Cardiorespiratory fitness and body mass index on metabolic syndrome in middle-aged Japanese adults under national health guidance: a cross-sectional study.

OBJECTIVES: Poor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults. METHODS: 421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS. RESULTS: Results showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with 'unfit and higher BMI' group, 'unfit and lower BMI', 'fit and higher BMI', and 'fit and lower BMI' groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women. CONCLUSIONS: This study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS.

Effects of small community walking intervention on physical activity, well-being, and social capital among older patients with cardiovascular disease in the maintenance phase: a randomized controlled trial.

[Purpose] Older patients with cardiovascular disease should increase their physical activity and prioritize positive psychological and social approaches in the maintenance phase of their cardiac rehabilitation. This study aimed to clarify the effect of small community walking on physical activity, well-being, and social capital in older patients with cardiovascular disease in the maintenance phase. [Participants and Methods] We conducted a multicenter study in Kumamoto, Japan. We randomly divided 55 patients with cardiovascular disease into two groups: small community walking and walking alone. For three months, a registered cardiac rehabilitation instructor provided walking guidance to both groups using a wearable device. We measured physical activity, social capital, and subjective happiness before and after the intervention. [Results] Results revealed a statistically significant main effect of time on physical activity and social participation. In the subjective happiness scale, there was an association between group and time. [Conclusion] Our results suggest that walking guidance using a wearable device was beneficial in improving overall physical activity, regardless of whether the individual did small community walking or walking alone. Furthermore, small community walking intervention may effectively enhance well-being. The relationship between physical activity and social participation needs to be further investigated.

Effects of Long-Term High-Ergosterol Intake on the Cholesterol and Vitamin D Biosynthetic Pathways of Rats Fed a High-Fat and High-Sucrose Diet.

Dyslipidemia is a lifestyle-related (physical inactivity or obesity) disease; therefore, dietary foods that can easily be consumed in daily life is important to prevent dyslipidemia. Ergosterol, a precursor of vitamin D2, is a fungal sterol present in the membranes of edible mushrooms and other fungi. Ergosterol is converted to brassicasterol by 7-dehydrocholesterol reductase (DHCR7), a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D3) into cholesterol. Previously, we reported that ergosterol increases 7-dehydrocholesterol, decreases cholesterol levels by competitive effect of DHCR7, and reduces DHCR7 mRNA and protein levels in human HepG2 hepatoma cells. Here, we investigated the effects of long-term high ergosterol intake on the cholesterol, vitamin D2, and D3 biosynthetic pathways of rats fed a high-fat and high-sucrose (HFHS) diet using GC-MS and LC with tandem mass spectrometry. In HFHS rats, oral ergosterol administration for 14 weeks significantly decreased plasma low-density lipoprotein cholesterol, total bile acid, and cholesterol precursor (squalene and desmosterol) levels and increased 7-dehydrocholesterol levels compared to HFHS rats without ergosterol. Ergosterol, brassicasterol, and vitamin D2 were detected, cholesterol levels were slightly decreased, and levels of vitamin D3 and its metabolites were slightly increased in rats fed HFHS with ergosterol. These results showed that ergosterol increased vitamin D2 levels, inhibited the cholesterol biosynthetic pathway, and possibly promoted vitamin D3 biosynthesis in vivo. Therefore, daily ergosterol intake may aid in the prevention of dyslipidemia.

New aspects of clinical and immunological characteristics in patients with anti-asparaginyl tRNA synthetase (anti-KS) autoantibody.

