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===Respiratory Bronchiolitis-Interstitial Lung Disease ===
===Respiratory Bronchiolitis-Interstitial Lung Disease ===
[[Cigarette smoking]] could be one of the major causative agent of Respiratory Bronchiolitis-Interstitial Lung Disease (RB-ILD). Some radiologic studies show a relation between the duration and the intensity of cigarette smoking and visualization of opacities on chest radiographs which could be associated to RB-ILD. <ref name="Carilli-1973">{{Cite journal | last1 = Carilli | first1 = AD. | last2 = Kotzen | first2 = LM. | last3 = Fischer | first3 = MJ. | title = The chest roentgenogram in smoking females. | journal = Am Rev Respir Dis | volume = 107 | issue = 1 | pages = 133-6 | month = Jan | year = 1973 | doi = | PMID = 4683317 }}</ref><ref name="Weiss-1984">{{Cite journal | last1 = Weiss | first1 = W. | title = Cigarette smoke, asbestos, and small irregular opacities. | journal = Am Rev Respir Dis | volume = 130 | issue = 2 | pages = 293-301 | month = Aug | year = 1984 | doi = | PMID = 6380358 }}</ref><ref name="Weiss-1991">{{Cite journal | last1 = Weiss | first1 = W. | title = Cigarette smoking and small irregular opacities. | journal = Br J Ind Med | volume = 48 | issue = 12 | pages = 841-4 | month = Dec | year = 1991 | doi = | PMID = 1772799 }}</ref><ref name="Dick-1992">{{Cite journal | last1 = Dick | first1 = JA. | last2 = Morgan | first2 = WK. | last3 = Muir | first3 = DF. | last4 = Reger | first4 = RB. | last5 = Sargent | first5 = N. | title = The significance of irregular opacities on the chest roentgenogram. | journal = Chest | volume = 102 | issue = 1 | pages = 251-60 | month = Jul | year = 1992 | doi = | PMID = 1623762 }}</ref> As the name suggests the pathology is in the bronchiole. It’s a more centrally distributed pathology especially in the lumen though the bronchioles, alveolar ducts and the peribronchiolar alveolar spaces which may show clusters of dusty brown macrophages. <ref name="Myers-1987">{{Cite journal | last1 = Myers | first1 = JL. | last2 = Veal | first2 = CF. | last3 = Shin | first3 = MS. | last4 = Katzenstein | first4 = AL. | title = Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases. | journal = Am Rev Respir Dis | volume = 135 | issue = 4 | pages = 880-4 | month = Apr | year = 1987 | doi = | PMID = 3565934 }}</ref><ref name="Yousem-1989">{{Cite journal | last1 = Yousem | first1 = SA. | last2 = Colby | first2 = TV. | last3 = Gaensler | first3 = EA. | title = Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. | journal = Mayo Clin Proc | volume = 64 | issue = 11 | pages = 1373-80 | month = Nov | year = 1989 | doi = | PMID = 2593722 }}</ref><ref name="Niewoehner-1974">{{Cite journal | last1 = Niewoehner | first1 = DE. | last2 = Kleinerman | first2 = J. | last3 = Rice | first3 = DB. | title = Pathologic changes in the peripheral airways of young cigarette smokers. | journal = N Engl J Med | volume = 291 | issue = 15 | pages = 755-8 | month = Oct | year = 1974 | doi = 10.1056/NEJM197410102911503 | PMID = 4414996 }}</ref><ref name="Churg-2010">{{Cite journal | last1 = Churg | first1 = A. | last2 = Müller | first2 = NL. | last3 = Wright | first3 = JL. | title = Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. | journal = Arch Pathol Lab Med | volume = 134 | issue = 1 | pages = 27-32 | month = Jan | year = 2010 | doi = 10.1043/1543-2165-134.1.27 | PMID = 20073602 }}</ref><ref name="Cosio-1980">{{Cite journal | last1 = Cosio | first1 = MG. | last2 = Hale | first2 = KA. | last3 = Niewoehner | first3 = DE. | title = Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. | journal = Am Rev Respir Dis | volume = 122 | issue = 2 | pages = 265-21 | month = Aug | year = 1980 | doi = | PMID = 7416603 }}</ref><ref name="Colby-1998">{{Cite journal | last1 = Colby | first1 = TV. | title = Bronchiolitis. Pathologic considerations. | journal = Am J Clin Pathol | volume = 109 | issue = 1 | pages = 101-9 | month = Jan | year = 1998 | doi = | PMID = 9426525 }}</ref> Granular golden brown particles having plenty of cytoplasm may be seen. These particles are PAS-positive and Prussian blue –positive which implies increased iron content in alveolar macrophage, which can be associated to smoking .