Macrophage-mannose receptor CD206 to discriminate connective tissue disease-associated usual interstitial pneumonia from IPF

2021 ◽  
Author(s):  
Xianhua Gui ◽  
Hui Ding ◽  
ShenYun Shi ◽  
Jingjing Ding ◽  
Mei Huang ◽  
...  
Keyword(s):  
Serum Level ◽  
Connective Tissue ◽  
Clinical Significance ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Usual Interstitial Pneumonia ◽  
Mannose Receptor ◽  
Healthy Controls ◽  
Activated Macrophages ◽  
Cox Regression Analysis

Abstract Background: Soluble mannose receptor, sCD206, is a marker of alternatively activated macrophages. Activated macrophages play important roles in connective tissue disease (CTD) and lung fibrosis. Interstitial lung disease (ILD) is a common complication of CTD, which leads to poor prognosis, especially in a pattern with usual interstitial pneumonia (UIP). Similarly, idiopathic pulmonary fibrosis (IPF) is also characterized by UIP. Compared with IPF, the prognosis of CTD-associated UIP is tightly correlated with early treatment. In the present study, we aimed to evaluate the clinical significance of sCD206 in discriminating CTD-associated UIP from IPF. Methods: The serum level of sCD206 was determined in 48 patients with CTD-associated UIP, 54 IPF patients and 27 healthy controls. The clinical significance of sCD206 was also evaluated. Result: Patients with CTD-associated UIP had a higher level of sCD206 compared with healthy controls and IPF patients (p<0.001, p<0.001, respectively). A cutoff value of sCD206 at 523.8 ng/mL could be a useful marker for distinguishing CTD-associated UIP from IPF. Moreover, 15 decedents with CTD-associated UIP exhibited a greater level of sCD206 compared with 33 survivors (p=0.030), and the elevated sCD206 level was associated with a higher mortality rate (log-rank test, p=0.003). Age and gender-adjusted multivariate Cox regression analysis showed that sCD206 (>444.2 ng/mL) was an independent predictor of survival (p= 0.026). Conclusions: Collectively, the serum level of sCD206 could be a useful marker for distinguishing CTD-associated UIP from IPF and associated with a poor survival of CTD-associated UIP.

Effect of Cotreatment with Corticosteroids in Connective Tissue Related Lung Disease (CTD-ILD) Patients on Mycophenolate Mofetil (MMF)

2021 ◽  
Author(s):  
Roberto Caricchio ◽  
Erin R Narewski ◽  
Ryan Townsend ◽  
Stephen Codella ◽  
Jin Sun Kim ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Connective Tissue ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Pulmonary Function Tests ◽  
Usual Interstitial Pneumonia ◽  
University Hospital ◽  
Inflammatory Myositis ◽  
Idiopathic Inflammatory Myositis

Abstract Introduction: Connective Tissue Disease Related Interstitial Lung Disease (CTD-ILD) is often treated with immunosuppressant medications; common among these is Mycophenolate Mofetil (MMF). We hypothesized that co-treatment with corticosteroids would impact disease progression.Methods: We examined a consecutive cohort of CTD-ILD patients followed at Temple University Hospital in Philadelphia, PA since 2015 who had pulmonary function tests (PFTs) performed by American Thoracic Society (ATS)/European Respiratory Society (ERS) Criteria at least one year apart. All patients were treated for CTD-ILD with MMF used either as sole therapy or as combination therapy with prednisone. Univariate logistic analyses were performed revealing the odds ratio (OR) for improvement or worsening of several PFT values (including forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), and six-minute walk (6MW)) greater than the minimal clinically important difference (MCID) for each value.Results: We included 103 patients (74 women) with an average age of 60 ± 11 years, 49% of our cohort were current or former smokers, and mean BMI was 29 ± 7 kg/m2. Patients were observed on treatment for an average of 23 months. CTD distribution included 25% mixed connective tissue disease (MCTD), 24% systemic sclerosis (SSc), 17% rheumatoid arthritis (RA), 14% systemic lupus erythematosus (SLE), 10% other idiopathic inflammatory myositis (IIM) syndromes, 7% Antisynthetase Syndrome, 5% Sjӧgren’s syndrome. Non-specific interstitial pneumonia (NSIP) was the majority (45%) ILD pattern noted, Usual Interstitial Pneumonia (UIP) 35%, and other types were less prevalent (20%). The majority of patients received corticosteroids as co-treatment with MMF (75 patients (72%)) with a mean daily dose of 15 ± 16 mg of prednisone. Mean daily MMF dose was 1144 ± 675 mg. Glucocorticoid treatment was not associated with significant improvements in PFT values, including FVC, DLCO, and 6MW distance walked.Conclusion: In this small cohort, patients with CTD-ILD receiving MMF did not demonstrate improved lung function when receiving co-treatment with corticosteroids, but larger prospective studies are needed to better elucidate the effect of corticosteroids on this vulnerable group of patients.

scholarly journals Centrilobular Fibrosis in Fibrotic (Chronic) Hypersensitivity Pneumonitis, Usual Interstitial Pneumonia, and Connective Tissue Disease–Associated Interstitial Lung Disease

2020 ◽  
Vol 144 (12) ◽  
pp. 1509-1516
Author(s):  
Andrew Churg
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Hypersensitivity Pneumonitis ◽  
Interstitial Fibrosis ◽  
Usual Interstitial Pneumonia ◽  
Diffuse Fibrosis ◽  
Chronic Hypersensitivity Pneumonitis

Context.— Various pulmonary diseases can produce centrilobular (peribronchiolar) fibrosis, which may be isolated or associated with other patterns of more diffuse fibrosis. The major forms of interstitial lung disease in which centrilobular fibrosis is found are fibrotic (chronic) hypersensitivity pneumonitis, connective tissue disease–associated interstitial lung disease, and (a disputed issue) usual interstitial pneumonia/idiopathic interstitial fibrosis. Objective.— To review recent literature that addresses separation of these entities. Data Sources.— Data comprised recent publications. Conclusions.— In a specially constructed multidisciplinary discussion exercise, it was found that peribronchiolar metaplasia affecting more than half the bronchioles or more than 2 foci of peribronchiolar metaplasia per square centimeter of biopsy area was strongly associated with a confident diagnosis of fibrotic hypersensitivity pneumonitis. Giant cells or granulomas were only found in cases with a greater than 50% diagnostic confidence in hypersensitivity pneumonitis. Conversely, greater numbers of fibroblast foci per square centimeter and increasing measured amounts of subpleural fibrosis favored a diagnosis of usual interstitial pneumonia. Recent data also suggest that centrilobular fibrosis can be found in usual interstitial pneumonia, although the presence of centrilobular fibrosis statistically favors an alternate diagnosis. Connective tissue disease is a major confounder because many patterns are very similar to fibrotic hypersensitivity pneumonitis or usual interstitial pneumonia. Genetic abnormalities, such as the MUC5B minor allele overlap, in these conditions and at this point cannot be used for discrimination. Thus, the separation of fibrotic hypersensitivity pneumonitis and usual interstitial pneumonia remains a difficult problem. Accurate biopsy diagnosis of all of these diseases requires correlation with imaging and clinical findings, and is crucial for treatment.

scholarly journals Pathologic Quantification of Connective Tissue Disease–Associated Versus Idiopathic Usual Interstitial Pneumonia

2012 ◽  
Vol 136 (10) ◽  
pp. 1253-1258 ◽  
Author(s):  
Nicole A. Cipriani ◽  
Mary Strek ◽  
Imre Noth ◽  
Ilyssa O. Gordon ◽  
Jeff Charbeneau ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Connective Tissue ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Interstitial Pneumonitis ◽  
Interobserver Variability ◽  
Usual Interstitial Pneumonia ◽  
Nonspecific Interstitial Pneumonia ◽  
Salient Features ◽  
Lymphoid Aggregates

