fatigue, weight loss, and low-grade fever. Nonproductive cough is common, but with occasional expectoration of "chunky" gelatinous material.

Pulmonary lymphangioleiomyomatosis Rare condition in premenopausal women; suspect in young women with emphysema, recurrent pneumothorax, or chylous pleural effusion White persons are affected much more commonly than members of other racial groups. Often misdiagnosed as asthma or chronic obstructive pulmonary disease Hemoptysis may be life threatening. Spontaneous pneumothorax occurs in 50% of patients.

Syndromes of ILD with DAH Clinical onset is often abrupt, with cough, fever, and dyspnea. Severe respiratory distress requiring ventilatory support may be evident at initial presentation. Although hemoptysis is expected, it can be absent at the time of presentation in one-third of cases. Evaluation of lung or renal tissue by immunofluorescent techniques indicates: o Absence of immune complexes (pauci-immune) in Wegeners granulomatosis, microscopic polyangiitis, pauci-immune glomerulonephritis, and isolated pulmonary capillaritis o Granular pattern is found in the CTDs, particularly SLE o Characteristic linear deposition is found in Goodpastures syndrome. o Granular deposition of immunoglobulin A containing immune complexes is present in Henoch Schnlein purpura.

Inherited disorders associated with ILD Tuberous sclerosis, neurofibromatosis, NiemannPick disease, Gauchers disease, HermanskyPudlak syndrome

ILD with a granulomatous response in lung tissue or vascular structures Hypersensitivity pneumonitis: caused by inhalation of organic dusts Inhalation of inorganic dusts Sarcoidosis PLCH o Rare, smoking-related, diffuse lung disease that primarily affects men 2040 years of age o Clinical presentation varies from asymptomatic to a rapidly progressive condition. o Pneumothorax occurs in about 25% of patients. Granulomatous vasculitides o Characterized by pulmonary angiitis with associated granuloma formation o Lungs are almost always involved, although any organ system may be affected. o Conditions associated with systemic vasculitis Wegeners granulomatosis Allergic angiitis and granulomatosis (Churg Strauss) o Conditions generally limited to the lung Necrotizing sarcoid granulomatosis Benign lymphocytic angiitis and granulomatosis

Lymphocytic infiltrative disorders Disorders either are benign or can behave as low-grade lymphomas. Angioimmunoblastic lymphadenopathy with dysproteinemia o Rare lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever, hepatosplenomegaly, and hemolytic anemia, with ILD in some cases Lymphocytic interstitial pneumonitis o Rare form of ILD occurs in adults, some with autoimmune disease or dysproteinemia o Has been reported in patients with Sjgrens syndrome and HIV o Lymphomatoid granulomatosis o Angiocentric malignant (T-cell) lymphoma characterized by a polymorphic lymphoid infiltrate, angiitis, and granulomatosis

Pulmonary, skin, and central nervous system are most frequently involved.
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Bronchocentric granulomatosis Descriptive histologic term for an uncommon and nonspecific pathologic response to a variety of airway injuries Approximately half of patients have chronic asthma, with severe wheezing and peripheral blood eosinophilia.

Diagnostic Approach
Clinical diagnosis is possible for many forms of ILD, especially if occupational and environmental histories are aggressively pursued.

History Acute presentation (days to weeks) is unusual, but can be seen with: o Allergy (drugs, fungi, helminths) o Acute idiopathic interstitial pneumonia o Eosinophilic pneumonia o Hypersensitivity pneumonitis Subacute presentation (weeks to months) may occur in all ILDs, especially in: o Sarcoidosis o Drug-induced ILDs o Alveolar hemorrhage syndromes o COP o Acute immunologic pneumonia that complicates SLE or polymyositis Chronic presentation (months to years) o Most ILDs present in this way, especially: IPF Sarcoidosis PLCH (Langerhans cell granulomatosis, eosinophilic granuloma, or histiocytosis X) Pneumoconioses CTD Episodic presentations are unusual and include: o Eosinophilic pneumonia o Hypersensitivity pneumonitis o COP o Vasculitides o Pulmonary hemorrhage o ChurgStrauss syndrome

Demographic factors

Age (see Epidemiology) Sex (see Epidemiology)

Family history Familial association with autosomal dominant pattern o Tuberous sclerosis o Neurofibromatosis Autosomal recessive pattern o Niemann-Pick disease o Gaucher disease o HermanskyPudlak syndrome Familial clustering o Sarcoidosis Familial lung fibrosis associated with mutations in surfactant protein C gene o NSIP o DIP o UIP

Smoking history Patients with the following ILDs are almost always current or former smokers. o PLCH o DIP o Goodpastures syndrome o Respiratory bronchiolitis o Pulmonary alveolar proteinosis Two-thirds to 75% of patients with IPF have a history of smoking.

