DYS P N E A Etiologies Asthma, COPD, bronchiectasis, cystic fibrosis, tumor, foreign body Pulmonary edema: cardiogenic or noncardiogenic ILD; pneumonia Large vessel: PE, tumor emboli Small vessel: PHT, vasculitis, ILD, emphysema, PNA Pleural disease: large effusion, fibrosis Chest wall/diaphragm: kyphoscoliosis, ↑ abd girth Neuromuscular disorders Hyperinflation (COPD, asthma) Chemoreceptors: hypoxemia, metabolic acidosis Mechanoreceptors: ILD, pulmonary edema, PHT, PE ↓ O2 carrying cap. (but nl PaO2) Anemia, methemoglobinemia, CO poisoning Psychological Anxiety, panic attack, depression, somatization
Dysp/PFTs 2-1
Pathophysiology Airway obstruction (↑ resistance to airflow) Parenchymal disease (↑ resistance to expansion) Vascular (V/Q mismatch) Bellows (↑ resistance to CW/diaphragm expansion; weakness of respiratory muscles) Stimulation of receptors
Evaluation • History: quality of sensation, tempo, positional dependence, exac./allev. factors, exertion • Cardiopulmonary exam, SaO2, CXR (see Appendix & Radiology inserts), ECG predictors of CHF: h/o CHF, PND, S3, CXR w/ venous congestion, AF ( JAMA 2005;294:1944) dyspnea w/ nl CXR → CAD, asthma, PE, PHT, early ILD, anemia, acidosis, NM disease • Based on results of initial evaluation: PFT, chest CT, TTE, cardiopulmonary testing • BNP & NT-proBNP ↑ in CHF (also ↑ in AF, RV strain from PE, COPD flare, PHT, ARDS) BNP 400 to r/i (NEJM 2002;347:161) NT-proBNP 450 pg/mL (900 (50–75 y), >1800 (>75 y) (EHJ 2006;27:330) ↑ in chronic heart failure, \ need to compare to known “dry BNP”
PULMONARY FUNCTION TESTS (PFTs) • Spirometry: evaluate for obstructive disease Flow-volume loops: diagnose and/or localize obstruction Bronchodilator: indicated if obstruction at baseline or asthma clinically suspected Methacholine challenge: helps dx asthma if spirometry nl, >20% ↓ FEV1 → asthma • Lung volumes: evaluate for hyperinflation or restrictive disease including NM causes • DLCO: evaluates functional surface area for gas exchange; helps differentiate causes of obstructive and restrictive diseases and screens for vascular disease & early ILD Figure 2-1 Approach to abnormal PFTs Approach to abnormal PFTs FEV1 / FVC 30
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Moderate, end-expir 95% Normal 60 120 >25 8 mm; if ≤8 mm, serial CT) (Chest 2013;143:840) • Low risk ( posterior uveitis; ↑ lacrimal gland Endo & renal (10%) Nephrolithiasis, hypercalcemia (10%), hypercalciuria (40%) Due to vitamin D hydroxylation by Mφ Neuro (10% clin, 25% path) CN VII palsy, periph neuropathies, CNS lesions, seizures Cardiac (5% clin, 25% path) Conduction block, VT, CMP Liver, spleen, BM Granulomatous hepatitis (25%), splenic & BM gran. (50%) Constitutional Fever, night sweats, anorexia & wt loss (a/w hepatic path) Musculoskeletal Arthralgias, periarticular swelling, bone cysts Organ system Pulmonary
• Löfgren’s syndrome: erythema nodosum + hilar adenopathy + arthritis (good prognosis) • Diagnostic studies: LN bx → noncaseating granulomas + multinucleated giant cells 18 FDG PET can be used to identify extent and potentially targets for dx bx ↑ ACE (Se 60%, 90% w/ active dis., Sp 80%, false in granulomatous diseases) • To assess extent: CXR, PFTs, full ophtho exam, ECG, CBC (lymphopenia, ↑ eos), Ca, 24-h urine for Ca, LFTs; ± Holter, echo, cardiac MRI, brain MRI, etc., based on s/s • Rx: steroids (eg, prednisone 20–40 mg/d) if sx or extrathoracic organ dysfxn (improves sx, but doesn’t D long-term course); hydroxychloroquine for extensive skin disease; anti-TNF, MTX, AZA, mycophenolate or cyclophosphamide for chronic/refractory disease • Prognosis: ~2/3 spontaneously remit w/in 10 y (60–80% of stage I, 50–60% stage II, 30% stage III), w/ relapses uncommon; ~1/3 have progressive disease Iatrogenic • Amiodarone (~10%; dose & duration depend.): chronic interstitial pneumonia ↔ ARDS; bx → vacuolized Mf w/ lamellar inclusions on EM; Rx: d/c amio, give steroids • Other drugs: nitrofurantoin, sulfonamides, thiazides, INH, hydralazine, gold • Chemo: bleomycin (triggered by hyperoxia), busulfan, cyclophosphamide, MTX, etc. • XRT: COP/BOOP w/ sharply linear, nonanatomic boundaries; DAH
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Idiopathic interstitial pneumonias (IIPs) (AJRCCM 2005;172:268) • Definition: ILD of unknown cause; dx by radiographic, histologic and clinical features Type UIP/IPF
ILD 2-10
NSIP
COP/BOOP AIP DIP RB-ILD
IIPs Imaging/Histology Reticular opacities, honeycombing, traction bronchiectasis; periph, subpl., & basal Homogenous ground glass opacities or consolid., reticular irreg lines; symmetric, periph, basal, subpl. Mimics CTD ILD. Cellular and fibrotic subtypes, latter similar to UIP but homogenous. Patchy bilat consolid., nodules; subpl. & peribronchial. Prolif of granulation tissue in small bronchioles & inflam of surrounding alveoli. Diffuse ground glass opacities, consolid. w/ lobular sparing. Path similar to DAD. Diffuse ground glass opacities, reticular lines; lower zones, periph. Mφ in alveoli. Bronchial thickening, centrilobular nodules, patchy ground glass opacities. Mφ in alveoli.
