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Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, and progressive airway damage and obstructive lung disease. While the association of ciliary ultrastructure defect/genotype with severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated.We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD.Cross-sectional analysis of children with PCD (N=146) enrolled in a prospective multicenter observational study, stratified by defect type: ODA (outer dynein arm), ODA/IDA (outer and inner dynein arm), IDA/MTD (inner dynein arm and microtubular disorganization), and Normal/Near Normal ultrastructure with associated genotypes. CTs were scored utilizing the Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD (MERAGMA-PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, mucus plugging/tree in bud opacities. Volume fraction of each component was expressed as % of total lung volume. %Disease was computed as the sum of all components. Regression analyses were utilized to describe the association between clinical predictors and CT scores.Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, 24 Normal/Near Normal. Mean (SD) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) % predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had higher %Disease compared to children with ODA defects (2.71% higher (95%CI: 1.37-4.06, p0.001)), driven by higher %Mucus plugging (2.35% higher (1.43-3.26, p0.001)). Increasing age, lower BMI, and lower FEV1 were associated with higher %Disease (0.23%, 95%CI: 0.11-0.35, p0.001; 0.03%, 95%CI: 0.01-0.04, p=0.008; and 0.05%, 95%CI: 0.01-0.08, p=0.011, respectively).Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared to children with ODA defects.

The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood.To determine if there is an association between presence/type of laterality abnormality and ciliary ultrastructural defect and genotype.Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of this data, the association of ciliary ultrastructural defect or genotype and likelihood of a laterality abnormality was evaluated by logistic regression adjusted for presence of two loss-of-function versus one or more not-loss-of-function variants.Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversus totalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%). Compared to group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (OR 2.07, 95% CI 1.21-3.54, P0.01) and less likely in the normal/near normal ultrastructure group (OR 0.04, 95% CI 0.013-0.151, P0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but zero of 96 in the inner dynein arm defects with microtubular disorganization group (P=0.038).In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructure defect. Pathophysiologic mechanisms underlying these differences require further exploration.

BACKGROUND: Organ laterality defects in primary ciliary dyskinesia (PCD) are common, ranging from complete mirror image organ arrangement, situs inversus totalis (SIT), to situs ambiguus (SA), which falls along the spectrum of situs solitus (SS) and SIT. Targeted investigations for organ laterality defects are not universally recommended in PCD consensus statements. Without investigations beyond chest radiography (CXR), clinically significant defects may go undetected leading to increased morbidity. We hypothesize that clinically significant SA defects remain undetected on CXR and targeted investigations are needed to detect various laterality defects associated with morbidity. METHODS: This retrospective study collected data from PCD clinics at two Canadian children’s hospitals from 2012 to 2020. Participants

Rationale: Integration of guidelines for severe asthma (SA) management into electronic medical records (EMRs) may greatly enhance asthma care and outcomes.Objectives: We aimed: 1) to develop an alg...

OBJECTIVE. This project aims to prospectively and objectively assess otolaryngological manifestations and quality of life of children with primary ciliary dyskinesia (PCD) and compare these findings with healthy pediatric controls. STUDY DESIGN. Cross-sectional. SETTING. Two high-volume pediatric PCD specialty centers. METHODS. Standardized clinical assessment; Sino-Nasal Outcome Test 22 (SNOT-22); Hearing Environment and Reflection Quality of Life (HEAR-QL); Reflux Symptom Index (RSI); standardized physical examination of the sinonasal, laryngeal, and otological systems; and investigations including pure-tone audiograms (PTAs) and sinonasal cultures were collected. RESULTS. Forty-seven children with PCD and 25 control participants were recruited. Children with PCD had more upper airway symptoms than healthy children. They had significantly higher scores in both SNOT-22 and RSI, indicating worse sinonasal and reflux symptoms, with worse quality of life on the HEAR-QL index compared to healthy children (P < .05). Fifty-two percent of children with PCD-related hearing loss were not aware of their hearing deficit that was present on audiological assessment, and only 23% of children who had ventilation tubes had chronic otorrhea, most of which was easily controlled with ototopic drops. Furthermore, although all children with PCD had chronic rhinosinusitis, only 36% of them were using topical nasal treatment. The most common bacteria cultured from the middle meatus were Staphylococcus aureus in 11 of 47 (23%), followed by Streptococcus pneumoniae in 10 of 47 (21%). CONCLUSION. This multisite cohort highlights the importance of otolaryngology involvement in the management of children with PCD. More rigorous otolaryngological management may lead to reductions in overall morbidity and improve quality of life for children with PCD.

Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is an important form of children’s interstitial and diffuse lung disease for which the diagnostic strategy has evolved. The prevalence of comorbidities in NEHI that may influence treatment has not been previously assessed. Objectives: To evaluate a previously unpublished NEHI clinical score for assistance in diagnosis of NEHI and to assess comorbidities in NEHI. Methods: We performed a retrospective chart review of 199 deidentified patients with NEHI from 11 centers. Data were collected in a centralized Research Electronic Data Capture registry and we performed descriptive statistics. Results: The majority of patients with NEHI were male (66%). The sensitivity of the NEHI Clinical Score was 87% (95% confidence interval [CI], 0.82–0.91) for all patients from included centers and 93% (95% CI, 0.86–0.97) for those with complete scores (e.g., no missing data). Findings were similar when we limited the population to the 75 patients diagnosed by lung biopsy (87%; 95% CI, 0.77–0.93). Of those patients evaluated for comorbidities, 51% had gastroesophageal reflux, 35% had aspiration or were at risk for aspiration, and 17% had evidence of immune system abnormalities. Conclusions: The NEHI Clinical Score is a sensitive tool for clinically evaluating NEHI; however, its specificity has not yet been addressed. Clinicians should consider evaluating patients with NEHI for comorbidities, including gastroesophageal reflux, aspiration, and immune system abnormalities, because these can contribute to the child’s clinical picture and may influence clinical course and treatment.

Nasal nitric oxide concentrations are extremely low in primary ciliary dyskinesia (PCD), and measurement of this nasal gas is recommended as a PCD diagnostic test in cooperative patients aged 5 years and older. However, nasal nitric oxide measurements must be performed with chemiluminescence analyzers using a standardized protocol to ensure proper results, because nasal nitric oxide values can be influenced by various internal and external factors. Repeat nasal nitric oxide testing on separate visits is required to ensure that low diagnostic values are persistent and consistent with PCD. This technical paper presents the standard operating procedures for nasal nitric oxide measurement used by the PCD Foundation Clinical and Research Centers Network at various specialty centers across North America. Adherence to this document ensures reliable nasal nitric oxide testing and high diagnostic accuracy when employed in a population with appropriate clinical phenotypes for PCD.

Rationale Having developed the first disease‐specific, health‐related quality of life (HRQoL) instruments for children with primary ciliary dyskinesia (PCD), we aimed to assess the psychometric performance of quality of life (QOL)‐PCD child, adolescent, and parent‐proxy versions in terms of reliability and validity across cross‐cultural settings and caring for patients with this rare disease. Methods Children (n = 71), adolescents (n = 85), and parents (n = 68) from multiple centers in the UK and North America completed age‐appropriate QOL‐PCD and generic QOL measures: pediatric QOL inventory, COPD assessment test (CAT), and Sino‐Nasal Outcome Test 20. Total of 13 children, 13 parents, and 17 adolescents repeated QOL‐PCD 10 to 14 days later to assess test‐retest reliability. Multitrait analysis evaluated how the items loaded to hypothesized scales: physical, emotional & social functioning, treatment burden, role, vitality, upper and lower respiratory symptoms, and ears and hearing symptoms. Examination of item‐to‐total correlations led to removal of three, five, and six items, respectively in the prototype child, adolescent and parent‐proxy versions; the validated measures now comprise between 34 and 38 items. Results The QOL‐PCD scales had good internal consistency; Cronbach's α for QOL‐PCD parent‐proxy ranged 0.62 to 0.86. Test‐retest reliability demonstrated stability across all scales; for example QOL‐PCD adolescent intraclass correlation coefficients ranged 0.71 to 0.89. Significant relationships were found between QOL‐PCD scales and similar constructs on generic questionnaires, for example, QOL‐PCD adolescent lower respiratory symptoms and the CAT score (r = .64, P

