Augustine Lee, MD Mayo Clinic Florida Lee.augustine@mayo.edu
Diffuse parenchymal lung disease (DPLD/ILD) Known causes/associations E.g. Asbestosis, Rheumatoid arthritis, Hypersensitivity pneumonitis Granulomatous E.g. Sarcoidosis, (hypersensitivity pneumonitis) Other well defined E.g. Lymphangioleiyomyomatosis (LAM), Pulmonary langerhans cell histiocytosis (PLCH), Eosinophilic pneumonia Idiopathic interstitial pneumonias (IIP)
Radiologic features High-Resolution CT chest Can be highly suggestive of diagnosis in: Classic UIP/IPF Sarcoidosis Asbestosis Hypersensitivity pneumonitis (subacute/chronic) Silicosis Pulmonary langerhans cell histiocytosis (PLCH) Lymphangioleiomyomatosis (LAM) Pulmonary alveolar proteinosis (PAP) Lymphangitic carcinomatosis UIP Not-UIP Differential by Distribution Mid-Upper lungs Histiocytosis X Sarcoidosis Hypersensitivity pneumonitis Eosinophilic pneumonia Tuberculosis Cystic fibrosis Pneumoconiosis (silica / coal) Ankylosing spondylitis Smokers emphysema (cystic) Lower lungs IPF, Asbestosis, UIP Aspiration Collagen-vascular disease associated ILD BOOP/COP (variable) Desquamative interstitial pneumonia Non-specific interstitial pneumonia Panlobular emphysema (cystic) Bronchoscopy Leslie, Chest 2005 Surgical lung biopsy: VAT IPF Prevalence 14-43 /100,000 (USA) Older age (75+ yo: 227/100,000) Male predominant, Smoking history Median survival still ~3-5 years Significant comorbidities PAH, cancer, depression, cardiovascular disease, thromboembolism Supportive care important Education, oxygen, rehabilitation, comorbidities, immunizations, end-of-life discussions IPF: Diagnosis Biopsy Video assisted thoracoscopic (VAT) biopsy Histology: Usual interstitial pneumonia (UIP) HRCT: UIP Honeycombing (Advanced scar Reticulation/linear opacities (Scar) Subpleural, basilar predominant distribution +/- Traction bronchiectasis Minimal ground glass No consolidations/nodules Familial forms ~5% MUC5B, Surfactant protein A2/C, Telomerase
ATS/ERJ Statement 2002, 2011 Usual interstital pneumonia (UIP) Poor prognostic markers Older age FVC decline ~10% DLCO decline ~15% HRCT pattern more UIP-ish Biopsy UIP (regardless of other NSIP) Fibrosis score on CT Fibroblast foci on biopsy Pulmonary hypertension
Natural history of IPF. Statistics vs. Your patient Symptoms Diagnosis D i s e a s e
D E A T H Time At the individual level Martinez AIM 2005) Acute exacerbation of IPF ~23% of IPF, may be first presentation of IPF Presents with acute-subacute worsening dyspnea, hypoxia, radiographic infiltrates No other apparent causes: ?Aspiration Resembles ARDS clinically & Biopsy: DAD (UIP) HRCT UIP in background, but superimposed ground glass Mortality >50% If require Mechanical ventilation ~90% death Therapy: steroids (in desperation) IPF Therapies No drug proven to improve survival Exception: lung transplant Things that do not work: Interferon-gamma, Imatinib, Etanercept, Bosentan, Sildenafil Things that may harm: Warfarin (ACE-IPF, Noth, AJRCCM 2012) Azathioprine, Prednisone, NAC (PANTHER, NEJM2012) Ambrisentan (Raghu, AIM 2013) PANTHER study, NEJM 2012 IPF Therapies Things that may work: Pirfenidone with possible FVC benefit (CAPACITY, Lancet 2011) Thalidomide may help with cough in IPF (Horton, AIM 2012) Notably pending: N-acetylcysteine (PANTHER), Pirfenidone (ASCEND) Many others in the pipeline, including biologics THE OTHER IIP NSIP Younger than IPF, Some series more women HRCT: More ground glass Two histologic flavors: Cellular (better prognosis) Fibrotic (worse) Three main associations CTD: Scleroderma, dermatomyositis, RA Hypersensitivity like Drug-reactions (also familial, pediatric) NSIP Treatment Identify and treat associated conditions Removing offending exposures Steroids & immunosuppressives Prognosis 5 year survival up to 70%, but differs per histology
Travis WD. AJSP 2000; 24(1):19-33. Travis WD. AJSP 2000; 24(1):19-33. Cellular NSIP Fibrotic NSIP UIP Cryptogenic Organizing Pneumonia (a.k.a. BOOP) Associations Drug-induced, Infectious, CTD, Radiation, DAD/ARDS, Hypersensitivity, Aspiration (foreign body reaction), toxic fumes, IBD Peripheral consolidation or ground-glass Can have any manifestation: Alveolar (ground-glass or consolidation), nodule (singly or multiple), mass, interstitial, diffuse, focal Typically, restrictive physiology Surgical lung biopsy usually required Presentation: chronic to acute/fulminant May clinically present identical to pneumonia Often dramatic response to corticosteroids Smoking related ILDs RB-ILD DIP (Respiratory Bronchiolitis Assoc. ILD) (Desquamative Interstital Pneumonia)
