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Primary ciliary dyskinesia (PCD) is an incurable, rare, inherited, chronic condition. Treatment includes the regular clearing of airway mucus, aggressive treatment of infections and management of hearing loss. Caregiver burden has not been explored, hence we interviewed 18 mothers and 6 fathers of children under 6 years to understand the impact of diagnostic testing and implications of a positive diagnosis. Interviews were transcribed and thematically analysed and five key themes were identified. These included the parents’ experiences following child’s diagnosis, impact of child’s treatment regimen on parent, impact of child’s health status on parent, parent’s coping strategies, and parental concerns for the future. Parents described their diagnostic journey, with the findings revealing how a lack of awareness among clinicians of the PCD symptom pattern can lead to a delayed diagnosis. Parents discussed the emotional and practical impact of a PCD diagnosis and the coping strategies employed to deal with challenges arising following a diagnosis. Parents use a variety of different lifestyle changes to accommodate their child’s treatment regimen and to cope with disruptive life events such as the COVID-19 pandemic. This study provides valuable insights into parental adjustment and adaptation to a PCD diagnosis and management regimen. Going forward, this research highlights the need for integrated social care for PCD patients and their families.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder that presents with a wide range of respiratory complaints. The most common otologic associated disorder is middle ear effusion. We ask if children with PCD suffer from vestibular impairment.Cross-sectional cohort study.Tertiary pediatric referral hospital.Children with confirmed PCD.All included participants were clinically assessed to be at baseline then basic demographics and medical histories were collected, including the specific genetic mutation these patients have. After which, all patients underwent two vestibular tests. The first was to assess their ability to stand on one foot with their eyes open and then with their eyes closed and the second was video head impulse test (vHIT).Ability standing on one foot with the eyes closed and vHIT.During this period, 25 children with PCD were recruited for the study. The mean age at recruitment was 11.26 years (4-18 yr). There were 11 women and 14 men. All patients were able to participate in both tests. Nineteen participants (76%) had vestibular impairment. Fifteen of them failed to stand on one foot with their eyes closed and six of 25 had abnormal vHIT. The most common involved gene was DNAH5 8/25 (32%) and it was associated with vestibular impairment in seven of eight participants (87.5%).The majority of children with PCD that we tested suffered from vestibular impairment that was previously undiagnosed. This potentially indicates that imbalance and vestibular pathology is under-diagnosed in children with PCD.

Rationale: Current spirometry quality grading for individuals 7 years and older include within test repeatability thresholds up to 250mls, which may be inappropriately wide for children. Objectives...

Owing to their greater outdoor activity and ongoing lung development, children are particularly vulnerable to the harmful effects of exposure to fine particulate matter (PM2.5). However, the effects of PM2.5 components are poorly understood. This study aimed to use a longitudinal birth cohort of children with physician-diagnosed incident asthma to investigate the effect of PM2.5 components at birth on morbidity measured by health services utilization. Of 1277 Toronto Child Health Evaluation Questionnaire (T-CHEQ) participants, the study population included 362 children diagnosed with asthma who were followed for a mean of 13 years from birth until March 31, 2016, or loss-to-follow-up. Concentrations of PM2.5 and its components were assigned based on participants’ postal codes at birth. Study outcomes included counts of asthma, asthma-related, and all-cause health services use. Poisson regression in single-, two-, and multi-pollutant models was used to estimate rate ratios (RR) per interquartile range (IQR) increase of exposures. Covariates were included in all models to further adjust for potential confounding. The adjusted RR for sulfate (SO4) and all-cause hospitalizations was statistically significant with RR = 2.23 (95% confidence interval [CI]: 1.25–3.96) in a multi-pollutant model with nitrogen dioxide (NO2) and ozone (O3). In multi-pollutant models with oxidants, the adjusted RRs for SO4 of all-cause hospitalizations and emergency department (ED) visits were also statistically significant with RR = 2.31 (95% CI: 1.32–4.03) and RR = 1.39 (95% CI: 1.02–1.90), respectively. While unadjusted single-pollutant RRs for asthma-specific and asthma-related health services use with the SO4 component of PM2.5 were above one, none were statistically significant. This study found significant associations with exposure to SO4 in PM2.5 and all-cause acute care, chiefly for hospitalizations, in children with asthma.

