Persistent chylothorax associated with lymphatic malformation type 6 due to biallelic pathogenic variants in PIEZO1.

PIEZO1 is required for lymphatic valve formation, and several lymphatic abnormalities have been reported to be associated with autosomal recessive PIEZO1 pathogenic variants including neonatal hydrops, lymphedema involving various body regions, and chylothorax. Persistent or recurrent chylothorax has been infrequently described in association with pathogenic variants in the PIEZO1 gene. We present a 4-year-old female with bilateral pleural effusions detected prenatally, who was diagnosed with bilateral chylothoraces post-partum. She subsequently had recurrent pleural effusions involving both pleural cavities, which tended to improve with restriction of her fat intake, and, one occasion, subcutaneous octreotide. She also had bilateral calf, and intermittent cheek swelling. Genetic testing revealed two deleterious variants in PIEZO1: c.2330-2_2330-1del and c.3860G > A (p.Trp1287*), both of which were classified as likely pathogenic. This supported a diagnosis of Lymphatic Malformation Type 6 (OMIM 616843), also known as Hereditary Lymphedema Type III. Hereditary Lymphedema type III can be associated with persistent chylothorax that can vary in size over time.

Skin morbidity in Indigenous children in relation to housing conditions in remote communities in Northwestern Ontario, Canada.

BACKGROUND: Elevated rates of eczema and skin infections in Canadian First Nation (FN) communities are of concern to families, community leaders and healthcare professionals. AIM: To determine whether skin morbidity was associated with indoor environmental quality factors in Canadian FN children living in remote communities. METHODS: We quantified indoor environmental quality (IEQ) in the homes of FN children aged < 4 years of age living in four remote communities in the Sioux Lookout region of Northwestern Ontario, Canada. We conducted a quantitative housing inspection, including measuring surface area of mould (SAM), and monitored air quality for 5 days in each home, including carbon dioxide and relative humidity and quantified endotoxin in settled floor dust. We reviewed the medical charts of participating children for skin conditions and administered a health questionnaire. Relationships between IEQ and skin infections or eczema were evaluated using multivariable regression. RESULTS: In total, 98 children were included in the descriptive analyses, of whom 86 had complete data and were evaluated in multivariate analyses for dermatological outcomes (mean age 1.6 years). Of these 86 children, 55% had made ≥ 1 visits to the local health centre (HC) for skin and soft tissue infections and 25.5% for eczema. Unexpectedly, annualized eczema visits were inversely associated with SAM (RR = 0.14; 95% CI 0.01-0.93). There was a trend suggesting an inverse relationship between endotoxin and HC encounters for eczema and skin and soft tissue infections. CONCLUSION: Skin infections were common in this population of FN children. IEQ did not appear to be associated with skin infections or eczema. Mould exposure appeared to be inversely associated with HC encounters for eczema, possibly related to complex microorganism-host interactions occurring early in life.

Housing conditions and respiratory morbidity in Indigenous children in remote communities in Northwestern Ontario, Canada.

BACKGROUND: Rates of lower respiratory tract infection (LRTI) among First Nations (FN) children living in Canada are elevated. We aimed to quantify indoor environmental quality (IEQ) in the homes of FN children in isolated communities and evaluate any associations with respiratory morbidity. METHODS: We performed a cross-sectional evaluation of 98 FN children (81 with complete data) aged 3 years or younger, living in 4 FN communities in the Sioux Lookout region of Northern Ontario. We performed medical chart reviews and administered questionnaires. We performed a housing inspection, including quantifying the interior surface area of mould (SAM). We monitored air quality for 5 days in each home and quantified the contaminant loading of settled floor dust, including endotoxin. We analyzed associations between IEQ variables and respiratory conditions using univariable and multivariable analyses. RESULTS: Participants had a mean age of 1.6 years and 21% had been admitted to hospital for respiratory infections before age 2 years. Houses were generally crowded (mean occupancy 6.6 [standard deviation 2.6, range 3-17] people per house). Serious housing concerns were frequent, including a lack of functioning controlled ventilation. The mean SAM in the occupied space was 0.2 m2. In multivariable modelling, there was evidence of an association of LRTI with log endotoxin (p = 0.07) and age (p = 0.02), and for upper respiratory tract infections, with SAM (p = 0.07) and age (p = 0.03). Wheeze with colds was associated with log endotoxin (p = 0.03) and age (p = 0.04). INTERPRETATION: We observed poor housing conditions and an association between endotoxin and wheezing in young FN children living in Northern Ontario.

