Lower skeletal muscle density and airway structure on computed tomography in asthma (12/15 words).

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 lower density of pectoralis muscles (PM) and erector spinae muscles (ESM) on chest computed tomography (CT) was associated with airway structural changes in patients with asthma. METHODS: Consecutive patients with asthma and healthy control subjects undergoing chest CT were retrospectively analysed. The ESM and PM density, areas of subcutaneous adipose tissue (SAT) near the PM and epicardial adipose tissue (EAT), wall area percent of the airways (WA%), and airway fractal dimension (AFD) were quantified on CT. RESULTS: The study included 179 patients with asthma (52% women) and 88 control subjects (47% women). All the control subjects were ≤ 60 years old. PM and ESM density in female patients with asthma who were ≤ 60 years old were significantly lower than those in control subjects after adjustment for BMI. In female patients with asthma at all ages, lower PM and ESM density (but not SAT or EAT area) was associated with greater WA% 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.

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.

Incidence, etiology, and outcome of hospital-acquired pneumonia in patients with acute exacerbation of fibrotic idiopathic interstitial pneumonia.

BACKGROUND: Acute exacerbations (AEs) of fibrotic idiopathic interstitial pneumonia (fIIP) that require hospitalization occur in some patients. During hospitalization, these patients can develop hospital-acquired pneumonia (HAP), a common hospital-acquired infection with a high mortality rate. However, the characteristics of HAP in AE-fIIP remain unknown. The purpose of this study was to determine the incidence, causative pathogens, and outcomes of HAP in patients with AE-fIIP. METHODS: The medical records of consecutive patients who were hospitalized with AE-fIIP from January 2008 to December 2019 were analyzed for the incidence, causative pathogen, and survival of HAP. The records of patients with an obvious infection-triggered AE were excluded from analysis. RESULTS: There were 128 patients with AE-fIIP (89 with idiopathic pulmonary fibrosis [IPF] and 39 with non-IPF fIIP) who were hospitalized a total of 155 times (111 with IPF and 44 with non-IPF fIIP). HAP occurred in 49 patients (40 with IPF and 9 with non-IPF fIIP). The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP were high, at 32.2% and 48.9%, respectively. Corynebacterium spp. was the most common causative pathogen, which was followed by human cytomegalovirus (HCMV). CONCLUSIONS: The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP are high. To improve their survival, patients with fIIP who had AEs and HAP should receive prompt empirical treatment for possible infections with Corynebacterium spp. and testing for HCMV.

Associations of fractional exhaled nitric oxide with airway dimension and mucus plugs on ultra-high-resolution computed tomography in former smokers and nonsmokers with asthma.

BACKGROUND: Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. METHODS: The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. RESULTS: Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20-35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. CONCLUSIONS: Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.

Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM. OBJECTIVE: Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi. RESULTS: Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008-0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA. CONCLUSIONS: Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

Significance of Self-Injectable Biologics in Japanese Patients with Severe Allergic Diseases: Focusing on Pen-Type Devices and Copayment.

Patients and Methods: A questionnaire survey was administered to 18, 14, and 3 patients introduced to home self-injection of dupilumab or mepolizumab using a pen-type device for atopic dermatitis, asthma alone, and asthma plus chronic rhinosinusitis with nasal polyps, respectively. Results: All but one participant wished to continue self-injection. Most participants affirmed the reduction in copayment (88.6%) and saving time and labor for hospital visits (88.6%). Six patients who received dupilumab complained of side effects, but all, except for one, continued the treatment. Of the 13 patients who had previously used a syringe-type device, 10 preferred the pen type because of its ease of use, while 3 (23%) preferred the syringe type because of the self-adjustable injection speed for pain control. Conclusion: Administration of biologics using pen-type devices is easier, and the introduction of home self-injection leads to a reduction in outpatient visits and copayment.

Association between blood eosinophil count and small airway eosinophils in smokers with and without COPD.

