Vitamin D Deficiency and Corticosteroid Use Are Risk Factors for Low Bone Mineral Density in Inflammatory Bowel Disease Patients

Background

As several factors can contribute to low bone mineral density (BMD), we investigated the role of vitamin D in low BMD while controlling for other risk factors in inflammatory bowel diseases (IBD) patients.

Methods

We conducted a prospective cross-sectional study between 2008 and 2012 in adult IBD patients. Demographic data including age, gender, ethnicity, BMI, along with disease type and location, vitamin D levels, prior corticosteroid use, and anti-TNF use were recorded and evaluated with DEXA results.

Results

A total of 166 patients [105 Crohn’s disease (CD), 61 ulcerative colitis (UC)] qualified for the study. Low BMD was found in 40 %, twice as frequently in CD than in UC (p = 0.048). Higher prevalence of low BMD was associated with those of male gender (p = 0.05), Asian ethnicity (p = 0.02), and history of corticosteroid use (p = 0.001). Age, body mass index, or disease location did not increase the risk of low BMD. The overall prevalence of low vitamin D was 60 %, with insufficiency (25-hydroxy levels between 20 and 30 ng/mL) found in 37 % and deficiency (levels <20 ng/mL) found in 23 % of the patients. Vitamin D insufficient and deficient patients were two times (p = 0.049) and almost 3 times (p = 0.02) as likely to have low BMD, respectively.

Conclusions

Low vitamin D, male gender, Asian ethnicity, CD, and corticosteroid use significantly increased the risk of having low BMD, while age and disease location did not affect BMD in our IBD population. It remains important to evaluate for vitamin D nutritional deficiency and limit corticosteroid use to help prevent low BMD in IBD patients.     

Vitamin D Deficiency Is Associated with Ulcerative Colitis Disease Activity

Purpose

Previous studies on experimental mouse models have suggested a role of vitamin D in immune system regulation and IBD disease severity. In this study, we examine the relationship between vitamin D levels and clinical disease activity in human subjects with ulcerative colitis (UC). We hypothesized that patients with vitamin D deficiency will display increased UC disease activity as compared to patients with normal vitamin D levels.

Methods

A cross-sectional study was performed by querying the outpatient electronic medical record of our health system for patients seen in the gastroenterology clinic from January 2007 to October 2009 who carried both a diagnosis of UC and a documented 25-OH vitamin D level within 30 days of their clinic visit. Demographic and clinical variables were collected. Clinical disease activity was calculated using the six-point partial Mayo index. Active disease was defined as a six-point index score of ≥1. Vitamin D deficiency was defined as a 25-OH D level below 30 ng/ml. Data were analyzed using the chi-square distribution test.

Results

Thirty-four patients met inclusion criteria (53 % female, mean age 45.7 ± 24.7 years). Fifteen patients had normal vitamin D levels and 19 patients were vitamin D deficient. Twelve patients had vitamin D levels <20 ng/ml. Vitamin D deficient patients were statistically more likely to have increased disease activity than patients with normal vitamin D levels (p = 0.04), with 68 % of deficient patients displaying active disease compared with 33 % in the sufficient group. There was also a statistically significant association between vitamin D status and need for treatment with steroids, with a higher percentage of vitamin D deficient patients (47 %) requiring such treatment compared with 7 % in the sufficient group (p = 0.02). There was no association between season of visit and disease activity.

Conclusion

Vitamin D deficiency is common among patients with active UC, particularly those requiring corticosteroids. Further investigation is needed to determine the clinical utility of vitamin D monitoring in patients with UC and whether there is a role for vitamin D as a treatment for UC.     

Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression

Aims/hypothesis

Vitamin D deficiency is common in people with type 1 diabetes, but its role in disease progression is unclear. Our aim was to assess the prevalence of vitamin D deficiency in prediabetes (defined as the presence of multiple islet autoantibodies), and investigate whether or not progression to type 1 diabetes is faster in children with vitamin D deficiency and multiple islet autoantibodies.

