Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 202 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Presence of focal usual interstitial pneumonia is a key prognostic factor in progressive pulmonary fibrosis.

AIMS: Progressive pulmonary fibrosis (PPF) is a newly recognised clinical phenotype of interstitial lung diseases in the 2022 interstitial pulmonary fibrosis (IPF) guidelines. This category is based entirely on clinical and radiological factors, and the background histopathology is unknown. Our objective was to investigate the histopathological characteristics of PPF and to examine the correlation between usual interstitial pneumonia (UIP) and prognosis in this new disease type. We hypothesised that the presence of UIP-like fibrosis predicts patients' survival in PPF cases. METHODS AND RESULTS: We selected 201 cases fulfilling the clinical criteria of PPF from case archives. Cases diagnosed as IPF by a multidisciplinary team were excluded. Whole slide images were evaluated by three pathologists who were blinded to clinical and radiological data. We measured areas of UIP-like fibrosis and calculated what percentage of the total lesion area they occupied. The presence of focal UIP-like fibrosis amounting to 10% or more of the lesion area was seen in 148 (73.6%), 168 (83.6%) and 165 (82.1%) cases for each pathologist, respectively. Agreement of the recognition of UIP-like fibrosis in PPF cases was above κ = 0.6 between all pairs. Survival analysis showed that the presence of focal UIP-like fibrosis correlated with worsened survival under all parameters tested (P < 0.001). CONCLUSIONS: The presence of UIP-like fibrosis is a core pathological feature of clinical PPF, and its presence within diseased areas is associated with poorer prognosis. This study highlights the importance of considering the presence of focal UIP-like fibrosis in the evaluation and management of PPF.

Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Physical activity in idiopathic pulmonary fibrosis: Longitudinal change and minimal clinically important difference.

BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.

Role of rituximab in the treatment of systemic sclerosis: A literature review.

This literature review aimed to evaluate the effectiveness of rituximab (RTX) in patients with systemic sclerosis (SSc). PubMed was searched for articles, published through 31 March 2022, on any controlled studies using RTX in the treatment of SSc. Of 85 identified articles, 9 were selected by title/abstract screening and full text examination. All nine articles reported outcomes of forced vital capacity (%FVC), and seven reported those of modified Rodnan skin scores (mRSS). The results showed that among the seven controlled studies evaluating skin lesions in patients with SSc, four showed a significant improvement of mRSS by RTX when compared with a control group, whereas three showed no significant effect. Among the nine controlled studies evaluating lung lesions, five showed a significant improvement of %FVC compared with a control group, whereas four showed no significant effect. In conclusion, RTX may be effective in the treatment of skin and lung lesions in patients with SSc. The profiles of SSc patients for whom RTX was indicated were unclear, although patients with diffuse cutaneous SSc and those positive for anti-topoisomerase I antibody were considered potential targets. Additional studies are needed to assess the long-term effectiveness of RTX in the treatment of patients with SSc.

Optimal Dose of Intravenous Cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: a retrospective cohort study of J-CANVAS.

OBJECTIVES: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively assessed patients with AAV who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes were also evaluated. RESULTS: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. CONCLUSION: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).

Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias.

BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

Clinical significance of anti-NOR90 antibodies in systemic sclerosis and idiopathic interstitial pneumonia.

OBJECTIVE: Anti-NOR90 antibodies are usually found in patients with SSc; however, their clinical relevance remains obscure. We developed an ELISA for measuring them to investigate the clinical features of patients with anti-NOR90 antibodies. METHODS: Serum samples from 1252 patients with various conditions from Nagoya University Hospital and 244 patients with idiopathic interstitial pneumonia (IIP) from Tosei General Hospital were included. Anti-NOR90 antibodies were assayed by an ELISA using the recombinant protein produced by in vitro transcription/translation. RESULTS: Five (0.4%) patients in the Nagoya University Hospital cohort had anti-NOR90 antibodies. One patient with diffuse cutaneous SSc, three with limited cutaneous SSc, and one with Raynaud's disease were positive for anti-NOR90 antibodies. Anti-NOR90 antibodies were found more frequently in patients with systemic scleroderma-spectrum disorders (SSDs) than without SSDs (5/316 vs 0/936, P <0.00101) and were found more frequently in patients with SSc than without SSc (4/249 vs 0/528, P <0.0104) in the systemic autoimmune rheumatic diseases cohort. Three of the four anti-NOR90-positive SSc patients had interstitial lung disease (ILD), and two of those four had cancer. Three (1.2%) patients in the Tosei General Hospital cohort had anti-NOR90 antibodies. All three of the anti-NOR90-positive IIP patients had gastrointestinal tract involvement, and two of those three had cancer or skin lesions observed in SSc. CONCLUSIONS: Although anti-NOR90 antibodies are rarely found in clinics, our ELISA is useful for their detection. Further studies are needed to confirm the association of anti-NOR90 antibodies with ILD and cancer in SSc and IIP patients.

