Intercept of minute ventilation versus carbon dioxide output relationship as an index of ventilatory inefficiency in chronic obstructive pulmonary disease

BackgroundVentilatory inefficiency contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V^˙ _E) vs. carbon dioxide output (V^˙ CO₂) plot is a key ventilatory inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate correlations between the V^˙ _E/V^˙ CO₂ intercept and LH and airflow limitation to determine its physiological interpretation as an index of functional impairment in COPD.MethodsWe conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls who performed incremental cardiopulmonary exercise tests (CPETs) and resting pulmonary function assessment. Ventilatory inefficiency was represented by parameters reflecting the V^˙ _E/V^˙ CO₂ nadir and slope (linear region) and the intercept of V^˙ _E/V^˙ CO₂ plot. Their correlations with measures of LH and airflow limitation were evaluated.ResultsCompared to control, the slope (30.58±3.62, P<0.001) and intercept (4.85±1.11 L/min, P<0.05) were higher in COPD_stages1-2, leading to a higher nadir (31.47±4.47, P<0.01). Despite an even higher intercept in COPD_stages3-4 (7.16±1.41, P<0.001), the slope diminished with disease progression (from 30.58±3.62 in COPD_stages1-2 to 26.84±4.96 in COPD_stages3-4, P<0.01). There was no difference in nadir among COPD groups and higher intercepts across all stages. The intercept was correlated with peak V^˙ _E/maximal voluntary ventilation (MVV) (r=0.489, P<0.001) and peak V^˙ O₂/Watt (r=0.354, P=0.003). The intercept was positively correlated with residual volume (RV) % predicted (r=0.571, P<0.001), RV/total lung capacity (TLC) (r=0.588, P<0.001), peak tidal volume (V_T)/FEV₁ (r=0.482, P<0.001) and negatively correlated with rest inspiratory capacity (IC)/TLC (r=−0.574, P<0.001), peak V_T/TLC (r=−0.585, P<0.001), airflow limitation forced expiratory volume in 1 s (FEV₁) % predicted (r=−0.606, P<0.001), and FEV₁/forced vital capacity (FVC) (r=−0.629, P<0.001).ConclusionsV^˙ _E/V^˙ CO₂ intercept was consistently correlated with worsening static and dynamic LH, pulmonary gas exchange, and airflow limitation in COPD. The V^˙ _E/V^˙ CO₂ intercept emerged as a useful index of ventilatory inefficiency in COPD patients.     

Prevalence and characteristics of chronic obstructive pulmonary disease in China with a diagnostic criterion of FEV1/FVC less than the lower limit of normal—a reanalysis of Chinese epidemiological survey of COPD (CESCOPD) study

BackgroundTo reappraise the prevalence and characteristics of chronic obstructive pulmonary disease (COPD) in China with a criterion of FEV₁/FVC < the lower limit of normal (LLN).MethodsWe assessed the incidence and characteristics of airflow limitation using data from the Chinese Epidemiological Survey of COPD study—a multicenter, randomized trial, with an age-dependent LLN reference equation [established by the Guangzhou Institute of Respiratory Health (GIRH)]. Questionnaire and spirometry data were collected for all eligible subjects. COPD prevalence, risk factors, severity distribution, as well as comparisons of characteristics between the LLN and 0.7 were analyzed.ResultsCOPD prevalence was 9.0% among participants aged 40–80 years in China with the criterion of LLN. Greater prevalence was observed in female sex, rural areas and never smokers than with the GOLD 0.7 fixed ratio. Age distribution showed a higher incidence of COPD in people under 60 years but lower in participants over 60 years of age. With the LLN FEV₁ reference equation, patients in stage I were decreased (15.8% vs. 24.6%, P<0.001), while the proportion of patients in stage III and IV were increased when compared with the China 2002 revised equation (27.7% vs. 21.1%, for stage III, P<0.001; 8.7% vs. 5.6% for stage IV, P=0.001). Only 30.8% of patients with COPD had ever been “diagnosed” with COPD and 60.6% of the patients had respiratory symptoms, both lower than that under the GOLD 0.7 fixed-ratio criterion (35.5%, P=0.004; 64.8% for symptoms, P=0.014).ConclusionsWith the GIRH-LLN criterion, COPD prevalence was slightly higher, and a large number of women, rural patients and nonsmokers with young age and little symptoms were diagnosed when compared with GOLD 0.7 fixed ratio. These subjects may, therefore, deserve further attention and may warrant regular follow-up.Trial RegistrationRegistration number: ChiCTR-ECS-13004110.     

