Interstitial Lung Diseases

Question 1

Interstitial lung disease: clinical

Answer 1

Dyspnea, noticed initially on exertion
Nonproductive cough
Crackles prominent at lung bases
Clubbing may be present

Question 2

Interstitial lung disease: patho

Answer 2

Decreased compliance (increased stiffness) of lungs
Decreased lung volumes
Loss of alveolar-capillary surface area resulting in impaired measured diffusion
Abnormalities in small airway function without generalized airflow obstruction
Hypoxemia without CO2 retention
Pulmonary hypertension

Question 3

Interstitial lung disease: CXR

Answer 3

Reticular – increased linear markings
Reticulonodular – increased linear and small nodular markings
10% have normal radiographic findings

High-resolution computed tomography (HRCT)
Can distinguish inflammation from fibrosis
Picks up early changes
Specific pattern may be suggestive of a particular diagnosis

Question 4

Idiopathic Interstitial Pneumonias

Answer 4

Usual interstitial pneumonia
Desquamative interstitial pneumonia
Respiratory bronchiolitis interstitial lung disease
Nonspecific interstitial pneumonia
Acute interstitial pneumonia
Cryptogenic organizing pneumonia
Lymphocytic interstitial pneumonia

Question 5

Usual interstitial pneumonia

Answer 5

Patchy areas of parenchymal fibrosis and interstitial inflammation interspersed between areas of relatively preserved lung tissue
Fibrosis is the most prominent component of the pathology
Honeycombing – cystic airspace from retraction of surrounding fibrotic tissue
Most important disorder in this category is idiopathic pulmonary fibrosis

Question 6

Desquamative interstitial pneumonia

Answer 6

More homogenous than UIP
Large number of intraalveolar mononuclear cells
Less prominent inflammation and little associated fibrosis
Uniform process
Minimal architectural distortion
Pigmented macrophages in respiratory bronchioles secondary to smoking
Smoking is believed to be an important underlying cause

Question 7

Respiratory bronchiolitis interstitial lung disease

Answer 7

Related to DIP
Associated with pigmented macrophages which are present within the lumen of respiratory bronchioles
Interstitial inflammation is not present
Almost always associated with smoking
Most important intervention is smoking cessation

Question 8

Nonspecific interstitial pneumonia

Answer 8

Mononuculear cell infiltration within the alveolar walls
Uniform process
Fibrosis is variable, but less than UIP
Idiopathic or connective tissue disorder
Better prognosis

Question 9

Acute interstitial pneumonia

Answer 9

Organizing or fibrotic stage of alveolar damage, which is the histologic pattern seen in ARDS.
No initial trigger identified.
Histology shows fibroblast proliferation and type II pneumocyte hyperplasia in the setting of what appears to be organizing alveolar damage

Question 10

Cryptogenic organizing pneumonia

Answer 10

Organizing fibrosis (granulation tissue) in small airways
Mild degree of chronic interstitial inflammation
Intraluminal airway involvement is a key feature
Idiopathic
Differential: infections, toxic inhalants, or connective tissue disease

Question 11

Idiopathic pulmonary fibrosis

Answer 11

No recognizable inciting agent
Dysregulated pattern of fibrosis in response to alveolar epithelial injury
Presents between ages 50-70
Insidious onset
Dyspnea is the most common complaint
Rales on lung examination
Patients frequently have clubbing

Question 12

Idiopathic pulmonary fibrosis: PE

Answer 12

Chest x-ray
Interstitial pattern that is generally bilateral and relatively diffuse
More prominent at lung bases, particularly in the peripheral subpleural regions
High Resolution CT
Interstitial densities that are patchy, peripheral, subpleural, and associated with small cystic spaces.
Honeycombing – indicated irreversible fibrosis

Question 13

Idiopathic pulmonary fibrosis: diagnosis & progonosis

Answer 13

Diagnosis made with surgical lung biopsy
HRCT with classic pattern of honeycombing – diagnostic in patient too frail for lung biopsy