BACKGROUND While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of sensitization and AD is less well defined. OBJECTIVE We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk of developing allergic diseases within each pattern in a general cohort. METHODS Children (n = 2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly-sensitization to foods and poly-sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group. RESULTS Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%) and persistent sensitization (3.2%). Using healthy children as the baseline, children in the "atopic dermatitis" group had the next lowest risk for all allergic outcomes at 3 years; those in the "inhalant sensitization" group had the highest risk for allergic rhinitis; children in the "transient sensitization" group were at an increased risk for food allergy; while children in the "persistent sensitization" group had the highest risk for all allergic diseases. CONCLUSION AND CLINICAL RELEVANCE There is substantial heterogeneity among allergen-sensitized children. Researchers and clinicians need to be aware of the non-specificity associated with labelling children simply as "atopic" and "non-atopic" without considering the timing of their atopic history, type of sensitization and AD status. Children with AD who were poly-sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.

Background The effect of infant feeding practices on the development of food allergy remains controversial. We examined the relationship between timing and patterns of food introduction and sensitization to foods at age 1 year in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study. Methods Nutrition questionnaire data prospectively collected at age 3, 6, 12, 18 and 24 months were used to determine timing of introduction of cow's milk products, egg and peanut. At age 1 year, infants underwent skin prick testing to cow's milk, egg white and peanut. Logistic regression models were fitted to assess the impact of timing of food exposures on sensitization outcomes, and latent class analysis was used to study patterns of food introduction within the cohort. Results Among 2124 children with sufficient data, delaying introduction of cow's milk products, egg and peanut beyond the first year of life significantly increased the odds of sensitization to that food (cow's milk adjOR 3.69, 95% CI 1.37-9.08; egg adjOR 1.89, 95% CI 1.25-2.80; peanut adjOR 1.76, 95% CI 1.07-3.01). Latent class analysis produced a three-class model: early, usual and delayed introduction. A pattern of delayed introduction, characterized by avoidance of egg and peanut during the first year of life, increased the odds of sensitization to any of the three tested foods (adjOR 1.78, 95% CI 1.26-2.49). Conclusions Avoidance of potentially allergenic foods during the first year of life significantly increased the odds of sensitization to the corresponding foods. This article is protected by copyright. All rights reserved.

Motile cilia are cellular beating machines that play a critical role in mucociliary clearance, cerebrospinal fluid movement, and fertility. In the airways, hundreds of motile cilia present on the surface of a multiciliated epithelia cell beat coordinately to protect the epithelium from bacteria, viruses, and harmful particulates. During multiciliated cell differentiation, motile cilia are templated from basal bodies, each extending a basal foot-an appendage linking motile cilia together to ensure coordinated beating. Here, we demonstrate that among the many motile cilia of a multiciliated cell, a hybrid cilium with structural features of both primary and motile cilia is harbored. The hybrid cilium is conserved in mammalian multiciliated cells, originates from parental centrioles, and its cellular position is biased and dependent on ciliary beating. Furthermore, we show that the hybrid cilium emerges independently of other motile cilia and functions in regulating basal body alignment.

Objective: To examine the associations between ambient nitrogen dioxide (NO2) and ozone (O3) exposures at birth and incidence of asthma, allergic rhinitis and eczema in childhood through adolescenc...

Background The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting. Objective To explore associations of infant gut microbiota and food sensitization. Methods Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population-based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing. Results Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food-sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23-0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07-3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae. Conclusions and clinical relevance Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.

Objective To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk. Study design We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals. Results At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39; breast milk and formula, aOR, 1.73, 95% CI, 1.17-2.57; formula only: aOR, 2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections. Conclusions Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding; indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma.

Africa’s heavy dependency on international scientific collaboration may be stifling research individualism and affecting the continent’s research evolution and priorities, according to recent research.

The human gut is host to a diverse and abundant community of bacteria that influence health and disease susceptibility. This community develops in infancy, and its composition is strongly influenced by environmental factors, notably perinatal anthropogenic exposures such as delivery mode (Cesarean vs. vaginal) and feeding method (breast vs. formula); however, the built environment as a possible source of exposure has not been considered. Here we report on a preliminary investigation of the associations between bacteria in house dust and the nascent fecal microbiota from 20 subjects from the Canadian Healthy Infant Longitudinal Development (CHILD) Study using high-throughput sequence analysis of portions of the 16S rRNA gene. Despite significant differences between the dust and fecal microbiota revealed by Nonmetric Multidimensional Scaling (NMDS) analysis, permutation analysis confirmed that 14 bacterial OTUs representing the classes Actinobacteria (3), Bacilli (3), Clostridia (6) and Gammaproteobacteria (2) co-occurred at a significantly higher frequency in matched dust-stool pairs than in randomly permuted pairs, indicating an association between these dust and stool communities. These associations could indicate a role for the indoor environment in shaping the nascent gut microbiota, but future studies will be needed to confirm that our findings do not solely reflect a reverse pathway. Although pet ownership was strongly associated with the presence of certain genera in the dust for dogs (Agrococcus, Carnobacterium, Exiguobacterium, Herbaspirillum, Leifsonia and Neisseria) and cats (Escherichia), no clear patterns were observed in the NMDS-resolved stool community profiles as a function of pet ownership.