Antimicrobial peptide LL-37 circulating levels in chronic obstructive pulmonary disease patients with high risk of frequent exacerbations

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) increase the decline in lung function, deterioration in health status and risk of death. The assessment of exacerbation risk is important in the grading of COPD. The most common cause of COPD exacerbation is respiratory tract infection. The only known human cathelicidin antimicrobial peptide, LL-37, play an important role in innate defense against infection. Its gene expression is regulated by the bioactive form of vitamin D. The objective of the present study was to explore the relationship between LL-37 plasma levels, vitamin D status and exacerbation risk in patients with COPD.

Methods

COPD patients and normal subjects were recruited from Beijing Hospital for this study. COPD patients were divided into low risk group and high risk group according to the criteria of GOLD strategy. The plasma concentrations of LL-37 were measured by ELISA technique to explore the difference in LL-37 levels between groups. The plasma levels of 25-hydroxy vitamin D [25(OH)D] were analyzed using electrochemiluminescence immunoassay (ECLIA).

Results

A total of 84 COPD patients and 51 normal subjects (control group) were recruited. COPD patients were divided into low risk group (37 cases) and high risk group (47 cases), depending on forced expiratory volume in one second (FEV₁)%pred and exacerbation frequency in the previous year. The plasma concentrations of LL-37 in control group, low risk group and high risk group were 20.7±5.8, 19.5±4.1 and 17.9±3.9 µg/L respectively. The plasma concentration of LL-37 was significantly lower in high risk group than in control group (P=0.006). But there was no significant difference between low risk group and high risk group (P=0.152). The plasma concentrations of 25(OH)D in control group, low risk group and high risk group were 18.1±9.4, 13.1±6.9 and 9.3±5.8 ng/mL respectively. The plasma concentration of 25(OH)D was significantly higher in control group than in low risk group (P=0.004) or high risk group (P<0.001). The plasma concentration of 25(OH)D was significantly lower in high risk group than in low risk group (P=0.031). Hospitalization frequency for COPD exacerbations was negative correlated with plasma levels of LL-37 (r=−0.290, P=0.048) and 25(OH)D (r=−0.341, P=0.020) in high risk group. There was not significant correlation between LL-37 and 25(OH)D in COPD patients (r=0.115, P=0.303).

Conclusions

The plasma levels of LL-37 and 25(OH)D were lower in COPD patients with high risk of frequent exacerbations than normal subjects. Low plasma levels of LL-37 and 25(OH)D might be predictors of exacerbation risk in COPD patients.     

Plasma homocysteine is elevated in COPD patients and is related to COPD severity

Background:

Although recent studies have found that total plasma homocysteine (tHCY) and chronic obstructive pulmonary disease (COPD) are both risk factors for cardiac disease, there have been few studies of plasma homocysteine levels in COPD patients. We tested the hypothesis that total plasma homocysteine (tHCY) would be elevated in patients diagnosed with COPD compared with controls.

Methods:

We studied 29 COPD outpatients and 25 asymptomatic subjects (controls) over age 55 years with measurement of forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), St. Georges Respiratory Questionnaire (SGRQ) score, tHCY and serum C-reactive protein (sCRP).

Results:

There was no difference between controls vs. COPD patients in mean age or gender but mean (SD) FEV₁ was 2.25 (0.77) vs 1.43 (0.60) L; FEV₁% predicted 76.1 (17.2) vs 49.1 (16.3) p < 0.001 in both cases. Median (IQR) tHCY was 8.22 (6.63, 9.55) in controls vs 10.96 (7.56, 13.60) micromol/l for COPD, p = 0.006 and sCRP 0.89 (0.47, 2.55) vs 2.05 (0.86, 6.19) mg/l, p = 0.023. tHCY(log) was also higher in (r, p) smokers (0.448, 0.001), patients with low FEV₁% (−0.397, 0.003), males (0.475, <0.001), but high SGRQ Total score (0.289, 0.034), and high sCRP (0.316, 0.038). tHCY(log) was independently related to (regression coefficient, p) sCRP(log) (0.087, 0.024), male gender (0.345, <0.001) and presence of COPD (0.194, 0.031). Median (IQR) tHCY GOLD Stage I and II 8.05 (7.28, 11.04), GOLD Stage III and IV: 11.83(9.30, 18.30); p = 0.023.

Conclusions:

Plasma homocysteine is significantly elevated in COPD patients relative to age and sex-matched controls and is related to serum CRP and COPD severity.     

Evolution of the COPD Assessment Test score during chronic obstructive pulmonary disease exacerbations: Determinants and prognostic value

BACKGROUND:

An adequate evaluation of exacerbations is a primary objective in managing patients with chronic obstructive pulmonary disease (COPD).

