Motor Progression and Nigrostriatal Neurodegeneration in Parkinson Disease.

OBJECTIVE: The motor severity in Parkinson disease (PD) is believed to parallel dopaminergic terminal degeneration in the striatum, although the terminal was reported to be virtually absent by 4 years postdiagnosis. Meanwhile, neuromelanin-laden dopamine neuron loss in the substantia nigra (SN) elucidated a variability at early stages and gradual loss with less variability 10 years postdiagnosis. Here, we aimed to clarify the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss at early to advanced stages of PD. METHODS: Ninety-three PD patients were divided into early and advanced subgroups based on motor symptom duration and whether motor fluctuation was present. Striatal dopaminergic terminal degeneration was evaluated using a presynaptic dopamine transporter tracer, 123 I-ioflupane single photon emission computed tomography (SPECT). Nigral neuromelanin-laden dopamine neuron density was assessed by neuromelanin-sensitive magnetic resonance imaging (NM-MRI). RESULTS: In patients with early stage PD (motor symptoms for ≤8 or 10 years), motor dysfunction during the drug-off state was paralleled by a decline in 123 I-ioflupane uptake in the striatum despite the absence of a correlation with reductions in NM-MRI signals in SN. Meanwhile, in patients with advanced stage PD (motor symptoms for >8 or 10 years and with fluctuation), the degree of motor deficits during the drug-off state was not correlated with 123 I-ioflupane uptake in the striatum, despite its significant negative correlation with NM-MRI signals in SN. INTERPRETATION: We propose striatal dopaminergic terminal loss measured using 123 I-ioflupane SPECT and nigral dopamine neuron loss assessed with NM-MRI as early stage and advanced stage motor impairment biomarkers, respectively. ANN NEUROL 2022;92:110-121.

ß-Glycyrrhetinic acid inhibits the bacterial growth and biofilm formation by supragingival plaque commensals.

ß-Glycyrrhetinic acid (BGA) is a natural antibacterial agent. Previous studies reported that BGA has antibacterial effects against several bacteria. This study evaluated the effects of BGA on the regulation of supragingival plaque bacteria. First, the minimum inhibitory concentrations (MICs) of BGA against oral bacteria were measured. Next, the minimum concentrations for inhibition of biofilm formation were evaluated against Streptococcus mutans and Streptococcus sobrinus, possessing insoluble glucan synthesis abilities. The MICs of biofilm formation by these bacteria ranged from 1/8 to 2× MIC. Furthermore, the inhibition effects of BGA against the coaggregation of Porphyromonas gingivalis and Streptococcus gordonii were evaluated. BGA at 32 or 64 µg/mL inhibited the coaggregation of these bacteria after a 30 min incubation. Lastly, the inhibition effects of BGA against human supragingival plaque bacteria were evaluated. Human supragingival plaque samples were obtained from 12 healthy donors. The inhibition effects of BGA against biofilm formation by these plaque bacteria were evaluated. Of 12 samples, the biofilm formation by 11 was significantly attenuated by 128-256 µg/mL of BGA. The number of colony forming units in these biofilms was also significantly attenuated. In conclusion, it was revealed that BGA inhibits the growth and biofilm formation of bacteria, furthermore, the same effect was confirmed with supragingival plaque bacteria. BGA is a good candidate for a natural agent that prevents the outbreak and progression of periodontal disease because it suppresses not only the growth and biofilm formation of bacteria, but also the coaggregation of P. gingivalis with plaque bacteria.

Characteristic chest CT findings for progressive cavities in Mycobacterium avium complex pulmonary disease: a retrospective cohort study.

