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.

Interstitial pneumonia with autoimmune features and histologic usual interstitial pneumonia treated with anti-fibrotic versus immunosuppressive therapy.

BACKGROUND: Therapeutic strategies in patients with interstitial pneumonia with autoimmune features (IPAF) and histological usual interstitial pneumonia (UIP) pattern (IPAF-UIP) have not been thoroughly evaluated. We compared the therapeutic efficacy of anti-fibrotic therapy with that of immunosuppressive treatment for patients with IPAF-UIP. METHODS: In this retrospective case series, we identified consecutive IPAF-UIP patients treated with anti-fibrotic therapy or immunosuppressive therapy. Clinical characteristics, one-year treatment response, acute exacerbation, and survival were studied. We performed a stratified analysis by the pathological presence or absence of inflammatory cell infiltration. RESULTS: Twenty-seven patients with anti-fibrotic therapy and 29 with immunosuppressive treatment were included. There was a significant difference in one-year forced vital capacity (FVC) change between patients with anti-fibrotic treatment (4 in 27 improved, 12 stable, and 11 worsened) and those with immunosuppressive treatment (16 in 29 improved, eight stable, and five worsened) (p = 0.006). There was also a significant difference in one-year St George's Respiratory Questionnaire (SGRQ) change between patients with anti-fibrotic therapy (2 in 27 improved, ten stable, and 15 worsened) and those with immunosuppressive treatment (14 in 29 improved, 12 stable, and worsened) (p < 0.001). There was no significant difference in survival between the groups (p = 0.32). However, in the subgroup with histological inflammatory cell infiltration, survival was significantly better with immunosuppressive therapy (p = 0.02). CONCLUSION: In IPAF-UIP, immunosuppressive therapy seemed to be superior to anti-fibrotic treatment in terms of therapeutic response, and provided better outcomes in the histological inflammatory subgroup. Further prospective studies are needed to clarify the therapeutic strategy in IPAF-UIP.

Intimal-protected adventitial inversion technique accelerates the obliteration of a patent false lumen.

BACKGROUND AND AIMS: The optimal procedure for reconstructing the dissected aortic stump for acute type A dissection remains controversial. We routinely used the intimal-protected adventitial inversion technique (iPAIT), a modified adventitial inversion technique, to protect the fragile intima by inserting a graft and assessed the safety and efficacy of this technique. METHODS: Between August 2008 and April 2020, 146 consecutive patients with acute type A dissections underwent thoracic aortic surgery in our hospital. Extended total aortic arch replacement was performed in 119 patients (81.5%). Sixty-nine patients underwent treatment for distal aortic anastomosis with the iPAIT. To compare the iPAIT to a historical control, we assessed 69 iPAIT patients and 25 patients who underwent total arch replacement using gelatin-resorcinol-formaldehyde (GRF) glue. RESULTS: Hospital mortality was 2.9% in the iPAIT group and 8.0% in the GRF group. Perioperative characteristics were similar between the two groups. However, postoperative computed tomography revealed that the obliteration rate was significantly higher in the iPAIT group (60/66, 90.9%) than in the GRF group (15/23, 65.2%) (p = .01), not including the patients who had died or developed severe renal dysfunction. The 8-year aortic event-free survival rate in the iPAIT group (81.3%) was significantly higher than that in the GRF group (47.4%). CONCLUSIONS: The use of this technique for acute type A dissections resulted in a low mortality rate and demonstrated promising midterm survival and may accelerate the obliteration of a patent false lumen and prevent late aortic events.

Fate of dissected arch vessels by adventitial inversion technique for acute type A aortic dissection repair.

OBJECTIVES: The adventitial inversion technique is used widely for aortic reconstruction for acute type A aortic dissection, as it easily controls the bleeding at anastomotic sites and closes the patent false lumen. However, this technique for arch vessel reconstruction has not been previously reported. Therefore, we applied the adventitial inversion technique for dissected arch vessel reconstruction to close the patent false lumen. METHODS: Among 57 consecutive patients who underwent emergency surgical treatment for acute type A aortic dissection from July 2006 to July 2012, the adventitial inversion technique for the dissected arch vessels was performed in 26 patients (42 arch vessel stumps). The patency and morphologic change of the false lumen of the arch vessels were evaluated using contrast-enhanced computed tomography. RESULTS: Overall, 2 hospital deaths were recorded, and the hospital mortality rate was 4%. No postoperative cerebral strokes and reoperations due to bleeding occurred. Follow-up by contrast-enhanced computed tomography was completed in 24 patients (37 stumps) with a mean duration of 99 ± 35 months. The postoperative closure rate of the false lumen after adventitial inversion was 86%, which was higher than when adventitial inversion was not used. No adverse events including stroke occurred during follow-up period. CONCLUSIONS: This technique facilitates the closure of the false lumen of dissected arch vessels and might improve clinical outcomes.

