Tidal volume expandability and ventilatory efficiency as predictors of mortality in Taiwanese male patients with chronic obstructive pulmonary disease: A 10-year follow-up study - Is V̇O2peak or FEV1% the gold standard?

Despite our knowledge of the risk factors for mortality associated with chronic obstructive pulmonary disease (COPD), the mortality rate for this condition continues to increase. This study aimed to investigate the predictive power of physiological variables on all-cause mortality in COPD patients compared to peak oxygen uptake (V˙O2peak) and forced expired volume in one second (FEV1). We conducted a retrospective study of 182 COPD patients with complete lung function tests, cardiopulmonary exercise testing (CPET), and survival data. Cox regression analysis was used to estimate the hazard ratios for all-cause mortality. The median follow-up period was 6.8 (IQR 3.9-9.2) years. Out of the 182 patients in our study, sixty-two (34.1%) succumbed to various causes. Of these, 27.4% (n = 17) experienced acute exacerbations, 24.2% (n = 15) had advanced cancer, and 12.9% (n = 8) had cardiovascular disease as the primary cause of death. Another 25.8% (n = 16) passed away due to other underlying conditions, while 6.5% (n = 4) had an unknown cause of death. One patient's demise was attributed to a benign tumor, and another's to a connective tissue disease. The ratio of tidal volume to total lung capacity (VTpeak/TLC) and the ratio of minute ventilation and V˙O2 at nadir (V˙E/V˙O2nadir) (AUR 0.83, 95% CI 0.76-0.91) were superior predictors of all-cause mortality compared to V˙O2peak and FEV1%. A mortality prediction formula was derived using these variables. This study highlights the potential of VTpeak/TLC and V˙E/V˙O2nadir as predictive markers for COPD all-cause mortality in COPD. CPET is an effective tool for evaluating COPD mortality; however, the predictive equation requires further validation.

Tidal volume expandability affected by flow, dynamic hyperinflation, and quasi-fixed inspiratory time in patients with COPD and healthy individuals.

Exertional dyspnea (ED) and impaired exercise performance (EP) are mainly caused by dynamic hyperinflation (DH) in chronic obstructive pulmonary disease (COPD) patients by constraining tidal volume expansion at peak exercise (VTpeak). As VTpeak is the product of inspiratory time (TIpeak) and flow (VT/TIpeak), it was hypothesized that VTpeak and VTpeak/total lung capacity (VTpeak/TLC) may be affected by TIpeak and VT/TIpeak. Hence, the study investigated the (1) effect of TIpeak and VT/TIpeak on VTpeak expansion, (2) factors associated with TIpeak, expiratory time (TEpeak), VT/TIpeak, and VTpeak/TLC, and (3) relationships between VT/TIpeak and VTpeak/TLC with ED and EP in COPD patients and controls. The study enrolled 126 male stable COPD patients and 33 sex-matched controls. At peak exercise, TIpeak was similar in all subjects (COPD versus controls, mean ± SD: 0.78 ± 0.17 s versus 0.81 ± 0.20 s, p = NS), whereas the COPD group had lower VT/TIpeak (1.71 ± 0.49 L/s versus 2.58 ± 0.69 L/s, p < .0001) and thus the COPD group had smaller VTpeak (1.31 ± 0.34 L versus 2.01 ± 0.45 L,p < .0001) and VTpeak/TLC (0.22 ± 0.06 vs 0.33 ± 0.05, p < .0001). TIpeak, TEpeak, and VT/TIpeak were mainly affected by exercise effort, whereas VTpeak/TLC was not. TEpeak, VT/TIpeak, and VTpeak/TLC were inversely changed by impaired lung function. TIpeak was not affected by lung function. Dynamic hyperinflation did not occur in the controls, however, VTpeak/TLC was strongly inversely related to DH (r = -0.79) and moderately to strongly related to lung function, ED, and EP in the COPD group. There was a slightly stronger correlation between VTpeak/TLC with ED and EP than VT/TIpeak in the COPD group (|r| = 0.55-0.56 vs 0.38-0.43). In summary, TIpeak was similar in both groups and the key to understanding how flow affects lung expansion. However, the DH volume effect was more important than the flow effect on ED and EP in the COPD group.

