Info
🌱 來自: Huppert’s Notes
Restrictive Lung Diseases🚧 施工中
Restrictive Lung Diseases
• Restrictive = ↓Compliance, ↑Elastance→ Problem getting air in.
- ↓DLCO in ILD. Normal DLCO in neuromuscular disorders. ↑DLCO in obesity
- ↓TLC, ↓RV. Increase in radial traction, so tethered more strongly and airways remain open
- FEV1↓, FVC↓↓ → FEV1/FVC ratio normal or increased
Extrapulmonary Restrictive Disease (Normal DLCO)
• Neuromuscular diseases: Guillain-Barré, myasthenia gravis, poliomyelitis, post-polio, ALS. These disorders may cause weakening of the respiratory muscles.
• Diaphragmatic disease
• Conditions affecting the chest wall: Kyphoscoliosis; obesity hypoventilation syndrome; “Pickwickian syndrome,” BMI >50, hypoventilation due to ↓central drive to breathe. Tx: Weight loss and noninvasive positive pressure ventilation. Consider “last resort” treatment with respiratory stimulants, such as progestin or acetazolamide.
Overview of Interstitial Lung Disease (ILD) (↓DLCO)
• Definitions: Large group of diagnoses, most of which cause progressive scarring/fibrosis of the lung, with resultant restrictive physiology
• Clinical presentation: Chronic progressive dyspnea with associated dry cough. “Velcro-like crackles,” wheezing, clubbing. May also present with symptoms or signs of an underlying pathology (e.g., clinical features of connective tissue disease). PFTs reveal restrictive physiology with low DLCO.
• Etiologies/classification: See Figure 2.13
FIGURE 2.13: Classification of interstitial lung diseases. Abbreviations defined in the chapter text.
• Imaging/pathology pattern correlates:
- Usual interstitial pneumonia (UIP) on high-resolution chest CT (honeycombing with or without traction bronchiectasis, reticular abnormalities, distributed in a subpleural, basilar predominant pattern) = UIP on path → often idiopathic pulmonary fibrosis (IPF) if other exposures are excluded
- Nonspecific interstitial pneumonia (NSIP) on high-resolution chest CT (symmetric bilateral ground glass opacities, fine reticulations, traction bronchiectasis, immediate subpleural sparing) = NSIP on path → Ddx: autoimmune, drug, XRT
• Clinical history:
- Hypersensitivity pneumonitis (HP) exposures (e.g., birds, down comforter/pillows, molds, sauna/indoor hot tub), occupational exposures (e.g., hard metals, coal, silica), smoking history
- Medications (nitrofurantoin, amiodarone), radiation
- Extra-pulmonary symptoms of connective tissue diseases (e.g., Raynaud’s, rash, arthritis)
- Family history of ILD, early graying of hair
• Diagnosis:
- PFTs: Restrictive pattern, low DLCO
- High-resolution chest CT (HRCT)
- Autoimmune serologies: Start with ANA, Jo1, SSA/SSB, RF, CCP +/− ANCA
• If positive, consider: MCTD (U1RNP) SLE (SM, dsDNA), scleroderma (Topo-1, RNA polymerase III)
• If negative, consider myositis panel if concern for myositis
• Treatment:
- Supplemental O2, pulmonary rehab, transplant referral if indicated
- IPF: Nintedanib vs. pirfenidone
- Most others: Immunosuppression
Additional Details About Specific ILD Diagnoses
• Idiopathic interstitial pneumonias (IIPs):
- Definition: A broad classification within ILDs of unknown cause. These are noninfectious interstitial lung diseases. Most common among them is idiopathic pulmonary fibrosis (IPF).
• Idiopathic pulmonary fibrosis (IPF)
- Etiology: Unknown. May be due to mucin gene mutation or related to telomere length. Older adults (typical age >60 yr), former smoker, absence of an underlying cause.