Clinical Sx >12 mo 5-y mort. ~80% Sx mos–y 5-y mort. 10% (fibrotic = UIP) Can be post-infxn, HSCT, XRT, rxn to drugs. 5-y mort 50% lymphs 80% of the time, ADA >40, pleural bx ~70% Se fungal, viral (usually small), parasitic (eg, amebiasis, echinococcosis, paragonimiasis) • Malignancy (15%): primary lung cancer most common, metastases (esp. breast, lymphoma, etc.), mesothelioma (✓ serum osteopontin levels; NEJM 2005;353:15) • Pulmonary embolism (10%): effusions in ~40% of PEs; exudate (75%) > transudate (25%); hemorrhagic—must have high suspicion b/c presentation highly variable • Collagen vascular disease: RA (large), SLE (small), Wegener’s, Churg-Strauss • Gastrointestinal diseases: pancreatitis, esophageal rupture, abdominal abscess • Hemothorax (Hcteff/Hctblood >50%): trauma, PE, malignancy, coagulopathy, leaking aortic aneurysm, aortic dissection, pulmonary vascular malformation • Chylothorax (triglycerides >110): thoracic duct damage due to trauma, malignancy, LAM • Other: post-CABG: left-sided; initially bloody, clears after several wks Dressler’s syndrome (pericarditis & pleuritis post-MI), uremia, postradiation therapy Asbestos exposure: benign; eosinophils Drug-induced (eg, nitrofurantoin, methysergide, bromocriptine, amiodarone): eos Uremia; post-XRT; sarcoidosis Meigs’ syndrome = benign ovarian tumor → ascites & pleural effusion Yellow-nail syndrome: yellow nails, lymphedema, pleural effusion, bronchiectasis Diagnostic studies • Thoracentesis (NEJM 2006;355:e16) Indications: all effusions >1 cm in decubitus view if suspect due to CHF, can diurese and see if effusions resolve (75% do so in 48 h) asymmetry, fever, chest pain or failure to resolve → thoracentesis parapneumonics should be tapped ASAP (cannot exclude infxn clinically) Diagnostic studies: ✓ total protein, LDH, glucose, cell count w/ differential, Gram stain & culture, pH; remaining fluid for additional studies as dictated by clinical scenario Complications: PTX (5–10%), hemothorax (~1%), re-expansion pulm edema (if >1.5 L removed), spleen/liver lac.; post-tap CXR not routinely needed (Annals 1996;124:816) ↓ PTX w/ U/S and experienced supervisor (Chest 2009;135:1315; Archives 2010;170:332) • Transudate vs. exudate (Annals 1972;77:507) Light’s criteria: exudate = TPeff/TPserum >0.5 or LDHeff/LDHserum >0.6 or LDHeff >2/3 ULN of LDHserum; 98% Se, 83% Sp; best Se of all methods (Chest 1995;107:1604); however, will misidentify 25% of transudates as exudates; \ if clinically suspect transudate but meets criterion for exudate, confirm w/ test w/ higher Sp exudative criteria w/ better Sp: serum-effusion alb gradient ≤1.2, Se 87%, Sp 92%; serum-effusion TP gradient ≤3.1, Se 84%, Sp 91%; choleff >45 mg/dL and LDHeff >200, 90% Se, 98% Sp (no serum required) CHF effusions: TP may ↑ with diuresis or chronicity → “pseudoexudate”; alb gradient ≤1.2, choleff >60 mg/dL (Se 54%, Sp 92%) or clin judgment to distinguish (Chest 2002;122:1524) • Complicated vs. uncomplicated parapneumonic (Chest 1995;108:299) complicated = Gram stain or culture or pH 10%) → blood, air, drug rxn, asbestos, paragonimiasis, Churg-Strauss, PE RBC: Hcteff 1–20% → cancer, PE, trauma; Hcteff/Hctblood >50% → hemothorax AFB: yield in TB 0–10% w/ stain, 11–50% w/ culture, ~70% w/ pleural bx adenosine deaminase (ADA): seen w/ granulomas, >70 suggests TB, 60; seen in chronic effusions (eg, CHF, RA, old TB) creatinine: effusion/serum ratio >1 → urinothorax fibulin-3: ↑ plasma and/or effusion levels → mesothelioma (NEJM 2012;367:1417) • Chest CT; pleural biopsy; VATS • Undiagnosed persistent pleural effusions (Clin Chest Med 2006;27:309) Transudative: most commonly CHF or hepatic hydrothorax. ✓ s/s CHF or cirrhosis, NT-proBNPeff; consider intraperitoneal injection of technetium-99m sulfur colloid Exudative (ensure using Sp test listed above): most commonly malig, empyema, TB, PE. ✓ s/s malig, chest CT (I+), ADA or IFN-g release assay; consider thoracoscopy. Characteristics of Pleural Fluid (not diagnostic criteria) Appear WBC diff RBC pH Glc Comments CHF clear, straw