Rationale Sleep duration is critical to growth, learning, and immune function development in infancy. Strategies to ensure that national recommendations for sleep duration in infants are met require knowledge of perinatal factors that affect infant sleep. Objectives To investigate the mechanistic pathways linking maternal education and infant sleep. Methods An observational study was conducted on 619 infants whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant sleep duration at three months was assessed using the Brief Infant Sleep Questionnaire. Maternal education was collected via maternal report. Prenatal and postnatal depression scores were obtained from the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Birth records and maternal report were the source of covariate measures. Mediation analysis (PROCESS v3.0) was used to examine the indirect effects of maternal education on infant sleep duration mediated through prenatal depression and birth mode. Measurements and main results At three months of age, infants slept on average 14.1 h. Lower maternal education and prenatal depression were associated with significantly shorter infant sleep duration. Emergency cesarean section birth was associated with 1-hour shorter sleep duration at three months compared to vaginal birth [without intrapartum antibiotic prophylaxis] (β: −0.99 h; 95% CI: −1.51, −0.48). Thirty percent of the effect of lower maternal education on infant total sleep duration was mediated sequentially through prenatal depression and birth mode (Total Indirect Effects: −0.12, 95% CI: −0.22, −0.03, p Conclusions Prenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration.

Rationale. Material deprivation has been proposed as a more comprehensive measure of socioeconomic status than parental income. Stronger associations between childhood emergency department visits for asthma and air pollution have been demonstrated among children living in neighborhoods with high levels of deprivation, but the associations with asthma development and ongoing asthma are not known. Objectives. We determined the associations between neighborhood material deprivation and the development of new and ongoing childhood asthma. Methods. Prospectively collected administrative data housed at the Institute for Clinical Evaluative Sciences were examined for Toronto children born from 1997 to 2003. Neighborhood material deprivation, comprising no high school graduation, lone parent families, government transfers, unemployment, low income, and homes needing major repairs, was reported in the Ontario Marginalization Index. Incident asthma was defined by the time of entry into the Ontario Asthma Surveillance Information System (OASIS) database. We measured the risk of incident asthma using Cox proportional hazards models and the associations between ongoing asthma visits and deprivation by year of life with generalized linear mixed models. Results. OASIS asthma criteria were met for 21% of the 326,383 children. After adjustment for characteristics strongly associated with asthma, including male sex, prematurity, obesity, and atopic conditions other than asthma, children with high birth neighborhood deprivation were at increased risk of incident asthma (HR 1.11; 95% CI, 1.09–1.13). High deprivation in a given year of life was associated with increased odds of ongoing asthma during that year of life (OR 1.03; 95% CI, 1.02–1.05). Conclusions. Children living in high-deprivation neighborhoods are at increased risk of incident and ongoing asthma. This study suggests that neighborhood material deprivation may represent a helpful tool for evaluating the effects of disparities in health and social advantages on the likelihood of developing and continuing to need healthcare visits for ongoing childhood asthma.

Primary ciliary dyskinesia is an incurable, rare, inherited, chronic condition. Treatment includes regular clearing of airway mucus, aggressive treatment of infections and management of hearing loss. Caregiver burden has not been explored, hence we interviewed 18 English speaking mothers and 6 English speaking fathers of children under 6 years who were diagnosed with PCD around the world. The parents described how the child’s diagnosis, treatment regimen, and health status impacted their life. They discussed the impact of the COVID-19 pandemic and they talked about the different ways they cope with challenges that arise. The need for integrated social care is discussed.

Airway clearance of pathogens and particulates relies on motile cilia. Impaired cilia motility can lead to reduction in lung function, lung transplant, or death in some cases. More than 50 proteins regulating cilia motility are linked to primary ciliary dyskinesia (PCD), a heterogeneous, mainly recessive genetic lung disease. Accurate PCD molecular diagnosis is essential for identifying therapeutic targets and for initiating therapies that can stabilize lung function, thereby reducing socioeconomic impact of the disease. To date, PCD diagnosis has mainly relied on nonquantitative methods that have limited sensitivity or require a priori knowledge of the genes involved. Here, we developed a quantitative super-resolution microscopy workflow: (i) to increase sensitivity and throughput, (ii) to detect structural defects in PCD patients' cells, and (iii) to quantify motility defects caused by yet to be found PCD genes. Toward these goals, we built a localization map of PCD proteins by three-dimensional structured illumination microscopy and implemented quantitative image analysis and machine learning to detect protein mislocalization, we analyzed axonemal structure by stochastic optical reconstruction microscopy, and we developed a high-throughput method for detecting motile cilia uncoordination by rotational polarity. Together, our data show that super-resolution methods are powerful tools for improving diagnosis of motile ciliopathies.

