Interstitial Lung Disease

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    Introduction

    • Now called "Diffuse Parenchymal Lung Disease"
      • because the term "Interstitial Lung Disease" is a misnormer, excludes vascular and other etiologies.
      • Still excludes pulmonary HTN and COPD.
    • Present with dyspnea
    • Imaging studies show diffuse pattern.
    • Many kinds (>100), and they are all rare.
    • Classified in different ways.

    Approach

    ILDApproach.png

    Approach

    • Careful history + exposures
    • Physical exam looking for underlying conditions.
    • PFTs
    • High Resolution CT ** GOLD STANDARD in assessment **
      • Do this even if CXR is normal in symptomatic pts (20% with normal CXR will have helpful CT findings).
      • 60% of pts get a diagnosis.
      • If no diagnosis, open lung biopsy is an option.

    History

    • Acuteness of Onset
    • Exposures:
      • Hypersensitivity Pneumonitis
        • Antigen Source

          Associated Disease

          Organic Antigens: Bacteria, Fungi, Mycobacteria

          Moldy hay, silage, or grain

          Farmer's lung

          Potatoes packed in moldy hay

          Potato worker's lung

          Moldy typesetting water

          Bible printer's lung

          Moldy cheese

          Cheese washer's lung

          Aerosolized hot tub water

          Hot tub lung

          Stagnant humidifier water

          Humidifier lung

          Moldy cork

          Suberosis

          Moldy wood dust

          Wood dust or wood trimmer's lung

          Organic Antigens: Animal Protein

          Bird feathers and droppings

          Bird fancier's lung

          Processed turkey or chicken serum

          Turkey or chicken handler's lung

          Animal pelts

          Furrier's lung

          Laboratory animal dander, serum, excrement

          Laboratory worker's lung

          Inorganic Antigens

          Diisocyanate(s)

          Chemical lung

          Aerosolized machine lubricants

          Machine operator's lung

          Pyrethrum

          Pesticide lung

      • Inorganic Dusts:
        • Mind Working, Stone Cutting (Silocosis)
        • Asbestos Exposure (Asbestosis)
        • Coal Minging (Coal Worker's Lung)
        • Beryllium Exposure
        • Gasses/fumes/vapours?
      • Smoking
    • Connective Tissue Disease (Head to toe)
      • Eyes: Scleritis? episcleritis?
      • Skin: rashes, sclerosis, clubbing.
      • Joints: active joints
      • GI: Reflux?
    • Medications:
      • Look up all medications on pneumotox.com
      • Classically: amiodarone, nitrofurantoin, chemo, methotrexate.
    • Familial (pulmonary fibrosis, autoimmune dz)
    • Physical Exam:
      • Lung: crackles, wheezes
      • Extrapulmonary signs; arthritis, clubbing, joint deformities (arthritis?), skin changes (systemic sclerosis?)

    Diagnostic Tests

    • High Resolution CT
    • PFTs
      • Restrictive vs. Obstructive
    • Surgical Open Lung Biopsy for ILD not obvious on CT/hx/px (Nowadays do VATS surgery)
      • If not contraindications (severe pulm. HTN, etc..).
      • Want areas that aren't too damaged (non-specific) and not too healthy.
    • Labs: (R/O connective tissue disease)
      • ABG (home O2)
      • ANA
      • ENA Screen (scleroderma ones included)
      • Anti-CCP
      • ESR/CRP
    • Often pathologist, pulmonologist and radiologist sit down and decide on diagnosis if not straight forward.

