Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry.

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

Association between annual change in FEV1 and comorbidities or impulse oscillometry in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The decline in forced expiratory volume in one second (FEV1) is considered to be one of the most important outcome measures for evaluating disease progression. However, the only intervention proven to improve COPD prognosis is smoking cessation. This study therefore investigated the factors associated with annual FEV1 decline in COPD. METHODS: This retrospective study followed up 65 patients treated for COPD for 5 years: 13 current smokers and 52 former smokers, 25 with pneumonia, 24 with asthma, 18 with cancer, and 17 with cardiovascular disease. The patients were divided into groups based on clinical cutoff parameters of the impulse oscillometry system (IOS): 11 high and 54 low R5, 8 high and 57 low R20, 21 high and 44 low R5-R20, 26 high and 39 low X5, 38 high and 27 low Fres, and 36 high and 29 low AX. We investigated whether the decline in FEV1 was associated with comorbidities and IOS parameters. RESULTS: The annual change in FEV1 over 5 years was significantly affected by smoking status (current - 66.2 mL/year vs. former - 5.7 mL/year, p < 0.01), pneumonia (with - 31.5 mL/year vs. without - 8.9 mL/year, p < 0.05), asthma (with - 30.2 mL/year vs. - 10.8 mL/year, p < 0.01), but not by cancer and cardiovascular disease. In the groups defined by IOS results, only the high AX group had significantly more annual decline in FEV1 and %FEV1 than the low AX group (- 22.1 vs. - 12.8, p < 0.05 and - 0.20 vs. 0.40, p < 0.05, respectively). CONCLUSIONS: Continuing smoking as well as complications in pneumonia and asthma would be risk factors for the progression of COPD. AX might be a suitable parameter to predict the prognosis of patients with COPD.

A retrospective analysis of usefulness of impulse oscillometry system in the treatment of asthma.

BACKGROUND: Bronchial asthma (BA) has different phenotypes, and it requires a clinically effective subtype classification system. The impulse oscillometry system (IOS) is an emerging technique device used in respiratory functional tests. However, its efficacy has not been validated. Therefore, this study aimed to assess the relationship between BA and the IOS parameters, and the difference in the therapeutic effects of inhaled corticosteroids (ICSs) among the subtype classifications was evaluated using the IOS. METHODS: Of the 245 patients with bronchial asthma who were screened, 108 were enrolled in this study. These patients were divided based on three subtypes according to the IOS result as follows: central predominant type (n = 34), peripheral predominant type (n = 58), and resistless type (n = 16). Then, the following ICSs were randomly prescribed in daily medical care: coarse-particle ICS (fluticasone propionate [FP]), fine-particle ICS (mometasone furoate [MF]), and moderate-particle ICS (budesonide [BUD]). The treatment effects were assessed using the Asthma Health Questionnaire (AHQ) and the Asthma Control Test (ACT) and were compared among the three subtypes. RESULTS: In the central predominant type, the AHQ score of the MF group was significantly higher than that of the FP group (15.4 vs. 3.6, p < 0.01) and the BUD group (15.4 vs. 8.8, p < 0.05); the ACT score of the FP group was significantly higher than that of the MF and BUD groups (24.3 vs. 21.7, 22.3, respectively, p < 0.05) at 4 weeks after treatment. In the peripheral predominant type, the AHQ score of the FP group was significantly higher than that of the MF group (14.1 vs. 3.4, p < 0.05); the ACT score of the FP group was lower than that of the MF and BUD groups (22.8 vs. 24.6, 24.4, respectively, p < 0.01) at 4 weeks after treatment. CONCLUSIONS: An association was observed between IOS subtype classification and ICS particle size in terms of therapeutic efficacy in BA. This result indicates that the IOS could be an effective tool in the selection of ICS and the evaluation of the BA phenotype.

Comparison of therapeutic effects of inhaled corticosteroids on three subtypes of cough variant asthma as classified by the impulse oscillometry system.

BACKGROUND: Cough variant asthma (CVA) is one of the most common causes of chronic persistent cough, and early treatment with inhaled corticosteroids (ICSs) is recommended to attenuate the inflammation and remodeling. The impulse oscillometry system (IOS) is a novel device for respiratory functional assessment that has not yet been assessed in terms of CVA. Therefore, we investigated the relationship between CVA and IOS, and the difference in therapeutic effects of ICSs among the subtype classifications by IOS. METHODS: The following ICSs were randomly prescribed in daily medical care: coarse-particle ICS (fluticasone propionate [FP]), fine-particle ICS (mometasone furoate [MF]), and moderate-particle ICS (budesonide [BUD]). Treatment effects were assessed by the Leicester cough questionnaire (LCQ) and were compared among three separated subtypes based on IOS measurements: central, peripheral, and resistless. RESULTS: Regarding LCQ scores, in the central type, the LCQ of the MF group was significantly lower than FP and BUD. In the peripheral type, the LCQ of the FP group was significantly lower than MF and BUD. In the resistless type, the LCQ of the MF group was significantly lower than BUD. Also, IOS factors were improved by 4 weeks of therapy with ICS. Thus, there was strong relationship between subtypes and particle size in terms of effectiveness. CONCLUSIONS: There is a strong relationship between IOS subtype classification and ICS particle size in terms of therapeutic efficiency in CVA. It appears important to determine the ICS particle size, based on the IOS subtype classification, before treatment.