Methods

Levels of 25-hydroxyvitamin D [25(OH)D] were measured in 108 children with multiple islet autoantibodies within 2 years of islet autoantibody seroconversion, in 406 children who remained islet autoantibody-negative and in 244 patients with newly diagnosed type 1 diabetes. Children with multiple islet autoantibodies were prospectively followed for a median of 5.8 years (interquartile range 3.4–8.6 years) to monitor progression to type 1 diabetes.

Results

In the cross-sectional analysis, 25(OH)D levels were lower and the prevalence of vitamin D deficiency (<50 nmol/l) was higher in children with prevalent multiple islet autoantibodies than in islet autoantibody-negative children (59.9?±?3.0 vs 71.9?±?1.5 nmol/l; p?<?0.001; 39.8% vs 28.3%; p?=?0.021). The differences in vitamin D levels between the groups were greatest in summer. The cumulative incidence of type 1 diabetes at 10 years after seroconversion was similar between children with vitamin D deficiency and those with sufficient vitamin D levels (51.8% [95% CI 29.3, 74.3] vs 55.4% [95% CI 35.5, 72.3], p?=?0.8).

Conclusions/interpretation

Vitamin D levels were lower in children with multiple islet autoantibodies and in children with type 1 diabetes than in autoantibody-negative children. However, vitamin D deficiency was not associated with faster progression to type 1 diabetes in children with multiple islet autoantibodies.     

Decreased Neuromuscular Function in Crohn’s Disease Patients Is Not Associated with Low Serum Vitamin D Levels

Background

Neuromuscular fatigue is a common complaint in Crohn’s disease (CD) patients. A correlation between serum vitamin D concentrations and neuromuscular function has been found in the elderly or non-ambulant populations.

Aims

The aim of this study was to determine whether CD patients exhibit impaired neuromuscular function and if so, is there a link between vitamin D and neuromuscular function.

Methods

Crohn’s disease patients (n = 19) with at least one prior small bowel resection and matched controls (n = 19) underwent muscle strength and endurance testing, vitamin D, and nerve function analysis.

Results

Knee extension and flexion peak torque (Nm/kg) were greater in the control group than in the CD patients (P = 0.04 and 0.014, respectively. A significant difference was found between fatigue rates of the rectus femoris (P = 0.015) between CD patients and controls, but no difference was found in serum vitamin D levels between groups (P = 0.317). Knee extension and flexion torque measurements, with age as a covariate, were compared with high and low vitamin D levels. Those subjects with high serum vitamin D levels had a significantly greater extension peak torque (P = 0.045) and extension average torque (Nm/kg) (P = 0.014) than those with low levels.

Conclusion

Crohn’s disease patients with sufficient vitamin D levels experienced a 43 % greater extension peak torque. Although vitamin D deficiency has been associated with neuromuscular dysfunction, there were no differences in serum vitamin D levels between the CD and healthy controls to explain the decreased muscle strength.     

Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?

Purpose

The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors.

Methods

We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry.

Results

We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89–32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13–17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77–19.96). HAART receipt was not associated with respiratory symptoms nor with COPD.

Conclusions

We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.     

No Significant Association Between Vitamin D and Nonalcoholic Fatty Liver Disease in a Chinese Population

Background

Some research evidence from Western populations suggests that lower vitamin D is associated with the prevalence and histologically assessed severity of nonalcoholic fatty liver disease (NAFLD).

Aims

To investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and vitamin D status (deficiency <20 ng/ml; insufficiency 20–30 ng/ml; sufficiency >30 ng/ml) with the prevalence of NAFLD in study population of Chinese.

Methods

Serum 25(OH)D, parathyroid hormone, lipids, liver enzymes, and anthropometric characteristics were measured in 1,248 subjects aged ≥20 years. NAFLD was diagnosed using abdominal ultrasound examination.