BACKGROUND: Although cavities are an important finding in Mycobacterium avium complex pulmonary disease (MAC-PD), there is little information regarding the types of cavities that indicate disease progression. This study was performed to identify cavity characteristics that were associated with disease progression in patients with MAC-PD. METHODS: This retrospective cohort study included 97 patients presenting with MAC-PD with cavities between December 2006 and June 2016. We compared initial and final computed tomography (CT) findings, classified 52 and 45 patients in the progressive and non-progressive cavity groups, respectively, and examined the progression-related imaging features in initial CT images. A progressive cavity was defined by more than two-fold increase in internal diameter or emergence of a new cavity around the initial cavity. RESULTS: Patients in the progressive group were older (p < 0.001), had a lower body mass index (p = 0.043), and showed higher diabetes complication rates (p = 0.005). The initial CT in the progressive group showed a longer maximum internal diameter of the cavity (p < 0.001) and higher rates of cavities close to the chest wall (p < 0.001), multiple cavities (p = 0.023), consolidation around the cavity (p < 0.001), atelectasis (p = 0.011), and pleural thickening (p < 0.001). Multivariable logistic regression analysis revealed that the maximum internal diameter of the cavity (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.02-1.21; p=0.012) and consolidation around the cavity (OR: 16.15, 95% CI: 4.05-64.46; p < 0.001) were significantly associated with progressive cavities. In cavities with a maximum internal diameter of ≥10 mm and simultaneous consolidation, the probability of progression was as high as 96.2%. The 10-year mortality rates in the progressive and non-progressive cavity groups were 46.7 and 9.8% (p < 0.001), respectively, while the 10-year respiratory failure rates were 28.1 and 0%, respectively (p < 0.001). CONCLUSIONS: Large cavity size and consolidation on CT showed strong relationships with disease progression, which led to respiratory failure and high mortality rate.

The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome.

BACKGROUND: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection. METHODS: We retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease. RESULTS: In the surgically treated patients, the median age was 58 (interquartile range, 47-65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence. CONCLUSIONS: NTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.

The association between erythromycin monotherapy for Mycobacterium avium complex lung disease and cross-resistance to clarithromycin: A retrospective case-series study.

Long-term, low-dose erythromycin monotherapy, based on the anti-inflammatory effects of macrolides, has been reported to have the potential to suppress the exacerbation of Mycobacterium avium complex (MAC) lung disease with less toxicity. It remains unclear whether erythromycin monotherapy induces cross-resistance to clarithromycin, a key drug for MAC. To clarify this point, we conducted a retrospective, single-center, case-series study on patients with MAC lung disease who underwent erythromycin monotherapy for at least 6 months. Drug susceptibility tests, before and after erythromycin treatment initiation, were analyzed. Thirty-three patients were included in our study. All 33 patients showed susceptibility to clarithromycin for MAC both before and after erythromycin monotherapy. There was no significant difference in clarithromycin minimum inhibitory concentrations between before and after erythromycin treatment (median difference = 0 µg/ml; P = .313, Wilcoxon's signed-rank test). We conclude that erythromycin monotherapy for MAC lung disease may not induce cross-resistance to clarithromycin.

Levels of Antibody against Glycopeptidolipid Core as a Marker for Monitoring Treatment Response in Mycobacterium avium Complex Pulmonary Disease: a Prospective Cohort Study.

The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) is sometimes complicated and time-consuming. A serodiagnostic kit that measures the serum levels of IgA antibodies against the glycopeptidolipid (GPL) core is commercially available and has good diagnostic accuracy for MAC-PD. However, the significance of measurement of GPL core IgA antibody levels in monitoring for chemotherapy response in patients with MAC-PD was not well investigated. Thirty-four treatment naive MAC-PD patients who were started on multidrug chemotherapy were enrolled. Their antibody levels were prospectively measured at regular intervals. The relationships between their antibody levels and the therapeutic outcomes were examined. The patients were classified into three groups (conversion, recurrence, and nonconversion) based on the bacteriological outcomes after chemotherapy. There were no significant differences in the antibody levels before treatment between the culture conversion (n = 19), recurrence (n = 7), and nonconversion (n = 8) groups (P = 0.9881). The levels decreased significantly after the chemotherapy (P < 0.0001). Recurrence and/or worsening of chest radiography findings were observed in cases whose antibody levels subsequently increased after cessation of the chemotherapy. No significant difference in the percent decrease in antibody levels by the chemotherapy was observed between the culture conversion and recurrence groups (P = 0.9338). The initial antibody levels are not a predictor of therapeutic outcomes, and also the percent decrease in antibody levels is not a sufficient indicator of the cessation of chemotherapy. However, serial measurements of antibody levels may allow objective monitoring of disease activity in individual MAC-PD patients.

