Download PDF
Semin Respir Crit Care Med 2008; 29(6): 603-609
DOI: 10.1055/s-0028-1101270
Published by Thieme Medical Publishers

Host–Environment Interactions in Exposure-Related Diffuse Lung Diseases

David M. Brass1 , 3 , Anastasia L. Wise1 , 2 , 4 , David A. Schwartz1 , 2 , 4
  • 1National Heart Lung and Blood Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
  • 2National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
  • 3current affiliation: Duke University Medical Center, Durham, North Carolina
  • 4current affiliation: National Jewish Health, Denver, Colorado
Further Information

Publication History

Publication Date:
16 February 2009 (online)

    Permissions and Reprints

ABSTRACT

Diffuse lung disease (DLD), also known as interstitial lung disease (ILD), comprises a group of relatively rare but devastating lung diseases that involve varying degrees of acute and chronic inflammation, and which may present with end-stage fibroproliferation. There are currently no proven therapeutic strategies to halt progression of DLDs. Thinking about DLDs has evolved over time from hypotheses invoking inflammation as the prime mover in the etiology of disease, to the current hypothesis that interactions between a damaged and frustrated epithelium, and the response of underlying mesenchymal cells that takes place, contribute to the fibroproliferative milieu. The greatest challenge to understanding the role of environmental exposures in pathogenesis of DLDs is that there is no clear consensus on the etiology and pathogenesis of these diseases. Emerging data on the relationship between loss of epithelial integrity and mesenchymal fibroproliferation support the hypothesis that the damage to the epithelium is a critical component in the development of DLDs that progress to a fibroproliferative presentation. Thus it follows that environmental stress which impacts the well-being of the epithelium may play a critical role in shifting the balance of lung homeostasis through ongoing insult as a result of exposure to environmental agents. Animal models that recapitulate the vulnerable epithelium observed in patients who develop fibrotic lung disease associated with DLDs will provide the best opportunity to understand mechanisms associated with the etiology of these diseases.

