Erica Nazzari

Possible molecular mechanisms linking air pollution and asthma in children

BackgroundAir pollution has many effects on the health of both adults and children, but children’s vulnerability is unique. The aim of this review is to discuss the possible molecular mechanisms linking air pollution and asthma in children, also taking into account their genetic and epigenetic characteristics.ResultsAir pollutants appear able to induce airway inflammation and increase asthma morbidity in children. A better definition of mechanisms related to pollution-induced airway inflammation in asthmatic children is needed in order to find new clinical and therapeutic strategies for preventing the exacerbation of asthma. Moreover, reducing pollution-induced oxidative stress and consequent lung injury could decrease children’s susceptibility to air pollution. This would be extremely useful not only for the asthmatic children who seem to have a genetic susceptibility to oxidative stress, but also for the healthy population. In addition, epigenetics seems to have a role in the lung damage induced by air pollution. Finally, a number of epidemiological studies have demonstrated that exposure to common air pollutants plays a role in the susceptibility to, and severity of respiratory infections.ConclusionsAir pollution has many negative effects on pediatric health and it is recognised as a serious health hazard. There seems to be an association of air pollution with an increased risk of asthma exacerbations and acute respiratory infections. However, further studies are needed in order to clarify the specific mechanism of action of different air pollutants, identify genetic polymorphisms that modify airway responses to pollution, and investigate the effectiveness of new preventive and/or therapeutic approaches for subjects with low antioxidant enzyme levels. Moreover, as that epigenetic changes are inheritable during cell division and may be transmitted to subsequent generations, it is very important to clarify the role of epigenetics in the relationship between air pollution and lung disease in asthmatic and healthy children.

Nasopharyngeal Biofilm-Producing Otopathogens in Children with Nonsevere Recurrent Acute Otitis Media

Objective. Bacterial biofilms have been detected in biopsies of the adenoid and middle ear mucosa of otitis-prone children and children with chronic middle otitis media. However, the invasiveness of biopsy makes it unsuitable for routine clinical practice, especially in pediatrics. This study aimed to investigate nasopharyngeal biofilm-producing otopathogens (BPOs) of nasopharyngeal swabs (NPS) in children with a history of nonsevere recurrent acute otitis media (RAOM) and healthy controls. Study Design. A cross-sectional study with planned data collection. Setting. University of Milan. Subjects and Methods. Transoral NPS were taken from infants and children aged 10 months to 11 years with nonsevere RAOM or healthy controls without adenoid hypertrophy. Nasopharyngeal colonization by otopathogens was assessed by means of microbiological cultures and standard bacterial identification, as well as nasopharyngeal BPOs by means of spectrophotometric analysis. Results. The study involved 113 children (56.6% males; median age 40 months; range, 10-132 months): 58 with a history of nonsevere RAOM (51.3%) and 55 controls (48.7%). Otopathogens were significantly more frequently detected in the RAOM group (24/58, 41.4%) than in controls (8/55, 14.5%; P = .003); the main pathogens were respectively Haemophilus influenzae (12/24, 50.0%) and Streptococcus pyogenes (3/8, 37.5%). Nasopharyngeal BPOs were more frequently isolated in the RAOM group (17/58, 29.3%) than in controls (6/55, 10.9%; P = .02). H influenzae (12/17, 70.6%) was confirmed as the main pathogen in the RAOM group. Conclusion. The presence of nasopharyngeal BPOs is an important factor favoring RAOM; it is therefore useful investigating biofilms even in children with nonsevere recurrences of AOM without adenoid hypertrophy.

Medical Education and Attitudes About Acute Otitis Media Guidelines : A Survey of Italian Pediatricians and Otolaryngologists

Background: Medical education and guidelines have been advocated as major means of improving the management of otitis media. Limited data are available concerning medical education in acute otitis media (AOM), and the association between medical education and attitudes about AOM guidelines has never been explored. Objectives: To assess the prevalence of medical education concerning AOM, of a positive attitude toward AOM guidelines and of appropriate diagnostic methods in a large sample of Italian pediatricians (PEDs) and otolaryngologist (ENTs) and to look for possible associations between them. Subjects and Methods: This cross-sectional survey was based on the responses of 2012 physicians (1160 PEDs and 852 ENTs) to a mailed anonymous questionnaire. Results: Very few (9%) of the responders had received any AOM medical education during medical school, but the number increased during residency (38%) and peaked in the postresidency period (53%) with slight differences between PEDs and ENTs. Forty percent reported a positive attitude toward AOM guidelines, with PEDs having a better attitude than ENTs (46% vs. 32%, P < 0.001). An appropriate diagnostic method for AOM was reported by only 21% of the physicians (PEDs 11% vs. ENTs 35%, P < 0.001). AOM medical education during postresidency and reporting the use of appropriate diagnostic methods were significantly associated with a positive attitude about AOM guidelines. Conclusions: Specific educational programs concerning AOM should be implemented and rigorously evaluated, before physicians become fully trained PEDs and ENTs, and maintained during postresidency. Evidence-based guidelines should be further incorporated into everyday practice of both PEDs and ENTs.