Context.—Usual interstitial pneumonia (UIP) is a common chronic interstitial pneumonitis. It can occur idiopathically (I-UIP) or in the setting of systemic connective tissue disease (CTD-UIP). Some studies suggest that CTD-UIP has a better prognosis than I-UIP. The histologic differences between CTD-UIP and I-UIP are not clearly defined. Objective.—The purpose of this study was to evaluate histologic criteria that may differentiate CTD-UIP from I-UIP, including fibroblastic foci (FFs), lymphoid aggregates (LAs), and the presence of nonspecific interstitial pneumonia pattern. Design.—Thirty-five patients with histologic diagnoses of UIP were identified (27 biopsies [77%]; 8 explants [23%]). Biopsy slides were scanned and analyzed quantitatively for FF size, FF area, LA size, and LA area. Biopsy and explant slides were examined qualitatively for the presence of a nonspecific interstitial pneumonia pattern in areas away from UIP fibrosis. Results.—Of 27 biopsies, the number and size of FFs in CTD-UIP were smaller than they were in I-UIP. The number and size of LAs were larger in patients with rheumatoid arthritis than they were in patients with I-UIP. There was no interobserver variability among 3 pathologists using this quantitative system. Of 35 biopsies and explants, there was a higher prevalence of the nonspecific interstitial pneumonia pattern among patients with CTD-UIP than there was among patients with I-UIP (P = .005). Conclusions.—Patients with CTD-UIP had fewer, smaller FFs than did patients with I-UIP, and patients with rheumatoid arthritis-UIP had more, larger LAs than did patients with I-UIP. Of importance, the coexistence of UIP and the nonspecific interstitial pneumonia patterns was one of the most salient features in distinguishing CTD-UIP from I-UIP because CTD-UIP demonstrated an increased prevalence of multilobar, cellular, nonspecific interstitial pneumonia patterns in areas away from the UIP fibrosis.

scholarly journals Morphologic Aspects of Interstitial Pneumonia With Autoimmune Features

2018 ◽  
Vol 142 (9) ◽  
pp. 1080-1089 ◽  
Author(s):  
Ellen Caroline Toledo do Nascimento ◽  
Bruno Guedes Baldi ◽  
Marcio Valente Yamada Sawamura ◽  
Marisa Dolhnikoff
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Usual Interstitial Pneumonia ◽  
Connective Tissue Diseases ◽  
Distinct Subgroup ◽  
Management Protocol ◽  
The Impact

Context.— Interstitial lung disease, a common complication observed in several connective tissue diseases, causes significant morbidity and mortality. Similar to individuals with connective tissue diseases, a significant subgroup of patients with clinical and serologic characteristics suggestive of autoimmunity but without confirmed specific connective tissue disease presents with associated interstitial lung disease. These patients have been classified using different controversial nomenclatures, such as undifferentiated connective tissue disease–associated interstitial lung disease, lung-dominant connective tissue disease, and autoimmune featured interstitial lung disease. The need for a better understanding and standardization of this entity, interstitial lung disease with autoimmune features, and the need for an adequate management protocol for patients resulted in the introduction of a new terminology in 2015: interstitial pneumonia with autoimmune features. This new classification requires a better comprehension of its diagnostic impact and the influence of its morphologic aspects on the prognosis of patients. Objective.— To review the diagnostic criteria for interstitial pneumonia with autoimmune features, with an emphasis on morphologic aspects. Data Sources.— The review is based on the available literature, and on pathologic, radiologic, and clinical experience. Conclusions.— The interstitial pneumonia with autoimmune features classification seems to identify a distinct subgroup of patients with different prognoses. Studies show that nonspecific interstitial pneumonia and usual interstitial pneumonia are the most prevalent morphologic patterns and show discrepant results on the impact of the usual interstitial pneumonia pattern on survival. Prospective investigations are necessary to better define this subgroup and to determine the prognosis and appropriate clinical management of these patients.

Computed Tomography Findings Suggestive of Connective Tissue Disease in the Setting of Usual Interstitial Pneumonia

2021 ◽  
Vol 45 (5) ◽  
pp. 776-781
Author(s):  
Jonathan H. Chung ◽  
Steven M. Montner ◽  
Prahasit Thirkateh ◽  
Brenna Cannon ◽  
Scott D. Barnett ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Connective Tissue ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Usual Interstitial Pneumonia

scholarly journals Histologic features suggesting connective tissue disease in idiopathic pulmonary fibrosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ho Cheol Kim ◽  
Joon Seon Song ◽  
Sojung Park ◽  
Hee-Young Yoon ◽  
So Yun Lim ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Clinical Course ◽  
Usual Interstitial Pneumonia ◽  
High Resolution Computed Tomography ◽  
Cox Analysis