Results

The prevalence of NAFLD was 30.3 % in the total study population, 37.9 % in the male subjects, and 20.8 % in the female subjects (P < 0.0001). Subjects with NAFLD had a significantly higher body mass index, higher levels of fasting blood glucose and liver enzymes, and a more atherogenic lipid profile. However, serum 25(OH)D concentrations were not significantly different between subjects with and without NAFLD (22.1 vs. 22.8 ng/ml, respectively; P = 0.21). In addition, a 10 ng/ml higher serum 25(OH)D concentrations [odds ratio (OR) 1.02, 95 % confidence interval (CI) 0.84–1.25, P = 0.82] or vitamin D status (vs. sufficiency: deficiency OR 0.86, 95 % CI 0.54–1.37, P = 0.52; insufficiency OR 0.96, 95 % CI 0.61–1.52, P = 0.87) were not significantly associated with the presence of NAFLD in the multivariate logistic regression analyses.

Conclusions

Serum 25(OH)D concentrations or vitamin D status were not significantly associated with the presence of NAFLD. More studies are needed to elucidate the relationship between vitamin D and the occurrence of NAFLD in Chinese.     

Association Between Cyclin D1 Polymorphism with CpG Island Promoter Methylation Status of Tumor Suppressor Genes in Gastric Cancer

Background

CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis.

Aims

We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer.

Methods

Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands.

Results

Although no association was found between methylation status and different stages and Lauren’s subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017).

Conclusions

Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.     

Increased Sympathetic Nerve Activity in COPD is Associated with Morbidity and Mortality

Background

Chronic obstructive lung disease (COPD) is a major cause of comorbidity and mortality. Systemic effects, such as sympathetic activation, might contribute to progression and severity of the disease.

Objectives

This study investigated whether increased sympathetic activity is associated with increased long-term morbidity and mortality with COPD.

Methods

Following a baseline registration of muscle sympathetic nerve activity (MSNA), 21 COPD patients and 21 matched healthy control subjects were contacted after a mean follow-up period of 7 years. Information about the number of hospitalizations during follow-up was obtained from patients who were still alive. Information about the time of death was collected from relatives of the deceased and local registration offices. The primary endpoint was the comparison of MSNA in living patients without hospitalizations versus MSNA in the patients who died or had at least one hospitalization due to exacerbation of COPD.

Results

At baseline, MSNA was significantly increased, whereas forced expiratory volume in 1 s and arterial oxygen tension (PaO₂) were significantly decreased in patients compared with controls. MSNA was significantly higher in COPD patients who had reached the combined endpoint of hospitalization or death during follow-up (n = 12) compared with patients who were still alive at follow-up and had not been hospitalized (n = 8): 60.3 ± 15.8 (SD) bursts/min versus 40.5 ± 17.5 bursts/min; p = 0.022.

Conclusions

Our data suggest that sympathetic activation is related to adverse outcome in COPD. Although this finding has to be replicated in larger studies, it implies that neurohumoral activation could be a potential therapeutic target in COPD.     

Exhaled Nitric Oxide Predicts Eosinophilic Airway Inflammation in COPD

Purpose

Chronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation may represent a unique phenotype, possibly with shared features of COPD and asthma. The role of exhaled nitric oxide (eNO) in identifying COPD patients with sputum eosinophilia was examined in this study.

Methods

Ninety COPD patients without past medical history of asthma or allergic diseases were prospectively enrolled, and their eNO, lung function, and cellular profile of induced sputum were measured. Eosinophil cationic protein and IgE in sputum and venous blood also were determined. Subjects with and without sputum eosinophilia (>3 %) were compared. The role of eNO in the prediction of sputum eosinophilia was assessed in a logistic regression model.