     

     

    CT Findings

    Pattern of High-Resolution CT Findings in Diffuse Parenchymal Lung Disease

    Pattern

    Characteristics

    Comments

    Septal

    Short lines that extend to the pleura in the periphery of the lung or as polygonal arcades that outline the pulmonary lobules more centrally

    - lymphatic enlargement

    - pulmonary edema (MOST COMMON)

    - lymphangitic spread of cancer

    Reticular

    Interlacing lines that suggest a mesh or lattice

     

    Nodular

    Spherical lesions (<1 cm) that accumulate within the interstitium

    - Sarcoidosis (diffuse nodular opacities)

    Reticulonodular

    Intersection of reticular lines or nodules on top of a reticular pattern or vice versa

    - Sarcoidosis

    - Pulmonary Langerhans cell histiocytosis

    - Lymphangitic carcinomatosis

    Ground-glass

    Hazy increased opacity that does not obscure the underlying vascular markings

    - Desquamative interstitial pneumonia (DIP)

    Consolidation

    Denser opacity that obscures vascular markings, unlike ground-glass opacity

     

    Honeycomb change

    (Often end-stage irreversible changes of many ILDs)

    - Septal lines are coarse and adjacent to cystic areas that stack in the peripheral portion of the lung

    - IPF (septal lines, honecombing)

    - End stage lung disease

    MKSAP 16

    Distribution

    Lung Disease

    Basal predominant

    IPF, asbestosis, NSIP

    Upper-lobe predominant

    Hypersensitivity pneumonitis, sarcoidosis, silicosis

    Peripheral

    IPF, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia

    Central

    Sarcoidosis, pulmonary alveolar proteinosis

    Mosaic attenuation

    (Neighboring lobules have varying density and with small airways disease

    this is accentuated on expiratory images)

    - Pulmonary vascular disease

        Small airways disease

    - hypersensitivity pneumonitis

    - RB-ILD

    MKSAP 16

     

    • NOTES:
      • Calcified pleural plaques --> asbestosis
      • Lymphadenopathy in mediastinum and hilum --> sarcoidosis

     

    Specific Diseases

    Idiopathic Pulmonary Fibrosis (IPF)

    • Most common idoipathic interstitial pneumonia ( more common in older ages).
    • Symptoms:
      • Progressive dyspnea x6mo.
    • CT:
      • Hallmark: Peripheral and Basal predominant distribution on CT in pt with progressive pulmonary symptoms.
    • Lung Biopsy
      • Described as "Usual Interstitial Pneumonia" (UIP) by pathologist.
      • Patchy involvment of lung parenchyma, with sub-pleural predominance.
      • Collagen deposition with temporal heterogeneity (areas of normal and advanced in lung).
      • Fibroblastic foci interspersed with normal lung.
    • Exam:
      • Velcro-like crackles at the bases.
    • Complications:
      • Pulmonary Hypertension --> no good evidence for PDE5 inhibitors.
    • Prognosis:
      • Poor prognosis 3-5y median survival from diagnosis
        • 1. Usually progression is steady decline
        • 2. IPF Exacerbation - > rapid progression.
      • Very intense area of research.
      • Steroids tried -> not beneficial, usually avoid.
      • Comorbidities:
        • Treat GERD if present.
        • OSA is common.
    • Treatment:
      • Pulmonary Rehab: improves exercise capacity.
      • Home O2 if O2sat <89% can improve sense of well-being, mental alertness, function.
      • Only intervention improving survival is ung transplant
    • Exacerbation Management:
      • Manifests as new ground glass opacities on chronic fibrotic changes.
      • Ensure not reversible (PE? HF? Infection?)
      • No good primary treatment, steroids tried but no consistent benefit.

     

    Non-Specific Interstitial Pneumonia (NSIP)

    • Usually associated with connective tissue disease (most common systemic sclerosis).
    • Like IPF: Basal predominant.
    • Unlike IPF: a lot more ground-glass than IPF, less honeycombing.
    • Diagnosis:
      • Often need an open lung biopsy (VATS)
    • Pathology:
      • Predominantly cellular pathology with extensive inflammatory infiltrate.
      • Collagen deposition with less cellularity.
    • Treatment:
      • WILL respond to steroids and immunosuppression! (unlike IPF).
        • Steroid trial is indicated.
      • Researched role of chronic cytotoxic therapy.
      • Treat underlying collagen vascular disease.

