Early-life Respiratory Infections Research Articles

Do early-life allergic sensitization and respiratory infection interact to increase asthma risk?

Objective The ‘two-hit’ hypothesis theorizes that early life allergic sensitization and respiratory infection interact to increase asthma risk. Methods We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitization and respiratory infection were associated with increased risk for asthma at ages 6–7 years and 18 years. Allergic sensitization was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported “cough, rattle, or wheeze” and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6–7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitization and respiratory infection were explored with adjustment made for potential confounders. Results Odds of asthma were higher in sensitized compared to nonsensitized children at age 6–7 years (OR = 14.46; 95% CI 3.99–52.4), There was no evidence for interactions between allergic sensitization and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6–7 years in both sensitized (OR = 1.13; 95% CI 1.02–1.25, n = 199) and nonsensitized children (OR = 1.31; 1.11–1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. Conclusions Our findings do not support ‘two-hit’ interactions between early life allergic sensitization and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitization were risk factors and children with either should be monitored closely for development of asthma.

Burden and Subtypes of Early Life Infections Increase the Risk of Asthma

Early-life respiratory tract infections have been linked to the development of asthma, but studies on burden and subtypes of common infections in asthma development are sparse. The study aimed to examine the association between burden of early-life infections, including subtypes, with risk of asthma from ages 3-10 years and lung function at age 10 years. We included 662 children from the COPSAC2010 birth cohort, where infections, i.e., colds, acute tonsillitis, acute otitis media (AOM), pneumonia, gastroenteritis, and fever were registered prospectively in daily diaries at age 0-3 years, and asthma was diagnosed longitudinally from ages 3-10 years. The association between infection burden and subtypes and risk of asthma was analysed by generalized estimating equations. The children experienced a median of 16 [IQR=12-23] infections age 0-3 years. Children with a high burden of infections (above median) had an increased risk of asthma age 3-10: aOR=3.61 (2.39-5.45), p<0.001, which was driven by colds, pneumonia, gastroenteritis, and fever episodes (p-values<0.05), but not by AOM and tonsillitis. Lower lung function measures age 10 were associated with burden of pneumonia, but not the overall infection burden. The association between colds and risk of asthma was significantly higher in children with allergic rhinitis at age 6 (p-interaction=0.032). High burden of early-life infections in terms of colds, pneumonia, gastroenteritis, and fever is associated with increased risk of developing asthma, particularly in children with respiratory allergy. Strategies to diminish these early-life infections could potentially offer a path for primary prevention of childhood asthma.

Fetal lung growth predicts the risk for early-life respiratory infections and childhood asthma.

Early-life respiratory infections and asthma are major health burdens during childhood. Markers predicting an increased risk for early-life respiratory diseases are sparse. Here, we identified the predictive value of ultrasound-monitored fetal lung growth for the risk of early-life respiratory infections and asthma. Fetal lung size was serially assessed at standardized time points by transabdominal ultrasound in pregnant women participating in a pregnancy cohort. Correlations between fetal lung growth and respiratory infections in infancy or early-onset asthma at five years were examined. Machine-learning models relying on extreme gradient boosting regressor or classifier algorithms were developed to predict respiratory infection or asthma risk based on fetal lung growth. For model development and validation, study participants were randomly divided into a training and a testing group, respectively, by the employed algorithm. Enhanced fetal lung growth throughout pregnancy predicted a lower early-life respiratory infection risk. Male sex was associated with a higher risk for respiratory infections in infancy. Fetal lung growth could also predict the risk of asthma at five years of age. We designed three machine-learning models to predict the risk and number of infections in infancy as well as the risk of early-onset asthma. The models' R2 values were 0.92, 0.90 and 0.93, respectively, underscoring a high accuracy and agreement between the actual and predicted values. Influential variables included known risk factors and novel predictors, such as ultrasound-monitored fetal lung growth. Sonographic monitoring of fetal lung growth allows to predict the risk for early-life respiratory infections and asthma.

Early-life Respiratory Tract Infections and the Risk of School-age Lower Lung Function and Asthma: a Meta-analysis of 150 000 European Children.

Early-life Respiratory Tract Infections and the Risk of School-age Lower Lung Function and Asthma: a Meta-analysis of 150 000 European Children.

Early-life respiratory infections and developmental immunity determine lifelong lung health.

