ILD Flashcards
this word means “in between”
Interstitium
the region of the alveolar wall exclusive of and separating the basement membranes of alveolar epithelial and pulmonary capillary endothelial cells.
lung interstitium
a group of pulmonary disorders (>200) characterized by a similar pathology with an insidious and progressive presentation
Interstitial Lung Disease
what are the insidious and progressive presentation of Interstitial Lung Disease? (5)
- damaged alveoli and surrounding tissue
- dyspnea on exertion (DOE)
- persistent dry cough
- late inspiratory rales on PE
- results from forced opening of alveoli - CXR - septal thickening and reticulonodular changes (MC)
- occasionally ILD will be found incidentally during work-up for another condition
What structures are affected by ILD’s?
- a collection of support tissues within the lung that includes:
- alveolar epithelium
- pulmonary capillary endothelium
- alveolar basement membrane
- perivascular tissues
- perilymphatic tissues
the tissue and space around the air sacs of the lungs
MC presentations of ILD
- Idiopathic pulmonary fibrosis (IPF)
- Occupational and environmental
- Sarcoidosis
- Drug and radiation
pathophys of ILD
Injury to the alveolar epithelial or capillary endothelial cells (alveolitis) –> progressive, irreversible scarring and stiffness of lung parenchyma –> poor O2 exchange
pathogenesis of ILD
- repetitive and/or excessive injury
- FOLLOWED BY - dysregulation of tissue repair
- genetic predisposition
- autoimmune d/o
- superimposed disease
accumulation of T lymphocytes, macrophages, and epithelioid cells organized into discrete structures within in the lung parenchyma
becomes fibrotic
which type of histopathological category?
Granulomatous Lung Disease
repetitive injury results in chronic inflammation leading to fibrotic alveoli
which type of histopathological category?
Inflammation and Fibrosis
what are the 2 histopathological categories of ILD?
- Granulomatous Lung Disease
- Inflammation and Fibrosis
etiologic ddx of ILD
- medication related, environmental, infectious, primary pulmonary disorders, systemic disorders
- Requires a thorough PAST/PRESENT history
- medication history
- social history - occupational exposure to organic and inorganic compounds
- family/past medical history - connective tissue disorders, infectious processes
onset of ILD? presentation of each?
Onset is varied
1. Acute - days to weeks
- Allergy, acute interstitial pneumonia, hypersensitivity pneumonitis
2. Subacute - weeks to months
- drug-induced, sarcoidosis
3. Chronic - months to years
- majority of ILD’s
age of presentation of ILD
- 20-40 y/o - majority
- > 60 - Interstitial Pulmonary Fibrosis (IPF)
social history that can cause ILD
- Smoking (past or present) increases risk
- Occupational and environmental exposure
- strict chronological history of possible exposures
- compare severity of symptoms during exposure vs non-exposure periods of time
MC symptoms of ILD
-
dyspnea, cough
- often progressive in nature; wheezing - uncommon
- nonproductive (“dry”)
hemoptysis rare - General - fatigue, weight loss
Extrapulmonary symptoms only if ILD is associated with what disorders? what are the sx?
CT disorders
MSK pain, weakness, fatigue, fever, joint pains or swelling, photosensitivity, Raynaud phenomenon, pleuritis, dry eyes, and dry mouth
PE findings of ILD
- General - varies based upon severity of condition
- normal or varying SOB, cachexia and fatigued - Respiratory
- tachypnea
- late inspiratory rales
- rhonchi (aka sonorous rhonchus) - heard with associated bronchiolitis
late inspiratory rales in ILD is often heard where?
first bibasilar, in the posterior axillary line
late respiratory rales is less common in what type of ILD
granulomatous disease
rhonchi (aka sonorous rhonchus) is heard with what associated disorder?
bronchiolitis
PE findings of late ILD
- Digital clubbing
- Pulmonary Hypertension
- Loud P2 component of the 2nd heart sound
- a fixed split S2
- a holosystolic tricuspid regurgitation murmur
- pedal edema
work-up needed for ILD (tools only, not including additionals)
- CXR / HRCT
- PFT
- spirometry
- DLco
- Pulse ox
- ABG
- 6MWT - EKG
- CBC, CMP, UA, (ANA & RF)
bibasilar reticular and/or reticulonodular pattern with honeycombing in late stage
what is this indicative of?
