WORKUP

Lab Studies:

• Intrinsic lung diseases

• Routine laboratory evaluations often fail to reveal positive findings. However, anemia can indicate vasculitis, polycythemia can indicate hypoxemia in advanced disease, and leukocytosis can suggest acute hypersensitivity pneumonitis.

• The decision to perform additional tests should be directed by the findings of the clinical assessment. Antinuclear antibodies and rheumatoid factor should be measured to screen for collagen vascular disorders, creatine kinase for polymyositis, antineutrophilic cytoplasmic antibodies for vasculitis, and antiglomerular basement membrane antibody for Goodpasture syndrome.

• The presence of precipitating antibodies to an antigen may help in diagnosing hypersensitivity pneumonitis. Serum angiotensin-converting enzyme levels are often elevated in patients with sarcoidosis, but this finding has poor specificity.

• Extrinsic disorders: An elevated creatine kinase level may indicate myositis, which may cause muscle weakness and restrictive lung disease.

Imaging Studies:

• Chest radiography for intrinsic lung disorders

• The diagnosis of an interstitial lung disorder is often initially based on abnormal chest radiograph findings, which can be normal in as many as 10% of patients. All previous chest films should be reviewed.

• The most common radiographic abnormality is a reticular pattern. Nodular, reticulonodular, or mixed patterns, such as alveolar filling (ie, ground-glass appearance), and increased interstitial markings are not unusual; however, these are not predictive of a specific pathological picture.

• Air-space opacities suggest pulmonary hemorrhage, eosinophilic pneumonia, and BOOP.

• Upper-zone predominance on chest radiographs is observed in patients with sarcoidosis, histiocytosis X, chronic hypersensitivity pneumonitis, pneumoconiosis, or ankylosing spondylitis. Lower-zone predominance is seen in patients with IPF, asbestosis, or collagen vascular diseases.

• The finding of honeycombing correlates with advanced fibrosis and indicates a poor prognosis. Bilateral hilar lymphadenopathy, with or without mediastinal adenopathy, suggests sarcoidosis.

• Computed tomography of the chest

• High-resolution computed tomography of the chest can be helpful, but the accuracy of the findings for helping determine a specific etiology is inconsistent. Bibasilar peripheral lung zone involvement is seen in patients with IPF, asbestosis, connective tissue disease, or eosinophilic pneumonia.

• Central disease along bronchovascular bundles is indicative of sarcoidosis or lymphangitic carcinoma.

• Upper-zone predominance is observed in patients with sarcoidosis, eosinophilic granuloma, or chronic hypersensitivity pneumonitis. Lower-zone predominance is seen in patients with IPF, asbestosis, or rheumatoid arthritis.

• Lower-zone and peripheral infiltration is ordinarily seen in patients with IPF or asbestosis.

• The presence of bilateral cysts and nodules, with preservation of lung volumes, may suggest a diagnosis of LAM or histiocytosis X.

• Bibasilar reticular fibrosis with coexisting retraction bronchiectasis indicates end-stage irreversible disease, and ground-glass attenuation may indicate the presence of an active inflammatory process with potential to respond to medical therapy.

• Tests for extrinsic disorders

• Evidence of nonmuscular diseases of the chest wall and associated deformities of the spinal column and ribs are readily appreciated on chest radiographs. The severity of kyphoscoliosis is determined by the Cobb angle, which, when greater than 100°, indicates severe deformity. Neuromuscular diseases are also diagnosed based on chest radiograph findings showing low volumes and basal atelectasis.

• Fluoroscopy is used to assess for diaphragm paralysis.

• A positive result from a sniff test may demonstrate paradoxical upward movement of the affected diaphragm.

Other Tests:

• Pulmonary function testing

• Complete lung function testing includes spirometry, lung volume, diffusing capacity, and arterial blood gas measurements. Pulmonary function test findings do not indicate a specific diagnosis or help distinguish alveolitis from fibrosis. Findings from sequential tests are invaluable for monitoring the course of the disease and assessing the response to therapy.

• All disorders are associated with a restrictive defect with a reduction in TLC, FRC, and residual volume (RV).

• While a reduction in the forced expiratory volume in one second (FEV₁) and the forced vital capacity (FVC) with a normal or increased FEV₁-to-FVC ratio suggests a restrictive pattern, the diagnosis of restriction is based on a decreased TLC. The assessment of the severity of restriction is also based on TLC.