Surgical lung biopsy often required for diagnosis Findings of Respiratory Bronchiolitis on biopsy is not specific Compatible clinical picture Radiographic : Diffuse ground glass >>> reticular/reticulonodular Small cystic changes Prognosis Better prognosis than IPF/UIP CT abnormalities can persist even after smoking cessation Treatment Stop smoking, ? Steroids, Transplant Other IIP LIP Associated with CTD (Sjogrens), HIV, Primary biliary cirrhosis, Castleman disease, SLE, Autoimmune thyroiditis, ? low grade lymphomas Ground glass, centrilobular, cystic lesions AIP Original Hamman-Rich Syndrome Acute, fulminant presentation DAD with variable degrees of organizing pneumonia on biopsy (seen with ARDS) Diagnosis of exclusion, Poor prognosis MISCELLANEOUS ENTITIES Pulmonary Langherans Cell Histiocytosis a.k.a. Eosinophilic granuloma, Histiocytosis X
Young male smokers (20-50yo), Pneumothoraces Upper lobe, nodular, irregular cystic Fibrosis Obstructive, Restrictive, or Mixed physiology Biopsy: aggregates of Langerhans cells, stellate nodule formation, positive S100 & CD1a staining PAH, particularly ?PVOD Treatment: Smoking cessation, ?Steroids, Lung transplant Lymphangioleiomyomatosis (LAM) Young women, child bearing age Rare in men, and in post-menopausal Also seen in tuberous sclerosis (15-30%) Atypical proliferation of smooth muscle cells (HMB45) Cystic lung disease, diffusely affected Pneumothorax (50%) Chylous effusion & ascites Angiomyolipoma: kidney, uterus, ovaries, lymph Elevated VEGF-D levels (correlates with FEV1) Sirolimus (Bissler, NEJM 2008, McCormack NEJM 2011) Hormonal manipulation, lung transplant Well defined cysts, evenly distributed, extending to bases Diffuse cystic lung diseases Pulmonary Langherhans Cell Histiocytosis (PLCH) Lymphangioleiomyomatosis (LAM) Tuberous Sclerosis Complex (TSC) Lymphocytic interstitial pneumonia (LIP) Desquamative interstitial pneumonia (DIP) Birt-Hogg Dube syndrome Skin: fibrofolliculomas, Folliculin (FLCN) gene Amyloidosis, light-chain deposition disease Cystic metastatic disease (usu. Sarcoma) Follicular bronchiolitis
CT may suggest aspiration distribution of ground glass or consolidation, Mosaicism, Fat density Vcuthoracicimaging.com Pulmonary alveolar proteinosis Pulmonary alveolar proteinosis, very rare Dysregulation in turnover of surfactant protein Alveolar accumulation of phospholipoproteins Deficiency or dysfunction of GM-CSF or its receptor Abnormalities in the surfactant protein Most idiopathic cases are now thought to be autoimmune Diagnosis HR-CT findings BAL: PAS+, Mississippi mud Biopsy Autoimmune = antibodies to GM-CSF Treatment Whole lung lavage GM-CSF (SQ or inhaled) Confirmed anti-GM-CSF autoantibodies, and no circulating GM-CSF Awaiting response Crazy-paving Summary Familiarize with the idiopathic interstitial pneumonias, the most important of which is IPF/UIP No known drug therapy. Pirfenidone may become available. Know what drugs not to try, & discontinue if they are on them currently. Always look for associated conditions or exposures to remove Has direct management & prognostic implications Extrapulmonary symptoms & findings may be strong clues HRCT chest is an invaluable tool in the differential of diffuse parenchymal lung diseases Combined with other tests, clinical features, may be diagnostic Some very rare diseases are easy to diagnose with unique radiographic & clinical features Treatment options are available (e.g. PAP, LAM) Bonus Slides Eosinophilic Lung Diseases - 2 Allergic bronchopulmonary aspergillosis (ABPA) Asthma, IgE, Blood eos., Serum precipitins, +/- Central bronchiectasis with mucoid impaction Loffler Syndrome (simple pulm. eosinophilia) Self limited, fleeting, symptomatic infiltrates, parasites (Ascaris, Dirofilaria) & drugs Churg-Strauss Syndrome (EGPA) Asthma, Tissue infiltration (sinus, skin, lung, GI, kidney, heart, CNS), vasculitis (mononeuritis multiplex, skin), rarely diffuse alveolar hemorrhage, MPO-ANCA/P-ANCA Hypereosinophilic syndrome Multiorgan manifestation, r/o hematologic disorder, consider CSS/EGPA Sarcoidosis 10-35/100,000 (USA) African-Americans, Scandinavians Asymptomatic ~50% Pulmonary /Lymphatics (>90%) Upper predominant, bronchovascular/ perilymphatic nodularity/ consolidation, Adenopathy, Fibrosis/scar (UIP), Conglomerate mass, Endobronchial, Pleural, Cutaneous EN, Lupus pernio, Darrier-Roussy, Maculopapular, Koebner phenomenon, Plaque, Ocular (20%): Uveitis (7% of uveitis is due to sarcoid), Iritis, Keratoconjunctivitis, Sicca
Mid-upper lungs
Peri-lymphatic Micronodules along pleura, fissure, bronchovasculature