ILD
honeycombing indicates poor prognosis
indicates small cystic spaces with fibrosis
which imaging option is better for ILD
HRCT (no contrast) > CXR
findings can help you narrow the ILD differential diagnosis
what diagnostic tool may assess severity of ILD and narrows DDx
PFT
most ILDs are what type of lung disease (obstructive/restrictive)? what would it show on spirometry?
restrictive
reduced TLC
reduced TLC → reduction in FEV1 and FVC
few ILDs will show (obstructive/restrictive) patterns, will reduced FEV1/FVC ratio. what is a common ILD with this type of lung disease?
obstructive
sarcoidosis (50%), hypersensitivity pneumonitis, ILD mixed with COPD
which diagnostic tool helps Assess the transfer of gas (O2/CO) from the lung to the blood cells? what would ILD look like?
DLco
< 80% DLco is common in ILD but not specific
often obtained to confirm results of Pulse Ox
performed at rest and after exertion
what type of diagnostic tool is this?
ABG
resting ABG often normal in early disease
what criteria for 6MWT is associated with increased mortality
desaturation <88% during 6 minute walk test (6MWT) is associated with increased mortality
EKG of ILD
- normal unless pulmonary hypertension (PH)
- pulm HTN: right axis deviation, evidence of right ventricular hypertrophy or right atrial enlargement - Consider evaluation for PH if clinical presentation is consistent with disease.
additional specialty work-up for ILD
- Bronchoalveolar Lavage (BAL)
- during flexible bronchoscopy
- gets samples of cells and pulmonary fluid for assessment of cell count, cultures and cytologic analysis
- usually nonspecific - Lung Biopsy
- last resort to confirm dx and/or stage disease
- histopathologic pattern is evaluated in combination with the clinical information to determine the diagnosis
ILD management goals
Is the patient symptomatic?
1. asx - reduce risk factors (remove offending agent and smoking cessation)
2. symptomatic
- remove offending agent (if known)
- manage hypoxemia - oxygen
- suppression of inflammatory process - steroids
- improve quality of life - pulm rehab
- manage complications - PH and cor pulmonale
ILD tx
- Remove offending agent - Adjust meds, Change jobs
- Supplemental oxygen
- Goal: O2 sat 90-92% - Glucocorticoids - prednisone
- reduce inflammation - reduce scarring/fibrosis
- mainstay despite low success rate and lack of controlled studies - If no improvement –> + immunosuppressant
- cyclophosphamide, azathioprine or mycophenolate mofetil (Cellcept)
indications for supplemental oxygen
- hypoxemia - O2 sat ≤ 88% at rest or with exertion
- Dose is determined by performing pulse ox testing (at rest and with exertion) while slowly titrating supplemental oxygen
after starting a steroid for ILD, what is the management afterwards? any consequences if done incorrectly?
- Pt is reevaluated after 4-12 wks
- if stable / improved, tapered to 0.25–0.5 mg/kg and is maintained at this level for an additional 4–12 wks
- Rapid tapering or a shortened course can result in recurrence
a program of exercise, education, and support to help patients function at the highest level possible
Pulmonary rehabilitation
components of Pulmonary rehabilitation
Exercise - close monitoring of VS
Breathing techniques
Nutrition
Relaxation
Emotional and group support
Learning more about your medications
monitoring for ILD
Follow up every 3-6 months
1. reassess sx, PFT (spirometry, DLCO, pulse ox)
2. monitoring for development of comorbid conditions
- hypoxemia, pulmonary hypertension, thromboembolic disease, COPD, heart failure, obstructive sleep apnea, depression
3. evaluate the clinical course and identify patients who develop accelerated deterioration
pathophys of Idiopathic Pulmonary Fibrosis
- An epithelial-fibroblastic disease, in which endogenous or environmental stimuli disrupt the homeostasis of alveolar epithelial cells leading to abnormal epithelial cell repair and fibrosis
- Excessive production and dysregulation of myofibroblasts
clinical findings of idiopathic pulmonary fibrosis
-
gradual onset of DOE w/ nonproductive cough
- MC onset 55-60 y/o with slight male predominance - fine inspiratory rales/crackles with or without digital clubbing
PFT of idiopathic pulmonary fibrosis
often reveals a restrictive pattern on PFT , a reduced DLCO and hypoxemia that is exaggerated or elicited by exercise
imaging findings of Idiopathic Pulmonary Fibrosis
HRCT scan typically shows:
bibasilar, reticular opacities
traction bronchiectasis
honeycombing
Idiopathic Pulmonary Fibrosis Often requires this diagnostic work-up? findings?
- biopsy
- alternating areas of healthy lung, interstitial inflammation, fibrosis, and honeycomb change
- Fibrosis predominates over inflammation
management for Idiopathic Pulmonary Fibrosis
-
Antifibrotics (FDA approved)
- nintedanib (Ofev) - tyrosine kinase inhibitor
- pirfenidone (Esbriet) - anti-inflammatory; antifibrotic agent
- Doesn’t reverse fibrosis but can prevent further scarring - Lung transplant even while attempting meds
- COVID-19 mRNA vax - benefit of vaccine outweighs risk
caution + CI w/ Antifibrotic Therapy
monitoring?
High risk of drug induced liver injury; CI in severe liver disease
monitor LFT’s before therapy, q1m x 6 months then q3m
what novel class of agents with both antifibrotic and immunomodulatory effects are in trial and have shown benefits for IPF
phosphodiesterase 4B (PDE4B) inhibitors
an inflammatory disease, of unknown etiology, characterized by the presence of noncaseating (non-necrotizing) granulomas involving two or more organ systems
Sarcoidosis
Sarcoidosis MC affects what organ? 2nd MC?
MC organ affected - lungs (including mediastinal LN)
2nd MC organs affected - skin, eye
a mass of granulation tissue, typically produced in response to infection, inflammation, or the presence of a foreign substance.
granuloma
sarcoidosis MC in who and at what age?
- African Americans (AA) and Northern European (NE) descent MC
- Onset - 20-60 years of age
- Research shows a genetic component to dz that protects some pts and predisposes others
in what ethnic groups is sarcoidosis more severe and more mild?
- AA’s - acute, severe disease
- women > men - NE’s - mild, chronic disease
Dyspnea & cough x 2-4 wks
ROS - insidious fatigue, fevers, night sweats, wt. loss
lung exam will likely be normal
what is the dx based on these pulmonary findings?
Sarcoidosis
sarcoidosis lung exam will likely be normal, but when wheezing is heard what does that indicate?
endobronchial involvement or traction bronchiectasis due to scarring
> 90 % of sarcoidosis patients develop what clinical finding?
lung involvement
A lower-extremity panniculitis with painful, erythematous nodules
Erythema nodosum
Violaceous rash on the cheeks or nose
Lupus pernio
MC chronic skin lesion of sarcoidosis
Maculopapular lesions
what ocular findings can be found with sarcoidosis
Anterior/posterior granulomatous uveitis
Conjunctival lesions and scleral plaques
May lead to blindness if left untreated
Erythema nodosum, Lupus pernio, Maculopapular lesions are skin findings for what dx
sarcoidosis
insidious onset, +/-pain, slight photophobia, blurred vision
what type of uveitis is seen in sarcoidosis
anterior
painless, floaters, loss of visual field, scotomas, decreased vision
what type of uveitis is seen in sarcoidosis
posterior
lab findings of sarcoidosis
- Hypercalcemia (5%), hypercalciuria (20%)
- Elevated ESR - Inflammatory response in tissues affected
- Elevated ACE (40-80% pts with active dz)
- ACE elevation is not sensitive / specific for sarcoidosis
granulomas produce what which increases intestinal absorption of Ca - ultimately results in a suppressed PTH
1,25 dihydroxyvitamin D
what secretes ACE that causes elevated ACE levels in sarcoidosis
Pulmonary granulomas
ACE is naturally produced in the lung endothelium
Consider using what med that will produce low ACE level in the presence of sarcoidosis
ACEI
PFT findings of sarcoidosis
- DLco is the most sensitive test - reduced (<80%)
- Spirometry - normal, restrictive or obstructive
- 6MWT - expected results depends on severity
- diminished distance, exercise induced hypoxia
CXR characterization for sarcoidosis
- Staged characterization (radiographic staging) of lung involvement
- Stage I - hilar adenopathy alone
- Stage 2 - adenopathy + infiltrates
- Stage 3 - infiltrates alone
- Stage 4 - fibrosis - Usually the infiltrates are predominantly found in the upper lobes
adenopathy >2 cm in the short axis
patchy reticular nodularity infilatrates
confluent nodularity infiltrates
these HRCT findings support which dx?