Large-Scale Moth-Eye-Structured Roll Mold Fabrication Using Sputtered Glassy Carbon Layer and Transferred Moth-Eye Film Characterization.

Currently, there is high demand for the development of a highly mass-producible technology for manufacturing moth-eye-structured films with an antireflection function. Conventional moth-eye-structured films have been produced by roll-to-roll (RTR) ultraviolet nanoimprint lithography (UV-NIL) using porous alumina, but the process of manufacturing the roll mold with aluminum is both complicated and time-consuming. To solve this problem, we proposed a sputtering process for forming a thin film of glassy carbon on a roll substrate and fabricated a moth-eye structure through the irradiation of oxygen plasma. A glassy carbon (GC) moth-eye-structure roll mold with a uniform reflectance of less than 0.1% over a length of 1560 mm was fabricated following this method. In addition, a superhydrophobic moth-eye-structured film was produced by RTR UV-NIL using the proposed roll mold, which exhibited a reflectance of 0.1%. In this study, a moth-eye-structure roll using porous alumina was compared with a film transferred from it. The GC moth-eye-structure roll mold was found to be superior in terms of antireflection, water repellency, and productivity. When the proposed large-area GC moth-eye-structured film was applied to window glass, significant anti-reflection and water-repellent functionalities were obtained.

Factors affecting the use of clinical practice guidelines by hospital physicians: the interplay of IT infrastructure and physician attitudes.

BACKGROUND: Compliance with clinical practice guidelines (CPGs) remains insufficient around the world, despite frequent updates and continuing efforts to disseminate and implement these guidelines through a variety of strategies. We describe the current status of young resident physician practices towards CPGs and investigate the multiple factors associated with the active use of CPGs, including the physician's knowledge, attitudes, behaviours, CPG-related education received, and the hospital's IT infrastructures. The aim is to identify a more effective point for intervention to promote CPG implementation. METHODS: We conducted a questionnaire survey among resident physicians working at 111 hospitals across Japan in 2015 and used results with hospital IT score data collected from a prior survey. Multivariable logistic regression analysis was performed to examine the determinants of frequent use of CPGs (defined at least once per week). The independent variables were selected based on physician demographics, clinical speciality and careers, daily knowledge and behaviour items, CPG-related education received, digital preference, and hospital IT score (high/medium/low), with and without interaction terms. RESULTS: Responses from 535 resident physicians, at 61 hospitals, were analysed. The median hospital IT score was 6 out of a possible 10 points. Physicians who had learned about CPGs tended to work at hospitals with medium to high IT scores, had easier access to paywalled medical databases, and had better knowledge of the guideline network 'Minds'. In addition, these physicians tended to use CPGs electronically. A physician's behaviour towards using CPGs for therapeutic decision-making was strongly associated with frequent use of CPGs (odds ratio [95% CI] 6.1 [3.6-10.4]), which indicated that a physician's habit strongly promotes CPG use. Moreover, CPG-related education was associated with active use of CPGs (OR1.7 [1.1-2.5]). The interaction effects between individual digital preferences and higher hospital IT score were also observed for frequent CPG use (OR2.9 [0.9-8.8]). CONCLUSIONS: A physician's habitual behaviours, CPG-related education, and a combination of individual digital preference and superior hospital IT infrastructure are key to bridging the gap between the use and implementation of CPGs.

Does hospital information technology infrastructure promote the implementation of clinical practice guidelines? A multicentre observational study of Japanese hospitals.

OBJECTIVES: It remains unclear whether insufficient information technology (IT) infrastructure in hospitals hinders implementation of clinical practice guidelines (CPGs) and affects healthcare quality. The objectives of this study were to describe the present state of IT infrastructure provided in acute care hospitals across Japan and to investigate its association with healthcare quality. METHODS: A questionnaire survey of hospital administrators was conducted in 2015 to gather information on hospital-level policies and elements of IT infrastructure. The number of positive responses by each respondent to the survey items was tallied. Next, a composite quality indicator (QI) score of hospital adherence to CPGs for perioperative antibiotic prophylaxis was calculated using administrative claims data. Based on this QI score, we performed a chi-squared automatic interaction detection (CHAID) analysis to identify correlates of hospital healthcare quality. The independent variables included hospital size and teaching status in addition to hospital policies and elements of IT infrastructure. RESULTS: Wide variations were observed in the availability of various IT infrastructure elements across hospitals, especially in local area network availability and access to paid evidence databases. The CHAID analysis showed that hospitals with a high level of access to paid databases (p<0.05) and internet (p<0.05) were strongly associated with increased care quality in larger or teaching hospitals. CONCLUSIONS: Hospitals with superior IT infrastructure may provide higher-quality care. This allows clinicians to easily access the latest information on evidence-based medicine and facilitate the dissemination of CPGs. The systematic improvement of hospital IT infrastructure may promote CPG use and narrow the evidence-practice gaps.

