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High-resolution CT scans of (A) normal, (B) 'early' idiopathic pulmonary fibrosis, (C) end-stage idiopathic pulmonary fibrosis, (D) nonspecific interstitial pneumonia and (E) chronic obstructive pulmonary disease. (B) Typically, the 'reticular pattern' in idiopathic pulmonary fibrosis is localized in subpleural areas. (D) The 'ground glass' finding presented in nonspecific interstitial pneumonia is not a specific finding and may be observed also in many lung reactions and infections. (E) Pulmonary emphysema is evenly distributed in this case but can vary markedly in different areas and/or subjects with chronic obstructive pulmonary disease.
Source publication
Parenchymal lung diseases comprise a wide variety of diseases, with different etiologies, pathogeneses and prognoses. This perspective provides an overview of two different disease types: chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Chronic obstructive pulmonary disease, which is related to smoking, is one of the leading...
Contexts in source publication
Context 1
... contrast to IPF/UIP, NSIP contains no FF and is more diffuse, with lung biopsies revealing parenchymal inflammation. These diseases also reveal different patterns in high-resolution computed tomography, IPF findings being typically reticular while NSIP appearing nonspecific (Figure 3A-3D). NSIP, however, exists in fibrotic and cellular forms, with the histopathology being either fibrotic or inflammatory [16]. ...
Context 2
... typical feature in emphysematous lung is the local occurrence of fibrotic lesions, which concentrate in the small airways and focal areas of the lung parenchyma. The emphy- sematous areas of COPD consist of enlarged and/or destroyed airspaces and airway walls (Figure 3e). The lung pathology exhib- its a destructive expression of several fibrosis-associated matrix proteins and proteases [19,20]. ...
Context 3
... fibrotic areas also represent old and/or end-stage areas of fibro- genesis, whereas some others may be new and/or active regions. Typically, UIP lesions are concentrated into the subpleural areas of the lung (see Figure 3B). In COPD, the lung may express even Some of the diseases listed above represent more alveolitis than pure interstitial disease; these include desquamative interstitial pneumonia, hypersensitivity pneumontis, pulmonary alveolar proteinosis and alveolar microlithiasis. ...
Similar publications
Usual interstitial pneumonia (UIP) is one type of idiopathic interstitial pneumonia, characterized by its poor prognosis and gradual deterioration of clinical course. So it is important to distinguish UIP from other interstitial pneumonia. Definitive histological diagnosis of UIP requires lung biopsy. The criteria for diagnosis of UIP in the absenc...
This retrospective study evaluates serial changes of lung abnormalities on high-resolution CT (HRCT) and clarifies prognostic determinants among CT findings in fibrotic idiopathic interstitial pneumonias (IIPs) with little honeycombing.
We enrolled 154 patients with a histologic diagnosis of a fibrotic IIP (< 5% honeycombing on CT) who were followe...
Rationale:
Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families.
Objectives:
To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of a...
In patients with fibrotic idiopathic interstitial pneumonia (f-IIP), the diffusing capacity for carbon monoxide (DLCO) has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. The aim of this study was to compare...
Idiopathic pulmonary fibrosis (IPF) is a very specific form of a chronic, progressive fibroproliferative interstitial pneumonia of unknown aetiology. The disease is generally associated with a poor prognosis. Several international evidence-based guidelines on the diagnosis and management of IPF and other interstitial lung diseases (ILDs) have been...
Citations
... It is an immunologically mediated inflammation of lung parenchyma that occurs in susceptible individuals that is triggered by a variety of antigens [3]. High-resolution computed tomography (HRCT), bronchoscopy and surgical lung biopsy are crucial steps in making a definite diagnosis of different ILDs [4]. Moreover, serial lung function tests are generally helpful in monitoring disease activity and/or predicting the prognosis in ILDs patients [5]. ...
... Several diagnostic tools are essential for making a definitive diagnosis of various interstitial lung diseases (ILDs), including IIPs 11 . Additionally, successive pulmonary function testing is largely used to check the clinical course of the disease and/ or predict the prognosis in patients with ILDs 12 . ...
... Serum KL-6 levels are also found to increase in various diseases including interstitial lung disease (ILD) and some cancers, such as lung cancer and breast cancer. [2][3][4] In fact, greater than 30% of patients with certain cancerous malignancies were positive for KL-6. 5 The cut-off value of KL-6 (500 U/ml) is well known as a diagnostic marker for distinguishing patients with ILD from healthy controls. However, the role of KL-6 as a diagnostic marker in idiopathic pulmonary fibrosis (IPF) has not been thoroughly verified. ...