Association Between Chronic Aspiration and Chronic Airway Infection with Pseudomonas aeruginosa and Other Gram-Negative Bacteria in Children with Cerebral Palsy.

PURPOSE: Children with cerebral palsy (CP) are at an increased risk for aspiration, and subsequent pneumonia or pneumonitis. Pneumonia is a common cause of hospital admission, intensive care unit (ICU) admission, and death in patients with CP, and may disproportionately contribute to mortality. The role of respiratory microflora is unknown. This study examined the relationship between respiratory infections with Gram-negative bacteria (GNB), particularly Pseudomonas aeruginosa, and the frequency/severity of pneumonia hospitalization. METHODS: Retrospective chart review of 69 patients with CP and hospitalization for pneumonia. Eligible patients required hospitalization for bacterial pneumonia, at least one respiratory culture, and fulfillment of Bax definition of CP. Group assignment was based on respiratory culture. Charts were analyzed for comorbid illness, hospitalization demographics, and disease severity. RESULTS: Children with isolation of P. aeruginosa or other GNB had increased frequency of ICU admission (77.4, 65.1, vs. 26.9 %, respectively, p < 0.01), intubation (45.2, 39.5 vs. 11.5 %, p = 0.02, p = 0.03 respectively), and large pleural effusions (37.5, vs. 0 %) than children without GNB. Children with isolation of GNB had more prolonged hospitalizations and were more likely to have multiple hospitalizations than those without GNB. CONCLUSION: Colonization with P. aeruginosa and other Gram-negative organisms in children with CP is associated with increased morbidity, prolonged hospitalization, and severity of pneumonia including need for PICU admission and intervention. Further research is required to determine causality, the role of antimicrobials active against Gram negative in pneumonia treatment, and the role of GNB eradication therapy in children with CP.

Efficacy of high-dose vitamin D in pediatric asthma: a systematic review and meta-analysis.

CONTEXT: Observational studies have suggested a relationship between vitamin D status and asthma-related respiratory outcomes. The benefit of vitamin D supplementation for pulmonary function, symptoms and exacerbations is not well established. OBJECTIVE: To systematically review paediatric clinical trials investigating the role of vitamin D on asthma-related respiratory outcomes. DATA SOURCES: MEDLINE, EMBASE and CENTRAL were searched until January 2014. No date or language restrictions. STUDY SELECTION: Clinical trials reporting asthma-related respiratory outcomes following vitamin D administration at a dose equal or greater than 500 IU per day were included and reviewed independently by two authors for full systematic review eligibility. DATA EXTRACTION: Two reviewers independently extracted and verified pre-defined data fields. RESULTS: We identified five studies that met study eligibility and assessed final data synthesis. The median trial size was 48 participants (range 17-430) and the average daily dose of cholecalciferol ranged from 500 to 2000 IU/day. Overall study methodological quality was high, but some heterogeneity in population and vitamin D dosing regimen was evident. Meta-analysis suggested a statistically significant reduction (RR 0.41, CI 0.27-0.63) in asthma exacerbation with vitamin D therapy. LIMITATIONS: Due to variability in outcome selection and missing data, it was not possible to perform meta-analysis for pulmonary function testing and asthma symptom scores. Vitamin D-related adverse events were not considered in four of five papers. CONCLUSIONS: Available evidence from this systematic review suggests that high dose vitamin D may prevent asthma exacerbation. This should be confirmed through larger well-designed randomised controlled trials.