Introduction: Airway eosinophilic inflammation is a pathological feature in a subgroup of patients with COPD and in some smokers with a high COPD risk. Although blood eosinophil count is used to define eosinophilic COPD, the association between blood eosinophil count and airway eosinophilic inflammation remains controversial. This cross-sectional study tested this association in smokers with and without COPD while considering potential confounders, such as smoking status and comorbidities. Methods: Lung specimens were obtained from smokers with and without COPD and non-COPD never-smokers undergoing lung lobectomy. Those with any asthma history were excluded. The infiltration of eosinophils into the small airway wall was quantified on histological sections stained with major basic protein (MBP). Results: The number of airway MBP-positive cells was greater in smokers (n=60) than in never-smokers (n=14). Smokers with and without COPD (n=30 each) exhibited significant associations between blood eosinophil count and airway MBP-positive cells (ρ=0.45 and 0.71). When smokers were divided into the high and low airway MBP groups based on their median value, blood eosinophil count was higher in the high-MBP group, with no difference in age, smoking status, comorbidities, emphysema or coronary artery calcification on computed tomography, and inhaled corticosteroid (ICS) use. The association between greater blood eosinophil count and the high-MBP group was confirmed in multivariable models adjusted for smoking status, airflow limitation and ICS use. Conclusion: The blood eosinophil count may reflect eosinophilic inflammation in the small airways in smokers with and without COPD.

Longitudinal Changes and Association of Respiratory Symptoms with Preserved Ratio Impaired Spirometry (PRISm): The Nagahama Study.

Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.

Prognostic value of the qSOFA in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have a slowly progressive clinical course, although some develop acute exacerbations (AEs). An easily obtained composite score is desirable for predicting the survival rate in patients with AE of IPF (AE-IPF). We investigated the quick sequential organ failure assessment (qSOFA), originally developed to identify sepsis, as a predictor of mortality in patients with AE-IPF and compared it to other composite assessments. METHODS: Consecutive patients with IPF admitted for their first AE between 2008 and 2019 were recruited retrospectively. The association between the qSOFA score obtained at admission and mortality was investigated. RESULTS: During the study period, 97 patients with AE-IPF were hospitalized. The hospital mortality was 30.9%. Multivariate logistic regression analysis revealed that both the qSOFA and the Japanese Association for Acute Medicine (JAAM)-disseminated intravascular coagulation (DIC) scores were significant predictors of hospital mortality (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.43-10.3; p = 0.007 and OR 2.71, 95% CI 1.56-4.67; p = 0.0004; respectively). Kaplan-Meier survival curves showed that both scores were consistently associated with survival. Furthermore, the sum of the two scores was a more effective predictor than the individual scores. CONCLUSIONS: The qSOFA score of patients admitted with AE-IPF was associated with both in-hospital and long-term mortality, which was also true for the JAAM-DIC score. The qSOFA score plus the JAAM-DIC score should be determined during the diagnostic evaluation of a patient with AE-IPF. Both scores combined may be more effective at predicting outcomes than individual scores.

Roles of Staphylococcus aureus and sensitization to staphylococcal enterotoxin in bronchiectasis.

Staphylococcus aureus (S. aureus) is an inducer of mucosal type 2 immune response. To test the hypothesis that airway colonization with S. aureus may reflect allergic predisposition with staphylococcal enterotoxin (SE) sensitization in bronchiectasis, we retrospectively examined the association between SE sensitization and S. aureus and Pseudomonas aeruginosa (P. aeruginosa) in sputum of patients with bronchiectasis (n = 35). Overall, 14 (40%) patients with bronchiectasis were sensitized to either staphylococcal enterotoxin A (SEA) or staphylococcal enterotoxin B (SEB). SEA sensitization was more frequently observed in patients with sputum S. aureus than those without it. Patients with sputum S. aureus but without P. aeruginosa exhibited the highest SEA sensitization frequency and serum total IgE levels. Patients with both S. aureus and P. aeruginosa exhibited the highest blood eosinophils. In conclusion, S. aureus in the lower airway may indicate an allergic predisposition with SE sensitization and blood eosinophilia in bronchiectasis.

Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes.

RATIONALE: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. OBJECTIVE: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. METHODS: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. RESULTS: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. CONCLUSIONS: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.

Outcome of patients who were incidentally diagnosed with idiopathic pulmonary fibrosis: How early in the disease should we identify patients?

