Interstitial Lung Disease
Terms in this set (134)
What is interstitial lung disease?
Interstitial lung diseases are chronic, nonmalignant, noninfectious diseases that cause fibrosis and derangement of the alveolar walls.
What is the general clinical presentation of interstitial lung disease?
They cause dyspnea and cough, show up with a reticular pattern of opacification on imaging and a restrictive defect on PFTs.
What causes interstitial lung disease?
About 60-70% of the time we can identify a cause: occupational exposures (silica, asbestos), connective tissue disease, medication reaction. About 30-40% of the time we see ILD in people who have no known reason to develop them.
What is the treatment for interstitial lung disease?
The treatment is steroids then cytotoxics, but response isn't always great. In fact, some ILDs have a very poor prognosis of either inexorable progression (asbestosis) or rapid compromise (IPF/UIP, AIP).
What does interstitial lung disease (ILD) mean?
Diffuse parenchymal lung diseases.
Describe diffuse parenchymal lung diseases (4).
They are a heterogeneous group of disorders that cause diffuse parenchymal lung damage, affecting the:
-Pulmonary capillary and lymphatic endothelium
-Perivascular and perilymphatic tissues
How are the different ILDs grouped together (3)?
Why is the name interstitial lung disease a misnomer?
In that airway disease, alveolar filling disease, vascular and pleural disease all can coexist with interstitial disease.
IILDs are subdivided according to their underlying histopathology, what are these subdivisions (2)?
-Predominantly inflammation and fibrosis (the majority)
-Predominantly granulomatous reactions (sarcoid, hypersensitivity pneumonitis)
Give a general description of ILDs with an inflammation and fibrosis pattern of histopathology (3).
-Common end pathway whatever the initial insult (medication, autoimmune, infectious, particulates)
-Starts with inflammation of the interstitial tissues
-Ultimately, leads to fibrosis (irreversible scarring) of the alveolar walls
List the ILDs that show inflammation and fibrosis patterns of histopathology (7).
-UIP: Usual interstitial pneumonia
-NIP: Nonspecific interstitial pneumonia
-RB: Respiratory bronchiolitis
-BOOP: Bronchiolitis obliterans organizing pneumonia
-DAD: Diffuse alveolar damage
-DIP: Desquamative interstitial pneumonia
-LIP: Lymphocytic interstitial pneumonia
Give a general description of ILDs with a granulomatous pattern of histopathology (3).
-Accumulation of T lymphocytes, macrophages, epithelioid cells organized into discrete structures in the parenchyma
-Can progress to fibrosis
List the ILDs that show granulomatous patterns of histopathology (2).
ILDs can also be subdivided by whether their cause is known or unknown. What are the types of ILD that have a known cause (2)?
ILDs caused by:
-Occupational and environmental exposures
-Associated connective tissue disorder or other primary disease (chronic pulmonary edema, neurofibromatosis, tuberous sclerosis, vasculitides, chronic gastric aspiration)
ILDs can also be subdivided by whether their cause is known or unknown. What are the types of ILD that have an unknown cause (2)?
-Idiopathic interstitial pneumonias.
-Idiopathic conditions that have distinct histology, clinical features and presentation and so are considered unique diseases
List the idiopathic ILDs which have distinct histologies patterns and are considered their own disease (6)
-Eosinophilic pulmonary diseases
-Pulmonary Langerhans' cell granulomatosis
-Pulmonary alveolar proteinosis
What is the name of clinical condition associated with usual interstitial pneumonia?
Idiopathic pulmonary fibrosis (IPF).
What is another term for bronchiolitis obliterans organizing pneumonia or BOOP?
Cryptogenic organizing pneumonia (COP).
What is another term for respiratory bronchiolitis or RB?
Respiratory bronchiolitis associated interstitial lung disease (RBIL).
Which clinical condition is associated with DAD?
Acute interstitial pneumonia (AIP).
What are the respiratory symptoms that present with an ILD (3)?
-Progressive exertional dyspnea
-Persistent, usually nonproductive cough
-Hemoptysis, wheezing, chest pain less common
What are the incidental findings that can be seen on a chest x-ray of a patient with an ILD
-Interstitial opacities in a reticular, nodular, or reticulonodular pattern
-Hilar lymphadenopathy for early stage sarcoidosis
List the acute ILDs (4)
-Acute idiopathic interstitial pneumonia
-Bronchiolitis obliterans organizing pneumonia
List the subacute ILDs (5).