The impact of pneumoperitoneum and Trendelenburg positioning on respiratory system mechanics during laparoscopic pelvic surgery in children: a prospective observational study.

PURPOSE: The aim of this study was to describe the changes in respiratory system compliance and other measures of respiratory mechanics associated with peritoneal insufflation (12 mmHg pressure) with carbon dioxide (PNP12) and 20° Trendelenburg positioning (TDG20) in pediatric patients undergoing laparoscopic surgery for abdominal cryptorchidism. METHODS: Twelve subjects with abdominal cryptorchidism undergoing orchiopexy were enrolled in the study. General anesthesia was conducted with sevoflurane/O2/air, fentanyl, and rocuronium. Pressure-controlled ventilation with a peak inspiratory pressure (PIP) of 10-15 cm H2O and a positive end-expiratory pressure of 5 cm H2O was titrated to achieve a tidal volume (VT/kg) of 6-10 mL·kg(-1) and end-tidal carbon dioxide (EtCO2) of 35-40 mmHg. Adjustments of PIP and respiratory rate (RR) were made to maintain the initial VT/kg and EtCO2 < 50 mmHg. Measurements of weight-corrected dynamic compliance (Cdyn/kg), VT/kg, and EtCO2 were recorded at baseline, after PNP12, at TDG20, and again after deflation and return to the level position. RESULTS: Adjustments in PIP were required in all subjects to maintain the target VT/kg. The Cdyn/kg decreased 42% (95% confidence interval [CI]: 30 to 51; P < 0.001) after PNP12, and it remained below baseline until deflation. The TDG20 caused only minimal additional reductions in Cdyn/kg (10% decrease; 95% CI: 0 to 19; P = 0.048). The VT/kg decreased 42% (95% CI: 31 to 52; P = 0.048) with PNP12, and after TDG20, it decreased a further 10% (95% CI: 4 to 19; P = 0.038). After deflation, the VT/kg increased by 56% (95% CI: 28 to 90; P = 0.001) and was then adjusted back to the initial values. CONCLUSION: The PNP12 significantly decreases Cdyn/kg and VT/kg in pediatric patients. The use of TDG20 produces a relatively minor additional impact in respiratory mechanics. This study emphasizes the need to adjust ventilator settings to maintain normal gas exchange during this procedure.

Families' perceptions of consumer-grade, inexpensive oxygen saturation monitors.

OBJECTIVES: We evaluated what proportion of families have a consumer-grade pulse oximeter, why they bought one, and how they choose to use it. WORKING HYPOTHESIS: We hypothesized that children followed in cardiorespiratory clinics would be more likely to have an oximeter than children attending a more general clinic. STUDY DESIGN AND SUBJECT SELECTION: We carried out a cross-sectional study using a convenience sample of children attending a respirology, cardiology, or gastroenterology clinic at a children's hospital. Consenting guardians completed a survey. RESULTS: Two-hundred families completed the survey. Fifty-three (26.5%; 53/200) had an oximeter at home. The proportion of children attending a cardiorespiratory clinic who had an oximeter was higher than another clinic (p = 0.08), but 15.5% of children attending the latter also had access to one. Of devices not funded by government insurance, over 80% of devices were "fingertip" clamp-style oximeters, and 50% were purchased online. Most devices were used only when the child was ill (83.7%; 36/43). Only about 1/3 of families had received education about using an oximeter, and a similar proportion had compared their oximeter to a medical-grade device. Only 2.4% (1/42) respondents did not feel that their device was "somewhat" or "very" accurate. The oxygen saturation that would prompt seeking emergency care was similar to most pediatric acute care guidelines. CONCLUSIONS: Many children, particularly those with cardiorespiratory conditions, have access to consumer-grade pulse oximeters. Asking about the presence of an oximeter should be part of the pediatric history, and families responding affirmatively should be offered education.

The Accuracy of Readily Available Consumer-Grade Oxygen Saturation Monitors in Pediatric Patients.

BACKGROUND: Pulse oximetry measurement is ubiquitous in acute health care settings in high-income countries and is familiar to any parent whose child has been treated in such a setting. Oximeters for home use are readily available online and are incorporated in several smartphones and smartwatches. METHODS: We wished to determine how accurate are oximeters available online that are designated for adult and pediatric use, and the saturation monitor integrated in a smartphone, when used in children, compared to reference, hospital-grade oximeters. We evaluated a fingertip oximeter marketed for children purchased online; an adult fingertip oximeter purchased online; the oximeter integrated in a smartphone; and reference, hospital-grade oximeters. Participants were < 18 y of age. Bland-Altman charts were generated, and the estimated root mean square error (EARMS) was calculated. Rates of failure to obtain a measurement, relationship between device and time to successful measurement, relationship between age and time to successful measurement, and relationship between error (vs the reference device) and age were evaluated for each consumer-grade device. RESULTS: We measured SpO2 in 74 children between 0.1-17.0 y of age. Subjects weighing < 30 kg had a median (interquartile range [IQR]) age of 2 (1.0 month-1.4 y) months, and subjects weighing ≥ 30 kg had a median (IQR) age of 14.3 (11.9-16.2) y. Readings could not be obtained in 7.5, 0, and 38.8% of subjects using the pediatric, adult, and smartphone oximeters, respectively. The time to successful reading had a modest negative correlation with age with the inexpensive adult and pediatric oximeters. The inexpensive pediatric oximeter had an overall negative bias, with a mean difference from the reference device of -4.5% (SD 7.9%) and an error that ranged from > 8% to < 33% the reference device. The EARMS was 7.92%. The inexpensive adult oximeter demonstrated no obvious trend in error in the limited saturation range evaluated of 87-99%. The overall mean difference was -0.7% (SD 2.5%). EARMS was 2.5%. The smartphone oximeter underestimated SpO2 at saturations < 94% and overestimated SpO2 for saturations > 94%. Saturations could read as much as > 4%, or < 17%, than the reference oximeter. The mean difference was -2.9% (SD 5.2%). EARMS was 5.1%. CONCLUSIONS: Our findings suggest that the performance of consumer-grade devices varies considerably by both subject age and device. The pediatric fingertip device and smartphone application we tested are poorly suited for use in infants. The adult fingertip device we tested performed quite well in larger children with relatively normal oxygen saturations, and the pediatric fingertip device performed moderately well in subjects > 1 y of age who weighed < 30 kg. Given the vast number of devices available online and ever-changing technology, research to evaluate nonclinical oximeters will continue to be required.

Indoor air quality in remote first nations communities in Ontario, Canada.

A recent study of the health of Indigenous children in four First Nations Communities in remote northwestern Ontario found that 21% of children had been admitted to hospital for respiratory infections before age 2 years. Here we report a detailed analysis of the housing conditions in these communities. We employed a variety of statistical methods, including linear regression, mixed models, and logistic regression, to assess the correlations between housing conditions and loadings of biocontaminants (dust mite allergens, fungal glucan, and endotoxin) and indoor concentrations of PM2.5, CO2, benzene, and formaldehyde. The houses (n = 101) were crowded with an average of approximately 7 people. Approximately 27% of the homes had sustained CO2 concentrations above 1500 ppm. Most homes had more than one smoker. Commercial tobacco smoking and the use of non-electric heating (e.g., wood, oil) were associated with increased fine particle concentrations. Over 90% of the homes lacked working Heat Recovery Ventilators (HRVs), which was associated with increased fine particle concentrations and higher CO2. Of the 101 homes, 12 had mold damage sufficient to increase the relative risk of respiratory disease. This resulted from roof leaks, through walls or around the windows due to construction defects or lack of maintenance. A similar percentage had mold resulting from condensation on windows. Endotoxin loadings were much higher than any previous study in Canada. This work provides evidence for the need for more effort to repair existing houses and to ensure the HRVs are properly installed and maintained.