KEYWORDS

Vulnerable epithelium - interstitial lung disease - fibrosis

REFERENCES

  • 1 Pitcher W D. Hypersensitivity pneumonitis.  Am J Med Sci. 1990;  300 251-266
    PubMedSearch in Google Scholar
  • 2 Wild L G, Lopez M. Hypersensitivity pneumonitis: a comprehensive review.  J Investig Allergol Clin Immunol. 2001;  11 3-15
    PubMedSearch in Google Scholar
  • 3 Moore J E, Convery R P, Millar B C, Rao J R, Elborn J S. Hypersensitivity pneumonitis associated with mushroom worker's lung: an update on the clinical significance of the importation of exotic mushroom varieties.  Int Arch Allergy Immunol. 2005;  136 98-102
    CrossrefPubMedSearch in Google Scholar
  • 4 Galland C, Reynaud C, De Haller R, Polla B S, Leuenberger P. Cheese-washer's disease: a current stable form of extrinsic allergic alveolitis in a rural setting.  Rev Mal Respir. 1991;  8 381-386
    PubMedSearch in Google Scholar
  • 5 American Thoracic Society . Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS).  Am J Respir Crit Care Med. 2000;  161(2 Pt 1) 646-664
    Search in Google Scholar
  • 6 Nicholson A G, Florio R, Hansell D M et al.. Pulmonary involvement by Niemann–Pick disease: a report of six cases.  Histopathology. 2006;  48 596-603
    CrossrefPubMedSearch in Google Scholar
  • 7 Mendelson D S, Wasserstein M P, Desnick R J et al.. Type B Niemann-Pick disease: findings at chest radiography, thin-section CT, and pulmonary function testing.  Radiology. 2006;  238 339-345
    PubMedSearch in Google Scholar
  • 8 Knight S, Vulliamy T, Copplestone A, Gluckman E, Mason P, Dokal I. Dyskeratosis Congenita (DC) Registry: identification of new features of DC.  Br J Haematol. 1998;  103 990-996
    CrossrefPubMedSearch in Google Scholar
  • 9 Selman M, King T E, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.  Ann Intern Med. 2001;  134 136-151
    CrossrefPubMedSearch in Google Scholar
  • 10 Noble P W, Homer R J. Back to the future: historical perspective on the pathogenesis of idiopathic pulmonary fibrosis.  Am J Respir Cell Mol Biol. 2005;  33 113-120
    CrossrefPubMedSearch in Google Scholar
  • 11 Baptista A L, Parra E R, Filho J V, Kairalla R A, de Carvalho C R, Capelozzi V L. Structural features of epithelial remodeling in usual interstitial pneumonia histologic pattern.  Lung. 2006;  184 239-244
    CrossrefPubMedSearch in Google Scholar
  • 12 Chilosi M, Poletti V, Murer B et al.. Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: the role of deltaN-p63.  Lab Invest. 2002;  82 1335-1345
    CrossrefPubMedSearch in Google Scholar
  • 13 Garantziotis S, Schwartz D A. Host–environment interactions in pulmonary fibrosis.  Semin Respir Crit Care Med. 2006;  27 574-580
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Baumgartner K B, Samet J M, Coultas D B et al.. Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study. Collaborating Centers.  Am J Epidemiol. 2000;  152 307-315
    CrossrefPubMedSearch in Google Scholar
  • 15 Hubbard R, Lewis S, Richards K, Johnston I, Britton J. Occupational exposure to metal or wood dust and aetiology of cryptogenic fibrosing alveolitis.  Lancet. 1996;  347 284-289
    CrossrefPubMedSearch in Google Scholar
  • 16 Hubbard R, Cooper M, Antoniak M et al.. Risk of cryptogenic fibrosing alveolitis in metal workers.  Lancet. 2000;  355 466-467
    CrossrefPubMedSearch in Google Scholar
  • 17 Baumgartner K B, Samet J M, Stidley C A, Colby T V, Waldron J A. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 1997;  155 242-248
    CrossrefPubMedSearch in Google Scholar
  • 18 Schwartz D A, Van Fossen D S, Davis C S et al.. Determinants of progression in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 1994;  149(2 Pt 1) 444-449
    CrossrefPubMedSearch in Google Scholar
  • 19 Steele M P, Speer M C, Loyd J E et al.. Clinical and pathologic features of familial interstitial pneumonia.  Am J Respir Crit Care Med. 2005;  172 1146-1152
    CrossrefPubMedSearch in Google Scholar
