Muscle sympathetic nerve activity and ventilation during exercise in subjects with and without chronic heart failure

BACKGROUND:

Changes within skeletal muscle, including augmentation of its capacity to elicit reflex increases in both efferent muscle sympathetic nerve activity (MSNA) and ventilation during work, contribute significantly to exercise intolerance in heart failure (HF). Previously, we demonstrated that peak oxygen uptake (pVO₂) in HF relates inversely to MSNA at rest and during exercise.

OBJECTIVE:

To test the hypothesis that there is an independent positive relationship between resting MSNA and the ratio of ventilation to carbon dioxide output during exercise (VE/VCO₂) that is augmented in HF.

METHODS:

MSNA at rest and VE/VCO₂ during stationary cycling were measured in 30 patients (27 men) with HF (mean ± SD ejection fraction 20±6%) and in 31 age-matched controls (29 men).

RESULTS:

MSNA was higher in HF patients than in controls (51.5±14.3 bursts/min versus 33.0±11.1 bursts/min; P<0.0001). The VE/VCO₂ slope was also higher in HF patients than in controls (33.7±5.7 versus 26.0±3.5; P<0.0001), whereas pVO₂ was lower in HF patients than in controls (18.6±6.6 versus 31.4±8.4 mL/kg/min; P<0.0001). There were significant relationships between MSNA and VE/VCO₂ in both HF (r=0.50; P=0.005) and control subjects (r=0.36; P=0.046). The slope of this regression equation was steeper in HF (0.20 versus 0.11 × MSNA; P=0.001). An analysis of covariance for main effects, including age and pVO₂, identified a significant independent relationship between MSNA burst frequency and VE/VCO₂ (P=0.013) that differed between HF and controls (P<0.01).

CONCLUSIONS:

The magnitude of resting sympathetic activity correlates positively with the VE/VCO₂ slope. Augmentation of this relationship in HF patients is consistent with the concept that enhanced mechanoreceptor reflex activity exaggerates their ventilatory response to exercise.     

Pulmonary rehabilitation program including respiratory conditioning for chronic obstructive pulmonary disease (COPD): Improved hyperinflation and expiratory flow during tidal breathing

Background

Pulmonary rehabilitation has generally relieved symptoms, strengthened exercise endurance and improved health-related quality of life (QOL) in patients with COPD, but recovery of pulmonary function remains questionable. This analysis of our innovative rehabilitation program is directed at documenting changes in patients’ expiratory airflow limitation, pulmonary symptoms and QOL. This program is designed to provide “respiratory conditioning”, a physical therapist-assisted intensive flexibility training that focuses on stretching and rib cage mobilization.

Methods

Thirty-one patients with COPD who attended rehabilitation sessions at Juntendo University Hospital from 1999 to 2006 were analyzed. Pulmonary function, expiratory flow limitation during tidal breathing, six minute walk distance (6MWD), respiratory muscle strength, and St. George Respiratory Questionnaire (SGRQ) were measured before and after pulmonary rehabilitation.

Results

In participants ages 68±7 years, the FEV₁% predicted was 39.3±15.7%. 6MWD, SGRQ and respiratory muscle strength were significantly improved after pulmonary rehabilitation. Although neither FEV₁% predicted nor FEV₁/FVC was affected to a significant extent, indicating little effect on airflow limitation, expiratory flow limitation in supine as well as seated during tidal breathing improved significantly. Moreover, rehabilitation significantly diminished TLC% predicted, FRC% predicted, RV% predicted and RV/TLC values, thus indicating a reduction of hyperinflation of the lungs at rest.

Conclusions

The present results suggest that our rehabilitation program with respiratory conditioning significantly lowered the hyperinflation of lungs at rest as well as the expiratory flow limitation during tidal breathing. In patients with COPD, overall pulmonary function improved, exercise endurance increased and health-related QOL was enhanced.Key Words: Expiratory flow limitation, hyperinflation, negative expiratory pressure, pulmonary rehabilitation, respiratory conditioning     

Using Telehealth technology to deliver pulmonary rehabilitation in chronic obstructive pulmonary disease patients

BACKGROUND:

Pulmonary rehabilitation (PR) is an effective therapeutic strategy to improve health outcomes in patients with chronic obstructive pulmonary disease (COPD); however, there is insufficient PR capacity to service all COPD patients, thus necessitating creative solutions to increase the availability of PR.