Cicatricial organising pneumonia associated with fibrosing interstitial pneumonia - a clinicopathological study.

AIMS: The recent recognition of cicatricial organising pneumonia (ciOP) indicates that the ciOP may resemble or simulate fibrotic interstitial pneumonia; however, there has been great uncertainty regarding the affected populations, pathogenesis, clinical relevance and characteristics. In this study, we compared the characteristics of fibrotic interstitial pneumonia with and without ciOP. METHODS AND RESULTS: We enrolled 121 patients from the consultation archive whose pathological findings were fibrotic interstitial pneumonia and for whom follow-up clinical data were available. We reviewed these cases histopathologically and classified them according to whether or not they showed ciOP. We compared the clinicopathological features between the two groups. CiOP, histopathologically characterised by deposition of dense collagenous fibres within the alveolar space without destruction of the lung structure, was found in 48 patients (39.7%). None of the cases with ciOP experienced acute exacerbation during 12 months' follow-up. The group with ciOP had more severe diffusion impairment but this, together with restrictive ventilatory impairment, improved significantly compared to the group without ciOP. CONCLUSION: CiOP is a histopathological finding commonly found in fibrotic interstitial pneumonia. It does not relate to acute exacerbation or decrease in pulmonary function.

Prevalence and prognosis of chronic fibrosing interstitial lung diseases with a progressive phenotype.

BACKGROUND AND OBJECTIVE: The development of clinically progressive fibrosis complicates a wide array of interstitial lung diseases (ILDs). However, there are limited data regarding its prevalence and prognosis. METHODS: We analysed consecutive patients seen for initial evaluation of a fibrosing form of ILD (FILD). Patients were evaluated for evidence of progressive fibrosis over the first 24 months of follow-up. We defined a progressive phenotype as the presence of at least one of the following: a relative decline in forced vital capacity (FVC) of ≥10%; a relative decline in FVC of ≥5%-<10% with a relative decline in diffusing capacity of the lung for carbon monoxide of ≥15%, increased fibrosis on HRCT or progressive symptoms. RESULTS: Eight hundred and forty-four patients (397 with idiopathic pulmonary fibrosis [IPF] and 447 non-IPF FILD) made up the final analysis cohort. Three hundred and fifty-five patients (42.1%) met the progressive phenotype criteria (59.4% of IPF patients and 26.6% of non-IPF FILD patients, p <0.01). In both IPF and non-IPF FILD, transplantation-free survival differed between patients with a progressive phenotype and those without (p <0.01). Multivariable analysis showed that a progressive phenotype was an independent predictor of transplantation-free survival (hazard ratio [HR]: 3.36, 95% CI: 2.68-4.23, p <0.01). Transplantation-free survival did not differ between non-IPF FILD with a progressive phenotype and IPF (HR: 1.12, 95% CI: 0.85-1.48, p = 0.42). CONCLUSION: Over one-fourth of non-IPF FILD patients develop a progressive phenotype compared to approximately 60% of IPF patients. The survival of non-IPF FILD patients with a progressive phenotype is similar to IPF.

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system.

INTRODUCTION: Monoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021. METHODS: According to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan. RESULTS: During Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12-0.53) and 0.10 (95% CI: 0.01-0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event. CONCLUSIONS: The administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.

Immune recognition of lysyl-tRNA synthetase and isoleucyl-tRNA synthetase by anti-OJ antibody-positive sera.