Results

Patients with sputum eosinophilia had significantly higher levels of eNO (29 vs. 18 ppb, p = 0.01) than those without. The difference in serum total IgE (168 vs. 84.9 IU/ml, p = 0.057) and percentages of positive allergen test results (48.3 vs. 29.5 %, p = 0.082) showed a trend toward significance. The sputum eosinophil level was significantly correlated to the eNO level (r = 0.485, p < 0.001). The eNO level at the cutoff of 23.5 ppb had the maximum sum of sensitivity (62.1 %) and specificity (70.5 %). The unadjusted and adjusted odds ratios of a higher eNO level (>23.5 ppb) in the prediction of sputum eosinophilia were 3.909 (confidence interval (CI) 1.542–9.91, p = 0.004) and 4.329 (CI 1.306–14.356, p = 0.017), respectively.

Conclusions

eNO is a good marker to identify COPD patients with eosinophilic airway inflammation.     

Collateral Damage: Depressive Symptoms in the Partners of COPD Patients

Background

Depression is a frequent comorbidity in COPD patients and is associated with greater physical impairment, increased health-care utilization, and worse outcomes. The presence of depressive symptoms in the partners of COPD patients has not been evaluated.

Methods

We evaluated the partners of 230 consecutive COPD patients included in a prospective study. Depressive symptoms were evaluated using Beck’s Depression Inventory (BDI) on the first day of admission for COPD exacerbation. Patients were followed-up for 1 year.

Results

Significant depressive symptoms were present in 39.6 % of the COPD patients and in 40.9 % of their partners. Beck scores were higher in the partners of patients with severe airflow obstruction and in those with ≥2 exacerbations and ≥1 hospitalizations for COPD exacerbation during the 1-year follow-up. The BDI score of the patients’ partners was significantly correlated with the BDI score of the COPD patients (r _s = 0.422). In multivariate analysis, depressive symptoms in the COPD patients were an independent predictor of depressive symptoms in their partners (OR 4.136, 95 % CI 1.991–8.594; p < 0.001).

Conclusions

A large proportion of the partners of COPD patients present significant depressive symptoms. The identification of those patients and their partners represents a possible target for intervention.     

Association of common gene variants in vitamin D modulating genes and colon cancer recurrence

Purpose

Low concentrations of 25-hydroxyvitamin D3 (25(OH)D) have been associated with increased risk and poor prognosis of various cancer types, including colon cancer. Common genetic variants in genes that influence circulating 25(OH)D levels may affect vitamin D concentrations and risk of vitamin D insufficiency. In the present study, we investigated the association of three functional gene variants in GC (rs2282679 T>G), DHCR7 (rs12785878 G>T) and CYP2R1 (rs10741657 A>G) with time to recurrence (TTR) in patients with stages II and III colon cancer.

Methods

Two hundred and sixty-four patients were included in this retrospective study. Genomic DNA was genotyped for GC rs2282679 T>G, DHCR7 rs12785878 G>T and CYP2R1 rs10741657 A>G by 5′-exonuclease (TaqMan?) technology.

Results

In the univariate analysis, GC rs2282679 GG was significantly associated with decreased TTR (HR = 3.30, 95 % CI 1.09–9.97, p = 0.034) in patients with surgery alone and remained significantly associated in multivariate analysis including lymph node involvement and clinical stage (HR = 3.64, 95 % CI 1.16–11.46, p = 0.027). In patients with adjuvant chemotherapy, GC rs2282679 T>G was not significantly associated with TTR (HR = 1.02, 95 % CI 0.44–2.37, p = 0.964). Furthermore, we observed a trend toward decreased TTR in patients harboring the CYP2R1 rs10741657 A>G gene variant including all patients (HR = 1.50, 95 % CI 0.98–2.28, p = 0.060). No association was found between DHCR7 rs12785878 G>T and TTR in our study cohort.

Conclusion

In conclusion, our results may indicate a prognostic effect of GC rs2282679 in stages II and III colon cancer patients with surgery alone. Larger studies have to be performed to validate our findings.     