<ref name="Niewoehner-1974">{{Cite journal | last1 = Niewoehner | first1 = DE. | last2 = Kleinerman | first2 = J. | last3 = Rice | first3 = DB. | title = Pathologic changes in the peripheral airways of young cigarette smokers. | journal = N Engl J Med | volume = 291 | issue = 15 | pages = 755-8 | month = Oct | year = 1974 | doi = 10.1056/NEJM197410102911503 | PMID = 4414996 }}</ref><ref name="Cosio-1980">{{Cite journal | last1 = Cosio | first1 = MG. | last2 = Hale | first2 = KA. | last3 = Niewoehner | first3 = DE. | title = Morphologic and morphometric effects of prolonged cigarette smoking on the smallairways. | journal = Am Rev Respir Dis | volume = 122 | issue = 2 | pages = 265-21 | month = Aug | year = 1980 | doi = | PMID = 7416603 }}</ref><ref name="Churg-2010">{{Cite journal | last1 = Churg | first1 = A. | last2 = Müller | first2 = NL. | last3 = Wright | first3 = JL. | title = Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. | journal = Arch Pathol Lab Med | volume = 134 | issue = 1 | pages = 27-32 | month = Jan | year = 2010 | doi = 10.1043/1543-2165-134.1.27 | PMID = 20073602 }}</ref>
*[[Cigarette smoking]] could be one of the major causative agent of Respiratory Bronchiolitis-Interstitial Lung Disease (RB-ILD). A relation between the duration and the intensity of cigarette smoking and visualization of opacities on chest radiographs could be associated to RB-ILD. <ref name="Carilli-1973">{{Cite journal | last1 = Carilli | first1 = AD. | last2 = Kotzen | first2 = LM. | last3 = Fischer | first3 = MJ. | title = The chest roentgenogram in smoking females. | journal = Am Rev Respir Dis | volume = 107 | issue = 1 | pages = 133-6 | month = Jan | year = 1973 | doi = | PMID = 4683317 }}</ref><ref name="Weiss-1984">{{Cite journal | last1 = Weiss | first1 = W. | title = Cigarette smoke, asbestos, and small irregular opacities. | journal = Am Rev Respir Dis | volume = 130 | issue = 2 | pages = 293-301 | month = Aug | year = 1984 | doi = | PMID = 6380358 }}</ref><ref name="Weiss-1991">{{Cite journal | last1 = Weiss | first1 = W. | title = Cigarette smoking and small irregular opacities. | journal = Br J Ind Med | volume = 48 | issue = 12 | pages = 841-4 | month = Dec | year = 1991 | doi = | PMID = 1772799 }}</ref><ref name="Dick-1992">{{Cite journal | last1 = Dick | first1 = JA. | last2 = Morgan | first2 = WK. | last3 = Muir | first3 = DF. | last4 = Reger | first4 = RB. | last5 = Sargent | first5 = N. | title = The significance of irregular opacities on the chest roentgenogram. | journal = Chest | volume = 102 | issue = 1 | pages = 251-60 | month = Jul | year = 1992 | doi = | PMID = 1623762 }}</ref>
A common appearance between DIP and respiratory bronchiolitis is a combination of alveolar septal thickening, epithelial hyperplasia and pigmented macrophages in the lumen. There are lymphocytes and histiocytes deposited in an irregular way in the submucosa. Similar to the black pigment in the [[macrophages]] a dark black anthracotic pigment is what could be seen in these histiocytes .<ref name="Yousem-1989">{{Cite journal | last1 = Yousem | first1 = SA. | last2 = Colby | first2 = TV. | last3 = Gaensler | first3 = EA. | title = Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. | journal = Mayo Clin Proc | volume = 64 | issue = 11 | pages = 1373-80 | month = Nov | year = 1989 | doi = | PMID = 2593722 }}</ref><ref name="Colby-1998">{{Cite journal | last1 = Colby | first1 = TV. | title = Bronchiolitis. Pathologic considerations. | journal = Am J Clin Pathol | volume = 109 | issue = 1 | pages = 101-9 | month = Jan | year = 1998 | doi = | PMID = 9426525 }}</ref> Type 2 hyerplastic cells and cuboidal bronchiolar type epithelium line the fibrosis around the bronchioles.  
