Index. I ICD-9 coding, 15 Idiopathic interstitial pneumonia (IIP), 6, 103 biopsy in patients with, 37
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1 A Aberrant fibroblast behavior, 150 Acute exacerbation of IPF (AE-IPF), 26, , 302, 303 antibiotic resistance, 349 CAPACITY trials, 440, 441 clinical presentation, 403 corticosteroids, 349 cyclophosphamide, 350 cyclosporine A, 350 decline in lung function, 402 definition, 348 diagnostic criteria, 408 double-blind, placebo-controlled RCTs, 352 emergent transplantation, 410 etiology, 403 evaluation and diagnosis, 406 gastroesophageal reflux, 404 gene expression, 404 high-resolution CT scans, 406 histopathologic evaluation, 407 incidence, 402 infection, 404 INPULSIS trials, 440 Japanese Shionogi Phase 2 and 3 trials, 440 medical therapy, non-ipf ILD, 403 occurrence, 403 oral anticoagulant, 351 pathobiology, 404 polymyxin-b immobilized fiber column hemoperfusion, 351 precipitating factor, 404 prevention, 409 procalcitonin-guided strategy, 349 prognosis, 411 risk factors, 403 rituximab with plasma exchange, 351 supportive care, 352 supportive therapy, 410 tacrolimus, 350 thrombomodulin, 351 Acute respiratory distress syndrome (ARDS), 409 Alveolar epithelial cell injury, 139 Alveolar epithelial (AEC2) cell type II, 101 Alveolar epithelial cells (AECs), Alveolar inflammation, 97 Alveolar re-epithelialization, 142 American Thoracic Society, 66 Angiogenesis, 154 Anti-acid therapy, , 384 Antibodies to anti-lysyl oxidase, 344 to interleukins, 345 Anticoagulant therapy, with warfarin, 330 Antiprotease imbalance, 211 Anxiety, 288 Apoptosis, in lung fibrosis, Asbestosis, 373 Aspergillomas, 74 Asymptomatic/subclinical disease, 29, 30 A Tool to Assess Quality of Life in IPF (ATAQ-IPF), 442 Autoantibodies, 124 Autoimmunity and IPF, Azathioprine, 328 Springer Nature Switzerland AG 2019 K. C. Meyer, S. D. Nathan (eds.), Idiopathic Pulmonary Fibrosis, Respiratory Medicine, 469
2 470 B Bilateral lung transplantation, 428, 429 Biomarkers, 461 definition, 242 diagnostic chemoattractants, circulating cells, club cell secretory protein 16 (CC16), 261 heat shock protein 70 (HSP70), 262 matrix metalloproteinases (MMPs), mucins, 259 neo-epitopes, periostin, 261 surfactant proteins, discovery of, ideal, 243 limitations, 265 novel, 244 pro-angiogenesis factors, 264 from sputum/urine, 264 Borg scale, 390 Bronchiolitis obliterans syndrome (BOS), 430 Bronchoalveolar lavage (BAL), 308, 382 Bronchoscopic lung cryobiopsy (BLC), 8 Bronchoscopy, 308 C Carbon monoxide (DL CO ), 85 Cardiovascular disease, IPF, 287 Caveolin-1 (cav-1), 151 CD4+/CD28+ T-cells, 262 Chemoattractants, Chemokines, 106, 153 four families of human, Chronic hypersensitivity pneumonitis, 313, 371 Chronic lung allograft dysfunction (CLAD), 430 Chronic obstructive pulmonary disease (COPD), pulmonary rehabilitation, 390 Circulating endothelial cells (CEC), 262 CleanUp-IPF study, 462 Clinical phenotypes, 30 Clinical trials, acute exacerbations of IPF (AE-IPF), forced vital capacity (FVC), future of, hospitalizations, minute walk test (6MWT), mortality-related measures, potential endpoints biomarkers, composite outcome measures, cough, 443 HRCT, 443 patient-reported outcome (PRO), and primary endpoints, RCTs, 448 Club cell secretory protein 16 (CC16), 261 Coagulation, 148 Cobblestone appearance, 43 