  • 20 Iwai K, Mori T, Yamada N, Yamaguchi M, Hosoda Y. Idiopathic pulmonary fibrosis: epidemiologic approaches to occupational exposure.  Am J Respir Crit Care Med. 1994;  150 670-675
    CrossrefPubMedSearch in Google Scholar
  • 21 Johnston I, Britton J, Kinnear W, Logan R. Rising mortality from cryptogenic fibrosing alveolitis.  BMJ. 1990;  301 1017-1021
    PubMedSearch in Google Scholar
  • 22 Brass D M, Hoyle G W, Poovey H G, Liu J Y, Brody A R. Reduced tumor necrosis factor-alpha and transforming growth factor-beta1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure.  Am J Pathol. 1999;  154 853-862
    PubMedSearch in Google Scholar
  • 23 Spees J L, Pociask D A, Sullivan D E et al.. Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis.  Am J Respir Crit Care Med. 2007;  176 385-394
    CrossrefPubMedSearch in Google Scholar
  • 24 Coin P G, Osornio-Vargas A R, Roggli V L, Brody A R. Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos.  Am J Respir Crit Care Med. 1996;  154 1511-1519
    PubMedSearch in Google Scholar
  • 25 Rivers D, Moris T G, Wise M E. The fibrogenicity of some respirable dusts measured in mice.  Br J Ind Med. 1963;  20 13-23
    PubMedSearch in Google Scholar
  • 26 Adamson I Y, Bowden D H. Role of polymorphonuclear leukocytes in silica-induced pulmonary fibrosis.  Am J Pathol. 1984;  117 37-43
    PubMedSearch in Google Scholar
  • 27 Brass D M, Savov J D, Gavett S H, Haykal-Coates N, Schwartz D A. Subchronic endotoxin inhalation causes persistent airway disease.  Am J Physiol Lung Cell Mol Physiol. 2003;  285 L755-761
    PubMedSearch in Google Scholar
  • 28 Hammond E C, Selikoff I J, Seidman H. Asbestos exposure, cigarette smoking and death rates.  Ann N Y Acad Sci. 1979;  330 473-490
    PubMedSearch in Google Scholar
  • 29 Adamson I Y, Bowden D H. Response of mouse lung to crocidolite asbestos, I: Minimal fibrotic reaction to short fibres.  J Pathol. 1987;  152 99-107
    PubMedSearch in Google Scholar
  • 30 Brass D M, Tsai S Y, Brody A R. Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro.  Exp Lung Res. 2001;  27 639-653
    PubMedSearch in Google Scholar
  • 31 Mac M J. Familial pulmonary fibrosis.  Dis Chest. 1951;  20 426-436
    PubMedSearch in Google Scholar
  • 32 Adelman A G, Chertkow G, Hayton R C. Familial fibrocystic pulmonary dysplasia: a detailed family study.  Can Med Assoc J. 1966;  95 603-610
    PubMedSearch in Google Scholar
  • 33 Barzo P. Familial idiopathic fibrosing alveolitis.  Eur J Respir Dis. 1985;  66 350-352
    PubMedSearch in Google Scholar
  • 34 Marshall R P, Puddicombe A, Cookson W O, Laurent G J. Adult familial cryptogenic fibrosing alveolitis in the United Kingdom.  Thorax. 2000;  55 143-146
    CrossrefPubMedSearch in Google Scholar
  • 35 Peabody J W, Peabody Jr J W, Hayes E W, Hayes Jr E W. Idiopathic pulmonary fibrosis; its occurrence in identical twin sisters.  Dis Chest. 1950;  18 330-344
    PubMedSearch in Google Scholar
  • 36 Javaheri S, Lederer D H, Pella J A, Mark G J, Levine B W. Idiopathic pulmonary fibrosis in monozygotic twins: the importance of genetic predisposition.  Chest. 1980;  78 591-594
    PubMedSearch in Google Scholar
  • 37 Hodgson U, Pulkkinen V, Dixon M et al.. ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis.  Am J Hum Genet. 2006;  79 149-154
    CrossrefPubMedSearch in Google Scholar
  • 38 Selman M, Pardo A, Barrera L et al.. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis.  Am J Respir Crit Care Med. 2006;  173 188-198
    CrossrefPubMedSearch in Google Scholar
  • 39 Kelly M M, Leigh R, Gilpin S E et al.. Cell-specific gene expression in patients with usual interstitial pneumonia.  Am J Respir Crit Care Med. 2006;  174 557-565
    CrossrefPubMedSearch in Google Scholar
  • 40 Pignatti P, Brunetti G, Moretto D et al.. Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis.  Am J Respir Crit Care Med. 2006;  173 310-317
    CrossrefPubMedSearch in Google Scholar