OBJECTIVES:

To define the profile of health status recovery during severe exacerbations of COPD using the COPD Assessment Test (CAT) questionnaire and to evaluate its prognostic value.

METHODS:

Forty-five patients with previous COPD diagnoses who were hospitalized due to severe exacerbation(s) were included in the study. These patients were treated by their respective physicians following current recommendations; health status was assessed daily using the CAT questionnaire. The CAT score, spirometry and recurrent hospitalizations were recorded one and three months after hospital discharge.

RESULTS:

Global initiative for chronic Obstructive Lung Disease (GOLD) stage was an independent determinant for increased CAT score during the first days of exacerbation with respect to postexacerbation values. From hospitalization day 5, the CAT score was similar to that obtained in the stable phase. Body mass index, GOLD stage and education level were related to health status recovery pattern. CAT score increase and the area under the curve of CAT recovery were inversely related to the forced expiratory volume in 1 s achieved three months after discharge (r= −0.606; P<0.001 and r= −0.532; P<0.001, respectively). Patients with recurrent hospitalizations showed higher CAT score increases and slower recovery.

CONCLUSIONS:

The CAT detects early health status improvement during severe COPD exacerbations. Its initial worsening and recovery pattern are related to lung function and recurrent hospitalizations.     

The paradoxical response to short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease

BackgroundThere are a few studies about paradoxical bronchodilator response (BDR), which means a decrease in forced expiratory volume in 1 second (FEV₁) or forced vital capacity (FVC) after short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease (COPD). We evaluated the effect of paradoxical BDR on the clinical outcomes of COPD patients in South Korea.MethodsWe analyzed the KOrea COpd Subgroup Study team (KOCOSS) cohort data in South Korea between January 2012 and December 2017. BDR was defined as at least a 12% and 200-mL reduction in FEV₁ or FVC after bronchodilator administration.ResultsA total of 1,991 patients were included in this study. A paradoxical BDR was noted in 57 (2.9%) patients and was independently associated with worse dyspnea and poor quality of life. High C-reactive protein (CRP) levels were associated with a paradoxical BDR (OR, 1.05; 95% CI, 1.01–1.09; P=0.003). However, paradoxical BDR was not associated with severe acute exacerbations. Pre-bronchodilator FEV₁ (L) showed a higher area under the curve (AUC) for predicting severe acute exacerbations than the post-bronchodilator FEV₁ (L) in the paradoxical BDR group (0.788 vs. 0.752).ConclusionA paradoxical reduction of FEV₁ or FVC after bronchodilator administration may be associated with chronic inflammation in the airway and independently associated with worse respiratory symptoms and poor quality of life.     

Thymus and activation-regulated chemokine (TARC/CCL17) predicts decline of pulmonary function in patients with chronic obstructive pulmonary disease

BackgroundThe deterioration of pulmonary function, such as FEV₁-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV₁-decline in COPD patients.MethodsWe recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV₁ or FEV₁ percent predicted (%FEV₁) per year.ResultsIn the FEV₁-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV₁ as a classifier instead of FEV₁, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group.ConclusionsTARC is an independent predictive biomarker for the rapid-decline in FEV₁. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV₁ decline.     

Native T1-mapping and diffusion-weighted imaging (DWI) can be used to identify lung cancer pathological types and their correlation with Ki-67 expression

BackgroundThis study aimed to explore the value of native T1-mapping and diffusion-weighted imaging (DWI) in differentiating the pathological types and degree of tumor differentiation of lung cancer and their correlation with Ki-67 protein expression.MethodsA total of 78 consecutive lung cancer patients who received chest magnetic resonance imaging (MRI) scans between May 2020 and June 2021 were enrolled in this study. Two radiologists independently analyzed the apparent diffusion coefficient (ADC) and T1 values for each lesion. The intraclass correlation coefficient (ICC) and Bland-Altman plots were generated to assess interobserver agreement of the T1 and ADC mean values in lesions. The difference in ADC and T1 values among different pathological types, as well as between high- and low-differentiated lung cancers were analyzed, and diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation between ADC value, T1 value, and Ki-67 protein expression index was determined.ResultsThe ADC and T1 values showed excellent interobserver agreement (ICC 0.820, 0.942, respectively). There was a significant difference in ADC values between small cell carcinoma and squamous carcinoma (P<0.05), and between small cell carcinoma and adenocarcinoma (P<0.05), but not between squamous carcinoma and adenocarcinoma (P>0.05). A significant difference in T1 values was observed between small cell carcinoma (P<0.05) and adenocarcinoma, and between squamous carcinoma (P<0.05) and adenocarcinoma, but not between squamous carcinoma and small cell carcinoma (P>0.05). There were statistically significant differences in ADC and T1 values between the moderately and highly differentiated group and the poorly differentiated group (P<0.05). ROC curve analysis showed that the T1 combined with ADC value had high diagnostic value for the degree of differentiation of the tumor [area under the curve (AUC) =0.912]. Pearson correlation analysis showed a significant positive correlation between T1 value and Ki-67 index (r=0.66, P<0.001) and a significant negative correlation between ADC value and Ki-67 index (r=−0.45, P<0.01).ConclusionsT1 and ADC values can be used to distinguish the pathological type and differentiation degree of lung cancer.     

