Mara Lelii

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.

Prospective evaluation of rhinovirus infection in healthy young children.

BACKGROUND Although the incidence of human rhinovirus (HRV) infection is highest in young, no study has yet been published concerning the types of HRV circulating in this population, the incidence of symptomatic infections due to the different types, or duration of shedding OBJECTIVES This prospective study evaluated the circulation of HRV species and types, and established the incidence of asymptomatic and symptomatic infections in young children. STUDY DESIGN The study enrolled 93 healthy children aged <2 years, 88 of whom completed the follow-up of weekly household visits from November 2013 to February 2014. At each visit, a record was made of any signs and symptoms of acute infection, and a nasopharyngeal (NP) swab was taken in order to identify the HRVs by means of RT-polymerase chain reaction and to construct the phylogenetic tree of the HRV-positive cases. RESULTS A total of 1408 NP samples were obtained and 326 HRV infections were diagnosed (23.1%), leading to a mean number of 3.7 ± 2.3 infections per child: HRV-A in 72 cases (22.1%), HRV-B in 29 (8.9%), HRV-C in 122 (37.4%), and non-typeable HRV in 103 (31.6%). Shedding was significantly longer for HRV-A (14 days) and HRV-B (14 days) than HRV-C (7 days; p = 0.002 and p = 0.012). Most of the HRV infections (209/326, 64.1%) remained asymptomatic and, when symptomatic, were of marginal clinical relevance. CONCLUSIONS In healthy young children, HRV infection is extremely frequent, generally asymptomatic or with a mild clinical presentation, and viral shedding is limited in time.

Streptococcus pneumoniae oropharyngeal colonization in children and adolescents with cystic fibrosis

BACKGROUND This study was designed to evaluate Streptococcus pneumoniae (S. pneumoniae) carriage rates in patients with cystic fibrosis (CF). METHODS An oropharyngeal swab was obtained from 212 CF children and adolescents enrolled during routine clinical visits. DNA from swabs was analyzed by real-time polymerase chain reaction. RESULTS A total of 42 (19.8%) CF patients (mean age±standard deviation [SD], 12.0±3.3years) were colonized by S. pneumoniae. Carriage was more common in younger patients and tended to decline with age. Administration of systemic and/or inhaled antibiotics in the last 3months significantly correlated with a reduced carrier state [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.69, and OR 0.26, 95% CI 0.08-0.77, respectively]. Vitamin D serum levels ≥30ng/mL were less common in carriers than that in non-carriers (OR 0.35; 95% CI 0.08-1.49). In both the vaccinated and unvaccinated subjects, serotypes 19F, 5, 4, and 9V were the most commonly carried serotypes. CONCLUSIONS S. pneumoniae carrier state of school-age children and adolescents with CF is more prevalent than previously thought, and pneumococcal conjugate vaccination administered in the first year of life does not reduce the risk of re-colonization in later childhood and adolescence.

Antibody response to respiratory syncytial virus infection in children <18 months old

ABSTRACT The development of a safe and effective respiratory syncytial virus (RSV) vaccine might be facilitated by knowledge of the natural immune response to this virus. The aims of this study were to evaluate the neutralizing antibody response of a cohort of healthy children <18 months old to RSV infection. During the RSV season, 89 healthy children <18 months old were enrolled and followed up weekly for 12 weeks. At each visit, a nasopharyngeal swab was obtained for RSV detection by real-time polymerase chain reaction (PCR). During the study period, 2 blood samples were drawn and they were used to determine RSV geometric mean neutralizing antibody titres (GMT) against RSV. A total of 35 (39.3%) children had RSV detected during the study period. Among RSV-positive patients, children ≥7 months showed a significantly higher increase in antibody response (p<0.001). A significantly higher number of patients with a ≥4 -fold increase in GMT were ≥7 months old (p = 0.02) and presented lower respiratory tract infections (LRTIs) during the study period (p = 0.01). Viral shedding was longer among children aged ≥7 months (p = 0.06), those with viral load ≥106 copies/mL (p = 0.03), and those with LRTIs during the study period (p = 0.03), but it was not associated with the immune response (p = 0.41). In conclusion, natural RSV infection seems to evoke a low immune response in younger children. To be effective in this infant population, which is at highest risk of developing severe LRTIs, vaccines must be able to induce in the first months of life a stronger immune response than that produced by the natural infection.

Impact of genetic polymorphisms on paediatric atopic dermatitis

In order to investigate whether polymorphisms of genes encoding some factors of innate and adaptive immunity play a role in the development of, or protection against atopic dermatitis (AD) and condition its severity, we genotyped 33 candidate genes and 47 single nucleotide polymorphisms (SNPs) using Custom TaqMan Array Microfluidic Cards and an ABI 7900HT analyser (Applied Biosystems, Foster City, CA, USA). The study involved 104 children with AD (29 with mild-to-moderate and 75 with severe disease; 42 girls; mean age ± SD, 5.8 ± 3.3 years) and 119 healthy controls (49 girls; mean age, 4.8 ± 3.0 years). IL10-rs1800872T, TG and MBL2-rs500737AG were all significantly more frequent among the children with AD (P = 0.015, P = 0.004 and P = 0.030), whereas IL10-rs1800896C and TC were more frequent in those without AD (P = 0.028 and P = 0.032). The VEGFA-rs2146326A and CTLA4-rs3087243AG SNPs were significantly more frequent in the children with mild/moderate AD than in those with severe AD (P = 0.048 andP = 0.036). IL10-rs1800872T and TG were significantly more frequent in the children with AD and other allergic diseases than in the controls (P = 0.014 and P = 0.007), whereas IL10-rs1800896TC and C were more frequent in the controls than in the children with AD and other allergic diseases (P = 0.0055 and P = 0.0034). These findings show that some of the polymorphisms involved in the immune response are also involved in some aspects of the development and course of AD and, although not conclusive, support the immunological hypothesis of the origin of the inflammatory lesions.