    Cryptogenic Organizing Pneumonia (COP)

    • Idiopathic form of Bronchiolitis Obliterans Organizing Pneumonia (BOOP).
    • Can be triggered by:
      • Drug Reaction
      • Collagen Vascular Disease
      • Viral 
    • NOTE:
      • If trigger is known it is termed BOOP.
      • If cause is unknown: COP.
    • Symptoms:
      • Presents as a cough, almost always diagnosed as community acquired pneumonia.
      • Consider if did not respond to one or more courses of abx.
      • Most symptomatic for >3months.   (IPF >6mo of sx).
    • Diagnosis:
      • Classic finding: bilateral diffuse alveolar opacities.
      • Need lung biopsy to confirm diagnosis.
    • Treatment:
      • Often responsive to systemic steroids.
      • Recurrence is common when tapering steroids, but respond if increase again (do slower taper).

     

    Acute Interstitial Pneumonia (AIP)

    • aka "Hamman-Rich Syndrome" or "Idiopathic Diffuse Alveolar Damage"
    • Rapid onset of disease in days-to-weeks resulting in hypoxemic respiratory failure.
    • Presentation:
      • Presents rapidly, but like a "slow-motion ARDS".
      • In days to weeks develops bilateral infiltrates (within a week of risk factor exposure) + severe hypoxemic resp failure.
    • Pathology:
      • Diffuse alveolar damage.
      • The same as ARDS (but no ARDS risk factors).
    • Treatment:
      • Corticosteroids, unclear if benefits patients.
      • 50% of pts will die in short term.
      • Manage same as ARDS - low tidal volume ventilator strategy.

     

    ILD of Known Etiology

    Smoking Related

    • Often see micronodular disease in many smokers on high-res CT.
    • SMOKING-Related ILD:
    • ONLY ACTIVE SMOKERS with subacute progressive cough and dyspnea
      • Micronodular --> RBILD (Respiratory Bronchiolitis with ILD)
      • Diffuse ground-glass --> DIP (Desquamative Interstitial Pneumonia)
      • Thin wall cysts with pulmonary nodules with upper lobe predominance --> Pulmonary Langerhan Cell Hisiocytosis
    • On PFT's: NOT restrictive, but OBSTRUCTIVE with DECREASED DLCO
    • Primary Treatment:
      • Smoking Cessation

     

    Connective Tissue Disease Related

    • (Can involve lung parenchyma, pleura, small airways, pulmonary vascular disease, MSK chest wall function).
    • Sometimes immunosuppressed from CTD, and could be atypical infection.
    • Treating CTD to help lungs --> but using methotrexate can worsen lungs.
    • Systemic Sclerosis:
      • In systemic sclerosis, progressive parenchymal lung disease is the leading cause of death
      • Most common finding is NSIP
        • Oral steroids not been shown to be beneficial
        • Some role for cyclosphophamide --> short term benefit.
    • RA -> pulmonary disease is very common, can even present before arthritis, get Anti-CCP 
      (can present as pleural dz, nodules, bronchitis, bronchiectasis etc..).

     

    Hypersensitivity Pneumonitis

    • Hypersensitivity pneumonitis caused by repeated inhalation of finely dispersed antigens.
      • Can be organisms(fungus, bacteria, protozoan), animal/insect proteins, small chemical compounds.
      • Most commonly:
        • Thermophilic actinomyces
        • Fungi / Moulds
        • Bird droppings
        • (MANY!!)  including "Bible Printer's Lung").
      • (SEE HISTORY/PHYSICAL SECTION FOR THE LIST)
    • Acute:
      • Flu-like symptoms 4-8 hours after intense exposure.
        • (Fever, chills malaise, headache, arthralgia/myalgia)
      • Dyspnea, chest tightness, dry cough.
      • CXR: Bilateral hazy opacities
      • High-Res CT: Groundglass opacities with nodules in centers of lobules (upper-mid lung distribution).
      • Treatment:
        • Avoid exposure to antigen.
    • Subacute/Chronic
      • Chronic low-level exposure. (I.e. domesticated caged birds)
      • Progressive symptoms over a long time with few acute symptoms.
      • Presenting: Dyspnea, fatigue, anorexia, weight loss
      • High-Res CT: fibrosis with reticular lines, traction bronchiectasis, honeycomb changes (architectural distortion).
      • Treatment:
        • Avoid exposure to offending antigen.
        • If severe: oral corticosteroids.

