Lower skeletal muscle density and airway structure on computed tomography in asthma.

BACKGROUND: Lower skeletal muscle density may reflect muscle adiposity and metabolic dysregulation that potentially impair disease control and lung function independent of high body mass index (BMI) in patients with asthma. OBJECTIVE: To investigate whether the lower density of pectoralis muscles (PMs) and erector spinae muscles (ESMs) on chest computed tomography was associated with airway structural changes in patients with asthma. METHODS: Consecutive patients with asthma and healthy controls undergoing chest computed tomography were retrospectively analyzed. The ESM and PM density, areas of subcutaneous adipose tissue near the PM and epicardial adipose tissue, wall area percent of the airways, and airway fractal dimension (AFD) were quantified on computed tomography. RESULTS: The study included 179 patients with asthma (52% women) and 88 controls (47% women). All the controls were 60 years old or younger. The PM and ESM density in female patients with asthma who were 60 years old or younger were significantly lower than those in controls after adjustment for BMI. In female patients with asthma at all ages, lower PM and ESM density (but not subcutaneous or epicardial adipose tissue area) was associated with greater wall area percent of the airways and lower AFD after adjusting for age, height, BMI, smoking status, blood eosinophil count, and oral corticosteroid use. The only association between ESM density and AFD was found in male patients with asthma. CONCLUSION: Lower skeletal muscle density may be associated with airway wall thickening and less complexity of the airway luminal tree in female patients with asthma.

Phase angle measured by bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease: Associations with physical inactivity and frailty.

BACKGROUND: Factors associated with early-stage frailty (pre-frailty) in patients with chronic obstructive pulmonary disease (COPD) remain unestablished. In addition to skeletal muscle quantity, skeletal muscle dysfunction can be estimated using an angular metric from bioelectrical impedance analyzer (BIA), termed the phase angle, that reflects cell membrane reactance representing the structural stability. This study examined whether the phase angle was more closely associated with pre-frailty compared with skeletal muscle quantity in patients with COPD. METHODS: This cross-sectional analysis included stable smokers with and without COPD whose frailty status was assessed using the Japanese version of the Cardiovascular Health Study criteria. The phase angle and skeletal muscle index (SMI) were measured using BIA, and physical activity over one week was assessed using triaxial accelerometers. RESULTS: A total of 159 patients were categorized into robust, pre-frail, and frail groups (n = 38, 92, and 29, respectively). The phase angle was significantly smaller in the pre-frail and frail groups than in the robust group after adjusting for age, sex, height, body mass index, smoking history, and lung function. In contrast, SMI did not differ between the robust and pre-frail groups. When combining the pre-frail and frail groups into a non-robust group, 4.8° was determined as the cutoff phase angle value to identify non-robust status. A phase angle <4.8° was associated with shorter durations of moderate-intensity physical activity but not with light physical activity. CONCLUSIONS: A smaller phase angle was associated with pre-frailty and impaired moderate-intensity physical activity in smokers with and without COPD.

Allelic frequency of pathogenic α1-antitrypsin variants in the Japanese population: Results from a survey of open Japanese genetic variation databases.

α1-antitrypsin deficiency (AATD) is a hereditary disorder with a global prevalence that differs across regions. AATD is highly prevalent in Europe and North America but rarely found in Asian countries, including Japan, possibly because of the founder effect of the pathogenic SERPINA1 variants PI*Z and PI*S. However, AATD remains underdiagnosed even in high-prevalence and low-prevalence regions, possibly because of lack of awareness. In this study, we surveyed open Japanese genetic variation databases to estimate AATD prevalence in Japan. We identified allelic frequencies (AFs) of 5 among the 14 major pathogenic SERPINA1 variants from three datasets, collectively derived from 63,119 Japanese participants. The mean AF was determined to be 8.56 × 10-4 (95% confidence interval [CI]: 6.43 × 10-4 to 1.12 × 10-3). Given that this represents the entire Japanese population, one AATD patient was speculated to be born per 1.37 × 106 births (95% CI: 7.97 × 105 to 2.42 × 106) in Japan. Our results support the prevailing notion that AATD is extremely rare in Japan.

Increased adiposity-to-muscle ratio and severity of sinusitis affect quality of life in asthma: Computed tomographic analysis.