Colchicine, 328 Combined pulmonary fibrosis and emphysema (CPFE), 31, 65, 85, 279, , Common variants, 185, 186 Comorbidity, 289 cardiovascular disease, 287 CPFE, 281 deconditioning, 290 depression and anxiety, diabetes mellitus, 287 gastroesophageal reflux disease, 285 lung cancer, 289 PH and IPF, 284 sleep disordered breathing, 291 venous thromboembolism, 286 Composite outcome measures, 446 Composite physiologic index (CPI), 243, 304, 446, 461 Concurrent diagnosis, IPF, 26 Connective tissue disease, associated interstitial lung disease, Connective tissue disease-related ILD (CTD-ILD), 313 Connective tissue growth factor (CTGF), COPD Assessment Test (CAT), 443 Coronary artery disease (CAD), IPF, 392 Corticosteroid, 327 acute exacerbation of IPF (AE-IPF), 349 Cough, 443 Cryobiopsy, 55 Cryptogenic fibrozing alveolitis, 97 CXC chemokines, in pulmonary fibrosis, Cyclophosphamide, 327, 350 Cyclosporine A, 350
3 471 D Danger-associated molecular patterns (DAMPs), 101 Dasatinib, 346 Deconditioning, 290 Defensins, 222 Demethylarginine demethylaaminohydrolase (DDAH), 384 Depression, 288 Desquamative interstitial pneumonia (DIP), 48 clinical features, 45, 46 natural history, 45 pathological diagnoses, 47 pathologic features, 46, 47 Diabetes mellitus (DM), Diffuse alveolar damage (DAD), usual interstitial pneumonia, 407 Diffuse parenchymal lung diseases (DPLDs), 300, 311 Distance-saturation product (DSP), 242 Dyskeratosis congenita (DC), 195 E Educational program, 394 Emphysema, 85 See also Combined pulmonary fibrosis and emphysema (CPFE) Endoplasmic reticulum (ER) stress, 144 Endothelin receptor antagonist (ERA) drugs, 332 Epidemiology mortality rates, 15 risk factors cigarette smoking, 18, 19 farming and livestock exposure, 20 genetic risk factors, 18 hairdressing, exposure, 20 limitations, 17, 18 metal dust exposure, 19 occupational exposures, 19 raising birds, exposure, 20 sand exposure, 20 silica dusts exposure, 20 stone exposure, 20 wood dust exposure, 20 Epigenetic mechanisms, Epigenetic regulation, 159 Epithelial cell phenotype, Epithelial-mesenchymal transition (EMT), 143 Epstein Barr virus, 302 Erdheim Chester disease (ECD), 373 European Respiratory Society, 66 Exercise intolerance, 87 Exogenous factors, 141 Extracellular matrix (ECM) to anti-lysyl oxidase, 344 autotaxin, 343 connective tissue growth factor, 341 galectin-3, 344 integrins, 342 JNK pathway, 344 LPA-receptor antagonists, 343 and myofibroblast, 457 phosphoinositide 3-kinases, Rho-associated protein kinases, 343 Extrinsic allergic alveolitis, see Hypersensitivity pneumonitis F Familial idiopathic pulmonary fibrosis, 280 Familial interstitial pneumonia (FIP), characteristics, 184 Familial pulmonary fibrosis (FPF) characteristics, 183 clinical evaluation, 198 clinical manifestations, 184 family history, 198 genetic heterogeneity, 194 genetic testing, 199 prevalence, 184 FG-3019, open-label phase II trial, 462 Fibroblast focus formation, 139 Fibroblastic foci, 136 Fibrocytes, 119, 262 Forced vital capacity (FVC), 22, 23, 85 G Gastroesophageal reflux disease (GERD), 61, 301 acute exacerbation of IPF, 382 IPF, mechanism, microaspiration, 380, 382, 384 prevalence, 381, 382, 384 progression, 381 treatment, 383 Gender-age-physiology (GAP) index, 90, 243 Gender-age-physiology (GAP) models, 461 Gene expression profiling classification, COPD vs. IPF, 220 familial pulmonary fibrosis vs. NSIP, 220 IPF vs. HP, 219 with disease severity,