OBJECTIVE: Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are useful for identifying a clinical subset of patients with idiopathic inflammatory myopathies (IIMs). Anti-OJ antibodies, which recognize multi-enzyme synthetase complexes including isoleucyl-tRNA synthetase (IARS) and lysyl-tRNA synthetase (KARS), are among the anti-ARS antibodies. Although testing antibodies to other ARSs have been used clinically, no validated immunoassays for detecting anti-OJ antibodies are available. We aimed to establish an anti-OJ ELISA. METHODS: Serum samples were collected from 279 patients with IIMs and 22 patients with idiopathic interstitial pneumonia. Sixty-four of the samples that had been confirmed to be negative for anti-OJ by standard immunoprecipitation were used as the negative control, and 12 anti-OJ-positive reference sera were used as the positive control. Antibodies to IARS and KARS were assayed by ELISA using biotinylated recombinant proteins generated by in vitro transcription/translation. RESULTS: The anti-OJ-positive sera strongly reacted with the KARS and IARS recombinant proteins in ELISA. Although all 12 reference sera were positive in the anti-KARS ELISA, 4 of the 64 anti-OJ-negative sera were also weakly positive. The sensitivity and the specificity were 100% and 93.8%, respectively. Since our anti-KARS ELISA performed well, showing a high agreement with the results for immunoprecipitation (Cohen's κ > 0.8), the remaining 237 samples were also tested. Thirteen anti-KARS-positive sera were newly found by ELISA, all of which were anti-OJ positive by immunoprecipitation. CONCLUSION: Immunoassays for detecting anti-OJ antibodies using KARS and IARS recombinant proteins were developed. Our ELISAs performed well, with very high agreement of the results by immunoprecipitation and can be applied to the first reliable, easy-to-use measurement assays for anti-OJ antibodies.

Cutoff Points for Step Count to Predict 1-year All-Cause Mortality in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Although physical activity is associated with mortality in patients with idiopathic pulmonary fibrosis (IPF), reference values to interpret levels of physical activity are lacking. OBJECTIVES: This study aimed to investigate the prognostic significance of physical activity assessed by step count and its cutoff points for all-cause mortality. METHODS: We measured physical activity (steps per day) using an accelerometer in patients with IPF at the time of diagnosis. Relationships among physical activity and mortality, as well as cutoff points of daily step count to predict all-cause mortality were examined. RESULTS: Eighty-seven patients (73 males) were enrolled. Forty-four patients (50.1%) died during the follow-up (median 54 months). In analysis adjusting for Gender-Age-Physiology stage and 6-min walk distance, daily step count was an independent predictor of all-cause mortality (hazard ratio (HR) = 0.820, 95% confidence interval (CI) = 0.694-0.968, p = 0.019). The optimal cutoff point (receiving operating characteristic analysis) for 1-year mortality was 3,473 steps per day (sensitivity = 0.818 and specificity = 0.724). Mortality was significantly lower in patients with a daily step count exceeding 3,473 steps than in those whose count was 3,473 or less (HR = 0.395, 95% CI = 0.218-0.715, p = 0.002). CONCLUSIONS: Step count, an easily interpretable measurement, was a significant predictor of all-cause mortality in patients with IPF. At the time of diagnosis, a count that exceeded the cutoff point of 3,473 steps/day more than halved mortality. These findings highlight the importance of assessing physical activity in this patient population.

Probable usual interstitial pneumonia pattern on chest CT: is it sufficient for a diagnosis of idiopathic pulmonary fibrosis?