* The pathology is more central in the bronchiole especially in the lumen .Sometimes the bronchioles, alveolar ducts and the peribronchiolar alveolar spaces may show clusters of dusty brown macrophages. <ref name="Myers-1987">{{Cite journal | last1 = Myers | first1 = JL. | last2 = Veal | first2 = CF. | last3 = Shin | first3 = MS. | last4 = Katzenstein | first4 = AL. | title = Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases. | journal = Am Rev Respir Dis | volume = 135 | issue = 4 | pages = 880-4 | month = Apr | year = 1987 | doi = | PMID = 3565934 }}</ref><ref name="Yousem-1989">{{Cite journal | last1 = Yousem | first1 = SA. | last2 = Colby | first2 = TV. | last3 = Gaensler | first3 = EA. | title = Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. | journal = Mayo Clin Proc | volume = 64 | issue = 11 | pages = 1373-80 | month = Nov | year = 1989 | doi = | PMID = 2593722 }}</ref><ref name="Niewoehner-1974">{{Cite journal | last1 = Niewoehner | first1 = DE. | last2 = Kleinerman | first2 = J. | last3 = Rice | first3 = DB. | title = Pathologic changes in the peripheral airways of young cigarette smokers. | journal = N Engl J Med | volume = 291 | issue = 15 | pages = 755-8 | month = Oct | year = 1974 | doi = 10.1056/NEJM197410102911503 | PMID = 4414996 }}</ref><ref name="Churg-2010">{{Cite journal | last1 = Churg | first1 = A. | last2 = Müller | first2 = NL. | last3 = Wright | first3 = JL. | title = Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. | journal = Arch Pathol Lab Med | volume = 134 | issue = 1 | pages = 27-32 | month = Jan | year = 2010 | doi = 10.1043/1543-2165-134.1.27 | PMID = 20073602 }}</ref><ref name="Cosio-1980">{{Cite journal | last1 = Cosio | first1 = MG. | last2 = Hale | first2 = KA. | last3 = Niewoehner | first3 = DE. | title = Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. | journal = Am Rev Respir Dis | volume = 122 | issue = 2 | pages = 265-21 | month = Aug | year = 1980 | doi = | PMID = 7416603 }}</ref><ref name="Colby-1998">{{Cite journal | last1 = Colby | first1 = TV. | title = Bronchiolitis. Pathologic considerations. | journal = Am J Clin Pathol | volume = 109 | issue = 1 | pages = 101-9 | month = Jan | year = 1998 | doi = | PMID = 9426525 }}</ref>  
*Granular golden brown particles having plenty of cytoplasm may be seen. These particles are PAS-positive and Prussian blue –positive which implies increased iron content in alveolar macrophage. This increased Iron content could be associated to smoking .<ref name="Niewoehner-1974">{{Cite journal | last1 = Niewoehner | first1 = DE. | last2 = Kleinerman | first2 = J. | last3 = Rice | first3 = DB. | title = Pathologic changes in the peripheral airways of young cigarette smokers. | journal = N Engl J Med | volume = 291 | issue = 15 | pages = 755-8 | month = Oct | year = 1974 | doi = 10.1056/NEJM197410102911503 | PMID = 4414996 }}</ref><ref name="Cosio-1980">{{Cite journal | last1 = Cosio | first1 = MG. | last2 = Hale | first2 = KA. | last3 = Niewoehner | first3 = DE. | title = Morphologic and morphometric effects of prolonged cigarette smoking on the smallairways. | journal = Am Rev Respir Dis | volume = 122 | issue = 2 | pages = 265-21 | month = Aug | year = 1980 | doi = | PMID = 7416603 }}</ref><ref name="Churg-2010">{{Cite journal | last1 = Churg | first1 = A. | last2 = Müller | first2 = NL. | last3 = Wright | first3 = JL. | title = Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. | journal = Arch Pathol Lab Med | volume = 134 | issue = 1 | pages = 27-32 | month = Jan | year = 2010 | doi = 10.1043/1543-2165-134.1.27 | PMID = 20073602 }}</ref>
*A common appearance between DIP and respiratory bronchiolitis is a mixture of alveolar septal thickening, epithelial hyperplasia and pigmented macrophages in the lumen. There are lymphocytes and histiocytes deposited in an irregular way in the submucosa. Similar to the black pigment in the [[macrophages]] a dark black anthracotic pigment is what could be seen in these histiocytes .<ref name="Yousem-1989">{{Cite journal | last1 = Yousem | first1 = SA. | last2 = Colby | first2 = TV. | last3 = Gaensler | first3 = EA. | title = Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. | journal = Mayo Clin Proc | volume = 64 | issue = 11 | pages = 1373-80 | month = Nov | year = 1989 | doi = | PMID = 2593722 }}</ref><ref name="Colby-1998">{{Cite journal | last1 = Colby | first1 = TV. | title = Bronchiolitis. Pathologic considerations. | journal = Am J Clin Pathol | volume = 109 | issue = 1 | pages = 101-9 | month = Jan | year = 1998 | doi = | PMID = 9426525 }}</ref> Type 2 hyerplastic cells and cuboidal bronchiolar type epithelium line the fibrosis around the bronchioles.


