Biomedical subjects

Piersante Sestini

Publications and source records attributed to Piersante Sestini.

13 recordsLinked to original sources

PubMed2006

Endothelin axis polymorphisms in patients with scleroderma.

OBJECTIVE: To evaluate the distribution of polymorphisms in the endothelin 1 (EDN1), endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) genes in systemic sclerosis (SSc; scleroderma) and SSc subsets. METHODS: Two hundred five patients with SSc and 255 healthy controls were screened for polymorphisms in EDN1, EDNRA, and EDNRB, using sequence-specific primer-polymerase chain reaction. The polymorphisms studied were at the following positions: for EDN1, -1370 (T-1370G) of the promoter, +138 of exon 1 (+138 A/-), +85 of exon 3 (E106E), and +23 of exon 5 (K198N); for EDNRA, -231 of exon 1 (G-231A), and +69(H323H) and +105 (E335E) of exon 6; for EDNRB, +2841 of exon 2 (EDNRB-3), -2547 of exon 3 (EDNRB-2), and -2446 of exon 3 (EDNRB-1). RESULTS: No significant differences between the SSc group as a whole and control subjects were observed for any of the investigated polymorphisms in EDN1, EDNRA, and EDNRB. However, compared with patients with limited cutaneous SSc, patients with diffuse skin involvement had an increased frequency of allele carriage of EDNRB-1A (76.8% versus 54.4%; P = 0.002), EDNRB-2A (79.7% versus 60.2%; P = 0.006), and EDNRB-3G (79.7% versus 56.6%; P = 0.001). Significantly increased carriage frequencies for EDNRA alleles H323H/C and E335E/A were observed in SSc patients with anti-RNA polymerase (anti-RNAP) antibodies, compared with both anti-RNAP-negative SSc patients (P < 0.05) and control subjects (P < 0.005). CONCLUSION: The finding of associations between endothelin receptors A and B and distinct clinical and immunologic SSc subsets supports the role of endothelin and its receptors in the pathogenesis of SSc. However, these findings and their functional significance need to be confirmed and investigated in future studies.

Endothelins↗

PubMed2006

Prescription bias and factors associated with improper use of inhalers.

Many different inhalers are available for delivering aerosol therapy in respiratory medicine. As a consequence, the prescribing physicians may have some difficulty tailoring the most suitable inhaler to each patient. This multicenter, observational study using a self-administered questionnaire analyzed the characteristics of a large sample of patients (n = 1,305; 55% females; mean age 57.4, with a range of 15-88 years; most suffering from asthma or chronic obstructive pulmonary disease [COPD]) familiar with several different types of inhalers in relation to their most commonly used delivery device. Data on the inhalation technique for 2,057 observations of 1,126 patients using device-specific checklists and factors associated to misuse were also evaluated. Prevalent usage of newer dry powder inhalers (DPIs) was significantly associated with male sex, higher education, better respiratory function, and prescription from a respiratory physician. Patients using DPIs had received less instruction by health caregivers and were more likely to have read the instruction leaflet than users of metered dose inhalers (MDIs). Under these conditions, inhaler misuse was common and similar for both pressurized metered dose inhalers (pMDIs) and DPIs. For both types of inhalers, misuse was significantly and equally associated to increased age, less education, and less instruction by health care personnel. We conclude that many doctors are not familiar with the relevant characteristics of currently available inhalers. The prescription of newer DPIs may be subjected to gender, socio-economic, and instruction bias. The simple change of device from the pMDI to the newer DPIs is not associated with improved inhalation technique.

Administration, Inhalation↗

PubMed2006

Changes in prevalence of asthma and allergies among children and adolescents in Italy: 1994-2002.