• An obstructive airflow limitation may be observed in patients with sarcoidosis, LAM, hypersensitivity pneumonitis, and pulmonary fibrosis with concomitant chronic obstructive pulmonary disease.

• Tests for extrinsic lung disorders

• In nonmuscular diseases of the chest wall, severe kyphoscoliosis produces a restrictive pattern. The TLC is markedly reduced, with relative preservation of the RV. The vital capacity is reduced, and the RV-to-TLC ratio is elevated. Chest wall components are reduced, and inspiratory muscle weakness may also contribute to the restrictive process. Maximal inspiratory and expiratory pressures are modestly decreased in patients with mild disease but are severely reduced in patients with advanced disease.

• Hypoxemia is due to a ventilation-perfusion mismatch caused by the underlying atelectasis and shunt.

• In neuromuscular diseases, the maximal inspiratory and expiratory mouth pressures vary from normal to severely reduced. When maximal inspiratory pressure falls below 30 cm of water, ventilatory failure commonly ensues.

• Patients with chronic muscular diseases have a decreased vital capacity and FRC, but the RV is preserved. TLC is also moderately reduced. Breathing during sleep is often abnormal in these patients. They have nocturnal desaturation during rapid eye movement sleep, secondary to hypoventilation.

• The diffusing capacity of lung for carbon monoxide (DLCO) is reduced in all patients with intrinsic lung disorders, and the severity of the reduction does not correlate well with the stage of the disease. The DLCO is the most sensitive parameter, and findings may be abnormal even when the lung volumes are preserved. A normal DLCO value excludes intrinsic lung disease and indicates a chest wall, pleural, or neuromuscular cause of restrictive lung disease.

• Arterial blood gas values at rest may reveal hypoxemia. Arterial oxygen desaturation occurs with exercise, along with an excessive increase in the respiratory rate and a high ratio of dead-space gas volume to tidal gas volume.

• Cardiopulmonary exercise testing with measurements of gas exchange and oxygenation is more sensitive, and findings correlate better with lung biopsy but do not help predict the prognosis. A 6-minute walk test with oximetry provides a measure of oxygen requirement and a quantifiable measure of disease progression.
  

Procedures:

• Bronchoalveolar lavage

• In selected cases, bronchoalveolar lavage (BAL) cellular analysis may be helpful to narrow the differential diagnosis. However, the utility of BAL in the clinical assessment and management of interstitial lung diseases remains to be established.

• Performing BAL lymphocytosis in patients with IPF may help predict steroid responsiveness. A predominance of T lymphocytes with an elevated CD4-to-CD8 ratio is characteristic but not diagnostic of sarcoidosis.

• BAL fluid may contain malignant cells, asbestos bodies, eosinophils, and hemosiderin macrophages, which assist in making a diagnosis.

• Lung biopsy

• A lung biopsy is not always required to make a diagnosis in patients suggested to have interstitial lung diseases. A lung biopsy can provide information that may help lead to a specific diagnosis, assess for disease activity, exclude neoplastic and infectious processes, establish a definitive diagnosis, and predict the prognosis.

• Fiberoptic bronchoscopy with transbronchial lung biopsy is often the initial procedure of choice, especially when sarcoidosis, lymphangitic carcinomatosis, eosinophilic pneumonia, Goodpasture syndrome, histiocytosis X, hypersensitivity pneumonitis, or infection is suggested based on clinical evidence.

• Surgical lung biopsy

• Video-assisted thoracoscopic lung biopsy is the preferred method for obtaining lung tissue samples for analysis.

• Histologic patterns may be helpful in narrowing the differential diagnosis. Honeycombing is seen in end-stage disease, in which the original disease process often cannot be differentiated.

   

  • The common histologic patterns include interstitial pneumonitis (ie, IPF). Subpleural and paraseptal inflammation is present, with an appearance of temporal heterogeneity. Patchy scarring of the lung parenchyma and normal, or nearly normal, alveoli interspersed between fibrotic areas is the hallmark of this disease. Also, the lung architecture is completely destroyed.

     

  • Desquamative interstitial pneumonitis is characterized by diffuse and temporally uniform involvement of the lung parenchyma. The alveoli are filled with macrophages and hyperplastic type II pneumocytes.

     

  • BOOP (also called proliferative bronchiolitis) is often patchy and peribronchiolar. The proliferation of granulation tissue within small airways and alveolar ducts is excessive and is associated with chronic inflammation of surrounding alveoli.