-Some drug indiced ILDs
-Alveolar hemorrhage syndromes
-Idiopathic bronchiolitis obliterans with organizing pneumonia
-Connective tissue disease (SLE or polymyosistis)
List the chronic ILDs (4)
-Idiopathic pulmoanry fibrosis
-Pulmonary Langerhans cell histiocytosis
What information is relevant when taking the history of a patient who may potentially have an ILD (7)?
-Duration of illness
-Prior medication use
-Occupational history and environmental exposures
Why is age important to ask about when taking a history of a patient who might have an ILD?
Some of the ILDs are more common in certain age groups. For example, the majority of patients with sarcoidosis, connective tissue disease-associated ILD, lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, inherited forms of ILD (familial IPF, Gaucher's disease, Hermansky-Pudlak syndrome) present between the ages of 20 and 40 years. In contrast, most patients with idiopathic pulmonary fibrosis are over age 50.
Why is gender important to ask about when taking a history of a patient who might have an ILD?
Lymphangioleiomyomatosis and pulmonary involvement in tuberous sclerosis occur exclusively in premenopausal women. Other diseases with a less pronounced female preponderance include lymphocytic interstitial pneumonitis, ILD in Hermansky-Pudlak syndrome, and the connective tissue diseases; the exception in the last group is ILD associated with rheumatoid arthritis, which is more common in men. Because of occupational exposures, men are also more likely to have a pneumoconiosis.
Why is smoking history important to ask about when taking a history of a patient who might have an ILD?
A history of tobacco use is important, since some diseases occur largely among current or former smokers (pulmonary Langerhans cell histiocytosis, desquamative interstitial pneumonitis, IPF, and respiratory bronchiolitis) or among never or former smokers (sarcoidosis and hypersensitivity pneumonitis). Active smoking can lead to complications in Goodpasture's syndrome, in which pulmonary hemorrhage is far more frequent in current smokers. In this setting, it is thought that smoking damages the alveolar wall, making the alveolar basement membrane more accessible to the circulating antibasement membrane antibodies.
Why is duration of illness important to ask about when taking a history of a patient who might have an ILD?
The duration of illness prior to presentation may help narrow the differential diagnosis. The acute or subacute processes are often confused with atypical pneumonias, since many have diffuse radiographic opacities, fever, or relapses of disease activity.
Why is prior medication use important to ask about when taking a history of a patient who might have an ILD?
A detailed history of the medications taken by the patient is needed to exclude the possibility of drug-induced disease. The medication history should also include over-the-counter medications, oily nose drops or petroleum products, and amino acid supplements. In some cases, lung disease may occur weeks to years after the drug has been discontinued (eg, carmustine).
Why is family history important to ask about when taking a history of a patient who might have an ILD?
The family history is occasionally helpful, since some familial associations have been identified.
Why is occupational history important to ask about when taking a history of a patient who might have an ILD?
A strict chronological listing of the patient's entire lifelong employment must be sought, including specific duties and known exposures to dusts, gases, and chemicals. The degree of exposure, duration, latency of exposure, and the use of protective devices should be elicited. A written questionnaire can be used to obtain this information in a systematic manner.
Why are environmental exposures important to ask about when taking a history of a patient who might have an ILD?
Review of the home and work environment, including that of spouse and children, is invaluable. In hypersensitivity pneumonitis (extrinsic allergic alveolitis), respiratory symptoms, fever, chills, and an abnormal chest roentgenogram are often temporally related to the workplace (farmer's lung) or to a hobby (pigeon breeder's disease). Symptoms may diminish or disappear after the patient leaves the exposure for several days and often reappear upon returning to the exposure. Thus, it is important to determine if the patient has had exposures to pets (especially any birds), air conditioners, humidifiers, hot tubs, evaporative cooling systems (eg, swamp coolers), or if there has been water damage to walls and carpets in the home or work environment. Family members may develop disease as a result of "passive" exposure to dusts from the hobby or occupation of another member of the family (eg, asbestosis, berylliosis).
What are typical physical exam findings in a patient with an ILD (5)?
-Crackles (velcro rales): may hear even if the chest film was normal
-Cor pulmonale - left parasternal systolic lift, loud S2 exaggerated in the pulmonic region
-Cyanosis - late stage
-Clubbing - late stage
Why are extra pulmonary findings important when diagnosing a patient with an ILD?
They can help narrow the differential diagnosis.
What are some important extrapulmonary findings to know (3)?
Which steps are involved in the work-up of an ILD (4)?
-History and physical exam
What is the purpose of a history and physical exam when working up ILD?
To evaluate for known causes and coexisting disease.
Which tests are included in the work-up of ILD (3)?
