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32 Cards in this Set
- Front
- Back
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Hypersensitivity pneumonitis: prevalence and incidence
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Vary from country to country and within certain regions of a country
Vary due to the local climate, season, geographic conditions, local customs, and the presence of industrial manufacturing plants Farmer's lung -Most common in cold, wet climates -Varies with local farming practices -One of the most common forms of HP Bird fancier’s lung -Prevalence higher among bird fanciers than among farmers because contact with the inciting avian antigens is less limited by season or geographic location Only small fraction exposed to potential antigens that cause HP actually develop clinical disease -Only after the weeks to months of exposure required to induce sensitization |
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Hypersensitivity pneumonitis: immunologic factors
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Combination of:
-Immune complex–mediated (type III) and -T cell–mediated, delayed (type IV) hypersensitivity reactions Precipitating immunoglobulin (Ig) G antibodies against offending agent in serum (most cases) Also host genetic component to susceptibility |
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Hypersensitivity pneumonitis: clinical features
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Symptoms may develop hours, weeks or months after exposure
History of allergic disease uncommon -Not predisposing factor for development of HP Persons with mild or subclinical HP -Often misdiagnosed as suffering viral illnesses or asthma -Either of which may have nonspecific clinical findings which mimic HP |
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Hypersensitivity pneumonitis: acute, subacute, and chronic pathologic features
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Acute HP
-Not well known -Neutrophilic infiltrate in alveoli and respiratory bronchioles (acute bronchiolitis) -Sometimes pattern of DAD -Temporally uniform, nonspecific, chronic interstitial pneumonia commonly seen Subacute HP -Lymphocytic interstitial pneumonitis, granulomas, organizing pneumonia-like pattern, and fibrosis Chronic HP -Most biopsies performed at this stage -Distinctive histologic appearance |
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Hypersensitivity pneumonitis: diagnostic triad of chronic phase
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(Most common) Temporally uniform chronic interstitial inflammation with peribronchiolar accentuation
-Bronchiolocentric cellular interstitial pneumonia (Two thirds) Nonnecrotizing poorly formed granulomas in peribronchiolar interstitium (Two thirds) Foci of OP pattern Intraluminal budding fibrosis or organizing pneumonia |
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Hypersensitivity pneumonitis: progression and pathology
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Progression
-May result in nonspecific fibrosis resembling UIP -Must examination of less fibrotic areas where characteristic lesions of cellular bronchiolitis, granulomas, or intraluminal fibrosis are more likely to be found Occasional lymphoid aggregates -Not prominent Foamy macrophages -Common -Within peribronchiolar airspaces -Prominent in approximately 5% Crystalline inclusions or cholesterol clefts -Seen within giant cells Pleural fibrosis Cryptostroma corticale -Maple bark stripper's disease |
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Hypersensitivity pneumonitis: differential diagnosis
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Must be separated histologically from other conditions:
-Infection, sarcoidosis, UIP, and NSIP -Special stains --Rule out acid-fast bacilli, fungi, and Pneumocystis carinii. NSIP -Presence of granulomas and exposure history Collagen vascular disease and drug reactions -Clinical information required to exclude |
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Compare and contrast sarcoidosis and hypersensitivity pneumonitis: granulomas, boop, lymphocytic infiltrates, dense fibrosis
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Sarcoidosis
-Granulomas in 100% of cases --well formed --lympangitic, peribronchiolar, perivascular -BOOP is usually absent -Lympocytic inflitrates are usually absent or minimal -Dense fibrosis in advanced cases Hypersensitivity pneumonitis -Granulomas in 2/3s of cases --poorly formed --random alveolar interstitial distribution, sometimes peribronchiolar -BOOP in 2/3 of cases -Mild to moderate lymphocytic infitrates, peribronchiolar -Dense fibrosis in advanced cases |
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Hypersensitivity pneumonitis: treatment and prognosis
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Removal of causative agent and corticosteroids
Majority near total recovery of lung function -May take several years after the inciting exposure ceases Bird fanciers have a worse prognosis than farmers with HP -May be due to higher exposure to the HP antigens and persistence of avian antigens in home environment Irreversible once dense fibrosis develops with honeycomb changes |
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Usual interstitial pneumonia: other names, onset, epidemiology
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Other names:
-Chronic interstitial pneumonitis -Cryptogenic fibrosing alveolitis Pathologic pattern corresponding to the clinical diagnosis of Idiopathic Pulmonary Fibrosis (IPF) Insidious onset of dyspnea with chronic, progressive downhill course Males >> Females Age between 50 and 70 years of age -Approximately two thirds over age 60 at time of presentation |
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Usual interstitial pneumonia: etiology
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Unknown etiology
No distinct geographic No predilection by race or ethnicity Potential genetic role -Supported by the findings of familial cases Cigarette smoking 1.6- to 2.3-fold excess risk Long-term exposure to metal dust or wood dust independent risk factor No cultural, serologic, or morphologic evidence viral etiologies |
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Usual interstitial pneumonia: pathogenesis
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Intrinsic abnormality of tissue repair
-Evidence: Familial pulmonary fibrosis have mutations that shorten telomeres TGF-β1 -Negatively regulates telomerase activity -Facilitates epithelial cell apoptosis, cycle of death and repair -Influences multiple pathways that regulate pulmonary fibrosis Caveolin-1 -Regulated by TGF-β1 -Predominant structural protein of caveolae, flask-shaped invaginations of the plasma membrane present in many terminally differentiated cells -Endogenous inhibitor of pulmonary fibrosis -Limiting TGF-β1–induced production of extracellular matrix -Restoring alveolar epithelial repair processes -Decreased in epithelial cells and fibroblasts of IPF patients --Such down-regulation may be mediated by the ability of TGF-β1 to attenuate the expression of caveolin-1 in fibroblasts -Overexpression in mouse models limits fibrosis |
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Usual interstitial pneumonia: clinical features
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Rarely normal
Most tachypneic, with rapid shallow breaths, probably because of increased work of breathing Crackles bibasilar, late inspiratory, fine crackles ("velcro" rales) Clubbing, pulmonary hypertension and cyanosis are late manifestations, indicative of advanced disease |
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Usual interstitial pneumonia: pathology in early, later, and end stages
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Early: firm lungs, pulmonary edema, hyaline membranes, mononuclear infiltration, type II pneumocyte hyperplasia
Later: fibrous tissue, fibrogenic foci (areas of active disease), thickened alveolar septa (solid and normal lung), hyperplastic smooth muscle, microcysts, loss of alveolar capillaries End stage: spaces lined by cuboidal/columnar epithelium separated by fibrosis and forming honeycomb lung (particularly in the superior portion of lobes); also lymphoid hyperplasia, thickening of intima and media of pulmonary arteries |
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Usual interstitial pneumonia: diagnosis
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Transbronchial biopsy inadequate!
-Malignancy, infections, sarcoidosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia, eosinophilic pneumonia, or Langerhans' cell histiocytosis Correlate to radiology! -50% have UIP pattern on HRCT Correlate to clinical and exclude other entities! |
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Usual interstitial pneumonia: histologic features
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Established fibrosis
Patchy parenchymal involvement with subpleural/paraseptal predominance Fibroblastic foci Mild interstitial chronic inflammation Honeycomb change Pertinent negative features include- Lack of inorganic dusts Lack of granulomas Lack of Langerhan’s cells Absence of other interstitial lung diseases |
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Usual interstitial pneumonia: treatment and prognosis
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Steroids
20% improve -Lung transplant Median survival from diagnosis 3 years Worse prognostic factors -Eosinophilia -Increased fibroblastic foci |
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Nonspecific interstitial pneumonia: incidence/prevalence, onset, epidemiology
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Incidence/prevalence undefined
-Less frequent than UIP -Much more common than other idiopathic interstitial pneumonias Average duration of illness prior to diagnosis -8 to 18 months Average age ranges from 46 to 57 -Has been found in children Slightly more common in women Idiopathic NSIP, cellular pattern -Younger (mean 39, range 26–50) than idiopathic UIP Idiopathic NSIP, fibrosing pattern -(mean 50, range 30 to 71) Correlated with smoking history |
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NSIP: etiology
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Cause Unknown
Can be associated with collagen vascular/connective tissue disease -Strong association with NSIP -Especially SLE, polymyositis, dermatomyositis, scleroderma, Sjogren’s syndrome, and rheumatoid arthritis. Drug reaction -Especially nitrofurantoin, amiodarone |
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NSIP: Symptoms, PE, lab
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Most common symptoms