Mechanisms affecting exercise ventilatory inefficiency-airflow obstruction relationship in male patients with chronic obstructive pulmonary disease.

BACKGROUND: Exercise ventilatory inefficiency is usually defined as high ventilation ([Formula: see text]) versus low CO2 output ([Formula: see text]). The inefficiency may be lowered when airflow obstruction is severe because [Formula: see text] cannot be adequately increased in response to exercise. However, the ventilatory inefficiency-airflow obstruction relationship differs to a varying degree. This has been hypothesized to be affected by increased dead space fraction of tidal volume (VD/VT), acidity, hypoxemia, and hypercapnia. METHODS: A total of 120 male patients with chronic obstructive pulmonary disease were enrolled. Lung function and incremental exercise tests were conducted, and [Formula: see text] versus [Formula: see text] slope ([Formula: see text]) and intercept ([Formula: see text]) were obtained by linear regression. Arterial blood gas analysis was also performed in 47 of the participants during exercise tests. VD/VT and lactate level were measured. RESULTS: VD/VTpeak was moderately positively related to [Formula: see text] (r = 0.41) and negatively related to forced expired volume in 1 sec % predicted (FEV1%) (r = - 0.27), and hence the FEV1%- [Formula: see text] relationship was paradoxical. The higher the [Formula: see text], the higher the pH and PaO2, and the lower the PaCO2 and exercise capacity. [Formula: see text] was marginally related to VD/VTrest. The higher the [Formula: see text], the higher the inspiratory airflow, work rate, and end-tidal PCO2peak. CONCLUSION: 1) Dead space ventilation perturbs the airflow- [Formula: see text] relationship, 2) increasing ventilation thereby increases [Formula: see text] to maintain biological homeostasis, and 3) the physiology- [Formula: see text]- [Formula: see text] relationships are inconsistent in the current and previous studies. TRIAL REGISTRATION: MOST 106-2314-B-040-025 .

Gastric Calcifying Fibrous Tumor: An Easy Misdiagnosis as Gastrointestinal Stromal Tumor-A Systemic Review.

Background and Objectives: Calcifying fibrous tumor (CFT) in the stomach is extremely rare and is easily misdiagnosed as a gastrointestinal stromal tumor (GIST). This study aims to determine the best method to differentiate between gastric CFT and GIST after a systemic review and meta-analysis. Materials and Methods: A systematic search of articles using electronic databases (MEDLINE, EMBASE, and LILACS) was conducted and resulted in 162 articles with 272 CFT cases published from January 1988 to September 2019. Results: Of these cases, 272 patients, 60 patients with gastric CFT (32 men and 28 women, mean age 49.2 years) were analyzed. The mean tumor size was 2.4 cm in patients with gastric CFT. Both endoscopic ultrasound (EUS) and computed tomography (CT) findings revealed well-defined (100% vs. 77.8%), heterogeneous (100% vs. 77.8%), iso-hypoechoic (71.4% vs. 33.3%), and calcified (85.7% vs. 77.8%) lesions, respectively. The majority of patients (53.3%) were symptomatic, with the most common symptom being abdominal discomfort (55.6%). None of the patients with gastric CFT showed recurrence after treatment, and most patients received nonendoscopic treatment (56%, n = 28/50). Both age and tumor size were statistically significant in patients with gastric CFT than GIST (49.2 vs. 65.0 years and 2.4 vs. 6.0 cm; both p < 0.001). The ratio of children among patients with CFT (5%) and GIST (0.05%) was also significantly different (p = 0.037). The calcification rates of gastric CFT had significantly higher calcification rates than GIST on images of EUS and CT (85.7% vs. 3.6% and 77.8% vs. 3.6%; both p < 0.001). Conclusions: Compared with patients with GIST, patients with gastric CFT were younger, had smaller tumor size, and were symptomatic. Furthermore, gastric CFT was well-defined, heterogeneous in the third layer, and had high calcification rates on the images.

Analyzing key elements of breathing patterns, deriving remaining variables, and identifying cutoff values in individuals with chronic respiratory disease and healthy subjects.

BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm. METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values. RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104 L/min may differentiate ILD from control, while V̇E of 54 L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99 s, and IDC of .45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90). CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.

The contribution of estimated dead space fraction to mortality prediction in patients with chronic obstructive pulmonary disease-a new proposal.

Background: Mortality due to chronic obstructive pulmonary disease (COPD) is increasing. However, dead space fractions at rest (VD/VTrest) and peak exercise (VD/VTpeak) and variables affecting survival have not been evaluated. This study aimed to investigate these issues. Methods: This retrospective observational cohort study was conducted from 2010-2020. Patients with COPD who smoked, met the Global Initiatives for Chronic Lung Diseases (GOLD) criteria, had available demographic, complete lung function test (CLFT), medication, acute exacerbation of COPD (AECOPD), Charlson Comorbidity Index, and survival data were enrolled. VD/VTrest and VD/VTpeak were estimated (estVD/VTrest and estVD/VTpeak). Univariate and multivariable Cox regression with stepwise variable selection were performed to estimate hazard ratios of all-cause mortality. Results: Overall, 14,910 patients with COPD were obtained from the hospital database, and 456 were analyzed after excluding those without CLFT or meeting the lung function criteria during the follow-up period (median (IQR) 597 (331-934.5) days). Of the 456 subjects, 81% had GOLD stages 2 and 3, highly elevated dead space fractions, mild air-trapping and diffusion impairment. The hospitalized AECOPD rate was 0.60 ± 2.84/person/year. Forty-eight subjects (10.5%) died, including 30 with advanced cancer. The incidence density of death was 6.03 per 100 person-years. The crude risk factors for mortality were elevated estVD/VTrest, estVD/VTpeak, ≥2 hospitalizations for AECOPD, advanced age, body mass index (BMI) <18.5 kg/m2, and cancer (hazard ratios (95% C.I.) from 1.03 [1.00-1.06] to 5.45 [3.04-9.79]). The protective factors were high peak expiratory flow%, adjusted diffusing capacity%, alveolar volume%, and BMI 24-26.9 kg/m2. In stepwise Cox regression analysis, after adjusting for all selected factors except cancer, estVD/VTrest and BMI <18.5 kg/m2 were risk factors, whereas BMI 24-26.9 kg/m2 was protective. Cancer was the main cause of all-cause mortality in this study; however, estVD/VTrest and BMI were independent prognostic factors for COPD after excluding cancer. Conclusions: The predictive formula for dead space fraction enables the estimation of VD/VTrest, and the mortality probability formula facilitates the estimation of COPD mortality. However, the clinical implications should be approached with caution until these formulas have been validated.

A comparative study of dynamic lung hyperinflation and tidal volume to total lung capacity ratios during exercise in patients with chronic respiratory disease and healthy individuals.

BACKGROUND: Current measures of tidal volume/forced vital capacity (VT/FVC) and VT/inspiratory capacity (VT/IC) at peak exercise cannot differentiate restrictive from obstructive ventilation patterns. This study aimed to investigate the utility of VT/total lung capacity (VT/TLC) as a marker for dynamic lung hyperinflation (DH) in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). METHODS: 267 subjects were screened: 23 ILD, 126 COPD, and 33 healthy individuals were enrolled. Lung function tests and cardiopulmonary exercise tests with repeated IC maneuver were conducted and compared at three exercise efforts: unloaded, middle of exercise, and peak exercise. RESULTS: During exercise, ILD patients demonstrated normal end-expiratory lung volume/TLC (EELV/TLC) ratios, but elevated end-inspiratory lung volume/TLC (EILV/TLC) ratios, except for peak exercise. COPD patients exhibited elevated ratios for both EELV/TLC and EILV/TLC during exercise with a larger EELV/TLC ratio compared to ILD patients at peak exercise (p < 0.05). The VT/TLC ratio distinguished ILD, COPD, and healthy controls at peak exercise (p < 0.05). A VT/TLC ratio of ≤ 0.22 or ≥ 0.30 indicated airflow obstruction with hyperinflation or normal lung expansion, respectively (AUC: 0.74 or 0.88). Furthermore, VT/TLC outperformed VT/FVC and VT/IC in differentiating lung expansion between ILD and COPD during exercise (all p < 0.05). CONCLUSION: Exercise-induced DH was absent in ILD patients but observed in COPD patients. Excessive lung expansion occurred in all patients during exercise, except for limited expansion in ILD at peak exercise probably due to specific lung properties. VT/TLC can distinguish between restrictive, obstructive, and normal ventilatory patterns.

