A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib.

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

Changes in diaphragm thickness and 6-min walking distance improvement after inspiratory muscle training in patients with chronic obstructive pulmonary disease: Clinical trial.

Aim: Inspiratory muscle training (IMT) improves respiratory muscle function and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD), but the detailed mechanism is unclear. The purpose of this study is to elucidate the mechanism of functional improvement by IMT from P0.1, an index of respiratory central output, and thickness of diaphragm (Tdi), a noninvasive and reliable ultrasound examination. Methods: This clinical trial study enrolled 13 elderly patients with COPD. IMT was performed using the POWER breathe® Medic Plus breathing trainer in combination with each participant's outpatient rehabilitation regimen. Starting at 20% of the maximal inspiratory pressure (PImax) and increasing to 50%, the participants performed 30 IMT repetitions twice a day for 2 months. P0.1 is the value of airway-occlusion pressure at 0.1 s after the start of inspiratory flow, and Tdi was measured at rest and maximal breathing. Results: PImax and 6-min walking distance(6MWD) significantly increased after training. Tdi at resting inspiration and expiration, and maximal inspiration also significantly increased after training. In addition, the Borg Scale scores for dyspnea and leg fatigue and the respiratory rate of the 1-min recovery period after the 6MWD significantly decreased. There was no significant difference in P0.1. Conclusions: These results suggest that the effects of IMT may be attributed to the improved peripheral factors rather than to the central factors in elderly COPD patients.

Differences in Characteristics Between Physical Frailty Assessments in Chronic Obstructive Pulmonary Disease: A Multicenter Cross-Sectional Observational Study.

Purpose: Assessment for frailty is important as it enables timely intervention to prevent or delay poor prognosis in chronic obstructive pulmonary disease (COPD). The aims of this study, in a sample of outpatients with COPD, were to (i) assess the prevalence of physical frailty using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria and the Short Physical Performance Battery (SPPB) and the degree of agreement between the findings of the two assessments and (ii) identify factors associated with the disparity in the results obtained with these instruments. Patients and Methods: This was a multicenter cross-sectional study of individuals with stable COPD enrolled in four institutions. Frailty was assessed using the J-CHS criteria and the SPPB. Weighted Cohen's kappa (k) statistic was performed to investigate the magnitude of agreement between the instruments. We divided participants into two groups depending on whether there was agreement or non-agreement between the results of the two frailty assessments. The two groups were then compared with respect to their clinical data. Results: A total of 103 participants (81 male) were included in the analysis. The median age and FEV1 (%predicted) were 77 years and 62%, respectively. The prevalence of frailty and pre-frail was 21% and 56% with the J-CHS criteria and 10% and 17% with the SPPB. The degree of agreement was fair (k = 0.36 [95% CI: 0.22-0.50], P<0.001). There were no significant differences in the clinical characteristics between the agreement group (n = 44) and the non-agreement group (n = 59). Conclusion: We showed that the degree of agreement was fair with the J-CHS criteria detecting a higher prevalence than the SPPB. Our findings suggest that the J-CHS criteria may be useful in people with COPD with the aim of providing interventions to reverse frailty in the early stages.

Multimodal Telemonitoring for Weight Reduction in Patients With Sleep Apnea: A Randomized Controlled Trial.

BACKGROUND: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA. RESEARCH QUESTION: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP? STUDY DESIGN AND METHODS: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline. RESULTS: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm.

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).

Early Intervention of Pulmonary Rehabilitation for Fibrotic Interstitial Lung Disease Is a Favorable Factor for Short-Term Improvement in Health-Related Quality of Life.

