Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

Background and objectives: Idiopathic pulmonary fibrosis (IPF) has a particularly poor prognosis, and most IPF-related deaths are due to acute exacerbation (AE) of this condition. Few reports about biomarkers to predict prognosis of AE-IPF have been published since the release of the new AE-IPF criteria in 2016. The present study investigated relationships between serological markers and in-hospital mortality after the onset of AE-IPF. Methods: Demographic, serological, and imaging data from patients hospitalized at the Maebashi Red Cross Hospital (Gunma, Japan) between 1 January 2013, and 31 December 2017, were retrospectively reviewed. Subjects fulfilling the diagnostic criteria for AE-IPF were divided into those who survived or died; statistical analysis of risk factors was performed using data from these two groups. Results: Diagnostic criteria for AE-IPF were fulfilled by 84 patients (59 males (70.2%)), with a median age of 78 years (range, 56–95 years). IPF was diagnosed before hospitalization in 50 (59.5%) patients and 38 (45.2%) died in hospital. Among the serological markers at hospitalization in the deceased group, C-reactive protein (CRP) was significantly higher than in the survivor group (p = 0.002), while total serum protein (p = 0.031), albumin (p = 0.047) and total cholesterol (p = 0.039) were significantly lower. Cox hazard analysis of factors predicting mortality, corrected for age, sex and BMI, revealed the following: CRP (hazard ratio (HR) 1.080 (95% confidence interval (CI) 1.022–1.141); p = 0.006), LDH (HR 1.003 (95% CI 1.000–1.006); p = 0.037), and total cholesterol (HR 0.985 (95% CI 0.972–0.997); p = 0.018). Conclusions: Our data suggest that CRP, LDH, and total cholesterol may be biomarkers predicting mortality in patients with AE-IPF. However, only prospective controlled studies can confirm or not our observation as a generalizable one.

Periostin, an extracellular matrix molecule, is associated with idiopathic pulmonary fibrosis (IPF). It is known that the frequency of familial IPF (FIPF) ranges from 0.5% to 2.2% among IPF cases. However, the relationship between periostin and FIPF has not been previously described. We report the first case of periostin accumulation in the lungs of a patient with an acute exacerbation of FIPF. A 72-year-old woman, diagnosed with FIPF, had been followed up for 5 years. The patient experienced increased dyspnea within a 1-month period and was referred to our hospital. The patient was hypoxic, and chest computed tomography showed rapidly expanding bilateral reticular shadows. Despite pulse-steroid and intravenous-cyclophosphamide therapy, the patient died 25 days after admission. On admission, serum periostin levels were not significantly elevated, while serum fibrotic marker levels were elevated. Immunohistochemical analysis of the lungs on autopsy showed marked accumulation of periostin in the active fibrotic lesions, whereas intact and burned-out areas did not show significant expression of periostin. This case might provide insight into the role of periostin in acute exacerbation of IPF.

Background: Although the association between nontuberculous mycobacterial lung disease (NTM-LD) and malnutrition is known, there are a few reports on the association between the nutritional score and death in patients with NTM-LD. This study investigated the association between the nutrition data at the time of NTM-LD diagnosis and death. Methods: A retrospective study was conducted for patients with NTM-LD who visited the Maebashi Red Cross Hospital from January 2014 to December 2018. The patients were divided into the survival and death groups and analyzed statistically. Results: The diagnostic criteria for NTM-LD were met by 150 patients. The median age was 70 years (range, 20-94 years). There were 51 (34.0%) men and 99 (66.0%) women. In the death group, the body mass index was significantly low, and there were significantly more patients with asthma. Further, computed tomography at the first visit revealed significantly fewer cases of the nodular bronchiectasis type. In the hematologic examination at the time of NTM-LD diagnosis, the white blood cell, neutrophil, and platelet counts and C-reactive protein and serum calcium levels were significantly higher in the death group, while the serum albumin level was significantly lower. In the death group, the prognostic nutritional index (PNI), calculated from the hematologic findings, was significantly lower, while the Glasgow Prognostic Score (GPS) was significantly higher. A logistic regression analysis was performed on items with significant differences, and the PNI and platelet count were independent factors predicting death. Conclusions: PNI might be effective as a prognostic factor for NTM-LD.

Immune reconstitution inflammatory syndrome (IRIS) is an immune reaction that occurs along with the recovery of the patient’s immunity. Tuberculosis-related IRIS (TB-IRIS) upon tumor necrosis factor (TNF)-α inhibitor treatment has been reported in non-human immunodeficiency virus (HIV) patients. However, the importance of biological treatment, as a risk factor of IRIS, has not yet been established. In this study, we examined TB-IRIS in non-HIV patients to explore the role of TNF-α inhibitor treatment. Out of 188 patients with pulmonary TB, seven patients had IRIS. We examined univariate logistic and multivariate analysis to elucidate risk factors of TB-IRIS. Univariate analysis indicated that usage of immunosuppressive drugs, TNF-α inhibitors, and history of food or drug allergy were significantly related with TB-IRIS. On initial treatment, the values of serological markers such as serum albumin and serum calcium were significantly related with TB-IRIS. There was a higher mortality rate in patients with TB-IRIS. Furthermore, multivariate analysis revealed that usage of TNF-α inhibitors, history of allergy, and serum hypercalcemia were related to TB-IRIS. Usage of TNF-α inhibitors, history of allergy, and serum hypercalcemia may be independent predictors of TB-IRIS in non-HIV patients. Since higher mortality has been reported for TB-IRIS, we should pay attention to TB patients with these risk factors.