9/15- Interstitial Lung Disease Flashcards
What are the components of the pulmonary interstitium?
- Alveolar epithelium
- Pulmonary capillary endothelium
- Basement membrane
- Perivascular and perilymphatic tissues
What does ILD refer to?
Interstitial Lung Diseases
- Diffuse Parenchymal Lung Disorders
- Heterogeneous group of disorders grouped together due to similar clinical, physiologic, radiographic, and pathologic features
May be classified by:
- Known causes or unknown causes
- Based on histo-pathology: alveolitis/fibrosis or granulomatous or alveolar filling
- Based on onset: acute or chronic
Flowchart classification of diffuse parenchymal lung disease
- Known cause (drugs, collagen vascular dz…) - Idiopathic interstitial pneumonia
- Idiopathic pulmonary fibrosis
- IIP other than idiopathic pulmonary fibrosis (different pneumonias)
- Granulomatus DPLD (sarcoidosis)
- Other forms of DPLD
Diagnostic approach to ILD diagnosis?
Multidisciplinary Clinical + Radiology + Pathology
Typical presentation of ILD
- Age
- Gender
- Symptoms
- Typ > 50 yo
- Mostly women > men EXCEPT rheumatoid arthritis and IPF
Symptoms:
- Progressive dyspnea
- Dry cough
- Occ. weight loss
What are some ILDs with acute onset (days-weeks)?
- AIP (Hamman-Rich Syndrome)
- Acute pneumonitis from collagen vascular disease (especially SLE)
- Cryptogenic organizing pneumonia
- Drugs
- Diffuse alveolar hemorrhage
- Eosinophilic lung disease
- Hypersensitivity pneumonitis
What are some ILDs with subacute onset (weeks - months)?
- Collagen vascular disease-associated ILD
- Cryptogenic organizing pneumonia
- Drugs
- Subacute hypersensitivity pneumonitis
What are some ILDs with chronic onset (months - years)?
- IPF, NSIP, and other IIPs
- Pneumoconioses (lung disorders caused by occpational disorders)
- Chronic hypersensitivity pneumonitis
- Collagen vascular disease-associated ILD
What illness are associated with ILDs that you might expect to find in past medical history?
- Collagen vascular disorders
- Rheumatoid arthritis
- SLE
What diseases might be expected in family history for someone with ILD?
- Sarcoidosis
- Interstitial pulmonary fibrosis
What medication history might you find for someone with ILD?
MANY
- Methotrexate
- Amiodarone
- Also some illicit drugs
What might you look for in the social history of someone with ILD?
- Occupation: ship-building (demolition– asbestos), insulator, sand-blasting (silica exposure), farming
- Smoking history: IPF, RB-ILD, DIP
(RB-ILD so associated that it may get better upon smoking cessation)
What might be expected in the physical exam for someone with ILD?
Most findings from auscultation
- Tachypnea
- Rales (“Velcro” crackles)*
- Clubbing
- Exercise desaturation
Late stages:
- Signs of right heart failure
- Cyanosis
What labs might you find for someone with ILD?
- ABG
- Certain disease disorder labs
- Others
ABG
- Early stages: no changes
- Late stages: hypoxemia; elevated A-a gradient
Connective tissue disorder labs:
- ANA
- Rheumatoid factor
Others:
- ACE and Ca elevated in Sarcoidosis
Describe pulmonary function tests for patients with ILD?
- FEV1/FVC
- TLC
- DLCO
Restrictive pattern
- Decreased lung volumes; TLC reduction determines severity of disease
- Normal FEV1/FVC
Reduced DLCO (diffusion capacity) secondary to physiological alveolar-capillary block
T/F: PFT can help determine specific disease/etiology of ILD?
False
What are the radiologic patterns of ILD?
- Reticular: fine lines due to thickening and fibrosis of interstitium
- Nodular
- Reticulo-nodular
- Ground glass: hazy; can see through it, but somewhat obscure (more in acute-onset ILDs)
- Alveolar
What conditions fall into the following radiologic patterns of ILD:
- Reticular
- Nodular
- Reticulo-nodular
- Ground glass
- Alveolar
Reticular
- IPF (idiopathic pulmonary fibrosis)
- Asbestosis
- Connective-tissue associated
Nodular
- Sarcoidosis
- Silicosis
- Hypersensitivity
- Pneumonitis
Reticulo-nodular
Ground glass
- NSIP (nonspecific interstitial pneumonia)
- DIP (desquamative interstitial pneumonia)
- RBILD (respiratory bronchiolitis interstitial lung dz)
- Pulmonary hemorrhage
Alveolar
- Cryptogenic organizing pneumonia
Which ILDs are predominantly in the upper lobe? Lower lobe?