    Drug Induced

    • Check pneumotox.com (check each drug)
    • Temporal association between symptoms and starting drug.
    • Amiodarone:
      • High incidence of pulmonary toxicity.  Stop the drug.
      • More commonly in elderly, higher doses, and accumulation of high doses over time.
      • Can occur within a few days to more than 10 years after initiating therapy.
      • Usually starts within 1st year of treatment.
      • CT Scan: can manifest multiple ways
        • Acute: Patchy groundglass, diffuse opacities
        • Chronic: Pulmonary fibrosis
        • Other: Organizing pneumonia, diffuse alveolar damage, subpleural masses,
          • Subclinical pneumonitis (CXR normal, can only see on high-res CT).
      • After stopping can take long time to clear (autopsy results show can be in lung for >1yr after stopping).
      • Unfortunately parenchymal abnormalities slowly improve after stopping the drug, and can recur when tapering steroids (even 2-3 months after initial response).
    • Methotrexate
      • Pneumonitis in 5% pts on methotrexate.
      • Fever, cough, dyspnea.
      • CXR: diffuse pulmonary infiltrates
      • Timing very variable. 
      • CT: Diffuse reticular and groundglass attenuation.
        • Severe: dense consolidation.
      • Mild-to-Moderate peripheral eosinophils in peripheral blood.
      • Lung biopsy: see interstitial pneumonitis with granuloma formation (hypersensitivity pneumonitis).
      • Other findings: BOOP, diffuse alveolar damage.
      • Treatment:
        • D/C drug
        • Corticosteroids.
    • Nitrofurantoin
      • Acute: days after starting furantoin (even after previously tolerating)
        • Fever, chills, dyspnea, cough, wheezing myalgia, chest pain.
        • 10-20% will have a cutanous rash.
        • Peripheral eosinophils are common.
        • CXR: faint bibasilar markings, Kerley B-lines, moderate occasional pleural effusions.
      • Chronic:
        • Does not develop after acute phase (separate entity)
        • CXR: reticular infiltrates, coarse central lines converging to hila, subpleural lines, thickened peribronchovascular areas, sometimes reduced lung volumes.
      • Treatment:
        • D/C drug, abnormalities return if restart nitrofurantoin.
        • Corticosteroids: unclear if benefit. (often improves with d/c drug).

     

    Radiation Pneumonitis

    • Symptoms usually 6 weeks post-exposure. (1.5 months)
      • Cough, dyspnea
    • CT: hazy opacities with groundglass attenuation.  Mostly within the radiation field (occasionally outside of field).
      • I.e. breast cancer radiation on one side, can develop organizing pneumonia in the other side.
    • Classically resolves in 6 months, but can progress to volume loss, bronchectasis, fibrosis. 
    • R/O opportunistic infection.
    • Treatment:
      • Corticosteroids may be helpful (esp if early), but based on severity.

    ILD Exacerbations

    • Diagnostic criteria include:
      • Unexplained worsening or development of dyspnea in < 30 days
      • High-resolution CT showing new bilateral ground-glass opacity and/or consolidation superimposed on a background of findings consistent with usual interstitial pneumonia (For UIP specifically)
      • No evidence of alternative causes.
    • The only intervention shown to improve survival in selected patients with IPF is lung transplantation. 
    • Treatment:...

    Notes

    • Acute Onset of DPLD:
      • UIP
      • Acute Eosinophilic Pneumonia
      • Acute Hypersensitivity Pneumonitis
      • Drug-Induced Pneumonitis
      • BOOP / COP
      • Diffuse Alveolar Hemorrhage Syndromes
      • Vasculitis

     