     

  • Diffuse alveolar damage is marked by a nonspecific reaction with diffuse temporally uniform involvement and marked thickening of the alveolar septa; inflammatory cell infiltration and type II cell hyperplasia and fibroblast proliferation are present.

     

  • For acute interstitial pneumonia, the pathological appearance is identical to that of diffuse alveolar damage.

     

  • In eosinophilic pneumonia, the eosinophils and macrophages are the predominant alveolar inflammatory cells, and they also extend into the interstitium.

     

  • Lymphocytic interstitial pneumonitis marked by a lymphoid infiltrate that involves both the interstitium and alveolar spaces is the prominent finding.

     

  • In nonspecific interstitial pneumonia, the lesions are characterized by a relatively uniform appearance consisting of mononuclear interstitial infiltrates associated with varying degrees of interstitial fibrosis.

     

  • Granulomatous lung diseases are marked by granulomas characterized by the accumulation of T lymphocytes, macrophages, and epithelioid cells. These may progress to pulmonary fibrosis.

Table. Contrasting Clinical, Radiologic, and Histologic Features of Acute Interstitial Pneumonia (AIP), Usual Interstitial Pneumonia (UIP), Nonspecific Interstitial Pneumonia (NSIP), and BOOP

Features	AIP	UIP	NSIP	BOOP
Pathologic
Temporal appearance	Uniform	Heterogeneous	Uniform	Uniform
Interstitial inflammation	Scant	Scant	Usually prominent	Variable
Collagen fibrosis	No	Patchy	Variable, diffuse	No
Fibroblast proliferation	Diffuse, interstitial	Patchy (fibroblast foci)	Occasional	Patchy, airspace
BOOP areas	Rare	No	Rare	--
Honeycomb changes	Rare	Yes	Rare	No
Hyaline membranes	Yes, often focal	No	No	No

TREATMENT

Medical Care: Treatment depends on the specific diagnosis, which is based on findings from the clinical evaluation, imaging studies, and lung biopsy.

Corticosteroids, immunosuppressive agents, and cytotoxic agents are the mainstay of therapy for many of the interstitial lung diseases. Objective data assessing the risks and benefits of immunosuppressive and cytotoxic agents to treat diverse interstitial lung disorders are sparse. Direct comparisons among these agents are lacking.

Ancillary therapies include supplemental oxygen therapy, which alleviates exercise-induced hypoxemia and improves performance.

• Idiopathic pulmonary fibrosis

   

  • The rate of progression of IPF is highly variable, and controversy exists regarding the timing of treatment. The disease may be responsive to treatment in the early, so-called inflammatory stage. IPF always progresses insidiously, and documenting the changes over short periods is difficult. Initiate a trial of therapy for 6-12 weeks, starting as early as possible, with the hope of slowing disease progression. Discontinue therapy if no benefit is observed or if adverse effects develop.

     

  • The prognosis for patients with IPF who do not respond to medical therapy is poor. They usually die within 2-3 years. These and other patients with severe functional impairment, oxygen dependency, and a deteriorating course should be listed for lung transplantation

• Corticosteroids

   

  • Corticosteroids are a first-line therapy but are associated with myriad adverse effects. Corticosteroids, the most commonly used drugs, halt or slow the progression of pulmonary parenchymal fibrosis with variable success.

     

  • Questions about which patients should be treated, when therapy should be started, and what constitutes the best therapy receive uncertain answers at present.

     

  • Although subjectively most patients with IPF feel better, an objective improvement occurs in 20-30% patients. A favorable response is a reduction in symptoms; the clearing of radiographs; and improvements in FVC, TLC, and DLCO. The optimal duration of therapy is not known, but treatment for 1-2 years is suggested.

• Cytotoxic therapy

   

  • Immunosuppressive cytotoxic agents may be considered for patients who do not respond to steroids, experience adverse effects, or have contraindications to high-dose corticosteroid therapy. The failure of steroid therapy is defined as a fall in FVC or TLC by 10%, a worsened radiographic appearance, and a decreased gas exchange at rest or with exercise.

     

  • Azathioprine is less toxic than methotrexate or cyclophosphamide and may be preferred as a corticosteroid-sparing agent for disorders that are not life threatening. A response to therapy may not occur for 3-6 months.

     

  • Because of potentially serious toxicities, cyclophosphamide is reserved for fulminant or severe inflammatory disorders refractory to alternate therapy.

• Antifibrotic therapies

   

  • These therapies, including colchicine, are suggested for a variety of fibrotic disorders, including IPF.

     

  • Recent studies demonstrate no difference in the decline of pulmonary function with either colchicine or prednisone; therefore, a trial of therapy with colchicine is reasonable in less symptomatic patients or those who are experiencing adverse effects with steroid therapy.

• Collagen vascular disease

   

  • Therapy for pulmonary fibrosis associated with collagen vascular disease is controversial because the course may be indolent. Because these diseases begin as an alveolitis, an aggressive approach may be warranted.

     

  • Patients with severe disease or those who have a deteriorating course must be treated with corticosteroids, cytotoxic therapy, or both.

• Sarcoidosis

   

  • Because the disease remits spontaneously, patients with respiratory symptoms and radiographic or pulmonary function evidence of extensive disease may benefit from corticosteroids. Patients with hypercalcemia or extrapulmonary involvement generally require treatment. Therapy should be continued for 6 months or longer; however, even after prolonged treatment, up to 50% of patients relapse after therapy is discontinued.

     

  • For patients who do not respond to corticosteroids, alternate therapies (eg, chloroquine, methotrexate, azathioprine) may be used; however, data are limited.

   

• Treatment of extrinsic lung disorders

   

  • Patients with nonmuscular chest wall disorders and neuromuscular disease may develop problems with ventilation and gas exchange during sleep. The effect of decreased chest wall and lung compliance or decreased muscle strength is hypercapnia and hypoxemia, which occurs initially during sleep. Identify and treat the cause of muscle weakness.

     

  • Treatment of neuromuscular diseases includes preventive therapies to minimize the impact of impaired secretion clearance and the prevention and prompt treatment of respiratory infections.

     

  • The patients who develop respiratory failure or have severe gas exchange abnormalities during sleep may be treated with noninvasive positive-pressure ventilation via a nasal or oronasal mask. Patients in whom these devices fail may require a permanent tracheotomy and ventilator assistance with a portable ventilator.

     

  • Noninvasive ventilation with body-wrap ventilators or positive-pressure ventilation has been proven beneficial because it helps relieve dyspnea and pulmonary hypertension and helps improve RV and gas exchange. Also, hospitalization rates are markedly reduced and the activities of daily living are enhanced.

     

  • Treatment for massive obesity consists of weight loss, which causes dramatic improvement in pulmonary function test findings but is harder to achieve. These patients require polysomnographic study because of the high incidence of nocturnal hypoventilation or upper airway obstructions. Either continuous positive airway pressure or noninvasive pressure ventilation helps correct hypoventilation and upper airway obstruction.

     

  • In advanced disease, when respiratory failure develops, these patients are treated with mechanical ventilation. If they have copious secretions, cannot control their upper airway, or are not cooperative, then invasive ventilation with a tracheotomy tube is indicated. In other patients, eg, those who have good airway control and minimal secretions, use noninvasive ventilation, initially nocturnal, and then intermittently.

Consultations:

• Consultation with a pulmonologist is helpful for diagnosis and management.

MEDICATION

Medications are best employed for the specific diagnosis. Corticosteroids, cytotoxic agents, and immunosuppressive agents have been used with varying success.

Drug Category: Corticosteroids -- Have anti-inflammatory properties and can modify the body's immune response.

Drug Name	Prednisone (Deltasone, Orasone, Meticorten) -- Used as an immunosuppressant in the treatment of autoimmune disorders. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Oral corticosteroid with relatively less mineralocorticoid activity. Therapy is best prescribed in consultation with a pulmonary disease specialist.
Adult Dose	1 mg/kg/d PO, up to 100 mg/d initially, followed by a taper after 8 wk to a maintenance dose of 0.25-0.5 mg/kg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur

Drug Category: Cytotoxic agents

Drug Name	Cyclophosphamide (Cytoxan, Neosar) -- Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells of immune system. Possible steroid-sparing medication.
Adult Dose	2 mg/kg/d IV; adjust dose according to leukocyte count
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severely depressed bone marrow function
Interactions	Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy	D - Unsafe in pregnancy
Precautions	Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis

Drug Name	Azathioprine (Imuran) -- Inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins. These effects may decrease proliferation of immune cells and result in lower autoimmune activity. Possible steroid-sparing medication.
Adult Dose	3 mg/kg/d PO/IV; not to exceed 200 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
Interactions	Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Pregnancy	D - Unsafe in pregnancy
Precautions	Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated

Drug Category: Anti-inflammatory agents -- Reduce inflammation by inhibiting key steps of the immune system.

