Yumiko Sasaki

Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. Recently, pirfenidone was reported to slow the rate of decline in vital capacity and improve progression-free survival in IPF. The purpose of this study was to clarify the factors that predicted a good response to pirfenidone, as well as its adverse effects. METHODS Forty-one IPF cases, treated with pirfenidone from January 2009 to January 2011, were enrolled in this investigation. Disease severity was classified into grades I-IV, as defined by the Japanese Respiratory Society (JRS). Short-term responsiveness to pirfenidone was evaluated by the modified criteria of the JRS. Predictors of nausea, anorexia, or both that represented important adverse effects were examined by multivariate Cox proportional hazard analyses. Predictors of short-time responsiveness were examined by multivariate logistic regression analyses. RESULTS Diagnosed by a surgical lung biopsy (SLB), the mild cases of grade I/II were predictors of good, short-term responsiveness. Patients taking acid-secretion inhibitors, including proton pump inhibitors and histamine H2-receptor antagonists, showed less anorexia, nausea, or both. Only 1 case was administered drugs to activate gastrointestinal motility. CONCLUSIONS We concluded that IPF patients with a mild disease, diagnosis by SLB, or both showed indications of a good response to pirfenidone. In addition, acid-secretion inhibitors may reduce the frequency of anorexia, nausea, or both from pirfenidone.

Heterogeneity of incidence and outcome of acute exacerbation in idiopathic interstitial pneumonia.

Acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonia (IIP) have a poor prognosis. This study aims to clarify the incidence and prognosis of AE in IPF and the other IIP.

Tracheobronchial lesions in eosinophilic pneumonia

BACKGROUND Eosinophilic pneumonia (EP) is characterized by eosinophil infiltration in the lung parenchyma. However, tracheobronchial lesions associated with the disease have been poorly described. To clarify the frequency and characteristics of cases with tracheobronchial lesions in EP, we performed a retrospective review of EP patients. METHODS We included 36 EP cases seen from January 2004 to December 2007 at the Kinki-Chuo Chest Medical Center. The incidence of tracheobronchial nodules and associated clinical features were analyzed. RESULTS Of these 36 patients, 29 had chronic eosinophilic pneumonia (CEP); 1, acute EP; 3, drug-induced EP; 2, allergic bronchopulmonary aspergillosis; and 1, parasite-related EP. Only 2 of the 29 CEP cases had tracheobronchial lesions. For both of these cases, bronchoscopy revealed multiple whitish nodules on the tracheobronchial mucosa. The associated histopathological findings revealed squamous metaplasia and eosinophil infiltration in the subepithelial region. In both cases, the nodules disappeared after steroid therapy. The prevalence of tracheobronchial lesions was 6.9% in CEP patients and 5.6% in EP patients overall. EP patients were divided into 3 groups: CEP with nodules (n=2), CEP without nodules (n=27), and other EP (n=7). We found that the CEP with nodules group showed a relatively higher incidence of respiratory symptoms, higher white blood cell (WBC) count, and higher levels of peripheral and bronchoalveolar eosinophilia than the other groups. CONCLUSIONS Tracheobronchial nodules represent rare observations within the EP population, which are likely to reflect a severe disease condition.

Cytomegalovirus infection during immunosuppressive therapy for diffuse parenchymal lung disease.

Background and objective:  Cytomegalovirus (CMV) infection is a life‐threatening condition in patients with diffuse parenchymal lung diseases (DPLDs), who are receiving immunosuppressive therapy. The aim of this study was to describe the clinical features of CMV infection and to propose a strategy for managing CMV infection in patients with DPLD who are receiving immunosuppressive therapy.

Severe acute interstitial lung disease after nivolumab in three non-small cell lung cancer patients with imaging findings of airway obstruction adjacent to lung tumors

Nivolumab has been associated with unique adverse events known as immune-related adverse events. Although interstitial lung disease (ILD) is a life-threatening immune-related adverse event, the risk of ILD during nivolumab treatment is unclear. In this report, we encountered three patients with stage IV non-small cell lung cancer with signs of lung obstruction caused by tumor-mediated compression on imaging who developed acute ILD within 10 days of commencing nivolumab treatment. The first case involved a 74-year-old Japanese female never-smoker, the second a 67-year-old Japanese female never-smoker, and the third a 75-year-old Japanese female current-smoker. The first patient was administered nivolumab as third-line chemotherapy, the second was administered nivolumab as fifth-line chemotherapy, and the third was administered nivolumab as second-line chemotherapy. Regardless of aggressive treatments for ILD, 2 of 3 patients died. The findings of these cases suggest that obstructive findings in the lungs, which easily cause infections, may be an important risk factor for nivolumab-induced ILD.