Recent studies have suggested that in patients with an idiopathic interstitial pneumonia (IIP), a probable usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT) is sufficient to diagnose idiopathic pulmonary fibrosis (IPF) without histopathology.We retrospectively compared the prognosis and time to first acute exacerbation (AE) in IIP patients with a UIP and a probable UIP pattern on initial chest CT.One hundred and sixty IIP patients with a UIP pattern and 242 with a probable UIP pattern were identified. Probable UIP pattern was independently associated with longer survival time (adjusted hazard ratio 0.713, 95% CI 0.536-0.950; p=0.021) and time to first AE (adjusted hazard ratio 0.580, 95% CI 0.389-0.866; p=0.008). In subjects with a probable UIP pattern who underwent surgical lung biopsy, the probability of a histopathological UIP pattern was 83%. After multidisciplinary discussion and the inclusion of longitudinal behaviour, a diagnosis of IPF was made in 66% of cases. In IPF patients, survival time and time to first AE were not associated with CT pattern. Among subjects with a probable UIP pattern, compared to non-IPF patients, survival time and time to first AE were shorter in IPF patients.In conclusion, IIP patients with a probable UIP pattern on initial chest CT had a better prognosis and longer time to first AE than those with a UIP pattern. However, when baseline data and longitudinal behaviour provided a final diagnosis of IPF, CT pattern was not associated with these outcomes. This suggests diagnostic heterogeneity among patients with a probable UIP pattern.

Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus.

BACKGROUND AND OBJECTIVE: Corticosteroids and immunosuppressive agents are considered mainstays of therapy for connective tissue disease-related interstitial lung disease (CTD-ILD); however, tacrolimus with corticosteroid therapy has not been fully investigated. Our objectives were to examine the multidimensional therapeutic benefit and tolerability of the combined therapy for the initial treatment of patients with CTD-ILD. METHODS: In this retrospective case series, we identified consecutive CTD-ILD patients treated with tacrolimus plus intravenous (i.v.) methylprednisolone (1000 mg i.v. 3 days a week for 2 weeks) followed by low-dose prednisolone (10 mg/day). We assessed the multidimensional therapeutic benefit and tolerability including lung physiology, exercise capacity, exercise oxygen desaturation, modified Medical Research Council (MMRC) and St George's Respiratory Questionnaire (SGRQ). RESULTS: A total of 26 ILD patients with the underlying CTD diagnoses included 11 with rheumatoid arthritis, 9 with dermatomyositis, 4 with Sjögren's syndrome and 2 others. From baseline to 12 months, the combined therapy significantly improved forced vital capacity (FVC; 77.8% to 94.6%, P < 0.001), diffusing capacity of the lung for carbon monoxide (DLCO ; 66.1% to 75.1%, P < 0.001), 6-min walk distance (6MWD; 530 to 568 m, P = 0.02), lowest oxygen saturation on pulse oximetry (SpO2 ; 85% to 89%, P = 0.01), MMRC (1.3 to 0.8, P = 0.01) and SGRQ (38 to 21, P < 0.001). During the study period, only one patient's therapy was discontinued due to an adverse event and none had a life-threatening adverse event attributed to the combined therapy. CONCLUSION: In our cohort of CTD-ILD, two courses of pulse dose methylprednisolone therapy followed by prednisone and oral tacrolimus appeared to be well tolerated, and to have multidimensional efficacy.

Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease.

BACKGROUND AND OBJECTIVE: The St George's Respiratory Questionnaire (SGRQ) is a self-administered questionnaire used to assess health-related quality of life (HRQoL) in various chronic respiratory diseases. Few studies have assessed the performance of the SGRQ in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). We aimed to examine the SGRQ's performance characteristics and generate data to support its reliability and validity in patients with CTD-ILD. METHODS: We used data from 193 CTD-ILD patients evaluated at Tosei General Hospital from May 2007 to July 2016 to assess the cross-sectional and longitudinal validity of the SGRQ. RESULTS: The mean age of the patients was 64.2 years and 122 (63.2%) were women. There were no significant differences in SGRQ scores between any of the CTD groups. Internal consistency (Cronbach's α = 0.905) and repeatability (intraclass correlation coefficient (ICC) = 0.873) for the SGRQ total score were excellent. At baseline, SGRQ total score was significantly associated with clinically meaningful measures of physiological function, exercise capacity and dyspnoea. Change in SGRQ total score over 6 months was also associated with change in other measures. Cox proportional hazards models showed that higher baseline SGRQ total score was a significant predictor of mortality. The estimated minimal clinically important difference of SGRQ total score was 4-13 points. CONCLUSION: These data support the validity and reliability of SGRQ as a sensitive measure for capturing HRQoL in patients with CTD-ILD.