Interstitial Lung Diseases Flashcards
Interstitial lung disease: clinical
Dyspnea, noticed initially on exertion
Nonproductive cough
Crackles prominent at lung bases
Clubbing may be present
Interstitial lung disease: patho
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
Interstitial lung disease: CXR
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
Idiopathic Interstitial Pneumonias
Usual interstitial pneumonia Desquamative interstitial pneumonia Respiratory bronchiolitis interstitial lung disease Nonspecific interstitial pneumonia Acute interstitial pneumonia Cryptogenic organizing pneumonia Lymphocytic interstitial pneumonia
Usual interstitial pneumonia
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
Desquamative interstitial pneumonia
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
Respiratory bronchiolitis interstitial lung disease
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
Nonspecific interstitial pneumonia
Mononuculear cell infiltration within the alveolar walls Uniform process Fibrosis is variable, but less than UIP Idiopathic or connective tissue disorder Better prognosis
Acute interstitial pneumonia
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
Cryptogenic organizing pneumonia
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
Idiopathic pulmonary fibrosis
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
Idiopathic pulmonary fibrosis: PE
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
Idiopathic pulmonary fibrosis: diagnosis & progonosis
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
Desquamative interstitial pneumonia
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
Nonspecific interstitial pneumonia
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
Cryptogenic organizing pneumonia
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
Acute Interstitial Pneumonia
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
Rheumatoid Arthritis
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
Systemic lupus erythematosus
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
Progressive systemic sclerosis ( scleroderma)
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
Polymyositis-dermatomyositis
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
Pulmonary Langerhans Histiocytosis
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
Pulmonary Langerhans Cell Histiocytosis: PE
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
Lymphangioleiomyomatosis
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
Lymphangioleiomyomatosis: clinical
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
Lymphangioleiomyomatosis: PE
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
Wegener Granulomatosis
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
Churg-Strauss Syndrome
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
Churg-Strauss Syndrome: PE
Chest x-ray Bilateral patchy, fleeting infiltrates Diffuse nodular infiltrates Diffuse reticulonodular infiltrates Biopsy Granulomatous angiitis or vasculitis Treatment Corticosteroids
Chronic eosinophilic pneumonia
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
Chronic eosinophilic pneumonia: treatment
Dramatic response to corticosteroids within days to weeks
Therapy must often be prolonged for months to prevent recurrence
Pulmonary alveolar proteinosis
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
Pulmonary alveolar proteinosis: clinical
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
Hypersensitivity Pneumonitis
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
Suspect Hypersensitivity Pneumonitis
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
Hypersensitivity Pneumonitis: clinical
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
Hypersensitivity Pneumonitis: PE
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
Sarcoidosis
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
Sarcoidosis: pulmonary involvement
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
Lofgren’s Syndrome
Acute manifestation of sarcoidosis Erythema nodosum More common in women Arthritis More common in men Bilateral Hilar Lymphadenopathy Prognosis is favorable
Sarcoidosis: symptoms
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
Sarcoidosis: signs
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
Sarcoidosis: diagnosis
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
Sarcoidosis - Testing
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
Sarcoidosis Treatment
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.
Sarcoidosis Prognosis
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
Silicosis: CXR
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
Coal Worker’s Pneumoconiosis: pathology
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
Coal Worker’s Pneumoconiosis: associated diseases
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
Coal Worker’s Pneumoconiosis: CXR
Resembles silicosis
Small rounded opacities in the lung parenchyma
Can progress to Progressive Massive Fibrosis with nodules from 0.5 to 5 cm
Asbestosis: clinical presentation
Symptoms
Dyspnea
Dry cough
Chest tightness/pain
Signs
Inspiratory crackles
clubbing
Asbestosis: CXR
Pleural plaques Pleural effusion 10-15 year latency Pleural thickening Rounded atelectasis with “comet tail” Lower lobe and subpleural disease prominent
Beryllium Disease: Acute Toxic Pneumonitis
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
Chronic beryllium disease
Clinical features are similar to sarcoidosis ranging from asymptomatic to severe granulomatous restrictive lung disease Symptoms: Dyspnea Cough Chest pain Weight loss Fatigue Arthralgias
Beryllium disease: CXR
Enlarged hilar or mediastinal nodes OR Multiple lung nodules OR Both Later stages patchy fibrosis, hyperinflation, and honeycombing