OBJECTIVES: Anti-asparaginyl tRNA synthetase (anti-KS) antibody is present in patients with interstitial lung disease (ILD) accompanied by polymyositis/dermatomyositis. We examined clinical/immunological features of these patients. METHODS: Polymyositis/dermatomyositis or ILD patients were screened for autoantibodies, and clinical/immunological data were collected retrospectively. ILD was diagnosed by computed tomography, and clinical/immunological features of anti-KS-positive patients were compared with those of anti-Jo-1-positive patients. RESULTS: Sixteen anti-KS-positive patients [female = 11; male = 5; average age 63.6 years (range, 40-81) years] were diagnosed: seven had ILD, four had clinically amyopathic DM (CADM) and ILD, three had Sjögren's syndrome (SS) and ILD one each had rheumatoid arthritis and ILD, or CADM/SS overlap and ILD. All patients had ILD with chronic onset and clinical course; 11/16 (69%) had nonspecific interstitial pneumonia, and five (31%) had usual interstitial pneumonia pattern. Regarding skin manifestations, 4 (27%) had typical DM rash and 11 (69%) had mechanic's hands. All anti-KS-positive patients had no clinical muscle weakness or serum creatine kinase elevation; 8/16 patients (50%) had sicca symptoms at a significantly high frequency compared with anti-Jo-1-positive patients (50% vs 11%, P = 0.01). CONCLUSIONS: Anti-KS-positive patients might form a distinguishable subset closely associated with sicca symptoms, CADM and chronic-type ILD with a relatively favourable prognosis.

Determinants of Peak Oxygen Uptake at Each Stage of Renal Dysfunction in Patients with Heart Disease.

Background: Identifying the causes of low peak oxygen uptake (peak V̇ O 2 ) in heart disease patients with renal dysfunction is necessary for prognostic improvement strategies. The purpose of this study was to verify the determinants of peak V̇ O 2 for each stage of renal function in heart disease patients, focusing on end-tidal oxygen partial pressure ( PETO 2 ). Methods: Two hundred fifty heart disease patients who underwent cardiopulmonary exercise testing (CPET) in our institution were consecutively enrolled. Patients were divided into three groups by their estimated glomerular filtration rate (eGFR): < 45, 45-59 and ≥ 60 mL/min/1.73 m 2 . Patient characteristics and CPET parameters including Δ 2 (rest-anaerobic threshold) were compared between the groups. The relationship between Δ PETO PETO 2 and peak V̇ O 2 was also investigated for each group. Results: In total, 201 patients were analyzed. Δ PETO 2 decreased with the deterioration of renal function (eGFR < 45, 0.1 mmHg vs. eGFR 45-59, 2.4 mmHg vs. eGFR ≥ 60, 5.2 mmHg, p < 0.001). In the eGFR < 45 group, left ventricular ejection fraction (LVEF) and hemoglobin (Hb) were significantly associated with peak V̇ O 2 ß = 0.518, p < 0.001 and ß = 0.567, p < 0.001, respectively), whereas Δ PETO 2 was not. In the eGFR 45-59 group, age, Hb, and Δ PETO 2 showed a significant association with peak V̇ O 2 ( ß = -0.354, p = 0.006; ß = 0.258, p = 0.007; ß = 0.501, p < 0.001; respectively). In the univariate analysis, eGFR 45-59 group showed the highest coefficient of determination of Δ PETO 2 to peak V̇ O 2 ( R 2 = 0.247, p < 0.001). Conclusions: The determinants of peak V̇ O 2 in heart disease patients depended on the stage of renal function. The determinants of peak V̇ O 2 in patients with eGFR < 45 were LVEF and Hb, while Δ PETO 2 was the strongest predictor of peak V̇ O 2 in patients with eGFR 45-59.

New Inhibitory Effect of Latilactobacillus sakei UONUMA on the Cholesterol Biosynthesis Pathway in Human HepG2 Cells.

Many pharmaceuticals and dietary foods have been reported to inhibit cholesterol biosynthesis, mainly by inhibiting the presqualene enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase rather than a postsqualene enzyme. In this study, we examined the inhibitory effects of Latilactobacillus sakei UONUMA on cholesterol biosynthesis, especially postsqualene, in human HepG2 hepatoma cells. We quantified cholesterol and its precursors, and the mRNA and protein levels of enzymes involved in cholesterol biosynthesis. Three L. sakei UONUMA strains exhibited new inhibitory effects on cholesterol biosynthesis and inhibited the mRNA level of sterol-delta24-reductase (DHCR24), which is involved in the postsqualene cholesterol biosynthesis pathway. These strains will be useful for the prevention and treatment of hyperlipidemia.