-Cardiopulmonary exercise testing
Which imaging studies are included in the work-up of ILD (2)?
-High resolution CT
How is a tissue diagnosis obtained during the work-up of ILD (2)?
-Bronchoscopy with bronchoalveolar lavage or transbronchial biopsy
Why is it so important to know whether there is a known cause or not for a patient's ILD?
For treatment strategy. If you can identify an environmental etiology or systemic disease as the cause of the patient's problems, then treat that. If not, you'll need tissue to get your diagnosis.
When is a tissue biopsy appropriate for an ILD work-up?
Where there is no known cause for the ILD.
Which tests are included in a complete pulmonary function test (3)?
Which type of lung disorder do ILDs typically produce, restrictive or obstructive?
Most forms of ILD produce a restrictive defect with reduced:
-Total lung capacity
-Functional residual capacity
Describe the FEV1/FVC ratio in an ILD.
Flow rates are decreased (forced expiratory volume in one second and forced vital capacity), but changes are in proportion to the decreased lung volumes; thus, the FEV1/FVC ratio is usually normal or increased.
Why do lung volumes decrease progressively in ILD?
They decrease as lung stiffness worsens with disease progression.
Which types of ILDs may have an obstructive component (2)?
For which ILDs do pulmonary function tests have prognostic value (2)
Idiopathic interstitial pneumonias:
-Nonspecific interstitial pneumonia (NIP)
-Idiopathic pulmonary fibrosis (IPF)
A reduction in the DLCO is a commonly found but nonspecific finding in ILDs. Explain why.
The decrease in DLCO is due, in part, to effacement of the alveolar capillary units but more importantly to the extent of mismatching of ventilation and perfusion of the alveoli. The severity of the DLCO reduction does not correlate well with disease stage. In some ILDs, particularly sarcoidosis, there can be considerable reduction in lung volumes and/or severe hypoxemia but normal or only slightly reduced DLCO.
Summarize obstructive lung disorders.
Characterized by a limitation of expiratory airflow so that airways cannot empty as rapidly compared to normal (such as through narrowed airways from bronchospasm, inflammation, etc).
Give some examples of obstructive lung disorders (4).
-COPD (emphysema/chronic bronchitis)
Summarize restrictive lung disorders.
Characterized by reduced lung volumes/decreased lung compliance.
Give some examples of restrictive lung disorders (6).
What ABG results are typical in a patient with ILD (4)?
-CO2 retention at end stages of disease
What is a potential problem with using oxygen in patients with hypercapnia?
CO2 retainers raise red flags for medical management. Traditional teaching tells us that these patients are at increased risk of 'forgetting to breath', especially if you try to raise their SAO2 by increasing their O2 flow rate. They are dependent on hypoxia to get the signal to breath. If you 'help' them by decreasing their hypoxia, they lose their ventilatory drive.
Why are cardiopulmonary exercise tests advantageous for a patient not currently presenting with symptoms of an ILD?
Sometimes patients with normal O2 sat at rest quickly desaturate with exertion (or with sleep). To detect this important condition, exercise testing with pulse-ox and ABGs can be performed.
Why do ILD patients with normal O2 saturation at rest quickly desaturate with exertion (or with sleep)?
This happens because the patient fails to decrease dead space appropriately with exercise (high VD/VT ratio).
What is the normal alveolar arterial oxygen gradient?
Less than 10.
What does an increase in a patient's alveolar arterial oxygen gradient indicate?
A defect in diffusion of oxygen across the alveolar wall, ie a ventilation/perfusion mismatch.
What are the two imaging modalities used to examine a patient with ILD?
-High resolution CT
Why is high resolution CT the gold standard for imaging ILD (4)?
-Distinguishes airspace from interstitial disease
-Better assesses extent and distribution of disease
-More likely to detect underlying or coexisting disease (occult mediastinal adenopathy, carcinoma, emphysema)
-May help avoid biopsy if there is a diagnostic pattern
Why do you still need to proceed with a full work-up for a patient with suspected ILD if their chest x-ray is normal?
As many as 10% of patients with ILD will have a normal chest x-ray.
Which type of ILD commonly presents with a normal chest x-ray?
Why do you still need to proceed in a complete evaluation for an asymptomatic patient with an abnormal chest x-ray indicative of ILD?
You want to treat before the disease progresses and causes irreversible damage.
What is the most common radiographic abnormality seen with ILD?
A reticular pattern; however, nodular or mixed patterns are not unusual.
What causes the abnormal radiographic findings in ILD?
They are due to alveolar filling and increased interstitial markings.
