Determinants of self-reported adherence to inhaler therapy in patients with chronic obstructive pulmonary disease.

BACKGROUND: Adherence to therapy is crucial for COPD patients, since non-adherence leads to worse quality of life, increased health-care expenditure and poor clinical outcome. The aim of this study was to identify the main determinants of suboptimal adherence to therapy in a cohort of COPD patients. METHODS: General information (age, BMI, smoking, comorbidities, education, life style), lung function, exacerbations, symptoms and COPD treatment were collected. Adherence to therapy was assessed by self-reported 4-item Morisky Medication Adherence Scale (MMAS-4), and was related to anthropometric, socio/economic and health status data, obtained by questionnaires (COPD Assessment Test, CAT; Treatment Satisfaction Questionnaire, HRQoL; Katz Index of Independence of Daily Living Activities, Lawton Instrumental Activities of Daily Living Scale). RESULTS: 136 COPD patients were studied (age 72±8 yrs; 73.5% men; BMI 28.5±7.4 kg/m2; FEV1 53.5±19.0 % predicted). Nearly half of the patients (46.3%) had suboptimal adherence to therapy (score >0) and, as compared to those with optimal adherence, had higher prevalence of women and coronary artery disease, heavier smoking history and worse CCQ overall score. The results of multivariate analysis showed that the determinants of suboptimal adherence were female sex (OR 4.339, 95%CI 1.509-12.474, p=0.006), amount of pack/years smoked (OR 1.947, 95%CI 1.141-3.323, p=0.015), higher CCQ overall score (OR 3.318, 95%CI 1.050-9.892, p=0.049) and higher education (OR 2.758, 95%CI 1.083-7.022, p=0.033). Adherence was better in patients assuming triple inhaler therapy. CONCLUSIONS: Suboptimal adherence is frequent among COPD patients, particularly in women, heavy smokers and subjects with high educational level. Interventions to improve adherence should be especially addressed to patients with these characteristics.

Retraction: Determinants of self-reported adherence to inhaler therapy in patients with chronic obstructive pulmonary disease.

[This retracts the article DOI: 10.4081/mrm.2020.654.].

Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study.

BACKGROUND: Omalizumab may modulate airway remodeling in severe asthma. Using forced expiratory volume in 1 second (FEV1) as a surrogate of airway remodeling, we aimed to investigate if an omalizumab add-on in severe allergic asthma may lead to a persistent reversal of airway obstruction and to evaluate the potential biomarkers of airway obstruction reversibility. METHODS: Data were collected before (T0) and after omalizumab add-on for 1 year (T1, 32 patients), 2 years (T2, 26 patients) and 4 years (T4, 13 patients). All patients had baseline FEV1 below 80 % predicted (60.5 ± 12.5 %). After omalizumab, 18 patients showed FEV1 normalization (reversible airway obstruction; RAO+) already at T1 (88.7 ± 14.9 %, p < 0.0001) that persisted up to T4 (83.2 ± 7.9, p < 0.01), while 14 patients (RAO-) had FEV1 persistently decreased, from T1 (65.2 ± 8.4%, p < 0.05) up to T4 (61.4 ± 6.2%, not significant). Both groups had significant improvement of symptoms and exacerbations after omalizumab at T1, which persisted up to T4. The comparison between pretreatment characteristics of the two groups showed that RAO+ patients, had higher values of circulating eosinophils, exhaled nitric oxide (FENO), prevalence of rhinitis and nasal polyps, need of oral corticosteroids, shorter asthma duration, higher FEV1 and response to albuterol test. The optimal cut-off points predicting FEV1 normalization after omalizumab add-on were 30.5 ppb for FENO and 305 cells/µl for eosinophils. CONCLUSIONS: This study suggests that omalizumab add-on contributes to the persistent reversal of airway obstruction in a consistent number of patients with severe allergic asthma, and this beneficial effect is predicted by elevated pretreatment FENO and circulating eosinophils.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a valuable method for estimating fat-free mass and fat mass in patients with COPD by using specific predictive equations. In addition, raw BIA variables such as high- to low-frequency impedance ratios (IRs) and phase angle, most likely as a result of providing information on muscle quality, have been related to disease severity and mortality in patients with several diseases but never in COPD. The aim of this study was to investigate the predictive role of raw BIA variables on 2-year survival in COPD. METHODS: Impedance (Z) at 5-10-50-100-250 kHz and phase angle at 50 kHz were determined in 210 patients with COPD. Three IRs were calculated: Z at 50 kHz/Z at 5 kHz (50/5 IR), Z at 100 kHz/Z at 5 kHz (100/5 IR), and Z at 250 kHz/Z at 5 kHz (250/5 IR). Demographic, respiratory, and body composition data at baseline were recorded. All-cause mortality was assessed during 2 years of follow-up. RESULTS: After the follow-up period, all-cause mortality was 13.8%. Statistically significant differences between nonsurvivors and survivors emerged in terms of age, weight, BMI, FEV1, inspiratory capacity, and modified Medical Research Council dyspnea score. With respect to nutritional variables, nonsurvivors had lower fat-free mass (P = .031), lower fat mass (P = .015), higher IRs (P < .001 for all the ratios), and lower phase angle (P < .001) compared with survivors. After adjustment for confounding factors, each unit increase of IRs and each unit decrease of phase angle were associated with a higher risk of death. CONCLUSIONS: IRs and phase angle, as raw BIA variables, are independent and powerful predictors of all-cause mortality in COPD and should be considered, together with inspiratory capacity and 6-min walk distance, as significant prognostic factors in the short- to middle-term.

Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy.

BACKGROUND: Skeletal muscle dysfunction and poor functional capacity are important extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), especially in COPD patients on long-term O2 therapy (LTOT). Beside the role of pulmonary rehabilitation, the effect of nutritional interventions is still controversial, and there are knowledge gaps on the effective role of nutraceutical supplementation on hard endpoints. The aim of this study was to investigate the effects of nutritional supplementation with Coenzyme Q10 (QTer®) - a powerful antioxidant with the potential to reduce oxidative stress and improve mitochondrial function - and Creatine on functional, nutritional, and metabolomic profile in COPD patients on long-term O2 therapy. METHODS: One-hundred and eight patients with COPD from 9 Italian hospitals were enrolled in this double-blinded randomized placebo-controlled clinical study. At baseline and after 2 months of therapy, the patients underwent spirometry, 6-minute walk test (6MWT), bioelectrical impedance analysis, and activities of daily living questionnaire (ADL). Also, dyspnea scores and BODE index were calculated. At both time points, plasma concentration of CoQ10 and metabolomic profiling were measured. FINDINGS: Ninety patients, who randomly received supplementation with QTer® and Creatine or placebo, completed the study. Compared with placebo, supplemented patients showed improvements in 6MWT (51 ±â€¯69 versus 15 ±â€¯91 m, p < 0.05), body cell mass and phase angle, sodium/potassium ratio, dyspnea indices and ADL score. The CoQ10 plasma concentration increased in the supplementation group whereas it did not change in the placebo group. The metabolomics profile also differed between groups. Adverse events were similar in both groups. INTERPRETATION: These results show that in patients with COPD, dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea. A systemic increase in some anti-inflammatory metabolites supports a pathobiological mechanism as a reason for these benefits. Further trials should help clarifying the role of QTer® and Creatine supplementation in patients with COPD.

Malnutrition and sarcopenia assessment in patients with chronic obstructive pulmonary disease according to international diagnostic criteria, and evaluation of raw BIA variables.

BACKGROUND: Various criteria have been used so far for the diagnosis of malnutrition or sarcopenia in patients suffering from chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine the prevalence of malnutrition and sarcopenia in COPD, as defined by international diagnostic criteria, and determine their relationships with raw BIA variables. METHODS: Two-hundred and sixty-three COPD patients (185 males and 78 females) underwent both clinical examination and respiratory, anthropometric, bioelectrical impedance analysis (BIA raw variables: phase angle and impedance ratio), handgrip strength (HGS), 4 m gait speed and biochemical measurements. Malnutrition and sarcopenia were diagnosed based on European Society for Clinical Nutrition and Metabolism (ESPEN) criteria and European Working Group on Sarcopenia in Older People (EWGSOP) criteria, respectively. RESULTS: The overall prevalence of malnutrition and sarcopenia was 19.8% and 24.0% respectively, increasing with disease severity. The prevalence of sarcopenia was significantly higher in patients with malnutrition (71.2% vs 12.3%; p < 0.001), especially in those with systemic inflammation (cachectic patients) (85.7% vs 61.3%; p < 0.001). Malnourished patients with sarcopenia had a significant reduction in BMI, fat-free mass and HGS compared to non-sarcopenic patients. Finally, impedance ratio significantly increased and phase angle decreased in patients with severe sarcopenia and in cachectic patients. CONCLUSION: A relatively high prevalence of malnutrition and sarcopenia was found in COPD patients applying international standard criteria, with some discrepancy between the two diagnoses. In addition, clear-cut changes in raw BIA variables were observed in malnourished patients with systemic inflammation and sarcopenic patients.

Asthmatic Patients with Vitamin D Deficiency have Decreased Exacerbations after Vitamin Replacement.