===Desquamative Interstitial Pneumonia ===
===Desquamative Interstitial Pneumonia ===

Revision as of 20:05, 18 November 2013

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

Overview

Pathophysiology

Idiopathic Pulmonary Fibrosis

Pulmonary fibrosis has often been called an autoimmune disease. However, it is perhaps better characterized as an abnormal and excessive deposition of fibrotic tissue in the pulmonary interstitium with minimal associated inflammation.[1] Autoantibodies, a hallmark of autoimmune diseases, are found in a minority of patients with truly idiopathic pulmonary fibrosis. Moreover, many autoimmune diseases associated with "pulmonary fibrosis", such as scleroderma, are more frequently associated with a related but more inflammatory disease, nonspecific interstitial pneumonitis.[2] It is associated with smoking[3] and exhibits some dependency on the amount of smoking.[4]

Idiopathic Non-specific Interstitial Pneumonia

NSIP findings are very inconsistent and irregular just like its name.[5][6][7] Changes similar to other cases of interstitial pneumonia are seen which are migration of inflammatory cell migration in the alveolar septa and causing its widening with or without fibrosis. NSIP can be divided into three groups based on histopathological changes.[8]

Stage Pathological Feature
Group I Inflammatory cells predominant stage
Group II Accompanying fibrosis
Group III Fibrosis prevalent

A bronchoalveloar lavage (BAL) revealed the presence of lymphocytes in the alveolar septum,which proves the involvement of the immune system.[6][9][10][11] A greater number of dendritic cells (DC), which help in antigen presentation, are visualized in close association to CD4 and CD8 lymphocytes in the biopsy of NSIS patients than UIP .[12] Fibroblasts are key cells involved in fibrotic lung diseases .[13]

Pathological mechanism involves [14][15][16][17][18][19][20][21][22][23][24][25][26][27]

  • Epithelial injury and dysregulated repair - major role.[28]
  • Cytokines
  • Proteins like epimorphin (a cell surface associated protein), matrix metalloproteinases, heat shock protein, surfactant protein C
  • The coagulation system
  • Intercellular adhesion molecules-1, IL-4, IL-13, IL-18,
  • Interferon-gamma
  • Pro fibrotic chemokines
  • CCL7, and CCL5
  • Lymphocytes
  • Dendritic cells
  • Fibroblasts



Some common associations between Idiopathic Non-specific Interstitial Pneumonia (NSIP)and Usual Interstitial Pneumonia (UIP) have been noted. Histologically patients can manifest lesions of both UIP and NSIP simultaneously.The reason for this manifestation is still unknown. A few common reason between the two like similar disease association,exposures and genetic mutation are seen .[29][5]

NSIP And UIP differ in their prognosis .NSIP has a better prognosis than UIP. Other features differentiating them are:

  • Uneven fibrosis
  • Honeycombing
  • Fibroblast predominant foci
  • Fibroblasts secreting transforming growth factor–Beta (TGF-β) and fibronectin.[30]


Respiratory Bronchiolitis-Interstitial Lung Disease

  • Cigarette smoking could be one of the major causative agent of Respiratory Bronchiolitis-Interstitial Lung Disease (RB-ILD). A relation between the duration and the intensity of cigarette smoking and visualization of opacities on chest radiographs could be associated to RB-ILD. [31][32][33][34]
  • The pathology is more central in the bronchiole especially in the lumen .Sometimes the bronchioles, alveolar ducts and the peribronchiolar alveolar spaces may show clusters of dusty brown macrophages. [35][36][37][38][39][40]
  • Granular golden brown particles having plenty of cytoplasm may be seen. These particles are PAS-positive and Prussian blue –positive which implies increased iron content in alveolar macrophage. This increased Iron content could be associated to smoking .[37][39][38]
  • A common appearance between DIP and respiratory bronchiolitis is a mixture of alveolar septal thickening, epithelial hyperplasia and pigmented macrophages in the lumen. There are lymphocytes and histiocytes deposited in an irregular way in the submucosa. Similar to the black pigment in the macrophages a dark black anthracotic pigment is what could be seen in these histiocytes .[36][40] Type 2 hyerplastic cells and cuboidal bronchiolar type epithelium line the fibrosis around the bronchioles.

Desquamative Interstitial Pneumonia

Desquamative Interstitial Pneumonia (DIP) lacks the patchy appearance that UIP normally presents with .In DIP alveolar walls are lined with chronic inflammatory cells and dense connective tissue and the alveolar spaces are filled with macrophages. In desquamative interstitial pneumonia mild fibrosis without honeycomb changes are seen sometimes. Key points are mononuclear changes at the most distal spaces. These mononuclear cells appear as finely granular brown pigment with mottled tiny black particles. These may be called as smoker’s macrophage, which are different than desquamated pneumocytes. Some common overlapping changes between DIP and respiratory bronchiolitis are seen.[41][36]

Cryptogenic-Organizing Pneumonia

Cryptogenic organizing pneumonia lesions consist more of fibroblasts and myofibroblasts in the alveolar ducts and alveoli. There might be involvement of polyps in the bronchial lumen in some patients. There is excess of granulation tissue deposition and sometimes this pattern of extension may appear like a butterfly. Dysorganization of the alveolar epithelium is what causes cryptogenic organizing pneumonia. This dysorganization leads to plasma protein leakage, fibroblast migration and fibrin deposition inside the lumen. Involvement of the vascular endothelial growth factors and matrix metalloproteinases also adds up to the cause.[42] Some recent studies also show that it is a rare extra-intestinal manifestation of Crohn's Disease.[43]