Occupational and environmental history Chronologic listing of lifelong employment, including specific duties and known exposures In hypersensitivity pneumonitis, respiratory symptoms, fever, chills, and abnormal findings on chest radiography are often temporally related to a hobby or the workplace. o Pigeon breeders disease o Farmers lung Symptoms may diminish or disappear after leaving the site of exposure for several days and reappear on return.

Other important history Travel history o Parasitic infections may cause pulmonary eosinophilia. Risk factors for HIV infection; associated conditions include: o BOOP o AIP o Lymphocytic interstitial pneumonitis o Diffuse alveolar hemorrhage (DAH)

Studies to consider

Laboratory testing when appropriate Chest radiography Chest CT Pulmonary function tests Cardiopulmonary exercise testing Fiberoptic bronchoscopy and bronchoalveolar lavage Lung biopsy is often needed to confirm diagnosis. Blood analysis o With a few exceptions, notably connective tissue diseases, laboratory testing is not diagnostically specific for any particular condition. o The following are most helpful: Elevated circulating immune-complex titers, serum immunoglobulin levels, and erythrocyte sedimentation rate in IPF Markedly elevated serum levels of lung surfactant proteins A and D in pulmonary alveolar proteinosis Elevated leukocyte count in DAH Decreased hematocrit in DAH Elevated serum angiotensin-converting enzyme level in sarcoidosis Serum precipitins confirm exposure if hypersensitivity pneumonitis is suspected, although they are not diagnostic. Antineutrophil cytoplasmic or antibasement membrane antibodies if vasculitis is suspected Antinuclear antibodies, anti-immunoglobulin antibodies (rheumatoid factors), and circulating immune complexes are identified in some patients, even in the absence of a defined CTD.

Laboratory Tests

An elevated lactate dehydrogenase level is a nonspecific finding common to ILDs. Anti-basement cytoplasmic antibody is elevated in Goodpastures syndrome. Urinalysis o Abnormalities may be seen with connective tissue disease, vasculitides, and drug-induced disease.

Imaging
Chest radiography Nonspecific in most cases o ~ 20% of patients with ILD have normal chest radiographs. o Findings correlate poorly with the clinical or histopathologic stage of the disease. Bibasilar reticular pattern is most common. Other findings that may be seen:

Nodular or mixed pattern of alveolar filling and increased reticular markings o Nodular opacities with a predilection for the upper lung zones Sarcoidosis PLCH Chronic hypersensitivity pneumonitis Silicosis Berylliosis Rheumatoid arthritis (necrobiotic nodular form) Ankylosing spondylitis o Diffuse alveolar opacities may cause the following conditions to be confused with atypical pneumonias. ILD secondary to allergy (drugs, fungi, helminths) Acute idiopathic interstitial pneumonia Eosinophilic pneumonia Hypersensitivity pneumonitis o Extensive parenchymal lung disease on chest radiography without significant dyspnea Sarcoidosis Silicosis PLCH Hypersensitivity pneumonitis Lipoid pneumonia
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Lymphangitis carcinomatosis, especially early in the course of the illness o DIP: diffuse, hazy opacities o AIP: diffuse, bilateral, air-space opacification o ILD associated with polymyositis and dermatomyositis: diffuse reticular or nodular opacities with a predilection for the lung bases o COP: bilateral, patchy, or diffuse alveolar opacities in the presence of normal lung volume o Pulmonary alveolar proteinosis: Bilateral symmetric alveolar opacities located centrally in mid and lower lung zones result in a "bat-wing" distribution. o ILD with DAH: nonspecific, new patchy or diffuse alveolar opacities o PLCH: poorly defined or stellate nodules (210 mm in diameter), reticular or nodular opacities, bizarreshaped upper-zone cysts, preservation of lung volume, sparing of the costophrenic angles o Bronchocentric granulomatosis: irregularly shaped, unilateral and solitary nodular or mass lesions with poorly defined margins and upper-lobe predominance