- Diagnostics: HRCT: UIP pattern (usual interstitial pneumonitis). Fibrosis worst at the bases (basilar predominant) and peripherally distributed. Honeycombing with traction bronchiectasis. Lack of air trapping (which would suggest HP). Pathology: UIP pattern (can forego obtaining pathology in certain classic populations, typically elderly white men).
• Ddx: Rule out 1) hypersensitivity pneumonitis (ask about exposures) and 2) connective tissue disease (ask about rheumatology ROS)
- Treatment: Two options: nintedanib or pirfenidone (both slow progression and may reduce risk of ILD flare but do not improve function or halt progression). Immunosuppression is harmful (PANTHER trial, New Engl J Med 2012). Avoid intubation if possible.
• Nintedanib (BID, side effect: nausea, GI side effects. Contraindication: CAD or anticoagulation)
• Pirfenidone (TID, side effect: photosensitivity)
• Nonspecific interstitial pneumonia (NSIP): Can be idiopathic, overlap with other IIP, or be associated with HIV, connective tissue diseases, drugs, and hypersensitivity pneumonitis. Idiopathic NSIP predominantly affects never-smoker, middle-aged women. Imaging: HRCT findings are basilar predominant and include reticular markings, subpleural sparing, and ground glass opacities. Classic finding: Basilar GGO with subpleural sparing. Tx: Mild disease may be self-limited; otherwise, initial treatment is steroids or other immunosuppressive adjuncts.
• Cryptogenic organizing pneumonia (COP, formerly BOOP): Rare form of ILD in which the bronchioles and alveoli become inflammed. Most common in patients 40–50 yr. Clinically mimics pnumonia. Chest imaging often with recurrent, “migratory,” peripheral-predominant opacities. Tx: Steroids. High risk of recurrence.
• Acute interstitial pneumonia (AIP, Hamman-Rich syndrome): Acute onset, rapidly progressive course (unlike other IIPs). Median age ~50 yr. Presents with fever, cough, progressive dyspnea over 7–14 days. Imaging findings mimic ARDS (bilateral opacification, often symmetric on CT chest). Tx: Supportive care, steroids. Prognosis: 50% mortality.
• Desquamative interstitial pneumonia (DIP): Most common in patients with heavy smoking history (>90%). Median age 30–40 yr. Imaging: CXR may be normal (20%). HRCT reveals GGO/centrilobular nodules; no peripheral reticulation (i.e., which helps distinguish from UIP pattern). Tx: Smoking cessation, ?steroids.
• Respiratory bronchiolitis-associated ILD (RB-ILD): On a clinical spectrum with DIP. Median age 30–40 yr, typically smokers, M:F = 2:1. Imaging: Similar to DIP. Tx: Smoking cessation, ?steroids.
• Lymphoid interstitial pneumonia (LIP): Usually associated with rheumatic disease, immunodeficiency, or infection (such as EBV), less commonly idiopathic (<20%). Imaging: Similar to NSIP; HRCT findings are basilar predominant and include GGO, centrilobular nodules, and interstitial thickening. Cysts are common (>60%), and not seen in NSIP. Tx: Depends on underlying cause. Complications: May progress to lymphoma (5%).
• Pleuroparenchymal fibroelastosis (PPFE): Rare. Idiopathic or associated with chemotherapy. Imaging: HRCT reveals upper lobe predominant pleural and subpleural lung parenchymal fibrosis.
• Exposure-related:
- Environmental/occupational:
• Hypersensitivity pneumonitis (HP, also called “extrinsic allergic alveolitis”): Results from exposure to a causative agent, such as bird feathers or mold. Presentation is variable, ranging from acute (i.e., 4–6 hours after exposure and self-limited with exposure removal) to chronic (insidious onset of cough with constitutional symptoms and fibrosis). For chronic HP, HRCT demonstrates small centrilobular nodules, ground-glass attenuation, and lobular areas of decreased attenuation and vascularity; rarely HRCT shows UIP but with air trapping, which is suggestive of HP. Tx: Detailed history and removal of all potential exposures. Partial lung function may return.