OBJECTIVE:

To examine the efficacy of PR delivered via Telehealth (Telehealth-PR) compared with PR delivered in person through a standard outpatient hospital-based program (Standard-PR).

METHODS:

One hundred forty-seven COPD patients participated in an eight-week rural PR program delivered via Telehealth-PR. Data were compared with a parallel group of 262 COPD patients who attended Standard-PR. Education sessions were administered two days per week via Telehealth, and patients exercised at their satellite centre under direct supervision. Standard-PR patients viewed the same education sessions in person and exercised at the main PR site. The primary outcome measure was change in quality of life as evaluated by the St George’s Respiratory Questionnaire (SGRQ). A noninferiority analysis was performed using both intention-to-treat and per-protocol approaches.

RESULTS:

Both Telehealth-PR and Standard-PR resulted in clinically and statistically significant improvements in SGRQ scores (4.5±0.8% versus 4.1±0.6%; P<0.05 versus baseline for both groups), and the improvement in SGRQ was not different between the two programs. Similarly, exercise capacity, as assessed by 12 min walk test, improved equally in both Telehealth-PR and Standard-PR programs (81±10 m versus 82±10 m; P<0.05 versus baseline for both groups).

CONCLUSION:

Telehealth-PR was an effective tool for increasing COPD PR services, and demonstrated improvements in quality of life and exercise capacity comparable with Standard-PR.     

Can bronchodilators improve exercise tolerance in COPD patients without dynamic hyperinflation?

OBJECTIVE:

To investigate the modulatory effects that dynamic hyperinflation (DH), defined as a reduction in inspiratory capacity (IC), has on exercise tolerance after bronchodilator in patients with COPD.

METHODS:

An experimental, randomized study involving 30 COPD patients without severe hypoxemia. At baseline, the patients underwent clinical assessment, spirometry, and incremental cardiopulmonary exercise testing (CPET). On two subsequent visits, the patients were randomized to receive a combination of inhaled fenoterol/ipratropium or placebo. All patients then underwent spirometry and submaximal CPET at constant speed up to the limit of tolerance (Tlim). The patients who showed ΔIC(peak-rest) < 0 were considered to present with DH (DH+).

RESULTS:

In this sample, 21 patients (70%) had DH. The DH+ patients had higher airflow obstruction and lower Tlim than did the patients without DH (DH-). Despite equivalent improvement in FEV₁ after bronchodilator, the DH- group showed higher ΔIC(bronchodilator-placebo) at rest in relation to the DH+ group (p < 0.05). However, this was not found in relation to ΔIC at peak exercise between DH+ and DH- groups (0.19 ± 0.17 L vs. 0.17 ± 0.15 L, p > 0.05). In addition, both groups showed similar improvements in Tlim after bronchodilator (median [interquartile range]: 22% [3-60%] vs. 10% [3-53%]; p > 0.05).

CONCLUSIONS:

Improvement in TLim was associated with an increase in IC at rest after bronchodilator in HD- patients with COPD. However, even without that improvement, COPD patients can present with greater exercise tolerance after bronchodilator provided that they develop DH during exercise.     

Effect of add-on therapy of tiotropium in COPD treated with theophylline

Background

Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators.

Objective

We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients.

Methods

In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD.

Results

Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV₁) 1.5 L [62.5% predicted]). FEV₁ in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 ± 0.13 L, p < 0.001) and 8 weeks (1.60 ± 0.13 L, p < 0.001) from the baseline (1.40 ± 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p < 0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV₁.

Conclusion

Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.     

Outpatient pulmonary rehabilitation in patients with chronic obstructive pulmonary disease

Objective

To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD, using St.George’s Respiratory questionnaire (SGRQ), the 6-minutes walking test (6-MWT) and BODE index as the primary outcome measures.

Methods

A prospective, parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD (67 men and 13 women; mean age 64.8 ± 10.6 years; FEV₁, 42.8% ± 7.6% of the predicted value. The active group (n = 40) took part in a 14-week rehabilitation program [3 h/wk, 1.5 h of education and exercise and 1.5 h of cycling]. The control group (n = 40) was reviewed routinely as medical outpatients. The following evaluations were carried out at study entry and after14 weeks: (1) pulmonary function studies; (2) 6-minutes walking test 6MWT; (3) quality of life; and (4) BODE index.