Background
Serum Krebs von den Lungen‐6 (KL‐6) has been reported to be elevated in patients with idiopathic pulmonary fibrosis (IPF).
Objective
The aim of this study was to evaluate the diagnostic value of KL‐6 and whether the expression value of KL‐6 could indicate the severity of the disease in IPF patients. To address this question, it is necessary to see whether the patients' physical characteristics and other clinical conditions could affect the baseline KL‐6 level.
Design
We conducted a study of 100 patients who were diagnosed with IPF. Lung function, computed tomography (CT), and serological lab tests data were analyzed.
Results
The tests showed that there is a significant elevation of KL‐6 in IPF patients compared with other interstitial lung disease (ILD) and healthy controls. It was noted that serum KL‐6 is a stable biomarker not affected by lung infection and smoking, though IPF patients with antinuclear antibody (ANA) showed higher KL‐6 levels. KL‐6, in conjunction with poor pulmonary function and higher radiological fibrosis scores, indicates the severity of the disease but not poor survival.
Conclusions
It is identified that serum KL‐6 is a useful noninvasive biomarker to help improve the certainty of IPF diagnosis from other interstitial lung disease and assist evaluation of disease severity and prognosis.
... Several diagnostic tools are essential for making a definitive diagnosis of various interstitial lung diseases (ILDs), including IIPs 11 . Additionally, successive pulmonary function testing is largely used to check the clinical course of the disease and/ or predict the prognosis in patients with ILDs 12 . ...
Background:
Hypersensitivity pneumonitis (HP) is an increasingly recognized form of diffuse parenchymal lung disease. Krebs von den Lungen-6 (KL-6) is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with ILD. Serum KL-6/MUC1 levels have been demonstrated to be useful for evaluating various ILD.
Objective:
To determine the role of circulating KL-6 in evaluating the disease activity and management of HP.
Methods:
An observational cross-sectional study was conducted on 51 patients with HP. Serum KL-6 levels were measured. Patients were further assessed by chest high-resolution computed tomography (HRCT), pulmonary function tests, six-minute walk test, echocardiography, bronchioalveolar lavage, and/or transbronchial biopsy. Patients were divided into the fibrotic and non-fibrotic groups according to the HRCT findings.
Results:
The median serum KL-6 levels were significantly higher in HP patients as compared to the control group. The median serum KL-6 levels were found to be higher in the non -fibrotic HP group (1900 IU/mL) as compared to the fibrotic group (1200 IU/mL). There was a significant inverse correlation between serum KL-6 serum level and the dose of steroids as well as duration of steroid therapy.
Conclusion:
The presence of higher KL-6 levels in the non-fibrotic HP group implies its enhanced production by regenerating pneumocytes in response to alveolar injury. The significant association between serum KL-6 levels and the dose and the duration of steroid therapy emphasized the important role of steroids in stabilization of the disease.
... High resolution computed tomography (HRCT), bronchoscopic examination and surgical lung biopsy (SLB) are the basic investigations required to make a definite diagnosis of sarcoidosis. [5][6][7] Transbronchial lung biopsy (TLB) is the procedure of choice in most cases. Its diagnostic yield depends largely on the experience of the operator, ranging from 40% to more than 90% when four to five lung biopsies are carried out. ...
Sarcoidosis is a multi-system inflammatory disease of unknown origin characterized
by non-caseating epithelioid cell granuloma and lymphocytic alveolitis.1 It has
unidentified etiology, heterogeneous clinical presentation and unpredictable disease
course. Since injury and regeneration of type II pneumocytes is a significant histological
feature of Sarcoidosis, substances derived from type II pneumocytes have been the
focus of research in Sarcoidosis and other interstitial lung diseases. One important
biomarker under research for Sarcoidosis is the high molecular weight glycoprotein,
Krebs von den Lungen-6 (KL-6). KL-6 is a glycoprotein present on the membrane of
type 2 alveolar cells, bronchiolar epithelial cells and also on epithelial cells of other
organs.2 It is reported to be elevated in the serum and broncho-alveolar lavage (BAL)
fluid of patients with Sarcoidosis. Its role in patients with Interstitial Lung Diseases
(ILDs) and connective tissue diseases is being studied.3 It has been revealed that
serum KL-6 is elevated in 70–100% of patients with parenchymal sarcoidosis and in
30-70% of patients with other forms of Sarcoidosis. In this review, we highlight the
use of KL-6 as a biomarker in the diagnosis and severity of pulmonary sarcoidosis.