Respiratory infections are common in infants and young children. However, the immune system develops and matures as the child grows, thus the effects of infection during this time of dynamic change may have long-term consequences. The infant immune system develops in conjunction with the seeding of the microbiome at the respiratory mucosal surface, at a time that the lungs themselves are maturing. We are now recognizing that any disturbance of this developmental trajectory can have implications for lifelong lung health. Here, we outline our current understanding of the molecular mechanisms underlying relationships between immune and structural cells in the lung with the local microorganisms. We highlight the importance of gaining greater clarity as to what constitutes a healthy respiratory ecosystem and how environmental exposures influencing this network will aid efforts to mitigate harmful effects and restore lung immune health.

T cell repertoire breadth is associated with the number of acute respiratory infections in the LoewenKIDS birth cohort

We set out to gain insight into peripheral blood B and T cell repertoires from 120 infants of the LoewenKIDS birth cohort to investigate potential determinants of early life respiratory infections. Low antigen-dependent somatic hypermutation of B cell repertoires, as well as low T and B cell repertoire clonality, high diversity, and high richness especially in public T cell clonotypes reflected the immunological naivety at 12 months of age when high thymic and bone marrow output are associated with relatively few prior antigen encounters. Infants with inadequately low T cell repertoire diversity or high clonality showed higher numbers of acute respiratory infections over the first 4 years of life. No correlation of T or B cell repertoire metrics with other parameters such as sex, birth mode, older siblings, pets, the onset of daycare, or duration of breast feeding was noted. Together, this study supports that—regardless of T cell functionality—the breadth of the T cell repertoire is associated with the number of acute respiratory infections in the first 4 years of life. Moreover, this study provides a valuable resource of millions of T and B cell receptor sequences from infants with available metadata for researchers in the field.

Early-life infection of the airways with Streptococcus pneumoniae exacerbates HDM-induced asthma in a murine model

Respiratory tract infection early in life plays a significant role in the pathogenesis of asthma. In the present study we examine, using a murine surrogate, the effects of early life respiratory infection with Streptococcus pneumoniae (SP) on adult asthma induced by sensitisation and exposure to house dust mite (HDM) allergen. Mice (one week old) were infected with SP, then 3 weeks later sensitised to HDM emulsified with Al (OH)3 intraperitoneally and challenged intranasally with same allergen for up to a further 5 weeks to establish the asthma surrogate. Outcome measures were quantified using the FlexiVent apparatus, histology and immunohistology, ELISA and flow cytometry. The murine surrogates of asthma infected with SP early in life exhibited significantly more severe disease compared with the controls of mice without SP infection, as shown by airways responsiveness, inflammatory cellular infiltration of the airways, expression of markers of airways remodelling, serum concentrations of HDM-specific IgE and the concentrations of Th2-type cytokines and the numbers of activated Th2 and ILC2 cells in the lung tissues. These data are compatible with the hypothesis that early-life infection of the airways with SP exacerbates, at least in some individuals, subsequent HDM-induced allergic airways inflammation and associated asthma in adulthood in this murine surrogate.

Low-Dose Cadmium Potentiates Metabolic Reprogramming Following Early-Life Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models. C57BL/6J mice at 8 days old were exposed to RSV 2 times with a 4-week interval. A subset of RSV-infected mice was subsequently treated with Cd at a low dose in drinking water (RSV infection at infant age [RSVinf]+Cd) for 16 weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSVinf+Cd group than other groups, implying that low-dose Cd following early-life RSV infection enhanced lung inflammation. Moreover, histopathology data showed that inflammatory cells and thickening of the alveolar walls as a profibrotic signature were evident in RSVinf+Cd. The metabolomics data revealed that RSVinf+Cd-caused metabolic disruption in histamine and histidine, vitamin D and urea cycle, and pyrimidine pathway accompanying with mechanistic target of rapamycin complex-1 activation. Taken together, our study demonstrates for the first time that cumulative Cd exposure following early-life RSV infection has a significant impact on subsequent inflammation and lung metabolism. Thus, early-life respiratory infection may reprogram metabolism and potentiate Cd toxicity, enhance inflammation, and cause fibrosis later in life.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

BackgroundEarly-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age.MethodsWe used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4–15) years.ResultsChildren with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: −0.09 (95% CI −0.14– −0.04) to −0.30 (95% CI −0.36– −0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98–2.22) to 6.30 (95% CI 5.64–7.04) and 1.25 (95% CI 1.18–1.32) to 1.55 (95% CI 1.47–1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma.ConclusionsOur findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Transmission electron microscopy study of suspected primary ciliary dyskinesia patients