4 472 Genetic IPF research, 459 Genetic mutation, 280 Genetic susceptibility, 140 Genetic testing, 185 for FPF, Genetic variants, 186 classification, 185 Genome scale transcript profiling analysis of, 211 concept of, 208 emergence of, 213 experiments, 209 hypothesis-driven experimental approaches, 211 MMP family, 212 Genome wide association studies (GWAS), 186, 459 Genomic dataset, 209 H Hamman Rich syndrome, 1 3 Healthcare resource utilization (HRU), 89 Health-related quality of life (HRQoL), 288 Heat shock protein 70 (HSP70), 262 Hermansky Pudlak syndrome (HPS), 372 High-resolution computed tomography (HRCT), 3, 306 accuracy of, 66 fibrotic lung diseases, guidelines, 66 helical CT acquisition, 63 IPF, 26 mild mediastinal and hilar lymph node enlargement, 64 pulmonary findings, 63, 64 step-and-shoot method, 63 technical aspects, 62, 63 Histopathology, IPF, 135 Homeostatic signaling, 146 Honeycombing, 63 Hoyeraal Hreidarsson syndrome, 195 Human leukocyte antigen (HLA) region, 154 Hyaluronan synthase 2 (HAS2) enzyme, 101 Hypersensitivity pneumonitis (HP), 76, 300, Hypoxemia, 305 I ICD-9 coding, 15 Idiopathic interstitial pneumonia (IIP), 6, 103 biopsy in patients with, 37 characteristics, 184 classification, 6 cyclophosphamide, 327 histopathologic classification, histopathology, 366 morphologic classification, 37 NSIP, 49 surgical lung biopsy, pattern vs. diagnosis, 53, 54 UIP vs. NSIP, 54 Idiopathic non-specific interstitial pneumonia (NSIP), 307, 311, 313 Idiopathic pulmonary fibrosis (IPF) clinical course, 302, 303 clinical trials, 462 clinician s diagnostic confidence, 308, 315 coronary artery disease, 392 diagnosis, 302, 461 dyspnea, 389 elderly patient, histopathology, 310 home daily spirometry, 92, 93 incidence, age strata and gender, 13 inflammation, 458 interdisciplinary algorithm, 315 median survival, 379 mildly progressive course, 25 mimics, , 366, 367 pathogenesis, 460 physiologic evaluation, 305 prevalence, 384 age strata and gender, 13 pulmonary fibrosis and emphysema, 31 radiographic evaluation, 306 symptoms, 300 treatment, 379 IgG4-related disease, 373 Imatinib, 332 Immune activation, Immune cells and inflammatory mediators, 153 Immune system, role for IPF, 99 Immunity, adaptive, Inflammation, and acute exacerbations of IPF, Interferon-γ (IFN-γ), Interleukin 13, 116 Interstitial lung disease (ILD) classification, 3 comprehensive classification scheme, 4 5 connective tissue disease, 313, 369 epigenetic mechanisms, 5 medication/drug exposures, 7
5 473 non-ipf diagnosis, 7 occupational or environmental exposures, 7 radiologists assessment, 313, 315 surgical lung biopsy, terminology, 2 unclassifiable disease, 374 Interstitial pneumonia with autoimmune feature (IPAF), 43, 314 IPF clinical syndrome (IPF-CS), 15 IPF therapy nintedanib, 117 J Japanese Respiratory Society, 66 Matrix remodeling, 155 Microbiome role, MicroRNAs, 228 Mildly progressive course, 25 Monocyte-derived lung macrophages, 458 Morphologic phenotyping, 278 Mortality odds ratio (MOR), 19 MUC5B, 187 Mucins, Multi-parameter lung function models, 461 Myeloid-derived suppressor cells (MDSC), 263 Myofibroblast, 148 activation, 137 research, K King's Brief Interstitial Lung Disease (K- BILD) questionnaire, 