A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells.

Plant leaf epidermal cells exhibit a jigsaw puzzle-like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo.

A new mathematical model for pattern formation by cranial sutures.

Cranial sutures are narrow mesenchymal tissues that connect skull bones to each other. Given that they serve as growth centers in the skull, these undifferentiated tissues play crucial roles in skull development. Cranial sutures are also of clinical importance, because the premature fusion of skull bones results in a pathological condition called craniosynostosis. In newborns, skull sutures are wide and straight; during adolescence, they become thinner and start winding to form an interdigitating pattern. From a functional aspect, as the degree of interdigitation becomes larger, the strength of the connection between bones increases. However, the mechanisms underlying the maintenance of mesenchymal narrow bands or formation of interdigitation remain poorly understood. In the present study, we presented a new mathematical model that can reproduce the suture width maintenance and interdigitation formation. We can predict the width of the mesenchyme bands and wavelengths of suture interdigitations from the model.

Identification of three exercise-induced mortality risk factors in patients with COPD.

The survival rate of chronic obstructive pulmonary disease (COPD) patients with severely reduced exercise capacity is extremely low. We recently identified three life-threatening pathophysiological conditions during cardiopulmonary exercise testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and (3) progressive respiratory acidosis at low-intensity exercise. The present prospective observation study aimed to determine whether these parameters constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six COPD patients were followed-up, monthly, for >3 years. Subsequently, spirometry and CPET were performed to examine parameters of exercise-induced hypoxemia ([PaO2 slope, mmHg/L · min(-1)] = Decrease in PaO2/ΔV˙ O2 (Difference in ΔV˙ O2 between at rest and at peak exercise)), progression of acidosis ([ΔpH/ΔV˙ O2,/L · min(-1)] = Decrease in pH/ΔV˙ O2), and sympathetic overactivity ([Δnorepinephrine (NE)/ΔV˙ O2, ng/mL/L · min(-1)] = Increase in NE/ΔV˙ O2). Univariate analysis revealed a significant association between the three conditions with increased mortality. Kaplan-Meier analysis showed that the quartile combining the steepest PaO2 slope (≤-55 mmHg/ΔV˙ O2 [L/min]), steepest decrease in arterial blood pH (≤ -1.72/ΔV˙ O2 [L/min]), and most rapid increase in plasma NE level (≥ 5.2 ng/VO2 [L/min]) during incremental exercise was associated with higher all-cause mortality. These conditions showed cumulative effects on COPD patients' survival. Multivariate analyses revealed that these three life-threatening factors are also independent predictors of mortality based on age, heart rate and PaO2 at rest, body mass index, and forced expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors may lead to more efficient pulmonary rehabilitation programs for COPD patients based on patient-specific exercise-induced pathophysiological profiles.

Frontoparietal-Striatal Network and Nucleus Basalis Modulation in Patients With Parkinson Disease and Gait Disturbance.

BACKGROUND AND OBJECTIVES: Neural computations underlying gait disorders in Parkinson disease (PD) are multifactorial and involve impaired expression of stereotactic locomotor patterns and compensatory recruitment of cognitive functions. This study aimed to clarify the network mechanisms of cognitive contribution to gait control and its breakdown in patients with PD. METHODS: Patients with PD were instructed to walk at a comfortable pace on a mat with pressure sensors. The characterization of cognitive-motor interplay was enhanced by using a gait with a secondary cognitive task (dual-task condition) and a gait without additional tasks (single-task condition). Participants were scanned using 3-T MRI and 123I-ioflupane SPECT. RESULTS: According to gait characteristics, cluster analysis assisted by a nonlinear dimensionality reduction technique, t-distributed stochastic neighbor embedding, categorized 56 patients with PD into 3 subpopulations. The preserved gait (PG) subgroup (n = 23) showed preserved speed and variability during gait, both with and without additional cognitive load. Compared with the PG subgroup, the mildly impaired gait (MIG) subgroup (n = 16) demonstrated deteriorated gait variability with additional cognitive load and impaired speed and gait variability without additional cognitive load. The severely impaired gait (SIG) subgroup (n = 17) revealed the slowest speed and highest gait variability. In addition, group differences were found in attention/working memory and executive function domains, with the lowest performance in the SIG subgroup than in the PG and MIG subgroups. Using resting-state functional MRI, the SIG subgroup demonstrated lower functional connectivity of the left and right frontoparietal network (FPN) with the caudate than the PG subgroup did (left FPN, d = 1.21, p < 0.001; right FPN, d = 1.05, p = 0.004). Cortical thickness in the FPN and 123I-ioflupane uptake in the striatum did not differ among the 3 subgroups. By contrast, the severity of Ch4 density loss was significantly correlated with the level of functional connectivity degradation of the FPN and caudate (left FPN-caudate, r = 0.27, p = 0.04). DISCUSSION: These findings suggest that the functional connectivity of the FPN with the caudate, as mediated by the cholinergic Ch4 projection system, underlies the compensatory recruitment of attention and executive function for damaged automaticity in gait in patients with PD.