Upper lobe
- Sarcoidosis
- Silicosis
- Acute
- Hypersensitivity pneumonitis (HP)
- Ankylosing spondylosis
Lower lobes:
- IPF
- Chronic HP
- Asbestosis
Pneumothorax hints at which ILD?
Lymphangioleiomyomatosis (LAM)
Pleural plaques hints at which ILD?
Asbestosis
- Asbestos fibers can go down all the way to pleura and cause irritation -> thickening of pleura (doesn’t progress to cancer, but is a marker of exposure)
Hilar adenopathy hints at which ILD?
Sarcoidosis
What is seen here?
Reticular pattern, lower lobe predominant
- Increased “haziness”, esp at base
- Very fine lines
This could be:
- IPF
- CT-disease related
- Asbestosis
What imaging is used to evaluate ILD?
High resolution CT; superior to CXR
- Extent and distribution of disease
- Patterns
What are some pathologic diagnostic tests?
Bronchoscopy
- Bronchoalveolar lavage
- Transbronchial lung biopsy
Surgical lung biopsy
Other biopsy:
- Skin: sarcoid
What are the pathologic categories and ILDs within them (that we will cover specifically)?
Alveolitis/Fibrotic
- IPF
- NSIP
- CT disease related
- Pneumoconiosis
Granulomatous
- Sarcoidosis
- Hypersensitivity pneumonitis
Alveolar filling
- COP (cryptogenic organizing pneumonia)
Characteristics of Idiopathic Pulmonary Fibrosis (IPF)
- Age of onset
- Gender bias
- Onset
- PE findings
- Pathology
- Imaging
- Age of onset 6th-7th decade (rare under 50 yo)
- Men > women
- Chronic onset
- PE: velcro rales and clubbing
- Pathology: usual interstitial pneumonia
Imaging:
- Reticular infiltrates
- Lower lobe predominant
- Subpleural with honeycombing in late stages (pockets of scared-down lung)
- Temporal heterogeneity
What is seen here?
IPF findings/reticular pattern
Arrows point to honeycombing (burnt out lung)
Treatment for IPF?
Best supportive care
- O2 therapy
- Pulmonary rehab
- Early recognition of terminal decline and liaison with health care specialists
Lung transplantation only option for some:
- DLCO under 40% predicted or progressive (>10% decline in FVC)
- Refer early
- Single or double
Most pts die on transplant list (typ life expectancy = 5yrs?)
Medications (conditional recommendation):
- Nintedanib (TK inhib with multiple targets, including VEGF, FGF, and PDGF receptors)
- Pirfernidone (oral antifibrotic with pleiotropic effects: regulate important profibrotic/proinflammatory cyotkine cascades while reducing fibroblast proliferation and collagen synthesis)
- Anti-acid therapy (reflux/GERD may contribute to chronic lung inflammation and resultant IPF)
What treatments are strongly NOT recommended in IPF?
What about conditionally not recommended?
- Anticoagulation (warfarin)
- Imatinib (selective TK inhibitor against PDGF)
- Combo prednisone, azathioprine, and N-acetylcysteine
- Selective endothelin receptor antagonist (ambrisentan)
(No steroids! Although these are common treatment for some other ILDs)
Conditionally not recommended:
- PDE5 inhibitor (sildenafil)
- Dual endothelin receptor antagonists (macitentan, bosentan)
- N-acetyl monotherapy
T/F: Honeycomb lung is specific for IPF?
False
- Sign of “burnt out lung”; any end-stage ILD
- At this point, lung transplant is really your only hope
Characteristics of NSIP?
- Commonality
- Age
- Epidemiology
- History
- PE findings
- Pathology
- Imaging
- Diagnosis
- 2nd most common diagnosis
- Middle aged
- Majority are smokers
- Similar hx to IFP
- Similar PE to IFP, but less clubbing
- Pathology: homogeneous interstitial thickening
- Imaging: diffuse ground glass infiltrates
- Surgical biopsy required to make diagnosis
How do connective tissue disease related ILDs differ from IPF?
- Part of multisystem disease, usually apparent prior to pulmonary involvement
- Pleural involvement common
What CT diseases most common involve pulmonary manifestations in CT disease related ILDs?
- SLE
- Rheumatoid arthritis
What does pulmonary involvement in SLE look like?
- Pleuritis/pleural effusion (most common)
- Alveolar hemorrhage
- Acute pneumonitis
- ILD (0-4%)
- Diaphragmatic weakness
What does pulmonary involvement in rheumatoid arthritis?