Respiratory morbidity in children with repaired congenital esophageal atresia with or without tracheoesophageal fistula

Congenital esophageal atresia with or without tracheoesophageal fistula (CEA ± TEF) is a relatively common malformation that occurs in 1 of 2500–4500 live births. Despite the refinement of surgical techniques, a considerable proportion of children experience short- and long-term respiratory complications, which can significantly affect their health through adulthood. This review focuses on the underlying mechanisms and clinical presentation of respiratory morbidity in children with repaired CEA ± TEF. The reasons for the short-term pulmonary impairments are multifactorial and related to the surgical complications, such as anastomotic leaks, stenosis, and recurrence of fistula. Long-term respiratory morbidity is grouped into four categories according to the body section or function mainly involved: upper respiratory tract, lower respiratory tract, gastrointestinal tract, and aspiration and dysphagia. The reasons for the persistence of respiratory morbidity to adulthood are not univocal. The malformation itself, the acquired damage after the surgical repair, various co-morbidities, and the recurrence of lower respiratory tract infections at an early age can contribute to pulmonary impairment. Nevertheless, other conditions, including smoking habits and, in particular, atopy can play a role in the recurrence of infections. In conclusion, our manuscript shows that most children born with CEA ± TEF survive into adulthood, but many comorbidities, mainly esophageal and respiratory issues, may persist. The pulmonary impairment involves many underlying mechanisms, which begin in the first years of life. Therefore, early detection and management of pulmonary morbidity may be important to prevent impairment in pulmonary function and serious long-term complications. To obtain a successful outcome, it is fundamental to ensure a standardized follow-up that must continue until adulthood.

Kikuchi-Fujimoto disease in children: two case reports and a review of the literature

BackgroundKikuchi-Fujimoto disease is a rare, idiopathic and generally self-limiting cause of lymphadenitis of unknow etiology with a low recurrence rate. The typical clinical signs are cervical lymphadenopathy, fever, and symptoms of respiratory infection, and less frequently chills, night sweats, arthralgia, rash, and weight loss.Case presentationHere we describe two case reports of Kikuchi Fujimoto disease presenting in Milan within the space of a few months. The first involved the recurrence of KFD in a young boy from Sri Lanka; the second was a rare case of severe KFD complicated by HLH.ConclusionsPediatricians must consider KFD in the differential diagnosis of fever of unknown origin in children, even in western countries. Although rare, recurrence and severe complications are possible. Where symptoms suggest KFD, a systematic diagnostic approach is key. Since no guidelines on the management of KFD are available, further studies should be conducted to investigate the therapeutic options and long term outcome in children.

Role of high-resolution chest computed tomography in a child with persistent tachypnoea and intercostal retractions: A case report of neuroendocrine cell hyperplasia

Background: Chronic interstitial lung diseases in children (chILD) are a heterogeneous group of disorders that can represent a clinical challenge for pediatric pneumologists. Among them, neuroendocrine cell hyperplasia of infancy (NEHI) is a diffuse lung disease prevalent in the first years of life that spontaneously improves over time. The clinical presentation of NEHI is indistinguishable from other interstitial lung diseases, so a correct and non-invasive diagnosis by chest computed tomography (CT) without lung biopsy might not be simple. Case presentation: An 8-month-old male infant presented with a history of chronic tachypnoea and dyspnoea since 6 months of age. The patient was born at term, with APGAR scores of 9 and 10 at 1 and 5 min, respectively. Since his second month of life, the patient suffered from abnormal breathing, which was characterized by mild tachypnoea and costal retractions that worsened during breastfeeding, crying, and respiratory infections. Bilateral inspiratory crackles, preferential to the lung bases, without oxygen desaturation were detected. A chest X-ray showed a diffuse over-inflation of the lungs, but laboratory tests did not reveal any abnormalities. High-resolution chest CT documented patchy areas of ground-glass opacity involving the right upper lobe, middle lobe, and lingula, and showed mosaic areas of air-trapping, suggesting a diagnosis of NEHI. The infant was discharged without therapy and gradually improved over time. At 1 year of age, the patient was eupnoeic and chest auscultation had normalized. Conclusions: NEHI is an interstitial disease of infancy characterized by tachypnoea from the first months of life, with a good prognosis and for which a rational diagnostic approach is crucial for making a specific, early diagnosis. Initially, clinical suspicions can be confirmed with reasonable accuracy by a CT scan of the chest. Other more invasive and more expensive investigations should be reserved for selected cases that do not show a spontaneous, favourable clinical evolution.