Effects of ghrelin treatment on exercise capacity in underweight COPD patients: a substudy of a multicenter, randomized, double-blind, placebo-controlled trial of ghrelin treatment.

BACKGROUND: The aim of this substudy of the ghrelin treatment, multicenter, randomized, double-blind, placebo-controlled trial was to investigate the effects of ghrelin administration on exercise capacity and the underlying mechanisms in underweight patients with chronic obstructive pulmonary disease (COPD) using cardiopulmonary exercise testing. METHODS: Twenty underweight COPD patients were randomized to pulmonary rehabilitation with intravenous ghrelin (2 µg/kg, n = 10) or placebo (n = 10) twice daily for 3 weeks in a double-blind fashion. The primary outcome was changes in peak oxygen uptake V•o2. Secondary outcomes included changes in exertional cardio-respiratory functions: O2-pulse, physiologic dead space/tidal volume-ratio (VD/VT), ventilatory equivalent for oxygen V•E/V•o2, and ventilatory equivalent for carbon dioxide V•E/V•co2. RESULTS: With incremental exercise, at peak exercise, there was a significant difference in the mean difference (ghrelin minus placebo), i.e., treatment effect in: i) peak V•o2 (1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii) V•E/V•o2 (-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii) V•E/V•co2 (-4.1, 95% CI: -8.2 to -0.1, between-group p = 0.045); iv) VD/VT (-0.04, 95% CI: -0.08 to -0.00, between-group p = 0.041); and v) O2-pulse (0.7 mL/beat, 95% CI: 0.3 to 1.2 mL/beat, between-group p = 0.003). Additionally, repeated-measures analysis of variance (ANOVA) indicated a significant time-course effect of ghrelin versus placebo in the peak V•o2 (p = 0.025). CONCLUSION: Ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters. TRIAL REGISTRATION: UMIN (University Hospital Medical Information Network in Japan) C000000061.

Effects of oxygen on exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: The results of studies on the oxygen response in patients with COPD should provide important clues to the pathophysiology of exertional dyspnoea. We investigated the exercise responses to hyperoxia in relation to dyspnoea profile, as well as cardiopulmonary, acidotic and sympathetic parameters in 35 patients with stable COPD (mean FEV(1) 46% predicted). METHODS: This was a single-blind trial, in which patients breathed 24% O(2) or compressed air (CA) in random order during two incremental cycle exercise tests. RESULTS: PaO(2) and PaCO(2) were higher (P < 0.0001 and P < 0.05, respectively) at each exercise point while patients were breathing 24% O(2) compared with CA. At a standardized time point near peak exercise, use of O(2) resulted in reduced plasma lactate and plasma noradrenaline concentrations (P < 0.01). Peak minute ventilation/indirect maximum voluntary ventilation was similar while breathing 24% O(2) and CA. At peak exercise, the dyspnoea score, pH and plasma noradrenaline concentrations were similar while breathing 24% O(2) and CA. The dyspnoea-ratio (%) of Δoxygen uptake (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point while breathing 24% O(2) or CA. CONCLUSIONS: Regardless of whether they breathed CA or 24% O(2) , patients with COPD did not develop ventilatory compensation for exertional acidosis, and the pH values measured were similar. Hyperoxia during a standardized exercise protocol did not alter the pattern of exertional dyspnoea in these patients, compared with breathing CA, although hyperoxia resulted in miscellaneous effects.