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive condition often presenting with chronic respiratory infections in early life. Transmission electron microscopy (TEM) is used to detect ciliary ultrastructural defects. In this study, we aimed to assess ciliary ultrastructural defects using quantitative methods on TEM to identify its diagnostic role in confirming PCD. Nasal samples of 67 patients, including 37 females and 30 males (20.3 ± 10.7 years old), with suspected PCD symptoms were examined by TEM. The most common presentations were bronchiectasis: 26 (38.8%), chronic sinusitis: 23 (34.3%), and recurrent lower respiratory infections: 21 (31.3%). Secondary ciliary dyskinesia, including compound cilia (41.4%) and extra-tubules (44.3%), were the most prevalent TEM finding. Twelve patients (17.9%) had hallmark diagnostic criteria for PCD (class 1) consisting of 11 (16.4%) outer and inner dynein arm (ODA and IDA) defects and only one concurrent IDA defect and microtubular disorganization. Also, 11 patients (16.4%) had probable criteria for PCD (class 2), 26 (38.8%) had other defects, and 18 (26.9%) had normal ciliary ultrastructure. Among our suspected PCD patients, the most common ultrastructural ciliary defects were extra-tubules and compound cilia. However, the most prevalent hallmark diagnostic defect confirming PCD was simultaneous defects of IDA and ODA.

Early-Life Respiratory Infections in Infants with Cow's Milk Allergy: An Expert Opinion on the Available Evidence and Recommendations for Future Research.

Acute respiratory infections are a common cause of morbidity in infants and young children. This high rate of respiratory infections in early life has a major impact on healthcare resources and antibiotic use, with the associated risk of increasing antibiotic resistance, changes in intestinal microbiota composition and activity and, consequently, on the future health of children. An international group of clinicians and researchers working in infant nutrition and cow’s milk allergy (CMA) met to review the available evidence on the prevalence of infections in healthy infants and in those with allergies, particularly CMA; the factors that influence susceptibility to infection in early life; links between infant feeding, CMA and infection risk; and potential strategies to modulate the gut microbiota and infection outcomes. The increased susceptibility of infants with CMA to infections, and the reported potential benefits with prebiotics, probiotics and synbiotics with regard to improving infection outcomes and reducing antibiotic usage in infants with CMA, makes this a clinically important issue that merits further research.

Infant immunity against viral infections is advanced by the placenta-dependent vertical transfer of maternal antibodies

Neonatal passive immunity, derived from transplacental transfer of IgG antibodies from mother to fetus during pregnancy, can mitigate the risk for severe infections in the early postnatal period. Understanding the placenta as the gateway organ in this process, we aimed to evaluate the influence of specific factors modulating the transplacental IgG transfer rate (TPTR) in 141 mother/neonate pairs. We further evaluated the potential health advantage elicited by maternal IgG with regard to respiratory tract infections during infancy and early childhood. Data and biological samples collected within the prospective longitudinal pregnancy cohort study PRINCE (Prenatal Identification of Children’s Health) were used for these analyses. We tested IgG antibody levels against seven pathogens (measles, mumps, rubella, tetanus, diphtheria, pertussis and influenza A) by ELISA and detected seropositivity in 72.6–100% of pregnant women and in 76.3–100% of their neonates, respectively. Cord blood IgG levels reached 137–160% of levels detected in maternal blood. Strikingly, assessment of TPTR for all seven antigens highlighted that TPTR strongly depends on individual placental function. Subsequent in-depth analysis of anti-influenza A IgG revealed a link between cord blood levels and uterine perfusion, measured by uterine artery pulsatility index. Moreover, higher cord blood anti-influenza A IgG levels were associated with a significantly reduced risk for respiratory tract infections during the first six months of life, indicating a high degree of cross-reactivity and possible pathogen-agnostic effects of anti-influenza A antibodies. Taken together, our data suggest that early life immunity is modulated by maternal IgG levels and individual placental features such as perfusion. Vaccination of pregnant women, i.e. against influenza, can increase neonatal antibody levels and hereby protect against early life respiratory infections. Consequently, specific guidelines should evolve in order to safeguard neonates born from pregnancies with poorer placental capacity for vertical transfer of protective antibodies.