Results

The following patients completed the study: 35 patients (87.5%) from the active group (mean age, 63.7 ± 11.9 years; mean forced expiratory volume in one second (FEV₁), 41.9 ± 2.6% of the predicted value); and 36 patients (88%) from the control group (mean age, 65.9 ± 10.3 years; mean FEV₁, 43.33 ± 3.6% of the predicted value). We found no changes in pulmonary function parameters in the active group and the control one at 14weeks. On the other hand, there were significant changes within the components of the SGRQ (12.3 for the score total) for the patients of the active group but not for the patients of the control one (only 1.5 for the score total), we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one, and finally a decrease of two points (from 6 to 4) was noted in the score of the active group’s BODE index without any change in the control group’s one.

Conclusion

An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD, and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index.     

Effect of Exercise on Blood Pressure in Type 2 Diabetes: A Randomized Controlled Trial

BACKGROUND

Increased blood pressure (BP) in type 2 diabetes (T2DM) markedly increases cardiovascular disease morbidity and mortality risk compared to having increased BP alone.

OBJECTIVE

To investigate whether exercise reduces suboptimal levels of untreated suboptimal BP or treated hypertension.

DESIGN

Prospective, randomized controlled trial for 6 months.

SETTING

Single center in Baltimore, MD, USA.

PATIENTS

140 participants with T2DM not requiring insulin and untreated SBP of 120–159 or DBP of 85–99 mmHg, or, if being treated for hypertension, any SBP <159 mmHg or DBP < 99 mmHg; 114 completed the study.

INTERVENTION

Supervised exercise, 3 times per week for 6 months compared with general advice about physical activity.

MEASUREMENTS

Resting SBP and DBP (primary outcome); diabetes status, arterial stiffness assessed as carotid-femoral pulse-wave velocity (PWV), body composition and fitness (secondary outcomes).

RESULTS

Overall baseline BP was 126.8 ± 13.5 / 71.7 ± 9.0 mmHg, with no group differences. At 6 months, BP was unchanged from baseline in either group, BP 125.8 ± 13.2 / 70.7 ± 8.8 mmHg in controls; and 126.0 ± 14.2 / 70.3 ± 9.0 mmHg in exercisers, despite attaining a training effects as evidenced by increased aerobic and strength fitness and lean mass and reduced fat mass (all p < 0.05), Overall baseline PWV was 959.9 ± 333.1 cm/s, with no group difference. At 6-months, PWV did not change and was not different between group; exercisers, 923.7 ± 319.8 cm/s, 905.5 ± 344.7, controls.

LIMITATIONS

A completion rate of 81 %.

CONCLUSIONS

Though exercisers improve fitness and body composition, there were no reductions in BP. The lack of change in arterial stiffness suggests a resistance to exercise-induced BP reduction in persons with T2DM.KEY WORDS: exercise training, diabetes, high blood pressure, randomized trial     

Vertical P-wave axis: the electrocardiographic synonym for pulmonary emphysema and its severity

Background

The correlation between vertical P-wave axis (P-axis > 60°) and pulmonary emphysema was investigated on a very large controlled series to see if P-axis verticalisation as lone criterion can be effectively used to screen emphysema in general population. Correlation between degrees of P-axis verticalisation and the severity of the obstructive lung disease (as per global initiative for chronic obstructive lung disease [GOLD] criteria) was also studied to see if this criterion can be used for gross quantification of the chronic obstructive pulmonary disease (COPD) in routine clinical practice.

Materials and methods

Around 6500 unselected, routine electrocardiograms (ECGs) were reviewed which yielded 600 ECGs with vertical P-axis in sinus rhythm. 635 ECGs from the same continuum were selected with P-axis ≤60° matched for patient''s age and sex serving as controls. Charts were reviewed for the diagnosis of COPD and emphysema based on medical history, pulmonary function tests, and imaging studies.

Results

Prevalence of emphysema in patients with vertical P-axis was strikingly higher than in the control group: 85% vs 4.4%. The sensitivity and specificity of vertical P-axis for diagnosing emphysema was 94.76% and 86.47%, respectively. Vertical P-axis and forced expiratory volume (FEV1) were inversely correlated (Pearson correlation coefficient=−0.683). Prevalence of severe COPD was strikingly higher in patients with P-axis > 75° as compared to the group with P-axis 60°–75°: 96.3% vs 4.6%. Close to 80% of the emphysema patients with P-axis > 85° had very severe disease (FEV1 < 30%).

Conclusion

P-axis verticalisation is highly effective for screening emphysema and degree of verticalisation provides a gross quantification of the disease.     