Treatment of giant emphysamous bulla with endobronchial valves in patients with chronic obstructive pulmonary disease: a case series

Background

Giant emphysamtous bulla (GEB) can negatively affect the pulmonary functions of chronic obstructive pulmonary diseases (COPD) patients, including decreased forced expiratory volume in 1 s (FEV₁) and increased functional residual capacity (FRC). The aim of this study was to evaluate the efficacy of endobronchial valve (EBV) to treat bullae and to find efficacy predictors of successful treatment.

Methods

Five COPD patients with giant bulla were treated using EBVs. Before the EBV deployment, collateral ventilation (CV) between the targeted and adjacent lobes was evaluated with Chartis system.

Results

In the two patients with negative CV, the mean value of FEV₁ increased from 27.1±11.4% of predicted value before EBV treatment to 32.8±12.0% (P>0.05) at 1 month after EBV treatment, than to 31.7±24.5% (P>0.05) at 6 months after EBV treatment. Only one patient, whose bulla occupied the whole right middle lung, displayed sustained improvement of FEV₁ at 6 months after EBV treatment. In the three patients with positive CV, the mean value of FEV₁ decreased from 28.8±19.0% of predicted value before EBV treatment to 24.8±12.6% (P>0.05) at 1 month after EBV treatment, than to 22.1±10.8% (P>0.05) at 6 months after EBV treatment.

Conclusions

EBV is an effective measure to treat highly selected COPD patients with giant bulla. Although, EBV treatment can achieve transient improvement of lung function at patients with CV negative bulla, long-term benefit was merely observed at the patient with a bulla at right middle lobe (RML).     

Association among fraction of exhaled nitrous oxide,bronchodilator response and inhaled corticosteroid type

BACKGROUND:Fraction of exhaled nitrous oxide (FeNO) is a known marker of airway inflammation and a topic of recent investigation for asthma control in children.OBJECTIVE:To investigate the relationship among FeNO and bronchodilator response measured by spirometry and types of inhaled corticosteroids (ICS).METHODS:A one-year review of children tested with spirometry and FeNO in a regional pediatric asthma centre was conducted.RESULTS:A total of 183 children were included (mean [± SD] age 12.8±2.8 years). Fluticasone was used most commonly (n=66 [36.1%]), followed by ciclesonide (n=50 [27.3%]). Most children (n=73 [39.9%]) had moderate persistent asthma. Increased FeNO was associated with percent change in forced expiratory volume in 1 s (FEV₁) after bronchodilator adjusted for allergic rhinitis, parental smoking and ICS type (B=0.08 [95% CI 0.04 to 0.12]; P<0.001). Similarly, FeNO was associated with percent change in forced expiratory flow at 25% to 75% of the pulmonary volume (FEF_25–75) after bronchodilator adjusted for parental smoking and ICS type (B=0.13 [95% CI 0.01 to 0.24]; P=0.03). FeNO accounted for only 16% and 9% of the variability in FEV₁ and FEF_25–75, respectively. Mean-adjusted FeNO was lowest in fluticasone users compared with no ICS (mean difference 18.6 parts per billion [ppb] [95% CI 1.0 to 36.2]) and there was no difference in adjusted FeNO level between ciclesonide and no ICS (5.9 ppb [95% CI −9.0 to 20.8]).CONCLUSION:FeNO levels correlated with bronchodilator response in a regional pediatric asthma centre. However, FeNO accounted for only 16% and 9% of the variability in FEV₁ and FEF_25–75, respectively. Mean adjusted FeNO varied according to ICS type, suggesting a difference in relative efficacy between ICS beyond their dose equivalents.     