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.

Feasibility of open chest management with modified negative pressure wound therapy immediately after cardiac surgery.

OBJECTIVES: To evaluate the feasibility of open chest management with our modified negative pressure wound therapy immediately after cardiac surgery as a therapy for atypical tamponade. METHODS: Open chest with modified negative pressure wound therapy was performed immediately after cardiac surgery. The surface of the heart and the vessels were covered with non-adherent siliconized gauze. The sternal halves were stented using edge-cut disposable syringes to maintain a larger mediastinal cavity. Approximately 45 mm of distance was kept between the sternal edges. A trimmed sterile polyvinyl foam sponge was inserted into the mediastinum, the entire wound was sealed and negative pressure (-50 to -75 mmHg) was applied using a suction generator. Delayed chest closure was performed in a standard manner once the haemodynamic status was stabilizsed. RESULTS: The mortality rate was 3/15 (20%) patients. Deep sternal wound infection occurred in 1/15 (6.7%) patients. Five patients were extubated during the open chest management. Sternal closure was delayed for median of 3 days after the initial surgery. There was no incidence of bleeding complications or need for additional haemostatic procedures. CONCLUSIONS: Negative pressure wound therapy performed immediately after cardiac surgery was feasible in our small number of patients. CLINICAL REGISTRATION NUMBER: Study ID: 2020-149.

Weekly nanoparticle albumin-bound paclitaxel and paclitaxel for relapsed small cell lung cancer: A retrospective observational study.

ABSTRACT: In addition to advanced non-small cell lung cancer, nanoparticle albumin-bound paclitaxel (nab-PTX) may also harbor potential benefit for patients with relapsed small cell lung cancer (SCLC), since weekly paclitaxel (PTX) shows modest activity for relapsed SCLC. We evaluated the efficacy and safety of both weekly nab-PTX and PTX for relapsed SCLC.We retrospectively reviewed 52 consecutive relapsed SCLC patients who were treated with weekly nab-PTX or PTX at our hospital.The response rate, median progression-free survival and overall survival with nab-PTX and PTX were 5.6 vs 8.8%, 3.2 vs 1.7 months, and 5.4 vs 4.5 months, respectively. No statistically significant differences were observed. There was no statistical difference between the 2 groups for ≥Grade 3 adverse events.Weekly nab-PTX and PTX showed similar activity for relapsed SCLC. The toxicity profile of nab-PTX was equally tolerable to that of PTX.

Validity of direct bilateral axillary arterial cannulation in emergency surgery for acute type A aortic dissection.

BACKGROUND AND AIM OF THE STUDY: To assess the validity and long-term outcomes of direct bilateral axillary arterial cannulation for acute type A aortic dissection. METHODS: Between 2003 and 2020, 208 consecutive patients with acute type A aortic dissection underwent emergency surgical repair. Cardiopulmonary bypass was attempted to establish direct bilateral axillary arterial cannulation and bicaval drainage. Antegrade selective cerebral perfusion was established by axillary perfusion and direct cannulation of the left common carotid artery. RESULTS: Ascending aortic, partial arch, and extended total aortic arch replacement were performed in 50 (24.0%), 7 (3.4%), and 151 (72.6%) patients, respectively. Aortic root surgery and coronary artery bypass grafting were performed concomitantly in 23 and seven patients, respectively. Cardiopulmonary bypass was attempted only through bilateral axillary cannulation in all patients but was successful in 13 (6.3%) patients without bilateral axillary cannulation. No postoperative complications occurred related to this technique. There were seven hospital deaths (early mortality rate, 3.4%). Five patients had postoperative reoperation for bleeding, and nine (4.3%) were transferred to other hospitals due to postoperative permanent cerebral infarction, particularly two with arm ischemia. The 10-year survival rate of patients who underwent emergency surgical repair with this technique was 71.4%. CONCLUSIONS: Direct bilateral axillary arterial cannulation followed by selective cerebral perfusion was successful in 93.7% of patients and this may be an optimal solution for providing stable outcomes after emergency surgery for acute type A aortic dissection. However, we experienced two complications of arm ischemia, attention should be paid to potential arm ischemia.

The prognostic value of the COPD Assessment Test in fibrotic interstitial lung disease.