    Sarcoidosis

    • Definition:
      • Multiorgan inflammatory disease see tissue infiltration by mononuclear phagocytes, lymphocytes, and formation of non-caseating granulomas (caseating granulomas are usually infections like TB).
      • Involves lymph nodes and lung parenchyma.
    • Presentation
      • Presents with varying time courses.
      • Classic acute form of sarcoid "Lofgren's Syndrome": 
        • Erythema nodosum, fever, arthralgia, hilar lymphadenopathy.
        • 90% have pulmonary involvement.
        • Often misdiagnosed as asthma or bronchitis, but be suspicious if PFTs show restriction (sarcoid).  Can cause obstruction but rare.
      • Heerfordt syndrome
    1. Uveitis
    2. Parotid Gland Enlargement
    3. Fever
    • Diagnosis:
      • Upper lobe predominance is characteristic (on Xray - Upper Lobe infiltrates).
      • Diagnosis of Sarcoid:

        • Dx of exclusion (exclude other causes)
        • Show multi-organ involvement
        • Histologic evidence of non-caseating granulomas
      • Löfgren syndrome and Heerfordt syndrome
        • Often do not require biopsy, if classic Lofgren's or Heerfordt.
      • Tissue biopsy often needed:
        • Lymphadenopathy
        • Endobronchial Ultrasound (EBUS) sensitivity >85%.
        • Bronchoscopy with transbronchial biopsies combined with endobronchial biopsies >90% sensitivity.
      • Stage:
        • Stage based on CXR findings.
          •  

            Stage

            Radiographic Pattern

            0

            Normal

            I

            Hilar lymphadenopathy with normal lung parenchyma

            II

            Hilar lymphadenopathy with abnormal lung parenchyma

            III

            No lymphadenopathy with abnormal lung parenchyma

            IV

            Parenchymal changes with fibrosis and architectural distortion

     

    • Treatment:
      • Most spontaneously resolve, but the higher the stage the less likely to spontaneously resolve. (i.e. 1/3 ppl remit in Stage III).
      • Treat if symptomatic
        • Corticosteroids --> new report shows can use lower doses of steroids (esp for acute exacerbations of sarcoid).  Treat for 6 weeks
          • Treat if:
            • Worsening radiographic opacities (Stage II or III)
            • Worsening PFTs
            • Bothersome symptoms
        • If mild and no significant organ involvement, can use naproxen or colchicine
    • Cardiac Involvement

       

       

      • Cardiac Involvement (25% of pts, mostly subclinical, few have symptoms), few get cardiomyopathy.
        • Echo typically shows restrictive cardiomyopathy (restrictive filling, reduced peak diastolic annular velocity, biatrial enlargement, normal ejection fraction)

          To diagnose cardiac sarcoid do cardiac MRI (CMR)  --> shows delayed gadolinium hyperenhancement (mid-myocardial wall or epicardium), indicative of fibrosis/inflammation in a non-CAD distribution. 

          • CMR also rules out constrictive pericarditis. 

        • If inconclusive, do biopsy.

      • If patient develops heart failure secondary to sarcoid restrictive cardiomyopathy --> ICD is indicated as per guidelines to reduce sudden cardiac death + additional immunosuppressive agents.

      • Steroids, often 24 week taper.  2/3 improve.

    Lymphangioleiomyomatosis

    • Known as LAM.
    • Rare cystic lung disease, sporadically in women of childbearing age or in association with tuberous sclerosis.
    • Active area of research.
      • New finding: due to pulmononary parenchymal infiltration of smooth muscle cells that have inactivating mutations of tuberous sclerosis complex gene. 
    • Now viewed as a low-grade metastatic neoplasm that selectively targets the lung and recurs after transplant.
    • Diagnosis:
      • Misdiagnosed as emphysema.
      • Cassically: Young person with spotaneous pneumothorax or chylothorax.
        • High- Res CT: diffuse thin-walled small cysts.
      • Serum Marker: VEGF-D (vascular endothelial growth factor D), specific marker.
    • Treatment:
      • Progressive disease.
      • Lung transplant.
      • Biologics are being investigated.

     

    Asbestosis

    TODO: Under construction

    • Exposures:
      • Shipbuilding
      • Car manufacturing
      • Construction
    • Ask: was visibility poor at your workplace, etc..
    • CT findings:
      • Pleural thickening and subpleural linear densities parallel to the pleura
      • Basilar lung parenchymal fibrosis with peribronchiolar, intralobular, and interlobular septal fibrosis, and parenchymal bands.
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