Exercise Capacity and Ventilatory Response During Exercise in COPD Patients With and Without β Blockade

Background

Although β blockade (BB) in patients with chronic obstructive pulmonary disease (COPD) does not show signs of worsening pulmonary function or respiratory symptoms, the effects on cardiopulmonary exercise testing (CPET) remain unclear. The aim of this study was to determine whether BB affects exercise capacity, gas exchange, and hemodynamic responses in patients with COPD.

Methods

Twenty-four COPD subjects on BB were matched to 24 COPD subjects without BB according to age, gender, body mass index, and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET.

Results

Comparing COPD patients with and without BB revealed that percent peak oxygen consumption and VE/VCO₂ nadir were not significantly different (45 ± 16 vs. 51 ± 23 %, p = 0.30, and 35.1 ± 8.5 vs. 36.2 ± 11.6 %, p = 0.69). Systolic blood pressure and heart rate at peak exercise were significantly decreased in COPD patients with BB (168 ± 16 vs. 185 ± 20 mmHg, and 109 ± 16 vs. 122 ± 14 bpm, respectively, p < 0.05).

Conclusion

Exercise capacity and gas exchange remain unaffected in patients with COPD in the presence of BB, although heart rate and blood pressure are lower. These findings imply that BB does not adversely affect functional capacity in patients with COPD.     

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21–29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.     

XPC gene variants: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy

Purpose

To investigate the association between two Xeroderma pigmentosum group C polymorphism (XPC Lys939Gln and insertion/deletion PAT ?/+ in intron 9) and bladder cancer (BC) susceptibility.

Materials and methods

Genotyping was performed in 208 BC patients and 245 controls by PCR–RFLP method.

Results

XPC PAT +/+ genotype was associated with elevated risk of BC (p = 0.021, OR = 2.49). XPC Lys939Gln AC + CC genotype was significantly associated with risk in invasive stage of BC (p = 0.041, OR = 2.52). Haplotype analysis revealed that variant genotypes C of XPC Lys939Gln and + of PAT, C+ were significantly associated with risk of BC (p = 0.004, OR = 1.70). The CC genotype of Lys939Gln was associated with high risk for recurrence in BCG-treated patients (HR = 3.21, p = 0.036) thus, showing reduced recurrence-free survival (AC + CC/AA = 36/60 months; log rank p = 0.045).

Conclusion

Polymorphisms and haplotypes in XPC appear to influence susceptibility to BC risk. The variant C allele at Lys939Gln may be responsible for early recurrence in BCG-treated patients.     

Survival Benefit of CPAP Favors Hypercapnic Patients with the Overlap Syndrome

Background

Patients with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), known as the “overlap syndrome,” have a substantially greater risk of morbidity and mortality compared to those with either COPD or OSA alone. The study’s objective was to report on the long-term outcome of hypercapnic (PaCO₂ ≥ 45 mmHg) and normocapnic patients with the overlap syndrome treated with continuous positive airway pressure (CPAP).

Methods

A nonconcurrent cohort of consecutive patients with the overlap syndrome was followed for a median duration of 71 months (range 1–100) at a VA sleep center. All patients were managed according to the prevailing recommendations of both diseases. The end point of the study was all-cause mortality.

Results

Of the 271 patients identified, 104 were hypercapnic (PaCO₂ = 51.6 ± 4.3 mmHg). Both normocapnic and hypercapnic patients had comparable apnea–hypopnea indexes (AHI) (29.2 ± 23.8 and 35.2 ± 29.2/h, respectively; p = 0.07) and similar adherence rates to CPAP (43 and 42 %, respectively, p = 0.9). Survival analysis revealed that hypercapnic patients who were adherent to CPAP had reduced mortality compared to nonadherent hypercapnic patients (p = 0.04). In contrast, the cumulative mortality rate for normocapnic patients was not significantly different between the adherent and the nonadherent group (p = 0.42). In multivariate analysis, the comorbidity index was the only independent predictor of mortality in normocapnic patients with the overlap syndrome [hazard ratio (HR) 1.68; p < 0.001] while CPAP adherence was associated with improved survival (HR 0.65; p = 0.04).

