Interstitial lung disease
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D.
Synonyms and keywords: Diffuse parenchymal lung disease; DPLD; ILD
Overview
Classification
Interstitial lung disease may be classified on the basis of lung response to tissue injury and include:[1]
- Lung response: Granulomatous
- Lung response: Alveolitis, interstitial inflammation, and fibrosis
| Interstitial lung disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lung Response: Granulomatous | Lung Response: Alveolitis, Interstitial Inflammation, and Fibrosis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Known | Idiopathic (Unknown) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypersensitivity pneumonitis (organic dusts) | Inorganic dusts | Sarcoidosis | Lymphomatoid granulomatosis | Granulomatous vasculitides | Bronchocentric granulomatosis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beryllium | Silica | Eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) | Granulomatosis with polyangiitis (Wegener) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Known cause | Idiopathic (Unknown) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Drug-induced pulmonary toxicity | Occupational and environmental exposure | Radiation-induced lung injury | Aspiration pneumonia | Smoking-related | Residual of acute respiratory distress syndrome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inhaled inorganic dust | Inhaled organic dusts | Inhaled agents other than inorganic or organic dusts | Desquamative interstitial pneumonia | Respiratory bronchiolitis–associated interstitial lung disease | Pulmonary Langerhans cell granulomatosis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary alveolar proteinosis | Idiopathic interstitial pneumonias | Lymphocytic infiltrative disorders (lymphocytic interstitial pneumonitis associated with connective tissue disease) | Connective tissue diseases | Gastrointestinal or liver diseases | Inherited diseases | Graft-versus-host disease | Pulmonary hemorrhage syndromes | Eosinophilic pneumonias | Lymphangioleiomyomatosis | Amyloidosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Major idiopathic interstitial pneumonias | Rare idiopathic interstitial pneumonias | Unclassifiable idiopathic interstitial pneumonias | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| • Idiopathic pulmonary fibrosis • Idiopathic nonspecific interstitial pneumonia • Respiratory bronchiolitis-interstitial lung disease • Desquamative interstitial pneumonia • Cryptogenic organising pneumonia • Acute interstitial pneumonia | • Idiopathic lymphoid interstitial pneumonia • Idiopathic pleuroparenchymal fibroelastosis | • Systemic lupus erythematosus • Rheumatoid arthritis • Ankylosing spondylitis • Systemic sclerosis • Sjögren syndrome • Polymyositis • Dermatomyositis | • Crohn disease • Primary biliary cirrhosis • Chronic active hepatitis • Ulcerative colitis | • Tuberous sclerosis • Neurofibromatosis • Niemann-Pick disease • Gaucher disease • Hermansky-Pudlak syndrome | • Bone marrow transplantation • Solid organ transplantation | • Goodpasture syndrome • Idiopathic pulmonary hemosiderosis • Isolated pulmonary capillaritis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pathophysiology
Algorithm showing pathophysiology of Interstitial Lung Disease[2]
| Tissue injury in lungs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Parenchymal injury | Vascular injury | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mast cells in lungs in response to tissue injury | LPA6, LPA2, and LPA4 receptors | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Decreased sFRP-1 (secreted frizzled-related protein 1) in fibroblasts | Secretes tryptase | Transforming growth factor-β (TGF-β) | Insulin-like growth factor (IGF) signalling[3] | Reduced expression of angiogenic factors, vascular endothelial growth factor (VEGF) | Elevation of angiostatic factors, pigment epithelium-derived factor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wnt/β-catenin signalling pathway | PAR-2/protein kinase (PK)C-α/Raf-1/p44/42 signaling pathway | Upregulation of Egr-1 (early growth response protein 1)[4] | IGF-binding protein 5 (IGFBP-5)[5] | IGF-binding protein 3 (IGFBP-3) | Loss of endothelial barrier function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dysregulation of repair in lung tissue and activation of fibroblasts | Regulates transforming growth factor-β (TGF-β) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Induction of syndecan-2 (SDC2)[6] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Activation,proliferation, and migration of fibroblast to the site of injury | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fibroblasts | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Altered PTEN (phosphatase and tensin homologue)/Akt axis | Acquire contractile stress fibres | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inactivates Fox (forkhead box) O3a[7] | Protomyofibroblast, composed of cytoplasmic actins | Pleural mesothelial cells (PMCs) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Downregulation of caveolin-1 (cav-1) and Fas expression[8] | De novo expression of α-smooth muscle actin (α-SMA) | TGF-β1-dependent mesothelial–mesenchymal transition | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fibroblast resistant to apoptosis[9] | Myofibroblasts[10] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Different ranges of contractions mediated by RhoA/Rho-associated kinase | Changes in intracellular calcium concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Recruitement of fibrocytes in lungs | Lock step mechanism of cyclic and contractile events[11] | T-helper cell type 2 on site of injury | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Upregulation of C-X-C chemokine receptor type 4 (CXCR4) on fibrocytes and its ligand CXCL12 (stromal cell-derived factor 1) | Excess extracellular matrix production | Exerting traction force | Interleukin-13 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Migration of fibrocytes to the site of injury | Tissue remodelling[12] | Alternate pathway activation of macrophages | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lung Fibrosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References
- ↑ Kasper, Dennis (2015). "315: Interstitial Lung Diseases". In Talmadge, E. King, Jr. Harrison's principles of internal medicine. New York: McGraw Hill Education. ISBN 0071802150.