AbstractSome patients with idiopathic pulmonary fibrosis (IPF) have histopathologic features suggesting connective tissue disease (CTD); however, their clinical course and prognosis remain unclear. Thus, we aimed to investigate the clinical course and prognosis of these patients with histologic autoimmune features. Among 114 patients with biopsy-proven IPF, the histologic features were semi-quantitatively graded, and CTD scores (range: 0–9) were calculated as the sum of each score of plasma cell infiltration, lymphoid aggregates, and germinal centres. Patients with high CTD scores (≥ 4) were classified into the interstitial pneumonia with histologic autoimmune features (IP-hAF) group. The mean age of the patients was 60.0 years; 74.6% were men, 69.3% were ever-smokers, and 35.1% had IP-hAF. During follow-up, the IP-hAF group showed slower decline in lung function, and better prognosis (median survival, 48.7 vs. 40.4 months; p = 0.015) than the no-IP-hAF group. On multivariate Cox analysis, IP-hAF was an independent prognostic factor (hazard ratio, 0.522; p = 0.016), along with the lower diffusing capacity for carbon monoxide, higher scores of reticulation and honeycombing, and usual interstitial pneumonia pattern on high-resolution computed tomography. Patients with IPF having histologic autoimmune features show distinct clinical characteristics and better outcome than those without histologic autoimmune features.

Cumulative Incidences of Lung Cancer in Various Interstitial Lung Diseases

2021 ◽  
Author(s):  
Takafumi Suzuki ◽  
Hiroyuki Sakashita ◽  
Masako Akiyama ◽  
Takayuki Honda ◽  
Masaru Ejima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Connective Tissue ◽  
Interstitial Pneumonia ◽  
Connective Tissue Disease ◽  
Hypersensitivity Pneumonitis ◽  
Usual Interstitial Pneumonia ◽  
Idiopathic Interstitial Pneumonia ◽  
Cancer Development ◽  
Idiopathic Interstitial Pneumonias ◽  
Chronic Hypersensitivity Pneumonitis

Abstract Background Interstitial lung disease (ILD) patients often develop lung cancer. However, previous studies on the incidences of lung cancer in ILD patients focused on specific aetiologies, such as idiopathic pulmonary fibrosis (IPF). The lung cancer incidences in these patients have not been investigated, and thus, we aimed to evaluate them here. Methods ILD patients at our hospital were retrospectively reviewed. The cumulative incidences of lung cancer in patients with various ILDs were estimated with Kaplan-Meier curves and compared between ILD groups using log-rank tests. The association between several variables at initial diagnosis and lung cancer development was assessed with Cox proportional hazards regression analysis to identify predictors. Results In all, 606 ILD patients, including 161 with IPF, 133 with non-IPF idiopathic interstitial pneumonias, 160 with chronic hypersensitivity pneumonitis, 87 with connective tissue disease-related ILDs, 19 with pulmonary sarcoidosis, and 46 with other ILDs, were included. Twenty-eight patients developed lung cancer. The cumulative incidences of lung cancer at 1, 3, and 5 years were: 1.9, 5.7, and 12.3% with IPF, respectively; 0.8, 0.8, and 4.0% in non-IPF idiopathic interstitial pneumonias; 2.0, 4.6, and 11.0% in chronic hypersensitivity pneumonitis; and 1.1, 1.1, and 2.9% in connective tissue disease-related ILDs. IPF patients had a higher incidence of lung cancer than non-IPF idiopathic interstitial pneumonia patients (p = 0.036). A radiological usual interstitial pneumonia pattern, forced vital capacity value, and pack-years were associated with lung cancer development (hazard ratios 2.959, 1.031, 1.011; 95% confidence intervals 1.257–6.963, 1.006–1.057, 1.002–1.020, p = 0.013, 0.017, 0.020, respectively). Conclusions The lung cancer incidence is higher in IPF patients than in non-IPF idiopathic interstitial pneumonia patients and is equally high in patients with chronic hypersensitivity pneumonitis and IPF.

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