Background: Deteriorated sinusitis and increased adiposity relative to muscle mass may affect quality of life in patients with asthma. However, whether these effects are observed regardless of intrapulmonary pathology is unknown. Objectives: We evaluated the correlation of the cross-sectional ratio of abdominal visceral fat (VF) to erector spinae muscle (ESM) and sinus findings based on Lund-Mackey scoring system (LMS) on computed tomography (CT) with the impaired score of the Asthma Quality of Life Questionnaire (AQLQ), regardless of airway and parenchymal disease, in patients with asthma. Methods: We recruited participants from the Hokkaido-based severe asthma cohort who had completed AQLQ and CT examination at the entry. The participants were divided into high (highest) and low (other quartiles) groups on the bases of the extrapulmonary indices. Multivariate analysis examined the association of VF/ESM for the adiposity-to-muscle ratio and LMS with AQLQ after adjusting for the airway fractal dimension for airway index and percentage of low attenuation volume to lung volume for parenchymal index. Results: No significant differences were observed in VF/ESM and LMS in terms of sex. The AQLQ score in the high VF/ESM group and high LMS group was lower than those in low VF/ESM group and low LMS group (63 male and 100 female subjects). High VF/ESM (estimate [95% confidence interval] (-0.43 [-0.61, -0.25]) and high LMS scores (-0.22 [-0.41, -0.03]) were associated with low AQLQ scores when adjusted for age, body mass index, smoking status, blood eosinophil count, and intrapulmonary CT indices. Conclusions: Increased VF relative to ESM mass and high LMS may deteriorate asthma-related quality of life, regardless of presence of intrapulmonary disease.

Mucus plugging on computed tomography and the sputum microbiome in patients with asthma, chronic obstructive pulmonary disease, and asthma-COPD overlap.

BACKGROUND: Despite clinical implications, the pathogenesis of mucus plugging in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) remains unclear. We hypothesized that distinct airway microbiomes might affect mucus plugging differently among ACO, asthma, and COPD and among different extents of airway eosinophilic inflammation. METHODS: The sputum microbiome, sputum cell differential count, and mucus plug score on computed tomography were cross-sectionally evaluated in patients with chronic airflow limitation. RESULTS: Patients with ACO, asthma, or COPD were enrolled (n = 56, 10, and 25). Higher mucus plug scores were associated with a greater relative abundance of the phylum Proteobacteria (rho = 0.29) only in patients with ACO and a greater relative abundance of the phylum Actinobacteria (rho = 0.46) only in patients with COPD. In multivariable models including only patients with ACO, the presence of mucus plugs was associated with a greater relative abundance of the phylum Proteobacteria and the genus Haemophilus, independent of smoking status, airflow limitation, and emphysema severity. Moreover, the mucus score was associated with a greater relative abundance of the genus Streptococcus (rho = 0.46) in patients with a high sputum eosinophil count (n = 22) and with that of the genus Haemophilus (rho = 0.46) in those with a moderate sputum eosinophil count (n = 26). CONCLUSIONS: The associations between mucus plugging and the microbiome in ACO differed from those in COPD and asthma. Greater relative abundances of the phylum Proteobacteria and genus Haemophilus may be involved in mucus plugging in patients with ACO and moderate airway eosinophilic inflammation.

Computed tomography mucus plugs and airway tree structure in patients with chronic obstructive pulmonary disease: Associations with airflow limitation, health-related independence and mortality.

BACKGROUND AND OBJECTIVE: Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema. METHODS: Based on visual CT assessment, patients with mucus plugs in 0, 1-2 and ≥3 lung segments were assigned to no-, low- and high-mucus groups. Loss of health-related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto-Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT. RESULTS: Of 199 and 96 patients in the Kyoto-Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high-mucus group than in the no-mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality. CONCLUSION: Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health-related independence and mortality in patients with COPD.

Neuromuscular electrical stimulation, muscle mass, and physical function decline in the early phase after living donor liver transplantation.

This study aims to investigate the effects of neuromuscular electrical stimulation (NMES) in addition to conventional early mobilization in the early postoperative period after living donor liver transplantation (LTx) on body composition and physical function. This was a retrospective single-center cohort study. Adult subjects who were admitted for living donor LTx from 2018 to 2023 were included in the analysis. After April 2020, patients underwent 4 weeks of NMES in addition to conventional rehabilitation. The skeletal muscle mass index, body cell mass, and physical function, including the 6-minute walking distance, were assessed before surgery and at discharge, and changes in these outcomes were compared before and after the introduction of NMES. Sixty-one patients were in the NMES group, and 53 patients before the introduction of NMES were in the control group. ANCOVA with etiology, obstructive ventilatory impairment, Child-Pugh classification, and initial body composition value as covariates demonstrated that there was a significantly smaller decline of body cell mass (-2.9±2.7 kg vs. -4.4±2.7 kg, p = 0.01), as well as of the skeletal muscle mass index (-0.78±0.73 kg/m2 vs. -1.29±1.21 kg/m2, p = 0.04), from baseline to discharge in the NMES group than in the control group; thus, the decline after surgery was suppressed in the NMES group. Four weeks of NMES, in addition to conventional rehabilitation in the early period after LTx, may attenuate the deterioration of muscle mass. It is suggested that NMES is an option for developing optimized rehabilitation programs in the acute postoperative period after LTx.

