Hideya Kitamura

Safety and efficacy of pirfenidone in idiopathic pulmonary fibrosis in clinical practice

BACKGROUND Previous pirfenidone trials have only involved patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the safety and efficacy of pirfenidone in patients with mild-to-severe IPF in clinical practice. METHODS The clinical records of 76 patients who were diagnosed with IPF and received pirfenidone were reviewed. RESULTS The most frequent adverse event was anorexia, although the grade of anorexia in most patients was mild. Dose reduction of pirfenidone improved anorexia in 84% affected patients, which resulted in a high medication compliance rate. The mean forced vital capacity (FVC) at the initiation of pirfenidone therapy in this study was approximately 10% lower than that in previous clinical trials. The mean change in FVC during the 6-month period prior to the therapy initiation was -188 mL, which improved to -19 mL during the 6-month period after therapy. Significant attenuation in percentage predicted diffusion capacity of the lung for carbon monoxide decline was also achieved after pirfenidone therapy initiation. The efficacy of pirfenidone in attenuating the degree of FVC decline was higher in the group with FVC decline of ≥150 mL during the 6-month period prior to therapy initiation. The levels of serum markers, such as KL-6 and SP-D, were also lowered by the therapy. CONCLUSIONS These results showed that pirfenidone was well-tolerated and had beneficial effects in patients with mild-to-severe and/or progressive IPF. The degree of disease progression prior to the initiation of pirfenidone therapy had an impact on the response to the therapy.

Distinct characteristics of pleuroparenchymal fibroelastosis with usual interstitial pneumonia compared with idiopathic pulmonary fibrosis.

BACKGROUND Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonia and sometimes coexists with a histologic usual interstitial pneumonia (UIP) pattern. This study aimed to describe the distinct clinical features of PPFE with UIP pattern compared with idiopathic pulmonary fibrosis (IPF). METHODS We conducted a retrospective review of the medical records of 110 consecutive patients with IPF with a histologic UIP pattern on surgical lung biopsy specimen. Patients meeting radiologic criteria for the diagnosis of PPFE based on high-resolution CT scan and with a histologic UIP pattern were included. RESULTS Nine of eleven patients meeting radiologic criteria for the diagnosis of PPFE were histologically confirmed as having PPFE with UIP pattern. The PPFE with UIP pattern group showed a significantly higher residual volume (1.8 L vs 1.3 L, P < .01), higher Paco2 (44.6 mm Hg vs 41.7 mm Hg, P = .04), and higher complication rate of pneumothorax and pneumomediastinum than the 99 patients with IPF/UIP. The ratio of anteroposterior to transthoracic diameter in patients with PPFE with UIP pattern was significantly lower than that in patients with IPF/UIP (P = .04). Survival time tended to be shorter in patients with PPFE with UIP pattern. CONCLUSIONS The results support the view that PPFE with UIP pattern is a disease entity distinct from IPF/UIP and may well be classified as PPFE.

Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis.

Myeloperoxidase anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO‐ANCA (ANCA/UIP).

A Case of Henoch-Schönlein Purpura Nephritis in Pulmonary Tuberculosis

A 38-year-old man with pulmonary tuberculosis developed purpura over both lower extremities and renal disturbance after starting antituberculosis treatment. A renal biopsy and skin biopsy were performed to diagnose the new clinical manifestations, and leukocytoclastic vasculitis with IgA and C3 deposition were detected. Henoch-Schönlein purpura nephritis (HSPN) was diagnosed on the basis of the clinical and pathologic findings, and prednisolone therapy was added. The skin lesions disappeared in 7 days after starting steroid therapy, and renal function gradually improved. These results suggested that the pathogenesis of HSPN might be the consequence of the deposition of the circulating immune complexes. The treatment of HSPN has been not established yet. We should consider how to use steroid therapy for HSPN and call attention to the recurrences of renal disturbance and pulmonary tuberculosis. It is thus recommended to follow patients with HSPN in tuberculosis for long periods.