The sST2 level is an independent influencing factor associated with atrial fibrillation in heart failure patients: a case-control study

BackgroundMost heart failure (HF) patients were complicated with atrial fibrillation (AF). Previous study has reported a correlation between soluble suppression of tumorigenicity 2 (sST2) and HF. While the association between sST2 and AF in HF patients remains elusive, which will strengthen our understanding of sST2 in HF patients.MethodsIn the study, a case-control study was conducted with 306 HF patients enrolled from June 2019 to June 2020 at Beijing Anzhen Hospital. All the patients were divided into the following two groups, based on whether they AF complications prior to admission: (I) the HF group (patients with HF alone) and the HF-AF group (HF patients complicated with AF). Baseline data and sST2 levels were assessed and compared between the two groups, and the influencing factors associated with AF in HF patients were screened.ResultsThe sST2 level in the HF-AF group was 40.6 (25.9–53.6) ng/mL, which was significantly higher than that in the HF group [23.7 (16.3–35.9) ng/mL] (P<0.001). Correlation analysis showed that sST2 level in the HF-AF group was positively correlated with age (r=0.287, P=0.001), New York Heart Association (NYHA) grade (r=0.470, P<0.0001), left ventricular diameter (LVD) (r=0.311, P=0.001), serum creatinine (r=0.320, P<0.0001), NT-pro-brain natriuretic peptide (r=0.540, P<0.0001), and D-dimer (r=0.322, P<0.0001), and negatively correlated with left ventricular ejection fraction (LVEF) (r=−0.259, P=0.004), hemoglobin (r=−0.188, P=0.039), and glomerular filtration rate (r=−0.283, P=0.002). Logistic regression analysis results indicated that history of coronary heart disease [odds ratio (OR): 0.176, 95% confidence interval (CI): 0.081–0.380, P<0.0001], LVEF (OR: 0.956, 95% CI: 0.915–0.998, P=0.039), LVD (OR: 1.156, 95% CI: 1.059–1.261, P=0.001), left arterial diameter (OR: 0.761, 95% CI: 0.695–0.833, P<0.0001), and sST2 (OR: 0.942, 95% CI: 0.917–0.967, P<0.0001) were independent influencing factors associated with AF in HF patients.ConclusionsThe sST2 level is an independent influencing factor associated with AF in HF patients, which may favor to optimize the clinical strategies in the management of HF patients complicated with AF.     

Changes of HMGB1 and sRAGE during the recovery of COPD exacerbation

Background

Acute exacerbation of chronic obstructive pulmonary disease is associated with increased airway and systemic inflammation. However, the correlation between acute exacerbation/convalescence of chronic obstructive pulmonary disease (COPD) and simultaneous changes of high mobility group protein B1 (HMGB1) and soluble RAGE (sRAGE) levels has not been clearly clarified. The aim of this study was to assess these issues.

Methods

A total of 44 COPD patients were recruited. Following a structured interview, plasma levels of HMGB1, sRAGE, fibrinogen and serum level of high-sensitivity C-reactive protein (hsCRP) were measured in patients with acute exacerbation of COPD (AECOPD) within 24 h of hospitalization and pre-discharge (convalescence). All patients were examined with spirometry in convalescence of COPD.

Results

There was a significant decline in plasma HMGB1 (P<0.01), sRAGE (P<0.05), fibrinogen (P<0.01) and serum hsCRP (P<0.01) levels from acute exacerbation to convalescence phase of COPD. Changes of sRAGE was significantly correlated with changes of HMGB1 (r=0.4, P=0.007). COPD disease status correlated with the ratio of HMGB1/sRAGE, but not gender, age, course of disease, smoking history and FEV1% pred. Levels of HMGB1 and sRAGE were the highest in the current smoker group, and significantly decreased in ex-smoker group in both acute exacerbation and convalescence phase of COPD, however, their levels in never smoker group were higher than ex-smoker group in either phase of COPD.

Conclusions

HMGB1 and sRAGE levels were dynamically changed between exacerbation and convalescence phase of COPD, HMGB1 and sRAGE were likely not only a potential marker in COPD exacerbation but also a therapeutic target for COPD treatment.     

