Idiopathic interstitial pneumonia pathophysiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Synonyms and keywords:
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 withsmoking[3] and exhibits some dependency on the amount of smoking.[4]
Idiopathic Non-specific Interstitial Pneumonia (NSIP)
There are some common associations between NSIP and usual interstitial pneumonia(UIP). Histologically patients can manifest lesions of UIP and NSIP simultaneously. Some common factors include exposures, genetic mutations. Exact cause and nature is still unknown. Recent studies conclude that epithelial injury and dysregulated repair play a major role. Cytokines and some proteins like epimorphin (a cell surface associated protein), matrix metalloproteinases, heat shock protein, surfactant protein C, the coagulation system, intercellular adhesionmolecules-1, IL-4, IL-13, IL-18, interferon-gamma, pro fibrotic chemokine, CCL7 and CCL5. A bronchoalveloar lavage (BAL) revealed the presence of lymphocytes in the alveolar septum, which suggests the involvement of the immune system. A greater number of dendritic cells (DC), which help in antigen presentation, are visualized in close association to CD4 and CD8 lymphocytes in biopsy in NSIS patients than UIP.Fibroblasts are key pathological cells involved in fibrotic lung diseases. Fibroblasts secreting transforming growth factor–Beta (TGF-β) and fibronectin are the differentiating characters in NSIS and UIP.
Respiratory Bronchiolitis-Interstitial Lung Disease (RB-ILD)
As the name suggests the pathology is in the bronchiole. It’s a more centrally distributed pathology in the lumen though the bronchioles, alveolar ducts and the peribronchiolar alveolar spaces may show clusters of macrophages which are dusty and brown. 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 might be associated to smoking. A common appearance between DIP and respiratory bronchiolitis would be a combination of alveolar septal thickening, epithelial hyperplasia and pigmented macrophages in the lumen. There are lymphocytes and histiocytes present in an irregular way in the submucosa. Similar to the black pigment in the macrophage a dark black anthracotic pigment is what could be seen in the cytoplasm. Type 2 hyerplastic cells and cuboidal bronchiolar type epithelium could be seen lining the peribronchiolar fibrosis.
Desquamative interstitial pneumonia (DIP)
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 alveolar spaces are filled with macrophages. In desquamative interstitial pneumonia mild fibrosis without honeycomb changes are seen. Key changes are visualization of mononuclear changes at the 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 changes between DIP and respiratory bronchiolitis are seen.
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 disorganization leads to plasma protein leakage, fibroblast migration and fibrin deposition inside the lumen. Involvement of the vascular endothelial growth factors and matrix metalloproteinase also adds up to the cause.
Acute Interstitial pneumonia (AIP)
AIP has similar appearance as to diffuse alveolar damage (DAD). A majority of lung injury reacts via the same mechanism as diffuse interstitial pneumonia. It has three stages earlier exudative, then organized proliferative and last the chronic healed or fibrotic.
1. Exudative stage: Histology specimen never obtained since patient presents late and biopsy are never obtained. 2. Proliferative stage: Most typical change. A lot of inflammatory infiltration seen in the septa with destruction and hyaline membrane formation leading to thickening of the septa and interstitium. 3. 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 period of time.
Release of tumor necrosis factor alpha, interleukin 1beta, monocyte chemoattractant factor and neutrophils cause further damage and release of toxic oxygen radicals and proteases. These causes exudate and cellular damage. A fibroblast proliferation and differentiation into myofibroblasts leads to collagen formation and widening of 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.
References
- ↑ 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) - ↑ 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.
- ↑ Nagai, Sonoko (2000). "Smoking-related interstitial lung diseases". Current Opinion in Pulmonary Medicine. 6 (5): 415–9. PMID 10958232. Unknown parameter
|coauthors=ignored (help) - ↑ 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)