  • 41 Jiang D, Liang J, Hodge J et al.. Regulation of pulmonary fibrosis by chemokine receptor CXCR3 .  J Clin Invest. 2004;  114 291-299
    PubMedSearch in Google Scholar
  • 42 Tager A M, Kradin R L, LaCamera P et al.. Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10.  Am J Respir Cell Mol Biol. 2004;  31 395-404
    CrossrefPubMedSearch in Google Scholar
  • 43 Burdick M D, Murray L A, Keane M P et al.. CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular remodeling.  Am J Respir Crit Care Med. 2005;  171 261-268
    PubMedSearch in Google Scholar
  • 44 Belperio J A, Dy M, Murray L et al.. The role of the Th2 CC chemokine ligand CCL17 in pulmonary fibrosis.  J Immunol. 2004;  173 4692-4698
    PubMedSearch in Google Scholar
  • 45 Yang I V, Burch L H, Steele M P et al.. Gene expression profiling of familial and sporadic interstitial pneumonia.  Am J Respir Crit Care Med. 2007;  175 45-54
    CrossrefPubMedSearch in Google Scholar
  • 46 Nogee L M, Dunbar III A E, Wert S E, Askin F, Hamvas A, Whitsett J A. A mutation in the surfactant protein C gene associated with familial interstitial lung disease.  N Engl J Med. 2001;  344 573-579
    CrossrefPubMedSearch in Google Scholar
  • 47 Nogee L M, Dunbar III A E, Wert S, Askin F, Hamvas A, Whitsett J A. Mutations in the surfactant protein C gene associated with interstitial lung disease.  Chest. 2002;  121(3, Suppl) 20S-21S
    CrossrefPubMedSearch in Google Scholar
  • 48 Cameron H S, Somaschini M, Carrera P et al.. A common mutation in the surfactant protein C gene associated with lung disease.  J Pediatr. 2005;  146 370-375
    CrossrefPubMedSearch in Google Scholar
  • 49 Thomas A Q, Lane K, Phillips III J et al.. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred.  Am J Respir Crit Care Med. 2002;  165 1322-1328
    CrossrefPubMedSearch in Google Scholar
  • 50 Tredano M, Griese M, Brasch F et al.. Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease.  Am J Med Genet A. 2004;  126A 18-26
    CrossrefPubMedSearch in Google Scholar
  • 51 Stevens P A, Pettenazzo A, Brasch F et al.. Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene.  Pediatr Res. 2005;  57 89-98
    PubMedSearch in Google Scholar
  • 52 Wang W J, Mulugeta S, Russo S J, Beers M F. Deletion of exon 4 from human surfactant protein C results in aggresome formation and generation of a dominant negative.  J Cell Sci. 2003;  116(Pt 4) 683-692
    CrossrefPubMedSearch in Google Scholar
  • 53 Mulugeta S, Nguyen V, Russo S J, Muniswamy M, Beers M F. A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation.  Am J Respir Cell Mol Biol. 2005;  32 521-530
    CrossrefPubMedSearch in Google Scholar
  • 54 Mulugeta S, Maguire J A, Newitt J L, Russo S J, Kotorashvili A, Beers M F. Misfolded BRICHOS SP-C mutant proteins induce apoptosis via caspase-4- and cytochrome c-related mechanisms.  Am J Physiol Lung Cell Mol Physiol. 2007;  293 L720-729
    CrossrefPubMedSearch in Google Scholar
  • 55 Lawson W E, Grant S W, Ambrosini V et al.. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF.  Thorax. 2004;  59 977-980
    CrossrefPubMedSearch in Google Scholar
  • 56 Armanios M Y, Chen J J, Cogan J D et al.. Telomerase mutations in families with idiopathic pulmonary fibrosis.  N Engl J Med. 2007;  356 1317-1326
    CrossrefPubMedSearch in Google Scholar
  • 57 Tsakiri K D, Cronkhite J T, Kuan P J et al.. Adult-onset pulmonary fibrosis caused by mutations in telomerase.  Proc Natl Acad Sci U S A. 2007;  104 7552-7557
    CrossrefPubMedSearch in Google Scholar
  • 58 Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti A G. Telomere shortening in smokers with and without COPD.  Eur Respir J. 2006;  27 525-528
    CrossrefPubMedSearch in Google Scholar
  • 59 Bowzard J B, Cheng D, Peng J, Kahn R A. ELMOD2 is an Arl2 GTPase-activating protein that also acts on Arfs.  J Biol Chem. 2007;  282 17568-17580
    CrossrefPubMedSearch in Google Scholar