Association between prenatal exposure to perfluoroalkyl substances and respiratory tract infections in preschool children

BackgroundPrenatal exposure to perfluoroalkyl substances (PFAS) is considered to affect adversely the immune function. However, the effect of prenatal PFAS exposure on respiratory tract infections (RTIs) in children is unclear. Thus, we evaluated whether cord blood PFAS levels were associated with RTI in the first 5 years of life. MethodsThe Shanghai Prenatal Cohort is an on-going birth cohort, which included all the mothers during pregnancy. Children were followed by paediatricians once a year after birth. The levels of 10 PFAS in cord blood were tested using liquid chromatography-mass spectrometry. RTIs were diagnosed based on face-to-face interviews with the parents and review of medical records. Immunoglobulin G (IgG) and immunoglobulin E (IgE) levels, as biomarkers of humoral immunity, were assessed using enzyme-linked immunosorbent assay at age 5 years. Multivariable logistic and linear regression models were applied to study the association between prenatal PFAS exposure and RTIs. ResultsA total of 743 children completed the follow-up, 344 of them had detail information of cord blood PFAS, IgG, and IgE concentrations. Eight PFAS were detected in more than 90% of the cord blood samples, except for perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (FOSA). During the 5-year follow-up period, the frequency of RTIs increased with age, reaching a peak at age 4. Moreover, 20.6% of the children were diagnosed with recurrent RTIs. Children with recurrent RTIs had higher prenatal perfluorobutane sulfonic acid (PFBS) concentration. Higher prenatal PFBS concentration was positively associated with total RTI frequency (β = 6.05, 95% CI [0.84, 11.26]) in first 5 years of life and negatively associated with IgG level (β = −0.82, 95% CI [-1.67, −0.01]) at age 5. ConclusionsChildren with higher prenatal PFBS were more vulnerable to RTIs in early life, which may be attributed to immunosuppression of IgG production. These findings need to be further verified in larger prospective studies.

Innate IFN-lambda responses to dsRNA in the human infant airway epithelium and clinical regulatory factors during viral respiratory infections in early life.

IFN lambda (type III-IFN-λ1) is a molecule primarily produced by epithelial cells that provides an important first-line defence against viral respiratory infections and has been linked to the pathogenesis of viral-induced wheezing in early life. The goal of this study was to better understand the regulation of innate IFN-lambda responses in vitro in primary human infant airway epithelial cells (AECs) and in vivo using nasal aspirates during viral respiratory infections. IFN-lambda protein levels were quantified: (a) in human infant AECs exposed to (poly(I:C) dsRNA) under different experimental conditions (n=8 donors); and (b) in nasal aspirates of young children (≤3years) hospitalized with viral respiratory infection (n=138) and in uninfected controls (n=74). In vivo IFN-lambda airway levels during viral infections were correlated with individual characteristics and respiratory disease parameters. Our in vitro experiments showed that the poly(I:C)-induced innate production of IFN lambda in human infant AECs is regulated by (a) p38-MAPK/NF-kB dependent mechanism; and (b) exposure to pro-inflammatory signals such as IL1β. Our in vivo studies demonstrated that (a) infants (<18months) had higher virus-induced IFN-lambda airway secretion; (b) subjects with RSV infection showed the highest IFN-lambda airway levels; and (c) individuals with the highest virus-induced IFN-lambda levels (>90th percentile) had higher viral loads and were more likely to have respiratory sick visits within 12months of discharge (OR=5.8). IFN-lambda responses to dsRNA in the human infant airway epithelium are regulated by p38-MAPK and NF-kB signalling. High in vivo IFN-lambda production is influenced by virus type and associated with recurrent respiratory sick visits in young children.

Determinants of Allergic Sensitization, Asthma and Lung Function: Results from a Cross-Sectional Study in Italian Schoolchildren.

Prenatal smoking exposure and early-life respiratory infections are major determinants of asthma during childhood. We investigate the factors influencing allergic sensitization (AS), asthma, and lung function in children and the balance between individual and environmental characteristics at different life stages. 1714 children aged 7–16 years and living in southern Italy were investigated using a parental questionnaire, skin prick tests, and spirometry. We found 41.0% AS prevalence: among children without parental history of asthma, male sex, maternal smoking during pregnancy (MatSmoke), and acute respiratory diseases in the first two years of life (ARD2Y) were significant risk factors for AS. MatSmoke was associated (OR = 1.79) with ARD2Y, and this association was influenced by sex. ARD2Y was, in turn, a significant risk factor (OR = 8.53) for childhood current asthma, along with AS (OR up to 3.03) and rhinoconjuctivitis (OR = 3.59). Forced mid-expiratory flow (FEF25–75%) was negatively affected by ARD2Y, with a sex-related effect. Thus, males exposed to MatSmoke had significantly lower FEF25–75% than unexposed males. Despite the difficulty of discriminating among the complex interactions underlying the development of allergic respiratory diseases, ARD2Y appears to strongly influence both asthma and lung function during childhood. In turn, ARD2Y is influenced by prenatal exposure to tobacco smoke with a sex-dependent effect.

