Evaluation of Bone Mineral Density in Lung Transplant Recipients by Chest Computed Tomography.

INTRODUCTION: Lung transplantation (LT) recipients are at risk of bone mineral density (BMD) loss. Pre- and post-LT BMD loss has been reported in some cross-sectional studies; however, there are limited studies regarding the serial BMD change in LT recipients. The aim of this study was to investigate the serial BMD changes and the clinical characteristics associated with BMD decline. METHODS: This was a single-center, retrospective observational study. BMD was serially measured in thoracic vertebral bodies (Th4, 7, 10) using computed tomography (CT) before and 3 and 12 months after LT. The frequency of osteoporosis and factors associated with pre-LT osteoporosis and post-LT BMD loss were evaluated. The frequency of post-LT compression fracture and its associated factors were also analyzed. RESULTS: This study included 128 adult LT recipients. LT recipients had decreased BMD (151.8 ± 42.2 mg/mL) before LT compared with age-, sex-, and smoking index-matched controls (176.2 ± 35.7 mg/mL). The diagnosis of COPD was associated with pre-LT osteoporosis. LT recipients experience further BMD decline after transplantation, and the percentage of recipients classified as exhibiting osteoporosis increased from 20% at baseline to 43% at 12 months. Recipients who had been taking no or small doses of glucocorticoids before LT had rapid BMD loss after LT. Early bisphosphonate use (within 3 months) after LT attenuated BMD loss and decreased new-onset compression fracture. CONCLUSION: LT recipients are at high risk for BMD loss and compression fracture after LT. Early bisphosphonate use may decrease BMD loss and compression fracture.

Laryngeal widening and adequate ventilation by expiratory pressure load training improve aerobic capacity in COPD: a randomised controlled trial.

RATIONALE: Despite strategies acting on peripheral airway obstruction in chronic obstructive pulmonary disease (COPD), exercise intolerance remains inadequately improved. We hypothesised that laryngeal narrowing is a potential treatment target of expiratory pressure load training (EPT) to improve exercise intolerance in COPD. METHODS: The effect of 3-month EPT was assessed in 47 patients with COPD divided into Global Initiative for Chronic Obstructive Lung Disease (GOLD) mild-to-moderate (I-II) and severe-to-very severe (III-IV), randomly allocating 1:1 to EPT or control groups. The primary outcome was endurance time in the constant work rate exercise test in GOLD III-IV patients. RESULTS: Compared with controls, EPT increased: (1) endurance time, with estimated treatment effect: +703 (95% CI: 379 to 1031) s, p=0.0008 (GOLD I-II); +390 (95% CI: 205 to 574) s, p=0.0006 (GOLD III-IV); (2) peak oxygen uptake (p=0.0086 in GOLD I-II; p=0.0004 in GOLD III-IV); (3) glottic dilatation ratio at maximum collapse on laryngoscopy in the submaximal exercise (p=0.0062 in GOLD I-II; p=0.0001 in GOLD III-IV); and (4) the inflection point of expiratory tidal volume relative to minute ventilation during the incremental exercise (p=0.0015 in GOLD I-II; p=0.0075 in GOLD III-IV). Across GOLD grades, the responses of glottic dilatation ratio at maximum collapse and the expiratory tidal volume at the inflection point were selected as more influential variables correlating with the improvement in peak oxygen uptake and endurance time, respectively. CONCLUSION: These results show that EPT improved aerobic capacity and endurance time with larger laryngeal widening and adequate ventilation despite advanced COPD. TRIAL REGISTRATION NUMBER: UMIN000041250.

Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Nutritional status in female patients with nontuberculous mycobacterial lung disease and its association with disease severity.