442 L Latin American Thoracic Association, 66 Leicester Cough Monitor (LCM), 443 Leukocytes role, in fibrotic repair process, 458 Leukotrienes, 345 Longer-term pulmonary rehabilitation, 392 Lung Allocation Score (LAS) system, 426 Lung cancer, IPF, 289 Lung transplantation, 196, 433 candidate evaluation, chronic lung allograft dysfunction, 430 contraindications, 422, 423 deceased donor lung allocation, in United States, ISHLT recommendations for, 421, 423 metabolic and cardiovascular complications, 430 patient selection, 421, 423 risk, 430 survival time, 419 timing of listing, 425 timing of referral, 421 types of, United States, 420, 429 Lysophosphatidic acid (LPA), 152 Lysyl oxidase-like 2 (LOXL2), 157, 344 M Macrophages, 110, 112 Matrix metalloproteinase (MMP) family, 211 N N-acetylcysteine (NAC) antioxidant properties, 329 clinical outcomes, 329 combination with prednisone and azathioprine, 328 genotype-stratified prospective clinical trial, 329 post hoc analysis, 329 Neutrophils, Nintedanib, , 389, 441, 456 and pirfenidone, 338 Non-coding RNAs, Non-specific interstitial pneumonia (NSIP), 50, 51, 99, clinical features, 49 diagnosis, 49 natural history, 48 pathologic features, 49, 50 provisional diagnosis, 48 vs. UIP, 54, 55 O Osteopontin, 264 Oxygen therapy, 19 P Paracrine mediators, Paraseptal emphysema, 308 Pathogen-associated molecular patterns (PAMPs), 101 Patient-reported outcome (PRO), 441 Pentraxins, 346 Periostin, 261
6 474 Peripheral blood mononuclear cell (PBMC) gene expression profiles, 105 Phenotyping, , 301, 305, 311 acute exacerbation of IPF, 276 CPFE, 279 demographic and physiologic variables, 275 disease progression, 275 epigenetic, 281 morphologic, PH-ILD, 279 rapidity of progression, 276 slow progressor, 276 Phosphodiesterase type 5 (PDE-5) inhibitor, 331 Pirfenidone, 113, 389, 441, 456 ASCEND study, 336 CAPACITY program, 335 dose modification guidelines, 337 liver chemistry tests, 336 long-term safety and tolerability, 336 and nintedanib, 338 PASSPORT study, 336 phase II open-label trial, 335 RECAP study, 336 Pleuroparenchymal fibroelastosis (PPFE), 52, 184 clinical features, 51, 52 differential diagnosis, 52 histologic findings, 52 natural history, 51 pathologic features, 52 Pneumonia, 74 Polymyxin-B immobilized fiber column hemoperfusion, 351 Preclinical models, for IPF research, Prednisone, 328 Pro-angiogenesis factors, 264 Progression-free survival (PFS), 105, 446 Proportionate mortality ratio (PMR), 19 Prostaglandin E2 (PGE2), 146 Proteomics, 159 Proton pump inhibitors (PPIs), 339 Pulmonary disease, connective tissue disease, 313 Pulmonary fibrosis drug toxicity, 373 lung cancer, pulmonary hypertension, 304 scleroderma, 301 Pulmonary function tests, 65, 279 arterial blood gas analysis, 87 clinical practice DLco, FVC, 88 clinical trials DLco, FVC, 88, ergo-receptor activation, 87 gas exchange impairment, 86 inspiratory muscle function, 87 mild-to-moderate exercise, 87 respiratory rate, 87 Pulmonary hypertension (PH), 30, 65, 75, , 304, 394 Pulmonary Langerhans cell histiocytosis (PLCH), 373 Pulmonary rehabilitation cardiac stress testing, chronic obstructive pulmonary disease, 390 considerations, duration of, 392 dyspnea, 390, 391 effects on emotional well-being, 391 endurance training, 393 exercise-induced oxyhemoglobin desaturation, 393 IPF, 289 6MWD, 