Efficacy of injectable trivalent virosomal-adjuvanted inactivated influenza vaccine in preventing acute otitis media in children with recurrent complicated or noncomplicated acute otitis media.

Background: Most cases of acute otitis media (AOM) follow an upper respiratory infection due to viruses, including influenza viruses. As effective and safe influenza vaccines are available, their use has been considered among the possible measures of AOM prophylaxis. Objectives: To evaluate the efficacy of an inactivated virosomal-adjuvanted influenza vaccine in preventing AOM in children with a history of noncomplicated recurrent AOM (rAOM) or rAOM complicated by spontaneous perforation. Methods: In this prospective, randomized, single-blinded, placebo-controlled study, 180 children aged 1 to 5 years with a history of rAOM and previously unvaccinated against influenza were randomized to receive the inactivated virosomal-adjuvanted subunit influenza vaccine (n = 90) or no treatment (n = 90), and AOM-related morbidity was monitored every 4 to 6 weeks for 6 months. Results: The number of children experiencing at least 1 AOM episode was significantly smaller in the vaccinated group (P < 0.001), as was the mean number of AOM episodes (P = 0.03), the mean number of AOM episodes without perforation (P < 0.001), and the mean number of antibiotic courses (P < 0.001); the mean duration of bilateral OME was significantly shorter (P = 0.03). The only factor that seemed to be associated with the significantly greater efficacy of influenza vaccine in preventing AOM was the absence of a history of recurrent perforation (crude odds ratio, P = 0.01; adjusted odds ratio, P = 0.006). Conclusions: The intramuscular administration of injectable trivalent inactivated virosomal-adjuvanted influenza vaccine in children with a history of rAOM significantly reduces AOM-related morbidity. However, the efficacy of this preventive measure seems to be reduced in children with rAOM associated with repeated tympanic membrane perforation.

Adenovirus 36 infection and obesity

The most important factors leading to fat accumulation in children are genetic inheritance, endocrine alterations, and behavioural/environmental causes. In addition, experimental animal studies have shown that infections due to various pathogens can lead to overweight and obesity conditions, and studies of humans have found that the incidence of seroconversion against some of these may be significantly more frequent in obese adults and children than in normal subjects. However, the results of these studies are not conclusive and, in some cases, have raised more questions than answers. We reviewed the literature concerning the role of adenovirus 36 (AD-36), the most widely studied infectious agent in animals and humans, because of its potential association with childhood obesity. The available evidence suggests that more studies are needed to evaluate whether or not the association between the presence of AD-36 antibodies and obesity is simply unrelated, and to verify whether there are subjects that have greater tendency to become obese because more easily susceptible to AD-36 infection or with a predisposition to suffer from persistent viral infection more easily leading to the development of obesity. If it is demonstrated that AD-36 does play a role in obesity, it will be important to investigate possible vaccines against the infection itself or antiviral drugs capable of inhibiting disease progression.

Role of biofilm in children with recurrent upper respiratory tract infections

Recurrent respiratory tract infections (RRTIs) are very common in children and a major challenge for pediatricians. In the last few years, bacterial biofilms have been linked to RRTIs and antibiotic resistance, and have raised serious concerns regarding the therapeutic management of recurrent middle ear diseases, chronic rhinosinusitis, and recurrent pharyngotonsillitis. This paper aims to review the new insights into biofilm-related upper respiratory tract infections in children and possible therapeutic strategies. It focuses on the clinical implications for recurrent disease and on studies in pediatric patients. Analysis of the literature showed that the involvement of bacterial biofilm in recurrent upper airway tract infections is an emerging problem that may lead to serious concerns about infection control. Despite the large amount of research within this field, detailed insight into the complex structure of bacterial biofilms and the ultrastructural and biochemical mechanisms responsible for its evasion of the immune system and resistance to treatments is currently lacking. In the future, additional emphasis should be placed on biofilm management as a component of therapeutic strategies. This goal can be attained by finding feasible methods for detecting biofilms in vivo and identifying effective methods for administering treatments that eradicate preexisting bacterial biofilms or hinder bacterial adhesion to respiratory cells.