Clinical impact of forced vital capacity on exercise performance in patients with chronic obstructive pulmonary disease

BackgroundForced vital capacity (FVC) has been suggested to be a good biomarker for decreased exercise performance in patients with chronic obstructive pulmonary disease (COPD). However, as FVC is highly correlated with forced expiratory volume in 1 second (FEV₁), the relationship between FVC and exercise capacity should be assessed within the category of FEV1, i.e., COPD severity. However, this was not considered in previous studies. Thus, limited data are available on the association between reduced FVC and exercise capacity measured by 6-min walk distance (6MWD) based on COPD severity.MethodsWe performed a cross-sectional study using data from the Korean COPD Subgroup Study (KOCOSS) cohort. We evaluated 1,386 patients with moderate (n=895) and severe-to-very severe (n=491) COPD. Reduced FVC was defined as FVC <80% predicted and short 6MWD as <350 m. Multivariable logistic regression was used to evaluate the association between reduced FVC and short 6MWD.ResultsThere were no significant differences in respiratory symptoms and quality of life between the patients with reduced FVC and those with preserved FVC. However, patients with reduced FVC had shorter 6MWD (30.5 cm in moderate and 34.5 cm in severe-to-very severe COPD) and higher BODE index scores than those with preserved FVC. The cubic spline model revealed 6MWD peaked around 93% predicted of FVC in moderate COPD, whereas FVC showed a positive association with 6MWD in severe-to-very severe COPD. Multivariable analyses showed that reduced FVC was significantly associated with short 6MWD in both moderate [adjusted odds ratio (aOR) =1.44, 95% confidence interval (CI): 1.03–2.02] and severe-to-very severe (adjusted OR =1.55, 95% CI: 1.01–2.40) COPD.ConclusionsReduced FVC was significantly associated with shorter 6MWD in moderate-to-very severe COPD patients, suggesting that reduced FVC might be reflective of 6MWD-measured exercise capacity in moderate-to-very severe COPD.     

Reliability of the Brazilian Portuguese version of the fatigue severity scale and its correlation with pulmonary function,dyspnea, and functional capacity in patients with COPD

OBJECTIVE:

To describe the intra-rater and inter-rater reliability of the Brazilian Portuguese version of the fatigue severity scale (FSS) in patients with COPD and to identify the presence of its association with parameters of pulmonary function, dyspnea, and functional capacity.

METHODS:

This was an observational cross-sectional study involving 50 patients with COPD, who completed the FSS in interviews with two researchers in two visits. The FSS scores were correlated with those of the Medical Research Council (MRC) scale, as well as with FEV₁, FVC, and six-minute walk distance (6MWD).

RESULTS:

The mean age of the patients was 69.4 ± 8.23 years, whereas the mean FEV₁ was 46.5 ± 20.4% of the predicted value. The scale was reliable, with an intraclass correlation coefficient of 0.90 (95% CI, 0.81-0.94; p < 0.01). The FSS scores showed significant correlations with those of MRC scale (r = 0.70; p < 0.01), as well as with 6MWD (r = –0.77; p < 0.01), FEV₁ (r = –0.38; p < 0.01), FVC (r = –0.35; p < 0.01), and stage of the disease in accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria (r = 0.37; p < 0.01).

CONCLUSIONS:

The Brazilian Portuguese version of the FSS proved reliable for use in COPD patients in Brazil and showed significant correlations with sensation of dyspnea, functional capacity, pulmonary function, and stage of the disease.     

Long‐term oxygen treatment need is less frequent in eosinophilic COPD patients

IntroductionEosinophilic airway inflammation is a recognized inflammatory pattern in subgroups of patients with chronic obstructive pulmonary disease (COPD). However, there are still conflicting results between various studies concerning the effect of eosinophils in COPD patients. Our aim with this study was to evaluate eosinophilic inflammation and its relation to the clinical characteristics in a group of COPD patients.MethodsStable COPD patients with FEV₁% predicted < 50 or with ≥ 1 exacerbation leading to hospital admission or ≥2 moderate or severe exacerbation history were consecutively enrolled from outpatient clinics.ResultsWe included 90 male COPD patients, with a mean age of 63.3 ± 9.2. Mean FEV₁% predicted was 35.9 ± 11.3. Eosinophilic inflammation (eosinophil percentage ≥2%) was evident in 54 (60%) of the patients. Participants with eosinophilic inflammation were significantly older and had better FEV₁ predicted % values. Eosinophilic COPD patients were characterized with better quality of life and fewer symptoms. COPD patients with noneosinophilic inflammation used supplemental long‐term oxygen therapy (LTOT) more frequently compared to patients with eosinophilic inflammation (36.1% vs. 14.8%, p = 0.01). Eosinophilic inflammation is associated with less dyspnea severity measured by mMRC (OR: 0.542 95% CI: 0.342–0.859, p = 0.009) and less LTOT use (OR: 0.334 95% CI: 0.115–0.968, p = 0.04) regardless of age, severity of airflow limitation, and having frequent exacerbation phenotype.ConclusionOur study supports the growing evidence for a potential role of eosinophilic inflammation phenotype in COPD with distinctive clinical characteristics. Eosinophilic inflammation is inversely associated with dyspnea severity measured by mMRC and LTOT use independently from age, total number of exacerbations, St. George Respiratory Questionnaire (SGRQ) total score and FEV₁% predicted.     