BACKGROUND: Several studies conducted during the 1990s indicated an increase in the prevalence of symptoms of asthma; more recent investigations suggest that the trend is stabilizing or may even be reversing. OBJECTIVE: We compared 2 cross-sectional surveys conducted in 1994 and 2002 in 8 areas in northern and central Italy, to evaluate prevalence changes for asthma, allergic rhinitis, and eczema. METHODS: The International Study of Asthma and Allergies in Childhood methods and questionnaires were used to investigate 6- to 7-year-old children (16,115 and 11,287 questionnaires completed by parents in 1994-1995 and 2002, respectively) and 13- to 14-year-old adolescents (19,723 and 10,267 questionnaires completed by adolescents in 1994-1995 and 2002, respectively). In each phase, the overall response rate was >90%. Prevalence changes were calculated as the absolute difference between the prevalence recorded on the 2 occasions. RESULTS: The prevalence of wheeze (past 12 months) increased slightly among children (change: 0.8%; 95% confidence interval [CI]: 0.0% to 1.6%) and was rather stable among adolescents. Symptoms of allergic rhinitis (children: change: 5.2%; 95% CI: 4.0% to 6.4%; adolescents: change: 4.1%; 95% CI: 1.9% to 6.3%) and symptoms of atopic eczema (children: change: 4.4%; 95% CI: 3.6% to 5.2%; adolescents: change: 2.1%; 95% CI: 1.2% to 3.0%) increased clearly in both age groups. There was some heterogeneity across the centers among adolescents, especially for allergic rhinitis, with larger increases seen in the 3 metropolitan areas. The changes observed paralleled profound family changes, ie, better parental education, higher rates of maternal employment, and lower rates of exposure to parental smoke. These factors, however, do not explain all of the observed changes in prevalence. CONCLUSIONS: The results indicate that the epidemiologic features of asthma and allergies in Italy are changing rapidly, although the causes are still uncertain.

Adolescent↗

PubMed2005

Long-term oxygen therapy in chronic respiratory failure: a Multicenter Italian Study on Oxygen Therapy Adherence (MISOTA).

BACKGROUND: The adherence to the prescribed oxygen therapy is difficult to obtain for patients on long-term oxygen therapy (LTOT). There is little information on the modalities of oxygen utilisation for patients on LTOT who are using liquid oxygen in real life. STUDY OBJECTIVE: Evaluation of the behaviour and the knowledge regarding LTOT in a large group of patients mainly using liquid oxygen. DESIGN AND SETTING: Questionnaire administered to consecutive outpatients on domiciliary LTOT for at least 6 months referring to one of 20 clinics throughout Italy. Blinded to this result, the physician who cared for the patient completed another questionnaire. RESULTS: We evaluated 1504 patients (mean age 71.6 years; males 64%; 74% suffering from COPD). Most respondents (93%) used liquid oxygen with mobile device. Fifteen per cent of patients had a prescribed length of oxygen therapy less than 15 h/day; 21% reported to practice oxygen for less than 15 h/day. Patients reported using oxygen for less hours than had been prescribed during the day at rest (P=0.02, k=0.80) during exercise (P=0.002, k=0.72) and at night (P=0.0036, k=0.77). There was no difference between the flow prescribed by the physician and that known and practised by the patient at rest or during sleep; during exercise the flow reported by patients was lower than that prescribed by the physician. Patients used in the night but not at rest or during exercise, a lower level of oxygen flow than what they knew had been prescribed. Fifty-five per cent of patients received indications to modify the oxygen flow in the various situations of life. Liquid oxygen was almost always useful to decrease breathlessness. Most (84%) patients possessed a mobile device, but only 40% declared they used it daily, 'shame' being indicated as the principal barrier. On the physicians' side, we found that the criteria used in prescribing did not always correspond to evidence-based recommendations. CONCLUSION: The widespread use of liquid oxygen did not automatically assure optimal adherence to the prescribed treatment as regards times and modality of oxygen use. A better education of patients, relatives, and the general public, as well as increased self-assessment on the part of health caregivers would improve the practice of LTOT in Italy.

Aged↗

PubMed2004

Gene expression profiling reveals novel TGFbeta targets in adult lung fibroblasts.