Relationship of end-tidal oxygen partial pressure to the determinants of anaerobic threshold in post-myocardial infarction patients.

The anaerobic threshold (AT), obtained during cardiopulmonary exercise testing (CPET), is an important prognostic measure and can be used to develop an exercise prescription in patients after a myocardial infarction (post-MI). The purpose of this study was to examine the central and peripheral determinants of AT in post-MI patients end-tidal oxygen partial pressure (PETO2) measures. We performed cardiopulmonary exercise testing (CPET) on 148 consecutively enrolled post-MI patients to determine PETO2 measured at the AT (AT PETO2) and ΔPETO2 (difference between resting PETO2 and AT PETO2). We subsequently investigated the relationship between these measures of PETO2 and the individual AT for each patient. Multivariate linear regression analysis indicated that AT PETO2 and ΔPETO2 were independently and significantly associated with the AT (ß = -0.344, p < 0.001 and ß = 0.228, p < 0.001, respectively). Furthermore, the independent factors of AT PETO2 were left ventricular ejection fraction (p = 0.005), resting ventilatory equivalent for carbon dioxide (p = 0.002), and resting dead-space gas volume to tidal volume ratio (p < 0.001). However, the independent factors for ΔPETO2 were history of diabetes (p = 0.047), estimated glomerular filtration rate (p = 0.001), and resting systolic blood pressure (p = 0.017). These findings suggested that AT PETO2 was associated with central determinants; whereas, and ΔPETO2 was associated with peripheral determinants, The AT PETO2 and ΔPETO2 provide variable insight regarding the cause of exercise intolerance and can be used to determine appropriate therapies.

Identification of dipyrrolone pigments and their precursors formed in the Maillard reaction of carnosine and pentose under weakly acidic conditions.

Colored compounds formed by the Maillard reaction of carnosine with xylose or glucose were investigated in this study. Yellow pigments showing an absorption maximum at 450 nm were found in a heated solution of carnosine with xylose at pH 5.0. These pigments were then isolated and identified as dicarnosyl-dipyrrolones A and B. The generation of dipyrrolones in the absence of lysine suggests that dipyrrolone pigments can be formed by pentose as well as every amino compound such as amino acids, peptides and proteins possessing a free amino group. Analysis of α-dicarbonyls using LC-MS/MS showed that pentosone, 1-deoxypentosone, 3-deoxypentosone (3-DP), and methylglyoxal were predominantly generated via degradation of Amadori compounds. Also, a potential formation pathway of dypyrrolones was established, indicating that an Amadori compound that could form 3-DP is likely to play a role as a main precursor for dipyrrolones.

Effects of social network incentives and financial incentives on physical activity and social capital among older women: a randomized controlled trial.

BACKGROUND: Financial incentives have been used to increase physical activity. However, the benefit of financial incentives is lost when an intervention ends. Thus, for this study, we combined social network incentives that leverage the power of peer pressure with financial incentives. Few reports have examined the impact of physical activity on social capital. Therefore, the main goal of this study was to ascertain whether a combination of two incentives could lead to more significant changes in physical activity and social capital during and after an intervention. METHODS: The participants were 39 older women over 65 years of age in Kumamoto, Japan. The participants were randomly divided into a financial incentive group (FI group) and a social network incentive plus financial incentive group (SNI + FI group). Both groups underwent a three-month intervention. Measurements of physical activity and social capital were performed before and after the intervention. Additionally, the effects of the incentives on physical activity and social capital maintenance were measured 6 months postintervention. The financial incentive group received a payment ranging from US$4.40 to US$6.20 per month, depending on the number of steps taken during the intervention. For the other group, we provided a social network incentive in addition to the financial incentive. The SNI + FI group walked in groups of three people to use the power of peer pressure. RESULTS: A two-way ANOVA revealed that in terms of physical activity, there was a statistically significant interaction between group and time (p = 0.017). The FI group showed no statistically significant improvement in physical activity during the observation period. In terms of the value of social capital, there was no significant interaction between group and time. CONCLUSION: Our results suggest that social network incentives, in combination with financial incentives, are more effective for promoting physical activity than financial incentives alone among older women and that these effects can continue after an intervention. In the meantime, further studies should be conducted on the effect of physical activity on social capital. TRIAL REGISTRATION: UMIN000038080 , registered on 09/22/2019 (Retrospectively registered).