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

Creatine supplementation and physical training in patients with COPD: A double blind, placebo-controlled study

Study objectives

Patients with chronic obstructive pulmonary disease (COPD) have low exercise capacity and low content of high energetic phosphates in their skeletal muscles. The aim of the present study was to investigate whether creatine supplementation together with exercise training may increase physical performance compared with exercise training in patients with COPD.

Design

In a randomized, double-blind, placebo-controlled study, 23 patients with COPD (forced expiratory volume in one second [FEV₁] < 70% of predicted) were randomized to oral creatine (n = 13) or placebo (n = 10) supplementation during an 8-week rehabilitation programme including exercise training. Physical performance was assessed by Endurance Shuttle Walking Test (ESWT), dyspnea and leg fatigue with Borg CR-10, quality of life with St George’s Respiratory Questionnaire (SGRQ). In addition, lung function test, artery blood gases, grip strength test, muscle strength and fatigue in knee extensors were measured.

Results

COPD patients receiving creatine supplementation increased their average walking time by 61% (ESWT) (p < 0.05) after the training period compared with 48% (p = 0.07) in the placebo group. Rated dyspnea directly after the ESWT decreased significantly from 7 to 5 (p < 0.05) in the creatine group. However, the difference between the groups was not statistically significant neither in walking time nor in rated dyspnea. Creatine supplementation did not increase the health related quality of life, lung function, artery blood gases, grip strength and knee extensor strength/fatigue.

Conclusions

Oral creatine supplementation in combination with exercise training showed no significant improvement in physical performance, measured as ESWT, in patients with COPD compared with exercise training alone.     

Barriers associated with reduced physical activity in COPD patients

OBJECTIVE:

To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score.

METHODS:

In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT.

RESULTS:

We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results.

CONCLUSIONS:

Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.     

COPD heterogeneity: Gender differences in the multidimensional BODE index

Background:

The BODE index was recently validated as a multidimensional tool for the evaluation of patients with COPD. The influence of gender on the BODE index has not been studied.

Hypothesis:

The contribution of each component of the disease to the BODE index may differ according to gender.

Methods:

We evaluated age, forced expiratory volume in one second (FEV₁), Modified Medical Research Council (MMRC) score, 6-min walk distance (6MWD), and body mass index (BMI) in 52 men and 52 women with COPD and the same BODE index. We compared the studied parameters between men and women and then performed a multiple regression analysis by gender.

Results:

We found statistically significant differences between men and women in all parameters: FEV₁ % (55 ± 17 vs 63 ± 18, p < 0.001), MMRC [1 (0–2) vs 1 (1–2) p = 0.03], BMI [28 (26–30) vs 25 (22–30), p = 0.05], and 6MWD [546 (451–592) vs 462 (419–520), p = 0.001]. Multiple regression analysis revealed that each component of the BODE index had different weight (β standardized coefficient) in men and women respectively: FEV₁% (0.74 vs 0.62), MMRC (0.31 vs 0.48), BMI (−0.09 vs −0.17), and 6MWD (0.13 vs 0.10).

Conclusions:

The contribution of each component to the BODE index differs by gender in subjects with similar BODE scores. Long term longitudinal studies will help determine the significance of our findings.     

Reliability of Lightguide Spectrophotometry (O2C?) for the Investigation of Skin Tissue Microvascular Blood Flow and Tissue Oxygen Supply in Diabetic and Nondiabetic Subjects

Background and Aims

Skin microvascular assessment has progressed to an important evaluation in patients with diabetes mellitus. This study was done to evaluate a new device using micro-lightguide spectrophotometry in the assessment of skin microvascular function.

Material and Methods

Twenty nondiabetic subjects (age 46.6 ± 14.8 years; mean ± SD) and 20 diabetic patients (age 59.4 ± 8.4 years) participated in repeated microvascular measurements using micro-lightguide spectrophotometry. This technique allows simultaneous, noninvasive measurement of microvascular blood flow and hemoglobin oxygenation (SO₂) at the same anatomical area in different tissue layers. A skin probe was placed on nonhairy skin at the thenar eminence of the left hand for the measurement of SO₂, and the postischemic reactive hyperemia response (PRH) was measured in skin and underlying muscle tissue.