... Two dimensional gel electrophoresis (2-DE) is an easy and widely proteomic separation technique used to analyze differentially expressed proteins in biological samples. By proteomics analysis can be simultaneously identifyied multiple proteins associated with different disease states [13]; that has been applied to investigate the protein changes in the lung tissue [14,15], bronchoalveolar lavage fluid (BALF), and induced sputum of COPD patients [16][17][18][19][20][21]. However, the identification of specific proteomic signatures from plasma might provide a simpler, and safer, approach. ...
... Idiopathic interstitial pneumonia (IIP) encompasses a group of diffuse parenchymal lung diseases characterized by interstitial involvement resulting from various patterns of inflammation and fibrosis of unknown cause. Based on histological features, IIP has been further classified into several subtypes, including idiopathic pulmonary fibrosis (IPF), which has the hallmark histopathologic feature described as usual interstitial pneumonia and nonspecific interstitial pneumonia (NSIP) [1][2][3]. The latest statement from American Thoracic Society (ATS) and European Respiratory Society (ERS) proposed the category "chronic fibrosing IIP" encompassing both IPF and NSIP [3], because separation between these two diseases is difficult, with significant clinical, radiological, and pathological overlap between them [4]. ...
Background
Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This study aims to investigate the genetic backgrounds of IIP through gene expression profiling and pathway analysis, and to identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic targets. MethodsRNA extracted from lung specimens of 12 patients with chronic fibrosing IIP was profiled using Illumina Human WG-6 v3 BeadChips, and Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways. For validating the results from gene expression analysis, immunohistochemical staining of 10 patients with chronic fibrosing IIP was performed. ResultsNinety-eight genes were upregulated in IIP patients relative to control subjects. Some of the upregulated genes, namely desmoglein 3 (DSG3), protocadherin gamma-A9 (PCDHGA9) and discoidin domain-containing receptor 1 (DDR1) are implicated in cell-cell interaction and/or adhesion; some, namely collagen type VII, alpha 1 (COL7A1), contactin-associated protein-like 3B (CNTNAP3B) and mucin-1 (MUC1) are encoding the extracellular matrix molecule or the molecules involved in cell-matrix interactions; and the others, namely CDC25C and growth factor independent protein 1B (GFI1B) are known to affect cell proliferation by affecting the progression of cell cycle or regulating transcription. According to pathway analysis, alternated pathways in IIP were related to cell death and survival and cellular growth and proliferation, which are more similar to cancer than to inflammatory response and immunological diseases. Using immunohistochemistry, we further validate that DSG3, the most highly upregulated gene, shows higher expression in chronic fibrosing IIP lung as compared to control lung. Conclusion
We identified several genes upregulated in chronic fibrosing IIP patients as compared to control, and found genes and pathways implicated in cancer, rather than in inflammatory or immunological disease to play important roles in the pathogenesis of IIPs. Moreover, DSG3 is a novel potential biomarker for chronic fibrosing IIP with its significantly high expression in IIP lung.
... При воздействии внешних факторов неоргани ческой и органической природы (аллергенов, токси ческих факторов, фиброгенной пыли) нарушается структура мембраны пневмоцитов, активация син теза белков, которые рассматриваются как биомар керы ИЗЛ. Сывороточные биомаркеры наряду с компьютерной томографией и показателями внеш него дыхания могут быть использованы при диаг ностике, оценке активности, тяжести течения ИЗЛ, а также как прогностический фактор [2]. Биомарке ры могут применяться также для скринингового исследования при подозрении на профессиональ ные ИЗЛ. ...
The aim of this study was to investigate values of pulmonary fibrosis markers alveomucin and KL-16 and the airway damage marker CC-16 for eval-uating activity and progressing of extrinsic interstitial lung diseases (ILD) in dependence on etiology. Methods. Levels of Krebs von den Lungen-6 glycoprotein (KL-6), alveomucin and Clara cell protein (CC16) were measured using the ELISA method. The study involved 13 patients with pneu-moconiosis, 26 patients with extrinsic allergic alveolitis (EAA) and 20 patients with extrinsic toxic alveolitis (ETA) both in active and stable status. Results. KL-6 and alveomucin were found to be more valuable markers for assessing activity of extrinsic fibrosing alveolitis compared to CC16. Alveomucin had higher specificity but lower sensitivity compared to KL-6. Conclusion. Alveomucin could be used as a screening test in cases with clinical susceptibility for extrinsic alveolitis. On contrary, KL-6 and alveomucin could be used for assessing therapeutic efficacy of EAA and ETA.
... The search for diseasespecific biomarkers in BALF or serum of humans with IPF has been extensive in recent years. 9,10 Although numerous biomarkers have been proposed for IPF in humans and 1 biomarker (endothelin-1) has been proposed for IPF in dogs, 11 none have been validated or implemented in clinical practice. 9,10 Proteomics, defined as a large-scale characterization of proteins expressed by a genome, 12 can be used to identify biomarkers and reveal disease-specific mechanisms. ...