High-resolution CT Superior to plain chest radiography for early detection and confirmation Better assessment of extent and distribution of disease Especially useful in the investigation of patients with normal chest radiographs Coexisting disease (e.g., mediastinal adenopathy, carcinoma, or emphysema) is often best recognized on high-resolution CT. Useful for determining the most appropriate area for biopsy May be sufficiently characteristic to preclude the need for lung biopsy in: o IPF (See Figure 1.) o Sarcoidosis o Hypersensitivity pneumonitis o Asbestosis o Lymphangitic carcinoma o PLCH IPF: patchy, predominantly basilar, subpleural reticular opacities, often associated with traction bronchiectasis and honeycombing DIP: diffuse hazy opacities

AIP: bilateral, patchy, symmetric areas of ground-glass attenuation NSIP: bilateral, subpleural ground-glass opacities, often associated with lower-lobe volume loss and possibly patchy areas of airspace consolidation and reticular abnormalities (See Figure 2.) COP: areas of airspace consolidation, ground-glass opacities, small nodular opacities, and bronchial wall thickening and dilation Pulmonary alveolar proteinosis: ground-glass opacification, thickened intralobular structures, interlobular septa Lymphangioleiomyomatosis: thin-walled cysts surrounded by normal lung without zonal predominance PLCH: Nodules and thin-walled cysts are virtually diagnostic.

Diagnostic Procedures
Tissue and cellular examination o Lung biopsy is the most effective method for confirming diagnosis and assessing disease activity. o Fiberoptic bronchoscopy with multiple transbronchial lung biopsies (48 biopsy samples) is often the initial procedure of choice. o If a specific diagnosis is not made by transbronchial biopsy, surgical lung biopsy by videoassisted thoracic surgery or open thoracotomy is indicated. o Relative contraindications to lung biopsy Serious cardiovascular disease, honeycombing, and other radiographic evidence of diffuse end-stage disease Severe pulmonary dysfunction Other major operative risks, especially in elderly persons Pulmonary function testing o Abnormalities are seen in most patients. Spirometry and lung volumes

Important in assessing extent of pulmonary involvement Most common is a restrictive defect with: o Reduced total lung capacity o Reduced functional residual capacity o Reduced residual volume o Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) are reduced secondary to decreased total lung capacity.

o FEV1/FVC ratio is usually normal or increased. Diffusing capacity o Reduction in the diffusing capacity of the lung for carbon monoxide (DLCO) is a common but nonspecific finding in most ILDs. o Severity of DLCO reduction does not correlate with disease stage. Arterial blood gas o Resting arterial blood gas may be normal or reveal hypoxemia and respiratory alkalosis. o Carbon dioxide retention is rare and is usually a manifestation of end-stage disease. Pulmonary function studies have proven to have prognostic value in patients with idiopathic interstitial pneumonias, particularly IPF or NSIP. Cardiopulmonary exercise testing o Because severe exercise-induced hypoxemia may go undetected, perform exercise testing with measurement of arterial blood gases. o Serial assessment of resting and exercise gas exchange is excellent for following disease activity and response to treatment (especially in IPF). Fiberoptic bronchoscopy and bronchoalveolar lavage

In selected patients, cellular analysis of bronchoalveolar lavage fluid may be useful in narrowing the differential diagnostic possibilities among various types of ILD. o See Bronchoscopy for details. Electrocardiography o Usually normal o In pulmonary hypertension, electrocardiography demonstrates right-axis deviation, right ventricular hypertrophy, or right atrial enlargement or hypertrophy. Echocardiography o In pulmonary hypertension: right ventricular dilatation and/or hypertrophy
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Treatment Approach
ILD is often associated with considerable morbidity and mortality. There is little consensus regarding the best management of most patients. Goals of treatment o Early identification

Permanent removal of the offending agent, when known o Aggressive suppression of acute and chronic inflammatory process to reduce further lung damage Smoking cessation Hypoxemia (partial pressure of arterial oxygen [PaO2] < 55 mmHg) at rest and/or with exercise should be managed by supplemental oxygen. If cor pulmonale develops, diuretic therapy and phlebotomy may occasionally be required. Lung transplantation may be considered in certain patients.
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Specific Treatments
Glucocorticoids Mainstay of therapy for suppression of active alveolitis Success rate is low; no direct evidence that steroids improve survival or quality of life in many ILDs for which they are commonly used Recommended for symptomatic ILD patients with: o Idiopathic interstitial pneumonias o Eosinophilic pneumonias o COP o CTDs o Sarcoidosis o Acute inorganic dust exposures o Acute radiation pneumonitis o DAH o Drug-induced ILD o DIP o Acute and chronic stages of organic dust disease Optimal dose and proper length of therapy with glucocorticoids in the treatment of most ILDs are not known. o Starting dose: prednisone, 0.51 mg/kg in a oncedaily oral dose (based on the patients lean body weight) o Dose is continued for 412 weeks, at which time the patient is reevaluated. o If patient is stable or improved, dose is tapered to 0.250.5 mg/kg and maintained for an additional 412 weeks, depending on course. o Rapid tapering or a shortened course of glucocorticoid treatment can result in recurrence.

If the patients condition continues to decline while on glucocorticoids, a second agent (see below) is often added and the prednisone dose is lowered to or maintained at 0.25 mg/kg per day. Mainstay of therapy for DAH associated with systemic vasculitis, CTD, Goodpastures syndrome, and isolated pulmonary capillaritis o IV methylprednisolone, 0.52.0 g daily in divided doses for up to 5 days o Followed by a gradual tapering o Maintenance on an oral preparation o Prompt initiation of therapy is important, particularly in the face of renal insufficiency, since early initiation of therapy has the best chance of preserving renal function.
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Cytotoxic agents: cyclophosphamide and azathioprine Used with variable success in IPF, vasculitis, and other ILDs Dosage: 12 mg/kg lean body weight per day, with or without glucocorticoids Objective response usually requires at least 812 weeks. If the above drugs fail or are not tolerated, other agents may be tried:methotrexate, colchicine, penicillamine, and cyclosporine.

Antifibrotic agents (for IPF) Colchicine Pirfenidone Interferon 1b No evidence that any of these treatments improves survival or quality of life

Supplemental oxygen When PaO2 < 55 mmHg at rest and/or with exercise To prevent or delay the onset of pulmonary hypertension and cor pulmonale

Lung transplantation See Lung Transplantation for details. May be considered in patients who experience progressive deterioration despite optimal medical

management and who meet established criteria of chronic and irreversible ILD IPF: indications o Vital capacity or total lung capacity < 6070% of predicted normal value o DLCO < 5060% of predicted normal value o Pulmonary arterial hypertension o Hypoxemia (PaO2 < 60 mmHg or arterial oxygen saturation < 90%) at rest or with activity (on room air) o Progressive disease in spite of drug therapy Other Pulmonary alveolar proteinosis: whole-lung lavage o Provides relief of dyspnea or progressive hypoxemia o May provide long-term benefit Pulmonary lymphangioleiomyomatosis o Hormonal therapy has been tried but without proven efficacy. Progesterone, 10 mg/d Luteinizing hormonereleasing hormone analogues Oophorectomy is no longer recommended, and estrogen-containing drugs should be discontinued. Goodpastures syndrome o Plasmapheresis as adjunctive treatment Hypersensitivity pneumonitis o Avoidance of the antigen causing the allergic alveolitis

Monitoring

Cardiopulmonary exercise testing o Excellent for following disease activity and response to treatment (especially in IPF) o Serial assessment of resting and exercise gas exchange o Increasingly, the 6-minute walk test is used to obtain a global evaluation of submaximal exercise capacity in patients with ILD. The walk distance and level of oxygen desaturation tend to correlate with the patients baseline lung function. Progressive respiratory impairment Pulmonary embolism