BACKGROUND: The COPD Assessment Test (CAT) has been studied as a measure of health status in idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disease. However, its prognostic value is unknown. The present study explored the association between CAT score and mortality in fibrotic interstitial lung disease (FILD), including IPF and other forms of ILD. METHODS: We retrospectively analyzed 501 consecutive patients with FILD who underwent clinical assessment, including pulmonary function test and CAT. The association between CAT score and 3-year mortality was assessed using Cox proportional hazard analysis, Kaplan-Meier plots, and the log-rank test for trend. To handle missing data, the imputed method was used. RESULTS: The patients' median age was 68 years, and 320 were male (63.9%). Regarding CAT severity, 203 patients had a low impact level (score <10), 195 had a medium level (10-20), 80 had a high level (21-30), and 23 had a very high level (31-40). During the 3-year study period, 118 patients died. After adjusting for age, sex, forced vital capacity, diffusion capacity for carbon monoxide, IPF diagnosis, and usual interstitial pneumonia pattern on high-resolution computed tomography, the CAT score was significantly associated with 3-year mortality (hazard ratio in increments of 10 points: 1.458, 95% confidence interval 1.161-1.830; p < 0.001). In addition, patients with high and very high impact levels had twofold and threefold higher mortality risk than those with low levels, respectively. CONCLUSION: The CAT has prognostic value in FILD.

Anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with diffuse alveolar damage diagnosed by transbronchial lung cryobiopsy: A case report.

Diffuse alveolar damage (DAD) is known to be a pathological hallmark of acute respiratory distress syndrome or acute interstitial pneumonia, and to have a poor prognosis. We report a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD), in which DAD was confirmed by transbronchial lung cryobiopsy at an early stage without respiratory failure. Although this patient initially did not show respiratory failure, his respiratory condition gradually worsened despite intensive immunosuppression therapy and he died 3 months later. Therefore, the early pathological findings of DAD did not match the clinical picture, which showed no respiratory failure. However, these findings were consistent with the subsequent course and poor outcome. Histological DAD, even in the absence of respiratory failure, may indicate a subsequent poor prognosis and explain the refractory course of RP-ILD with anti-MDA5 antibody-positive CADM.

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.

Serial 6-month change in forced vital capacity predicts subsequent decline and mortality in Japanese patients with newly diagnosed idiopathic pulmonary fibrosis.

BACKGROUND: The clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in lung function; however, predicting changes in lung function is difficult. We sought to determine whether the prior 6-month trend in forced vital capacity (FVC) could predict mortality and the subsequent 6-month trend in FVC. METHODS: We retrospectively analyzed consecutive patients with newly diagnosed IPF who underwent serial pulmonary function tests. The immediate two years after the initial evaluation were divided into four terms of six months each and stratified on the basis of presence or absence of a ≥10% relative decline in FVC at six months (declined and stable groups, respectively). RESULTS: We included 107 patients with %predicted FVC of 80.8% and %predicted diffusing capacity of the lung for carbon monoxide of 58.9%. In multivariate analysis, a decline in %predicted FVC in the initial six months was found to be an independent prognostic factor (hazard ratio 4.45, 95% confidence interval 2.62-7.56, p < 0.01). Among the 46 terms in which the FVC declined during the initial 1.5-year study period, a decline in FVC was exhibited in 23 (50.0%) of the subsequent terms. Among 231 terms in which FVC remained stable, a decline was observed in 32 (13.9%) of the subsequent terms (relative risk 3.61, p < 0.01). The frequency of FVC decline in each term was 16-27%. FVC was stable or declined in all four terms in 50.5% and 15.9% of cases, respectively. CONCLUSIONS: Six-month decline in FVC predicts subsequent FVC change and mortality in IPF patients in the era of antifibrotic agents.

Mesalazine-induced lung injury with severe respiratory failure successfully treated with steroids and non-invasive positive pressure ventilation.

Drug-induced lung injury (DLI) has become more common because of the increasing number of therapeutic agents in use. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is one of the key drugs for the treatment of ulcerative colitis (UC). Although mesalazine-induced lung injury has been previously reported, few cases have included severe respiratory failure. In this report, we present a case of mesalazine-induced lung injury with severe respiratory failure, which was improved by discontinuation of mesalazine and introduction of corticosteroid therapy and ventilation support with non-invasive positive pressure ventilation (NPPV). We also review the previous literature on mesalazine-induced lung injury.

Pulse oximetry saturation can predict prognosis of idiopathic pulmonary fibrosis.