Real-Time Particle Emission Monitoring for the Non-Invasive Prediction of Lung Deposition via a Dry Powder Inhaler.

Although inhalation therapy represents a promising drug delivery route for the treatment of respiratory diseases, the real-time evaluation of lung drug deposition remains an area yet to be fully explored. To evaluate the utility of the photo reflection method (PRM) as a real-time non-invasive monitoring of pulmonary drug delivery, the relationship between particle emission signals measured by the PRM and in vitro inhalation performance was evaluated in this study. Symbicort® Turbuhaler® was used as a model dry powder inhaler. In vitro aerodynamic particle deposition was evaluated using a twin-stage liquid impinger (TSLI). Four different inhalation patterns were defined based on the slope of increased flow rate (4.9-9.8 L/s2) and peak flow rate (30 L/min and 60 L/min). The inhalation flow rate and particle emission profile were measured using an inhalation flow meter and a PRM drug release detector, respectively. The inhalation performance was characterized by output efficiency (OE, %) and stage 2 deposition of TSLI (an index of the deagglomerating efficiency, St2, %). The OE × St2 is defined as the amount delivered to the lungs. The particle emissions generated by four different inhalation patterns were completed within 0.4 s after the start of inhalation, and were observed as a sharper and larger peak under conditions of a higher flow increase rate. These were significantly correlated between the OE or OE × St2 and the photo reflection signal (p < 0.001). The particle emission signal by PRM could be a useful non-invasive real-time monitoring tool for dry powder inhalers.

Fabrication of polycrystalline phosphorus-doped diamond electrodes from red phosphorus.

Polycrystalline phosphorus-doped diamond was fabricated by the quartz-tube-type microwave plasma-assisted chemical vapor deposition method. Significantly, red phosphorus was used as a source of phosphorous, instead of PH3. Phosphorus-doped diamond electrodes with hydrogen-terminated and oxygen-terminated surfaces were investigated for the redox reactions of K3[Fe(CN)6] and [Ru(NH3)6]Cl3. The carrier concentration was estimated as 2.1-5.3 × 1018 cm-3 from electrochemical impedance measurements. Polycrystalline phosphorus-doped diamond shows great promise as chemical electrode materials.

Longitudinal assessment of interstitial lung abnormalities on CT in patients with COPD using artificial intelligence-based segmentation: a prospective observational study.

BACKGROUND: Interstitial lung abnormalities (ILAs) on CT may affect the clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), but their quantification remains unestablished. This study examined whether artificial intelligence (AI)-based segmentation could be applied to identify ILAs using two COPD cohorts. METHODS: ILAs were diagnosed visually based on the Fleischner Society definition. Using an AI-based method, ground-glass opacities, reticulations, and honeycombing were segmented, and their volumes were summed to obtain the percentage ratio of interstitial lung disease-associated volume to total lung volume (ILDvol%). The optimal ILDvol% threshold for ILA detection was determined in cross-sectional data of the discovery and validation cohorts. The 5-year longitudinal changes in ILDvol% were calculated in discovery cohort patients who underwent baseline and follow-up CT scans. RESULTS: ILAs were found in 32 (14%) and 15 (10%) patients with COPD in the discovery (n = 234) and validation (n = 153) cohorts, respectively. ILDvol% was higher in patients with ILAs than in those without ILA in both cohorts. The optimal ILDvol% threshold in the discovery cohort was 1.203%, and good sensitivity and specificity (93.3% and 76.3%) were confirmed in the validation cohort. 124 patients took follow-up CT scan during 5 ± 1 years. 8 out of 124 patients (7%) developed ILAs. In a multivariable model, an increase in ILDvol% was associated with ILA development after adjusting for age, sex, BMI, and smoking exposure. CONCLUSION: AI-based CT quantification of ILDvol% may be a reproducible method for identifying and monitoring ILAs in patients with COPD.