Personal and early life factors associated with new-onset asthma, remission, and persistence of asthma in a 2-year follow-up of schoolchildren

Objective The natural course of childhood asthma, after its onset, is characterized by periods of persistence, relapse and remission. To investigate personal and early life factors associated with new-onset asthma, persistence and remission among children. Methods The study was conducted in the province of Saskatchewan, Canada. Children in grades Kindergarten to Grade 8 (ages 5–14 years) participated in a cross-sectional study in 2013. In 2015, we approached those who gave consent in 2013 to be re-contacted, creating a prospective cohort. Data were collected using questionnaires in both years. Participants in 2013 who also had data in 2015 (25%: n = 324/1,348) had their asthma status reclassified and longitudinal descriptors were applied: “no asthma”, “new-onset asthma”, “persistent” or “remission”. Personal and early life factors associations with asthma outcomes in 2015 were evaluated. Results Among those without asthma in 2013 (n = 245), the incidence of new-onset asthma in 2015 was 7.2%. Among those with asthma in 2013 (n = 79), 47.1% had remission and 52.9% had persistent asthma in 2015. Parental history of asthma (adjusted odds ratio (aOR): 4.99; 95% confidence interval (CI): 1.88–28.27), early life respiratory infection (aOR: 1.92; 95%CI: 1.47–7.88), early life allergy [aOR: 6.39; 95%CI: 1.34–30.58) and early life infection (aOR: 4.99; 95%CI: 1.19–20.93) were associated with new onset asthma. Similarly, while parental history of asthma (aOR: 1.13; 95%CI: 0.29–4.34), early life respiratory infection (aOR: 2.71; 95%CI: 0.70–10.45), and early life ear infection (aOR: 1.34; 95%CI: 0.36–5.05) were also positively association with persistent asthma, the associations were not statistically significant. Conclusion Parental history of asthma, early life respiratory infection and allergy might not only influence the onset of childhood asthma but also be associated with asthma persistence.

Association Between Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection in Early Life and Recurrent Wheeze and Asthma in Later Childhood.

Recurrent wheeze and asthma in childhood are commons causes of chronic respiratory morbidity globally. We aimed to explore the association between respiratory syncytial virus (RSV) infection in early life and subsequent respiratory sequelae up to age 12 years. We estimated the strength of association by 3 control groups and 3 follow-up age groups, with data from studies published between January 1995 and May 2018. We also estimated associations by diagnostic criteria, age at infection, and high-risk population. Overall, we included 41 studies. A statistically significant association was observed between early life RSV infection and subsequent childhood recurrent wheeze, in comparison to those who were healthy or those without respiratory symptoms: OR 3.05 (95% confidence interval [CI], 2.50-3.71) for 0 to <36 months follow-up age; OR 2.60 (95% CI, 1.67-4.04) for 36-72 months; and OR 2.14 (95% CI, 1.33-3.45) for 73-144 months. For the subsequent development of asthma, a statistically significant association was observed only in relation to those aged 73-144 months at follow-up: OR 2.95 (95% CI, 1.96-4.46). Further studies using standardized definitions and from diverse settings are needed to elucidate the role of confounders and provide more robust estimates.

High-resolution computed tomography features of lung disease in perinatally HIV-infected adolescents on combined antiretroviral therapy.

