Maria Elisabetta Zanolin

The Coexistence of Asthma and Chronic Obstructive Pulmonary Disease (COPD): Prevalence and Risk Factors in Young, Middle-aged and Elderly People from the General Population

Background The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors. Methods A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20–44 (n = 5163) 45–64 (n = 2167) and 65–84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Results A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65–84 years respectively. Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%). The prevalence of the overlap of asthma and COPD was 1.6% (1.3%–2.0%), 2.1% (1.5%–2.8%) and 4.5% (3.2%–5.9%) in the 20–44, 45–64 and 65–84 age groups. Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01). Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions. Conclusion Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects. The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research.

Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20–44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991–1993; n=6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998–2000; n=18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007–2010; n=10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19–1.59) from 1998–2000 to 2007–2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

Divergences in Insulin Resistance Between the Different Phenotypes of the Polycystic Ovary Syndrome

CONTEXT/OBJECTIVE Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. PATIENTS/DESIGN A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. RESULTS Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). CONCLUSIONS There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group.

Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects A randomized controlled trial (the RAED2 study)

OBJECTIVE To assess differences between the effects of aerobic and resistance training on HbA1c (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (n = 40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA1c, glucose clamp–measured insulin sensitivity, and oral glucose tolerance test–assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured. RESULTS After training, increase in peak oxygen consumption (VO2peak) was greater in the aerobic group (time-by-group interaction P = 0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P < 0.0001). HbA1c was similarly reduced in both groups (−0.40% [95% CI −0.61 to −0.18] vs. −0.35% [−0.59 to −0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA1c after training was independently predicted by baseline HbA1c and by changes in VO2peak and truncal fat. CONCLUSIONS Resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Changes after training in VO2peak and truncal fat may be primary determinants of exercise-induced metabolic improvement.

A new questionnaire for the repeat of the first stage of the European Community Respiratory Health Survey: a pilot study

In the early 1990s a multicentre survey on asthma was performed on the young adult population (European Community Respiratory Health Survey - ECRHS). This study is to be repeated in order to estimate changes in the prevalence of asthma-like symptoms during the last decade and to assess the social and economic costs of the disease and their variations among countries. The self-administered questionnaire devised for this purpose is a two-page questionnaire. The first page contains the same items as those used in the first survey with four additional questions related to: 1) the frequency and severity of asthma attacks; 2) the presence of chronic bronchitis; 3) smoking habits; and 4) a visual analogue scale assessing perception of outdoor pollution. The second page aims to collect information regarding the direct and indirect costs of asthma. The influence of the length of the questionnaire on the response rate was assessed in a pilot study in Italy. Two random samples of 150 subjects received either the one-page questionnaire (first page) or the two-page questionnaire. The response rate was compared with that obtained from the first postal wave in the 1991-1992 survey. Although the response rate was unchanged when using the one-page questionnaire (45% versus 45%), it decreased by 7% when the two-page questionnaire was used (38% versus 45%). On the basis of these results, no problem should arise if four more questions are added to the one-page questionnaire. The slight reduction in the response rate of the two-page questionnaire is worrying but could be corrected by the use of telephone interviews.

The role of climate on the geographic variability of asthma, allergic rhinitis and respiratory symptoms: results from the Italian study of asthma in young adults

Background:  Variations in the prevalence of respiratory symptoms according to geo‐climatic factors could provide important clues to the knowledge of the aetiology of asthma.

Progressive polarization towards a T helper/cytotoxic type-1 cytokine pattern during age-dependent maturation of the immune response inversely correlates with CD30 cell expression and serum concentration

In order to investigate the T cell cytokine profile during age‐dependent maturation of the immune response, we evaluated the cytokine expression of CD4+ and CD8+ circulating cells by flow cytometric single‐cell analysis after non‐specific stimulation in vitro in different age groups of normal individuals, from cord blood to adulthood. Moreover, we correlated these lymphocyte cytokine patterns with the expression/release of CD30, a member of the tumour necrosis factor (TNF) receptor superfamily, which has been suggested to be related to the T helper/cytotoxic (Th(c))2‐type immune responses, in order to verify this association in vivo, in non‐pathological conditions. The results showed a progressive increase of circulating Th(c)1‐type, interferon‐gamma (IFN‐γ)‐ and/or IL‐2‐producing T cells along with ageing and, conversely, a stable number, although higher than in cord blood samples, of CD4+/IL‐4+ T cells in the post‐natal groups. In addition, serum levels of soluble CD30 (sCD30) and numbers of circulating CD4+/CD30+ and CD8+/CD30+ T cells were significantly higher in children aged < 5 years in comparison with those found either in cord blood or in blood from both older children and adults. These data support the concept of a progressive polarization of the Th(c) cell cytokine profile towards the Th(c)1 pattern during age‐dependent maturation of the immune response. Moreover, the peak of CD30 expression/release in early infancy before the Th(c)1 shifting occurs, although not associated with a significant increase of circulating IL‐4+ T cells, raises the question of the possible relationship in vivo between CD30 and Th(c)2‐type immune responses.