Prognosis
Poor with mean survival at time of diagnosis 2-5 years
No proven effective treatment

Question 14

Desquamative interstitial pneumonia

Answer 14

Smokers
Subacute
Ground glass appearance on imaging
Lung biopsy with a uniform accumulation of intraalveolar macrophages with little or no fibrosis
Prognosis better than IPF
Improves with smoking cessation and may respond to corticosteroids

Question 15

Nonspecific interstitial pneumonia

Answer 15

Ground glass appearance on imaging – inflammation
Lung biopsy with predominantly inflammatory response in the alveolar walls , with little fibrosis
Prognosis depends on degree of fibrosis
Patients often respond to corticosteroids

Question 16

Cryptogenic organizing pneumonia

Answer 16

Connective tissue plug in small airway accompanied by mononuclear cell infiltration of the surrounding lung parenchyma
Large majority have no specific cause
Chest x-ray often mimics pneumonia with one or more alveolar infiltrates
Subacute presentation over weeks to months with constitutional as well as respiratory symptoms
Response to steroid is dramatic and occurs over days to weeks.
Therapy is usually prolonged for months to prevent relapse

Question 17

Acute Interstitial Pneumonia

Answer 17

Acute disease that begins with the clinical picture of ARDS but without any usual inciting causes
Imaging with ground glass appearance, alveolar filling
Histology of diffuse alveolar damage, often showing some organization and fibrosis
Mortality is high
Small percentage of patients do well with clinical resolution and no long term sequelae

Question 18

Rheumatoid Arthritis

Answer 18

Primary manifestation is inflammatory joint disease
Most common site of thorax involvement is the pleura
Pleurisy, pleural effusions or both
Lung parenchymal involvement includes one or multiple nodules or the development of interstitial lung disease
Interstitial lung disease is usually mild, but can be severe in some cases

Question 19

Systemic lupus erythematosus

Answer 19

Multisystem disease that affects joints and skin
Serious organ involvement includes kidneys, lungs, nervous system, and heart
Involvement of the thorax includes pleural disease presenting with pleuritic chest pain, pleural effusion, or both
Acute pneumonitis in which infiltrates often involve the alveolar spaces as well as the alveolar walls
Less frequently chronic interstitial lung disease – extensive fibrosis usually not prominent

Question 20

Progressive systemic sclerosis ( scleroderma)

Answer 20

Most obvious manifestation involve the skin and small blood vessels
Other organ system involvement include GI tract, lungs, kidneys, and heart
Pulmonary involvement tends to be severe with significant scarring of the pulmonary parenchyma
Pulmonary fibrosis strongly associated with an autoantibody to topoisomerase I (antitopoisomerase I, also called Scl70)
Pulmonary Artery Hypertension – small pulmonary vessel disease independent of the fibrosis

Question 21

Polymyositis-dermatomyositis

Answer 21

Muscles and skin are the primary sites of the inflammatory process
Interstitial lung disease is relatively infrequent
Respiratory difficulty secondary to weakness of the diaphragm
Involvement of the striated muscles in the proximal esophagus may lead to dysphagia and recurrent aspiration pneumonia

Question 22

Pulmonary Langerhans Histiocytosis

Answer 22

Also called eosinophilic granuloma of the lung or pulmonary histiocytosis X
Differential diagnosis of unexplained interstitial disease in the young or middle aged adult
Histiocytic cell appears to be an antigen-presenting dendritic or phagocytic cell called a Langerhans cell
Cytoplasmic rod like structures called X bodies (Burbeck Granules) which can be seen by electron microscopy
Light microscopy reveals histiocytes, eosinophils, lymphocytes, macrophages, and plasma cells