Results

Repeated measurements in PRH revealed a good correlation at the superficial skin layer (r = 0.97, p < 0.0001) with a coefficient of variation at 9.2 ± 1.7% and at the superficial muscle layer (r = 0.80, p < 0.0002) with a coefficient of variation at 9.7 ± 1.5%. A slightly weaker correlation was observed for the SO₂ measurement at the skin layer (r = 0.69 ± p < 0.0001) with a coefficient of variation at 17.5 ± 3.8% and at the muscle layer (r = 0.48; p = 0.0016) with a coefficient of variation at 18.1 ± 10.5%.

Conclusions

Lightguide spectrophotometry is an easy, noninvasive, and reliable method for simultaneous measurement of superficial microvascular blood flow by laser Doppler fluxmetry and skin oxygenation by spectrophotometry. Further studies are required to clarify the validity of these measures in special patient populations such as diabetes mellitus with specified microvascular complications.     

Incremental shuttle and six-minute walking tests in the assessment of functional capacity in chronic heart failure

BACKGROUND

The incremental shuttle test presents some theoretical advantages over the six-minute walk test in chronic heart failure (CHF), including better standardization and less dependency on collaboration.

OBJECTIVES

The present study evaluated test-retest repeatability, test accuracy in predicting a peak oxygen consumption (VO₂) of 14 mL/kg/min or less, as well as the prognostic value of both walking tests in stable CHF patients.

METHODS

Sixty-three patients (44 men; New York Heart Association functional class II to IV) underwent an incremental treadmill exercise test and, on another day, the walk test in duplicate.

RESULTS

Patients showed well-preserved functional capacity according to the distance walked in both tests (six-minute walk test 491±94 m versus incremental shuttle walk test 422±119 m; P<0.001). Interestingly, the six-minute and incremental shuttle walk test differences in distance walked were higher in more disabled patients. The mean bias ±95% CI of the within-test differences were similar (7±40 m and 8±45 m, respectively). Peak VO₂, but not distance walked in either test, was associated with survival (P<0.05).

CONCLUSIONS

The incremental shuttle walk test showed similar repeatability and accuracy in estimating peak VO₂ compared with the six-minute walk test in CHF patients. Direct measurement of peak VO₂, however, remains superior to either walking test in predicting survival – at least in patients with well-preserved functional capacity.     

Chronic obstructive pulmonary disease in women

BACKGROUND:

Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD) between women and men and about women’s response to pulmonary rehabilitation.

OBJECTIVES:

To compare lung function, disability, mortality and response to pulmonary rehabilitation between women and men with COPD.

METHODS:

In the present retrospective study, 68 women (mean age 62.5±8.9 years) and 168 men (mean age 66.3±8.4 years) were evaluated by means of pulmonary function testing and an incremental symptom-limited cycle exercise test. Forty women and 84 men also participated in a 12-week pulmonary rehabilitation program. A 6 min walking test and the chronic respiratory questionnaire were used to assess the effects of pulmonary rehabilitation. Survival status was also evaluated.

RESULTS:

Compared with men, women had a smaller tobacco exposure (31±24 versus 48±27 pack-years, P<0.05), displayed better forced expiratory volume in 1 s (44±13 versus 39±14 % predicted, P<0.05), a higher functional residual capacity (161±37 versus 149±36 % predicted, P<0.05) and total lung capacity (125±20 versus 115±19 % predicted, P<0.001). Peak oxygen consumption was not different between women and men when expressed in predicted values but lower in women when expressed in absolute values. Pulmonary rehabilitation resulted in significant improvements in 6 min walking test and quality of life in both sexes, but women had a greater improvement in chronic respiratory questionnaire dyspnea. Survival status was similar between sexes, but predictors of mortality were different between sexes.

CONCLUSIONS:

Women may be more susceptible to COPD than men. The clinical expression of COPD may differ between sexes with greater degree of hyperinflation in women, who also benefit from pulmonary rehabilitation.     

Postprandial glucose monitoring further improved glycemia, lipids, and weight in persons with type 2 diabetes mellitus who had already reached hemoglobin A1c goal

Background

Postprandial hyperglycemia contributes to poor glucose control and is associated with increased cardiovascular risk in type 2 diabetes mellitus (T2DM). The objective of the study was to determine the effect of postprandial self-monitoring of blood glucose (pp-SMBG) on glucose control, lipids, body weight, and cardiovascular events.

Method

Subjects with T2DM hemoglobin A1c (A1C) between 6.5 to 7.0% were randomized into the study group (at least two pp-SMBG a day and dietary modification based on glucose readings) and control group (dietary modification based on glucose readings but no mandatory pp-SMBG) for a 6-month, observational study. Oral antidiabetic drugs or insulin regimen was unchanged in either group if A1C remained less than 7.0% during the study. End points included A1C, lipids, body weight, and cardiovascular events.