-Exertional dyspnea -Cough -Fever Physical Exam -Crackles on chest auscultation -Clubbing Routine laboratory studies -Nonspecific -Antinuclear antigen (ANA) and/or rheumatoid factor positive (minority) |
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NSIP: Radiologic features
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Variable and nonspecific
(Most common) Areas of consolidation or hazy increased opacity (ground-glass opacities) -May be diffuse -Tend to involve mainly the lower lobes Mimics DIP and hypersensitivity pneumonitis; occasionally BOOP or UIP |
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NSIP: Pathologic features
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Temporally uniform interstitial inflammatory and fibrosing process
-Retains architecture of lung Containing varying proportions of inflammation and fibrosis Usually diffuse involvement of the lung -Sometimes process patchy |
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NSIP: Cellular form histology
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Mild to moderate chronic inflammation
Diffuse involvement of affected parenchyma Preservation of alveolar architecture Pertinent negative features- Dense interstitial fibrosis Lack of inorganic dusts Lack of granulomas Lack or few eosinophils Lack of organisms |
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NSIP: Fibrotic form histology
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Mild to moderate interstitial chronic inflammation
Diffuse involvement of affected parenchyma Mild/moderate loss of alveolar architecture Variable degree of interstitial fibrosis Pertinent negative features- Lack of inorganic dusts Lack of granulomas/Langeran’s cells Lack of few eosinophils Lack of organisms Lack of few fibroblastic foci Lack or few honeycomb changes |
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NSIP: Treatment and prognosis
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Spontaneous remissions do not occur
-Expected disease progression and shortened survival times (if untreated) Very corticosteroid-responsive -Unlike UIP (for which NSIP most often confused symptomatically), better responsiveness to treatment and prognosis -Improvement or recovery up to 75% (with or without immunosuppressive agents) -Especially if started early phases |
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NSIP Differential diagnosis
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Interobserver variability in diagnosis
Considerable overlap with HP -HP shows presence of granulomas and an exposure history -Some have both HP and NSIP Diagnosis of exclusion -Histologic pattern lacks features of DAD/AIP, idiopathic BOOP/COP, UIP, or DIP |
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Desquamative insterstitial pneumonia: clinical presentation, epidemiology
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Approximately 90% of patients are cigarette smokers
Clinical presentation similar to UIP -Subacute (weeks to months) -Insidious onset of dyspnea and cough More commonly male; male to female ratio of 2 to 1 Middle aged adults most often affected -Fourth to fifth decade of life Rare cases in children -Probably different disorder than adult DIP -Surfactant deficiency or alveolar proteinosis which show prominent alveolar macrophage accumulation |
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Desquamative interstitial pneumonia: PE, lab, LFT, BAL
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Physical examination
-Shows crackles on auscultation of chest not as prominent as other idiopathic interstitial pneumonias -Clubbing Laboratory investigations -Usually unremarkable Lung function tests -Restrictive pattern with reduced DLCO -Hypoxemia on arterial blood gas analysis BAL -Marked increase in total cells recovered -Predominance of macrophages |
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Desquamative interstitial pneumonia: histology
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Uniform involvement of lung parenchyma
Marked accumulation of macrophages Brown pigment laden macrophages Pertinent negative features- No honeycomb change Lack of fibroblastic foci No eosinophilic microabscesses Lack of inorganic dusts Lack of granulomas |
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Dewquamative interstitial pneumonia: treatment and prognosis
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Cessation of smoking
-Often leading to spontaneous regression -Recurrence if patient starts smoking or is exposed to passive smoke Corticosteroid therapy -Moderate to severe symptoms and gas exchange abnormalities -Better response than UIP Lung transplantation in endstage disease from DIP -Disease recurrence in transplanted lung has been reported Prognosis -Much better than other idiopathic interstitial pneumonias, especially UIP -Progression (small subset) -Fulminant DIP leading to death rare |
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Respiratory bronchiolitis: epideimiology
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Incidental histopathologic finding in heavy smokers
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Respiratory bronchiolitis: Histologic features
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Bronchocentric accumulation of macrophages
Bronchiolar fibrosis and chronic inflammation Light brown cytoplasmic pigment in macrophages Pertinent negative fingings: Lack of diffuse acinar involvement No honeycomb change No other airway damaging agents |