BACKGROUND: In women, slender body habitus has been reported to be one of the predisposing factors underlying the development and poor prognosis of non-tuberculous mycobacterial lung disease (NTM-LD). Given the lack of nutritional data contributing to treatment strategies, we aimed to clarify the nutritional status of female patients with NTM-LD and its association with disease severity. METHODS: In this single-center observational study, we enrolled 81 female outpatients with NTM-LD. Data on healthy women of similar ages were selected from our previous survey data and categorized as controls. First, we compared anthropometric and dietary survey data between patients and controls. Second, after the patients were categorized into relatively mild (mild, n = 40) and relatively severe groups (severe, n = 41) based on pulmonary X-ray-image finding scores, body composition, nutritional intake, and biochemical markers were compared between the groups. To identify nutritional factors associated with disease severity, logistic regression analyses were performed. RESULTS: Compared with controls, patients with NTM-LD had significantly lower energy intake, body mass index, body fat, and skeletal muscle mass (all p < 0.001). Compared with the mild group, the severe group had significantly lower skeletal muscle mass (p = 0.037), albumin (p = 0.029), transthyretin (prealbumin) (p = 0.002), retinol-binding protein (p = 0.011), and hemoglobin (p = 0.001); however, no between-group differences were observed in energy or nutrient intake. Logistic analyses revealed that transthyretin (p = 0.025) and hemoglobin (p = 0.003) levels were independent factors associated with disease severity. CONCLUSIONS: This is the first study to comprehensively report the association between NTM-LD severity and nutritional status, including body composition, nutrient intake, and biomarkers. The results suggest that initiating nutritional therapy from the mild stage of the disease to prevent undernutrition is warranted.

Legionnaire's disease presenting as bilateral central scotomata: a case report.

BACKGROUND: Legionnaire's disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire's disease are limited. CASE PRESENTATION: We report the case of a patient with Legionnaire's disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire's disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire's disease. CONCLUSIONS: This case demonstrates that Legionnaire's disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire's disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.

Prognostic significance of crazy paving ground grass opacities in non-HIV Pneumocystis jirovecii pneumonia: an observational cohort study.

BACKGROUND: In patients with non-HIV Pneumocystis jirovecii pneumonia (PjP), computed tomography imaging reveals ground grass opacities (GGO). Previous reports show that some patients with non-HIV PjP exhibit GGO with crazy paving. However, there have been no studies on the association between crazy paving GGO and non-HIV PjP clinical outcomes. Here, at the diagnosis of non-HIV PjP, we reviewed high-resolution computed tomography (HRCT) findings that included GGO types and evaluated the prognostic impact of crazy paving GGO on the clinical outcomes of non-HIV PjP immunocompromised patients. METHODS: We retrospectively reviewed the clinical information including the HRCT findings of patients diagnosed with non-HIV PjP from five institutions between 2006 and 2015. The GGO types included those with or without crazy paving. The associations between clinical factors such as HRCT findings and in-hospital mortality were assessed using the Cox regression model. RESULTS: Sixty-one patients were included in our study. Nineteen patients died at a hospital. All patients exhibited GGO on HRCT imaging at diagnosis of non-HIV PjP. The HRCT findings included crazy paving GGO (29 patients, 47.5%), consolidations (23 patients, 37.7%), bronchiectasis (14 patients, 23.0%), and centrilobular small nodules (30 patients, 49.2%). Cysts were not observed in any patient. Multivariate analysis revealed that crazy paving GGO and low serum albumin levels were independent risk factors for mortality. CONCLUSIONS: At the diagnosis of non-HIV PjP, patients with crazy paving GGO on HRCT imaging and low serum albumin levels may have a poor prognosis.

Perspectives on End-of-Life Treatment among Patients with COPD: A Multicenter, Cross-sectional Study in Japan.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality. Since patients with severe COPD may experience exacerbations and eventually face mortality, advanced care planning (ACP) has been increasingly emphasized in the recent COPD guidelines. We conducted a multicenter, cross-sectional study to survey the current perspectives of Japanese COPD patients toward ACP. "High-risk" COPD patients and their attending physicians were consecutively recruited. The patients' family configurations, understanding of COPD pathophysiology, current end-of-life care communication with physicians and family members, and preferences for invasive life-sustaining treatments including mechanical ventilation (MV) and cardiopulmonary resuscitation (CPR) were evaluated using a custom-made, structured, self-administered questionnaire. Attending physicians were also interviewed, and we evaluated the patient-physician agreement. Among the 224 eligible "high-risk" patients, 162 participated. Half of the physicians (54.4%) thought they had communicated detailed information; however, only 19.4% of the COPD patients thought the physicians did so (κ score = 0.16). Less than 10% of patients wanted to receive invasive treatment (MV, 6.3% and CPR, 9.4%); interestingly, more than half marked their decision as "refer to the physician" (MV 42.5% and CPR 44.4%) or "refer to family" (MV, 13.8% and CPR, 14.4%). Patients with less knowledge of COPD were less likely to indicate that they had already made a decision. Although ACP is necessary to cope with severe COPD, Japanese "high-risk" COPD patients were unable to make a decision on their preferences for invasive treatments. Lack of disease knowledge and communication gaps between patients and physicians should be addressed as part of these patients' care.