Comparison of laboratory parameters in mild vs. severe cases and died vs. survived patients with COVID-19: systematic review and meta-analysis

BackgroundThis study aimed to summarize the available data on the association between the severity of (COVID-19) and routine blood indicators, inflammatory, biochemical parameters and coagulation parameter.MethodsA literature search was conducted of PubMed, EMBASE, and Web of Sciences, CNKI, WanFang database providing relevant data. Random-effects meta-analysis was used to pool effect sizes.ResultsIn patients with severe symptoms, interleukin-6, [IL-6; standardized mean difference (SMD) =1.15, 95% confidence interval (95% CI): 1.01, 1.29, P<0.001, n=1,121], interleukin-10 (IL-10; SMD =0.92, 95% CI: 0.75, 1.08, P<0.001, n=782), interleukin-4 (IL-4; SMD =0.2, 95% CI: 0.01, 0.39, P=0.04, n=500), procalcitonin (PCT; SMD =1.16, 95% CI: 0.99, 1.33, P<0.001, n=734), C-reactive protein (CRP; SMD =1.42, 95% CI: 1.27, 1.57, P<0.001, n=1,286), serum amyloid A (SAA; SMD =2.82, 95% CI: 2.53, 3.11, P<0.001, n=502) neutrophil count (SMD =0.63, 95% CI: 0.44, 0.82, P<0.001, n=558), alanine aminotransferase (ALT; SMD =2.72, 95% CI: 2.43, 3.02, P<0.001, n=538), aspartate aminotransferase (AST; SMD =2.75, 95% CI: 2.37, 3.12, P<0.001, n=313), lactate dehydrogenase (LDH; SMD =4.01, 95% CI: 3.79, 4.24, P<0.001, n=1,055), creatine kinase (CK; SMD =2.62, 95% CI: 2.2, 3.03, P<0.001, n=230;), CK-MB isoenzyme (CK-MB; SMD =3.07, 95% CI: 2.81, 3.34, P<0.001, n=600, activated partial thromboplastin time (APTT; SMD =0.63, 95% CI: 0.39, 0.87, P<0.001, n=351), and prothrombin time (P-T; SMD =1.83, 95% CI: 1.55, 2.11, P<0.001, n=351) were significantly higher than in patients with mild symptoms. On the contrary, lymphocyte count (SMD =−1.04, 95% CI: −1.21, −0.86, P<0.001, n=805) platelets (SMD =−1.47, 95% CI: −1.7, −1.24, P<0.001, n=653), monocyte count (SMD =−0.56, 95% CI: −0.8, −0.32, P<0.001, n=403), and albumin (SMD =−2.95, 95% CI: −3.21, −2.7, P<0.001, n=637) was significantly lower in patients with severe symptoms than in patients with mild symptoms. IL-6 (SMD =2.62, 95% CI: 2.15, 3.09, P<0.001, n=185), PCT (SMD =0.2, 95% CI: 0.16, 0.23, P<0.001, n=156), creatinine (SMD =2.29, 95% CI: 1.87, 2.7, P<0.001, n=213), and neutrophil counts (SMD =2.77, 95% CI: 2.38, 3.16, P<0.001, n=260) in patients with COVID-19 in the death group were significantly higher than that in patients in the survival group, while the lymphocyte count was significantly lower.ConclusionsIn summary, current evidence show that those laboratory indicators are associated with the severity of COVID-19 and thus could be used as prognostic risk stratification of patients with COVID-19.     

Gender differences in the association between C-reactive protein, lung function impairment, and COPD

Individuals with COPD have systemic inflammation that can be assessed by measuring C-reactive protein (CRP). In this paper we evaluated whether CRP is related to COPD, lung function and rate of lung function decline.We included 1237 randomly selected subjects (mean age 42, range 28–56 years) from three centers in the European Community Respiratory Health Survey: Reykjavik, Uppsala and Tartu. CRP was measured at the end of the follow-up (mean 8.3 years) and the values were divided into 4 quartiles.Fifty-three non-asthmatic subjects fulfilled spirometric criteria for COPD (FEV₁/FVC < 70%). COPD occurred more often in the 4th CRP quartile (OR (95% CI) 3.21 (1.13–9.08)) after adjustment for age, gender, body weight and smoking. High CRP levels were related to lower FEV₁ values in both men (−437 (−596, −279) mL) and women (−144 (−243, −44) mL). The negative association between CRP and FEV₁ was significantly larger in men than women (p = 0.04). The decline in FEV₁ was larger (16 (5, 27) mL) in men with high CRP levels whereas no significant association between CRP and FEV₁ decline was found in women.Higher CRP values are significantly associated with COPD and lower lung function in men and women. In men higher CRP values are related to a larger decline in FEV₁.     

