Connective Tissue Disease-associated Interstitial Pneumonia Research Articles

Systematic review and meta-analysis of the prognosis and prognostic factors of interstitial pneumonia with autoimmune features

ObjectiveTo clarify the prognosis and prognostic factors of interstitial pneumonia with autoimmune features (IPAF) in comparison to idiopathic pulmonary fibrosis (IPF), the most common idiopathic interstitial pneumonia, and connective tissue...

Proposed method of histological separation between connective tissue disease-associated interstitial pneumonia and idiopathic interstitial pneumonias.

ObjectivesIdiopathic interstitial pneumonia (IIP) and connective tissue disease -associated interstitial pneumonia (CTD-IP) are the two most common types of interstitial pneumonia. IIP and CTD-IP share common histological features, yet their clinical management is different. Separation of the two conditions based solely on histology can be challenging, and there are no established criteria.Materials and methodsWe selected 105 consecutive cases of IIP (79 usual interstitial pneumonia and 26 non-specific interstitial pneumonia) and 49 cases of CTD-IP for derivation and 32 cases of IIP and 10 cases of CTD-IP for validation. Fourteen histological parameters were evaluated independently by two pathologists for derivation group and graded into 0 to 3. The association between the score for each marker and a diagnosis of CTD was investigated using Fisher’s exact test and stepwise logistic regression analysis. A formula for calculating the probability of IIP and CTD-IP was constructed by the markers identified in the regression test with coefficients for each finding. The formula was confirmed using validation case group.ResultsStepwise logistic regression analysis showed that plasmacytosis, lymphoid follicle with germinal center, and airspace fibrin were suggestive of CTD-IP and that fibroblastic foci, smooth muscle hyperplasia, cellular IP, dense perivascular collagen, and fat metaplasia were suggestive of IIP. The formula used to calculate the probabilities based on estimated values for each finding was created, and user-friendly web based app was composed at www.ctdip.com.On the validation study, 30 out of 32 IIP and eight out of 10 CTD-IPs were distinguished correctly by the app (Specificity: 93%, Sensitivity: 80%).ConclusionsWe identified histological markers and derived a practical formula and user-friendly app to distinguish CTD-IPs from IIP.

Clinical features and outcome of acute exacerbation of interstitial pneumonia associated with connective tissue disease.

Acute exacerbation (AE) of interstitial lung disease is reported to be developed in not only idiopathic pulmonary fibrosis but also connective tissue disease-associated interstitial pneumonia (CTD-IP). As the significance of AE of CTD-IP has not been so widely recognized, its clinical feature is not fully elucidated. In the present study, we investigated the incidence, clinical features and outcome of AE of CTD-IP. We retrospectively reviewed admitted cases in our department with medical record from 2011 to 2015. Among 155 patients with CTD-IP, 10 (6.5%) cases developed AE (6 rheumatoid arthritis, 2 polymyositis/dermatomyositis, 1 systemic lupus erythematosus, 1 Sjögren syndrome), and one died of AE within 30 days. Median survival time after the onset of AE was 169 days in all 10 patients. The treatment with immunosuppressant just before AE onset might improve the prognosis of AE. The median survival time after the onset of AE was significantly longer in patients showing good response to corticosteroid compared with those with poor response to corticosteroid (805 days and 45 days, respectively) (p <0.05), suggesting that there are some cases in CTD-IP, showing the good response to corticosteroid even when AE was complicated. J. Med. Invest. 63: 294-299, August, 2016.

Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis

The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other interstitial pneumonia markers were measured. In this study, 30 patients with stable IPF and 11 patients with acute exacerbation of IPF were collected. Mean sICAM-1 levels were 434 ± 139 ng/mL for the stable phase of IPF, 645 ± 247 ng/mL for early phase of acute exacerbation of IPF, 534 ± 223 ng/mL for connective tissue disease-associated interstitial pneumonia, 221 ± 42 for chronic obstructive pulmonary disease, and 150 ± 32 ng/mL in healthy volunteers. For the stable phase of IPF, sICAM-1 levels correlated with Krebs von den Lungen-6 (KL-6) (r value: 0.41; p value: 0.036). Mean sICAM-1 levels were significantly higher in patients with early phase of acute exacerbation of IPF than with stable phase of IPF (p = 0.0199). Multiple logistic analyses indicated that the predictors for early phase of acute exacerbation of IPF were only sICAM-1 and C-reactive protein (odds ratio: 1.0093; 1.6069). In patients with stable IPF, sICAM-1 levels correlated with KL-6; sICAM-1 might be a predictive indicator for prognosis. In the early phase of acute exacerbation of IPF, sICAM-1 might be more useful for diagnosis than other interstitial pneumonia markers.

Quantitative diagnosis of connective tissue disease-associated interstitial pneumonia using thoracic computed tomography images.

Patients with polymyositis (PM) or dermatomyositis (DM) frequently show interstitial pneumonia (IP), which is sometimes rapidly progressive or resistant to treatment, thereby significantly affecting the prognosis. The diagnosis and response evaluation of IP are commonly performed qualitatively based on imaging findings, which may cause disagreement among rheumatologists in the evaluation of early lesions and atypical interstitial changes. To determine whether IP could be diagnosed in a quantitative manner during the early stage of PM/DM using a workstation that allows quantitative image processing. Thoracic computed tomography (CT) images of 20 PM/DM patients were reconstructed into a three-dimensional (3D) image using an image processing workstation. The CT values of the constituent voxels were arranged in a histogram of -1000 to +1000 Hounsfield units (HU). The most frequent lung field density was -900 to -801 HU, and relative size was as follows: IP (+) group 0.45 and IP (-) group 0.53. Between -1000 and -701 HU, relative size was not significantly different between the IP (+) group and IP (-) group. Between -700 and -1 HU, the relative size of the lung field was significantly larger in the IP (+) than in the IP (-) group, demonstrating its IP-diagnosing ability. Particularly, within the range from -700 to -301 HU, the macroscopically-assessed ground glass opacity was consistent with the CT value, which, in turn, was closely correlated with KL-6, the pre-existing marker for IP diagnosis. The results of this study may lead to the establishment of quantitative methods of evaluating IP and possible elucidation of the pathogenesis of IP.

Pulmonary infections following immunosuppressive treatments during hospitalization worsen the short-term vital prognosis for patients with connective tissue disease-associated interstitial pneumonia

Objective. Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP.Methods. A multicenter, retrospective study was conducted that collected data from patients with CTD who had been hospitalized for commencing or intensifying immunosuppressive treatment of CTD-IP using a standardized case report form. Risk factors were identified using the Cox proportional hazard regression model.Results. A total of 322 CTD-IP patients were enrolled with rheumatoid arthritis (n = 84), systemic lupus erythematosus (n = 13), polymyositis (n = 33), dermatomyositis (n = 69), systemic sclerosis (n = 55), mixed connective tissue disease (n = 21), microscopic polyangiitis (n = 19), and overlap syndrome (n = 28). Of the 42patients who died during hospitalization, 22 died from CTD-IP, 15 from CTD-IP and pulmonary infection, 2 from pulmonary infection, and 3 from other causes. Age ≥ 65 years and development of pulmonary infections after commencing or intensifying immunosuppressive treatments were identified as risk factors for death during hospitalization after adjusting for covariates.Conclusion. Careful consideration of the benefit–risk balance of immunosuppressive treatment for CTD-IP is indispensable for improving the short-term vital prognosis of these patients.