Rationale There is growing evidence that air pollution may contribute to the development of childhood asthma and other allergic diseases. In this follow-up of the Toronto Child Health Evaluation Questionnaire (T-CHEQ) study, we examined associations between early life exposures to air pollution and incidence of asthma, allergic rhinitis and eczema from birth through adolescence. Methods 1286 T-CHEQ participants were followed from birth until outcome (March 31, 2016) or loss to follow-up, with a mean of 17 years of follow-up. Concentrations of nitrogen dioxide (NO2), ozone (O3) and particulate matter with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5) from January 1, 1999 to December 31, 2012 were assigned to participants based on their postal codes at birth using ground observations, chemical/meteorological models, remote sensing and land-use regression models. Study outcomes included incidence of physician-diagnosed asthma, allergic rhinitis and eczema. Cox proportional hazard regression models were used to estimate hazard ratios per interquartile range of exposures and outcomes, adjusting for potential confounders. Results Hazard ratios of 1.17 (95% CI 1.05–1.31) for asthma and 1.07 (95% CI 0.99–1.15) for eczema were observed for total oxidants (O3 and NO2) at birth. No significant increase in risk was found for PM2.5. Conclusions Exposures to oxidant air pollutants (O3 and NO2) but not PM2.5 were associated with an increased risk of incident asthma and eczema in children. This suggests that improving air quality may contribute to the prevention of asthma and other allergic disease in childhood and adolescence., This study found that exposure to total oxidants at birth increased the risk of developing asthma by 17% and eczema by 7%. Adverse impacts of exposure to air pollutants, particularly ozone and nitrogen dioxide, may have their origins in early life. http://bit.ly/33PClYN

Objective We sought to determine the prevalence of, and identify factors associated with, parent questions about physical activity for their child with a chronic cardiac, respiratory, or rheumatologic condition. Methods This cross-sectional study of 56 children (32 [57%] female), 3 to 18 years of age, with chronic cardiac (n=21), respiratory (n=18), or rheumatologic (n=17) conditions involved a parent questionnaire about their child's physical activity participation and measurement of the child's activity with an omni-directional accelerometer for 1 week. Results Parents of 20 (36%) children had at least one question about their child's physical activity participation, and the prevalence of questions did not vary by age (Wald chi square = 0.77, P=0.38), gender (Wald chi square = 0.11, P=0.74), or clinic (Wald chi square = 1.77, P=0.41). Parent questions were associated (P = 0.04) with lower levels of activity for boys (95% confidence interval [CI] for estimated marginal means: With questions: 197, 395; Without questions: 346, 500) and higher levels of activity for girls (95% CI for estimated marginal means: With questions: 268, 448; Without questions: 239, 369). A multivariable logistic regression model found that parents with questions had higher odds of having a child who was less well (odds ratio [OR]=19.9 for unwell, OR=5.6 for generally well with some symptoms versus well and asymptomatic) and had a history of cardiac arrhythmia (OR=7.6). Conclusions Over one-third of parents reported having questions about physical activity for their child with a chronic medical condition, suggesting substantial uncertainty even among children reported as active. Presence of parent uncertainty is associated with parent reports of the child being unwell or a history of cardiac arrhythmia. By asking parents if they have questions about their child's activity, health care professionals may be better able to identify inactive boys and overprotective attitudes toward active girls.

RATIONALE: Few studies have examined trends in the rates of severe exacerbations of childhood asthma.OBJECTIVES: Our objective was to measure changes over time, and factors associated with severe a...

Childhood asthma has shown variable associations with children's physical activity. Neighborhood walkability captures community features that promote walking and is protective against some chronic conditions, such as obesity and diabetes.We evaluated associations between home neighborhood walkability and incident and ongoing childhood asthma.In this population-based cohort study, we used prospectively collected administrative healthcare data for the Province of Ontario housed at the Institute for Clinical Evaluative Sciences. We followed an administrative data cohort of 326,383 Toronto children born between 1997 and 2003, inclusive, until ages 8-15 years. Home neighborhood walkability quintile was measured using a validated walkability index with four dimensions: population density, dwelling density, access to retail and services, and street connectivity. Incident asthma was defined by time of entry into the validated Ontario Asthma Surveillance Information System database, which requires two outpatient visits for asthma within two consecutive years or any hospitalization for asthma and follows children with asthma longitudinally starting at any age. Associations between walkability and incident asthma were examined using Cox proportional hazards models. Associations between ongoing asthma and walkability in each year of life were examined using generalized linear mixed models.Twenty-one percent of children (n = 69,628) developed incident asthma and were followed longitudinally in the Ontario Asthma Surveillance Information System database. Low birth home neighborhood walkability was associated with an increased incidence of asthma (hazard ratio, 1.11; 95% confidence interval, 1.08-1.14). Among children with asthma, low walkability in a given year of a child`s life was associated with greater odds of ongoing asthma in the same year (odds ratio, 1.12; 95% confidence interval, 1.09-1.14).Children living in neighborhoods with low walkability were at increased risk of incident and ongoing asthma. Neighborhood walkability improvement, such as by adding pedestrian paths to improve street connectivity, offers potential strategies to contribute to primary asthma prevention.

Purpose Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. Methods We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. Results WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. Conclusion WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous condition. The number of genes associated with primary ciliary dyskinesia is rising, and the link between genotype and clinical phenotype is largely unknown (1). Recent advances in molecular genotyping have helped establish the association between genetic defects and aberrant cilia ultrastructure in PCD, as detected by transmission electron microscopy. However, up to 30% of PCD cases do not show any specific ultrastructural defects and thus cannot be detected using this method. A classic example of this occurs in PCD cases caused by mutations in the DNAH11 (dynein axonemal heavy chain 1) protein, where aberrant ciliary beating can be detected via high-speed video microscopy (HSVM) analysis, but no ultrastructural defect is observed (2, 3). Even in cases where ultrastructural defects do exist, they can be difficult to detect using standard transmission electron microscopy techniques, and therefore patients who harbor such subtle defects are at risk of being misdiagnosed. PCD caused by mutations in the protein HYDIN, for example, display normal ciliary beat frequency and rarely exhibit abnormal ciliary transmission electron microscopy, yet mucociliary clearance is compromised.

A 4-year-old boy with pulmonary capillaritis, treated with rituximab, steroids, and azathioprine for 2 years, presented with a 6-month history of falls and paucity of speech. Examination revealed irritability, mutism, hyperreflexia, and wide-based gait, and he had an Expanded Disability Status Scale (EDSS) score of 6.5. MRI brain revealed volume loss with extensive, bilateral T2/fluid-attenuated inversion recovery hyperintensities in the deep subcortical white matter, mesial temporal lobes, insula, globus pallidi, thalami, brainstem, and cerebellum (figure). MRI spine revealed increased T2 signal within the central dorsal aspect of the cervical cord. Lumbar puncture showed leukocyte count of 13 × 106/L (65% lymphocytes), erythrocyte count of 1 × 106/L, glucose 2.7 mmol/L, and protein 0.36 g/L. NMDAR antibody testing was negative (serum/CSF). Nasopharyngeal and bronchoalveolar lavage samples tested positive for enterovirus/rhinovirus by multiplex PCR and enterovirus was detected by RT-PCR (serum/CSF).

RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma.OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches.METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomiz...

Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia that is predominantly inherited in an autosomal-recessive fashion. It is associated with abnormal ciliary structure and/or function leading to chronic upper and lower respiratory tract infections, male infertility, and situs inversus. The estimated prevalence of primary ciliary dyskinesia is approximately one in 10,000-40,000 live births. Diagnosis depends on clinical presentation, nasal nitric oxide, high-speed video-microscopy analysis, transmission electron microscopy, genetic testing, and immunofluorescence. Here, we review its clinical features, diagnostic methods, molecular basis, and available therapies.