Conclusions

CPAP mitigates the excess risk of mortality in hypercapnic patients but not in normocapnic patients with the overlap syndrome.     

Correlations Between Small Airway Function,Ventilation Distribution,and Functional Exercise Capacity in COPD Patients

Background

Interest in using the nitrogen single-breath washout (N₂SBW) test to measure ventilation inhomogeneity and small airway function in COPD patients has grown in recent years. Our aim was to assess the correlation of the measures obtained by the N₂SBW test and other pulmonary function parameters with the six-minute walk distance (6MWD), the degree of dyspnea score, and health status in COPD patients.

Methods

In this cross-sectional study, 31 patients with COPD were subjected to the N₂SBW test, spirometry, whole-body plethysmography, carbon monoxide diffusing capacity measurement, the six-minute walk test, the modified Medical Research Council (mMRC) scale, and the COPD Assessment Test (CAT).

Results

We found a strong correlation between the 6MWD and the phase III slope of the nitrogen single-breath washout (Phase III slope_N2SBW) (r = ?0.796; p = 0.0001). We found moderate correlations between the 6MWD and the residual volume (RV) (r = ?0.651; p = 0.0001) and RV/total lung capacity (RV/TLC) (r = ?0.600; p = 0.0004). We also found moderate correlations between the CAT score and Phase III slope_N2SBW (r = 0.728; p = 0.0001), RV (r = 0.646; p = 0.0001) and RV/TLC (r = 0.603; p = 0.0003). There was a significant difference between the mMRC grades for the following variables: Phase III slope_N2SBW (p = 0.0001), RV (p = 0.0001), and smoking history (p = 0.008). Multivariate analysis showed that Phase III slope_N2SBW was the only independent predictor of the 6MWD (R ²  = 0.703; p = 0.0001), CAT score (R ²  = 0.586; p = 0.0001), and mMRC scale (relative risk = 1.14; p = 0.0001).

Conclusions

In patients with COPD, our findings suggest that the ventilation inhomogeneity impacts the functional exercise capacity, the degree of dyspnea, and health status.     

Effects of calcium–vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial

Aims/hypothesis

This study was performed to assess the effects of vitamin D and calcium supplementation on the metabolic profiles of vitamin D insufficient persons with type 2 diabetes.

Methods

In a parallel designed randomised placebo-controlled clinical trial, a total of 118 non-smoker individuals with type 2 diabetes and insufficient 25-hydroxyvitamin D, aged >30 years, were recruited from the Isfahan Endocrine and Metabolism Research Centre. Participants were randomly assigned to four groups receiving: (1) 50,000 U/week vitamin D + calcium placebo; (2) 1,000 mg/day calcium + vitamin D placebo; (3) 50,000 U/week vitamin D + 1,000 mg/day calcium; or (4) vitamin D placebo + calcium placebo for 8 weeks. A study technician carried out the random allocations using a random numbers table. All investigators, participants and laboratory technicians were blinded to the random assignments. All participants provided 3 days of dietary records and 3 days of physical activity records throughout the intervention. Blood samples were taken to quantify glycaemic and lipid profiles at study baseline and after 8 weeks of intervention.

Results

30 participants were randomised in each group. During the intervention, one participant from the calcium group and one from the vitamin D group were excluded because of personal problems. Calcium–vitamin D co-supplementation resulted in reduced serum insulin (changes from baseline: ?14.8?±?3.9 pmol/l, p?=?0.01), HbA_1c [?0.70?±?0.19% (?8.0?±?0.4 mmol/mol), p?=?0.02], HOMA-IR (?0.46?±?0.20, p?=?0.001), LDL-cholesterol (?10.36?±?0.10 mmol/l, p?=?0.04) and total/HDL-cholesterol levels (?0.91?±?0.16, p?=?0.03) compared with other groups. We found a significant increase in QUICKI (0.025?±?0.01, p?=?0.004), HOMA of beta cell function (HOMA-B; 11.8?±?12.17, p?=?0.001) and HDL-cholesterol (0.46?±?0.05 mmol/l, p?=?0.03) in the calcium–vitamin D group compared with others.