Patients with fibrosing interstitial lung disease (FILD) have poor health-related quality of life (HRQOL). We analyzed predictors of short-term improvement of HRQOL after starting pulmonary rehabilitation (PR) in moderate to severe FILD patients. This study involved 28 consecutive patients with FILD (20 males, median age of 77.5 years), who participated in PR program of our hospital for >6 weeks. The St. George's Respiratory Questionnaire (SGRQ) score and the 6-min walk distance (6MWD) were evaluated before and after PR, and the predictors of efficacy of PR were analyzed. The duration from diagnosis of FILD to start of PR showed a positive correlation with the increase in the SGRQ score, and the baseline SGRQ score showed a negative correlation with increase in the 6MWD. The FILD subtype, modified Medical Research Council score, and treatment history were not associated with the endpoints. According to the receiver operating characteristic curve (ROC) analyses, starting PR within 514 days after diagnosis of FILD was a significant favorable predictor of improvement in the SGRQ total score more than a minimal clinically important difference of 4. In this study, early intervention of PR and lower SGRQ score were associated with the favorable response to PR. PR for FILD should be initiated early before the disease becomes severe.

Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry.

BACKGROUND: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. MATERIALS AND METHODS: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. RESULTS: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). CONCLUSIONS: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.

Characteristics of tobacco-related lung diseases in Fukuoka Prefecture, Japan: A prospective, multi-institutional, observational study.

BACKGROUND: Tobacco smoking causes a variety of smoking-related diseases, death, and economic damage. Despite targeted anti-smoking campaigns, tobacco-related deaths are expected to increase in Japan. We investigated the current state of non-cancerous lung diseases such as idiopathic interstitial pneumonias (IIPs), chronic obstructive pulmonary disease (COPD), and combined pulmonary fibrosis and emphysema (CPFE), which are known to be highly related to tobacco smoking. METHODS: This prospective multi-institutional observational study involved 29 major hospitals within the Fukuoka Prefecture area (Fukuoka tobacco-related lung disease registry study group). Patients diagnosed with IIPs, including CPFE and COPD, registered from September 1, 2013 to April 30, 2016 were included. Clinical background information, laboratory and pulmonary function test results, findings of imaging tests, including chest radiography and chest computed tomography, and DNA isolated from peripheral blood were collected from each patient. Follow-up surveillance involved collection of data regarding the exacerbation of disease and death until 5 years of registration. In the present study, we report the baseline characteristics of the patients registered in this surveillance study. RESULTS: Overall, 1016 patients (524 with IIPs, including 145 CPFE and 492 with COPD) were enrolled. Among the patients with COPD, 96.8% were current or former smokers. Among the patients with IIPs, 69.9% were current or former smokers. CONCLUSION: This study revealed the current status of lung diseases potentially related to tobacco smoking in Fukuoka Prefecture. Both COPD and CPFE were highly related to tobacco smoking, whereas 30% of patients with IIPs had never smoked.

A Randomized Controlled Trial of Telemedicine for Long-Term Sleep Apnea Continuous Positive Airway Pressure Management.

Rationale: The effects of telemedicine on adherence in patients with obstructive sleep apnea with long-term continuous positive airway pressure (CPAP) use have never been investigated.Objectives: To examine effects of a telemedicine intervention on adherence in long-term CPAP users.Methods: In a prospective, randomized, multicenter noninferiority trial conducted in 17 sleep centers across Japan, patients who had used CPAP for >3 months and were receiving face-to-face follow-up by physicians every 1 or 2 months were randomized by a coordinating center in a blind manner to the following three groups: 1) follow-up every 3 months accompanied by a monthly telemedicine intervention (telemedicine group: TM-group), 2) follow-up every 3 months (3-month group: 3M-group), or 3) monthly follow-up (1-month group: 1M-group). Each group was followed up for 6 months. The change in percentage of days with ≥4 h/night of CPAP use from baseline to the end of the study period was evaluated. A decline of ≥5% from baseline was considered deterioration of adherence. Noninferiority of TM- and 3M-groups compared with the 1M-group according to the number of patients with deterioration of adherence was evaluated with the Farrington and Manning test (noninferiority margin 15%).Results: A total of 483 patients were analyzed (median duration of CPAP use, 29 [interquartile range, 12-71] mo), and deterioration of adherence was found in 41 of 161 (25.5%), 55 of 166 (33.1%), and 35 of 156 (22.4%) patients in the TM-, 3M-, and 1M-groups, respectively. The noninferiority of the TM-group compared with the 1M-group was verified (difference in percentage of patients with adherence deterioration, 3.0%; 95% confidence interval [CI], -4.8% to 10.9%; P < 0.01). Conversely, the 3M-group did not show noninferiority to the 1M-group (percentage difference, 10.7%; 95% CI, 2.6% to 18.8%; P = 0.19). In the stratified analysis, adherence in TM- and 1M-group patients with poor adherence at baseline improved (TM: 45.8% ± 18.2% to 57.3% ± 24.4%; P < 0.01; 1M: 43.1% ± 18.5% to 53.6% ± 24.3%; P < 0.01), whereas that of the 3M-group did not (39.3% ± 20.8% to 39.8% ± 24.8%; P = 0.84).Conclusions: Intensive telemedicine support could help to optimize CPAP adherence even after long-term CPAP use.Clinical trial registered with www.umin.ac.jp/ctr/index.htm (trial number: UMIN000023118).

