Interstitial lung disease Flashcards
Interstitial Lung Diseases (ILD)
general
Collection of disorders that involves inflammation and scarring (fibrosis) of the lung interstitium (the space between the capillaryendotheliumand the alveolarepithelium
The lung becomes “stiff” (reduced distensibility) and compromises lung expansion
Causes
Idiopathic or secondary to connective tissue diseases, medications, malignancies, occupational exposure, or allergens
ILD
pattern on spirometry
Restrictive pattern on spirometry
Normal FEV1/FVC ratio (> 0.70) and a reduction in TLC below 80% of the predicted value
Decreased diffusion capacity for carbon monoxide (DLCO)
Impaired gasdiffusionacross the alveolar membrane:
Idiopathic pulmonaryfibrosis (IPF)
general and RF
Characterized by chronic, progressive, irreversiblefibrosis (“scar tissue”) of the lung parenchyma
Epidemiology:
Estimatedprevalencein the United States: 10–60 per 100,000
Occurs primarily in elderly individuals
Commonly diagnosed in the 50-60 years old
Men > Women
Risk factors: male, advanced age, history of tobacco use
Idiopathic pulmonaryfibrosis
patho
The mechanism triggering IPF is poorly understood
Environmental exposure and possible genetic predisposition
Recurrent alveolar epithelial damage → type I pneumocytes release transforming growth factor beta1 → proliferation of type II pneumocytes → stimulate fibroblasts that are found in the interstitial tissue
Activated fibroblastsdevelop into myofibroblast (fibroblasts with smooth muscle cell properties)
Myofibroblast secrete:
Reticular fibers - a type of collagen which provides structural strength
Elastic fibers - provide the rubber-band like elasticity of the lungs
Failure of normal myofibroblastapoptosis→ accumulation of collagen leads to thickening of the interstitial layer
Consequences:
Restrictive lung - poor air in and out of the lung
↓gas exchange
Fundamental problem….too many myofibroblasts and too much collagen!
Idiopathic pulmonaryfibrosis
clin man
progressive disease
Asymptomatic early in the disease process
Moderate to advanced stage:
Chronic dyspnea-Initially exertional, Progressive, eventually occurring at rest
Chronic nonproductive cough
Reduced exercisetolerance
Chest pain
Associated systemic symptoms (uncommon):
Fatigue
Low-grade fever
Weight loss
Myalgias
will lead to r sided heart failure and pulm HTN
Idiopathic pulmonaryfibrosis
PE findings
Auscultation
secondary disease sx
Bibasilar fine inspiratory (“Velcro-like”) crackles on auscultation
End-inspiratory “squeaks” in advanced disease withbronchiectasis
Digitalclubbing
Cyanosis
Patients can present withpulmonary hypertension (PH) andcor pulmonale:
Pitting edema (pedal or sacral)
Jugular venous distention
Cyanosis
Split second heart sound
(this is later as disease progresses)
Idiopathic pulmonaryfibrosis
Hx Dx
Med use
Diagnosed by a combination of radiologic, pathologic, and clinical investigations
Critical to obtain a complete patient history
Occupational history
Recreational history
Environmental history
Radiationexposure
Notable medications associated with pulmonary fibrosis:
Amiodarone
Bleomycin
Nitrofurantoin
Methotrexate
Idiopathic pulmonaryfibrosis –
Diagnosis Spirometry
Pulmonary function test
Reveals ↓ lung volumes (restrictive pattern):
Vital capacity
Total lung capacity(TLC)
Forcedvital capacity(FVC)
Forced expiratory volume in 1 sec
FEV1/FVC ratio is greater than 80% (increased) due to a significant decrease in forced vital capacity (FVC)
Idiopathic pulmonaryfibrosis
imaging
Chestx-ray
May look normal in early disease
Reticulonodular infiltrates
Bilateral, basal, and symmetrical
High-resolution CT scan
Significantly more sensitive and specific
Features (predominantly seen in the lower lobes):
Peripheral and subpleural reticular septal thickening
Tractionbronchiectasis
Honeycombing
Lung architecturaldistortion
Superimposed ground-glass opacities may be seen
Idiopathic pulmonaryfibrosis
biopsy and labs
Lung biopsy- best for Dx
Surgical specimens can be obtained using video-assisted thoracoscopic surgery (VATS)
Supporting laboratory evaluation to exclude other causes ofILD and guide management:
Erythrocyte sedimentation rateand CRP
Antinuclearantibodies
Rheumatoid factorand anti–cyclic citrullinated peptideantibodies
Aldolaseand CK
Myositis-specificantibodies