First reports of primary ciliary dyskinesia caused by a shared DNAH11 allele in Canadian Inuit.

BACKGROUND: Primary ciliary dyskinesia (PCD) is typically an autosomal recessive disease characterized by recurrent infections of the lower respiratory tract, frequent and severe otitis media, chronic rhinosinusitis, neonatal respiratory distress, and organ laterality defects. While severe lower respiratory tract infections and bronchiectasis are common in Inuit, PCD has not been recognized in this population. METHODS: We report a case series of seven Inuit patients with PCD identified by genetic testing in three Canadian PCD centers. RESULTS: Patients ranged from 4 to 59 years of age (at time of last evaluation) and originated in the Qikiqtaaluk region (Baffin Island, n = 5), Nunavut, or Nunavik (northern Quebec, n = 2), Canada. They had typical features of PCD, including neonatal respiratory distress (five patients), situs inversus totalis (four patients), bronchiectasis (four patients), chronic atelectasis (six patients), and chronic otitis media (six patients). Most had chronic rhinitis. Genetic evaluation demonstrated that all had homozygous pathogenic variants in DNAH11 at NM_001277115.1:c.4095+2C>A. CONCLUSIONS: The discovery of this homozygous DNAH11 variant in widely disparate parts of the Nunangat (Inuit homelands) suggests this is a founder mutation that may be widespread in Inuit. Thus, PCD may be an important cause of chronic lung, sinus, and middle ear disease in this population. Inuit with chronic lung disease, including bronchiectasis or laterality defects, should undergo genetic testing for PCD. Consideration of including PCD genetic analysis in routine newborn screening should be considered in Inuit regions.

The International Network on Oesophageal Atresia (INoEA) consensus guidelines on the transition of patients with oesophageal atresia-tracheoesophageal fistula.

Oesophageal atresia-tracheoesophageal fistula (EA-TEF) is a common congenital digestive disease. Patients with EA-TEF face gastrointestinal, surgical, respiratory, otolaryngological, nutritional, psychological and quality of life issues in childhood, adolescence and adulthood. Although consensus guidelines exist for the management of gastrointestinal, nutritional, surgical and respiratory problems in childhood, a systematic approach to the care of these patients in adolescence, during transition to adulthood and in adulthood is currently lacking. The Transition Working Group of the International Network on Oesophageal Atresia (INoEA) was charged with the task of developing uniform evidence-based guidelines for the management of complications through the transition from adolescence into adulthood. Forty-two questions addressing the diagnosis, treatment and prognosis of gastrointestinal, surgical, respiratory, otolaryngological, nutritional, psychological and quality of life complications that patients with EA-TEF face during adolescence and after the transition to adulthood were formulated. A systematic literature search was performed based on which recommendations were made. All recommendations were discussed and finalized during consensus meetings, and the group members voted on each recommendation. Expert opinion was used when no randomized controlled trials were available to support the recommendation. The list of the 42 statements, all based on expert opinion, was voted on and agreed upon.

Respiratory disease in Canadian First Nations and Inuit children.

First Nations and Inuit Children are disproportionately affected by respiratory infections such as viral bronchiolitis, pneumonia and tuberculosis. Rates of long-term lung disease following severe respiratory infections early in life, such as bronchiectasis, are also elevated. In contrast, rates of asthma may be somewhat less than in other Canadian children, although rates of poor asthma control are increased. Causes for the high rates of infections include poverty, overcrowding, housing in need of major repairs and better ventilation, and increased exposure to environmental tobacco smoke. Improving these issues will require addressing the social origins of health in First Nations and Inuit communities, including poverty and employment, building more and improving existing housing, and will likely require developing enhanced immunization and surveillance strategies.