Generally, the correlation between severity of the xray and clinical condition is poor. What is the exception?
Honeycombing, which does correlate with pathologic findings and a poor prognosis.
Image of a chest x-ray of ILD with reticular opacities.
Image of a chest x-ray of ILD with a nodular pattern.
How are lung tissue biopsies obtained?
Bronchoscopy may suffice, but may need surgical biopsy, either by video-assisted or open procedure.
Describe the fiberoptic bronchoscopy and bronchoalveolar lavage method of biopsy.
Bronchoscopy performed, fluid squirted into alveolus, then collected for analysis of cells obtained.
What are the different types of therapies used to manage ILD (4)?
-Remove inciting agent when known
-Reduce further lung damage
-Some ILDs are chronic and irreversible, lung transplantation may be considered
What is included in symptomatic support of ILD (2)?
-Respiratory support with supplemental O2, mechanical ventilation PRN
-Treatment of cor pulmonale if required
How is further lung damage prevented in ILD (3)?
-Fibrotic damage is not reversible
-Suppress inflammatory process with glucocorticoids +/- cytotoxics
Describe glucocorticoid therapy for ILD (3).
-Mainstay of therapy despite low success rate
-No direct evidence from placebo controlled trials to show improved survival
-No consensus on optimal dose and length of therapy, but we might start with oral prednisone 1 mg/kg/d x 4-12 wk, then taper down to maintenance, guided by symptoms and PFTs
Describe cytotoxic therapy for ILD (4).
-Cyclophosphamide and azathioprine are usually the first we try, with or without glucocorticoids
-Wait 8-12 weeks to reassess
-If drug failure or intolerance, try methotrexate, colchicine, penicillamine, cyclosporine, but no consensus
Which interstitial idiopathic pneumonias have a worse prognosis (2)?
-Idiopathic pulmonary fibrosis
-Acute interstitial pneumonitis (Hamman Rich)
Which interstitial idiopathic pneumonias have a better prognosis (5)?
-Nonspecific interstitial pneumonia
-Desquamative interstitial pneumonia
-Respiratory bronchiolitis associated interstitial lung disease
-Cryptogenic organizing pneumonia
-Lymphoid interstitial pneumonia
What is the most common form of idiopathic interstitial pneumonia?
Idiopathic pulmonary fibrosis (usual interstitial pneumonia).
Which patients re more likely to develop idiopathic pulmonary fibrosis?
Describe the clinical presentation of idiopathic pulmonary fibrosis (5).
-Chronic onset (>12wk)
-With or without digital clubbing
What do high resolution CT scans of idiopathic pulmonary fibrosis typically reveal?
Patchy, predominantly basilar, subpleural reticular opacities, often associated with traction bronchiectasis and honeycombing.
What results are typical of pulmonary function tests for idiopathic pulmonary fibrosis (3)?
-Arterial hypoxemia that is exaggerated or elicited by exercise
What is the prognosis for idiopathic pulmonary fibrosis (2)?
-Distinctly poor response to therapy
-50-70% mortality within 5 years
What diagnosis is required to make a diagnosis of idiopathic pulmonary fibrosis?
What instigates deterioration in idiopathic pulmonary fibrosis (5)?
-Acute exacerbation of the IPF itself
Image of a CT scan of idiopathic pulmonary fibrosis with marked honeycombing.
Image of a CT scan of idiopathic pulmonary fibrosis with honeycomb cysts.
Image of a honeycomb lung seen in end stage idiopathic pulmonary fibrosis.
Summarize acute interstitial pneumonia (5).
-Acute presentation with fever, cough, dyspnea x 1-2 wk
-Fulminant course with rapid development of Acute Respiratory Distress Syndrome
-CXR with diffuse, bilateral, opacification; HRCT ground-glass attentuation, air-space consolidation.
-More than 60% mortality within 6 months
Summarize ILD associated with collagen vascular or connective tissue diseases (4).
-May precede other connective tissue disease (CTD) symptoms
-May not correlate to severity of other CTD symptoms
-Most common histological appearance is of UIP, but course may or may not be that of IPF (progressive)
-Pulmonary symptoms always deserve a work-up for acute pulmonary infection
Occupational lung disease caused by dust inhalation.
Summarize asbestosis (3).
Patients exposed to asbestos develop:
-Pleural disease: focal and diffuse benign pleural plaques
-Pulmonary malignancies: non small cell, small cell carcinomas, malignant mesothelioma
Describe the latency seen with the onset of symptoms of asbestosis.
Latency roughly 20 years from first exposure, shorter latency with heavier exposure.