Acute Interstitial pneumonia (Hamman-Rich Syndrome)

Acute Interstitial Pneumonia (AIP) has similar appearance as to diffuse alveolar damage (DAD). A majority of lung injury reacts via the same mechanism as diffuse alveolar damage. It has three stages earlier exudative, then organized proliferative and last the chronic healed or fibrotic .[44][45]

  • Exudative stage: Histology specimen is never obtained since patient presents late .
  • Proliferative stage: Most typical change seen. A lot of inflammatory infiltration seen in the septa causing destruction and hyaline membrane formation leading to thickening of the septa and interstitium.
  • Chronic or healed phase: Diffuse scarring seen. A major differentiating factor between AIP and UIP in this phase is that AIP has similar type of lesion at one point of time whereas UIP has lesions of different ages and no specific one pattern could be found out at a given period of time

Release of tumor necrosis factor alpha, interleukin 1β, monocyte chemoattractant factor and neutrophils cause further damage and also causes release of toxic oxygen radicals and proteases. These causes lead to exudate formation and cellular damage. A fibroblast proliferation and differentiation into myofibroblasts leads to collagen formation which widens the septa. Later hyaline membrane decrease in number and there is a rise in the number of type II epithelial cells. A few patients resolve after this stage whereas a majority progress to the next stage of fibrosis . AIP shows prominent myofibroblastic proliferation whereas this finding is not always seen in cases of ARDS due to infection or drug toxicity .[46][47]

Lymphoid Interstitial Pneumonia

Characteristic findings of Lymphoid Interstitial Pneumonia (LIP) are lymphoid and chronic cell infiltration predominantly seen in the alveolar septa but sometimes may also be seen along bronchi and vessels. Granulomas specially non –caseating, fibrotic changes, honeycombing and loss of normal lung tissue could also be seen as the disease progresses .[48][49]In LIP B cell polyclonality is seen which differentiates it from pulmonary lymphoma. In HIV T cells are more predominant. Some times no specific cell types are seen though .[49][50][51] A Bcl-6 gene mutation is somewhat believed to be associated with mucosa-associated lymphoid tissue (MALT), HIV and EBV and other virus negative LIP. [52] Features like monoclonality, hilar involvement, pleural involvement, bronchial wall involvement all point towards a malignant transformation .[53]