Question 23

Pulmonary Langerhans Cell Histiocytosis: PE

Answer 23

Starts as a peribronchiolar distribution and later becomes more diffuse
Disease occurs almost exclusively in smokers
Chest x-ray
Nodular or reticulonodular disease
Upper lobe prominent
HRCT
Small cysts in addition to the nodular and reticulonodular changes
Cysts may rupture and cause pneumothorax
Some cases extensive honeycombing

Question 24

Lymphangioleiomyomatosis

Answer 24

Rare pulmonary disease
Characterized by proliferation of atypical smooth muscle cells around lymphatics, blood vessels, and airways, accompanied by numerous small cysts throughout the pulmonary parenchyma
Occurs almost exclusively in women of childbearing age
Develops in 30-40% of female patients with the genetic condition tuberous sclerosis complex

Question 25

Lymphangioleiomyomatosis: clinical

Answer 25

Dyspnea and cough Vascular involvement may lead to hemoptysis Lymphatic obstruction may produce a chylous pleural effusion Airway involvement may lead to airflow obstruction Rupture of subpleural cysts can lead to spontaneous pneumothorax

Question 26

Lymphangioleiomyomatosis: PE

Answer 26

Chest x-ray Reticular pattern, cystic changes Lung volumes normal or increased HRCT Cystic disease throughout the pulmonary parenchyma Pulmonary Function Testing Obstructive disease, restrictive disease, or both

Question 27

Wegener Granulomatosis

Answer 27

Upper respiratory tract, lungs, and kidneys Upper respiratory tract and lungs – necrotizing small-vessel granulomatous vasculitis Kidneys with focal glomerulonephritis Chest x-ray Nodules, infiltrates, cavitation Diffuse interstitial lung disease is not characteristic cANCA + Treatment - Cyclophosphamide, prednisone

Question 28

Churg-Strauss Syndrome

Answer 28

Systemic necrotizing vasculitis Affects upper and lower respiratory tracts Preceded by allergic disorders such as asthma , allergic rhinitis, sinusitis or drug reaction Peripheral and lung eosinophilia Increased immunoglobulin E levels Rashes

Question 29

Churg-Strauss Syndrome: PE

Answer 29

``` Chest x-ray Bilateral patchy, fleeting infiltrates Diffuse nodular infiltrates Diffuse reticulonodular infiltrates Biopsy Granulomatous angiitis or vasculitis Treatment Corticosteroids ```

Question 30

Chronic eosinophilic pneumonia

Answer 30

Pulmonary interstitium and alveolar spaces are infiltrated by eosinophils and to a lesser extent macrophages Clinical Manifestations Occurs over weeks to months Fever, weight loss, dyspnea, and productive cough Pulmonary infiltrates with a peripheral distribution and more suggestive of alveolar than interstitial disease Increased eosinophils in the peripheral smear BAL with increased eosinophils

Question 31

Chronic eosinophilic pneumonia: treatment

Answer 31

Dramatic response to corticosteroids within days to weeks | Therapy must often be prolonged for months to prevent recurrence

Question 32

Pulmonary alveolar proteinosis

Answer 32

Primary pathologic process affects the alveolar spaces, not the alveolar cells Alveolar spaces are filled with a proteinaceous phospholipid material that represents components of pulmonary surfactant

Question 33

Pulmonary alveolar proteinosis: clinical

Answer 33

``` Clinical manifestations Dyspnea and cough Bilateral alveolar infiltrates HRCT crazy paving pattern produced by thickening of interlobular septa accompanied by ground –glass alveolar filling Superimposed to respiratory infections - Nocardia Treatment Whole-lung lavage Prognosis is good ```

Question 34

Hypersensitivity Pneumonitis

Answer 34

Hyperimmune respiratory syndrome caused by inhalation of a wide variety of allergic antigens that are usually organic Causative antigens include bacteria, fungi, protozoa, animal proteins, and reactive chemicals Treatment Identify causative antigen and avoid exposure Prevent progressive permanent lung damage Corticosteroids hasten resolution