[Susceptibility to rifabutin and novel fluoroquinolones in Mycobacterium avium complex isolates from patients with sputum culture-positive pulmonary disease who are undergoing standard chemotherapy].

We investigated the susceptibility to conventional and newer antimycobacterial agents including rifabutin (RBT) and novel fluoroquinolones (NFQs) among 48 clinical Mycobacterium avium complex (MAC) isolates from patients with sputum culture-positive MAC disease who were undergoing standard chemotherapy. RBT and NFQs were superior to conventional agents because of higher rates of susceptibility and lower minimum inhibitory concentration. NFQs showed cross-resistance among quinolones. In contrast, RBT did not show cross-resistance to RFP. Most clarithromycin-resistant or rifampicin-resistant cases were susceptible to RBT and NFQs. In conclusion, RBT and NFQs possess good in vitro antimicrobial activity among clinical isolates of culture-positive pulmonary MAC disease, which suggests that a combination of such microbiologically active agents may improve clinical effectiveness more than standard chemotherapy regimens.

Noise-induced scaling in skull suture interdigitation.

Sutures, the thin, soft tissue between skull bones, serve as the major craniofacial growth centers during postnatal development. In a newborn skull, the sutures are straight; however, as the skull develops, the sutures wind dynamically to form an interdigitation pattern. Moreover, the final winding pattern had been shown to have fractal characteristics. Although various molecules involved in suture development have been identified, the mechanism underlying the pattern formation remains unknown. In a previous study, we reproduced the formation of the interdigitation pattern in a mathematical model combining an interface equation and a convolution kernel. However, the generated pattern had a specific characteristic length, and the model was unable to produce a fractal structure with the model. In the present study, we focused on the anterior part of the sagittal suture and formulated a new mathematical model with time-space-dependent noise that was able to generate the fractal structure. We reduced our previous model to represent the linear dynamics of the centerline of the suture tissue and included a time-space-dependent noise term. We showed theoretically that the final pattern from the model follows a scaling law due to the scaling of the dispersion relation in the full model, which we confirmed numerically. Furthermore, we observed experimentally that stochastic fluctuation of the osteogenic signal exists in the developing skull, and found that actual suture patterns followed a scaling law similar to that of the theoretical prediction.

Evaluation of Exertional Ventilatory Parameters Using Oscillometry in COPD.

Background: Oscillometry is a tool to measure respiratory impedance that requires minimal patients' effort. In patients with chronic obstructive pulmonary disease (COPD), the correlation of respiratory impedance at rest with exertional ventilatory parameters, including exercise tolerance, has scarcely been reported. In addition, the utility of oscillometric parameters might differ between the inspiratory and expiratory phases due to airflow obstruction during expiration, but the hypothesis had not been validated. The aim of the present study was to investigate whether oscillometric parameters are associated with exertional ventilatory parameters in patients with COPD. Methods: Fifty-five subjects with COPD who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center performed spirometry, oscillometry, and cardiopulmonary exercise testing (CPET) within 2 weeks. The correlations between parameters of spirometry, oscillometry, and CPET were analyzed using Spearman's rank correlation coefficient, univariate, and multivariate analyses. Results: Respiratory reactance had better correlations with the CPET parameters than respiratory resistance. Moreover, inspiratory reactance at rest correlated with the CPET parameters stronger than expiratory reactance. In particular, inspiratory resonant frequency (Fres-ins) correlated with peak oxygen uptake (rS=-0.549, p<0.01) and dead space to tidal volume ratio at peak exercise (rS=0.677, p<0.01) and the best predicted expiratory tidal volume (VT ex) at peak exercise of all the oscillometric parameters (rS=-0.679, p<0.01). However, the correlation between Fres-ins and VT ex at peak exercise became weak in subjects with severe and very severe COPD during exercise. Conclusion: Measurement of respiratory reactance is useful for the effortless evaluation of not only exertional ventilatory parameters but exercise tolerance in patients with COPD. The correlation of respiratory impedance with exertional ventilatory parameters can become weak in patients with advanced COPD; thus, the measurement of oscillometry might not be appropriate for evaluating exertional ventilatory parameters of patients with advanced COPD.