References

  1. ↑ Selman, Moisés (2001). "Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy". Annals of Internal Medicine. 134 (2): 136–51. Unknown parameter |coauthors= ignored (help)
  2. ↑ King, Jr., Talmadge E. (2005). "Centennial review: clinical advances in the diagnosis and therapy of the interstitial lung diseases". American Journal of Respiratory and Critical Care Medicine. 172 (3): 268–79.
  3. ↑ Nagai, Sonoko (2000). "Smoking-related interstitial lung diseases". Current Opinion in Pulmonary Medicine. 6 (5): 415–9. PMID 10958232. Unknown parameter |coauthors= ignored (help)
  4. ↑ Baumgartner, KB (1997). "Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis". American Journal of Respiratory and Critical Care Medicine. 155 (1): 242–248. PMID 9001319. Unknown parameter |coauthors= ignored (help)
  5. ↑ 5.0 5.1 Flaherty, KR.; Travis, WD.; Colby, TV.; Toews, GB.; Kazerooni, EA.; Gross, BH.; Jain, A.; Strawderman, RL.; Flint, A. (2001). "Histopathologic variability in usual and nonspecific interstitial pneumonias". Am J Respir Crit Care Med. 164 (9): 1722–7. doi:10.1164/ajrccm.164.9.2103074. PMID 11719316. Unknown parameter |month= ignored (help)
  6. ↑ 6.0 6.1 Cottin, V.; Donsbeck, AV.; Revel, D.; Loire, R.; Cordier, JF. (1998). "Nonspecific interstitial pneumonia. Individualization of a clinicopathologic entity in a series of 12 patients". Am J Respir Crit Care Med. 158 (4): 1286–93. doi:10.1164/ajrccm.158.4.9802119. PMID 9769293. Unknown parameter |month= ignored (help)
  7. ↑ Katzenstein, AL.; Myers, JL. (2000). "Nonspecific interstitial pneumonia and the other idiopathic interstitial pneumonias: classification and diagnostic criteria". Am J Surg Pathol. 24 (1): 1–3. PMID 10632482. Unknown parameter |month= ignored (help)
  8. ↑ Katzenstein, AL.; Fiorelli, RF. (1994). "Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance". Am J Surg Pathol. 18 (2): 136–47. PMID 8291652. Unknown parameter |month= ignored (help)
  9. ↑ Fujita, J.; Yamadori, I.; Suemitsu, I.; Yoshinouchi, T.; Ohtsuki, Y.; Yamaji, Y.; Kamei, T.; Kobayashi, M.; Nakamura, Y. (1999). "Clinical features of non-specific interstitial pneumonia". Respir Med. 93 (2): 113–8. PMID 10464862. Unknown parameter |month= ignored (help)
  10. ↑ Nagai, S.; Kitaichi, M.; Itoh, H.; Nishimura, K.; Izumi, T.; Colby, TV. (1998). "Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP". Eur Respir J. 12 (5): 1010–9. PMID 9863989. Unknown parameter |month= ignored (help)
  11. ↑ Park, CS.; Jeon, JW.; Park, SW.; Lim, GI.; Jeong, SH.; Uh, ST.; Park, JS.; Choi, DL.; Jin, SY. (1996). "Nonspecific interstitial pneumonia/fibrosis: clinical manifestations, histologic and radiologic features". Korean J Intern Med. 11 (2): 122–32. PMID 8854648. Unknown parameter |month= ignored (help)
  12. ↑ Shimizu, S.; Yoshinouchi, T.; Ohtsuki, Y.; Fujita, J.; Sugiura, Y.; Banno, S.; Yamadori, I.; Eimoto, T.; Ueda, R. (2002). "The appearance of S-100 protein-positive dendritic cells and the distribution of lymphocyte subsets in idiopathic nonspecific interstitial pneumonia". Respir Med. 96 (10): 770–6. PMID 12412975. Unknown parameter |month= ignored (help)
  13. ↑ Selman, M.; King, TE.; Pardo, A. (2001). "Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy". Ann Intern Med. 134 (2): 136–51. PMID 11177318. Unknown parameter |month= ignored (help)
  14. ↑ Terasaki, Y.; Fukuda, Y.; Ishizaki, M.; Yamanaka, N. (2000). "Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in mice". Am J Respir Cell Mol Biol. 23 (2): 168–74. doi:10.1165/ajrcmb.23.2.3973. PMID 10919982. Unknown parameter |month= ignored (help)
  15. ↑ Suga, M.; Iyonaga, K.; Okamoto, T.; Gushima, Y.; Miyakawa, H.; Akaike, T.; Ando, M. (2000). "Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias". Am J Respir Crit Care Med. 162 (5): 1949–56. doi:10.1164/ajrccm.162.5.9906096. PMID 11069839. Unknown parameter |month= ignored (help)
  16. ↑ Kakugawa, T.; Mukae, H.; Hayashi, T.; Ishii, H.; Nakayama, S.; Sakamoto, N.; Yoshioka, S.; Sugiyama, K.; Mine, M. (2005). "Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia". Respir Res. 6: 57. doi:10.1186/1465-9921-6-57. PMID 15955241.
  17. ↑ Thomas, AQ.; Lane, K.; Phillips, J.; Prince, M.; Markin, C.; Speer, M.; Schwartz, DA.; Gaddipati, R.; Marney, A. (2002). "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. 165 (9): 1322–8. doi:10.1164/rccm.200112-123OC. PMID 11991887. Unknown parameter |month= ignored (help)