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is diagnosed incidentally in some patients with minimal or no respiratory symptoms. The clinical features of such patients are unknown. Herein we aimed to clarify the prevalence, clinical course, and prognostic factors of patients who were incidentally diagnosed with IPF. METHODS: The files of consecutive patients with newly diagnosed IPF were retrospectively reviewed to determine the methods involved in their diagnosis, and their outcomes. RESULTS: Among a total of 107 patients with newly diagnosed IPF, 35 (32.7%) were diagnosed incidentally, including 18 undergoing annual health check-ups and 17 undergoing assessment for other medical problems. The median survival from the time of diagnosis was 4.9 years for the 35 patients diagnosed incidentally, which was comparable to the median survival of 3.9 years for the 72 who were not diagnosed incidentally. The body mass index (BMI) was the sole independent predictor of survival (hazard ratio 0.78, 95% confidence interval 0.65-0.93, p = 0.006) in patients diagnosed incidentally. CONCLUSIONS: Nearly one third of patients with IPF were diagnosed incidentally, and their survival was still poor. Identifying patients during the earliest stage of IPF, particularly those with a low BMI, is warranted.

Measurement of particulate matter 2.5 in surgical smoke and its health hazards.

PURPOSE: Surgical smoke is generated during the cauterization, coagulation, and incision of biological tissues by electrocautery, ultrasonic coagulation, incising devices, and lasers. Surgical smoke comprises water, water vapor, steam, and some particulate matter, including bacteria, viruses, cell fragments, and volatile organic compounds, which can pose health risks to the operating room personnel. In this study, we measured the concentration of particulate matter 2.5 (particles with a diameter of ≤ 2.5 µm) in surgical smoke. METHODS: We used digital dust counters for real-time monitoring of particulate matter 2.5 generated intraoperatively in breast and gastrointestinal surgeries performed at our hospitals between 2019 and 2020. RESULTS: Concentrations of particulate matter 2.5 were measured in surgical smoke generated when performing 14 different surgeries. Immediately after electrocautery, the concentration of particulate matter 2.5 increased to 2258 µg/m3 and then, when we stopped using the devices, it decreased rapidly to the initial levels. Interestingly, the concentrations increased after each intermittent electrocautery procedure. Higher concentrations of particulate matter 2.5 were observed during breast surgeries than during laparoscopic procedures. CONCLUSION: Surgical smoke poses potential health risks to operating room personnel by contaminating their breathing zone with high concentrations of particulate matter 2.5. A local exhaust ventilation system is needed to reduce exposure.

Bronchiectasis in severe asthma and asthmatic components in bronchiectasis.

Asthma and bronchiectasis are different diseases; however, differentiating them can be difficult because they share several symptomatic and physiological similarities. Approximately 20% of patients with bronchiectasis have eosinophilic inflammation, 34% show wheezing, and 7-46% have comorbid asthma, although comorbidity with severe asthma may be limited as shown in 3.3% of cases of bronchiectasis. Meanwhile, 25-68% of patients with severe asthma have comorbid bronchiectasis, and at least two phenotypes are present in the accompanying bronchiectasis: eosinophilic bronchiectasis and chronic infectious bronchiolitis/bronchiectasis. Recent studies show that type-2-targeted biologics are effective for eosinophilic bronchiectasis and theoretically effective for some of the remaining cases when used before oral corticosteroids. Further studies are needed to identify treatment strategies for severe asthma with comorbid bronchiectasis and vice versa.

Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma.

BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature of asthma. MUC5AC and MUC5B are the major secreted polymeric mucins in airways, and their compositions affect mucus properties. Despite the increasing appreciation of MUC5AC and MUC5B compositions in asthmatic airways, their pathophysiological relevance remains to be fully understood in humans. METHODS: In this cross-sectional study, we prospectively enrolled newly referred steroid-untreated patients with mild asthma and healthy controls. We compared induced sputum MUC5AC and MUC5B levels between patients and controls. Subsequently, we assessed the correlation between MUC5AC and MUC5B levels and clinical indices in patients. Sputum MUC5AC and MUC5B levels were measured using enzyme-linked immunosorbent assays. RESULTS: Sputum MUC5AC and MUC5B levels were significantly higher in patients (n = 87) than in controls (n = 22) (p = 0.0002 and p = 0.006, respectively). The ratio of sputum MUC5AC to MUC5B tended to be higher in patients than in controls (p = 0.07). Sputum MUC5AC levels significantly and positively correlated with fractional exhaled nitric oxide at expiratory flow of 50 mL/s (Spearman's rho = 0.29, p = 0.006), sputum eosinophil proportion (rho = 0.34, p = 0.0013), and airway sensitivity (rho = 0.39, p = 0.0005). By contrast, sputum MUC5B levels significantly and positively correlated with airway sensitivity (rho = 0.35, p = 0.002) and negatively correlated with airway reactivity (rho = -0.33, p = 0.004). CONCLUSIONS: Sputum MUC5AC is increased by protein levels and involved in airway type 2/eosinophilic inflammation and airway hyperresponsiveness in steroid-untreated patients with mild asthma.