Intolerance to and limitations of inspiratory muscle training in patients with advanced chronic obstructive pulmonary disease: A report of two cases.

Inspiratory muscle training (IMT) has been attracting attention as one of the useful treatments in patients with chronic obstructive pulmonary disease (COPD). IMT is reportedly effective in most patients with COPD. However, little is known about the benefits of IMT, especially in patients with advanced COPD. We reported two cases of COPD that received 12-week IMT to explore intolerance to and the limitations of IMT in advanced COPD. The effectiveness of IMT was evaluated using cardiopulmonary exercise testing (CPET), spirometry, and respiratory muscle strength testing before and after the training. A 75-year-old man with normal body mass index (BMI) and forced expiratory volume in 1 s (FEV1) of 1.63 L responded well to IMT, but a 78-year-old man with low BMI and FEV1 of 0.83 L did not. In the responder, IMT resulted in increased minute ventilation (V' E) and oxygen uptake at peak exercise in incremental load testing. Moreover, IMT increased endurance time in constant load testing and maximal inspiratory pressure. In both patients, breathing frequency (f R) increased, but tidal volume and the inspiratory-expiratory ratio were not improved during exercise. Despite the high f R obtained after IMT, V' E at peak exercise did not increase and endurance time shortened in the non-responder. In underweight patients with advanced COPD, IMT might lead to tachypnea and ventilatory inefficiency, which in turn might decrease exercise performance. Therefore, underweight patients with advanced COPD might be unable to tolerate IMT and should avoid receiving the training.

Managing COPD with expiratory or inspiratory pressure load training based on a prolonged expiration pattern.

BACKGROUND: Exertional prolonged expiration should be identified as a therapeutic target in COPD. The efficacy of expiratory or inspiratory pressure load training (EPT/IPT) based on the degree of prolonged expiration was investigated. METHODS: A total of 21 patients with COPD were divided into two groups according to the exertional change in the inspiratory duty cycle (T I/Ttot). For 12 weeks, patients whose exertional T I/Ttot decreased received EPT (EPT group, n=11, mean percentage forced expiratory volume in 1 s (%FEV1), 32.8%) and those whose exertional T I/Ttot increased received IPT (IPT group, n=10, mean %FEV1, 45.1%). RESULTS: The therapeutic responses were as follows. In both groups, endurance time (EPT, +5.7 min, p<0.0001; IPT, +6.1 min, p=0.0004) on the constant work rate exercise test (WRET) and peak oxygen uptake increased (EPT, p=0.0028; IPT, p=0.0072). In the EPT group the following occurred: 1) soon after commencement of exercise with the constant WRET, the expiratory tidal volume (V Tex) increased, reducing dyspnoea; 2) V Tex and mean expiratory flow increased and then prolonged expiration (p=0.0001) improved at peak exercise with the incremental exercise test (ET); and 3) St. George's Respiratory Questionnaire total, activity and impact scores were improved. In the IPT group, on both the constant WRET and incremental ET, breathing frequency increased, which led to greater exercise performance with effort dyspnoea. CONCLUSIONS: This study showed the benefits of EPT/IPT on exercise performance. If the choice of managing COPD with EPT/IPT is appropriate, inexpensive EPT/IPT may become widespread as home-based training.

Diagnostic Validity of Gastric Aspirate Culture in Nontuberculous Mycobacterial Pulmonary Disease.