Sarcoidosis
what is needed to confirm sarcoidosis dx? Findings?
-
biopsy
- transbronchial bx via bronchoscopy for pulmonary granuloma
- extrapulmonary location is ok: skin lesion, palpable LN
- lung and/or mediastinal LN bx via thoracoscopy - only if atypical on imaging or less invasive testing is indeterminate -
histologic finding - noncaseating granulomas
- r/o infection or malignancy
Bronchoalveolar lavage Shows increased lymphocytes, high CD4/CD8 cell ratio
what is the dx?
sarcoidosis
how to look for cardiac involvement in sarcoidosis? what would you see?
- EKG, 24 hour holter monitor, Echo
- cardiac sarcoidosis seen in 5% of patients
- Evidenced by: restrictive cardiomyopathy, cardiac dysrhythmias, and conduction disturbances
cardiomyopathy, cardiac dysrhythmias, and conduction disturbances
tx indications for sarcoidosis
hypercalcemia
iritis
uveitis
arthritis
CNS involvement
cardiac involvement
granulomatous hepatitis
cutaneous lesions other than erythema nodosum
progressive pulmonary lesions
severe constitutional symptoms
standard care for acute sarcoidosis
second-line?
Standard - oral/topical glucocorticoids
Second-line - immunomodulators (MTX, hydroxychloroquine, azathioprine)
Chronic disease is defined by ?
a lack of resolution within 2-5 years
For patients with advanced pulmonary fibrosis, _____ _____ remains the only hope for long-term survival
lung transplantation
prognosis for sarcoidosis
- Spontaneous remission within 2-5 years occurs in most patients
- Likelihood of remission decreases with higher disease staging - A chronic sarcoid disease state, leads to worse outcomes
referral and f/u for sarcoidosis
- Referral
- Ophthalmology at onset and yearly
- Refer to cardiology, pulmonology ect. based upon organs affected - Follow up
- Minimum yearly exam
- Yearly PFT’s, chemistry panel, CXR and EKG - may be ordered more frequently based upon patient symptoms and response to treatment
types of Occupational and Environmental Lung Disease
- Pneumoconiosis
- Coal workers pneumoconiosis
- Silicosis
- Asbestosis - Pneumonitis
- Radiation Injury
what MUST be taken to discover underlying workplace or general environmental exposure of occuptional/environmental lung disease
A careful “exposure” history
Why is knowledge of occupational or environmental etiology so important?
without proper knowledge of exposure, d/c exposure can’t occur = inadequate response to therapy = worsening course of disease and poorer outcomes
additional historical questions for occuptional/environmental lung disease
the presence of visible dusts or chemical odors
the size and ventilation of workspaces
use of respiratory protective equipment
similar complaints in co-workers
correlation between symptoms and exposure
hobbies
home characteristics
exposure to secondhand smoke
proximity to traffic or industrial facilities
what testing can be misleading due to ILD complicated by environmentally induced asthma/COPD
PFT
uncomplicated and complicated diseases would display what patterns and DLco in PFTs?
- uncomplicated disease - restrictive pattern and a decreased DLCO
- complicated disease - obstructive pattern with decreased DLCO
A chronic fibrotic lung disease caused by the inhalation of inorganic dusts
Pneumoconiosis
presentation of pneumoconiosis ranges from ?