[Sleep-disordered breathing in occupational places: from screening to Health and Productivity Management].

BACKGROUND: Sleep-disordered breathing (SDB), represented by sleep apnea, is highly prevalent in the general population and is associated with alcohol intake and obesity. Since SDB is further associated with hypertension, diabetes, and future cardiovascular diseases, as well as accidents and injuries in workplaces, there is a need for complete SDB assessment in workers, including screening and the application of diagnostic and therapeutic approaches. RESULTS: Currently, it appears that SDB assessment is not sufficiently conducted, even among commercial motor vehicle (CMV) drivers, despite CMV drivers with SDB being at a high risk of serious traffic accidents. Based on a discussion conducted in The Study Group for Sleep Disordered Breathing in Work Places, we summarized the current situation in Japan and tried to elucidate the bottleneck of these approaches. Then, the situation in Japan was compared with that in South Korea; Professor Chol Shin substantiated that the situation in South Korea was similar to that in Japan. However, recently published data on CMV drivers in the United States showed that appropriate treatment of SDB reduced the risk of traffic accidents among CMV drivers. This will encourage the implementation of the required processes, from screening to maintenance of treatment. CONCLUSION: We propose a new approach based on "harmonizing work with treatment and prevention" and "Health and Productivity Management (HPM)" as a solution for implementing SDB programs.

Oral health under use of continuous positive airway pressure and interest in alternative therapy in patients with obstructive sleep apnoea: a questionnaire-based survey.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with a variety of adverse health outcomes. Continuous positive airway pressure (CPAP) is considered first-line treatment for sleep apnoea patients, but there are few studies on oral health in patients with OSA who are using CPAP. OBJECTIVE: This study aimed to estimate the prevalence of oral symptoms and interest in alternative treatments such as oral appliance (OA) therapy in CPAP users. METHODS: A questionnaire was used to ascertain oral health including denture use, oral symptoms at present and since the start of CPAP, and interest in OA therapy. Relevant demographic and clinical data were collected from medical records. RESULTS: The 744 participants who completed the questionnaire had following characteristics (mean ± standard deviation): age (55.1 ± 12.9 years); apnoea-hypopnoea index (40.9 ± 23.2/h); body mass index (27.9 ± 5.2 kg/m(2) ) and length of CPAP usage (49.1 ± 30.7 months); halitosis (30.4%); and gingival bleeding (27.5%). Nearly half (44.6%) complained of dry mouth since beginning CPAP therapy. Patients with diabetes were older (57.8 ± 11.9 vs. 54.2 ± 12.8 years), had a higher rate of denture use (28.3 vs. 19.0%), more dental clinic visits (71.4 vs. 58.7%) and more oral symptoms (50.0 vs. 38.2%) than non-diabetes patients (p < 0.05). Thirty-eight per cent of subjects were interested in OA therapy. CONCLUSIONS: This study exhibited that almost 40% of CPAP users had oral symptoms. In particular, OSA patients with diabetes may be at high risk of oral disease.