Resting pulmonary function and artery pressure and cardiopulmonary exercise testing in chronic heart failure patients in Taiwan - a prospective observational cross-sectional study comparing healthy subjects and interstitial lung disease patients.

BACKGROUND: Restrictive ventilatory defects and elevated pulmonary artery pressure (PAP) are common in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD). However, as oxyhemoglobin desaturation seldom occurs in stable CHF patients at peak exercise, we hypothesized that the pathophysiology may be different between them. This study aimed to investigate: (1) PAP and lung function at rest, (2) pulmonary gas exchange (PGX) and breathing patterns at peak exercise, (3) mechanisms of dyspnea at peak exercise in patients with CHF compared to healthy subjects and ILD patients. METHODS: We consecutively enrolled 83 participants (27 with CHF, 23 with ILD, and 33 healthy controls). The CHF and ILD groups had similar functional status. Lung function and cardiopulmonary exercise tests with Borg Dyspnea Score were performed. PAP was estimated using echocardiography. Resting lung function, PAP and peak exercise data in the CHF group were compared to the healthy and ILD groups. Correlation analysis was performed to elucidate the mechanisms of dyspnea in the CHF and ILD groups. RESULTS: Compared to the healthy group, the CHF group had normal lung function, PAP at rest, and normal dyspnea score and PGX at peak exercise, whereas the ILD group had abnormal values compared to the CHF group. Dyspnea score was positively correlated with pressure gradient, lung expansion capabilities, and expiratory tidal flow in the CHF group (all p < 0.05), but inversely correlated with inspiratory time-related variables in the ILD group (all p < 0.05). CONCLUSION: Normal lung function and PAP at rest, and dyspnea scores and PGX at peak exercise indicated that pulmonary hypertension and fibrosis were insignificant in the patients with CHF. The factors affecting dyspnea at peak exercise were different between the CHF and ILD groups. As the sample size in this study was small, large-scale studies are warranted to confirm our findings.

Normal lung function and pulmonary arterial pressure at rest, and dyspnea scores and pulmonary gas exchange at peak exercise indicated that pulmonary hypertension and fibrosis in the patients with chronic heart failure were not significant.Dyspnea score was correlated with different physiological variables between the groups with chronic heart failure and interstitial lung disease.

Using statistical techniques to predict dynamic arterial P(CO(2)) in patients with COPD during maximum exercise.

BACKGROUND: P(aCO(2)) as measured during exercise in patients with COPD is poorly predicted (predicted P(aCO(2))) from lung function testing and some noninvasive measurements, such as end-tidal P(CO(2)) (P(ETCO(2))). OBJECTIVE: We performed a number of statistical techniques on P(ETCO(2)) and its interaction with other physiologic variables during exercise testing, in order to improve our ability to predict P(aCO(2)). The estimated P(aCO(2)) as determined from these techniques may therefore be used to contrast the P(ETCO(2)) readings that are measured during an incremental exercise test on a breath-by-breath basis (ie, P(aCO(2)) - P(ETCO(2))), and to identify exercise-induced hypercapnia. METHODS: Forty-seven men with COPD underwent both pulmonary function testing and incremental exercise testing until limited by symptoms. Arterial blood gases and exercise physiological measurements were performed during maximal exercise testing. The prediction equations for P(aCO(2)) were generated using regression techniques with the leave-one-out cross-validation technique. RESULTS: Forty-one patients were included in the final analysis after 6 patients were excluded due to inadequate data collection. The best prediction equation we found was: predicted P(aCO(2)) = 23.71 + P(ETCO(2)) × (0.9-0.01 × D(LCO) -0.04 × V(T)) - 2.61 × SVC - 0.04 × MEP, where D(LCO) is diffusing capacity for carbon monoxide in mL/min/mm Hg, V(T) is tidal volume in L, SVC is slow vital capacity in L, and MEP is maximum expiratory pressure in cm H(2)O. The difference between the measured and predicted P(aCO(2)) at each time point was not statistically significant (all P > .05). The standard errors of the estimated P(aCO(2)) at each time point were 0.91-1.12 mm Hg. CONCLUSIONS: A validated mixed-model regression derived equation yields a predicted P(aCO(2)) trend during exercise that can be helpful when interpreting exercise testing to determine P(aCO(2)) - P(ETCO(2)) and exercise-induced hypercapnia.