392 patient evaluation, randomized, controlled trials, 390 United States, 393 Pulmonary vascular resistance (PVR), 88 R Rapidly progressive clinical course, 25 Rare variants, pathogenic, 197 in pulmonary fibrosis, 189 in surfactant metabolism genes, in telomere maintenance genes, in telomere-related genes, 196 Receptor for advanced glycation end products (RAGE), 143 Regulator of telomere length 1 (RTEL1), 194 Respiratory bronchiolitis interstitial lung disease (RBILD), 310 clinical features, 45, 46 natural history, 45 pathologic features, 46, 47 pathological diagnoses, 47, 48 Restrictive allograft disorder (RAD), 430 Rituximab, 346 with plasma exchange, 351 RNA expression profiling, 159 RNA sequencing (RNA-seq), 208
7 475 S St George's Respiratory Questionnaire (SGRQ), 442 Sarcoidosis, 300, 372 Sarcopenia, see Deconditioning Senescence-associated secretory phenotype (SASP), 144 Sildenafil, combination therapy with nintedanib, 341 with pirfenidone, 341 Single-cell RNA sequencing analysis, of epithelial cells, 456 Single lung transplantation, 429 Single nucleotide polymorphism (SNP), 186, 280 Sleep-disordered breathing, 291 Smoking-related interstitial fibrosis (SRIF), 47, 307, 310, 311, 374 Spontaneous pneumomediastinum, 75 Squamous cell carcinomas, 289 Supplemental oxygen, Supportive care, 352 Suppressor T cells, 263 Surfactant, metabolism genes, Surfactant protein C (SP-C), 140 Surfactant proteins (SP), 258 Surgical lung biopsy (SLB), 309 Survivors, long-term, 25 T Tacrolimus, 350 Telomerase, 189, 194, 195 Telomerase reverse transcriptase (TERT), 189, 197 Telomere(s), 140 length, 188, 189, 196 maintenance genes, Temporal heterogeneity, 135 Thoracic complications, 72 74, 76 Thrombin, 148 Thrombomodulin, 351 Toll-interacting protein (TOLLIP), 153, 188 and MUC5B genes, polymorphisms of, 329 Toll-like receptor 9 (TLR9), 276 Total lung capacity (TLC), 85 Transbronchial biopsies, Transbronchial lung biopsy (TBLB), 308 Transbronchial lung cryobiospy, 308 Transcript profiling, 210 T-regulatory cells, 263 Triple therapy (Azathioprine + N-Acetylcysteine + prednisone), 328 Type V collagen-induced immunotolerance, 346 Tyrosine kinase inhibitor (TKI), 332, 337 U Underlying cause of death (UCD), University Of California San Diego Shortness Of Breath Questionnaire (UCSD SOBQ), Usual interstitial pneumonia (UIP), 61, architectural distortion characteristic, 42 clinical features, 39 diagnostic criteria, 455 diagnostic feature, 42 diffuse alveolar damage, 407 elastotic fibrosis, 53 fibroblast, 41 histologic diagnosis, 70 histologic hallmark, 41 honeycomb, 42, 62 HRCT accuracy, 66 imaging features, 71 imaging findings, 62 IPF histopathology, 135 lymphoid hyperplasia, 44 natural history, 39 patchwork fibrosis and honeycomb, 45 pathologic features, pattern in lung biopsies, 221 prognosis, 72 radiographic pattern, 62 respiratory bronchiolitis, 46 subpleural scarring, 43 V Vascular remodelling, in pulmonary fibrosis, 109 Venous thromboembolism, Video-assisted thoracoscopic surgery (VATS), 8, 309 Vismodegib treatment, 341 W Warfarin, WNT/β-catenin signaling pathway, 146 Wnt pathway, WRAP-IPF trial, 462
Index A ABCA3. See Adenosine triphosphate (ATP)-binding cassette transporter A3 (ABCA3) Acute exacerbations (AEx/AEs) ARDS/AIP, 315 biopsies, 42 clini
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