[Efficacy and safety of azithromycin infusion in patients with mild or moderate community-acquired pneumonia].

Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

High-resolution CT scoring system-based grading scale predicts the clinical outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The 2011 idiopathic pulmonary fibrosis (IPF) guidelines are based on the diagnosis of IPF using only high-resolution computed tomography (HRCT). However, few studies have thus far reviewed the usefulness of the HRCT scoring system based on the grading scale provided in the guidelines. We retrospectively studied 98 patients with respect to assess the prognostic value of changes in HRCT findings using a new HRCT scoring system based on the grading scale published in the guidelines. METHODS: Consecutive patients with IPF who were diagnosed using HRCT alone between January 2008 and January 2012 were evaluated. HRCT examinations and pulmonary function tests were performed at six-month intervals for the first year after diagnosis. The HRCT findings were evaluated using the new HRCT scoring system (HRCT fibrosis score) over time. The findings and survival rates were analyzed using a Kaplan-Meier analysis. RESULTS: The HRCT fibrosis scores at six and 12 months after diagnosis were significantly increased compared to those observed at the initial diagnosis (p < 0.001). The patients with an elevated HRCT fibrosis score at six months based on a receiver operating characteristic (ROC) curves analysis had a poor prognosis (log-rank, hazard ratio [HR] 2.435, 95% CI 1.196-4.962; p = 0.0142). Furthermore, among the patients without marked changes in %FVC, those with an elevated score above the cut-off value had a poor prognosis (HR 2.192, 95% CI 1.003-4.791; p = 0.0491). CONCLUSIONS: Our data demonstrate that the HRCT scoring system based on the grading scale is useful for predicting the clinical outcomes of IPF and identifying patients with an adverse prognosis when used in combination with spirometry.

The relationship between cephalometric carotid artery calcification and Framingham Risk Score profile in patients with obstructive sleep apnea.

PURPOSE: The morbidity rate of arteriosclerosis becomes clinically manifested as acute cardiovascular events. In the progress of atherosclerosis, the carotid artery calcifies and sometimes appears as a calcified mass on a cephalometric radiograph. This study was designed to evaluate cardiovascular risks according to the Framingham Risk Score (FRS) between subjects with and without visible carotid artery calcification on a cephalogram. METHODS: Subjects diagnosed with obstructive sleep apnea (OSA) were divided into two groups according to whether or not calcification was visible on a cephalometric radiograph in the carotid artery area, and the characteristic differences between the two groups were analyzed. The evaluated variables included age, BMI, apnea-hypopnea index (AHI), SpO2, ESS, blood pressure, medication history, diabetes mellitus (DM), drinking, smoking, and lipid-related measurements. FRSs for stroke, general cardiovascular disease (GCD), and coronary heart disease (CHD) were calculated. Statistical analyses were performed (SPSS 18.0) with significance defined as a two-tailed p value less than 0.05. RESULTS: A total of 811 subjects completed the data collection (727 males, age 53.0 ± 12.5 years, AHI 31.7 ± 22.6, times/h). From FRSs, probabilities of a GCD, stroke, and CHD within 10 years were 16.0 ± 9.7, 9.8 ± 6.7, and 11.9 ± 8.3 %, respectively. Some 84 subjects exhibited calcification in the carotid arterial area. Calcification subjects were higher GCD risk and older than subjects who had no identified calcification (20.3 ± 10.1 vs 15.6 ± 20.3 %, p = 0.013, 58.8 ± 11.4 vs. 52.3 ± 12.5 years, p < 0.001). Although there is no significant difference in OSA-related variables and FRSs, subjects with visible calcifications have higher prevalence of high blood pressure medication and DM (p < 0.01). CONCLUSION: While the presence of a calcified mass on a cephalometric radiograph is not diagnostic of atherosclerosis, this information indicates some cardiovascular risk.