Chronic lung disease is common in perinatally HIV-infected children as they increasingly surviving into adolescence. There are few data on the radiologic spectrum of disease in this population. Contrasted high-resolution computed tomography (HRCT) was performed in ambulatory South African adolescents enrolled in a prospective study of perinatally-infected adolescents aged 9 to 14 years established on combined antiretroviral therapy (cART) and followed for 36 months. Consecutive participants with reduced lung function (defined by a forced expiratory volume in 1 second [FEV1] of <80% normal and/or lung diffusion capacity [DLCO] <80% normal] underwent HRCT. History, clinical, and laboratory data were collected. Two radiologists blinded to clinical data and to each other, reported scans using standardized methodology; a third radiologist resolved discrepancies. Amongst 100 participants undergoing HRCT, median age was 13.8 years (12.8-15.1). The median duration on cART was 8.4 years (IQR = 5.7-9.8). Mosaic attenuation was the most common finding (73%). Of these 71 (91%) demonstrated associated air trapping radiologically consistent with bronchiolitis obliterans. Bronchiectasis occurred in 39% with significant correlation between extent of bronchiectasis and mosaic attenuation (r = 0.57, P < .001). Prior hospitaliszation for childhood pneumonia at any time before enrollment was associated with mosaic attenuation (OR = 3.9, 95%CI, [1.2-12.5]); prior pulmonary tuberculosis (TB) was associated with the combination of mosaic attenuation and bronchiectasis (OR = 4.9, 95%CI, [1.6-15.7]). Most participants (86%) with mosaic attenuation had stage III or IV HIV disease at time of HIV diagnosis (OR = 3.6; [0.9-14.9]). Inter observer agreement between the two readers was good for bronchiectasis (K = 0.71) and moderate for mosaic attenuation (K = 0.51). Despite well-controlled HIV and long duration of cART, HRCT changes were common in perinatally HIV-infected adolescents. There was a high prevalence of small airways disease with and without associated bronchiectasis. These changes were associated with prior pulmonary TB or prior severe pneumonia. Strategies to prevent and treat early life respiratory infection must be strengthened to reduce the burden of chronic lung disease in HIV-infected adolescents.

Relationship between early life respiratory infections and childhood asthma

Viral infections in early life, especially respiratory syncytial virus and human rhinovirus, are closely related to childhood asthma.An initial wheezing of the lower respiratory tract infection of human rhinovirus can serve as a marker of asthma predisposition, whereas respiratory syncytial virus bronchiolitis (particularly severe infection) in early life can have a causative role in asthma attacks.The interaction of viral infections with the bacterial microbiological environment of respiratory tract is an important determinant of childhood asthma. Key words: Viral infection; Microbial environment; Asthma; Early life; Children

Vitamin D prenatal programming of respiratory and allergic outcomes in childhood: What are observational studies telling us?

Introduction Prenatal vitamin D status may influence offspring's respiratory and allergic outcomes; however, evidence is inconclusive. A systematic review and meta-analysis was conducted on the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or cord blood at birth with the risk of offspring's respiratory and allergic conditions. Methods Two independent researchers conducted systematic searches for observational studies published using defined keywords on vitamin D and health outcomes, including respiratory tract infections (RTIs), wheeze, asthma, atopic eczema, allergic rhinitis, allergic sensitization and lung function. Random-effects meta-analyses were conducted. Heterogeneity among studies was tested by using the Cochran Q test and quantified by using the I2 statistic. Publication bias was examined by using Funnel plot and Egger's regression asymmetry test. Modification of effects by selected factors was assessed, including time at exposure assessment, offspring's age at health endpoint, outcome assessment, optimal 25(OH)D blood levels (30 ng/mL or greater) versus all the rest and geographical location. Results A total of 34 from 547 retrieved articles were included. Articles were based on 26 separate study populations, including 25 longitudinal birth cohorts and one case control study, from 16 different countries (latitude ranging from 55°N to 31°S). Increased prenatal exposure to 25(OH)D was inversely associated with risk of RTIs. Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratio was 0.64 (95% CI 0.47, 0.87). A positive borderline association was found for lung function at school age (FEV1 z-score coefficient 0.07, 95% CI −0.01, 0.15). No associations were found for wheeze, asthma, atopic eczema, allergic rhinitis and allergic sensitization. After subgroup analysis, stronger inverse associations were found between prenatal vitamin D and risk of RTIs within the first 6 months of life, and between cord blood vitamin D levels and RTIs. A stronger inverse association was found for asthma occurrence within the first 5 years of life, but no later in childhood. A stronger association between prenatal vitamin D levels and risk of atopic eczema during childhood was detected at higher latitude. Conclusions Current evidence from observational studies indicates that exposure to higher levels of vitamin D in utero may protect against early-life respiratory tract infections in offspring during childhood. However, epidemiological evidence from observational studies does not support an impact of prenatal vitamin D status in offspring's risk of asthma and allergic manifestations. Additional studies are warranted to confirm the potential benefits for lung function development.