Shinji Motojima

Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis

Objectives Biological therapy represents important advances in alleviating rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has been controversial. The objective of this study was to assess the risk of such treatment for patients with ILD. Design Case–control cohorts. Setting Single centre in Japan. Participants This study included 163 patients with RA who underwent biological therapy. Outcome measured We assessed chest CT before initiation of biological therapy and grouped 163 patients according to the presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we evaluated serial changes of chest CT after treatment and visually assessed the emergence of ILD or its progression, which was referred to as an ‘ILD event’. Then, we also classified the patients according to the presence of ILD events and analysed their characteristics. Results Tumour necrosis factor (TNF) inhibitors were administered to more patients with ILD events than those without ILD events (88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and that proportion was greater than for those without pre-existing ILD (24% vs 3%, p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four patients developed generalised lung disease and two died from ILD progression. Baseline levels of KL-6 were similar in both groups, but increased in patients with ILD events. Conclusions TNF inhibitors have the potential risk of ILD events, particularly for patients with pre-existing ILD, and KL-6 is a valuable surrogate marker for detecting ILD events. Our data suggest that non-TNF inhibitors are a better treatment option for these patients.

Effect of glucocorticoid monotherapy on pulmonary function and survival in Japanese patients with scleroderma-related interstitial lung disease

BACKGROUNDnScleroderma-related interstitial lung disease (SSc-ILD) is a chronic, progressive condition that is characterized by a restrictive ventilator defect. Cyclophosphamide (CYC), with or without glucocorticoid, effectively alters the course of SSc-ILD. However, the effect of glucocorticoid monotherapy remains unclear.nnnMETHODSnSeventy-one patients with SSc-ILD were classified into 2 groups: 21 in the treatment group (glucocorticoid monotherapy [n=14] or immunosuppressive agents [n=7]) and 50 in the non-treatment group. Their backgrounds and prognoses were analyzed retrospectively. We also classified these patients into survival (n=55) and non-survival (n=16) groups to assess prognostic factors.nnnRESULTSnThe median follow-up period was 9.8 years. The treatment group had a greater proportion of patients with diffuse systemic sclerosis or respiratory symptoms than the non-treatment group. The treatment groups annual change in forced vital capacity (FVC) compared to baseline, which was 170.4mL (157.8mL for the glucocorticoid monotherapy subgroup and 191.3mL for the immunosuppressive agent subgroup), was better than that of the non-treatment group, -60.8mL (p<0.01). Still, in terms of 5- and 10-year survival, there was no statistically significant difference between these groups. No incidence of SSc renal crisis was reported in the treatment group. The non-survival group included more patients with pulmonary hypertension than the survival group, but multivariate analysis showed no other statistically significantly difference between these groups.nnnCONCLUSIONSnSimilar to CYC, glucocorticoid alone improved pulmonary function of Japanese SSc-ILD patients, suggesting that this monotherapy is a good alternative when CYC is contraindicated.

Possible effect of abatacept on the progression of interstitial lung disease in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a generally progressive, systemic autoimmune condition characterized by chronic erosive synovitis. Interstitial lung disease (ILD) is a common extraarticular manifestation of RA and is substantially more likely to cause morbidity and mortality [1]. Several diseasemodifying anti-rheumatic drugs and numerous biological therapies for RA have been widely used. These treatments, targeted at alleviating symptoms and preventing joint destruction, represent an important advancement in RA treatment [2,3]. However, these agents pose a potential risk to RA patients, with ILD having been reported [4,5]. Furthermore, the optimal treatment of RA-ILD has not been determined.

Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

BackgroundNon-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP.MethodsA total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients’ characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups.ResultsBased on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group.ConclusionsConventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality. The most important factor to improve the mortality of non-HIV PCP is early diagnosis and starting of specific-PCP therapy as soon as possible.

Associations between peripheral blood eosinophil counts in patients with systemic sclerosis and disease severity

Increased levels of serum pro-fibrotic cytokines have been reported in patients with systemic sclerosis (SSc). Some of these cytokines also play an important role in the differentiation and migration of eosinophils. The aim of this study was to determine whether eosinophilic inflammation is caused in SSc. We retrospectively reviewed the peripheral blood eosinophil counts in 70 untreated patients with SSc and compared them with those in patients with other major collagen diseases. We additionally evaluated a possible association with disease severity. Eosinophil counts were significantly higher levels in patients with SSc than in those with other collagen diseases, whereas total leukocyte counts were not. Eosinophil counts correlated positively with both severe interstitial lung disease (ILD; rxa0=xa00.255, pxa0=xa00.033) and modified Rodnan total skin thickness score (m-Rodnan TSS) in SSc (rxa0=xa00.347, pxa0=xa00.003), but did not correlate with ILD severity in other collagen diseases. In conclusion, peripheral eosinophil counts were higher in patients with SSc than in those with other collagen diseases and were correlated with increased disease severity. Our data suggest that eosinophilic inflammation is involved in the pathogenesis and progression of SSc.