Metabolic Inflexibility Is a Feature of Women With Polycystic Ovary Syndrome and Is Associated With Both Insulin Resistance and Hyperandrogenism

CONTEXT Metabolic inflexibility, ie, the impaired ability of the body to switch from fat to carbohydrate oxidation under insulin-stimulated conditions, is associated with insulin resistance. This alteration in metabolic plasticity can lead to organ dysfunction and is considered a key issue among the abnormalities of the metabolic syndrome. It is still unknown whether this phenomenon occurs in women with polycystic ovary syndrome (PCOS). OBJECTIVE Our objective was to examine whether metabolic inflexibility is a feature of PCOS women and whether hyperandrogenism may contribute to this phenomenon. DESIGN AND PATIENTS Eighty-nine Caucasian women with PCOS were submitted to hyperinsulinemic-euglycemic clamp. Respiratory exchange ratios were evaluated at baseline and during hyperinsulinemia by indirect calorimetry to quantify substrate oxidative metabolism. Total testosterone was measured by liquid chromatography mass spectrometry and free testosterone by equilibrium dialysis. SETTING Outpatients were seen in a tertiary care academic center. MAIN OUTCOME MEASURE Metabolic flexibility was assessed by the change in respiratory quotient upon insulin stimulation. RESULTS Sixty-five of the 89 PCOS women (73%) had increased serum free testosterone, 68 (76%) were insulin resistant, and 62 (70%) had an impaired metabolic flexibility. Comparison of hyperandrogenemic and normoandrogenemic women showed that the 2 subgroups were of similar age but differed in terms of several anthropometric and metabolic features. In particular, hyperandrogenemic women had greater body mass index (32.9 ± 1.0 vs 24.7 ± 0.9 kg/m(2), P < .001) and lower glucose utilization during the clamp (9.2 ± 0.4 vs 10.9 ± 0.7 mg/kg fat-free mass · min, P = .023) and metabolic flexibility (0.09 ± 0.06 vs 0.12 ± 0.01, P = .014). In univariate analysis, metabolic flexibility was associated with several anthropometric, endocrine, and metabolic features. In multivariate analysis, this feature was directly associated with baseline respiratory quotient and insulin sensitivity and inversely with free testosterone and free fatty acids concentrations under insulin suppression (R(2) = 0.634, P < .001). CONCLUSIONS Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

Differences in the Acute Effects of Aerobic and Resistance Exercise in Subjects with Type 2 Diabetes: Results from the RAED2 Randomized Trial

Objective Both aerobic (AER) and resistance (RES) training, if maintained over a period of several months, reduce HbA1c levels in type 2 diabetes subjects. However, it is still unknown whether the short-term effects of these types of exercise on blood glucose are similar. Our objective was to assess whether there may be a difference in acute blood glucose changes after a single bout of AER or RES exercise. Study Design Twenty-five patients participating in the RAED2 Study, a RCT comparing AER and RES training in diabetic subjects, were submitted to continuous glucose monitoring during a 60-min exercise session and over the following 47 h. These measurements were performed after 10.9+0.4 weeks of training. Glucose concentration areas under the curve (AUC) during exercise, the subsequent night, and the 24-h period following exercise, as well as the corresponding periods of the non-exercise day, were assessed. Moreover, the low (LBGI) and high (HBGI) blood glucose indices, which summarize the duration and extent of hypoglycaemia or hyperglycaemia, respectively, were measured. Results AER and RES training similarly reduced HbA1c. Forty-eight hour glucose AUC was similar in both groups. However, a comparison of glucose AUC during the 60-min exercise period and the corresponding period of the non-exercise day showed that glucose levels were lower during exercise in the AER but not in the RES group (time-by-group interaction p = 0.04). Similar differences were observed in the nocturnal periods (time-by-group interaction p = 0.02). Accordingly, nocturnal LBGI was higher in the exercise day than in the non-exercise day in the AER (p = 0.012) but not in the RES group (p = 0.62). Conclusions Although AER and RES training have similar long-term metabolic effects in diabetic subjects, the acute effects of single bouts of these exercise types differ, with a potential increase in late-onset hypoglycaemia risk after AER exercise. Trial registration ClinicalTrials.gov NCT01182948