The reliability and validity of the Japanese version of the Appraisal of Diabetes Scale for type 2 diabetes patients.

AIMS: An appropriate questionnaire for measurement of the psychological burden of self-management or behavior modification in type-2 diabetes patients has yet to be developed in Japan. This study was conducted to test the reliability and validity of the Japanese version of the Appraisal of Diabetes Scale (ADS). METHODS: the study enrolled 346 Japanese patients with type 2 diabetes: 200 men and 146 women who were 63.2 ± 10.1 and 62.2 ± 11.9 years of age and had HbA1c levels of 6.9 ± 1.2% and 7.3 ± 1.9%, respectively. RESULTS: the questionnaire was divided into three components: "Psychological impact of diabetes", "Sense of self-control", and "Efforts for symptom management". Cronbach's alpha was 0.746-0.628. Significant correlations were observed between "Sense of self-control" and self-managed dietary and exercise behaviors and HbA1c levels; between "Psychological impact of diabetes" and various treatments, symptoms causing anxiety, and HbA1c levels; and between "Efforts for symptom management" and dietary and nutritional behaviors. The questionnaire showed better evidence of internal consistency, test-retest reliability and validity. CONCLUSION: our results suggested that the Japanese version of ADS may be a useful tool for the quick assessment of common anxieties and motivation toward treatment in patients with type 2 diabetes.

[Retrospective analysis of the safety of four hours administration of liposomal amphotericin B in patients with chronic necrotizing pulmonary aspergillosis].

We have retrospectively analyzed the safety of 4 hours administration of liposomal amphotericin B (L-AMB) compared to less than or equal to 3 hours administration in patients with chronic necrotizing pulmonary aspergillosis (CNPA). The elevation of serum creatinine in the group with 4 hours administration of L-AMB in patients with CNPA was equal to the group with shorter administration time (less than or equal to three hours). During the administration of L-AMB, the group with 4 hours administration of LAMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment than the group with shorter administration time. Additionally, white cell counts, platelet counts, serum creatinine, AST, ALT were not significantly different between L-AMB 4 hours administration group and less than or equal to 3 hours administration group. As the group with 4 hours administration of L-AMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment, this modality can be one of the safer ways in the treatment of CNPA. As L-AMB is one of the fungicidal agents, 4 hours administration of L-AMB can be an optimal way of treating CNPA.

Craniofacial changes after 2 years of nasal continuous positive airway pressure use in patients with obstructive sleep apnea.

BACKGROUND: Many patients with obstructive sleep apnea (OSA) use nasal continuous positive airway pressure (nCPAP) as a first-line therapy. Previous studies have reported midfacial hypoplasia in children using nCPAP. The aim of this study is to assess the craniofacial changes in adult subjects with OSA after nCPAP use. METHODS: Forty-six Japanese subjects who used nCPAP for a minimum of 2 years had both a baseline and a follow-up cephalometric radiograph taken. These two radiographs were analyzed, and changes in craniofacial structures were assessed. The cephalometric measurements evaluated were related to face height, interarch relationship, and tooth position. RESULTS: Most of the patients with OSA were men (89.1%), and the mean baseline values for age, BMI, and apnea-hypopnea index (AHI) were 56.3 ± 13.4 years, 26.8 ± 5.6 kg/m(2), and 42.0 ± 18.6/h. The average duration of nCPAP use was 35.0 ± 6.7 months. After nCPAP use, cephalometric variables demonstrated a significant retrusion of the anterior maxilla, a decrease in maxillary-mandibular discrepancy, a setback of the supramentale and chin positions, a retroclination of maxillary incisors, and a decrease of convexity. However, significant correlations between the craniofacial changes, demographic variables, or the duration of nCPAP use could not be identified. None of the patients self-reported any permanent change of occlusion or facial profile. CONCLUSION: The use of an nCPAP machine for > 2 years may change craniofacial form by reducing maxillary and mandibular prominence and/or by altering the relationship between the dental arches.