Composting cattle dung wastes by using a hyperthermophilic pre-treatment process: characterization by physicochemical and molecular biological analysis.

To solve malodorous odor problems by ammonia emission in composting of cattle dung wastes, we developed an alternative composting method consisting of a hyperthrmophilic pre-treatment reactor (HTPRT) (first step) combined with a general windrow post-treatment system (WPOT) (second step). In this study, physicochemical and microbiological differences in compost materials during the HTPRT-WPOT process and a simple windrow composing process (SWC) were investigated. The HTPRT-WPOT process removed excess ammonia in the compost materials by physical ammonia stripping, and controlled the malodorous ammonia emission. The organic matter evolution index showed that the HTPRT-WPOT process also contributed to accelerate formation of humic acids in composting. Quantitative real-time PCR analyses using Bacterial-, Archaeal- and fungal-protozoan-specific primer sets showed that small subunit ribosomal RNA (SSU rRNA) gene copy numbers differed much between composting materials of these two processes. Particularly, the SSU rRNA gene copy of eukaryotic microbes (fungi-protozoa) in the HTPRT-WPOT process was much higher than in the SWC process. From these results, we conclude that the HTPRT-WPOT process has great advantages for the control of malodorous odor problems caused by ammonia emission, and for high rate of composting evaluated by the humification rate and microbial characterization of the composting materials.

Workplace-related chronic cough on a mushroom farm.

BACKGROUND: Mushroom spores have frequently been associated with respiratory allergy. The aims of this study were to elucidate the incidence and causes of chronic cough in a mushroom farm. METHODS: Participants were 69 mushroom workers who produce Hypsizigus marmoreus (Bunashimeji) and 35 control subjects. We excluded six workers because they had had asthma or allergic rhinitis before working. Participants completed a cross-sectional health survey 2 years after starting work at the mushroom farm. RESULTS: The mean airborne endotoxin levels in the harvesting and packing rooms were approximately 60-fold higher than those in the offices. Of 63 workers, 42 workers (67%) reported chronic cough after working on this farm, 19 workers had no cough, while 2 workers had hypersensitivity pneumonitis develop to the spore, which has been previously reported by us. Of the 42 workers with cough, 6 workers had organic dust toxic syndrome (ODTS), 18 workers had postnasal drip syndrome, 15 workers had cough variant asthma, and 3 workers had eosinophilic bronchitis. Seventy-one percent of the workers noticed the cough in the first 3 months, and the mean latent period in ODTS workers was the shortest. The cough had a trend to improve or disappear after weekend holidays. Bronchial hyperresponsiveness but not FEV(1)/FVC% in the 42 workers with cough was significantly (p < 0.001) increased as compared with the control subjects. CONCLUSIONS: Working on a mushroom farm carries a significant risk for chronic cough from inhalation of mushroom spores, and we suggest that elevated airborne endotoxin on this farm is the cause.

Hypersensitivity pneumonitis induced by the spore of Pleurotus Eryngii (Eringi).

We reported the first case of hypersensitivity pneumonitis (HP) by an edible mushroom, Pleurotus Eryngii (Eringi). A 54-year-old woman had worked in a Bunashimeji mushroom factory for 42 months, and she moved to a new factory producing Eringi. Two months after, she was found to have HP by the spore of Eringi. Although no radiological finding was detected 6 months before the onset of HP, serum surfactant protein D (SP-D) had been elevated. We speculated that type II pneumocyte activation might prepare the ground for HP during the former exposure to Bunashimeji, and serum SP-D levels might reflect their conditions.

An Unusual Case of Multiple Gastric Carcinoids Associated with Diffuse Endocrine Cell Hyperplasia and Parietal Cell Hypertrophy.

We describe a case of multiple gastric carcinoid tumors in a 47 year-old Japanese man. The patient had markedly elevated serum gastrin levels (>800 pg/mL), which were suppressed by secretin-pancreozymin administration. In the partial gastrectomy specimen, a total of 19 carcinoids arose from diffuse linear and micronodular hyperplasia of the oxyntic mucosal endocrine cells. The carcinoid cells were chromogranin A-positive. Except for a very small number of serotonin-positive cells in several carcinoids, none of the 19 reacted with a battery of antibodies to other bioactive neuroendocrine substances. The most prominent findings in this case were peculiar fundic glands that were distended with a proteinaceous substance and lined with large hypertrophic parietal cells. At the ultra-structural level, these cells showed poorly developed intracytoplasmic canaliculi and vesicotubular profiles, yet their large cytoplasm had numerous mitochondria. On the basis of our histological and ultrastructural findings we suggest that an intrinsic HCI secretion abnormality of the parietal cells may be responsible for the patient's hypergastranemia. Since there have been no reports on similar parietal cells changes, it is possible that our case may represent a pathological entity not previously described.