Salvatore Leonardi

Emerging pathogens in cystic fibrosis: ten years of follow-up in a cohort of patients

In patients with cystic fibrosis (CF), there is an increasing incidence of some uncommon respiratory pathogens, such as Burkholderia cepacia complex (Bcc), Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. In order to evaluate the prevalence and the clinical impact of these pathogens, we retrospectively studied a total of 109 patients followed in our center from 1996 to 2006 and reviewed the results of 1,550 sputum samples. The isolation of Pseudomonas aeruginosa slightly decreased over the observed decade, whereas Staphylococcus aureus exhibited an irregular trend. Infection with Bcc reached a peak in 1998 and successively decreased to a stable 4%. S. maltophilia and A. xylosoxidans were the real emerging pathogens, since first isolation occurred in 2004; however, the percentage of infected patients remained low (7% and 3.2%, respectively) through the years. In conclusion, in our center for CF, the reduced prevalence of P. aeruginosa over the last decade has been associated with a concurrent reduction of infections by Bcc and, as compared to other centers in Italy, Europe, and the US, with a low incidence of emerging pathogens such as S. maltophilia and A. xylosoxidans.

Forest management and plant species diversity in chestnut stands of three Mediterranean areas

Over many centuries, chestnut fruits had an important role as food, while chestnut wood was used for local purposes. Today sweet chestnut stands are very common around the western Mediterranean Basin, and it is necessary to analyze the dynamic of plant species diversity in different chestnut stand types (groves and coppices) to guide management strategies that will allow the conservation of biodiversity. Our objective was to analyze consequences on plant species diversity of various management strategies in chestnut stands of three Mediterranean areas, Salamanca (Spain), the Cevennes (France), and Etna volcano (Italy). We found that plant species diversity is different according to management types; it is higher in groves than in coppice stands. We also demonstrated that Castanea sativa cultivated groves were characterized by small heliophillous therophytes. C. sativa abandoned groves, mixed C. sativa-Quercus pyrenaica coppice stands, Q. pyrenaica coppice stands, and young C. sativa coppice stands were characterized by hemicryptophytes with anemochorous dispersal mode and chamaephytes. Medium and old C. sativa coppice stands (that differ by the shoot age) were characterized by phanerophytes with zoochorous dispersal mode. Human perturbations maintain a quite high level of species diversity. In contrast, the abandonment of chestnut stands leads to homogeneous vegetation with decreasing diversity. One solution could be to maintain a landscape mosaic constituted of diverse chestnut stands modified by human activities (groves, cultivated or abandoned, and coppice stands). This could enhance regional plant diversity.

Allergic conjunctivitis: a comprehensive review of the literature

Ocular allergy represents one of the most common conditions encountered by allergists and ophthalmologists. Allergic conjunctivitis is often underdiagnosed and consequently undertreated. Basic and clinical research has provided a better understanding of the cells, mediators, and immunologic events, which occur in ocular allergy. New pharmacological agents have improved the efficacy and safety of ocular allergy treatment. An understanding of the immunologic mechanisms, clinical features, differential diagnosis, and treatment of ocular allergy may be useful to all specialists who deal with these patients. The purpose of this review is to systematically review literature underlining all the forms classified as ocular allergy: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratocongiuntivitis, contact allergy, and giant papillary conjunctivitis.

Hepatitis B vaccination failure in celiac disease: is there a need to reassess current immunization strategies?

Human leukocyte antigen (HLA) phenotype DQ2 is considered the most important genetic marker for un-responsiveness to hepatitis B vaccine. Since celiac disease (CD) is also strongly associated with the same haplo-type it may be hypothesized that celiac patients are less able to respond to the vaccine. We report a retrospective study on celiac patients vaccinated with three doses of 10 microg at 3, 5 and 11 months of age by an intramuscular injection of a recombinant hepatitis B vaccine (Engerix B). We found 30 of 60 celiac patients (50%) unresponsive to vaccination and a significant higher number of responders among patients younger than 18 months at the time of celiac disease diagnosis. Our study confirms that celiac patients have a lower percentage of response to hepatitis B vaccination than healthy subjects. These findings provide useful information to evaluate if current vaccine strategies should be reassessed and if revaccination should be recommended.

Liver expression in cystic fibrosis could be modulated by genetic factors different from the cystic fibrosis transmembrane regulator genotype.