BACKGROUND: Transforming growth factor beta (TGFbeta), a multifunctional cytokine, plays a crucial role in the accumulation of extracellular matrix components in lung fibrosis, where lung fibroblasts are considered to play a major role. Even though the effects of TGFbeta on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown. METHODS: We used Affymetrix oligonucleotide microarrays U95v2, containing approximately 12,000 human genes, to study the transcriptional profile in response to a four hour treatment with TGFbeta in control lung fibroblasts and in fibroblasts from patients with idiopathic and scleroderma-associated pulmonary fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5) and of analysis of variance models was used to identify TGFbeta-regulated genes. Additional criteria were an average up- or down- regulation of at least two fold. RESULTS: Exposure of fibroblasts to TGFbeta had a profound impact on gene expression, resulting in regulation of 129 transcripts. We focused on genes not previously found to be regulated by TGFbeta in lung fibroblasts or other cell types, including nuclear co-repressor 2, SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), bone morphogenetic protein 4, and angiotensin II receptor type 1 (AGTR1), and confirmed the microarray results by real time-PCR. Western Blotting confirmed induction at the protein level of AGTR1, the most highly induced gene in both control and fibrotic lung fibroblasts among genes encoding for signal transduction molecules. Upregulation of AGTR1 occurred through the MKK1/MKK2 signalling pathway. Immunohistochemical staining showed AGTR1 expression by lung fibroblasts in fibroblastic foci within biopsies of idiopathic pulmonary fibrosis. CONCLUSIONS: This study identifies several novel TGFbeta targets in lung fibroblasts, and confirms with independent methods the induction of angiotensin II receptor type 1, underlining a potential role for angiotensin II receptor 1 antagonism in the treatment of lung fibrosis.

Cells, Cultured↗

PubMed2004

Inhalation technique and variables associated with misuse of conventional metered-dose inhalers and newer dry powder inhalers in experienced adults.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) are often poorly used, but little information is available concerning use of the newer dry powder inhalers (DPIs). OBJECTIVE: To estimate the inhalation technique and variables associated with the misuse of pMDIs and newer DPIs in clinical practice. METHODS: A multicenter, observational survey was used to evaluate the inhalation technique in 1,404 experienced outpatients aged 15 to 88 years affected mostly by asthma (47%) and chronic obstructive pulmonary disease (39%). A total of 1,056 patients were using pMDIs, 190 in conjunction with a large volume spacer (LVS); regarding DPIs, 230 patients were using the Aerolizer Inhaler, 524 were using the Turbuhaler, and 475 were using the Diskus. In each center, a trained observer recorded patients' inhalation techniques for each inhaler used against a standardized step-by-step checklist. RESULTS: Twenty-four percent and 3% of patients used pMDIs poorly, alone or with an add-on LVS, respectively. Failure to correctly perform essential steps for reliable lung delivery with the Aerolizer Inhaler, Turbuhaler, and Diskus was found in 17%, 23%, and 24% of patients, respectively. There was no difference in most variables correlated with poor inhalation between patients using pMDIs and those using DPIs. CONCLUSIONS: The use of DPIs is associated with a similar percentage of inadequate inhalation technique as the use of pMDIs in clinical practice. The addition of an LVS to a pMDI and education from health care personnel, rather than simply changing inhalers, represent the best strategies for minimizing poor inhalation technique.

Administration, Inhalation↗

PubMed2003

C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome.

Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host's genetic susceptibility. We hypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-Löfgren sarcoidosis, 47 Löfgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1-9). In patients with Löfgren's syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position -6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p < 0.0001), whereas no difference was found between non-Löfgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and Löfgren's syndrome (odds ratio, 4.4; p < 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p < 0.0001) and female sex (odds ratio, 3.2; p = 0.003), two known risk factors for Löfgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and Löfgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.

Arthralgia↗

PubMed2002

Interstitial vascularity in fibrosing alveolitis.

The aim of this study was to evaluate interstitial vascularity in cryptogenic fibrosing alveolitis (CFA) and in fibrosing alveolitis associated with systemic sclerosis (FASSc). Open lung biopsies from eight patients with CFA, nine patients with FASSc, and normal lung from 12 patients undergoing surgery for lung cancer were studied. Markers for endothelial cells (CD34) and cell proliferation (proliferating cell nuclear antigen) were localized by sequential immunohistochemistry and quantified using computer-assisted analysis. Vascular distribution was evaluated at increasing distances (up to 160 microm) from the airspaces. Vessel density was markedly reduced in both FASSc (3.9%) and in CFA (4.5%) compared with control samples (20.4%, p < 0.0001). The percentage of tissue occupied by vessels decreased with increasing distance from alveoli in control samples but not in CFA or FASSc samples. Endothelial cell proliferation indices were increased in FASSc but not in CFA, compared with control samples (p = 0.006). In conclusion, there is net vascular ablation and redistribution of blood vessels in areas of interstitial thickening in both CFA and FASSc, which may contribute to gas exchange impairment.

Adult↗

PubMedDate not supplied

[Environmental, social and demographic characteristics of children and adolescents, resident in different Italian areas].

