Mucus Plugs and Small Airway Dysfunction in Asthma,COPD, and Asthma-COPD Overlap

PurposeThere are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study.MethodsSubjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs.ResultsMucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population.ConclusionsSAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.     

High‐throughput screening in colorectal cancer tissue‐originated spheroids

Patient‐derived cancer organoid culture is an important live material that reflects clinical heterogeneity. However, the limited amount of organoids available for each case as well as the considerable amount of time and cost to expand in vitro makes it impractical to perform high‐throughput drug screening using organoid cultures from multiple patients. Here, we report an advanced system for the high‐throughput screening of 2427 drugs using the cancer tissue‐originated spheroid (CTOS) method. In this system, we apply the CTOS method in an ex vivo platform from xenograft tumors, using machines to handle CTOS and reagents, and testing a CTOS reference panel of multiple CTOS lines for the hit drugs. CTOS passages in xenograft tumors resulted in minimal changes of morphological and genomic status, and xenograft tumor generation efficiently expanded the number of CTOS to evaluate multiple drugs. Our panel of colorectal cancer CTOS lines exhibited diverse sensitivities to the hit compounds, demonstrating the usefulness of this system for investigating highly heterogeneous disease.     

Clinical characteristics of Japanese pustular psoriasis: A multicenter observational study

Generalized pustular psoriasis (GPP) is a rare and severe subtype of psoriasis. Because of its rarity, GPP studies with a large sample size have been scarce. We studied the characteristics of GPP and pustular psoriasis using data from the West Japan Psoriasis Registry that had been registered until the end of December 2020. The dataset included 104 patients with pustular psoriasis and 1290 patients with other subtypes of psoriasis. Multivariate analysis revealed a significantly greater number of female patients, a significantly lower mean body mass index, and a significantly lower ratio of habitual drinkers in pustular psoriasis, compared to other subtypes of psoriasis. Of the 104 patients, 102 had GPP, including 88 von Zumbusch, 10 juvenile-onset, and four annular pustular psoriasis. Although the male : female ratio of GPP with psoriasis vulgaris (GPP+PsV) (47/20) was similar to that of psoriasis in Japan, the GPP without PsV (GPP?PsV) group highlighted a female predominance (13/22). The mean age at GPP onset was 45.3 years, and the mean interval from PsV onset to GPP onset was 12.5 years. Four of nine patients with GPP had an IL36RN gene mutation. Infection, medicine, and pregnancy were the precipitating factors for GPP. A family history of psoriasis was present in eight (7.8%) patients with GPP. Twenty-four patients with GPP had psoriatic arthritis. Biologics were used in 76.5% of patients with GPP, followed by etretinate (37.3%), cyclosporine (24.5%), methotrexate (13.7%), apremilast (8.8%), and granulocyte and monocyte adsorption apheresis (6.9%). Etretinate was used in 17 (51.5%) of 33 patients with GPP with less than 10-year history. Thus, etretinate remains a good treatment option for GPP even in the era of biologics. Hypertension was the most commonly identified comorbidity, followed by diabetes. We believe that the characteristics revealed in this study can further contribute to effective GPP management.     

A case of giant hemorrhagic adrenal pseudocystectomy with a flank incision

The patient was a 43-year-old woman who underwent detailed examinations for a retroperitoneal cystic lesion that was incidentally found during orthopedic treatment. Although the tumor was a non-functioning tumor, and diagnostic imaging was negative for malignancy, the tumor was surgically resected with a flank incision. The histopathological diagnosis was adrenal pseudocyst.     