Complications

Prognosis

Cor pulmonale Infection Pneumothorax Drug-related complications Death IPF Poor response to therapy and poor prognosis The clinical course is variable, with a 5-year survival rate of 2040% after diagnosis. o Patients with acute exacerbations (an accelerated phase of rapid clinical decline) of IPF have a poor prognosis. Acute exacerbations are defined by: o Worsening of dyspnea within a few days to 4 weeks o Newly developing diffuse radiographic opacities o Worsening hypoxemia o Absence of infectious pneumonia, heart failure, and sepsis Rate of these acute exacerbations ranges from 1057%. DIP o DIP is associated with better response to smoking cessation and systemic glucocorticoids than the more common IPF. o 10-year survival rate: ~70% AIP o Mortality rate is high (>60%), with most patients dying within 6 months of presentation. o Recurrences have been reported. o Those who recover often have substantial improvements in lung function. NSIP o The majority have a good prognosis, showing improvement after treatment with glucocorticoids, often used in combination withazathioprine. ILD associated with progressive systemic sclerosis o Pulmonary vascular disease, alone or in association with pulmonary fibrosis, pleuritis, or recurrent aspiration pneumonitis, is strikingly resistant to current modes of therapy. COP
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Glucocorticoid therapy induces clinical recovery in two-thirds of patients. o A few patients have rapidly progressive courses with fatal outcomes despite glucocorticoids. Pulmonary lymphangioleiomyomatosis o Progression is common, with a median survival of 810 years from diagnosis. PLCH o Discontinuance of smoking results in clinical improvement in one-third of patients. o Most patients have persistent or progressive disease. o Death due to respiratory failure occurs in ~10%.
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Prevention ICD-9-CM
136.3 Pneumocystosis (includes acute interstitial lung disease) 515 Postinflammatory pulmonary fibrosis (includes chronic interstitial lung disease)

Smoking cessation

See Also
Asthma Berylliosis Bronchoscopy Chronic Obstructive Lung Disease Community-Acquired Pneumonia Desquamative Interstitial Pneumonia Drug-Induced Lung Diseases Histoplasmosis Hospital-Acquired Pneumonia Hypersensitivity Pneumonitis Interstitial Lung Disease Associated with Collagen Vascular Disorders Lung Transplantation Pulmonary Function Tests Pulmonary Arterial Hypertension, Secondary Sarcoidosis Tuberculosis

Internet Sites

Professionals o Clinical Trials, Interstitial Lung Disease ClinicalTrials.gov o Homepage National Heart, Lung, and Blood Institute Patients

Diffuse interstitial lung disease MedlinePlus

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General Bibliography
American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161:646, 2000 [PMID:10673212] Gal AA, Staton GW: Current concepts in the classification of interstitial lung disease. Am J Clin Pathol 123 Suppl:S67, 2005 [PMID:16100869] Khalil N, OConnor R: Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment. CMAJ 171:163, 2004 King TE: Clinical advances in the diagnosis and therapy of the interstitial lung diseases. Am J Respir Crit Care Med 172:268, 2005 [PMID:15879420] Lynch DA et al: Idiopathic interstitial pneumonias: CT features. Radiology236:10, 2005 [PMID:15987960] Martinez FJ: Idiopathic interstitial pneumonias: usual interstitial pneumonia versus nonspecific interstitial pneumonia. Proc Am Thorac Soc 3:81, 2006 [PMID:16493155] Sullivan EJ: Lymphangioleiomyomatosis: a review. Chest 114:1689, 1998 [PMID:9872207] Swigris JJ et al: Idiopathic pulmonary fibrosis: challenges and opportunities for the clinician and investigator. Chest 127:275, 2005 [PMID:15653995] Vassallo R et al: Clinical outcomes of pulmonary Langerhans'-cell histiocytosis in adults. N Engl J Med 346:484, 2002 [PMID:11844849] Walter N, Collard HR, King TE: Current perspectives on the treatment of idiopathic pulmonary fibrosis. Proc Am Thorac Soc 3:330, 2006 [PMID:16738197] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 255, Interstitial Lung Diseases by TE King Jr.

PEARLS
Cough and dyspnea are the most important symptoms of IPF, and clubbing of the digits is a common physical finding. Lymphangioleiomyomatosis is the most common interstitial lung disease in premenopausal women. o Oral or intramuscular medroxyprogesterone is an effective therapy.