Anti-SSA/Ro and anti-SSB/Laantibodies
Serum ACE level
pulmonologist would do this
Idiopathic pulmonaryfibrosis
lifestyle mods
Smoking cessation
Vaccinations: influenza, Covid-19, and pneumonia
Idiopathic pulmonaryfibrosis
Tx
Antifibrotic drugs
Approved for delaying progression
Do not significantly improvemortality
Oxygen therapy
Indicated when the patient’sresting or ambulatory oxygen saturation are < 88%
Lung transplant
Only definitive treatment
Bilaterallung transplantationis more commonly used than singlelung transplantation
Early referral should be considered
Sarcoidosis
general
Multisystem inflammatory disease characterized by the formation ofnoncaseating granulomas that are most likely caused by a cell-mediated immune reaction
Etiology is undetermined but is most likely multifactorial
more common in african american women
Potential triggering exposure: environmental exposure or infectious agent
Genetic predisposition
sarcoidosis
pulmonary or extrapulmonary
Pulmonary sarcoidosisis a restrictive interstitial lung disease with granuloma formation in the:
Lungs(90% ofpatients)
Thoraciclymph nodes(hilar and mediastinal)
Extrapulmonary sarcoidosisis characterized by granuloma formation in:
Eyes – uveitis
Skin – erythema nodosum; macular or papular lesions
Joints
Heart – arrhythmias
Kidney
CNS andperipheral nervous system
Exocrine glands
sarcoidosis
Patho
Phagocytosisof a newantigenbyantigen-presenting cells (macrophagesanddendritic cells)
Activated macrophages present the antigento helper T cellsvia the HLA-CD4 complex
Activated T cellsandmacrophagesrelease inflammatory mediators (Th1response):
Interleukin 2 (IL-2)
Interferon gamma
Tumornecrosisfactor (TNF)
Othercytokinesandchemokines
Inflammatory mediators causemacrophagesto fuse into multinucleatedgiant cells
Unable to destroy the antigens, the multinucleatedgiant cellswall them off →noncaseating granulomaformation
Fibroblasts are recruited and surround granulomas and may progress tofibrosis
NON CASEATING
Sarcoidosis
CLin man
Initially progresses slowly, with few symptoms
Symptoms appear as an increasing number of granulomas affecting organ function
Cutaneous sarcoidosisis known as one of the “great imitators”\
Sarcoidiosis
imaging
Chestx-ray
Bilateral hilarlymphadenopathy(classic finding)
Bilateral reticulonodular infiltrates (often upper lobes)
Honeycombing (end-stage disease)- not for exam though
Chest CT scan
Bilateral hilar and mediastinallymphadenopathy
Small centrilobular parenchymal nodules
Ground-glass opacification
sarcoidosis
BAL
Bronchoalveolar lavage (BAL)
Obtained primarily to exclude alternative diagnosis
Lymphocytosis (T-cells)≥ 25% suggests a granulomatous process
sarcoidosis
labs
Labs
Elevated ACE level
Measure of the level of angiotensin-convertingenzyme in the blood
Elevated due to additional production by activated macrophages and epithelioid cells in the granulomas
sarcoidosis
biopsy
Gold standard for diagnosis
Obtained from the most accessible affected site (skinlesions)
Lung biopsies can be obtained via bronchoscopy or surgically
Key finding: well-defined noncaseating granulomas
Noncaseating: no centralnecrosis
Multinucleated giant cells
sarcoidosis
Tx
Minimal symptoms → observation
Most symptoms resolve spontaneously within a few weeks
Complete remission from sarcoidosis typically happens within a few years
Moderate-severe symptoms
Corticosteroids: first-line therapy
Steroid-sparing agents:second-line therapy:
Azathioprine
Methotrexate
Lung transplantation:in cases of advanced pulmonaryfibrosis
Pneumoconiosis
Pneumoconiosis is an occupational disease that results from the inhalation and deposition of mineral dusts and other inorganic particles in the lung; categorized according to the type of causative particle involved or by the type of response provoked
Asbestosis
Silicosis
Coal Worker’s Pneumoconiosis
Exposure has greatly decreased due to the enforcement of environmental rules and regulations
Pneumoconiosis
patho
Inhaled toxic fibers/dust cannot be metabolized by the body and accumulate in the alveolar ducts
Particles ofappropriate sizeto be retained in lung (1-5μm)
The fibers are engulfed bymacrophages, which undergo lysis and releasecytokines
Cytokines induce an inflammatory reaction, producingairway obstruction and stimulatingfibroblasts
