Sleep disordered breathing and daytime hypoventilation in a male with MECP2 mutation.

Rett syndrome (RTT, MIM * 312750) is an X-linked neurodevelopmental disorder caused by pathogenic variants at the Xq28 region involving the gene methyl-CpG-binding protein 2 (MECP2, MIM * 300005). The spectrum of MECP2-related phenotypes is wide and it ranges from asymptomatic female carriers to severe neonatal-onset encephalopathy in males. Abnormal breathing represents one of the leading features, but today little is known about polysomnographic features in RTT females; no data are available about males. We report the case of a male of Moroccan origins with a MECP2 pathogenic variant and a history of encephalopathy and severe breathing disturbances in the absence of dysmorphic features. For the first time we describe in detail the polysomnographic characteristics of a MECP2-mutated male and we show the relevance of severe central apneas, which may represent a new clinical clue to suggest the diagnosis. Moreover, we want to highlight the importance to maintain a high index of suspicion for MECP2-related disorders in the presence of severe hypotonia, apneic crises, and respiratory insufficiency in males to permit an earlier diagnosis and the consequent definition of recurrence risk of the family and to avoid other useless and invasive exams.

Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine.

BACKGROUND: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9%), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction. RESULTS: S. pneumoniae was identified in the swabs of 192 subjects (45.4%): 48.4% of whom were aged <10 years, 46.9% aged 10-14 years, and 4.7% aged ≥15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95% confidence interval [95% CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95% CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95% CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95% CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects. CONCLUSIONS: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.

Transient symptomatic hyperglycaemia secondary to inhaled fluticasone propionate in a young child.

BACKGROUND: Inhaled corticosteroids (ICSs) are currently used to prevent and treat asthma and recurrent wheezing attacks in children. Fluticasone propionate (FP) is one of the most commonly prescribed ICSs because it is considered effective and well tolerated. CASE PRESENTATION: A male infant of approximately 1 year of age, who was born to parents without relevant clinical problems or family histories including diabetes, was brought to our attention for recurrent wheezing. When he was approximately 2 years old, a regular daily inhaled treatment with FP given using a spacer was prescribed. With this therapy, the child obtained good control of his symptoms with no further recurrences, but after approximately 2 months of treatment he was admitted to the emergency room because he was whining and agitated and exhibited increased diuresis and water intake. Laboratory tests revealed hyperglycaemia (181 mg/dL), mild glycosuria, blood alkalosis (pH 7.49), a bicarbonate level of 31 mmol/L, a pCO2 level of 39 mmHg, a serum sodium level of 135 mEq/L and a serum potassium level of 3.5 mEq/L. The parents confirmed that the recommended dose of FP had been administered with no increase in the amount of drug. The child was immediately treated with endovenous infusion of physiological saline for 24 h, and his glycaemic levels as well as venous blood gas analysis returned to normal, with an absence of glucose in the urine. Oral glucose tolerance test results and glycated haemoglobin levels were normal. Monitoring of blood glucose levels before and after meals for three consecutive days did not reveal any further increase above normal levels. He was discharged with a diagnosis of transient symptomatic hyperglycaemia during ICS therapy and the suggestion to replace his inhaled FP therapy with oral montelukast. Montelukast was continued for 6 months; during this time, the child did not present any other hyperglycaemia episodes. CONCLUSIONS: Although there is no evidence of causation, this case report represents an interesting and unusual description of paediatric transient symptomatic hyperglycaemia after treatment with inhaled FP and highlights the importance of considering this potential adverse event and the necessity of informing parents of the possible clinically relevant risks associated with this drug.

Vitamin D and respiratory tract infections in childhood.

BACKGROUND: Respiratory tract infections (RTIs) remain among of the most important causes of morbidity and mortality among children. Several studies have associated vitamin D deficiency with an increased risk of RTIs, and vitamin D supplementation has been proposed as a possible preventive measure against RTIs in children. The main aim of this review is to summarize the current evidence from the literature about the link between vitamin D and RTIs in children. DISCUSSION: Several recent studies have shown that vitamin D has different immunomodulatory properties associated with the risk of RTIs in childhood. In this regard, it is very important to understand the definition of deficiency and insufficiency of vitamin D and when and how to treat this condition. Unfortunately, there is no consensus, although a level of at least 10 ng/mL 25-hydroxycholecalciferol (25[OH]D) is thought to be necessary to promote bone mineralization and calcium homeostasis, and a concentration between 20 ng/mL and 50 ng/mL is considered adequate to provide an immunomodulatory effect. Available data support a role for vitamin D deficiency in the risk of pediatric tuberculosis, recurrent acute otitis media, and severe bronchiolitis, whereas further studies are needed to confirm an association in children with recurrent pharyngotonsillitis, acute rhinosinusitis and community-acquired pneumonia. CONCLUSIONS: Maintenance of adequate vitamin D status may be an effective and inexpensive prophylactic method against some RTIs, but the supplementation regimen has not been clearly defined. Further clinical trials are needed to determine the 25(OH)D concentrations associated with an increased risk of RTIs and optimal vitamin D supplementation regimen according to the type of RTI while also taking into consideration vitamin D receptor polymorphisms.

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.

Possible molecular mechanisms linking air pollution and asthma in children.

BACKGROUND: Air 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. RESULTS: Air 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. CONCLUSIONS: Air 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.

Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma.

BACKGROUND: Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms. METHODS: This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants. RESULTS: Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p=0.005) and cough (p<0.001), episodes of rhinitis (p=0.04) and tracheitis (p=0.01), asthma attacks (p<0.001), episodes of pneumonia (p<0.001) and hospitalizations (p=0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR]=1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR=0.50; 95% CI, 0.31 -0.80). An increase of 10 µg/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR]=1.08, 95% CI: 1.00-1.17 for PM10; continuous RR=1.08, 95% CI: 1.01-1.17 for NO2). CONCLUSIONS: There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.

Using electrical impedance tomography to characterize lung impairment of children with primary ciliary dyskinesia: A pilot cross-sectional study.

BACKGROUND: In children with primary ciliary dyskinesia (PCD), measures more sensitive than spirometry are needed to characterize underlying pulmonary impairment. Electrical impedance tomography (EIT) is a promising noninvasive method for monitoring the distribution of lung ventilation, and it does not require patient collaboration. We aimed to provide an assessment of the feasibility and clinical usefulness of EIT in characterizing lung impairment in children with PCD, compared to spirometry and multiple breath nitrogen washout (MBWN2 ) test. METHODS: Children and adolescents with PCD underwent MBWN2 test as first respiratory assessment, followed by EIT monitoring and spirometry during outpatient follow-up. RESULTS: We included 12 out of 16 individuals regularly followed at our clinic. A total of 41.7% (5/12) showed abnormal forced expiratory volume in 1 s (FEV1 ), whereas 11/12 (91.7%) had abnormal ventilation inhomogeneity measured with MBWN2 test. Using EIT, the global inhomogeneity (GITOT ) index showed moderate to strong correlation with FEV1 (ρ = -0.55, 95% confidence interval [CI]: -0.87 to 0.02) and ranged from 37 to 44, with the highest inhomogeneity detected in the dorsal right quadrant. GITOT was moderately correlated with RV/TLC %predicted (ρ = 0.38, 95% CI: -0.17 to 0.74), while we detected a weak correlation between GITOT and lung clearance index (ρ = 0.29, 95% CI: -0.45 to 0.82). CONCLUSION: EIT appears promising as a noninvasive technique to characterize ventilation distribution in children with PCD, thus providing a complementary assessment to static and dynamic lung function measures of PCD disease.

Pediatric Sleep Respiratory Disorders: A Narrative Review of Epidemiology and Risk Factors.

Sleep is a fundamental biological necessity, the lack of which has severe repercussions on the mental and physical well-being in individuals of all ages. The phrase "sleep-disordered breathing (SDB)" indicates a wide array of conditions characterized by snoring and/or respiratory distress due to increased upper airway resistance and pharyngeal collapsibility; these range from primary snoring to obstructive sleep apnea (OSA) and occur in all age groups. In the general pediatric population, the prevalence of OSA varies between 2% and 5%, but in some particular clinical conditions, it can be much higher. While adenotonsillar hypertrophy ("classic phenotype") is the main cause of OSA in preschool age (3-5 years), obesity ("adult phenotype") is the most common cause in adolescence. There is also a "congenital-structural" phenotype that is characterized by a high prevalence of OSA, appearing from the earliest ages of life, supported by morpho-structural abnormalities or craniofacial changes and associated with genetic syndromes such as Pierre Robin syndrome, Prader-Willi, achondroplasia, and Down syndrome. Neuromuscular disorders and lysosomal storage disorders are also frequently accompanied by a high prevalence of OSA in all life ages. Early recognition and proper treatment are crucial to avoid major neuro-cognitive, cardiovascular, and metabolic morbidities.

Therapeutic Strategies for COVID-19 Lung Disease in Children.

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has milder presentation in children than in adults, mostly requiring only supportive therapy. The immunopathogenic course of COVID-19 can be divided in two distinct but overlapping phases: the first triggered by the virus itself and the second one by the host immune response (cytokine storm). Respiratory failure or systemic involvement as Multisystem Inflammatory Syndrome in Children (MIS-C) requiring intensive care are described only in a small portion of infected children. Less severe lung injury in children could be explained by qualitative and quantitative differences in age-related immune response. Evidence on the best therapeutic approach for COVID-19 lung disease in children is lacking. Currently, the approach is mainly conservative and based on supportive therapy. However, in hospitalized children with critical illness and worsening lung function, antiviral therapy with remdesivir and immunomodulant treatment could be considered the "therapeutic pillars."