Effectiveness of a propolis and zinc solution in preventing acute otitis media in children with a history of recurrent acute otitis media

Recurrent acute otitis media (rAOM) is frequently encountered in infants and children and the lack of any definitive treatment has led parents and physicians to try complementary and alternative therapies. We evaluated the efficacy of a propolis and zinc suspension in preventing AOM in 122 children aged 1–5 years with a documented history of rAOM, who were prospectively, blindly, randomized 1:1 to receive the suspension plus elimination of environmental risk factors or elimination of environmental risk factors only. AOM- and respiratory-related morbidity were assessed at study entry and every four weeks. In the 3-month treatment period AOM was diagnosed in 31 (50.8%) children given the propolis and zinc suspension and in 43 (70.5%) controls (p=0.04). The mean number of episodes of AOM per child/month was 0.23 ± 0.26 in the propolis and zinc group and 0.34 ± 0.29 in controls (reduction 32.0%, p=0.03). The administration of a propolis and zinc suspension to children with a history of rAOM can significantly reduce the risk of new AOM episodes and AOM-related antibiotic courses, with no problem of safety or tolerability, and with a very good degree of parental satisfaction. No effect can be expected on respiratory infections other than AOM.

Clinical assessment of adenoidal obstruction based on the nasal obstruction index is no longer useful in children

Objective: To evaluate the accuracy of clinical assessment of adenoidal obstruction based on a standardized score of the degree of mouth breathing and speech hyponasality (nasal obstruction index [NOI]) in comparison to nasal fiberoptic endoscopy. Study Design: Cross-sectional study with planned data collection. Setting: Outpatient clinics of the Departments of Maternal and Pediatric Sciences and Specialized Surgical Sciences, University of Milan, Italy. Subjects and Methods: Children aged three to 12 years with adenoidal obstruction suspected on the grounds of persistent/recurrent otitis media or perceived obstructive nasal breathing were eligible. Ear, nose, and throat examination, allergy testing, NOI measurement, and nasal fiberoptic endoscopy to assess the degree of adenoidal hypertrophy were performed. Agreement between the NOI and adenoidal hypertrophy grade was assessed in the patients as a whole and by clinical subgroups. Results: A total of 202 children were enrolled: 54.9 percent had otological diseases and 45.1 percent had perceived obstructive nasal breathing. Most of the children (79.2%) showed mild or moderate clinical nasal obstruction. Adenoidal hypertrophy ranged from no obstruction (18%) to severe obstruction (38%). There was no substantial agreement between the NOI and the degree of adenoidal obstruction in the population as a whole and in all the clinical subgroups. False positive findings were significantly more frequent among allergic children (50%) than non-allergic children (22.4%, P = 0.009). Conclusion: Clinical assessment based on the NOI is incapable of accurately predicting the degree of adenoidal obstruction. In children with clinical nasal obstruction not explainable by adenoidal size, the clinician should consider, among causes of more anterior obstruction, nasal allergy.

Medical prevention of recurrent acute otitis media: an updated overview

Acute otitis media (AOM) is one of the most common pediatric diseases; almost all children experience at least one episode, and a third have two or more episodes in the first three years of life. The disease burden of AOM has important medical, social and economic effects. AOM requires considerable financial assistance due to needing at least one doctor visit and a prescription for antipyretics and/or antibiotics. AOM is also associated with high indirect costs, which are mostly related to lost days of work for one parent. Moreover, due to its acute symptoms and frequent recurrences, AOM considerably impacts both the child and family’s quality of life. AOM prevention, particularly recurrent AOM (rAOM), is a primary goal of pediatric practice. In this paper, we review current evidence regarding the efficacy of medical treatments and vaccines for preventing rAOM and suggest the best approaches for AOM-prone children.

Genetic polymorphisms of functional candidate genes and recurrent acute otitis media with or without tympanic membrane perforation

Abstract Evaluation of the genetic contribution to the development of recurrent acute otitis media (rAOM) remains challenging. This study aimed to evaluate the potential association between single nucleotide polymorphisms (SNPs) in selected genes and rAOM and to analyze whether genetic variations might predispose to the development of complicated recurrent cases, such as those with tympanic membrane perforation (TMP). A total of 33 candidate genes and 47 SNPs were genotyped in 200 children with rAOM (116 with a history of TMP) and in 200 healthy controls. INF&ggr; rs 12369470CT was significantly less common in the children with rAOM than in healthy controls (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.25–1, P = 0.04). Although not significant, interleukin (IL)-1&bgr; rs 1143627G and toll-like receptor (TLR)-4 rs2737191AG were less frequently detected in the children with rAOM than in controls. The opposite was true for IL-8 rs2227306CT, which was found more frequently in the children with rAOM than in healthy controls. The IL-10 rs1800896TC SNP and the IL-1&agr; rs6746923A and AG SNPs were significantly more and less common, respectively, among children without a history of TMP than among those who suffered from this complication (OR 2.17, 95% CI 1.09–4.41, P = 0.02, and OR 0.42, 95% CI 0.21–0.84, P = 0.01). This study is the first report suggesting an association between variants in genes encoding for factors of innate or adaptive immunity and the occurrence of rAOM with or without TMP, which confirms the role of genetics in conditioning susceptibility to AOM.