The association between asthma exacerbation during pregnancy and adverse maternal and child health outcomes have not been investigated appropriately. Our objective was to determine the short- and long-term intergenerational effect of asthma exacerbation in pregnant women with asthma.A population cohort study was conducted using data from the Ontario asthma surveillance system and population-level health administrative data. Asthma exacerbation in pregnant women with asthma was defined as at least one of the following criteria: at least five physician visits, or one emergency department visit or one hospital admission for asthma during pregnancy. Pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders were identified using International Classification of Disease codes (9th and 10th revisions).The cohort consisted of 103 424 singleton pregnancies in women with asthma. Asthma exacerbation in pregnant women with asthma was associated with higher odds of pre-eclampsia (OR 1.30, 95% CI 1.12–1.51) and pregnancy-induced hypertension (OR 1.17, 95% CI 1.02–1.33); babies had higher odds of low birthweight (OR 1.14, 95% CI 1.00–1.31), preterm birth (OR 1.14, 95% CI 1.01–1.29) and congenital malformations (OR 1.21, 95% CI 1.05–1.39). Children born to women with asthma exacerbation during pregnancy had elevated risk of asthma (OR 1.23, 95% CI 1.13–1.33) and pneumonia (OR 1.12, 95% CI 1.03–1.22) during the first 5 years of life.Asthma exacerbation during pregnancy in women with asthma showed increased risk of pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders in their children, indicating that appropriate asthma management may reduce the risk of adverse health outcomes.

Introduction The accuracy of primary ciliary dyskinesia (PCD) diagnosis has improved but no single test is diagnostic and some cases remain unsolved. Data regarding the accuracy of pulmonary radioaerosol mucociliary clearance scan (PRMCC) for the diagnosis of PCD are limited to predominantly adults using a 24-hour test. This study was performed to determine the accuracy of a 60-minute PRMCC test for diagnosing PCD in children. Methods Children with suspected PCD and inconclusive clinical diagnostic testing in an expert center were selected for PRMCC testing. Nebulized 99m Tc sulfur colloid was inhaled and dynamic imaging acquired for 60 to 120 minutes. Two independent radiologists blinded to the clinical diagnosis and health records overread PRMCC studies. The PRMCC result was compared with the reference standard diagnosis of PCD made by two physicians using the cumulative health record, blinded to PRMCC results. Results From 2008 to 2018, 57 patients (6-17 years) participated, of which 16 met criteria for the reference diagnosis of PCD. The PRMCC test was conclusive in 54 patients (94.7%) and had a sensitivity of 100% (95% confidence interval [CI] = 78.2-100), specificity of 85.7% (95% CI = 69.7-95.2), positive predictive value of 75% (95% CI = 57.1-87.1), negative predictive value of 100% (95% CI = 90.2-100), and accuracy of 90% (95% CI = 78.2-96.7). Conclusion The 60-minute PRMCC test is noninvasive and feasible in children with a high negative predictive value for PCD. It may be a helpful adjunctive test to rule out PCD when clinical suspicion remains after guideline recommended first-line clinical testing.

ERS and ATS guidelines for PCD diagnosis present different recommendations. Authors from both guidelines clarify similarities, differences and steps required to develop an internationally agreed pathway. TEM or genotyping confirm a diagnosis of PCD.http://bit.ly/2SR7GWm

This document presents detailed steps to analysing the waveforms of beating cilia, measured in high speed video microscopy. We show that in the case of PCD caused by mutations inDNAH11andHYDINthe classification by a handful of parameters describing ciliary dynamics allows to distinguish the genotype, as well as (much more easily) distinguishing healthy from PCD samples. This document is intended to complement the brief highlight (1) and presents the details of the datasets used in that letter.

Respiratory distress occurs in 5% to 7% of live births at term gestation. Most cases are mild and transient and can be attributed to transient tachypnea of the newborn or “wet lung.” Severe respiratory distress is often due to nonpulmonary causes such as sepsis or congenital heart disease. Occasionally, term neonatal respiratory distress is associated with an inherited primary lung disease such as primary ciliary dyskinesia or surfactant metabolism defects. These lung diseases have characteristic presentations in the neonatal period and are important to recognize, as they necessitate different management approaches and have lifelong implications. Suspicion for these diseases should prompt referral to a pediatric pulmonologist. [ Pediatr Ann . 2019;48(4):e175–e181.]