- asx disorders w/ diffuse nodular opacities on CXR to severe, symptomatic, life-shortening disorders
- Treatment for each is supportive
aka “black lung”
Coal Workers Pneumoconiosis
pathophys of Coal Workers Pneumoconiosis
alveolar macrophages ingest inhaled coal dust leading to the formation of “coal macules”, usually 2–5 mm in diameter
what are the 2 types of Coal Workers Pneumoconiosis
- Simple: asx, minimal changes on PFT, small (<1 cm) rounded opacities on CXR
- Complicated: symptomatic, diminished lung function on PFT, nodules ≥1 cm in diameter generally confined to the upper half of the lungs
Silicosis exposure from what occupations/actions?
Rock mining
coal mining (via rock dust)
quarrying
stone cutting
tunneling
masonry
sandblasting
pottery
a fibronodular lung disease caused by inhalation of dust containing crystalline silica
silicosis
pathophys of silicosis
alveolar macrophages ingest the particles inducing an inflammatory response resulting in cell damage and fibroblast release leading to fibrosis
presentation of acute vs chronic silicosis
- acute
- occurs in heavily exposed environments
- few weeks to years after exposure
- cough, SOB, pleuritic pain, weight loss, fatigue - chronic silicosis
- results from long-term, less intense exposure
- may take 15-20 years to develop symptoms or radiographic changes
what are the types of chronic silicosis
- simple silicosis- asymptomatic or exertional dyspnea and cough with sputum production
- complicated silicosis - cough, SOB, loss of appetite, wt loss, malaise/fatigue
PE of silicosis
rales
multiple small (< 10 mm) nodules that are scattered diffusely throughout the lungs but may be more prominent in the upper lung fields.
what is the dx
simple silicosis
bilateral upper lobe masses, which are formed by the coalescence of nodules
what is the dx
complicated silicosis
in a silicosis CT chest, small nodules are seen coalesced into ?
larger masses
silicosis pts are at an increased risk for what other condition? why? what is their maintenance then?
- pulmonary TB
- Silica causes alveolar macrophage dysfunction.
- initial immune response to TB is through alveolar macrophages - annual tuberculin skin test (PPD) and screening CXR
A group of minerals that are shaped like long, thin fibers and used in insulation for pipe, cements, textile, spackling on walls, patching, gaskets, sheet material, ceiling tiles in homes or schools
Asbestos
A nodular interstitial fibrosis occurring in workers exposed to asbestos fibers over many years
Asbestosis
pathophys of Asbestosis
asbestos fibers are inhaled and completely or partially ingested by macrophages depending on the size of the fiber resulting in an inflammatory response, fibroblast proliferation and chronic scarring
presentation of asbestosis
- sx - only after latent period of +20 years
- Dyspnea on exertion (DOE) - MC, progressive with time
- PE - may be normal
- bibasilar, fine end-inspiratory crackles
- clubbing (<½ of patients)
linear (reticular) opacities (often seen first)
multinodular parenchymal opacities of various size and shape
pleural plaques
honeycomb changes in advanced cases
what is the dx?
Asbestosis
Visceral pleura may be fibrotic and associated with parietal pleural plaques, while the central portions of the lung are relatively spared
what are these findings associated with?
asbestosis
most sensitive imaging for asbestosis. why is CXR not enough?
- High Resolution CT (HRCT) - more sensitive
- up to 30% of asbestos exposed pts have normal CXR and abnormal CT
- All findings on CXR can be seen with more clarity on HRCT
used only if HRCT isn’t diagnostic for asbestos
what is this diagnostic work-up?
what would be shown?
Bronchoalveolar Lavage (BAL)
BAL fluid will show asbestos bodies
even in asx pts
autopsy shows small, stiff lungs with fibrosis in the subpleural regions of the lower lobes
what is this condition?
asbestosis
Smoking cessation is esp important in asbestosis due to increased risk of lung carcinoma, especially ____
mesothelioma
A nonatopic, nonasthmatic inflammatory pulmonary disease resulting from exposure to inhaled organic antigens leading to an acute illness
Hypersensitivity Pneumonitis
aka: extrinsic inflammatory alveolitis
pathophys of Hypersensitivity Pneumonitis
immune-mediated disorders characterized by diffuse inflammation of interstitial lung, terminal bronchioles, and alveoli
- Flu like illness with fever, chills, malaise, cough, chest tightness, dyspnea, and headache
- Onset - within hours following significant exposure
- Course - gradual improvement within 12 hours to several days following exposure removal
- May recur following re-exposure
what is this dx?
acute Hypersensitivity Pneumonitis
hx is vital
CXR shows a poorly defined micronodular or diffuse interstitial pattern
what is this dx?