What are the radiographic findings typical of asbestosis (2)?
-Pleural plaques and or calcifications
Image of asbestos.
Image of a chest x-ray of early asbestosis.
Image of a chest x-ray of advanced asbestosis.
Image of a lung with asbestosis.
What is sarcoidosis?
Inflammatory disease characterized by the presence of noncaseating granulomas.
Describe the epidemiology of sarcoidosis (2).
-Worldwide incidence, especially in Swedes, but in the US, seen more in blacks than whites
-Often in young, otherwise healthy adults
What organs are affected by sarcoidosis from most commn to least common (9)?
-Lymph nodes (75%)
What are the typical respiratory complaints seen with sarcoidosis (2)?
What are the nonspecific constitutional symptoms seen with sarcoidosis (4)?
-Fatigue (most common)
How common is skin involvement in patients with sarcoidosis?
Identified in over a third of patients with sarcoidosis.
What are the classic cutaneous lesions seen with sarcoidosis (5)?
-Hyper- and hypopigmentation
What is erythema nodosum?
An inflammation of the fat cells under the skin (panniculitis) characterized by tender red nodules or lumps that are usually seen on both shins.
What is lupus pernio?
A specific complex of involvement of the bridge of the nose, the area beneath the eyes, and the cheeks is referred to as lupus pernio and is diagnostic for a chronic form of sarcoidosis.
What factor determines the degree of ocular involvement in sarcoidosis?
Race. In Japan, more than 70% of sarcoidosis patients develop ocular disease, while in the United States only 30% have eye disease, with problems more common in blacks than whites.
What are the common ocular symptoms seen with sarcoidosis (5)?
-Inflammation at the posterior of the eye, including retinitis and pars planitis
How is ocular sarcoidosis insidious?
Some asymptomatic patients still have active inflammation.
What is a consequence of ocular sarcoidosis?
Image depicting the symptoms of sarcoidosis.
Which symptoms usually lead to the diagnosis of sarcoidosis?
Skin and eye symptoms are more likely to get early attention than the more vague but more common symptoms of dyspnea and fatigue.
How is a diagnosis of sarcoidosis made?
Diagnosis can be challenging, it is usually made by a combination of clinical features, x-ray and biopsy.
Levels of which enzyme are elevated in sarcoidosis?
Angiotensin converting enzyme (ACE).
What are the two types of acute sarcoidosis?
Describe Lofgren's syndrome (3).
-Acute arthritis (starting in ankles)
Describe Heerfordt-Waldenstrom syndrome (4).
-Facial nerve palsy
What are the possible outcomes of sarcoidosis (3)?
-Often spontaneously remits in 2-5 years
-20% progress to a chronic form.
-50% are left with permanent organ dysfunction
How is sarcoidosis treated?
If symptoms and organ involvement (eye, heart,CNS) warrants treatment, glucocorticoids are usually the first line.
What other agents are used to treat sarcoidosis (4)?
Image of a chest x-ray of sarcoidosis. Note the hilar lymphadenopathy without parenchymal infiltrates.
Image of a CT scan of sarcoidosis. Note the bulky hilar and mediastinal lymphadenopathy (red arrows) without parenchymal infiltrates.
Image of a chest x-ray of sarcoidosis (later stage). Lymphadenopathy with parenchymal changes. Note apical predominance of disease. The diaphragms are also flattened, suggesting hyperinflation.
Image of a CT scan of sarcoidosis (later stage).
Image of a CT scan of sarcoidosis (later stage). Nodular parenchymal infiltrates (yellow arrows), no lymphadenopathy. Also note large pulmonary artery (red arrow).
Image of a CT scan of sarcoidosis. Note the unilateral left hilar enlargement and bilateral poorly defined nodules.
Image of a CT scan of miliary nodules in sarcoidosis.
Image of a CT scan of sarcoidosis that has progressed to fibrotic lung disease.
Image of a CT scan of scarring in sarcoidosis.
Summarize interstitial lung diseases (5).
-Interstitial lung diseases affect the interstitial tissues in the lung parenchyma
-They cause dyspnea and cough, show up with a reticular pattern of opacification on imaging and a restrictive defect on PFTs
-About 60-70% of the time we see ILD in folks with occupational exposures to different kinds of dust, with connective tissue diseases or medication reactions
-About 30-40% of the time we see ILD in people who have no known reason to develop them
-The treatment is steroids then cytotoxics, but response isn't always great; in fact, some ILDs have a very poor prognosis of either inexorable progression (asbestosis) or rapid compromise (IPF/UIP, AIP)