interstital lung diease

sarcoidosis affected organs: Parotid glands

•Paratitis •Facial nerve palsy •Bell's Palsy?

hi-res CT and 5 typical patterns

•Provides greater accuracy; most appropriate protocol for ILD •Typical patterns include: •Reticulation •Honeycombing •Ground glass appearance •Consolidation Micronodules

diagnostic testing PFTs

•Quantitatively assess respiratory symptoms •Monitor severity of lung involvement, progression, and response to interventions •Most show restrictive disorder •Useful information •But not diagnostic

sarcoidosis affected organs: myocardium

•Restrictive cardiomyopathy- •Restriction to stretch during diastole •Arrythmia, If it effects the SA or VA node •Pericardititits: pericardial effusion

exercise test

•Six-minute walk (6MWT) with pulse oximetry •Cardiopulmonary exercise test •Overnight pulse oximetry

signs and symptoms

•Slow progressive onset of dyspnea and nonproductive (dry) cough •Fever, chills, night sweats, and weight loss with interstitial pulmonary infections and some collagen vascular disorders Fatigue •B/L fine inspiratory crackles

chest x-ray

•Usually done when patient is symptomatic •Results are dependent on severity of disease

Most critical step in initial evaluation of a patient suspected of ILD is

•obtaining a complete history •Family hx of ILD •Detailed work history •Travel history •Environmental exposures •Hobbies, hot tub •Smoking history

what is key to differnetial diagnosis of sarcoidosis

non caseating granulomas (NCG) and no tissue necrosis

•Most ILDs share the same type of structural remodeling... of the

of the distal airspaces leading to impaired gas exchange.

what part of the lung does ILD effect

•Affects more than the interstitium (space between the alveoli and cap) •Disorders also associated with extensive alteration of alveolar and airway architecture

sarcoidosis affected organs: lungs

•Bilateral lymphadenopathy •Bilateral NCG's in the hilar lymph nodes (Classic sign) •Fibrosis of lung tissue PFT's will show restrictive looks at TLC •Can lead to Interstitial Lung Disease

tissue sampling

•Bronchoscopy (EBUS)*, Transbronchial biopsies (pEBUS) cryobiopsy (freezing) VATS Traditional open biopsies Most likely method of definitive diagnosis is surgical lung biopsy

Pathogenesis of Sarcoidosis, Aggregation

•Causes other macrophages to be drawn in •T-Lymphocytes •Fibroblasts •Epithelioid cells

•ILD dominated by fibrosis:

•Characterized by fibroblastic foci

ILD definition

•Diseases affecting the tissue and space around alveoli, causing progressive scarring of lung tissue through inflammation and fibrosis •Exact diagnosis can be challenging •More than 200 different subtypes

ABGs

•Early ILD: Normal or mild hypoxemia/respiratory alkalosis at rest •Late ILD: Hypercapnea

•ILD secondary to amiodarone (see ppt)

•Ground glass opacities in RLL

ILD causes

•Heterogenous group with a variety of causes •Occupational exposures- miners, painters, farmers •Second hand cigarette smoke •Unknown examples •Sarcoidosis, Idiopathic pulmonary fibrosis

sarcoidosis affected organs: pituitary

•Hypopituitarism •Decrease in growth hormone

oxygen therapy

•Hypoxemia is a common finding with ILD •Titrate based on 6MWT results

•Major subgroups of ILD are now broadly defined as:

•Idiopathic interstitial pneumonias (IIPs) •Granulomatous ILD (e.g. sarcoidosis, hypersensitivity pneumonitis) •ILD with known associations (e.g., occupational and drug exposures, connective tissue diseases) •Miscellaneous ILD (e.g., pulmonary Langerhans cell histiocytosis [PLCH])

sarcoidosis affected organs: liver

•Liver •Hepatomegaly •Splenomegaly •Occurs if ducts become blocked

Pathogenesis of Sarcoidosis, granuloma

•Lymphocytes form a ring around Giant cell •Fibroblasts make connective tissue (CT tissue forms around lymphocytes) •Fibroblasts form outer layer, Results in fibrosis & NON-CASEATING GRANULOMAS!!!! •No tissue necrosis in giant cell •Necrosis occurs in TB