Question 35

Suspect Hypersensitivity Pneumonitis

Answer 35

``` Intermittent pulmonary and systemic symptoms Progressive pulmonary symptoms with interstitial chest x-ray changes Non-resolving pneumonia Workplace exposures Agricultural and cattle farming Recreational exposures Bird keeping Home exposures Contaminated home ventilation Hot tubs ```

Question 36

Hypersensitivity Pneumonitis: clinical

Answer 36

Acute Abrupt onset of cough, dyspnea, fever, and chest pain following heavy exposure to the offending antigen Symptoms begin 4-6 hours after exposure Subside within 24 hours of removal from exposure Subacute More gradual development of symptoms Less severe intensity Chronic Insidious progressive dyspnea, cough, weight loss, and fatigue Most progress toward pulmonary fibrosis, with respiratory failure

Question 37

Hypersensitivity Pneumonitis: PE

Answer 37

Chest x-ray Acute disease diffuse reticulonodular infiltrates Chronic disease with diffuse interstitial fibrosis HRCT Ground glass opacities early Chronic with traction bronchiectasis, honeycombing, and fibrosis PFT’s Restriction, small lung volumes, decreased diffusion capacity

Question 38

Sarcoidosis

Answer 38

Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized pathologically by the non-caseasting granuloma. Can effect almost any organ 90% of patients present with mediastinal or hilar lymphadenopathy and parenchymal lung disease Occurs at any age, but most commonly between the ages of 40-60 Peak Incidence between ages 20-39 Incidence 3.5 times higher in black Americans compared to white Americans Women have a higher incidence than men

Question 39

Sarcoidosis: pulmonary involvement

Answer 39

Pulmonary involvement frequent, but not necessary for the diagnosis Initial presentation may be an abnormal chest x-ray with mediastinal and hilar adenopathy 50% of patients have no symptoms at the time of diagnosis

Question 40

Lofgren’s Syndrome

Answer 40

``` Acute manifestation of sarcoidosis Erythema nodosum More common in women Arthritis More common in men Bilateral Hilar Lymphadenopathy Prognosis is favorable ```

Question 41

Sarcoidosis: symptoms

Answer 41

General: fatigue, fever, night sweats, and weight loss. Pulmonary: Cough, dyspnea with exertion, wheeze, chest discomfort – 50% of patients have only respiratory symptoms Skin: rash, macules, papules, nodules, hyperpigmentation or hypopigmentation, erythema nodosum Ocular: gritty or dry eyes, pain, redness, and or blurred vision Cardiac: arrhythmia, palpitations, near-syncope, syncope, lower extremity edema Nervous System: headaches, blurred vision, numbness, weakness, instability, seizures Gastrointestinal: epigastric pain, early satiety, RUQ pain, jaundice Musculoskeletal: swelling and joint stiffness, joint pain, muscle pain Upper Respiratory tract: nasal congestion, sinus pressure, nasal discharge

Question 42

Sarcoidosis: signs

Answer 42

Pulmonary: rales, expiratory wheezing, can also be normal Skin: Infiltration of old scars and tattoos, Maculopapular lesions of face, neck , upper back, and extremities, Lupus pernio of nose, cheeks, ears, and lips, Erythema nodosum Ocular: uveitis, iritis, scleral plaques, enlarged lacrimal glands Cardiac: usually normal, irregular rhythm Nervous System: cranial nerves II, VII, and VIII neuropathies, gait instability, weakness GI: hepatomegaly, splenomegaly, jaundice Musculoskeletal: Arthralgias, arthritis. Lymphatic: common sites of palpable adenopathy include cervical, supraclavicular, axillae, and inguinal regions