Effect of low protein intake on acute exacerbations in mild to moderate chronic obstructive pulmonary disease: data from the 2007–2012 KNHANES

BackgroundSeveral researchers have reported that the amount of protein intake is associated with lung function and airflow obstruction. However, few studies have investigated the effect of low protein intake on acute exacerbations of chronic obstructive pulmonary disease. This study aimed to investigate the effect of low protein intake on exacerbations in mild to moderate chronic obstructive pulmonary disease.MethodsWe used data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES) between 2007 and 2012, linked to the National Health Insurance claims data. The clinical outcomes and the rate of exacerbation were retrospectively compared between the low protein intake group and the non-low protein intake group which was stratified by quartile categories of protein intake in 2,069 patients with mild to moderate chronic obstructive pulmonary disease.ResultsThe low protein intake group was significantly associated with older age, women, never smoker, low household income, and low education level, compared with the non-low protein intake group. The low protein intake group was significantly associated with increased hospitalization (18.0% vs. 10.5%, P<0.001) and emergency department utilization (1.6±1.0 vs. 1.1±0.4, P=0.033) compared with the non-low protein intake group. In multivariate analysis, the low protein intake group was associated with hospitalization (odds ratio 1.46; 95% CI, 1.09–1.96; P=0.012). The multiple linear regression analysis revealed that the amount of protein intake was associated with FVC % predicted (β=0.048, P<0.001) and FEV_1% predicted (β=0.022, P=0.015).ConclusionsLow protein intake was associated with an increased risk of exacerbations in mild to moderate chronic obstructive pulmonary disease. The data are available at the KNHANES website (https://knhanes.cdc.go.kr).     

Glutathione and nitrite levels in induced sputum at COPD patients and healthy smokers

Objectives

The role of oxidative stress at the pathogenesis of chronic obstructive pulmonary disease (COPD) is known. The aim of this study is to investigate the oxidative stress with sputum induction that is a simple method in COPD patients and healthy smokers.

Methods

Sputum induction was performed in 21 COPD patients (10 stable, 11 acute exacerbations), nine healthy smokers, and ten healthy non-smokers. Glutathione, NO₂^– levels, and cell counts at sputum, and plasma NO₂^– contents were evaluated in all subjects.

Results

Mean sputum glutathione and NO₂^– levels were significantly higher in acute exacerbations with COPD patients than healthy smokers (P=0.007 and P<0.001 respectively), and non-smokers (P<0.001 and P<0.001 respectively). On the other hand, sputum glutathione and NO₂^– levels did not show significant differences between stable and acute exacerbations with COPD patients. Although, sputum glutathione levels were higher in stable COPD patients than healthy smokers’, no statistically significant difference was established. In addition, sputum glutathione levels were significantly higher in healthy smokers than non-smokers (P<0.001).

Conclusions

As a result, we can say that oxidative stress increases not only in COPD patients but also in healthy smokers. In addition, sputum induction that is a simple method can be used to demonstrate to show oxidative stress.     

Impairment of small airways in COPD patients with frequent exacerbations and effects of treatment with tiotropium

Disease exacerbations are an important aspect of COPD, because they affect its course and are associated with higher lung function decline. On the other hand, data obtained by biopsies have demonstrated that the progression of COPD is related to an increasing impairment of small airways. We sought to evaluate the small airway impairment (FEF25–75) in two groups of COPD patients (each group had 37 subjects) in relation to the frequency of exacerbations and the effectiveness of treatment with tiotropium bromide on the small airway impairment. The mean number of exacerbations was 3.6/year and 1.38/year in frequent and in infrequent exacerbators, respectively (p < 0.001). The mean value of FEF25–75 at baseline was 624 mL and 865 mL in frequent and in infrequent exacerbators respectively (p = 0.002). The changes in respiratory parameters versus baseline showed increases in mean FEV₁, FVC, and FEF25–75 in both groups but only the increase in FEF25–75 in frequent exacerbators was statistically significantly (p = 0.013). During the 3-month period of the study the mean number of exacerbations was 0.66 in frequent and 0.12 in infrequent exacerbators. These findings indicate that COPD patients with frequent exacerbations have a higher impairment of small airways. Treatment with tiotropium in COPD subjects with frequent exacerbations proved to be effective in improving small airway impairment.