During a multicentric study conducted in Southern Italy, we studied five sets of cystic fibrosis siblings bearing a strongly discordant liver phenotype, three with genotype DeltaF508/R553X, one with genotype DeltaF508/unknown, and one with genotype unknown/unknown. The siblings of each set were raised in the same family environment, and there were no interpair differences in nutritional state or in therapy compliance. All siblings had pancreatic insufficiency and moderate respiratory expression. One sibling of each of the five sets was free of liver involvement, and the other had severe liver expression. Other causes of liver disease (viral, metabolic, and genetic other than cystic fibrosis) were ruled out. Therefore, environmental factors, nutritional state, and therapy compliance are not involved in the liver expression of cystic fibrosis in the five unrelated sibships. This suggests that modifier genes, inherited independently of the cystic fibrosis transmembrane regulator gene, could modulate the liver expression in cystic fibrosis patients.

Hypertransaminasemia as the first symptom in infant celiac disease.

Two infants admitted for evaluation of hypertransaminasemia had high levels of anti-gliadin IgA and IgG antibodies and histological changes of the duodenal mucosa typical of celiac disease. Although the cause of the liver involvement could not be exactly identified, both the hypertransaminasemia and the histological changes of the mucosa disappeared after a short period of gluten-free diet. Even though two cases are not enough for definite conclusions, the authors suggest that an unexplained increase in transaminases would require an evaluation for celiac disease.

TLR2 and TLR4 gene polymorphisms and atopic dermatitis in Italian children: a multicenter study.

Background Genetic factors have an important role in atopic dermatitis (AD) predisposition. Toll like receptor (TLR) are important mediators between environment and immune system. There are incosnsitent studies about TLSR polymorphisms in AD. Objective This study examined whether single nucleotide polimorphisms (SNPs) in the genes for TLR2 and TLR4 could be associated with the AD phenotypes and with its clinical severity in a large group of Italian children. Methods 187 children with Ad and 150 healthy children were recruited. AD severity was assessed by SCORAD. TLR2 (A-16934T and R753Q polymorphisms) and TLR4 (D299G and T399I SNPs) were genotyped by PCR-RFLP. Results The frequency of the R753Q was significantly higher in AD children (16.0%) compared with controls (6.0%, P=0.004; OR2.99,95%CI 1.39–6.41; RR 1.46,95%CI 1.14–1.69). AD patients a significantly different frequency of the D299G SNP (14.9%) in comparison with the controls (6.6%, P = 0.01; OR 2.46, 95%CI 1.17–5.17; RR 2.24; 95%CI 1.15–4.45). Conclusion Children with AD may have a distinct genotype and the TLR-2 R753Q SNP was prevalent in a subset of patients with AD characterized by a more severe clinical picture.

Probiotics and food allergy.

The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the “hygiene hypothesis” low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions.Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells.Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.

Protein C and Antithrombin III in Polytransfused Thalassemic Patients

Seventy-four patients with beta-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p less than 0.02). PC correlated with age (p less than 0.001), transfusional iron (p less than 0.001) and ferritin (p less than 0.001). It also correlated with serum albumin (p less than 0.001), prothrombin time (p less than 0.001) and fibrinogen (p less than 0.02) and with serum transaminases (GPT) (p less than 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III.

Effectiveness of nebulized hypertonic saline and epinephrine in hospitalized infants with bronchiolitis.

The objective of the study is to verify effects of nebulized 3% saline hypertonic solution (HS) in comparison to normal saline (NS) in addition to epinephrine in hospitalized children with bronchiolitis. Infants were randomly assigned either to receive every 6 hours nebulized NS (group I) or 3% HS (group II) in addition to epinephrine (1.5 mg) and to conventional treatment. The main endpoints of this study were the length of stay (LOS) in hospital and the clinical response score (CSS). Patients presented a significant decrease in CSS from the first through the third day of treatment, present in the first group but even more evident in the second group (p=0.0001). Comparison between group I and II data shows significant decrease in CSS in the 3% HS-treated patients both at the second (p<0.005) and at the third day of treatment (p<0.005). Infants in the NS control group had a mean LOS of 5.6±1.6 days, whereas children treated with 3% HS were discharged with a LOS of 4.9±1.3 days, reaching a significant decrease in stay (p<0.05). In hospitalized patients bronchiolitis nebulized 3% HS and epinephrine significantly decreased symptoms and LOS as compared to 0.9% NS and epinephrine.