- ↑ Bagnato G, Harari S (2015). "Cellular interactions in the pathogenesis of interstitial lung diseases". Eur Respir Rev. 24 (135): 102–14. doi:10.1183/09059180.00003214. PMID 25726561.
- ↑ Hsu E, Shi H, Jordan RM, Lyons-Weiler J, Pilewski JM, Feghali-Bostwick CA (2011). "Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension". Arthritis Rheum. 63 (3): 783–94. doi:10.1002/art.30159. PMC 3139818. PMID 21360508.
- ↑ Yasuoka H, Hsu E, Ruiz XD, Steinman RA, Choi AM, Feghali-Bostwick CA (2009). "The fibrotic phenotype induced by IGFBP-5 is regulated by MAPK activation and egr-1-dependent and -independent mechanisms". Am J Pathol. 175 (2): 605–15. doi:10.2353/ajpath.2009.080991. PMC 2716960. PMID 19628764.
- ↑ Bhattacharyya S, Wu M, Fang F, Tourtellotte W, Feghali-Bostwick C, Varga J (2011). "Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy". Matrix Biol. 30 (4): 235–42. doi:10.1016/j.matbio.2011.03.005. PMC 3135176. PMID 21511034.
- ↑ Ruiz XD, Mlakar LR, Yamaguchi Y, Su Y, Larregina AT, Pilewski JM; et al. (2012). "Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis". PLoS One. 7 (8): e43049. doi:10.1371/journal.pone.0043049. PMC 3416749. PMID 22900087.
- ↑ Nho RS, Peterson M, Hergert P, Henke CA (2013). "FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas". PLoS One. 8 (4): e61017. doi:10.1371/journal.pone.0061017. PMC 3620276. PMID 23580232.
- ↑ Del Galdo F, Sotgia F, de Almeida CJ, Jasmin JF, Musick M, Lisanti MP; et al. (2008). "Decreased expression of caveolin 1 in patients with systemic sclerosis: crucial role in the pathogenesis of tissue fibrosis". Arthritis Rheum. 58 (9): 2854–65. doi:10.1002/art.23791. PMC 2770094. PMID 18759267.
- ↑ Thannickal VJ, Horowitz JC (2006). "Evolving concepts of apoptosis in idiopathic pulmonary fibrosis". Proc Am Thorac Soc. 3 (4): 350–6. doi:10.1513/pats.200601-001TK. PMC 2231523. PMID 16738200.
- ↑ Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA (2002). "Myofibroblasts and mechano-regulation of connective tissue remodelling". Nat Rev Mol Cell Biol. 3 (5): 349–63. doi:10.1038/nrm809. PMID 11988769.
- ↑ Castella LF, Buscemi L, Godbout C, Meister JJ, Hinz B (2010). "A new lock-step mechanism of matrix remodelling based on subcellular contractile events". J Cell Sci. 123 (Pt 10): 1751–60. doi:10.1242/jcs.066795. PMID 20427321.
- ↑ Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007). "The myofibroblast: one function, multiple origins". Am J Pathol. 170 (6): 1807–16. doi:10.2353/ajpath.2007.070112. PMC 1899462. PMID 17525249.