Hierarchical stratification of the factors related to exertional dyspnoea and exercise intolerance in male COPD patients.

BACKGROUND: The order and extent of interactions across the factors affecting exertional dyspnoea (ED) and exercise intolerance (EI) in patients with chronic obstructive pulmonary disease (COPD) are not clear. We hypothesized that lung and non-lung variables were the primary variables, ED was the secondary variable and EI was the tertiary variable. METHODS: Data on demographics, blood tests, cardiac imaging, lung function tests and invasive dead space fractions (VD/VT) during incremental exercise test of 46 male COPD subjects were obtained. These variables were categorized by factor analysis and pair-wise correlation analysis was conducted. The best factor of each category was selected and then multivariate regression was conducted. RESULTS: Peak tidal inspiratory flow (VT/TIpeak), VD/VTpeak and tidal lung expansion capability, and resting diffusing capacity of the lungs (DLCO)% predicted were the primary pulmonary factors most related to ED, whereas body mass index (BMI), haemoglobin and cholesterol levels were the primary non-pulmonary factors. In multivariate regression analysis, VT/TIpeak, VD/VTpeak and DLCO% were the primary factors most related to ED (r2 = 0.69); ED was most related to EI (r = -0.74 to -0.83). CONCLUSION: Using hierarchical stratification and statistical methods may improve understanding of the pathophysiology of ED and EI in patients with COPD. KEY MESSAGESThe pathophysiology of exertional dyspnoea (ED) and exercise intolerance (EI) in chronic obstructive pulmonary disease (COPD) is complex. The order and extent of interactions across factors are not clear. In multivariate regression analysis, we found that tidal inspiratory flow, dead space fraction and resting diffusing capacity of the lungs % but not the non-pulmonary factors affected ED.Using correlation coefficients, we further found that ED was the secondary variable and EI was the tertiary variable.Hierarchical stratification of the important factors associated with ED and EI in patients with COPD clarifies their relationships and could be incorporated into management programmes and outcome studies for these patients.

Prediction and types of dead-space fraction during exercise in male chronic obstructive pulmonary disease patients.

ABSTRACT: A high dead space (VD) to tidal volume (VT) ratio during peak exercise (VD/VTpeak) is a sensitive and consistent marker of gas exchange abnormalities; therefore, it is important in patients with chronic obstructive pulmonary disease (COPD). However, it is necessary to use invasive methods to obtain VD/VTpeak, as noninvasive methods, such as end-tidal PCO2 (PETCO2peak) and PETCO2 adjusted with Jones' equation (PJCO2peak) at peak exercise, have been reported to be inconsistent with arterial PCO2 at peak exercise (PaCO2peak). Hence, this study aimed to generate prediction equations for VD/VTpeak using statistical techniques, and to use PETCO2peak and PJCO2peak to calculate the corresponding VD/VTpeaks (i.e., VD/VTpeakETVD/VTpeakJ).A total of 46 male subjects diagnosed with COPD who underwent incremental cardiopulmonary exercise tests with PaCO2 measured via arterial catheterization were enrolled. Demographic data, blood laboratory tests, functional daily activities, chest radiography, two-dimensional echocardiography, and lung function tests were assessed.In multivariate analysis, diffusing capacity, vital capacity, mean inspiratory tidal flow, heart rate, and oxygen pulse at peak exercise were selected with a predictive power of 0.74. There were no significant differences in the PCO2peak values and the corresponding VD/VTpeak values across the three types (both p = NS).In subjects with COPD, VD/VTpeak can be estimated using statistical methods and the PETCO2peak and PJCO2peak. These methods may have similar predictive power and thus can be used in clinical practice.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.).