Arterial spin labeling magnetic resonance imaging at short post-labeling delay reflects cerebral perfusion pressure verified by oxygen-15-positron emission tomography in cerebrovascular steno-occlusive disease.

BACKGROUND: Arterial transit time correction by data acquisition with multiple post-labeling delays (PLDs) or relatively long PLDs is expected to obtain more accurate imaging in cases of the cerebrovascular steno-occlusive disease. However, there have so far been no reports describing the significance of arterial spin labeling (ASL) images at short PLDs regarding the evaluation of cerebral circulation in ischemic cerebrovascular disease. PURPOSE: To clarify the role of short-PLD ASL in cerebrovascular steno-occlusive disease. MATERIAL AND METHODS: Fifty-three patients with cerebrovascular steno-occlusive disease were included in this study. All patients underwent ASL magnetic resonance imaging and 15O-PET within two days of each modality. To compare the ASL findings with each parameter of PET, the right-to-left (R/L) ratio, defined as the right middle cerebral artery (MCA) value/left MCA value, was calculated. RESULTS: There is a significant correlation between the ASL images at a short PLD and the ratio of cerebral blood flow and cerebral blood volume by 15O-PET, which may accurately reflect the cerebral perfusion pressure. A receiver operating characteristic curve analysis indicated that ASL images at PLD 1000 and 1500 ms were more accurate than at PLD 2000-3000 ms for the detection of a ≥10% change in the PET cerebral blood flow. CONCLUSION: ASL images at shorter PLDs may be useful at least as a screening modality to detect the changes in the cerebral circulation in cerebrovascular steno-occlusive disease. We must evaluate ASL images at multiple PLDs while considering the arterial transit time of each case at present.

Clinical characteristics of cancer-associated myositis complicated by interstitial lung disease: a large-scale multicentre cohort study.

OBJECTIVE: To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. RESULTS: CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation-associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). CONCLUSION: Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.

Identification of a Novel Pyrrole Alkaloid from the Edible Mushroom Basidiomycetes-X (Echigoshirayukidake).

Three pyrrole alkaloid derivatives were isolated from the edible mushroom Basidiomycetes-X (Echigoshirayukidake) by water extraction followed by ethyl acetate fractionation. The chemical structures determined by MS and NMR were 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (compound I), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanamide (compound II), and 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (compound III). Compound I was found to be the major component, followed by compound II, and compound III was the minor component. The dry powder of Basidiomycetes-X contained approximately 825 µg g-1 compound I and 484 µg g-1 compound II. Compound II was found to be a novel pyrrole aldehyde homologue not previously reported and thus is a specific component of this mushroom.

Exploring disease-specific methylated CpGs in human male genital abnormalities by using methylated-site display-amplified fragment length polymorphism (MSD-AFLP).