Hypersensitivity Pneumonitis
- Insidious onset of productive cough, dyspnea, fatigue, anorexia, and weight loss
- Onset - over weeks to months
- Course - progresses to persistent cough and dyspnea
which ILD dx
Subacute/ Chronic Hypersensitivity Pneumonitis
Hypersensitivity Pneumonitis sx can be reversible if ?
offending antigen is detected and removed early in the course of illness
management/tx for Hypersensitivity Pneumonitis
- tx consists of identification and avoidance of offending agent
- Oral corticosteroids can be useful, especially in severe or protracted cases
the degree of Radiation Lung Injury is determine by several factors:
- Volume of lung irradiated
- Dose and rate of exposure
- Other potentiating factors:
- concurrent chemotherapy
- previous radiation therapy in same area
- simultaneous withdrawal of corticosteroid therapy
Radiation lung injury occurs in associated radiation therapy for what cancers
breast cancer (10%)
lung cancer (5–15%)
lymphoma (5–35%)
Two phases of the pulmonary response to radiation are common:
an acute phase (radiation pneumonitis)
chronic phase (pulmonary radiation fibrosis)
presentation of Radiation Pneumonitis
- Onset: 2-3 months (range 1-12 months) after completion of radiation therapy
- Clinical presentation
- insidious onset of dyspnea, intractable dry cough, chest fullness or pain, weakness, and fever
- In severe disease, respiratory distress and cyanosis occur that are characteristic of ARDS
- Inspiratory rales may be heard in the involved area
CXR
alveolar or nodular opacities limited to the irradiated area
Air bronchograms are often observed
what is the dx
Radiation Pneumonitis
tx for Radiation Pneumonitis
supportive; steroids may be given
Pulmonary Radiation Fibrosis Most common in patients who receive a ?
full course of radiation therapy for cancer of the lung or breast
May occur with or without prior hx of radiation pneumonitis
presentation of Pulmonary Radiation Fibrosis
most patients are asymptomatic, although slowly progressive dyspnea may occur
radiographic findings include of pulmonary radiation fibrosis
- obliteration of normal lung markings
- dense interstitial and pleural fibrosis
- reduced lung volumes
- tenting of the diaphragm
- sharp delineation of the irradiated area
tx for Pulmonary Radiation Fibrosis
No specific therapy is proven effective
Corticosteroids have no value
these disorders are autoimmune disorders of unknown etiology that lead to inflammation and damage to the connective tissues:
Connective Tissue Disorders
skin, fat, muscle, joints, tendons, ligaments, bone, cartilage, and even the eye, blood, and blood vessels
CTD’s most commonly associated with ILD:
Progressive Systemic Sclerosis
RA
SLE
Sjögren Syndrome
Polymyositis and Dermatomyositis
Patients with ILD should always be evaluated for ?
clinical findings suggestive of a CTDs
musculoskeletal pain, weakness, fatigue, fever, joint pain or swelling, photosensitivity, Raynaud’s phenomenon, pleuritis, dry eyes, dry mouth
what symptoms occasionally precede the more typical systemic manifestations of CTD’s and what is its timing?
Pulmonary symptoms
by months or years
MC sx of Drug Induced ILD
DOE and nonproductive cough
Many classes of drugs have the potential to induce diffuse ILD, but what are some common ones?
- antiarrhythmics
- antibacterials
- antineoplastics
- antirheumatics
- phenytoin
presentation and tx of drug-induced ILD
- In most cases, the pathogenesis is unknown
- The drug may have been taken for years before a reaction
- sx may begin weeks to years after the drug has been d/c
- tx - d/c any possible offending drug and supportive care