Resting Dead Space Fraction as Related to Clinical Characteristics, Lung Function, and Gas Exchange in Male Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Measures of forced expired volume in one second % predicted (FEV1%), residual volume to total lung capacity ratio (RV/TLC) and diffusing capacity for carbon monoxide measurements (DLCO) are the standard lung function test for evaluating patients with chronic obstructive pulmonary disease (COPD). The dead space fraction (VD/VT) has been shown to be a robust marker of gas exchange abnormality. However, the use of VD/VT has gradually become less common. As VD/VT measured at rest (VD/VTR) has been successfully used in non-COPD conditions, it was hypothesized that in COPD the VD/VTR was more sensitive than the standard lung function test in correlation with clinical characteristics and gas exchange. This study aimed to test the hypothesis and to identify the variables relevant to VD/VTR. METHODS: A total of 46 male subjects with COPD were enrolled. Clinical characteristics included demographic data, oxygen-cost diagram (OCD), and image studies for pulmonary hypertension. The standard lung function was obtained. To calculate VD/VT, invasive arterial blood gas and pulmonary gas exchange (PGX) were measured. The variables relevant to VD/VTR were analyzed by multiple linear regression. RESULTS: Compared to lung function, VD/VTR was more frequently and significantly related to smoking, carboxyhemoglobin level, pulmonary hypertension and PaCO2 (all p <0.05) whereas FEV1% was more related to lung function test, PaO2 and OCD score. VD/VTR and FEV1% were highly related to resting gas exchange but RV/TLC and DLCO% were not. Cigarette consumption, the equivalent for CO2 output, arterial oxyhemoglobin saturation, and the product of tidal volume and inspiratory duty cycle were identified as the parameters relevant to VD/VTR with a power of 0.72. CONCLUSION: Compared to lung function test, VD/VTR is more related to clinical characteristics and is a comprehensive marker of resting gas exchange. Further studies are warranted to provide a noninvasive measurement of VD/VTR. REGISTRATION NUMBER: MOST 106-2314-B-040-025 and CSH-2019-C-30.

Combining Dynamic Hyperinflation with Dead Space Volume during Maximal Exercise in Patients with Chronic Obstructive Pulmonary Disease.

Physiological dead space volume (VD) and dynamic hyperinflation (DH) are two different types of abnormal pulmonary physiology. Although they both involve lung volume, their combination has never been advocated, and thus their effect and implication are unclear. This study aimed (1) to combine VD and DH, and (2) investigate their relationship and clinical significance during exercise, as well as (3) identify a noninvasive variable to represent the VD fraction of tidal volume (VD/VT). Forty-six male subjects with chronic obstructive pulmonary disease (COPD) and 34 healthy male subjects matched for age and height were enrolled. Demographic data, lung function, and maximal exercise were investigated. End-expiratory lung volume (EELV) was measured for the control group and estimated for the study group using the formulae reported in our previous study. The VD/VT ratio was measured for the study group, and reference values of VD/VT were used for the control group. In the COPD group, the DHpeak/total lung capacity (TLC, DHpeak%) was 7% and the EELVpeak% was 70%. After adding the VDpeak% (8%), the VDDHpeak% was 15% and the VDEELVpeak% was 78%. Both were higher than those of the healthy controls. In the COPD group, the VDDHpeak% and VDEELVpeak% were more correlated with dyspnea score and exercise capacity than that of the DHpeak% and EELV%, and had a similar strength of correlation with minute ventilation. The VTpeak/TLC (VTpeak%), an inverse marker of DH, was inversely correlated with VD/VT (R2 ≈ 0.50). Therefore, we recommend that VD should be added to DH and EELV, as they are physiologically meaningful and VTpeak% represents not only DH but also dead space ventilation. To obtain VD, the VD/VT must be measured. Because obtaining VD/VT requires invasive arterial blood gases, further studies on noninvasive predicting VD/VT is warranted.