Cephalometric calcified carotid artery atheromas in patients with obstructive sleep apnea.

BACKGROUND: In the progress of atherosclerosis, the carotid artery calcifies and sometimes appears as a calcified mass on a cephalometric radiograph. PURPOSE: This study was designed to evaluate the prevalence of calcification in cephalometric radiographs of OSA patients and to identify the differences between subjects with and without carotid artery calcification. METHODS: A total of 1,520 X-rays were evaluated. Data for group A, 508 traditional X-rays, were collected from the UBC Sleep Apnea Dental Clinic and data for group B, 1,012 digital X-rays, were obtained from the Tsuda Hospital in Japan. Subjects were divided into two groups according to whether or not calcification was present in the carotid artery area and the characteristic differences between these two groups were analyzed. DISCUSSION: Group A had 34 (6.7%) subjects who exhibited calcification in the carotid arterial area, while group B had 96 (9.5%) subjects who revealed calcification. Group A calcification subjects had a significantly lower body mass index (BMI) than subjects who had no calcification (26.9 ± 3.2 vs. 29.7 ± 5.6, p<0.01). Group B calcification subjects were older than subjects who had no calcification (57.6 ± 12.6 vs. 49.8 ± 14.5, p<0.000). Previous reports have found the prevalence of calcification on X-rays of OSA patients to be higher than the prevalence of calcification found in the general population. CONCLUSION: While the presence of a calcified mass on a cephalometric radiograph is not diagnostic of atherosclerosis, this information might help to aid in screening for the condition.

Validation of "lung age" measured by spirometry and handy electronic FEV1/FEV6 meter in pulmonary diseases.

OBJECTIVE: The concept of "lung age" is thought to be useful for understanding pulmonary function. In this study, we validated "lung age" to detect pulmonary function abnormalities in pulmonary diseases. METHODS: We used both spirometry and an electronic FEV(1)/FEV(6) meter (FEV(6) meter) to perform pulmonary function tests. We evaluated the sensitivity and specificity of FEV(6) and FEV(1)/FEV(6), and calculated "lung age" in Japanese subjects including those with chronic obstructive pulmonary disease (COPD), bronchial asthma (BA), and interstitial lung diseases (ILD). RESULTS: FEV(1) (spirometer) vs. FEV(1) (FEV(6) meter), FVC (spirometer) vs. FEV(6) (FEV(6) meter), and FEV(1)/FVC (spirometer) vs. FEV(1)/FEV(6) (FEV(6) meter) measurements were all significantly and closely correlated. For the difference of "lung age" and "actual age", the area under the receiver operating characteristic curve (ROC-AUC) for detecting obstructive impairment was 0.807 (spirometer) and 0.772 (FEV(6) meter), respectively. The corresponding ROC-AUC for detecting restrictive impairment was 0.891 and 0.836, respectively, and that for detecting both obstructive and restrictive impairment was 0.918 and 0.853, respectively. For detection of both obstructive and restrictive impairment, the difference of the "lung age" and "actual age" cut-off value, corresponding to the greatest sum of sensitivity and specificity, was 18.3 years (spirometer) and 19.8 years (FEV(6) meter), respectively. The sensitivity was 0.783 (spirometer) and 0.801 (FEV(6) meter), and the specificity was 0.895 (spirometer) and 0.790 (FEV(6) meter), respectively. CONCLUSION: "Lung age" can provide an easy interpretation of the results, and can detect pulmonary function abnormalities in pulmonary diseases.

Effect of add-on therapy of tiotropium in COPD treated with theophylline.

BACKGROUND: Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators. OBJECTIVE: We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients. METHODS: In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD. RESULTS: Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV1) 1.5 L [62.5% predicted]). FEV1 in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 +/- 0.13 L, p < 0.001) and 8 weeks (1.60 +/- 0.13 L, p < 0.001) from the baseline (1.40 +/- 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p <0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV1. CONCLUSION: Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.