Results

One hundred sixty-nine subjects, mean age 63 years, and body weight 88 kg were recruited. Hemoglobin A1c, weight, low-density lipoprotein (LDL), and triglycerides (TGs) were similar in the groups at baseline. By the end of 6 months, A1C (6.7 ± 0.1 to 6.4 ± 0.1%, p < .05), body weight (88.5 ± 7.3 to 85.2 ± 6.3 kg, p < .05), LDL (92.3 ± 2 8.4 to 81.1 ± 22.6 mg/dl, p < .05), and TGs (141 ± 21 to 96 ± 17 mg/dl, p < .05) decreased in the study group, but did not change in the control group. No cardiovascular events were observed in either group during the 6-month study period.

Conclusions

In T2DM subjects who had already reached their A1C goal, pp-SMBG at least twice a day was associated with further improvement in glycemia, lipids, and weight, as well as exercise and dietary habit. We assume that lifestyle modification promoted by postprandial hyperglycemia awareness may underlie these findings. These results substantiate the importance of implementing pp-SMBG into lifestyle modification, and emphasize that pp-SMBG is critical in the control of T2DM.     

Influenza‐associated mortality in Thailand, 2006–2011

Background

Influenza-associated mortality in subtropical or tropical regions, particularly in developing countries, remains poorly quantified and often underestimated. We analyzed data in Thailand, a middle-income tropical country with good vital statistics and influenza surveillance data.

Methods

We obtained weekly mortality data for all-cause and three underlying causes of death (circulatory and respiratory diseases, and pneumonia and influenza), and weekly influenza virus data, from 2006 to 2011. A negative binomial regression model was used to estimate deaths attributable to influenza in two age groups (<65 and ≥65 years) by incorporating influenza viral data as covariates in the model.

Results

From 2006 to 2011, the average annual influenza-associated mortality per 100 000 persons was 4·0 (95% CI: −18 to 26). Eighty-three percent of influenza-associated deaths occurred among persons aged > 65 years. The average annual rate of influenza-associated deaths was 0·7 (95% CI: −8·2 to 10) per 100 000 population for person aged <65 years and 42 (95% CI: −137 to 216) for person aged ≥ 65 years.

Discussion

In Thailand, estimated excess mortality associated with influenza was considerable even during non-pandemic years. These data provide support for Thailand''s seasonal influenza vaccination campaign. Continued monitoring of mortality data is important to assess impact.     

Inhaled Technosphere? Insulin in Comparison to Subcutaneous Regular Human Insulin: Time Action Profile and Variability in Subjects with Type 2 Diabetes

Background

This study assessed time action profile and within- and between-subject variability of inhaled Technosphere® Insulin (TI) compared with subcutaneous regular human insulin (sc RHI).

Methods

Thirteen subjects with type 2 diabetes (age 56 ± 7 years, body mass index 30.4 ± 3.0 kg·m^-2; hemoglobin A1c 6.9 ± 0.9%; mean ± SD) participated in this six-period crossover isoglycemic glucose clamp study. In randomized order, each subject received three single doses of TI and sc RHI on separate study days.

Results

Inhalation of TI resulted in a higher maximum serum insulin concentration (858 vs 438 pmol·liter^-1; p = 0.0001) and shorter intervals to maximum insulin concentration (17 vs 135 minutes; p = 0.0001) than sc RHI. Overall, 48 units of TI and 24 units of sc RHI provided comparable 3-hour insulin exposure (INS area under the curve_{0–3 h} 55.8 vs 60.0 nmol·min·liter^-1, respectively). Time to maximum metabolic effect was shorter (79 vs 293 minutes; p < 0.0001), and percentage of glucose disposal during the first 3 hours was higher for TI compared with sc RHI (59 vs 27%). Within-subject variabilities of insulin exposure following inhalation of TI for 2 and 3 hours and end of study period were 19, 18, and 16% as compared with 27, 25, and 15% after sc RHI injection (p = not significant).

Conclusion

Technosphere Insulin has a more rapid onset of action than sc RHI. About 60% of the glucose-lowering effect of TI occurs during the first 3 hours after application. In contrast, <30% of the glucose-lowering effect of sc RHI occurs in this period. Technosphere Insulin demonstrated a lower intrasubject variability during the 3-hour postprandial period, without reaching statistical significance.