There is growing recognition and understanding of the entities that cause interstitial lung disease (ILD) in infants. These entities are distinct from those that cause ILD in older children and adults.A multidisciplinary panel was convened to develop evidence-based guidelines on the classification, diagnosis, and management of ILD in children, focusing on neonates and infants under 2 years of age. Recommendations were formulated using a systematic approach. Outcomes considered important included the accuracy of the diagnostic evaluation, complications of delayed or incorrect diagnosis, psychosocial complications affecting the patient's or family's quality of life, and death.No controlled clinical trials were identified. Therefore, observational evidence and clinical experience informed judgments. These guidelines: (1) describe the clinical characteristics of neonates and infants (2 yr of age) with diffuse lung disease (DLD); (2) list the common causes of DLD that should be eliminated during the evaluation of neonates and infants with DLD; (3) recommend methods for further clinical investigation of the remaining infants, who are regarded as having "childhood ILD syndrome"; (4) describe a new pathologic classification scheme of DLD in infants; (5) outline supportive and continuing care; and (6) suggest areas for future research.After common causes of DLD are excluded, neonates and infants with childhood ILD syndrome should be evaluated by a knowledgeable subspecialist. The evaluation may include echocardiography, controlled ventilation high-resolution computed tomography, infant pulmonary function testing, bronchoscopy with bronchoalveolar lavage, genetic testing, and/or lung biopsy. Preventive care, family education, and support are essential.

Background:Background: Assessment of health state and health-related quality of life (HR-QOL) are limited by a child's age and cognitive ability. Parent-proxy reports are known to differ from children's reports. Simultaneous assessment using a parent-child dyad is an alternative approach. Abstract: Objective:Objective: Our objective was to assess the validity, reliability and responsiveness of a parent-child dyad approach to utility and HR-QOL assessment of paediatric asthma health states. Abstract: Methods:Methods: The setting was specialist care in a hospital-based asthma clinic. Participants were 91 girls and boys with asthma aged 8 to 17 years and 91 parents. The intervention employed was parent-child dyad administration of the Health Utilities Index (HUI) 2 and 3, the Pediatric Quality of Life Inventory™ (PedsQL™) Core and Asthma modules, and the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). Questionnaires were administered by interview to children and parents separately and then together as a dyad to assess the child's health state. The dyad interview was repeated at the next clinic visit. Dyad-child agreement was measured by intra-class correlation (ICC) coefficient; Spearman correlations were used to assess convergent validity. Test-retest reliability was assessed in 28 children who remained clinically stable between visits with a two-way ICC coefficient. Responsiveness to change from baseline was assessed with Spearman coefficients in 30 children who demonstrated clinical change between visits. Abstract: Results:Results: There was no significant agreement between parent and child for the HUI2 or HUI3 whereas agreement between dyad and child was 0.55 (95% confidence interval &lsqb;CI&rsqb; 0.36, 0.69) for the HUI2 and 0.74 (95% CI 0.61, 0.82) for the HUI3 overall. With respect to dyad performance characteristics, both HUI2 and HUI3 overall scores demonstrated moderate convergent validity with the generic PedsQL™ Core domains (range r - 0.30-0.52; p < 0.01). Dyad HUI2 attributes demonstrated moderate convergent validity with the generic PedsQL™ Core domains of similar constructs (range r - 0.35-0.43; p < 0.001) and weaker convergent validity with disease-specific domains (range r - 0.13-0.32). Dyad HUI3 attributes demonstrated weaker convergent validity compared with the HUI2. For the assessment of test-retest reliability, significant agreement between baseline and follow-up was observed for dyad HUI2 total (r - 0.53), dyad PedsQL™ Core summary (r - 0.70) and select dyad disease-specific domains. Significant responsiveness (r > 0.4; p < 0.05) was observed for dyad HUI2 total score change over time as correlated with dyad HUI3, dyad PedsQL™ Core summary and select disease-specific domains. Abstract: Conclusions:Conclusions: The parent-child dyad approach demonstrated moderate to strong performance characteristics in generic and disease-specific questionnaires suggesting it may be a valuable alternative to relying on parent proxies for assessing children's utility and HR-QOL. Future research in additional paediatric populations, younger children and a population-based sample would be useful.

Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, Pv. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (β-coefficient, 0.37, P

Objective The aim of this study was to identify risk factors for long-term adverse outcomes in children with asthma after visiting the emergency department (ED). Methods A prospective observational study was conducted at the ED of a pediatric tertiary hospital in Ontario, Canada. Patient outcomes (ie, acute asthma episodes and ED visits) were measured at baseline and at 1- and 6-months post-ED discharge. Time trends in outcomes were assessed using the generalized estimating equations method. Multiple conditional logistic regressions were used to model outcomes at 6 months and examine the impact of drug insurance coverage while adjusting for confounders. Results Of the 269 children recruited, 81.8% completed both follow-ups. ED use significantly reduced from 39.4% at baseline to 26.8% at 6 months (P < .001), whereas the level of acute asthma episodes remained unchanged. Children with drug insurance coverage were less likely to have acute asthma episodes (adjusted odds ratio [AOR] = 0.36; 95% CI, 0.15–0.85; P < .02) or repeat ED visits (AOR = 0.45; 95% CI, 0.20–0.99; P < .05) at 6 months. Other risk factors for adverse outcomes included previous adverse asthma events and certain asthma triggers (eg, cold/sinus infection). Washing bed linens in hot water weekly was protective against subsequent acute asthma episodes. Conclusions Our study demonstrated significant improvements in long-term outcomes in children seeking acute care for asthma in the ED. Future efforts remain in targeting the sustainability of improved outcomes beyond 6 months. Risk factors identified can help target vulnerable populations for proper interventions, which may include efforts to maximize insurance coverage for asthma medications and strategies to improve asthma self-management through patient and provider education.

Children's Interstitial and Diffuse Lung Disease (chILD) is a heterogeneous group of disorders that is challenging to categorize. In previous study, a classification scheme was successfully applied to children 0 to 2 years of age who underwent lung biopsies for chILD. This classification scheme has not been evaluated in children 2 to 18 years of age.This multicenter interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in North America and to apply a previously reported classification scheme in children 2 to 18 years of age. Mortality and risk factors for mortality were also assessed.Patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease from 12 North American institutions were included. Demographic and clinical data were collected and described. The lung biopsies were reviewed by pediatric lung pathologists with expertise in diffuse lung disease and were classified by the chILD classification scheme. Logistic regression was used to determine risk factors for mortality.A total of 191 cases were included in the final analysis. Number of biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean, 10.6 yr). The most common classification category in this cohort was Disorders of the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy (4.7%). Immunocompromised patients suffered the highest mortality (52.8%). Additional associations with mortality included mechanical ventilation, worse clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary hypertension was found to be a risk factor for mortality but only in the immunocompetent patients.In patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses prevalent in infancy and more overlap with adult diagnoses. Immunocompromised patients with diffuse lung disease who underwent lung biopsies had less than 50% survival at time of last follow-up.

Primary ciliary dyskinesia (PCD) is an inherited disease affecting the structure and function of the cilia lining the respiratory tract. Because functioning cilia are paramount in mucociliary clearance mechanisms, PCD results in recurrent ear, nose and lung infections, as well as neonatal respiratory distress. Kartagener’s syndrome, a triad of situs inversus totalis, recurrent sinusitis and bronchiectasis was first described in 1933, and is now recognized as only one of the classical phenotypes of PCD (Figure 1). Infertility occurs in the majority of males with PCD. Hydrocephalus, complex heart disease, polysplenia and biliary atresia are uncommon associations. Figure 1) High resolution computed tomography scan of the chest of an eight-year-old boy with Kartagener’s syndrome (primary ciliary dyskinesia with situs inversus totalis) showing extensive bronchiectasis at a young age PCD is a rare disease with an estimated incidence of approximately 1:15,000; thus, it often does not get attention in a medical school curriculum and is not the focus of much research. As a result, it is often underdiagnosed and undertreated. There are many myths about the presentation and treatment of PCD that are only becoming evident with newer multicentre collaborative research efforts that have allowed larger numbers of patients to be studied together. The present brief commentary will touch on some of the myths and realities of PCD that have recently become evident.

Background: The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding. Methods: We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing. Results: We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium ) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity. Interpretation: These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.