Pathogenesis of Sarcoidosis, coalescence

•Macrophages fuse together •Epithelial cells coalesce and form one boundary around aggregated macrophages •Aggregated macrophage cell membranes fuse and form one membrane •Forms multi-nucleated Giant cell

lung transplant

•May be required for ongoing survival •Potentially curative option •Timely referral needed •Rate of decline in FVC and DLCO predictor of requirement

sarcoidosis affected organs: brain

Hypothalamus Decreases ADH production (diabetes insipidus) Cannot retain water in the kidneys Releases water and results in dehydration. Patient then drinks more water

Pathogenesis of Sarcoidosis, , deposition

NCG deposit into multi organ systems

meds: Antifibrotics (2) only for IPF

Nintedanib (OFEV): Kinase inhibitor, Slows rate of fibrosis in lung. Shown to slow decline in FEV1 and FVC. Pirfenidone (Esbriet): Antifibrotic, anti-inflammatory, and antioxidant. Inhibits collagen synthesis, Decreases production of multiple cytokines, Blocks fibroblast proliferation and stimulation in response to cytokines NP

meds: corticosteroids (3)

Prednisone: Cheapest, but liver has to convert to prednisolone. Prednisolone: More expensive, active metabolite of prednisone. Methylprednisolone: Stronger than prednisone, but still needs to be converted to prednisolone by liver

pathogenesis of sarcoidosis

-Exposure to antigen (Macrophages and Dendritic cells phagocytize antigen) -Combines in cell (Lysosome breaks down antigen) -Combines to form Phagolysosome -Forms MHC-II complex on surface of phagolysosome (Now 'coded' to antigen) -Travels to lymph node (Reacts with cells in lymph node)

Pathogenesis of Sarcoidosis, •Autocrine signaling

-In lymph node macrophage will find naïve t-cells (Has T-cell receptor that can bind to MHC-II complex. Uses CD4+ protein and Once binding takes place, cytokines are released back to T-cell) -T-cell then proliferates (Now primed to fight antigen) •T-cells proliferate throughout the body (T-cells are now 'coded' to the original antigen)

diagnostic testing

1. history exam, PFTs 2. X-rays 3. HRCT scan 4. Bronch, lavage 5. open lung biopsy

•Diffuse Parenchymal Lung Diseases (DPLDs)

•More accurate name but for now go with ILD's •Characterized by inflammation and fibrosis of the lung parenchyma

PFTs spiro, lung volumes, DLCO

Spirometry: Reduced FEV1, Reduced FVC, Normal or elevated FEV1/FVC Lung volumes: Reduced RV, Reduced TLC Diffusing Capacity: Commonly reduced ↓V/Q

Pathogenesis of Sarcoidosis, •Proliferation

T-cells released into body Deposit into tissues. Release specific cytokine (Interferon-gamma) (IFN-γ) IFN activates macrophages, and Macrophages aggregate to a specific area Release more cytokines (IFN-γ) (and Tumor necrotic factor alpha) (TNF-α)

•Radiography: Usual Interstitial Pneumonia (UIP) (see ppt)

B/L fibrotic changes Honeycombing Traction bronchiectasis Fibrotic lung pulling on the bronchi Irreversible dilation

diagnosis is made by

by combining Clinical findings, PATIENT HISTORY IS VITAL!, Pathophysiology, Immunology, Imaging (CXR is good, CT is better) Surgical biopsy with histological exam for precise diagnosis Still may not be 100% definitive

Lung fibrotic disorders

Characterized by accumulation of fibroblasts, myofibroblasts, and extracellular matrix. leading to chronic respiratory failure. Origins and activation of fibroblasts unknown

meds: immunosuppressive drugs (4)

•Mycophenolate mofetil (CellCept) •Azathioprine (Imuran) •Rituximab (Rituxan) •Cyclophosphamide (Cytoxan) (MARC)

prognosis

Depends on type of ILD and response to therapy. Better chance of survival if: Female, Younger, Have less dyspnea Overall prognosis is poor

sarcoidosis affected organs: kidney

•NCG can release 1-alpha hydroxylase •Also released by kidneys •Results in increased uptake of Ca++ in the GI system •Once the high Ca++ hits the kidney, it can lead to kidney stones

sarcoidosis affected organs: skin

•NCG's form in skin tissue •Large bumps on skin tissue in lower extremities •Erythema's

ILD dominated by inflammation

•Organizing pneumonia •Nonspecific interstitial pneumonitis

sarcoidosis affected organs: joints

arthralgias ankles

pulmonary rehab

can improve QOL

sarcoidosis affected organs: eyes

can lead to painless visual changes - floaters