  18. ↑ Brasch, F.; Griese, M.; Tredano, M.; Johnen, G.; Ochs, M.; Rieger, C.; Mulugeta, S.; Müller, KM.; Bahuau, M. (2004). "Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene". Eur Respir J. 24 (1): 30–9. PMID 15293602. Unknown parameter |month= ignored (help)
  19. ↑ Nogee, LM.; Dunbar, AE.; Wert, SE.; Askin, F.; Hamvas, A.; Whitsett, JA. (2001). "A mutation in the surfactant protein C gene associated with familial interstitial lung disease". N Engl J Med. 344 (8): 573–9. doi:10.1056/NEJM200102223440805. PMID 11207353. Unknown parameter |month= ignored (help)
  20. ↑ Stevens, PA.; Pettenazzo, A.; Brasch, F.; Mulugeta, S.; Baritussio, A.; Ochs, M.; Morrison, L.; Russo, SJ.; Beers, MF. (2005). "Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene". Pediatr Res. 57 (1): 89–98. doi:10.1203/01.PDR.0000147567.02473.5A. PMID 15557112. Unknown parameter |month= ignored (help)
  21. ↑ Chibbar, R.; Shih, F.; Baga, M.; Torlakovic, E.; Ramlall, K.; Skomro, R.; Cockcroft, DW.; Lemire, EG. (2004). "Nonspecific interstitial pneumonia and usual interstitial pneumonia with mutation in surfactant protein C in familial pulmonary fibrosis". Mod Pathol. 17 (8): 973–80. doi:10.1038/modpathol.3800149. PMID 15133475. Unknown parameter |month= ignored (help)
  22. ↑ Eitzman, DT.; McCoy, RD.; Zheng, X.; Fay, WP.; Shen, T.; Ginsburg, D.; Simon, RH. (1996). "Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene". J Clin Invest. 97 (1): 232–7. doi:10.1172/JCI118396. PMID 8550840. Unknown parameter |month= ignored (help)
  23. ↑ Kim, KK.; Flaherty, KR.; Long, Q.; Hattori, N.; Sisson, TH.; Colby, TV.; Travis, WD.; Martinez, FJ.; Murray, S. "A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia". Mol Med. 9 (1–2): 52–6. PMID 12765340.
  24. ↑ Takehara, H.; Tada, S.; Kataoka, M.; Matsuo, K.; Ueno, Y.; Ozaki, S.; Miyake, T.; Fujimori, Y.; Yamadori, I. (2001). "Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia". Acta Med Okayama. 55 (4): 205–11. PMID 11512562. Unknown parameter |month= ignored (help)
  25. ↑ Jakubzick, C.; Choi, ES.; Kunkel, SL.; Evanoff, H.; Martinez, FJ.; Puri, RK.; Flaherty, KR.; Toews, GB.; Colby, TV. (2004). "Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia". J Clin Pathol. 57 (5): 477–86. PMID 15113854. Unknown parameter |month= ignored (help)
  26. ↑ Keogh, KA.; Limper, AH. (2005). "Characterization of lymphocyte populations in nonspecific interstitial pneumonia". Respir Res. 6: 137. doi:10.1186/1465-9921-6-137. PMID 16287509.
  27. ↑ Choi, ES.; Jakubzick, C.; Carpenter, KJ.; Kunkel, SL.; Evanoff, H.; Martinez, FJ.; Flaherty, KR.; Toews, GB.; Colby, TV. (2004). "Enhanced monocyte chemoattractant protein-3/CC chemokine ligand-7 in usual interstitial pneumonia". Am J Respir Crit Care Med. 170 (5): 508–15. doi:10.1164/rccm.200401-002OC. PMID 15191918. Unknown parameter |month= ignored (help)
  28. ↑ Ishii, H.; Mukae, H.; Kadota, J.; Fujii, T.; Abe, K.; Ashitani, J.; Kohno, S. "Increased levels of interleukin-18 in bronchoalveolar lavage fluid of patients with idiopathic nonspecific interstitial pneumonia". Respiration. 72 (1): 39–45. doi:10.1159/000083399. PMID 15753633.
  29. ↑ Monaghan, H.; Wells, AU.; Colby, TV.; du Bois, RM.; Hansell, DM.; Nicholson, AG. (2004). "Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias". Chest. 125 (2): 522–6. PMID 14769733. Unknown parameter |month= ignored (help)
  30. ↑ Miki, H.; Mio, T.; Nagai, S.; Hoshino, Y.; Nagao, T.; Kitaichi, M.; Izumi, T. (2000). "Fibroblast contractility: usual interstitial pneumonia and nonspecific interstitial pneumonia". Am J Respir Crit Care Med. 162 (6): 2259–64. doi:10.1164/ajrccm.162.6.9812029. PMID 11112149. Unknown parameter |month= ignored (help)
  31. ↑ Carilli, AD.; Kotzen, LM.; Fischer, MJ. (1973). "The chest roentgenogram in smoking females". Am Rev Respir Dis. 107 (1): 133–6. PMID 4683317. Unknown parameter |month= ignored (help)
  32. ↑ Weiss, W. (1984). "Cigarette smoke, asbestos, and small irregular opacities". Am Rev Respir Dis. 130 (2): 293–301. PMID 6380358. Unknown parameter |month= ignored (help)
  33. ↑ Weiss, W. (1991). "Cigarette smoking and small irregular opacities". Br J Ind Med. 48 (12): 841–4. PMID 1772799. Unknown parameter |month= ignored (help)
  34. ↑ Dick, JA.; Morgan, WK.; Muir, DF.; Reger, RB.; Sargent, N. (1992). "The significance of irregular opacities on the chest roentgenogram". Chest. 102 (1): 251–60. PMID 1623762. Unknown parameter |month= ignored (help)
  35. ↑ Myers, JL.; Veal, CF.; Shin, MS.; Katzenstein, AL. (1987). "Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases". Am Rev Respir Dis. 135 (4): 880–4. PMID 3565934. Unknown parameter |month= ignored (help)