  • 60 Pierson D M, Ionescu D, Qing G et al.. Pulmonary fibrosis in Hermansky–Pudlak syndrome. a case report and review.  Respiration. 2006;  73 382-395
    CrossrefPubMedSearch in Google Scholar
  • 61 Nakatani Y, Nakamura N, Sano J et al.. Interstitial pneumonia in Hermansky–Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes.  Virchows Arch. 2000;  437 304-313
    CrossrefPubMedSearch in Google Scholar
  • 62 Tang X, Yamanaka S, Miyagi Y, Nagashima Y, Nakatani Y. Lung pathology of pale ear mouse (model of Hermansky–Pudlak syndrome 1) and beige mouse (model of Chediak–Higashi syndrome): severity of giant lamellar body degeneration of type II pneumocytes correlates with interstitial inflammation.  Pathol Int. 2005;  55 137-143
    CrossrefPubMedSearch in Google Scholar
  • 63 Lyerla T A, Rusiniak M E, Borchers M et al.. Aberrant lung structure, composition, and function in a murine model of Hermansky–Pudlak syndrome.  Am J Physiol Lung Cell Mol Physiol. 2003;  285 L643-653
    PubMedSearch in Google Scholar
  • 64 Liu J Y, Morris G F, Lei W H, Hart C E, Lasky J A, Brody A R. Rapid activation of PDGF-A and -B expression at sites of lung injury in asbestos-exposed rats.  Am J Respir Cell Mol Biol. 1997;  17 129-140
    PubMedSearch in Google Scholar
  • 65 Young L R, Pasula R, Gulleman P M, Deutsch G H, McCormack F X. Susceptibility of Hermansky–Pudlak mice to bleomycin-induced type II cell apoptosis and fibrosis.  Am J Respir Cell Mol Biol. 2007;  37 67-74
    CrossrefPubMedSearch in Google Scholar
  • 66 Riccardi V M. Von Recklinghausen neurofibromatosis.  N Engl J Med. 1981;  305 1617-1627
    CrossrefPubMedSearch in Google Scholar
  • 67 Zamora A C, Collard H R, Wolters P J, Webb W R, King T E. Neurofibromatosis-associated lung disease: a case series and literature review.  Eur Respir J. 2007;  29 210-214
    PubMedSearch in Google Scholar
  • 68 Ryu J H, Parambil J G, McGrann P S, Aughenbaugh G L. Lack of evidence for an association between neurofibromatosis and pulmonary fibrosis.  Chest. 2005;  128 2381-2386
    CrossrefPubMedSearch in Google Scholar
  • 69 Patchefsky A S, Atkinson W G, Hoch W S, Gordon G, Lipshitz H I. Interstitial pulmonary fibrosis and von Recklinghausen's disease: an ultrastructural and immunofluorescent study.  Chest. 1973;  64 459-464
    CrossrefPubMedSearch in Google Scholar
  • 70 Ikegami M, Dhami R, Schuchman E H. Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann–Pick disease.  Am J Physiol Lung Cell Mol Physiol. 2003;  284 L518-525
    PubMedSearch in Google Scholar
  • 71 Schneider E L, Epstein C J, Kaback M J, Brandes D. Severe pulmonary involvement in adult Gaucher's disease: report of three cases and review of the literature.  Am J Med. 1977;  63 475-480
    CrossrefPubMedSearch in Google Scholar
  • 72 Xu Y H, Quinn B, Witte D, Grabowski G A. Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease.  Am J Pathol. 2003;  163 2093-2101
    PubMedSearch in Google Scholar
  • 73 Sun Y, Quinn B, Witte D P, Grabowski G A. Gaucher disease mouse models: point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants.  J Lipid Res. 2005;  46 2102-2113
    CrossrefPubMedSearch in Google Scholar
  • 74 Auwerx J, Demedts M, Bouillon R, Desmet J. Coexistence of hypocalciuric hypercalcaemia and interstitial lung disease in a family: a cross-sectional study.  Eur J Clin Invest. 1985;  15 6-14
    CrossrefPubMedSearch in Google Scholar
  • 75 Demedts M, Auwerx J, Goddeeris P, Bouillon R, Gyselen A, Lauweryns J. The inherited association of interstitial lung disease, hypocalciuric hypercalcemia, and defective granulocyte function.  Am Rev Respir Dis. 1985;  131 470-475
    PubMedSearch in Google Scholar
  • 76 Ho C, Conner D A, Pollak M R et al.. A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.  Nat Genet. 1995;  11 389-394
    PubMedSearch in Google Scholar

David M BrassPh.D. 

DUMC Box 3373, Research Drive

Durham, NC 27710

Email: David.brass@duke.edu