Investigating the relationships among lung function variables in chronic obstructive pulmonary disease in men.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the independent contributions of individual lung function variables to outcomes may be lower when they are modelled together if they are collinear. In addition, lung volume measurements may not be necessary after spirometry data have been obtained. However, these hypotheses depend on whether forced vital capacity (FVC) can predict total lung capacity (TLC). Moreover, the definitions of hyperinflation and air trapping according to lung function variables overlap and need be clarified. Therefore, the aim of this study was to evaluate the relationships among various lung function parameters to elucidate these issues. METHODS: Demographic data and 26 parameters of full lung function were measured in 94 men with COPD and analyzed using factor and correlation analyses. RESULTS: Factor analysis revealed five latent factors. Inspiratory capacity (IC)/TLC and residual volume (RV)/TLC were most strongly correlated with all other lung volumes. IC/TLC, RV/TLC, and functional residual capacity (FRC)/TLC were collinear and were potential markers of air trapping, whereas TLC%, FRC%, and RV% were collinear and were potential markers of hyperinflation. RV/TLC >0.4 (or IC/TLC <0.4) was comparable with the ratio of forced expiratory volume in one second (FEV1) and FVC <0.7. FVC% and FEV1% were poorly correlated with TLC%. The correlation study showed that TLC%, RV/TLC, and FEV1% could be used to represent individual latent factors for hyperinflation, air trapping, inspiration, expiration, and obstruction. Combined with diffusion capacity%, these four factors could be used to represent comprehensive lung function. CONCLUSIONS: This study identified collinear relationships among individual lung function variables and thus selecting variables with close relationships for correlation studies should be performed with caution. This study also differentiated variables for air trapping and lung hyperinflation. Lung volume measurements are still required even when spirometry data are available. Four out of 26 lung function variables from individual latent factors could be used to concisely represent lung function.

More Impaired Dynamic Ventilatory Muscle Oxygenation in Congestive Heart Failure than in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) often have dyspnea. Despite differences in primary organ derangement and similarities in secondary skeletal muscle changes, both patient groups have prominent functional impairment. With similar daily exercise performance in patients with CHF and COPD, we hypothesized that patients with CHF would have worse ventilatory muscle oxygenation than patients with COPD. This study aimed to compare differences in tissue oxygenation and blood capacity between ventilatory muscles and leg muscles and between the two patient groups. Demographic data, lung function, and maximal cardiopulmonary exercise tests were performed in 134 subjects without acute illnesses. Muscle oxygenation and blood capacity were measured using frequency-domain near-infrared spectroscopy (fd-NIRS). We enrolled normal subjects and patients with COPD and CHF. The two patient groups were matched by oxygen-cost diagram scores, New York Heart Association functional classification scores, and modified Medical Research Council scores. COPD was defined as forced expired volume in one second and forced expired vital capacity ratio ≤0.7. CHF was defined as stable heart failure with an ejection fraction ≤49%. The healthy subjects were defined as those with no obvious history of chronic disease. Age, body mass index, cigarette consumption, lung function, and exercise capacity were different across the three groups. Muscle oxygenation and blood capacity were adjusted accordingly. Leg muscles had higher deoxygenation (HHb) and oxygenation (HbO2) and lower oxygen saturation (SmO2) than ventilatory muscles in all participants. The SmO2 of leg muscles was lower than that of ventilatory muscles because SmO2 was calculated as HbO2/(HHb+HbO2), and the HHb of leg muscles was relatively higher than the HbO2 of leg muscles. The healthy subjects had higher SmO2, the patients with COPD had higher HHb, and the patients with CHF had lower HbO2 in both muscle groups throughout the tests. The patients with CHF had lower SmO2 of ventilatory muscles than the patients with COPD at peak exercise (p < 0.01). We conclud that fd-NIRS can be used to discriminate tissue oxygenation of different musculatures and disease entities. More studies on interventions on ventilatory muscle oxygenation in patients with CHF and COPD are warranted.

Developing a New Marker of Dynamic Hyperinflation in Patients with Obstructive Airway Disease - an observational study.