Summary Background: A correct diagnosis of asthma is the cornerstone of asthma management. Few pediatric studies have examined the accuracy of physician-diagnosed asthma. Objectives: We determined the accuracy of parent reported physician-diagnosed asthma in children sampled from a community cohort. Methods: Nested case-control study that recruited 203 children, aged 9–12, from a community-based sample. Three groups were recruited: asthma cases had a parental report of physician-diagnosed asthma, symptomatic controls had respiratory symptoms without a diagnosis of asthma, and asymptomatic controls had no respiratory symptoms. All participants were assessed and assigned a clinical diagnosis by one of three study physicians, and then completed spirometry, methacholine challenge, and allergy skin testing. The reference standard of asthma required a study physician's clinical diagnosis of asthma and either reversible bronchoconstriction or a positive methacholine challenge. Diagnostic accuracy, sensitivity and specificity were calculated for parent-reported asthma diagnosis compared to the reference standard. Results: One hundred two asthma cases, 52 controls with respiratory symptoms but no asthma diagnosis, and 49 asymptomatic controls were assessed. Physician agreement for the diagnosis of asthma was moderate (kappa 0.46–0.81). Compared to the reference standard, 45% of asthma cases were overdiagnosed and 10% of symptomatic controls were underdiagnosed. Parental report of physician-diagnosed asthma had 75% sensitivity and 92% specificity for correctly identifying asthma. Conclusions: There is significant misclassification of childhood asthma when the diagnosis relies solely on a clinical history. This study highlights the importance of objective testing to confirm the diagnosis of asthma. Pediatr Pulmonol. 2016; 9999:XX–XX. © 2016 Wiley Periodicals, Inc.

Primary Ciliary Dyskinesia (PCD) is a rare heterogenic disorder leading to significant respiratory morbidity. Health-care providers who treat PCD must familiarize themselves with recommended treatment strategies. However, most of the treatments recommended in PCD have been extrapolated from cystic fibrosis (CF) and non-CF bronchiectasis literature. Mainstays of therapy are reviewed in detail, and should include at a minimum: regular airway clearance, routine microbiological surveillance, antibiotic treatment for pulmonary exacerbation, and health vaccinations. This review summarizes both medical and surgical pulmonary treatment considerations, as well as recommendations for the integration of non-pulmonary subspecialty care in the management of PCD.

Recent research suggests that the asthma epidemic observed in the 1980s and 1990s has stabilized. Changing trends in asthma may have an impact on the well-reported global phenomenon of the "asthma September peak." The 38th week of the year has been identified as the peak time for asthma exacerbations among children.The purposes of this study were to examine the longitudinal trend of the September peak and to see if it changed over time, differed by age groups, or varied across different geographical regions.Monthly rates of asthma emergency department (ED) and physician outpatient visits were calculated using data provided by the Ontario Asthma Surveillance Information System from 2003 to 2013 for patients of all ages. The Ontario Asthma Surveillance Information System is a population-based surveillance system with over 2 million individuals with asthma. Age-specific rates were calculated using the prevalent asthma population-asthma individuals with at least one health service claim for asthma in the respective year-as the denominator. Rates were stratified by age group and region of residence. Spatial relationships within the province were tested to examine if the September peak was more prominent in certain regions of Ontario.The highest September peak in ED visits was observed in 2005 for children aged 0-4 years and 5-9 years (18.35 and 8.11 per 1,000 asthma prevalence, respectively). The rate of asthma ED visits of all children was consistently highest in September; however, the spike became marginally less pronounced over time. Since 2005, there has been a 51.7% decrease in the September asthma ED visit rate for all age groups. Monthly physician visits for all age groups usually peaked in October, roughly 4 weeks following the peak in ED visits. Analysis by residence showed that rates throughout Ontario were higher in September than in other months, suggesting that the spike was widespread rather than localized.While the magnitude of the September peak has decreased over time, the asthma ED visit rate remains significantly higher in September than in other months. Physician visits are also highest in the fall. These findings stress the importance of empowering children and families to maintain good asthma control throughout the year, including hand washing, to minimize respiratory viral infections in September.

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive condition that is often asymptomatic despite significant changes in chest imaging. Diagnosis is often made when patients become symptomatic in adulthood. There are still no proven treatments, but earlier diagnosis may allow for evaluation of preventative strategies that could improve outcome. It is an important diagnosis to consider in children who have marked radiographic findings with no or very mild symptoms or physical findings. Diagnosis can be made with imaging alone but may necessitate lung biopsy for definitive diagnosis.