  36. ↑ 36.0 36.1 36.2 Yousem, SA.; Colby, TV.; Gaensler, EA. (1989). "Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia". Mayo Clin Proc. 64 (11): 1373–80. PMID 2593722. Unknown parameter |month= ignored (help)
  37. ↑ 37.0 37.1 Niewoehner, DE.; Kleinerman, J.; Rice, DB. (1974). "Pathologic changes in the peripheral airways of young cigarette smokers". N Engl J Med. 291 (15): 755–8. doi:10.1056/NEJM197410102911503. PMID 4414996. Unknown parameter |month= ignored (help)
  38. ↑ 38.0 38.1 Churg, A.; Müller, NL.; Wright, JL. (2010). "Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts". Arch Pathol Lab Med. 134 (1): 27–32. doi:10.1043/1543-2165-134.1.27. PMID 20073602. Unknown parameter |month= ignored (help)
  39. ↑ 39.0 39.1 Cosio, MG.; Hale, KA.; Niewoehner, DE. (1980). "Morphologic and morphometric effects of prolonged cigarette smoking on the small airways". Am Rev Respir Dis. 122 (2): 265–21. PMID 7416603. Unknown parameter |month= ignored (help)
  40. ↑ 40.0 40.1 Colby, TV. (1998). "Bronchiolitis. Pathologic considerations". Am J Clin Pathol. 109 (1): 101–9. PMID 9426525. Unknown parameter |month= ignored (help)
  41. ↑ Moon, J.; du Bois, RM.; Colby, TV.; Hansell, DM.; Nicholson, AG. (1999). "Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease". Thorax. 54 (11): 1009–14. PMID 10525560. Unknown parameter |month= ignored (help)
  42. ↑ Qiu, YY.; Miao, LY.; Cai, HR.; Xiao, YL.; Ye, Q.; Meng, FQ.; Feng, AN. (2013). "[The clinicopathological features of acute fibrinous and organizing pneumonia]". Zhonghua Jie He He Hu Xi Za Zhi. 36 (6): 425–30. PMID 24103205. Unknown parameter |month= ignored (help)
  43. ↑ Dinneen, HS.; Samiullah, S.; Lenza, C. (2013). "Cryptogenic organizing pneumonia: A rare extra-intestinal manifestation of Crohn's disease". J Crohns Colitis. doi:10.1016/j.crohns.2013.09.006. PMID 24090908. Unknown parameter |month= ignored (help)
  44. ↑ Olson, J.; Colby, TV.; Elliott, CG. (1990). "Hamman-Rich syndrome revisited". Mayo Clin Proc. 65 (12): 1538–48. PMID 2255216. Unknown parameter |month= ignored (help)
  45. ↑ Katzenstein, AL.; Myers, JL.; Mazur, MT. (1986). "Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study". Am J Surg Pathol. 10 (4): 256–67. PMID 3706612. Unknown parameter |month= ignored (help)
  46. ↑ Kang, D.; Nakayama, T.; Togashi, M.; Yamamoto, M.; Takahashi, M.; Kunugi, S.; Ishizaki, M.; Fukuda, Y. (2009). "Two forms of diffuse alveolar damage in the lungs of patients with acute respiratory distress syndrome". Hum Pathol. 40 (11): 1618–27. doi:10.1016/j.humpath.2009.04.019. PMID 19647854. Unknown parameter |month= ignored (help)
  47. ↑ Pache, JC.; Christakos, PG.; Gannon, DE.; Mitchell, JJ.; Low, RB.; Leslie, KO. (1998). "Myofibroblasts in diffuse alveolar damage of the lung". Mod Pathol. 11 (11): 1064–70. PMID 9831203. Unknown parameter |month= ignored (help)
  48. ↑ "American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001". Am J Respir Crit Care Med. 165 (2): 277–304. 2002. doi:10.1164/ajrccm.165.2.ats01. PMID 11790668. Unknown parameter |month= ignored (help)
  49. ↑ 49.0 49.1 Koss, MN.; Hochholzer, L.; Langloss, JM.; Wehunt, WD.; Lazarus, AA. (1987). "Lymphoid interstitial pneumonia: clinicopathological and immunopathological findings in 18 cases". Pathology. 19 (2): 178–85. PMID 3453998. Unknown parameter |month= ignored (help)
  50. ↑ Travis, WD.; Fox, CH.; Devaney, KO.; Weiss, LM.; O'Leary, TJ.; Ognibene, FP.; Suffredini, AF.; Rosen, MJ.; Cohen, MB. (1992). "Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis". Hum Pathol. 23 (5): 529–41. PMID 1314778. Unknown parameter |month= ignored (help)
  51. ↑ Lin, RY.; Gruber, PJ.; Saunders, R.; Perla, EN. (1988). "Lymphocytic interstitial pneumonitis in adult HIV infection". N Y State J Med. 88 (5): 273–6. PMID 3288914. Unknown parameter |month= ignored (help)
  52. ↑ Kurosu, K.; Weiden, MD.; Takiguchi, Y.; Rom, WN.; Yumoto, N.; Jaishree, J.; Nakata, K.; Kasahara, Y.; Tanabe, N. (2004). "BCL-6 mutations in pulmonary lymphoproliferative disorders: demonstration of an aberrant immunological reaction in HIV-related lymphoid interstitial pneumonia". J Immunol. 172 (11): 7116–22. PMID 15153535. Unknown parameter |month= ignored (help)
  53. ↑ Turner, RR.; Colby, TV.; Doggett, RS. (1984). "Well-differentiated lymphocytic lymphoma. A study of 47 patients with primary manifestation in the lung". Cancer. 54 (10): 2088–96. PMID 6386139. Unknown parameter |month= ignored (help)

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