Drug Name	Colchicine -- Decreases leukocyte motility and phagocytosis observed in inflammatory responses.
Adult Dose	0.6 mg/d PO
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias
Interactions	Toxicity of sympathomimetic agents and effects of CNS depressants are significantly increased
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Risk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count; dose-dependent GI upset is common

FOLLOW-UP

Deterrence/Prevention:

• Because the etiology of IPF is not known, prevention currently is not feasible. Several risk factors are known (eg, occupational metal or wood exposure and some common drugs have been identified); therefore, avoiding these may be prudent but is not proven.

Prognosis:

• The natural history of interstitial lung diseases is variable. It depends on the specific diagnosis and the extent and severity of lung involvement. IPF is typically a relentless progressive disorder, and patients have a mean survival of 4-6 years after diagnosis.

• Pulmonary sarcoidosis has a relatively benign self-limiting course, with spontaneous recovery or stabilization in most cases. Approximately 15% of patients develop pulmonary fibrosis and disability.

• Prognosis for collagen vascular diseases, eosinophilic pneumonia, BOOP, and drug-induced lung disease is generally favorable with treatment.

• Patients with chest wall diseases and neuromuscular disorders develop progressive respiratory failure and succumb during an intercurrent pulmonary infection.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Irrespective of lung biopsy findings, if patients are symptomatic, they should receive a trial period of therapy. For many years, the absolute standard for diagnosis of IPF was purported to be surgical lung biopsy. This theory (and subsequent biopsy findings) helped differentiate patients with cellular, as opposed to fibrotic, disease. In practice, the same histologic patterns are seen in both types of patients.

• Therapeutic options for IPF are limited. Drugs with antifibrotic properties or anti-inflammatory agents that work against growth factors and suppress inflammation are needed.

• An absolute requirement is that all patients with restrictive lung disease must be differentiated as having either intrinsic or extrinsic disorders, the determination of which is based on pulmonary function test findings.

Special Concerns:

• The clinical course of IPF is variable. In most cases, the course involves a progressive deterioration culminating in death from respiratory failure. The secular survival interval expectation among newly diagnosed patients is typically 3-5 years.

• A low FVC, low DLCO, low arterial oxygen at presentation, male sex, and older age are markers of a poor prognosis.

• Improvement after a trial corticosteroid therapy is associated with a favorable prognosis and is more probable in patients with cellular changes, which may be noted on lung biopsy findings, or ground-glass attenuation, which may be noted on a high-resolution CT scan image.