Successful treatment with alectinib after crizotinib-induced interstitial lung disease

We herein report a case of a 46-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged stage IV lung adenocarcinoma who received the ALK inhibitor crizotinib as second-line therapy. On the 47th day following crizotinib initiation, a chest computed tomography scan revealed ground-glass opacities with a clinical manifestation of desaturation, although a partial response to treatment was detected. The diagnosis of crizotinib-induced interstitial lung disease (ILD) was confirmed, and crizotinib was discontinued, followed by the initiation of corticosteroid therapy. After improvement of ILD with corticosteroid therapy, alectinib was administered as salvage therapy, resulting in tumor shrinkage without any recurrence of ILD. To the best of our knowledge, this is the first report of successful alectinib treatment following crizotinib-induced ILD. Our results indicate that alectinib could be a promising alternative treatment option in patients with crizotinib-induced ILD.

Co-exposure to refractory ceramic fibres and asbestos and risk of pleural mesothelioma

The aim of this study was to investigate the hypothesis of an increased risk of pleural mesothelioma due to co-exposure to asbestos and refractory ceramic fibres (RCF) compared to asbestos exposure alone. Males were selected from a French case–control study conducted in 1987–1993 and from the French National Mesothelioma Surveillance Program in 1998–2006. Two population controls were frequency matched to each case by year of birth. Complete job histories were collected and occupational asbestos and RCF exposures were assessed using job exposure matrices. The dose–response relationships for asbestos exposure were estimated from an unconditional logistic regression model in subjects exposed to asbestos only (group 1) and subjects exposed to both asbestos and RCF (group 2). A total of 988 cases and 1125 controls ever-exposed to asbestos were included. A dose–response relationship was observed in both groups but it was stronger in group 2. In comparison with subjects exposed at the minimum value of the cumulative index of exposure, the odds ratio was 2.6 (95% CI 1.9–3.4) for subjects exposed to 75 fibres·mL−1·year−1 in group 1 increasing to 12.4 (95% CI 4.6–33.7) in group 2. Our results suggest that the pleural carcinogenic effect of occupational asbestos exposure may be modified by additional exposure to RCF. Increased pleural mesothelioma risk due to asbestos and refractory ceramic fibre co-exposure compared to asbestos http://ow.ly/yAx2D

Hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis: A single-center experience

In Japan, nintedanib was approved for idiopathic pulmonary fibrosis (IPF) and was clinically used from September 2015. However, we have often encountered drug-induced hepatotoxicity, which has required interruptions and/or dose reductions. Therefore, the objectives of this study were to investigate the incidence of drug-induced hepatotoxicity following the commercialization of nintedanib and to clarify the treatment status of nintedanib in our hospital.

Pilot quasi-randomized controlled study of herbal medicine Hochuekkito as an adjunct to conventional treatment for progressed pulmonary Mycobacterium avium complex disease.

Introduction Hochuekkito, a traditional herbal medicine, is occasionally prescribed in Japan to treat patients with a poor general condition. We aimed to examine whether this medicine was beneficial and tolerable for patients with progressed pulmonary Mycobacterium avium complex (MAC) disease. Methods This pilot open-label quasi-randomized controlled trial enrolled 18 patients with progressed pulmonary MAC disease who had initiated antimycobacterial treatment over one year ago but were persistently culture-positive or intolerant. All patients continued their baseline treatment regimens with (n = 9) or without (n = 9) oral Hochuekkito for 24 weeks. Results Baseline characteristics were generally similar between the groups. Most patients were elderly (median age 70 years), female, had a low body mass index (<20 kg/m2), and a long-term disease duration (median approximately 8 years). After the 24-week treatment period, no patient achieved sputum conversion. Although the number of colonies in sputum tended to increase in the control group, it generally remained stable in the Hochuekkito group. Radiological disease control was frequently observed in the Hochuekkito group than the control group (8/9 vs. 3/9; p = 0.05). Patients in the Hochuekkito group tended to experience increase in body weight and serum albumin level compared with those in the control group (median body weight change: +0.4 kg vs. −0.8 kg; median albumin change: +0.2 g/dl vs. ±0.0 g/dl). No severe adverse events occurred. Conclusions Hochuekkito could be an effective, feasible adjunct to conventional therapy for patients with progressed pulmonary MAC disease. Future study is needed to explore this possibility. Trial Registration UMIN Clinical Trials Registry UMIN000009920

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis.

Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD.

An exploratory trial of intravenous immunoglobulin therapy for idiopathic pulmonary fibrosis: a preliminary multicenter report

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without specific treatments. Although the efficacy of intravenous immunoglobulin (IVIG) therapy for autoimmune diseases has been reported, that for IPF remains unknown. This study aims to determine the efficacy and safety of IVIG for IPF.