BACKGROUND: In Japan, the severity staging system for idiopathic pulmonary fibrosis (IPF) has been used to determine medical care subsidies. However, this system requires invasive procedures to measure arterial oxygen tension. Recently, noninvasive and simple measurements of oxygen saturation by pulse oximetry (SpO2) have been used for severity assessments. We propose a pulse oximetry saturation (POS) staging system consisting of SpO2 parameters to predict prognosis. METHODS: We developed four prototype staging systems based on SpO2 at rest and desaturation, and adopted the system with the highest C-statistic as the POS staging system. The cutoff SpO2 values at rest were 96% and 90%, and desaturation was defined as SpO2 < 90% at the end of the 6-min-walk test. RESULTS: Two-hundred and nineteen IPF patients were studied and the C-statistic values of models 1, 2, 3, and 4 were 0.633, 0.643, 0.630, and 0.673, respectively. We judged model 4 to be a superior POS staging system; it defined SpO2 ≥ 96% at rest without desaturation as stage Ⅰ; SpO2 ≥ 96% at rest with desaturation or SpO2 90%-95% at rest without desaturation as stage Ⅱ; and SpO2 90%-95% at rest with desaturation or SpO2 < 90% at rest as stage Ⅲ. The hazard ratios of POS stage Ⅰ, Ⅱ, and Ⅲ were 1.00, 2.25, and 4.99, respectively. The C-statistic of the POS staging system produced from 1000 bootstrap samples was similar (0.673), suggesting good internal validation. CONCLUSION: A noninvasive and simple POS staging system defined by SpO2 can easily predict prognosis.

Usefulness of new diagnostic criteria for chronic hypersensitivity pneumonitis established on the basis of a Delphi survey: A Japanese cohort study.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is a fibrotic interstitial lung disease (ILD) caused by repeated exposure to a variety of organic particles. In November 2017, new criteria for CHP diagnosis were proposed by Morisset et al. based on a modified Delphi survey of ILD experts. However, it remains unclear whether these criteria are useful to accurately diagnose CHP. We aimed to evaluate the newly proposed CHP diagnostic criteria. METHODS: We retrospectively applied Morisset's CHP diagnostic criteria to consecutive Japanese patients who underwent surgical lung biopsy for diagnosis of ILD from 2008 to 2015. All patients underwent bronchoalveolar lavage and pulmonary function testing. Patients who had connective tissue disease complications or showed an acute or subacute disease onset were excluded. RESULTS: A total of 251 patients were included. The diagnoses based on multidisciplinary discussion (MDD) were CHP (n = 27), idiopathic pulmonary fibrosis (n = 117), unclassifiable interstitial pneumonia (IP) (n = 65), and other diagnoses (n = 42). Of the 27 MDD-CHP patients, 14 were classified as a CHP group with diagnostic confidence >50% and 13 were not categorized (sensitivity, 51.9%; specificity, 77.7%). Morisset's CHP diagnostic criteria could help avoid SLB for the diagnosis of CHP in seven patients. Of the 13 MDD-CHP patients who were not categorized in the CHP group with diagnostic confidence >50%, the reason for the exclusion was an inconsistent with UIP pattern without CHP features. CONCLUSIONS: Half of the MDD-CHP patients were diagnosed with CHP using Morisset's CHP diagnostic criteria. Further investigation will be important for developing improved diagnostic criteria for CHP.

Acute exacerbations of fibrotic interstitial lung diseases.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE-IPF). In 2016, an international working group revised its definition and diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD). METHODS: We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non-specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease-associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE-IPF, we identified all subjects with an AE. RESULTS: During the observational period, 193 patients experienced a first AE (AE-FILD n = 69, AE-IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log-rank test, P < 0.001). After adjusting for potentially influential confounders, FILD remained a significant predictor of longer time to first AE compared with IPF (hazard ratio: 0.453; 95% CI: 0.317-0.647, P = 0.006). In a multivariate Cox proportional analysis, baseline disease severity was closely associated with the incidence of AE-ILD. Even after adjustment for other clinical variables, AE had a negative impact on overall survival. AE-FILD and AE-IPF showed similar poor short-term outcomes. CONCLUSION: All forms of ILD are at risk of AE and have a similar outcome to AE-IPF.

Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis.

BACKGROUND: Respiratory-related hospitalization, in particular acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), is common and associated with increasing mortality in patients with IPF. We aimed to evaluate the implications of a newly proposed framework of acute respiratory deterioration (ARD) and AE-IPF in hospitalized patients. METHODS: Using the data of an IPF cohort consisting of 225 consecutive patients, we retrospectively studied first hospitalizations from January 2008 to December 2017. We analysed the demographics and 90-day mortality of patients with AE-IPF and those with parenchymal cause of ARD other than AE. RESULTS: Among 122 patients with first hospitalization for ARD, 35 patients were diagnosed with AE-IPF, including 11 patients with triggered AE. Parenchymal cause of ARD other than AE was diagnosed in 71 patients, and extra-parenchymal cause in 16 patients. Almost all hospitalized patients (93%) underwent chest CT, and 83% of patients with AE-IPF underwent bronchoalveolar lavage. There was a significant difference in the anti-inflammatory therapy between the AE-IPF group and parenchymal cause of ARD other than AE group (p < 0.001). AE-IPF was independently associated with poor survival in multivariate Cox proportional regression analysis. CONCLUSIONS: AE-IPF accounted for about 30% of first hospitalizations for ARD, and differentiation between AE-IPF and the other categories in ARD is important from a therapeutic and a prognostic point of view.