... 9,10 Although numerous biomarkers have been proposed for IPF in humans and 1 biomarker (endothelin-1) has been proposed for IPF in dogs, 11 none have been validated or implemented in clinical practice. 9,10 Proteomics, defined as a large-scale characterization of proteins expressed by a genome, 12 can be used to identify biomarkers and reveal disease-specific mechanisms. 9 Epithelial lining fluid collected during BAL reflects the airway protein composition, which makes it a suitable material for proteomic studies. ...
... 43,44 Given that lysozyme is an antimicrobial protein that kills organisms via lysis, it was not expected that its expression would be upregulated in the present study because none of the dogs had positive results for bacterial cultures of BALF. 1 A challenge when conducting BALF proteomics is that the protein content of BALF mainly comprises bloodderived proteins that are in high abundance, which can interfere with detection of pathologically relevant proteins present in low amounts. 10 It is generally considered that these low-abundance proteins are produced locally by lung epithelial cells and therefore they are more pathologically relevant. 45 Although the number of BALF samples analyzed for each group was small, the 2-D differential gel electrophoresis technique incorporated a pooled internal standard that minimized the experimental variation associated with gel-to-gel comparisons. ...
Objective:
To evaluate protein expression in bronchoalveolar lavage fluid (BALF) obtained from West Highland White Terriers with idiopathic pulmonary fibrosis (IPF), dogs with chronic bronchitis, and healthy control dogs to identify potential biomarkers for IPF.
Samples:
BALF samples obtained from 6 West Highland White Terriers with histologically confirmed IPF, 5 dogs with chronic bronchitis, and 4 healthy Beagles.
Procedures:
Equal amounts of proteins in concentrated BALF samples were separated via 2-D differential gel electrophoresis. Proteins that were differentially expressed relative to results for healthy control dogs were identified with mass spectrometry and further verified via western blotting.
Results:
Expression of 6 proteins was upregulated and that of 1 protein was downregulated in dogs with IPF or chronic bronchitis, compared with results for healthy dogs. Expression of proteins β-actin, complement C3, α-1-antitrypsin, apolipoprotein A-1, haptoglobin, and transketolase was upregulated, whereas expression of lysozyme C was downregulated.
Conclusions and clinical relevance:
Proteomics can be used to search for biomarkers and to reveal disease-specific mechanisms. The quantitative comparison of proteomes for BALF obtained from dogs with IPF and chronic bronchitis and healthy dogs revealed similar changes for the dogs with IPF and chronic bronchitis, which suggested a common response to disease processes in otherwise different lung diseases. Specific biomarkers for IPF were not identified.
... 1e4 Since therapy with corticosteroids and/or immunosuppressants is largely ineffective for advanced stages of interstitial lung diseases (ILDs), early diagnosis is of utmost importance. 5,6 High-resolution computed tomography (HRCT) and/or surgical lung biopsy (SLB) are at present the fundamental modalities for definitive diagnosis of IIPs. 7,8 Compared to these diagnostic methods, an optimal biomarker for discriminating patients with IIPs from healthy subjects should be less invasive, more rapid and reproducible, and easier to obtain from patients. ...
KL-6 is a high-molecular-weight glycoprotein classified as human Mucin-1 (MUC1). KL-6 has been reported to be a sensitive biomarker for interstitial lung diseases (ILDs) in the Japanese population. It is also known that polymorphisms in the MUC1 gene affect serum levels of KL-6. This study was conducted to evaluate serum levels of KL-6 and MUC1 polymorphisms in both German and Japanese populations.
Serum levels of KL-6 were measured in 267 patients with ILDs (152 German and 115 Japanese) and 186 healthy subjects (HS) (76 German and 110 Japanese). In addition, rs4072037 single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction. The optimal cutoff values for discriminating patients with ILDs from HS was determined by receiver operating characteristic analysis based on ethnicity and rs4072037 genotypes.
The serum KL-6 levels in patients with ILDs were significantly higher compared with HS in both the German and the Japanese cohorts (both p<0.001). The discriminating cutoff value of serum KL-6 in the German cohort was significantly higher than the value in the Japanese cohort. The difference in the serum levels of KL-6 was significantly associated with the rs4072037 genotype distribution.
Even in the German cohort, the serum KL6 levels were significantly higher in patients with ILDs than HS. Because of differences in the genotype distribution of rs4072037, the KL-6 cutoff value for the German cohort that discriminated patients with ILDs from HS was significantly higher than the value in the Japanese cohort.