The importance of central airway dilatation in patients with bronchiolitis obliterans.

BACKGROUND: Bronchiolitis obliterans (BO) is a clinical syndrome characterised by progressive small airway obstruction, causing significant morbidity and mortality. Central airway dilatation is one of its radiological characteristics, but little is known about the clinical and pathological associations between airway dilatation and BO. METHODS: This retrospective study consecutively included patients who underwent lung transplantation due to BO at Kyoto University Hospital from 2009 to 2019. Demographic and histopathological findings of the resected lungs were compared between patients with and without airway dilatation measured by chest computed tomography (CT) at registration for lung transplantation. RESULTS: Of a total of 38 included patients (median age, 30 years), 34 (89%) had a history of hematopoietic stem-cell transplantation, and 22 (58%) had airway dilatation based on CT. Patients with airway dilatation had a higher frequency of Pseudomonas aeruginosa isolation with greater residual volume than those without airway dilatation. Quantitative CT analysis revealed an increase in lung volume to predictive total lung capacity and a percentage of low attenuation volume <-950 HU at inspiration in association with the extent of airway dilatation. Airway dilatation on CT was associated with an increased number of bronchioles with concentric narrowing of the lumen and thickening of the subepithelium of the walls on histology. CONCLUSIONS: In patients with BO, airway dilatation may reflect increased residual volume or air trapping and pathological extent of obstructive bronchioles, accompanied by a risk of Pseudomonas aeruginosa isolation. More attention should be paid to the development of airway dilatation in the management of BO.

Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo.

Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported. Herein, we established an expansion system of hLPs based on their three-dimensional culture in core-shell hydrogel microfibers, that ensures the maintenance of their bipotency for differentiation into alveolar and airway epithelial cells including alveolar type II (AT2) cells. Further, we developed an efficient in vivo transplantation method using an endoscope-assisted transtracheal administration system; the successful engraftment and in vivo differentiation of hLPs into alveolar epithelial cells (incorporated into the alveoli) was observed. Importantly, expanded hLPs in the context of microfibers were successfully transplanted into the murine lungs, opening avenues for cell-based therapies of lung diseases. Therefore, our novel method has potential regenerative medicine applications; additionally, the high-quality hLPs and AT2 cells generated via the microfiber-based technology are valuable for drug discovery purposes.

Change in Contralateral Muscle Blood Volume During Passive Unilateral Muscle Stretching Before and After Surgery.

OBJECTIVE: Passive muscle stretching is a common physical therapy for critically ill patients in the intensive care units. This study aimed to evaluate the effects of unilateral passive stretching of the gastrocnemius muscle (GM) before and after surgery on blood volume (BV) in the contralateral (non-stretched) GM in patients who are sedated after surgery. METHODS: We enrolled eight patients with esophageal cancer. The patients completed two sessions of passive cyclical stretching (20-s hold, 10-s release, 10 cycles) of the right GM: one before surgery (awake) and one after (under sedation). We used near-infrared spectroscopy to measure the BV in the stretched and contralateral GM. BV kinetics were compared between the ipsilateral and contralateral GM. RESULTS: In seven of the eight patients, BV in the stretched GM decreased during stretching and increased during the stretch-relaxation phase, both before and after surgery. Both before and after surgery, the change in the BV in the contralateral GM was inversely synchronized to the stretching cycle. CONCLUSIONS: Unilateral passive stretching of the GM influenced the microcirculation of the contralateral GM. The mechanism underlying the synchronous change in the BV in the contralateral GM remains to be clarified.