BACKGROUND: Intervention studies with vitamin D in asthma are inconclusive for several reasons, such as inadequate dosing or duration of supplementation or uncontrolled baseline vitamin D status. Our aim was to evaluate the benefit of long term vitamin D add-on in asthmatic patients with actual vitamin D deficiency, that is a serum 25-hydroxy vitamin D (25-OHD ) below 20 ng/mL. METHODS: Serum 25-OHD, asthma exacerbations, spirometry and inhaled corticosteroids (CS) dose were evaluated in a cohort of 119 asthmatic patients. Patients with deficiency were evaluated again after one year vitamin supplementation. RESULTS: 25-OHD was low in 111 patients and was negatively related to exacerbations (p < 0.001), inhaled CS dose (p = 0.008) and asthma severity (p = 0.001). Deficiency was found in 90 patients, 55 of whom took the supplement regularly for one year, while 24 discontinued the study and 11 were not adherent. Patients with vitamin D deficiency after 12 months supplementation showed significant decrease of exacerbations (from 2.6 ± 1.2 to 1.6 ± 1.1, p < 0.001), circulating eosinophils (from 395 ± 330 to 272 ± 212 106/L, p < 0.001), and need of oral CS courses (from 35 to 20, p = 0.007) and improvement of airway obstruction. CONCLUSIONS: Asthma exacerbations are favored by vitamin D deficiency and decrease after long-term vitamin D replacement. Patients who are vitamin D deficient benefit from vitamin D supplementation.

Evaluation of body composition in COPD patients using multifrequency bioelectrical impedance analysis.

BACKGROUND: Multifrequency bioelectrical impedance analysis (MF-BIA) is a technique that measures body impedance (Z) at different frequencies (5, 10, 50, 100, and 250 kHz). Body composition may be estimated using empirical equations, which include BIA variables or, alternatively, raw BIA data may provide direct information on water distribution and muscle quality. OBJECTIVES: To compare raw MF-BIA data between COPD patients and controls and to study their relationship with respiratory and functional parameters in COPD patients. METHODS: MF-BIA was performed (Human Im-Touch analyzer) in 212 COPD patients and 115 age- and BMI-matched controls. Fat-free mass (FFM) and fat mass were estimated from BIA data, and low- to high-frequency (5 kHz/250 kHz) impedance ratio was calculated. Physical fitness, lung function and respiratory muscle strength were also assessed in COPD patients. RESULTS: After adjusting for age, weight, and body mass index, FFM and the 5/250 impedance ratio were lower in COPD patients (P<0.001) and were negatively affected by disease severity. In both male and female patients, the 5/250 impedance ratio was significantly correlated mainly with age (r=-0.316 and r=-0.346, respectively). Patients with a 5/250 impedance ratio below median value had lower handgrip strength (P<0.001), 6-minute walk distance (P<0.005), respiratory muscle strength (P<0.005), forced expiratory volume in 1 second (P<0.05) and vital capacity (P<0.005). Finally, the 5/250 impedance ratio was reduced (P<0.05) in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) III and IV (compared to those with GOLD I and II) or a BODE index between 6 and 10 points (compared to those with BODE index between 1 and 5 points). CONCLUSION: MF-BIA may be a useful tool for assessing body composition and nutritional status in COPD patients. In particular, the impedance ratio could give valuable information on cellular integrity and muscle quality.

Preliminary study on the assessment of visceral adipose tissue using dual-energy x-ray absorptiometry in chronic obstructive pulmonary disease.

BACKGROUND: Visceral adipose tissue (VAT) was shown to be increased in patients with chronic obstructive pulmonary disease (COPD) compared to control subjects with comparable body mass index (BMI). Our aim was to determine the relation of VAT by dual-energy x-ray absorptiometry (DEXA) in patients with COPD by disease severity, BMI, other indices of body composition and static lung volumes. METHODS: 294 COPD patients admitted for rehabilitation were studied. Lung function, static lung volumes and body composition (i.e. BMI, waist circumference, fat-free mass, fat mass and fat distribution between android and gynoid fat mass) were assessed before entering pulmonary rehabilitation. VAT was estimated within the android region by using DEXA. Patients were stratified for gender, BMI (cut-off of 25 kg/m2) and GOLD stage. To assess the impact of VAT on lung volumes, patients were also stratified for VAT less and above 50th percentile. RESULTS: Both male and female patients with more severe airflow limitation had significantly lower VAT values, but these differences disappeared after stratification for BMI. VAT was significantly and strongly correlated with other body composition parameters (all p < 0.001). Patients with moderate to severe airflow limitation and lower VAT had increased static lung hyperinflation and lower diffusing capacity for carbon monoxide. Nevertheless, multivariate stepwise regression models including for BMI, age, gender and forced expiratory volume in 1 s (FEV1) as confounders did not confirm an independent role for VAT on static lung hyperinflation and diffusion capacity. CONCLUSION: After stratification for BMI, VAT is comparable in moderate to very severe COPD patients. Furthermore, BMI and demographics, but not VAT, were independent predictors of static lung hyperinflation and diffusing capacity in COPD.