2 unique issues:
1. Joint disease usually precedes pulmonary involvement
2. Males > females
Pulmonary complications are rare
- Pleural effusion is most common (under 5%)
Also:
- Fibrosing alveolitis/Fibrosis
- Necrobiotic nodules
- Pleural effusion
- Bronchiolitis obliterans
- ILD due to drug therapies (e.g. methotrexate)
Characteristics of asbestos associated lung disease
- Exposure
- Upper or lower lung fields
- Benign vs. malignant
- Natural history
- Symptoms
- Radiology
- Complications
- Exposure: shipyard workers (WWII), refineries, demolition of old buildings, construction ,insulation, bake repair
- Asbestosis (pulmonary fibrosis)- more in lower lung fields
- Benign asbestosis- related pleural disease (pleural plaques/adhesions)
- Bronchogenic cancer
- Mesothelioma: pleural malignancy (not associated with smoking at all)
- Natural hx: insidious onset; many years after exposure (usually > 20 yrs!)
- Sx: insidious onset of dyspnea and cough
Radiology
- Irregular opacities primarily in lower lobes
- May be associated with pleural plaques/thickening
Complications:
- Acts as co-carcinogen with tobacco smoke
- Up to 50x increase in lung cancer among asbestos workers who smoke compared to smokers in other trades
What is this?
Asbsestosis
Characteristics of Silicosis?
- Overall
- Work environment
- Natural history
- Radiographic features
- Diagnosis
- Complications
Chronic, fibronodular lung disease caused by long term exposure to crystalline silica
- Work environment: stone cutting/polishing, mining, foundry work, sandblastin
- Usually requires exposure of > 5 yrs
- Natural hx: variable; most commonly slowly progressive dyspnea, cough, sputum
Radiographically:
- Upper lobe (apex)
- Hilar adenopathy (egshell calcifications)
Diagnosis:
- CXR and history
- Occasionally need lung biopsy
- High resolution CT may be helpful
Complications:
- Increased risk for TB (5-43%)
- No increased risk for lung cancer (?)
Characteristics of Sarcoidosis:
- Gender
- Epidemiology
- Clinical presentation
- Symptoms
- Radiologic changes
- Multisystem disease of unknown etiology
- Females > males
- Black > white
- Usually under 40
Clinical presentation: multi-system disease which may present acutely, subacutely, or chronically
- CNS, eye, skin, bone, cardiac, endocrine
- Most commonly pts are asymptomatic with an abnormal CXR
Radiologic stages
0: no CXR anbormality (5-10%, ie sarcoid diagnosed in another organ system)
I: LN enlargement without parenchymal change, most common*
II: nodes +, diffuse parenchymal changes
III: nodes -, diffuse chagnes IV: evidence of fibrosis
Diagnosis of sarcoidosis?
- Rests on clinical assessment and compatible tissue biopsy
- Hallmark pathology is non-caseating granuloma
- Rule out other disorders, esp TB
- Tissue diagnosis: transbronchial biopsy + ve in 50-60% with normal CXR; 85-90% with abnormal CXR
Treatment of Sarcoidosis?
- Natural history
- When to treat
- Treat with what
Course:
- 30-50% spontaneously remit in 3 yr period
- 20-30% remain stable
- 30% progressive
Treat if symptomatic or vital organ involvement
Treat with immunosuppression
Characteristics of Hypersensitivity Pneumonitis
- Exposure
- Radiology
- Diagnosis
- Pathology
Exposure
- From inhalation of and sensitivity to organic dusts
- Antigens are quite varied but clinical response to all is similar
- Most common is after exposure to thermophilic actinomyces in moldy hay, silos etc. (Farmer’s lung)
Radiology
- Diffuse, small nodules that appears as ground glass infiltrates
- Acute upper lobe and chronic lower lobe
Diagnosis: requires a high index of suspicion
Pathology: Peribronchial lymphocytic infiltrates with poorly formed granulomas
Treatment for Hypersensitivity Pneumonitis?
- Avoidance of causative antigenic agent
- Corticosteroids may have role in treating severe or progressive disease
Characteristics of COP (Cryptogenic Organizing Pneumonia)
- Epidemiology
- Symptoms
- CXR features
- HRCT
- Pathology
- Prognosis
- Treatment
Idiopathic “BOOP”: bronchiolitis obliterans organizing pneumonia
- Unknown etiology
Epidemiology: 5th-6th decades (equal genders)
Symptoms:
- Malaise
- Weight loss
- Mylagias
- Cough
- SOB
- Typically following respiratory infection
CXR: patchy or diffuse infiltrates
- Often recurrent or migratory
HRCT: airspace around ground glass opacities and bronchial wall thickening/dilation
Pathology: patchy cellular airspace fibrosis in alveoli and alveolar ducts
Prognosis: good; spontaneous remission in 50%
Treatment: steroids; very sensitive
Summary