The incidence of male reproductive system disorders, especially hypospadias, has been increasing in developed countries since the latter half of the 20th century. Endocrine-disrupting chemicals from the environment are considered to be involved in hypospadias onset through epigenetic alterations. This pilot study aimed to explore disease-specific methylated CpGs in human patient samples using the methylated-site display-amplified fragment length polymorphism (MSD-AFLP) technique developed by our research group [1]. We compared clinical samples from hypospadias and phimosis patients. Foreskin and blood samples were collected from one- to two-year-old patients with hypospadias (N = 3) and phimosis (N = 3) during surgical treatment. MSD-AFLP analysis showed significantly decreased CpG-methylation levels of genes such as MYH11 and increased CpG-methylation levels of genes such as PLA2G15 in hypospadias patients. Hierarchical clustering analysis showed that genes with significantly altered CpG levels were more markedly altered in DNA from blood than from foreskin. Because of the small number of samples, further investigation is necessary to elucidate the association between variations in CpG levels in foreskin and blood DNA and male genital abnormalities. However, our MSD-AFLP method appears to be a useful tool for exploring disease-specific methylated-CpGs in human epidemiological studies.

[A Case of Recurrent Gallbladder Carcinoma Treated with Resection and Hepatic Arterial Infusion].

A 69-year-old woman underwent extended cholecystectomy for gallbladder cancer[T2N0M0, fStage Ⅱ(UICC 7th edition)]. She was then administered adjuvant S-1 and was treated for drug-induced neutropenia. One year later, recurrent lesions were detected in liver S4 and S5. We treated the patient with hepatectomy and hepatic arterial infusion adjuvant chemotherapy by cisplatin, along with the systemic administration of gemcitabine for 10 months. The patient is now doing well without any sign of recurrence 29 months after the initial operation and 16 months after the secondary liver resection.

Pretreatment evaluation of fluorescence resonance energy transfer-based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib.

Tyrosine kinase inhibitors (TKI) are used for primary therapy in patients with newly diagnosed CML. However, a reliable method for optimal selection of a TKI from the viewpoint of drug sensitivity of CML cells has not been established. We have developed a FRET-based drug sensitivity test in which a CrkL-derived fluorescent biosensor efficiently quantifies the kinase activity of BCR-ABL of living cells and sensitively evaluates the inhibitory activity of a TKI against BCR-ABL. Here, we validated the utility of the FRET-based drug sensitivity test carried out at diagnosis for predicting the molecular efficacy. Sixty-two patients with newly diagnosed chronic phase CML were enrolled in this study and treated with dasatinib. Bone marrow cells at diagnosis were subjected to FRET analysis. The ΔFRET value was calculated by subtraction of FRET efficiency in the presence of dasatinib from that in the absence of dasatinib. Treatment response was evaluated every 3 months by the BCR-ABL1 International Scale. Based on the ΔFRET value and molecular response, a threshold of the ΔFRET value in the top 10% of FRET efficiency was set to 0.31. Patients with ΔFRET value ≥0.31 had significantly superior molecular responses (MMR at 6 and 9 months and both MR4 and MR4.5 at 6, 9, and 12 months) compared with the responses in patients with ΔFRET value <0.31. These results suggest that the FRET-based drug sensitivity test at diagnosis can predict early and deep molecular responses. This study is registered with UMIN Clinical Trials Registry (UMIN000006358).

Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients.

OBJECTIVE: To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ⩾16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. RESULTS: JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ⩾60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ⩾1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). CONCLUSION: We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality.

Rapid reduction in BCR-ABL1 transcript predicts deep molecular response in dasatinib-treated chronic-phase chronic myeloid leukaemia patients.

OBJECTIVES: We conducted a phase-II study to evaluate the efficacy and safety of dasatinib in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP) in Japan (IMIDAS PART 2 study). METHODS: Seventy-nine patients were administered 100 mg dasatinib once daily. We examined pretreatment and post-treatment influences of various factors. The BCR-ABL1 international scale (IS), halving time (HT) and reduction rate of BCR-ABL1 transcript within the initial 1 or 3 months of therapy (RR-BCR-ABL11m,3m ) were the post-treatment factors investigated to predict the molecular response. RESULTS: The estimated major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) rates were 77.2%, 49.4% and 35.4%, respectively, at 12 months. Grade 3/4 non-haematologic adverse events were infrequent. Multivariate analysis showed that age >65 years was significantly correlated with MR4.0 and MR4.5 (deep molecular response: DMR) at 12 months. All post-treatment factors at 3 months predicted DMR by univariate analysis. However, RR-BCR-ABL13m was the only significant landmark for predicting DMR by multivariate analysis. CONCLUSIONS: Primary treatment of CML-CP with dasatinib enabled early achievement of MMR and DMR, particularly in elderly patients, with high safety. Furthermore, RR-BCR-ABL13m was found to be a more useful predictor of DMR than HT-BCR-ABL1 and BCR-ABL1 IS.