Association of UGT1A1 Gly71Arg with urine urobilinogen

Bilirubin is glucoronized by uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) mainly in the liver, and excreted into bile. The conjugated form is metabolized into the unconjugated form, and then into urobilinogen by bacteria in the intestine. Unconjugated bilirubin and urobilinogen are absorbed into the blood stream. The kidney filtrates conjugated bilurubin and urobilinogen into urine. Accordingly, the reduced enzyme activity of UGTIAI may decrease serum conjugated bilirubin levels, resulting in a lower frequency of positive results of urine bilirubin and urobilinogen. This study examined the associations of UGTIAI Gly71Arg (UGTIAI *6) with urine bilirubin and urobilinogen, as well as serum AST, ALT and GGT. Subjects were 5,172 inhabitants 35 to 69 years old who participated in a cohort study in Nagoya from June 2008 to May 2010. Among them, data from 5,151 participants (1,465 males and 3,686 females) were available for analysis. The age-sex-adjusted odds ratio (OR) of ArgArg relative to GlyGly was 1.37 (95% confidence interval (95% CI), 0.55-1.23) for bilirubin, and 1.67 (95% CI, 0.86-3.26) for urobilinogen. Those of ArgArg+ArgGly were 0.87 (95% CI, 0.59-1.27) and 1.50 (95% CI, 1.17-1.94), respectively. AST, ALT and GGT levels had no associations with the genotype. Although the significant association for urobilinogen was contrary to the biological expectation, this study indicated that UGTIA1 Gly71Arg may be a genetic factor of urine urobilinogen.     

Job demands, job resources, and work engagement of Japanese employees: a prospective cohort study

Purpose

Research on the prospective association of job demands and job resources with work engagement is still limited in Asian countries, such as Japan. The purpose of the present study was to investigate the prospective association of job demands (i.e., psychological demands and extrinsic effort) and job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward), based on the job demands-control (JD-C) [or demand-control-support (DCS)] model and the effort-reward imbalance (ERI) model, with work engagement among Japanese employees.

Methods

The participants included 423 males and 672 females from five branches of a manufacturing company in Japan. Self-administered questionnaires, including the Job Content Questionnaire (JCQ), the Effort-Reward Imbalance Questionnaire (ERIQ), the nine-item Utrecht Work Engagement Scale (UWES-9), and demographic characteristics, were administered at baseline (August 2009). At one-year follow-up (August 2010), the UWES-9 was used again to assess work engagement. Hierarchical multiple regression analyses were conducted.

Results

After adjusting for demographic characteristics and work engagement at baseline, higher psychological demands and decision latitude were positively and significantly associated with greater work engagement at follow-up (β = 0.054, p = 0.020 for psychological demands and β = 0.061, p = 0.020 for decision latitude).

Conclusions

Having higher psychological demands and decision latitude may enhance work engagement among Japanese employees.     

Comparison of urinary concentrations of 3-phenoxybenzoic acid among general residents in rural and suburban areas and employees of pest control firms

Objectives

The purpose of this study is to determine the levels of urinary 3-phenoxybenzoic acid (3-PBA) among general populations in rural and suburban areas and employees of pest control firms to evaluate the differences in the level of environmental or occupational pyrethroid (PYR) pesticides to which those populations are exposed.

Methods

Spot urine specimens were collected from male residents in a rural area (n = 143) and male residents in a suburban area (n = 66) in August of 2005 and 2007, respectively. Male employees of pest control firms, who also provided their urine specimens at the time of a health-checkup in August 2007, were classified either as sprayers (n = 14) or as non-sprayers (n = 16) according to the presence of spraying during the pre-checkup week. Urinary concentrations of 3-PBA were determined using gas chromatography–mass spectrometry and corrected for the urinary creatinine concentrations. An analysis of covariance was used to examine the statistical difference in 3-PBA concentrations between these four groups after adjustment for age, body mass index, and current smoking/drinking habits.

Results

Multiple comparisons indicated no differences in adjusted 3-PBA concentrations between the groups of general residents from the rural areas (0.33 μg/g cre in geometric mean) and suburban area (0.51 μg/g cre). The group of sprayers showed a much higher level of 3-PBA concentrations (25.0 μg/g cre) than the other three groups. A statistically significant difference, though to a lesser extent, was also exhibited in 3-PBA concentrations between the group of non-sprayers (5.6 μg/g cre) and that of general residents.

Conclusions

The results indicated that the levels of background low-dose exposure to PYRs are not likely to differ evidently among general populations according to the area of residence. Moreover, employees of pest control firms, who have been away from PYR spraying operations for a week or more, still retain much higher urinary 3-PBA concentrations than general populations.     

Current human T‐cell lymphotropic virus type 1 mother‐to‐child transmission prevention status in Kagoshima

The aim of this study was to assess the current human T‐cell lymphotropic virus type 1 (HTLV‐I) mother‐to‐child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow‐up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short‐term breast‐feeding. The HTLV‐I carrier rate among pregnant women in Kagoshima has declined. The current HTLV‐I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT.