Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

A biomarker assay to risk-stratify patients with symptoms of respiratory tract infection.

BACKGROUND: Patients who present to an emergency department (ED) with respiratory symptoms are often conservatively triaged in favour of hospitalisation. We sought to determine if an inflammatory biomarker panel that identifies the host response better predicts hospitalisation in order to improve the precision of clinical decision making in the ED. METHODS: From April 2020 to March 2021, plasma samples of 641 patients with symptoms of respiratory illness were collected from EDs in an international multicentre study: Canada (n=310), Italy (n=131) and Brazil (n=200). Patients were followed prospectively for 28 days. Subgroup analysis was conducted on confirmed coronavirus disease 2019 (COVID-19) patients (n=245). An inflammatory profile was determined using a rapid, 50-min, biomarker panel (RALI-Dx (Rapid Acute Lung Injury Diagnostic)), which measures interleukin (IL)-6, IL-8, IL-10, soluble tumour necrosis factor receptor 1 (sTNFR1) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1). RESULTS: RALI-Dx biomarkers were significantly elevated in patients who required hospitalisation across all three sites. A machine learning algorithm that was applied to predict hospitalisation using RALI-Dx biomarkers had a mean±sd area under the receiver operating characteristic curve of 76±6% (Canada), 84±4% (Italy) and 86±3% (Brazil). Model performance was 82±3% for COVID-19 patients and 87±7% for patients with a confirmed pneumonia diagnosis. CONCLUSIONS: The rapid diagnostic biomarker panel accurately identified the need for inpatient care in patients presenting with respiratory symptoms, including COVID-19. The RALI-Dx test is broadly and easily applicable across many jurisdictions, and represents an important diagnostic adjunct to advance ED decision-making protocols.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

The discovery BPD (D-BPD) program: study protocol of a prospective translational multicenter collaborative study to investigate determinants of chronic lung disease in very low birth weight infants.

BACKGROUND: Premature birth is a growing and serious public health problem affecting more than one of every ten infants worldwide. Bronchopulmonary dysplasia (BPD) is the most common neonatal morbidity associated with prematurity and infants with BPD suffer from increased incidence of respiratory infections, asthma, other forms of chronic lung illness, and death (Day and Ryan, Pediatr Res 81: 210-213, 2017; Isayama et la., JAMA Pediatr 171:271-279, 2017). BPD is now understood as a longitudinal disease process influenced by the intrauterine environment during gestation and modulated by gene-environment interactions throughout the neonatal and early childhood periods. Despite of this concept, there remains a paucity of multidisciplinary team-based approaches dedicated to the comprehensive study of this complex disease. METHODS: The Discovery BPD (D-BPD) Program involves a cohort of infants < 1,250 g at birth prospectively followed until 6 years of age. The program integrates analysis of detailed clinical data by machine learning, genetic susceptibility and molecular translation studies. DISCUSSION: The current gap in understanding BPD as a complex multi-trait spectrum of different disease endotypes will be addressed by a bedside-to-bench and bench-to-bedside approach in the D-BPD program. The D-BPD will provide enhanced understanding of mechanisms, evolution and consequences of lung diseases in preterm infants. The D-BPD program represents a unique opportunity to combine the expertise of biologists, neonatologists, pulmonologists, geneticists and biostatisticians to examine the disease process from multiple perspectives with a singular goal of improving outcomes of premature infants. TRIAL REGISTRATION: Does not apply for this study.

Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors.

BACKGROUND: Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. METHODS: Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. RESULTS: We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. CONCLUSIONS: Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes: a randomized, double-blinded, and placebo-controlled clinical trial.

OBJECTIVE: To test the hypothesis that azithromycin reduces the length of hospitalization and oxygen requirement in infants with acute viral bronchiolitis (AB). STUDY DESIGN: We performed a randomized, double-blinded, placebo-controlled trial in southern Brazil, from 2009 to 2011. Infants (<12 months of age) hospitalized with AB were recruited in 2 hospitals. Patients were randomized to receive either azithromycin or placebo, administered orally, for 7 days. At enrollment, clinical data were recorded and nasopharyngeal samples were collected for viral identification through immunofluorescence. Main outcomes were duration of oxygen requirement and length of hospitalization. RESULTS: One hundred eighty-four patients were included in the study (azithromycin 88 subjects, placebo 96 subjects). Baseline clinical characteristics and viral identification were not different between the groups studied. A virus was detected in 112 (63%) patients, and of those, 92% were positive for respiratory syncytial virus. The use of azithromycin did not reduce the median number of days of either hospitalization (P = .28) or oxygen requirement (P = .47). CONCLUSIONS: Azithromycin did not improve major clinical outcomes in a large sample of hospitalized infants with AB, even when restricting the findings to those with positive respiratory syncytial virus samples. Azithromycin therapy should not be given for AB because it provides no benefit and overuse increases overall antibiotic resistance.

Peripheral glucocorticoid sensitivity in children with controlled persistent asthma.

BACKGROUND: Persistent asthma in children is a chronic inflammatory disease and glucocorticoids (GCs) are currently recognized as the mainstay of therapy. Clinical and in vitro steroid resistance has been demonstrated in severe asthma. However, GC insensitivity has not been studied in children with controlled persistent asthma. OBJECTIVES: To analyze peripheral blood mononuclear cell (PBMC) sensitivity to GC in children (6-15 years) with persistent asthma and healthy controls. METHODS: Children with persistent asthma were selected and lung function and skin-prick tests were performed in all studied asthmatic children. PBMCs were isolated and cultured in vitro to assess mitogen-induced proliferation and cellular sensitivity to dexamethasone. RESULTS: Fifty-seven children with persistent and controlled asthma (mean age 10 years) were recruited and divided into 3 groups (severe, moderate and mild), and compared to healthy children (n = 18). Children with asthma, regardless of the severity of disease, presented similar sensitivity to GCs when compared to healthy children. Patients with mild asthma showed significantly less sensitivity to dexamethasone and children with severe asthma had similar sensitivity to dexamethasone when compared to controls. CONCLUSIONS: In vitro insensitivity to GCs was not demonstrated in children with controlled persistent asthma, even in those with severe disease. Our findings suggest that resistance to GCs in older patients with severe asthma might be an acquired process. However, future longitudinal studies are necessary to confirm this hypothesis.

Evaluation of airway reactivity and immune characteristics as risk factors for wheezing early in life.

BACKGROUND: Childhood asthma is most often characterized by recurrent wheezing, airway hyperreactivity, and atopy; however, our understanding of these relationships from early in life remains unclear. Respiratory tract illnesses and atopic sensitization early in life might produce an interaction between innate and acquired immune responses, leading to airway inflammation and heightened airway reactivity. OBJECTIVE: We hypothesized that premorbid airway reactivity and immunologic characteristics of infants without prior episodes of wheezing would be associated with subsequent wheezing during a 1-year follow-up. METHODS: One hundred sixteen infants with chronic dermatitis were enrolled before episodes of wheezing. Airway reactivity, allergen-specific IgE levels, cytokine production by stimulated PBMCs, and percentages of dendritic cells were measured on entry, and airway reactivity was reassessed at the 1-year follow-up. Linear regression models were used to evaluate a predictor's effect on continuous outcomes. RESULTS: Milk sensitization, egg sensitization, or both were associated with heightened airway reactivity before wheezing and after the onset of wheezing; however, these factors were not associated with an increased risk of wheezing. There was an interaction between initial airway reactivity and wheezing as a determinant of airway reactivity at follow-up. In addition, cytokine production by stimulated PBMCs was a risk factor for wheezing, whereas increased percentages of conventional dendritic cells were protective against wheezing. CONCLUSION: Our data in a selected cohort of infants support a model with multiple risk factors for subsequent wheezing that are independent of initial airway reactivity; however, the causative factors that produce wheezing very early in life might contribute to heightened airway reactivity.

Shorter telomeres in children with severe asthma, an indicative of accelerated aging.

Severe therapy-resistant asthma (STRA) is closely associated with distinct clinical and inflammatory pheno-endotypes, which may contribute to the development of age-related comorbidities. Evidence has demonstrated a contribution of accelerated telomere shortening on the poor prognosis of respiratory diseases in adults. Eotaxin-1 (CCL11) is an important chemokine for eosinophilic recruitment and the progression of asthma. In the last years has also been proposed as an age-promoting factor. This study aimed to investigate the association of relative telomere length (rTL) and eotaxin-1 in asthmatic children. Children aged 8-14 years (n=267) were classified as healthy control (HC, n=126), mild asthma (MA, n=124) or severe therapy-resistant asthma (STRA, n=17). rTL was performed by qPCR from peripheral blood. Eotaxin-1 was quantified by ELISA from fresh-frozen plasma. STRA had shorter telomeres compared to HC (p=0.02) and MA (p=0.006). Eotaxin-1 levels were up-regulated in STRA [median; IQR25-75)] [(1,190 pg/mL; 108-2,510)] compared to MA [(638 pg/mL; 134-1,460)] (p=0.03) or HC [(627 pg/mL; 108-1,750)] (p<0.01). Additionally, shorter telomeres were inversely correlated with eotaxin-1 levels in STRA (r=-0.6, p=0.013). Our results suggest that short telomeres and up-regulated eotaxin-1, features of accelerated aging, could prematurely contribute to a senescent phenotype increasing the risk for early development of age-related diseases in asthma.

Growth of the lung parenchyma early in life.

RATIONALE: Early in life, lung growth can occur by alveolarization, an increase in the number of alveoli, as well as expansion. We hypothesized that if lung growth early in life occurred primarily by alveolarization, then the ratio of pulmonary diffusion capacity of carbon monoxide (Dl(CO)) to alveolar volume (V(A)) would remain constant; however, if lung growth occurred primarily by alveolar expansion, then Dl(CO)/V(A) would decline with increasing age, as observed in older children and adolescents. OBJECTIVES: To evaluate the relationship between alveolar volume and pulmonary diffusion capacity early in life. METHODS: In 50 sleeping infants and toddlers, with equal number of males and females between the ages of 3 and 23 months, we measured Dl(CO) and V(A) using single breath-hold maneuvers at elevated lung volumes. MEASUREMENTS AND MAIN RESULTS: Dl(CO) and V(A) increased with increasing age and body length. Males had higher Dl(CO) and V(A) when adjusted for age, but not when adjusted for length. Dl(CO) increased with V(A); there was no gender difference when Dl(CO) was adjusted for V(A). The ratio of Dl(CO)/V(A) remained constant with age and body length. CONCLUSIONS: Our results suggest that surface area for diffusion increases proportionally with alveolar volume in the first 2 years of life. Larger Dl(CO) and V(A) for males than females when adjusted for age, but not when adjusted for length, is primarily related to greater body length in boys. The constant ratio for Dl(CO)/V(A) in infants and toddlers is consistent with lung growth in this age occurring primarily by the addition of alveoli rather than the expansion of alveoli.

Expired nitric oxide and airway reactivity in infants at risk for asthma.

BACKGROUND: Family histories of atopy, as well as histories of atopic dermatitis and food allergy, are important risk factors for an infant to have asthma. Although atopic sensitization appears to contribute to the development of asthma, it is unclear when the airways become involved with the atopic process and whether airway function relates to the atopic characteristics of the infant. OBJECTIVE: We sought to evaluate whether atopic infants without prior episodes of wheezing have increased expired nitric oxide (eNO) levels and heightened airway reactivity. METHODS: Infants with eczema were recruited, and atopic status was defined by specific IgE levels to foods or aeroallergens and total IgE levels. eNO, forced expiratory flow at 75% exhaled volume (FEF(75)), and airway reactivity to inhaled methacholine were measured in sedated infants. Airway reactivity was quantified by using the provocative concentration to decrease FEF(75) by 30%. RESULTS: Median age for the 114 infants evaluated was 10.7 months (range, 2.6-19.1 months). Infants sensitized to egg or milk compared with infants sensitized to neither egg nor milk had lower flows (FEF(75): 336 vs 285 mL/s, P < .003) and lower lnPC(30) (mg/mL) provocative concentrations to decrease FEF(75) by 30% (-0.6 vs -1.2, P < .02) but no difference in eNO levels. Infants with total serum IgE levels of greater than 20 IU/mL had higher eNO levels compared with infants with IgE levels of 20 IU/mL or less (14.6 vs 11.2 ppb, P < .023) but no difference in forced flows or airway reactivity. CONCLUSIONS: Our findings suggest that atopic characteristics of the infant might be important determinants of the airway physiology of forced expiratory flows, airway reactivity, and eNO.

Diagnosis of pulmonary aspiration: a mouse model using a starch granule test in bronchoalveolar lavage.

BACKGROUND AND OBJECTIVE: Pulmonary aspiration (PA) is a significant respiratory disease in children. However, the diagnosis of aspiration is often difficult owing to the poor efficacy of currently available diagnostic tests. The aim of this study was to assess in a mouse model the specificity of starch granule detection in BAL as a new method for detecting PA in children. METHODS: Twenty BALB/c mice were divided into the following groups according to the solution instilled into the airways: corn flour milk 7.5%-a source of starch (CM), Pseudomonas aeruginosa, normal saline and a control group. BAL was performed 2 days after instillation. Detection of starch granules and lipid-laden macrophages were compared in BAL. RESULTS: Starch granules were detected in BAL fluids from all mice in the CM group (food aspiration model), whereas no starch granules were detected in the other three groups, demonstrating a sensitivity and specificity of 100%. On the other hand, lipid-laden macrophages were found in all mice from all the groups studied. CONCLUSIONS: The detection of starch granules in BAL is a simple and highly specific method for the diagnosis of PA in an experimental model. Clinical studies using the starch granule detection method in BAL should be tested in at risk patients to evaluate the utility of this method for investigating PA.

Growth rate of lung function in healthy preterm infants.

RATIONALE: It remains unclear whether premature birth, in the absence of neonatal respiratory disease, results in abnormal growth and development of the lung. We previously reported that a group of healthy infants born at 32-34 weeks' gestation and without respiratory complications had decreased forced expiratory flows and normal forced vital capacities at 2 months of age. OBJECTIVES: Our current study evaluated whether these healthy infants born prematurely exhibited improvement or "catch-up" in their lung function during the second year of life. METHODS: Longitudinal measurements of forced expiratory flows by the raised volume rapid thoracic compression technique were obtained in the first and the second years of life for infants born prematurely at 32.7 (range, 30-34) weeks' gestation (n = 26) and infants born at full term (n = 24). MEASUREMENTS AND MAIN RESULTS: Healthy infants born prematurely demonstrate decreased forced expiratory flows and normal forced vital capacities in the first and second years of life. In addition, the increases in lung function with growth were similar to full-term infants. CONCLUSIONS: Persistently reduced flows in the presence of normal forced vital capacity and the absence of catch-up growth in airway function suggest that premature birth is associated with altered lung development.

The prevalence of symptoms of sleep-disordered breathing in Brazilian schoolchildren.

OBJECTIVE: To identify the prevalence of symptoms of sleep-disordered breathing among children of low socioeconomic status in the South of Brazil. METHODS: This was a cross-sectional study, carried out in the city of Uruguaiana, RS, in which specific questionnaire about the symptoms of sleep-disordered breathing was completed by the parents of a sample of schoolchildren aged 9 to 14 years, enrolled on the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: From the total of 1,011 eligible schoolchildren, 998 questionnaires were completed. The parents of 27.6% of the children reported habitual snoring, while 0.8% reported apnea, 15.5% described daytime mouth breathing and 7.8% complained of excessive daytime sleepiness. Children with excessive daytime sleepiness were at greater risk of habitual snoring (OR = 2.7; 95%CI 1.4-5.4), apnea (OR = 9.9; 95%CI 1.2-51), mouth breathing (OR = 13.1; 95%CI 6.2-27.4) and learning difficulties (OR = 9.9; 95%CI 1.9-51.0). Rhinitis, maternal smoking and positive allergy skin test results were significantly associated with habitual snoring and daytime mouth breathing. CONCLUSIONS: There is an elevated prevalence of symptoms of sleep-disordered breathing among children from 9 to 14 in the city of Uruguaiana. The prevalence of habitual snoring was almost twice that described in this age group in other populations. Children with excessive daytime sleepiness appear to have almost 10 times the risk of learning difficulties.

Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence.

PURPOSE OF REVIEW: To provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis. RECENT FINDINGS: Nonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population. Orally administered immunomodulators result in the mounting of innate and adaptive immune responses to infection in the respiratory mucosa and anti-inflammatory effects in proinflammatory environments. Clinical data reflect these mechanistic effects in reductions in the recurrence of respiratory infections and wheezing events in high-risk paediatric populations. A new generation of clinical studies is currently underway with the power to position the nonspecific bacterial lysate immunomodulator OM-85 as a potential antiasthma prophylactic. SUMMARY: An established mechanistic and clinical role for prophylaxis against paediatric respiratory infections by nonspecific immunomodulators exists. Clinical trials underway promise to provide high-quality data to establish whether a similar role exists in wheezing/asthma prevention.

Impact of omalizumab in children from a middle-income country with severe therapy-resistant asthma: A real-life study.

BACKGROUND: Severe asthma in children is a global health problem. Severe therapy-resistant asthma (STRA) in children is a major clinical challenge due to persistent symptoms despite high doses of corticosteroids and results in high public health costs. Omalizumab (anti-IgE monoclonal antibody) has been described as an effective add-on therapy in these patients. The characteristics of children with STRA from low- and middle-income countries have scarcely been reported, and no real-life study has been published on the effects of omalizumab in this group of patients. The aim of our study is to report the first clinical real-life experiences with omalizumab in Brazilian children with STRA. METHODS: Children (6-18 years old) from a referral center who were diagnosed with STRA were included in this retrospective study based on our clinical databases. The included children had undergone at least 6 months of omalizumab treatment and fulfilled the following initial criteria: 1) >6 years old; 2) a positive skin-prick test for at least one aeroallergen; and 3) a serum total IgE level between 30 and 1500 IU/mL. Clinical and lung function variables were analyzed before and after treatment. RESULTS: Fourteen children (mean age: 11.9 years; percentage female: 72%) were included in this study. Omalizumab treatment significantly increased control of the disease according to a standardized questionnaire administered at every visit (P < 0.0001), ceased hospitalizations in 70% (P = 0.02) of patients, and allowed 8/9 (89%) patients to be weaned off oral steroids (P = 0.004). CONCLUSIONS: In this retrospective report, the use of omalizumab in Brazilian children with STRA significantly improved disease control, decreased hospitalizations, and allowed suspension of continuous oral corticosteroids.

Asthma and Obesity in Children Are Independently Associated with Airway Dysanapsis.

BACKGROUND: An increase in the prevalence of overweight and asthma has been observed. Both conditions affect negatively lung function in adults and children. The aim of this study was to analyze the effect of overweight and asthma on lung function in children. METHODS: We designed a case-control study of healthy and asthmatic subjects nested within an epidemiological asthma prevalence study in children between 8 and 16 years of age. The effect of asthma and overweight on lung function was assessed by impulse oscillometry and spirometry obtained at baseline and 10-15 min after salbutamol. RESULTS: 188 children were recruited, 114 (61%) were asthmatics and 72 (38%) were overweight or obese. Children with asthma and overweight had a higher FVC (+1.16 z scores, p < 0.001) and higher FEV1 (+0.79 z scores, p = 0.004) and lower FEV1/FVC (-0.54 z scores, p = 0.008) when compared to healthy controls. Compared to normal weight asthmatics, the overweight had higher FVC (+0.78 z scores, p = 0.005) and lower FEV1/FVC (-0.50 z scores, p = 0.007). In the multivariate analysis, overweight was associated with an increase of 0.71 and 0.44 z scores in FVC and FEV1, respectively, and a reduction in FEV1/FVC by 0.40 z scores (p < 0.01 for all). Overweight had no effect on maximal flows and airway resistance at baseline, and this was not modified by inhalation of a bronchodilator. Asthma was also associated with higher post-BD FVC (0.45 z scores, p = 0.012) and FEV1 (0.35 z scores, p = 0.034) but not with FEV1/FVC and FEF25-75%. Two-way analysis of variance did not detect any interaction between asthma and overweight on lung function variables before or after bronchodilator. CONCLUSION: Our results suggest that asthma and overweight are independently associated with airway dysanaptic growth in children which can be further scrutinized using impulse oscillometry. Overweight contributed more to the reduction in FEV1/FVC than asthma in children without increasing airway resistance. Spirometry specificity and sensitivity for obstructive diseases may be reduced in populations with high prevalence of overweight. Adding impedance oscillometry to spirometry improves our understanding of the ventilatory abnormalities in overweight children.

Effects of Diet on Telomere Length: Systematic Review and Meta-Analysis.

BACKGROUND: The goal of this systematic review and meta-analysis is to determine the effect of diet on telomere length. METHODS: We searched the following databases: MEDLINE, Embase, LILACS, CINAHL, ISI Web of Science, and Scopus, as well as the Cochrane Central Register of Controlled Trials and the National Institutes of Health, from inception to December 2016. Articles that assessed effects of diet on telomere length were included. RESULTS: A total of 2,128 studies were identified, 30 were read in full, and 7 were systematically reviewed. Five RCTs were included in the meta-analysis, covering 9 diets; a total of 533 participants were included. Study heterogeneity (I2) was 89%, and differences were not identified regarding average telomere lengths (mean difference 1.06; 95% CI -1.53 to 3.65). CONCLUSION: The available evidence suggests that there is no effect of diet on telomere length, but the strong heterogeneity in the type and duration of dietary interventions does not allow any final statement on the absence of an effect of diet on telomere length.