Question 43

Sarcoidosis: diagnosis

Answer 43

Diagnosis is made on clinical, radiographic, and histologic evidence of noncaseating granulomas in one or more organs Lofgren’s syndrome alone is pathognomonic for sarcoidosis and may not require biopsy for diagnosis Biopsy should be taken from the safest site such as skin, peripheral lymph nodes, lacrimal glands, or conjunctiva Bronchoscopy with transbronchial lung biopsy has a diagnostic yield of at least 85% Bronchoalveolar lavage may be remarkable for lymphocytosis and an elevated CD4/CD8 ratio, however this is not diagnostic Sarcoid granulomas produce ACE. ACE levels are elevated in 60% of patients, but this is nonspecific

Question 44

Sarcoidosis - Testing

Answer 44

Chest x-ray staging Stage 0: Normal Stage 1: Bilateral hilar adenopathy Stage 2: Bilateral hilar adenopathy and parenchymal infiltrates Stage 3: Parenchymal infiltrates without lymphadenopathy Stage 4: Advanced parenchymal disease with fibrosis PFT Restrictive ventilatory defect, concurrent obstruction, decreased DLCO

Question 45

Sarcoidosis Treatment

Answer 45

Should only be initiated for symptomatic patients. Prednisone 20-40 mg daily for 3 months. Monitor for improvement with FVC. If improved wean to 10-15 mg daily for 6-9 months, then taper off. Cytotoxic and immunosuppressives are used for those not responding to prednisone.

Question 46

Sarcoidosis Prognosis

Answer 46

``` Spontaneous remission in 50% of patients at 3 years. Lofgren’s with the best prognosis 2/3 remission after 10 years. 1/3 with unrelenting disease Less than 5% die from sarcoidosis ```

Question 47

Silicosis: CXR

Answer 47

Symmetric nodular pattern involving the upper lobes Hilar adenopathy with eggshell calcification is strongly suggestive Progressive massive fibrosis is characterized by coalescence of the nodules with larger mass lesions Acute silicosis displays air space and interstitial pattern on x-ray

Question 48

Coal Worker’s Pneumoconiosis: pathology

Answer 48

Coal macule consisting of macrophages laden with coal dust within the walls of respiratory bronchioles and adjacent alveoli Coal nodules Progressive massive fibrosis may be seen

Question 49

Coal Worker’s Pneumoconiosis: associated diseases

Answer 49

Silicosis is also common in coal workers Scleroderma and rheumatoid arthritis Caplan Syndrome: rheumatoid arthritis with large cavitary pulmonary nodules associated with silicosis and coal worker’s pneumoconiosis Tb not increased unless associated silicosis Lung cancer not increased

Question 50

Coal Worker’s Pneumoconiosis: CXR

Answer 50

Resembles silicosis Small rounded opacities in the lung parenchyma Can progress to Progressive Massive Fibrosis with nodules from 0.5 to 5 cm

Question 51

Asbestosis: clinical presentation

Answer 51

Symptoms Dyspnea Dry cough Chest tightness/pain Signs Inspiratory crackles clubbing

Question 52

Asbestosis: CXR

Answer 52

``` Pleural plaques Pleural effusion 10-15 year latency Pleural thickening Rounded atelectasis with “comet tail” Lower lobe and subpleural disease prominent ```

Question 53

Beryllium Disease: Acute Toxic Pneumonitis

Answer 53

``` High exposure can lead to a hypersensitivity response that is now rare due to better recognition of beryllium associated disease Symptoms: Dyspnea Cough Chest pain Signs: Blood tinged sputum Crackles ```

Question 54

Chronic beryllium disease

Answer 54

``` Clinical features are similar to sarcoidosis ranging from asymptomatic to severe granulomatous restrictive lung disease Symptoms: Dyspnea Cough Chest pain Weight loss Fatigue Arthralgias ```

Question 55

Beryllium disease: CXR

Answer 55

``` Enlarged hilar or mediastinal nodes OR Multiple lung nodules OR Both Later stages patchy fibrosis, hyperinflation, and honeycombing ```