PICTURES

Caption: Picture 1. Restrictive lung disease. Approximately half of the patients with idiopathic pulmonary fibrosis develop clubbing. Clubbing is commonly seen in patients with asbestosis.
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Caption: Picture 2. Restrictive lung disease. Lung volume is plotted against transpulmonary pressure. Compliance is the change in volume for a given change in pressure. A patient with emphysema has much higher lung compliance compared to a patient with intrinsic lung disease.
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Caption: Picture 3. Restrictive lung disease. Idealized flow volume curves for normal, obstructive, and restrictive lungs.
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Caption: Picture 4. Restrictive lung disease. The expiratory flow volume curves of 2 patients are depicted graphically. A is a patient with restrictive lung disease (idiopathic pulmonary fibrosis), low forced vital capacity (FVC), but an increased ratio of forced expiratory volume in 1 second (FEV1) to FVC because of increased elastic recoil. B is a patient with chronic obstructive lung disease whose FEV1-to-FVC ratio is low but whose lung volumes are increased.
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Caption: Picture 5. Pulmonary function test results from a patient with restrictive lung disease.
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Caption: Picture 6. Gross pathology of small and firm lungs due to restrictive lung disease from advanced pulmonary fibrosis.
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Caption: Picture 7. Restrictive lung disease. Intrinsic lung disease may progress to extensive fibrosis, regardless of etiology. This is described as honeycomb lung.
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Caption: Picture 8. Restrictive lung disease. End-stage sarcoidosis.
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Caption: Picture 9. Restrictive lung disease. Usual interstitial pneumonitis (left).
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Caption: Picture 10. Restrictive lung disease. Usual interstitial pneumonitis (right).
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Caption: Picture 11. Restrictive lung disease. Histopathology of a case of idiopathic pulmonary fibrosis. Alveolitis with fibroblast proliferation and collagen deposition is present.
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Caption: Picture 12. Restrictive lung disease. Trichrome stain highlights the collagenous tissue of pulmonary fibrosis in blue.
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Caption: Picture 13. Restrictive lung disease. Hypersensitivity pneumonitis has features of interstitial pneumonitis, loosely formed granulomas, cholesterol clefts, and preservation of lung architecture in earlier stages.
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Caption: Picture 14. Restrictive lung disease. In usual interstitial pneumonitis or idiopathic pulmonary fibrosis, subpleural and paraseptal inflammation is present, with an appearance of temporal heterogeneity. Patchy scarring of the lung parenchyma and normal, or nearly normal, alveoli interspersed between fibrotic areas are the hallmarks of this disease. Also, the lung architecture is completely destroyed.
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Caption: Picture 15. Restrictive lung disease. Characteristic features of usual interstitial pneumonitis as described in Image 14.
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Caption: Picture 16. Restrictive lung disease. Bronchiolitis obliterans-organizing pneumonia (also called proliferative bronchiolitis) is often patchy and peribronchiolar. The proliferation of granulation tissue within small airways and alveolar ducts is excessive and is associated with chronic inflammation of surrounding alveoli.
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Caption: Picture 17. Restrictive lung disease. Bronchiolitis obliterans-organizing pneumonia, as described in Image 16, showing a close-up view of fibrogranulation tissue in terminal airspaces.
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Caption: Picture 18. Restrictive lung disease. Granulomatous lung diseases are marked by granulomas characterized by the accumulation of T lymphocytes, macrophages, and epithelioid cells. These may progress to pulmonary fibrosis. This low-power image shows well-formed granuloma along the airway.
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Caption: Picture 19. Restrictive lung disease. Multiple well-formed noncaseating granulomas secondary to sarcoidosis.
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Caption: Picture 20. Restrictive lung disease. Sarcoid granulomas.
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Caption: Picture 21. Restrictive lung disease. High-power view of sarcoid granuloma shows giant cells.
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Caption: Picture 22. A patient who developed restrictive lung disease had findings of bronchiolitis obliterans-organizing pneumonia on an open lung biopsy specimen.
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Caption: Picture 23. A patient who developed restrictive lung disease had findings of bronchiolitis obliterans-organizing pneumonia on an open lung biopsy specimen. The biopsy sample shows intraluminal buds of granulation tissue.
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Caption: Picture 24. Restrictive lung disease. Lymphocytic interstitial pneumonitis, for which the prominent finding is a lymphoid infiltrate that involves both the interstitium and alveolar spaces.
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Caption: Picture 25. Restrictive lung disease. Usual interstitial pneumonitis honeycombing.
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Caption: Picture 26. Restrictive lung disease. Chest radiograph of a 67-year-old man diagnosed with idiopathic pulmonary fibrosis, based on open lung biopsy findings. Extensive bilateral reticulonodular opacities are seen in both lower lobes.
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Caption: Picture 27. Restrictive lung disease. High-resolution CT scan of the same patient in Image 26 demonstrates peripheral honeycombing and several areas of ground-glass attenuation. Ground-glass opacification may correlate with active alveolitis and a favorable response to therapy.
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Caption: Picture 28. Restrictive lung disease. A CT scan image from a 59-year-old woman shows advanced pulmonary fibrosis. Extensive honeycombing and traction bronchiectasis are present.
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Caption: Picture 29. Restrictive lung disease may occur in stage II and stage III sarcoidosis. In this image, mediastinal lymphadenopathy is shown secondary to stage II disease.
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Caption: Picture 30. Restrictive lung disease. Sarcoidosis on CT scan shows nodules in midlung zones. These nodules are predominantly along the bronchovascular bundles and in a subpleural location.
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Caption: Picture 31. Restrictive lung disease secondary to sarcoidosis.
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Caption: Picture 32. Restrictive lung disease. A chest radiograph of stage III sarcoidosis. This stage refers to pulmonary infiltrates without evidence of mediastinal lymphadenopathy.
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Caption: Picture 33. Restrictive lung disease. Chest radiograph from a 39-year-old woman with severe kyphoscoliosis who developed hypercapnic respiratory failure. Spirometry findings showed a severe restrictive lung disease, with a forced expiratory volume in one second of 0.4 L/s and a forced vital capacity of 0.5 L.
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