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.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

Risks and Cough-Aggravating Factors in Prolonged Cough. Epidemiological Observations from the Nagahama Cohort Study.

RATIONALE: Chronic cough hypersensitivity, a potentially important concept of chronic or prolonged cough, is featured by heightened cough response to low-intensity stimuli, which may be generated in the absence of airflow limitations or allergic conditions. However, there is little epidemiological evidence to support this. OBJECTIVES: In this large-scale community survey, we aimed to determine risks and cough-aggravating factors of prolonged cough while focusing on serum IgE levels. METHODS: Prevalence of prolonged cough, defined as cough lasting 3 weeks or longer, was determined in 9,804 residents from a baseline measurement of the Nagahama Cohort Study, conducted from 2008 to 2010. Risk assessment of prolonged cough was confined to subjects without asthma (n = 9,402). A follow-up measurement of the Nagahama Study was successively conducted from 2013 to 2015, recruiting the same residents living in Nagahama City, Japan (n = 8,292). Validation analysis was performed in the follow-up measurement. RESULTS: In a baseline measurement, prolonged cough was reported by 9.5% of subjects without asthma and 32.3% of subjects with asthma. In subjects without asthma, various cough-aggravating factors were associated with prolonged cough. On the multivariate analysis, several cough-aggravating factors, including nighttime or early morning, weather, pollen season, and common cold, were associated with prolonged cough, independent of female sex, younger age, chronic obstructive pulmonary disease, postnasal drip, daytime sputum, and lower serum total IgE. Serum-specific IgE levels against Japanese cedar pollen were significantly higher in subjects who responded "yes" to "cough in the pollen season" than in those who did not respond, whereas, among subjects who responded "yes" to "cough in the pollen season," prolonged coughers showed lower serum IgE levels against Japanese cedar pollen than temporal coughers. Validation analysis in a follow-up measurement confirmed the associations between prolonged cough and cough-aggravating factors observed in the baseline measurement. CONCLUSIONS: The presence of several cough-aggravating factors in the absence of severe allergic conditions may support the presence of cough hypersensitivity.

The influence of environmental exposure on the response to antimicrobial treatment in pulmonary Mycobacterial avium complex disease.

BACKGROUND: Environmental exposure is a likely risk factor for the development of pulmonary Mycobacterium avium complex (MAC) disease. The influence of environmental exposure on the response to antimicrobial treatment and relapse is unknown. METHODS: We recruited 72 patients with pulmonary MAC disease (male [female], 18 [54]; age, 61.7 ± 10.3 years) who initiated and completed standard three-drug regimens for more than 12 months between January 2007 and December 2011. The factors associated with sputum conversion, relapse and treatment success without relapse were retrospectively evaluated after adjustments for confounding predictors. RESULTS: Fifty-two patients (72.2%) demonstrated sputum conversion, and 15 patients (28.8%) relapsed. A total of 37 patients (51.4%) demonstrated treatment success. Sputum conversion was associated with negative smears (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.27-12.60; P = 0.02). A relapse occurred in patients with low soil exposure after the start of treatment less frequently than in patients with high soil exposure (7/42 [16.7%] vs. 8/10 [80.0%], P = 0.0003). Treatment success was associated with low soil exposure after the beginning of treatment (OR, 13.46; 95% CI, 3.24-93.43; P = 0.0001) and a negative smear (OR, 2.97; 95% CI, 1.02-9.13; P = 0.047). CONCLUSION: Low soil exposure was independently associated with better microbiological outcomes in patients with pulmonary MAC disease after adjusting for confounding clinical, microbiological and radiographic findings.

A randomized, placebo-controlled trial of acupuncture in patients with chronic obstructive pulmonary disease (COPD): the COPD-acupuncture trial (CAT).

BACKGROUND: Dyspnea on exertion (DOE) is a major symptom of chronic obstructive pulmonary disease (COPD) and is difficult to control. This study was performed to determine whether acupuncture is superior to placebo needling in improving DOE in patients with COPD who are receiving standard medication. METHODS: Sixty-eight of 111 patients from the Kansai region of Japan who were diagnosed as having COPD and were receiving standard medication participated in a randomized, parallel-group, placebo-controlled trial (July 1, 2006, through March 31, 2009) in which the patients, evaluators, and statistician were unaware of the random allocation. Participants were randomly assigned to traditional acupuncture (real acupuncture group, n=34) or placebo needling (placebo acupuncture group, n=34). Both groups received real or placebo needling at the same acupoints once a week for 12 weeks. The primary end point was the modified Borg scale score evaluated immediately after the 6-minute walk test. Measurements were obtained at baseline and after 12 weeks of treatment. RESULT: After 12 weeks, the Borg scale score after the 6-minute walk test was significantly better in the real acupuncture group compared with the placebo acupuncture group (mean [SD] difference from baseline by analysis of covariance, -3.6 [1.9] vs 0.4 [1.2]; mean difference between groups by analysis of covariance, -3.58; 95% CI, -4.27 to -2.90). Patients with COPD who received real acupuncture also experienced improvement in the 6-minute walk distance during exercise, indicating better exercise tolerance and reduced DOE. CONCLUSION: This study clearly demonstrates that acupuncture is a useful adjunctive therapy in reducing DOE in patients with COPD. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000001277.

All-trans retinoic acid modulates radiation-induced proliferation of lung fibroblasts via IL-6/IL-6R system.

Although high-dose thoracic radiotherapy is an effective strategy for some malignancies including lung cancers and malignant lymphomas, it often causes complications of radiation fibrosis. To study the mechanism initiating tissue fibrosis, we investigated irradiation-induced cytokine production from human lung fibroblastic cells and found that IL-6 production was stimulated by irradiation. IL-6 is an autocrine growth factor for human myeloma cells, and retinoic acid is reported to inhibit their growth. Thus we evaluated the effect of all-trans retinoic acid (ATRA) on cell proliferation of lung fibroblasts along with the cytokine/receptor system. Irradiation-dependent stimulation of IL-6 production was correlated with increased NF-kappaB activity, and ATRA reduced this effect. Irradiation also increased the levels of mRNA for IL-6R and gp130, which were blocked by coexisting ATRA. Furthermore, IL-6 stimulated cell proliferation in dose-dependent manner but was overcome by pharmacological concentration of ATRA. These effects of ATRA were inhibited by rottlerin, which suggests ATRA abolished irradiation-induced stimulation through a PKCdelta-dependent pathway. Finally, we demonstrated that IL-6 transcripts in the lung were upregulated at 2 mo after irradiation, and the effect was inhibited by the intraperitoneal administration of ATRA. ATRA is expected to have an advantage for radiotherapy in its antitumor effects, as reported previously, and to prevent radiotherapy-induced pulmonary injury.