Effects of acupuncture on nutritional state of patients with stable chronic obstructive pulmonary disease (COPD): re-analysis of COPD acupuncture trial, a randomized controlled trial.

BACKGROUND: There are an increasing number of evidences that chronic obstructive pulmonary disease (COPD) is a systemic illness and that bodyweight loss is its prominent manifestation. We focused on the nutritional outcomes to find out the effectiveness of acupuncture on nutritional state of COPD patients and on their prognosis in our previous interventional study. METHODS: The present study is re-analysis of our previous interventional study, COPD Acupuncture Trial (CAT) published in 2012. Data from CAT was re-analyzed in terms of nutritional status, inflammatory biomarkers, and prognostic index. Nutritional states were evaluated by the measurements of body weight, body composition, and muscle strength, and the nutritional hematological examination results (retinol-binding protein (RBP), prealbumin (PA), transferrin (Tf), and hemoglobin (Hb) in serum), and inflammation biomarkers such as carboxyhemoglobin (COHb), High sensitivity C-reactive protein (Hs-CRP), Tumor Necrosis Factor-alpha (TNF-α), Interleukin 6 (IL-6), and Serum Amyloid A (SAA) were measured. The BODE index was measured in terms of prognosis. These measurements were compared between the real acupuncture group (RAG) and the placebo acupuncture group (PAG). All data are presented as mean (SD) or mean (95% CI). The difference between baseline and final volumes was compared using analysis of covariance (ANCOVA). Moreover, correlations between nutritional hematological examination scores and inflammation biomarker parameters were assessed using Spearman's rank correlation coefficient. RESULTS: After 12 weeks, the change in body weight was significantly greater in the RAG compared with the PAG (mean [SD] difference from baseline: 2.5 [0.4] in RAG vs - 0.5 [1.4] in PAG; mean difference between the groups: 3.00, 95% CI, 2.00 to 4.00 with ANCOVA). Patients in RAG also had improvements in the results of nutritional hematological examination (RBP, PA, Tf, Hb), Inflammation biomarkers (TNF-α, IL-6, SAA, Hs-CRP, COHb) and the BODE index. CONCLUSION: This study demonstrated some clear evidences that acupuncture can be a useful adjunctive therapy to improve nutritional state of COPD patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry ( UMIN000001277 ). Retrospectively registered.

Development and validation of a prognostic scoring model for Mycobacterium avium complex lung disease: an observational cohort study.

BACKGROUND: Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival. METHODS: We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2. RESULTS: Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index <18.5 kg/m2, lymphocyte count <1000 cells/µL, serum albumin levels <3.5 g/dL, and fibrocavitary disease. The areas under the receiver operating characteristic curves for the prognostic scoring model were 0.84 [95% confidence interval (CI), 0.80 - 0.89] for cohort 1 and 0.84 (95% CI, 0.75 - 0.92) for cohort 2. The 5-year OS rates of patients stratified into low-risk, intermediate-risk, and high-risk groups were 97.6, 76.6, and 30.8%, respectively (P < 0.001), in cohort 1, and 97.2, 82.3, and 45.4%, respectively (P < 0.001), in cohort 2. CONCLUSIONS: This study is the first to develop and validate a prognostic scoring model for patients with MAC-LD. This model may prove useful in clinical settings and practical in estimating the prognosis.

Nontuberculous Mycobacteria Infection and Prognosis after Surgery of Lung Cancer: A Retrospective Study.

To investigate the association between pulmonary nontuberculous mycobacteria infection (PNTMI) and prognosis after pulmonary resection for non small cell lung cancer (NSCLC), we retrospectively analyzed 391 consecutive patients with NSCLC who underwent surgery. Subjects were grouped based on with/without PNTMI defined by two criteria (12 and 23 PNTMI subjects). Kaplan-Meier analysis showed no significant difference between the two groups regarding overall survival (p = 0.800 and p = 0.912 by two criteria). PNTMI was not identified as a significant factor associated with prognosis by either univariate or multivariate analysis (hazard ratio [HR] = 0.950 and HR = 0.948, respectively).