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 or trigger.
Duration of illness
Acute disorders last days to weeks and include acute interstitial pneumonitis, eosinophilic pneumonia, and diffuse alveolar hemorrhage. [14]
Subacute disorders lasting weeks to months include sarcoidosis, drug-induced interstitial lung disease, alveolar hemorrhage syndrome, cryptogenic organizing pneumonia (COP), and connective-tissue diseases. [15]
Chronic cases lasting months to years include idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pulmonary Langerhans cell histiocytosis. [15]
Hypersensitivity pneumonitis and COP may manifest as acute, subacute, or chronic disease. [14]
Smoking history
Pulmonary Langerhans cell histiocytosis, desquamative interstitial pneumonitis, IPF, and respiratory bronchiolitis occur with increased frequency among persons who smoke or those who previously smoked. [16]
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, sulfonamides, thiazides, isoniazid, chemotherapeutic agents (eg, bleomycin, busulfan, cyclophosphamide, methotrexate), procainamide, and hydralazine.
Radiation may also cause pneumonitis and fibrosis.
Family history
Familial associations include IPF, sarcoidosis, and lymphangioleiomyomatosis (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. [18, 19]
Inhaled organic dust may cause hypersensitivity pneumonitis. [21]
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. It is helpful to use an objective quantification of the degree of dyspnea, such as the number of steps walked before becoming dyspneic.
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. [22]
Wheezing is an uncommon manifestation but can occur in patients with an airway-centered process, such as lymphangitic carcinomatosis, chronic eosinophilic pneumonia, and respiratory bronchiolitis or sarcoidosis. [23]
Chest pain is uncommon in most instances of the disease, but pleuritic chest pain can occur in patients and presents as serositis. This can occur with rheumatoid arthritis, systemic lupus erythematosus, and some drug-induced disorders. [20] Substernal chest pain is also commonly described in sarcoidosis. [24]
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. [25]
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. [26]
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. [27] Acute and chronic respiratory failure, pulmonary hypertension, and cor pulmonale eventually ensue.
Physical Examination
Intrinsic disorders
The physical examination in patients with intrinsic lung disorders may yield distinguishing physical findings.
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 IPF and is rare in others (eg, those with sarcoidosis or hypersensitivity pneumonitis). See the image below.
Approximately half of the patients with idiopathic pulmonary fibrosis develop clubbing. Clubbing is commonly seen in patients with asbestosis.
Extrapulmonary findings, including erythema nodosum, suggest sarcoidosis. A maculopapular rash can occur in those with connective-tissue diseases or drug-induced lung diseases. 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. Other signs of systemic vasculitis may include palpable purpura, signifying a leukocytoclastic vasculitis. In addition, renal involvement may be heralded by hematuria and anasarca.
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, jugulovenous distension with a prominent A wave, 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.
Complications
Acute exacerbation in patients with IPF is a recognized complication that occurs unpredictably and presents as worsening dyspnea. [28] Chest radiography demonstrates bilateral mixed alveolar-interstitial infiltrates, and CT scanning reveals ground-glass opacities and consolidation. Treatment includes high-dose systemic corticosteroids, although these are likely not effective, and the worsening disease portends an extremely poor prognosis. Series of patients with acute exacerbation of IPF reported in-hospital mortality rates between 78% and 96%. [29, 30, 31, 32]
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Approximately half of the patients with idiopathic pulmonary fibrosis develop clubbing. Clubbing is commonly seen in patients with asbestosis.
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Lung volume is plotted against transpulmonary pressure. Compliance is the change in volume for a given change in pressure. A patient with emphysema has a higher lung compliance compared with a patient with no lung disease, while a patient with restrictive lung disease has a reduction in compliance.
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Idealized flow volume curves for normal, obstructive, and restrictive lungs.
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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/FVC ratio is low but whose lung volumes are increased.
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Pulmonary function test results from a patient with restrictive lung disease.
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Gross pathology of small and firm lungs due to restrictive lung disease from advanced pulmonary fibrosis.
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Intrinsic lung disease may progress to extensive fibrosis, regardless of etiology. This is described as honeycomb lung.
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End-stage sarcoidosis.
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Usual interstitial pneumonitis (left).
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Usual interstitial pneumonitis (right).
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Histopathology of a case of idiopathic pulmonary fibrosis. Alveolitis with fibroblast proliferation and collagen deposition is present.
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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. Additionally, the lung architecture is completely destroyed.
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Characteristic features of usual interstitial pneumonitis as described in the image below.
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Cryptogenic 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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Cryptogenic organizing pneumonia, as described in the image below, showing a close-up view of fibrogranulation tissue in terminal airspaces.
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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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Multiple well-formed noncaseating granulomas secondary to sarcoidosis.
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Sarcoid granulomas.
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High-power view of sarcoid granuloma shows giant cells.
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A patient who developed restrictive lung disease had findings of cryptogenic organizing pneumonia on an open lung biopsy specimen.
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A patient who developed restrictive lung disease had findings of cryptogenic organizing pneumonia on an open lung biopsy specimen. The biopsy sample shows intraluminal buds of granulation tissue.
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Lymphocytic interstitial pneumonitis, for which the prominent finding is a lymphoid infiltrate that involves both the interstitium and alveolar spaces.
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Usual interstitial pneumonitis honeycombing.
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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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High-resolution CT scan of the same patient in the image below 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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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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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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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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Restrictive lung disease secondary to sarcoidosis.
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A chest radiograph of stage III sarcoidosis. This stage refers to pulmonary infiltrates without evidence of mediastinal lymphadenopathy.
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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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The flow volume curve of a patient with lung fibrosis.
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Likely case of idiopathic pulmonary fibrosis, which should be treated with prednisone.
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Pressure volume curve comparing lungs with emphysema, lungs with restrictive disease, and normal lungs.
Tables
Causes |
Examples |
Diagnosis |
PFT Findings |
Pleural |
Trapped lung, pleural scarring, large pleural effusions, chronic empyema, asbestosis |
Radiography, CT scanning, pleural manometry, pleural biopsy |
Low RVa, low TLC, low FVC |
Alveolar |
Edema, hemorrhage |
Radiography, CT scanning, physical examination |
Increased DLCOb in hemorrhage (Intrapulmonary hemoglobin absorbs the carbon monoxide, thus increasing the DLCO reading.) |
Interstitial |
Interstitial lung disease including IPFc, NSIPd, COPe |
Radiography, CT scanning, physical examination, echo often shows pulmonary hypertension |
Low RV, low FVC, low TLC, decreased DLCO, poor lung compliance |
Neuromuscular |
Myasthenia gravis, ALSf, myopathy |
Physical examination, EMGsg, serology |
Low RV, low TLC, low NIFh, low MMVi |
Thoracic/extrathoracic |
Obesity, kyphoscoliosis, ascites |
Physical examination |
Low ERVj and FRC in obesity, low VCk, TLC, FRCl in kyphoscoliosis |
aResidual volume. bDiffusion capacity of the lungs for carbon monoxide. cIdiopathic pulmonary fibrosis. dNonspecific interstitial pneumonitis. eCryptogenic organizing pneumonia. fAmyotrophic lateral sclerosis. gElectromyography. hNegative inspiratory force. iMaximal voluntary ventilation. jExpiratory reserve volume. kVital capacity. lFunctional residual capacity. |
|||
Features |
AIP |
UIP |
NSIP |
COP |
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 |
COP areas |
Rare |
No |
Rare |
-- |
Honeycomb changes |
Rare |
Yes |
Rare |
No |
Hyaline membranes |
Yes, often focal |
No |
No |
No |