Conclusions/interpretation

Joint calcium and vitamin D supplementation might improve the glycaemic status and lipid profiles of vitamin D insufficient people with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01662193 Funding: Clinical Research Council, Isfahan University of Medical Sciences, Isfahan, Iran     

Diaphragmatic Motion Studied by M-mode Ultrasonography in Combined Pulmonary Fibrosis and Emphysema

Background

The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare diaphragmatic motion measured by M-mode ultrasonography of patients with CPFE, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD).

Methods

Pulmonary function, high-resolution computed tomography (HRCT), and diaphragmatic motion were examined in patients with CPFE (n = 25), IPF (n = 18), and COPD (n = 60), and in healthy controls (n = 21). Diaphragmatic motions were measured on M-mode ultrasonographic images during quiet breathing and deep breathing.

Results

There were no significant differences in right or left diaphragmatic motion during quiet breathing among the four groups, whereas differences were significant in right and left motion during deep breathing. Diaphragmatic motion in CPFE patients was the lowest among the four groups. COPD patients, especially those with severe COPD, showed significantly lower diaphragmatic motion than IPF patients or healthy controls. There were no differences in diaphragmatic motion between IPF patients and healthy controls. Right diaphragmatic motions during deep breathing were negatively correlated with emphysema scores (r = ?0.606, p < 0.001), but were not correlated with fibrosis scores on HRCT.

Conclusions

Diaphragmatic weakness was found in CPFE patients. Emphysema but not fibrosis may be one cause of limited diaphragmatic motion in patients with CPFE. M-mode ultrasonographic evaluation of diaphragmatic motion during deep breathing may be a useful tool in diagnosing CPFE and in discriminating CPFE patients from IPF or COPD patients.     

Dynamic Hyperinflation Correlates with Exertional Oxygen Desaturation in Patients with Chronic Obstructive Pulmonary Disease

Background

Dynamic hyperinflation (DH) causes exercise limitation and exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD). Exertional desaturation (ED) also occurs commonly in COPD but neither routine physiologic parameters nor imaging predict ED accurately. In this study we evaluated the relationship between DH and ED during 6-min walk testing (6MWT).

Methods

We measured ED and DH in patients with stable COPD. SpO₂ was measured by continuous pulse oximetry during 6MWT. ED was defined as a decline in SpO₂ (ΔSpO₂) ≥4 %. DH was determined by measuring inspiratory capacity (IC) before and after the 6MWT using a handheld spirometer. DH was defined as ΔIC >0.0 L. We correlated DH and ED with clinical and pulmonary physiologic variables by regression analysis, χ ², and receiver operator curve (ROC) analysis.

Results

Thirty males [age = 65 ± 9.4 years, FEV₁ % predicted = 48 ± 14 %, and DLCO % predicted = 50 ± 21 % (mean ± SD)] were studied. ΔSpO₂ correlated with ΔIC (r = 0.49, p = 0.005) and age (r = 0.39, p = 0.03) by univariate analysis; however, only ΔIC correlated on multivariate regression analysis (p = 0.01). ΔSpO₂ did not correlate with FEV₁, FVC, FEF_25–75, RV, DLCO % predicted, BMI, smoking, BORG score, or distance covered in 6MWT. DH strongly correlated with ED (p = 0.001). On ROC analysis, DH had an area under the curve of 0.92 for the presence of ED (sensitivity = 90 %; specificity = 77 %, p < 0.001).

Conclusion

Routine pulmonary function test results and clinical variables did not correlate with ED in patients with stable COPD. Dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.