The second phase of the SIDRIA study provides important information regarding the family characteristics of Italian children (6-7 years old) and adolescents (13-14 years old), and the frequency of risk factors for asthma and allergies, allowing comparisons between study areas according to differences in latitude (North, Centre, South) and urbanization level (metropolitan areas, with at least 500,000 inhabitants, and other areas). Parental education level was higher in metropolitan and central areas. The frequency of children and adolescents born abroad, and the percentage of mothers and fathers employed were higher outside metropolitan areas and there was an increase from the South to the North of Italy. This trend was paralleled by an increase in maternal age at child's birth and in the frequency of low birth weight and day care attendance. The frequency of breastfeeding was greater in children than in adolescents; the opposite was registered for passive smoking, with a frequency of exposure higher in adolescents than in children, especially in the Northern and Central areas, even if the proportion of subjects having at least one parent who smokes was still high in both age groups. The prevalence of overweight children was striking, especially in the South where physical activity was less frequent and children had the unhealthy habit of consuming a lot of snacks and carbonated beverages. Frequency of exposure to traffic in the area of residence was particularly high, especially in the metropolitan areas.

Adolescent↗

PubMedDate not supplied

[Frequency of asthma and allergies in Italian children and adolescents: results from SIDRIA-2].

The present study investigated the prevalences of asthma, allergic rhinitis (both to pollen and to other causes) and eczema in Italian children (6-7 yr old) and adolescents (13-14 yr old) in the second phase of SIDRIA (2002), aiming also to highlight geographical differences in the prevalence of the studied diseases. Prevalence of lifetime asthma is 9.3% in children and 10.3% in adolescents; lifetime prevalences of allergic rhinitis and eczema are 12.3% and 15.9% in children, 20.9% and 11.9% in adolescents. In both age groups, prevalence of lifetime asthma and lifetime and past 12 months wheezing was greater in central than in northern and southern areas. A similar situation was also seen for allergic rhinitis but not for eczema whose prevalence decreased between North to South of Italy. An excess in prevalence of lifetime asthma and rhinitis was found in metropolitan areas compared to other areas; prevalence of eczema did not show any difference by urbanization level. Prevalence of asthma and, only in children, prevalence of rhinitis symptoms was greater in males than in females. On the contrary, prevalence of eczema and, only in adolescents, prevalence of rhinitis symptoms was greater in females. Prevalence of childhood asthma, allergic rhinitis and eczema in Italy ranks intermediate with respect to other countries participating in ISAAC phase three.

Adolescent↗

PubMedDate not supplied

[Asthma attacks at school in Italian adolescents].

We evaluated the occurrence of asthma attacks at school in a sample of 13,266 adolescents (13-14 year old) from 12 centers across Italy (SIDRIA-2 study). 23.8% of asthmatic subjects reported at least one wheezing attack at school in the previous 12 months. The attacks occurred in the gymnasium (55.4%), in the classroom (42.6%), outside (28.7%), in the bathroom (4.5%) and in other school environments (4%). During the attacks, self-administration of a bronchodilator was reported by 66% of the subjects. Educational programs and specific guidelines to deal with asthmatic schoolchildren are warranted.

Adolescent↗

PubMedDate not supplied

[Changes in social characteristics and risk factors for asthma and allergies among children and adolescents in Italy].

One of the main objectives of SIDRIA-2 study was to evaluate the possible changes in the occurrence of social characteristics and risk factors for asthma and allergies in childhood, comparing the data obtained in 2002 to those collected in 1994-1995. A positive change in socio-economic characteristics of the childrens' and adolescents' families was generally observed. The levels of exposure to outdoor (traffic) and indoor (passive smoking) pollutants are still high, although a decreasing trend in parents' smoking habits is evident.

Adolescent↗

PubMedDate not supplied

[Trends in the frequency of asthma and allergies].

The increase in the prevalence of asthma and allergies observed during the last decades has been largely investigated, but the reasons for such trend are still unclear. The distribution of factors traditionally considered responsible of the allergic disorders (such as pollen or moulds), do not explain the geographical differences observed internationally in the prevalence of asthma and allergies. The conduction of new studies aimed at monitoring the trend in asthma and allergies, and in the risk factors associated with these disorders, such as the SIDRIA study (Italian Studies on Respiratory Disorders in Children and the Environment), will shed new light on this phenomenon.

Adolescent↗