Tidal volume at peak exercise and vital capacity ratio (VTpeak/VC) and VTpeak/inspiratory capacity (IC) were used to differentiate lung expansion in subjects with normal health and chronic obstructive pulmonary disease (COPD) from that in subjects with restrictive ventilation. However, VC and IC variably change due to pseudorestriction of lung volumes. Thus, these variables are currently not recommended. In contrast, total lung capacity (TLC) does little change during exercise. The aims of the study investigated whether VTpeak/TLC is more significantly correlated with static air trapping and lung hyperinflation in patients with COPD than VTpeak/IC, VTpeak/FVC, and VTpeak/SVC (study 1), and developed a marker to replace dynamic IC maneuvers by evaluation of the relationship between end-expiratory lung volume (EELV) and VTpeak/TLC and identification of a cutoff value for VTpeak/TLC (study 2). One hundred adults with COPD (study 1) and 23 with COPD and 19 controls (study 2) were analyzed. Spirometry, lung volume, diffusing capacity, incremental cardiopulmonary exercise tests with dynamic IC maneuvers were compared between groups. An ROC curve was generated to identify a cut off value for VTpeak/TLC. In study 1, VTpeak/TLC was more significantly associated with airflow obstruction, static air trapping and hyperinflation. In study 2, VTpeak/TLC was highly correlated with EELV in the patients (r = -0.83), and VTpeak/TLC ≥ 0.27 predicted that 18% of the patients with static air trapping and hyperinflation can expand their VT equivalent to the controls. In conclusions, VTpeak/TLC was superior to other VTpeak/capacities. VTpeak/TLC may be a marker of dynamic hyperinflation in subjects with COPD, thereby avoiding the need for dynamic IC maneuvers. VTpeak/TLC < 0.27 identified approximately 82% of subjects with COPD who could not adequately expand their tidal volume. As most of our participants were male, further studies are required to elucidate whether the results of this study can be applied to female patients with COPD.

Muscle oxygenation dynamics in response to electrical stimulation as measured with near-infrared spectroscopy: A pilot study.

Neuromuscular electrical stimulation (NMES) is used for preventing muscle atrophy and improving muscle strength in patients and healthy people. However, the current intensity of NMES is usually set at a level that causes the stimulated muscles to contract. This typically causes pain. Quantifying the instantaneous changes in muscle microcirculation and metabolism during NMES before muscle contraction occurs is crucial, because it enables the current intensity to be optimally tuned, thereby reducing the NMES-induced muscle pain and fatigue. We applied near-infrared spectroscopy (NIRS) to measure instantaneous tissue oxygenation and deoxygenation changes in 43 healthy young adults during NMES at 10, 15, 20, 25, 30, and 35 mA. Having been stabilized at the NIRS signal baseline, the tissue oxygenation and total hemoglobin concentration increased immediately after stimulation in a dose-dependent manner (P < 0.05) until stimulation was stopped at the level causing muscle contraction without pain. Tissue deoxygenation appeared relatively unchanged during NMES. We conclude that NIRS can be used to determine the optimal NMES current intensity by monitoring oxygenation changes.

Pneumocystis jirovecii pneumonia in AIDS and non-AIDS immunocompromised patients - an update.

INTRODUCTION: Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients. METHODOLOGY: We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017. RESULTS: The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-ß-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial. CONCLUSIONS: Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.

Oxygenation dynamics of sepsis patients undergoing far-infrared intervention based on near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS; continuous wave type) is a noninvasive tool for detecting the relative change of oxyhemoglobin and deoxyhemoglobin. To make this change, intervention methods must be applied. This study determined the hemodynamics of 44 healthy participants and 35 patients with sepsis during exposure to FIR as a novel physical intervention approach. Local microcirculation of their brachioradialis was monitored during exposure and recovery through NIRS. The variations in blood flow and microvascular reaction were determined by conducting paired and unpaired t tests. The oxyhemoglobin levels of the healthy participants increased continuously, even during recovery. In contrast to expextations, the oxyhemoglobin levels of the patients plateaued after only 5 min of FIR illumination. The proposed method has potential applications for ensuring efficient treatment and facilitating doctors in diagnosing the functions of vessels in intensive care units. Mapping diagrams of HbO2 in healthy males and males with sepsis illustrated unique scenarios during the process.