Fibroticscarring leads to thickening of the airways, reducedelasticity, and impairedgas exchange
leading to restrictive pattern
Pneumoconiosis
general S/Sx
Progressive exertionaldyspnea
Dry cough
May be productive in the morning, with clear-to-white sputum
Chest discomfort due to heart failure following pulmonary hypertension
Inspiratoryralesor crackles
Digitalclubbingin advanced disease
Persistent cough with sputum and wheezing is unusual, but may be present if there has been associated cigarette smoking
pneumoconiosis
Dx
Documented exposure history to a known toxic agent
A typicallatent period between exposure and symptoms
Clinical and radiological features compatible with the known features of the disease
Exclusion of any other disease that could explain the findings
pneumoconiosis
Tx
No definitive treatment for pneumoconiosis, regardless of the clinical stage
Immediate cessation of exposure is recommended
Cessation of tobaccosmoking
Management is largely supportive and focuses on the prevention of further progression and complications (oxygen is dyspnea)
Prophylacticvaccinationagainstinfluenza, COVID-19and pneumococcal pneumonia
Oxygen therapy is often necessary to relievedyspnea
Early systemic oral glucocorticoid therapy may relieve symptoms, improve lung appearance on imaging, and normalizepulmonary function testing scores
Lung transplantationhas been performed for advanced pneumoconiosis with respiratory failure, but evidence on patient outcomes is lacking- not endorsed
Asbestosis
general
ILD caused by inhalation of asbestos fibers
Carcinogen
Known to cause mesothelioma, lung cancer (bronchogenic carcinoma), laryngeal cancer and ovarian cancer
Historically been used in construction, shipping, mining, and aerospace engineering commercial use because of their high electrical and thermal resistance and low cost
Dose-dependent disease
Most prevalent in disciplines where the intensity of exposure is high
Cigarette smoking accelerates disease progression
Onset after 10-20 years of exposure
Asbestosis
Xray and CT
Chest x-ray
Diffuse irregular opacities with a fine reticular pattern
Calcified or noncalcifiedpleural plaques
Chest CT scan
Reticular opacities in the lower lung zones
Interlobular pleural thickening
Calcified or noncalcified pleural plaques
Bronchiectasis
Pleural effusion
Asbestosis
BAL
Bronchoalveolar lavage (BAL)
Shows asbestosis bodies
dx depends on finding these
asbestosis
Silicosis
general
ILD caused by inhalation of crystalline silica dust
Most common form of occupational lung disease
Silica exposure
Mining, sandblasting, quarry, ceramics, and foundry workers; and in grinding, stone cutting, fiberglass, and glass manufacturing
Onset after > 10 years of exposure but can manifest after several months of intense daily exposure
Silica is known to weaken cell-mediated immunity
Increased susceptibility to infections, especially tuberculosis
When assessing patients for silicosis, screen for tuberculosis
Silicosis
Dx
start w imaging then BAL
Chest x-ray
Multiple, small nodular opacities (1-10 mm) in the upper lung fields
Calcification of nodules
Chest CT scan
Calcification of the periphery of mediastinal and hilar lymph nodes (referred to as eggshell calcifications)
Pleural thickening
Bronchoalveolar lavage (BAL)
Silica-laden macrophages
silicosis
“eggshell calcification”
Coal Worker’s Pneumoconiosis
general
ILD caused by exposure to coal dust
Onset after > 10 years of exposure
Large amorphous black masses develop that occasionally have a liquified centers
Anthracosis
general
Chronic, low level environmental exposure to coal dust or wood smoke
Black discoloration of the bronchial mucosa
Generally considered benign; can progress to anthracofibrosis (fibrotic changes and destruction of bronchial walls)
usually benign, milder col miners pneumoconiosis
coal miners
Dx
imaging to BAL
Chest x-ray
Small (1-5 mm) round nodular opacities in the upper lung fields
Occasional appearance of reticular or reticulonodular opacities
Conglomerate masses in advances disease
Chest CT scan
Diffuse (typicallyperilymphatic) distribution of small nodules throughout the lungs, which tend to favor the upper lungs
Bronchoalveolar lavage (BAL)
Black pigmented macrophages
Silicosis and CWP are not easily distinguished from one another on imaging studies