• Pneumoconiosis: Requires an exposure, such as silica, asbestos, coal, talc, beryllium, or hard metal. Imaging findings differ based on causative agent.
- Drug/radiation-induced: Nitrofurantoin, amiodarone, chemo, XRT, immunotherapy (e.g., PD-1 inhibitors or other immunotherapy)
- Smoking-related: See DIP, RB-ILD under IIP
• Connective tissue disease (CTD-ILD): Systemic sclerosis, RA, myositis, Sjogren’s, MCTD
• Granulomatous:
• Sarcoidosis:
- Epidemiology: Young to middle-age adults; more common in black individuals
- Etiology: The exact etiology and pathogenesis of sarcoidosis remain unknown
- Clinical features: Three classic features: 1) Bilateral hilar adenopathy; 2) Pulmonary reticular opacities; and 3) Skin, joint, and/or eye lesions. Other features include elevated ESR/CRP, hypercalciuria, and serum ACE level elevations, which are suggestive but of variable clinical utility in making the diagnosis
- Diagnostics: No single definitive test; diagnosis relies on compatible clinical/radiographic features, exclusion of other differential diagnoses (e.g., mycobacterial infection, fungal infection, other ILD), and noncaseating granulomas on pathology
- Treatment: Steroids as first-line
• Other:
- Acute eosinophilic pneumonia (AEP): Rare, cause unknown. Age varies, most commonly 20–40 yr. M:F = 2:1. Nonproductive cough, dyspnea, and fever are present in nearly all patients. Usually symptoms for less than 1 week, occasionally as long as 1 month. Leukocytosis initially neutrophilic, but may become eosinophilic. ESR/CRP, IgE elevated. Imaging: CXR: Subtle reticular or GGO, later diffuse GGO. HRCT not necessary, but helpful to select an area for BAL (BAL cell count shows eos >25%). Tx: Steroids.
- Chronic eosinophilic pneumonia (CEP): Rare, cause unknown. Age varies, most commonly 30–50 yr. M:F = 1:2. Association with asthma/atopy. Chronic onset of dyspnea, weight loss, fever, and productive cough. Imaging: Bilateral peripheral or pleural-based consolidations (“photographic negative” of pulmonary edema). BAL cell count shows eosinophils >25%. Tx: Steroids.
- Pulmonary alveolar proteinosis (PAP): Diffuse lung disease characterized by the accumulation of amorphous, PAS-positive material (mostly surfactant and apoproteins) in the distal airspaces. Can be primary (due to impaired surfactant clearance, excess surfactant production) or secondary (due to high-level dust exposure, hematologic dyscrasia, post-hematopoietic stem cell transplant). Age 40–50 yr, M:F=2:1, affects smokers disproportionately. Patients present with dyspnea on exertion, cough, fatigue, weight loss, fever over weeks to months, and rarely expectoration of “chunky” gelatinous material. Imaging: CXR reveals alveolar opacities in “bat wing” pattern, HRCT reveals GGO in homogenous distribution with or without “crazy paving” pattern on CT.
- Lymphangioleiomyomatosis (LAM): Rare, multisystem disease due to mTOR pathway activation that mostly affects young women. May be primary or associated with tuberous sclerosis complex (TSC-LAM). Classic feature is diffuse cystic lung disease due to infiltration of smooth muscle cells into the pulmonary parenchyma. Common symptoms include progressive dyspnea, spontaneous pneumothorax, pleural effusion, and fatigue, associated with chylothorax, chyloperitoneum, and benign masses of the kidneys, retroperitoneum/pelvis, and uterus. Imaging: CXR nonspecific, HRCT reveals hallmark thin-walled cysts. Tx: Sirolimus, everolimus (mTOR kinase inhibitors).
- Amyloidosis: May cause ILD, although more common pulmonary manifestations are tracheobronchial infiltration, persistent pleural effusions, parenchymal nodules (amyloidomas).