Prognostic factors and disease behaviour of pathologically proven fibrotic non-specific interstitial pneumonia.

BACKGROUND AND OBJECTIVE: Non-specific interstitial pneumonia (NSIP) has heterogeneous characteristics in terms of background, disease behaviour and prognosis. This study of fibrotic NSIP (f-NSIP) aimed to elucidate prognosis and disease behaviour from the viewpoint of clinical background and determine whether long-term change of pulmonary function could provide useful prognostic information. METHODS: We analysed the medical records of 157 consecutive patients diagnosed with f-NSIP by surgical lung biopsy. Disease behaviour was categorized into two groups depending on long-term change of pulmonary function: progressive type (relative ≥5%/year decline in the slope of forced vital capacity and/or relative ≥7.5%/year decline in the slope of %diffusing capacity of lung carbon monoxide) or stable type. Predictors of disease behaviour and prognosis were determined using logistic and Cox regression models. RESULTS: Our f-NSIP cohort included interstitial pneumonia with autoimmune features (IPAF) (36.9%), idiopathic (non-IPAF) (22.3%) and connective tissue disease-associated interstitial lung disease (40.8%). Multivariate analysis showed that idiopathic (non-IPAF) f-NSIP and progressive type disease were negative prognostic factors of mortality. Poor treatment response at 1 year was an independent predictor of progressive type disease, but was not related to survival. In terms of disease behaviour based on pulmonary function change, some patients with IPAF f-NSIP showed a progressive course. CONCLUSION: Although an IPAF diagnosis was useful for identifying good prognosis in idiopathic f-NSIP, some idiopathic f-NSIP patients with or without IPAF showed progressive disease despite therapy. The definition of progressive type disease may be useful in clinical decision-making when determining therapy for f-NSIP.

Predictive Factors for the Long-Term Deterioration of Pulmonary Function in Interstitial Lung Disease Associated with Anti-Aminoacyl-tRNA Synthetase Antibodies.

BACKGROUND: Little has been reported on long-term pulmonary function trends among patients with interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies (ARS-ILD). OBJECTIVES: To clarify the factors predictive of progression in ARS-ILD based on patients' initial clinical and radiological features. METHODS: The clinical courses of 88 patients with > 1 year of follow-up data on pulmonary function tests (PFTs) were retrospectively analyzed. Disease behavior was categorized into three groups: (1) improved or (2) worsened (defined as increases or decreases, respectively, of > 10% in forced vital capacity and > 15% in %diffusing capacity of lung carbon monoxide) or (3) stable based on PFT changes compared between 1-year results as the initial data and results at 3 years to assess the long-term course. RESULTS: In the initial course of 75 patients with ARS-ILD who received anti-inflammatory therapy within 6 months after diagnosis, 48 patients (64.0%) improved and 6 patients (8.0%) worsened. The radiological patterns in the patients with ARS-ILD included nonspecific interstitial pneumonia (NSIP) in 46.7% and NSIP with organizing pneumonia overlap in 52.0% of the cases. One-third of the initially improved patients who worsened over the long-term course were assigned to the unstable group. By multivariate logistic analysis, middle lobe traction bronchiectasis was a significant predictive factor for the patients in the unstable group. CONCLUSIONS: Most patients with ARS-ILD receiving anti-inflammatory therapy had improved or remained stable in the first year. However, over the long-term course, some patients worsened despite their initial improvement. Even though the extent of the disease is limited, middle lobe traction bronchiectasis in ARS-ILD may be a useful predictor of poor long-term disease behavior.