Cytokines Profile and Lung Function in Children with Obesity and Asthma: A Case Control Study.

The existence of common inflammatory biomarkers linking obesity and asthma in children has been hypothesized. Nevertheless, laboratory and clinical characteristics of children with obesity and asthma are still poorly defined. The primary aim of the present study is to investigate the lung function and the cytokine profile, in children with obesity and asthma. In this prospective, cross-sectional pilot study, pulmonary function tests, biochemical parameters, and serum cytokines levels were compared in three groups of 28 children each, matched for age and sex. Obese children showed normal forced spirometry values except an increased distal airway resistance in subjects with obesity and no asthma. Both groups including obese children showed higher leptin and IL-10 levels and lower adiponectin and TNF-alpha levels compared to children with no obesity and asthma. IL-33 and TGF-beta1 levels were higher in children with obesity and asthma vs. children with normal weight and asthma. Finally, IL-6 was undetectable in approximately 70% of obese children with no asthma, in 57% obese asthmatic children and in 100% of children with normal-weight and asthma. Children with obesity and asthma show the most striking cytokine profile, suggesting a pro-inflammatory role of fat mass in asthma development.

Can Asymptomatic or Non-Severe SARS-CoV-2 Infection Cause Medium-Term Pulmonary Sequelae in Children?

Pulmonary complications in adults who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported even in minimally symptomatic patients. In this study, lung ultrasound (LUS) findings and pulmonary function of children who recovered from an asymptomatic or mildly symptomatic SARS-CoV-2 infection were evaluated. We prospectively followed up for at least 30 days patients younger than 18 years who recovered from SARS-CoV-2 infection at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan (Italy). All enrolled patients underwent LUS. Airway resistance measured by the interrupter technique test was assessed in subjects aged 4-6 years, whereas forced spirometry and measurement of diffusing capacity of the lungs for carbon monoxide were performed in subjects older than 6 years. To evaluate a possible correlation between pulmonary alterations and immune response to SARS-CoV-2, two semiquantitative enzyme immune assays were used. We enrolled 16 out of 23 eligible children. The median age of enrolled subjects was 7.5 (0.5-10.5) years, with a male to female ratio of 1.7. No subject presented any abnormality on LUS, airway resistance test, forced spirometry, and diffusing capacity of the lungs for carbon monoxide. On the other hand, all subjects presented Ig G against SARS-CoV-2. In contrast in adults, we did not detect any pulmonary complications in our cohort. These preliminary observations suggest that children with an asymptomatic or mildly symptomatic SARS-CoV-2 infection might be less prone to develop pulmonary complications than adults.

Familial Sleep Disorders in Unknown Genetic Syndrome.

Sleep-disordered breathing (SDB) is common in children, especially in those with congenital or genetic diseases. The factors involved include obstructive sleep apnea, disrupted rapid eye movement sleep, and central hypoventilation. Diagnosing and treating SDB in these children have a positive impact on the quality of life of them and their families, reducing the risk of both further impairment of cognitive abilities and cardiopulmonary complications. We report a familial case of SDB with central hypoventilation, in which identification of the disorder in the younger sister led to the unfortunately late diagnosis and treatment of the same condition in the older sister.

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

BACKGROUND: Kikuchi-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 PRESENTATION: Here 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. CONCLUSIONS: Pediatricians 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.

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.

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.

Children with recurrent pneumonia and non-cystic fibrosis bronchiectasis.

BACKGROUND: Recurrent pneumonia (RP) is one of the most frequent causes of pediatric non-cystic fibrosis (CF) bronchiectasis (BE) and a consequent accelerated decline in lung function. The aim of this study was to analyse the clinical records of children with RP in attempt to identify factors that may lead to an early suspicion of non-CF BE. METHODS: We recorded the demographic and clinical data, and lung function test results of children without CF attending our outpatient RP clinic between January 2009 to December 2013 who had undergone chest high-resolution computed tomography ≥ 8 weeks after an acute pneumonia episode and ≤ 6 months before enrolment. RESULTS: The study involved 42 patients with RP: 21 with and 21 without non-CF BE. The most frequent underlying diseases in both groups were chronic rhinosinusitis with post-nasal drip and recurrent wheezing (81 % and 71.4 % of those with, and 85.7 % and 71.4 % of those without BE). FEV1 and FEF25-75 values were significantly lower in the children with non-CF BE than in those without (77.9 ± 17.8 vs 96.8 ± 12.4, p = 0.004; 69.3 ± 25.6 vs 89.3 ± 21.9, p = 0.048). Bronchodilator responsiveness was observed in seven children with BE (33.3 %) and two without (9.5 %; p = 0.13). CONCLUSIONS: Reduced FEV1 and FEF25-75 values seem associated with an increased risk of developing non-CF BE in children with RP. This suggests a need for further studies to confirm the diagnostic usefulness use of spirometry in such cases.

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.

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 ≥10(6) 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.