Change in lung function in never-smokers with nontuberculous mycobacterial lung disease: A retrospective study

Purpose Never-smokers account for a large proportion of subjects in general population studies on nontuberculous mycobacteria lung disease (NTM-LD). However, the influence of NTM infection on the lung function of never-smokers has not yet been evaluated. The aim of this study was to determine how NTM-LD impairs the lung function in never-smokers, and whether there are an association between successful NTM-LD treatment in radiologic outcomes and improvement in lung function of never-smokers with NTM-LD or not. Methods We performed a retrospective study of patients (1) who have never smoked during their lifetime; (2) with at least two respiratory specimens from sputum, one bronchial washing sample, or one lung tissue that were culture positive for the same NTM species; and (3) who underwent at least two pulmonary function tests. We enrolled healthy never-smokers as the control group. Results In 22 never-smokers with NTM-LD, the median forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at baseline was lower than those in 9 healthy never-smokers [1800 vs 2080 ml (p = 0.23) and 2230 vs 2620 ml (p = 0.06)], respectively. The median change in FEV1 in never-smokers with NTM-LD was lower than that in healthy never-smokers [−70 vs 20 ml per year (p = 0.07), respectively]. On univariate analysis, baseline %-predicted FEV1 in never-smokers with NTM-LD was associated with changes in FVC (p = 0.026) and FEV1 (p = 0.013). Anti-NTM treatment was administered for at least 1 year in 19 patients (86.4%). The relationship between worsening chest CT findings and rapid progressive decline in both FVC (p = 0.66) and FEV1 (p = 0.23) were not significant. Conclusion Never-smokers with NTM-LD showed lung function decline. There was no association between successful NTM-LD treatment in radiologic outcomes and improvement in lung function of never-smokers.

Combination of virtual bronchoscopic navigation, endobronchial ultrasound, and rapid on-site evaluation for diagnosing small peripheral pulmonary lesions: a prospective phase II study.

BACKGROUND The diagnostic yield of peripheral pulmonary lesions (PPLs) by flexible bronchoscopy (FB) is still insufficient. To improve the diagnostic yield of bronchoscopy, several techniques such as endobronchial ultrasound (EBUS), virtual bronchoscopic navigation (VBN), and rapid on-site evaluation (ROSE) have been examined. The primary purpose of the present study was to evaluate the usefulness of combining EBUS, VBN, and ROSE for diagnosing small PPLs. METHODS Patients with PPLs 30 mm or less on chest computed tomography (CT) were prospectively enrolled. We determined the responsible bronchus for the target lesions using VBN before bronchoscopy was performed. EBUS and ROSE were performed during the examination to determine whether the bronchus and specimen were adequate. On the basis of previous studies, we assumed that the diagnostic yield of 85% among eligible patients would indicate potential usefulness, whereas, the diagnostic yield of 75% would indicate the lower limit of interest. The required number of patients was estimated as 45 for a one-sided α value of 0.2 and a β value of 0.8. The primary study endpoint was the diagnostic yield. RESULTS Between June 2014 and July 2015, we enrolled 50 patients in the present study, and we excluded 5 patients. The total diagnostic yield of 45 PPLs was 77.7%. In cases of lung cancer, the diagnostic yield was 84.2%. The sensitivity, specificity, positive predictive value, and negative predictive value of ROSE were 90.6%, 92.3%, 96.7%, and 80.0%, respectively. The diagnostic yield of PPLs from 20 to 30 mm was 87.5%, and the diagnostic yield of PPLs less than 20 mm was 66.7%. PPLs for which the probe was located within the lesion had the highest diagnostic yield. CONCLUSIONS We could not demonstrate usefulness for diagnosing small PPLs by combining EBUS, VBN, and ROSE. However, combining these techniques may be useful for diagnosing lung cancer.

Corticosteroids determine clinical course of IIPs with possible UIP HRCT pattern

Background and Aims: Corticosteroids was not recommended for idiopathic pulmonary fibrosis (IPF) by IPF guideline (AJRCCM 2011). However, impact of corticosteroids on idiopathic interstitial pneumonias (IIPs) with possible usual interstitial pneumonia (UIP) HRCT pattern (IIPs/HRCT possible UIP) remains to be solved and this is the aims of this study. Subjects and Methods: Enrolled subjects of this trial were 98 cases with IIPs/HRCT possible UIP in our institute between 2005 and 2009: gender (M/F: 69/29), IPF/UIP (n=24) and Non-IPF (n=74), %FVC (median 80.6%) and %DLco (median 55.7%). Corticosteroids were introduced in 6 cases of IPF/UIP and 16 cases of Non-IPF. Impact of corticosteroids on IIPs/HRCT possible UIP was evaluated by Cox proportional hazard regression analysis. Results: Survival of IPF/UIP and Non-IPF was similar (p=0.886, Log-rank test). Survival of corticosteroids treated cases was significantly worse than that of non-treated cases both in IPF/UIP (p=0.045) and in Non-IPF (p=0.019) (Log-rank test); however, impact of corticosteroids on survival of IIPs/HRCT possible UIP was not significant after adjustment with significant prognostic factors in all cases; %FVC, %DLco and Male. Corticosteroids were not a significant predictor of AE in IPF/UIP (p=0.215), but significant in Non-IPF (p=0.007) by Log-rank test. However, impact of corticosteroids on incidence of AE was not significant after adjustment with predictors of AE in all cases; %DLco and %FVC. Conclusions: Corticosteroids did not alter the clinical course of IIPs/HRCT possible UIP. Acknowledgement: This study is partially supported by grant of National Hospital Organization and Japanese Ministry of Health Labour and Welfare.