Rationale: Although gastric aspirate culture is used for diagnosing pulmonary tuberculosis, its usefulness in diagnosing pulmonary infections of nontuberculous mycobacteria (NTM) is unknown.Objectives: To investigate the diagnostic validity of gastric aspirate culture for acid-fast bacilli in NTM pulmonary disease (NTM-PD).Methods: Gastric aspirates were collected from patients with suspected NTM-PD at the Osaka Toneyama Medical Center between December 2006 and February 2018. Patients with a final diagnosis of pulmonary tuberculosis, an observation period of less than 6 months, or fewer than three conducted sputum cultures were excluded from the study. NTM-PD was diagnosed as per American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) criteria. We retrospectively examined the diagnostic validity of gastric aspirate culture in Mycobacterium avium complex (MAC)-PD and M. kansasii-PD by comparing culture results with final diagnoses. This was done first for all patients, and subsequently for patients with negative results for early sputum cultures. In addition, we compared the time required for an NTM-PD diagnosis based on gastric aspiration with that based on ATS/IDSA criteria.Results: Among 475 total patients, 119 (25.1%) had positive NTM gastric aspirate cultures and 154 (32.4%) fulfilled the ATS/IDSA criteria for NTM-PD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPVs) of gastric aspiration were 63.9%, 95.8%, 83.5%, and 88.8% in MAC-PD and 82.4%, 99.6%, 87.5%, and 99.3% in M. kansasii-PD, respectively. Sensitivity, specificity, PPV, and NPV of gastric aspirate cultures of the 378 patients who were undiagnosed based on sputum culture within 120 days were 34.0%, 95.5%, 51.6%, and 91.1% for MAC-PD and 75.0%, 99.5%, 60.0%, and 99.7% for M. kansasii-PD, respectively. Furthermore, gastric aspirate cultures tested in addition to bronchoscopy yielded incremental sensitivity of 8.7% (95.7% vs. 87.0%) and an NPV of 1.3% (99.3% vs. 98.0%) in MAC-PD. In patients with NTM-PD with NTM-positive gastric aspirate cultures, the period between gastric aspirate collection and the positive culture result was shorter than the time between gastric aspirate collection and NTM-PD diagnosis (6 [9-36] d vs. 25 [12-69] d, median [interquartile range], P < 0.0001].Conclusions: In settings where acid-fast bacilli pulmonary diseases are suspected, gastric aspirate culture may be helpful for diagnosing MAC-PD and M. kansasii-PD.

The therapeutic effects of bronchial thermoplasty evaluated by cardiopulmonary exercise testing†:†a case series.

Bronchial thermoplasty (BT) had been reported to improve the symptoms of severe asthma. However, the exertional responses of BT based on the mechanisms have not been elucidated. A 57-year-old man and a 60-year-old woman underwent BT due to intractable severe asthma. We evaluated the therapeutic effects of BT using cardiopulmonary exercise testing (CPET). After BT, the exercise time during CPET substantially prolonged reducing exertional dyspnea in the former (good), but not in the latter (poor). In the good responder, the high air remaining in the lung after expiration (i.e., inspiratory tidal volume minus expiratory tidal volume) during CPET decreased after BT. In contrast, in the poor responder, the high air remaining after expiration during exercise was not obtained before BT. Further investigations are necessary to confirm that the presence or absence of the exertional wasted ventilation on CPET may be informative to evaluate the therapeutic effects of BT. J. Med. Invest. 67 : 386-390, August, 2020.

Evaluation of disease severity in bronchiectasis using impulse oscillometry.

Although the diagnostic value of impulse oscillometry (IOS) in bronchiectasis for the differential diagnosis of healthy subjects has been researched, the usefulness of each IOS parameter for predicting disease severity in bronchiectasis has not been thoroughly investigated. In addition, the usefulness of IOS in patients with nontuberculous mycobacteria (NTM) infection has not been reported. This study aimed to determine the predictive significance of respiratory impedance and detect the other most significant IOS parameters for predicting disease severity in bronchiectasis patients and to validate the usefulness of IOS in patients with NTM infection. A total of 206 patients with bronchiectasis who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center were included. Chest high-resolution computed tomography, spirometry and IOS were performed. Hospital admissions, mortality and disease severity indices for bronchiectasis (Bronchiectasis Severity Index (BSI), FACED, and E-FACED scores) were calculated to assess disease severity. The patients were divided into subgroups with and without NTM infection, and subgroup analyses were performed. Respiratory reactance, especially resonant frequency (f res), correlated with both BSI and FACED score better than respiratory resistance. Inspiratory but not expiratory impedance was strongly correlated with BSI, FACED and E-FACED scores. Inspiratory f res was the most useful predictor, increasing as the disease became more severe. The usefulness of IOS was almost equivalent in patients both with and without NTM infection. Inspiratory reactance measured by IOS is useful for estimating disease severity in bronchiectasis. Inspiratory f res best predicts disease severity in bronchiectasis patients both with and without NTM infection.