Le nombre d'enfants inuits et des Premières nations atteints d'infections respiratoires comme la bronchiolite virale, la pneumonie et la tuberculose est disproportionné. Le taux de maladies pulmonaires à long terme après de graves infections respiratoires contractées tôt dans la vie, telles que la bronchiectasie, est également élevé. Par contre, le taux d'asthme serait quelque peu inférieur à celui des autres enfants canadiens, même si le taux de mauvais contrôle de l'asthme est plus marqué. Ces forts taux d'infections s'expliquent, entre autres, par la pauvreté, les maisons surpeuplées, les habitations qui ont besoin de réparations majeures et d'une meilleure ventilation et par une exposition accrue à la fumée du tabac dans l'environnement. Pour atténuer ces problèmes, il faudra s'attaquer aux origines sociales de la santé dans les communautés inuites et des Premières nations, soit la pauvreté et l'emploi, la construction d'un plus grand nombre d'habitations et l'amélioration des habitations existantes, et il faudra probablement élaborer de meilleures stratégies de vaccination et de surveillance.

Severe early lower respiratory tract infection is associated with subsequent respiratory morbidity in preschool Inuit children in Nunavut, Canada.

BACKGROUND: Inuit children in Nunavut, Canada, have high rates of lower respiratory tract infection (LRTI) early in life. Whether this commonly results in chronic respiratory symptoms later in life is unknown. METHODS: A cross-sectional survey of 3- to 5-years-old Inuit children was conducted in all three regions of Nunavut, as part of the "Qanuippitali, what about us, how are we?" survey. RESULTS: Reported chronic cough and wheezing were common in preschool Inuit children, although reported asthma diagnosed by a healthcare professional was uncommon. The presence of smokers in the home tended to be associated with severe LRTI in the first 2 years of life. Reported wheezing as well as reported bronchitis or pneumonia in the previous 12 months was significantly associated with severe LRTI in the first 2 years of life. Reported wheezing was also strongly associated with reported bronchitis or pneumonia in the past 12 months. The prevalence of chronic moist cough could not be clearly assessed, due to limitations in the questionnaire. INTERPRETATION: Severe LRTI in the first 2 years of life was associated with ongoing respiratory morbidity in preschool Inuit children, although symptoms appeared to lessen in severity over time.

Reversal of adrenal suppression with ciclesonide.

BACKGROUND: Adrenal suppression secondary to high-dose inhaled corticosteroid use has been reported in children. METHODS: The authors report the use of ciclesonide to reverse adrenal suppression secondary to inhaled fluticasone use in four pediatric patients. RESULTS: In these four children, hypothalamic-pituitary-adrenal axis function normalized after the patients were changed to ciclesonide, while good asthma control was maintained. CONCLUSIONS: Ciclesonide should be considered for the reversal of adrenal suppression secondary to the use of fluticasone, and perhaps other older inhaled corticosteroids as well.

Variation in lung function and nutritional decline in cystic fibrosis by genotype: An analysis of the Canadian cystic fibrosis registry.

BACKGROUND: This study aimed to improve our understanding of the natural history of cystic fibrosis (CF) by comparing lung function and body mass index z-score (zBMI) between patients with different genotypes and identify a genotype with outcomes most comparable to homozygous ΔF508 patients. METHODS: Data was obtained from the Canadian CF Registry between January 1st 2007-January 1st 2016. Patients were categorized into one of five groups based on their genotype. A mixed-effects model was conducted with adjustments for age, sex, age of diagnosis, and baseline clinical measures. RESULTS: Among 2612 patients, those with non-mild forms of CF, and particularly adult patients with the same functional allele classification were found to have a lung function trajectory comparable to individuals with the homozygous ∆F508 genotype (annual change in percent predicted forced expiratory volume in 1 s of -0.83, 95% CI: -0.93, -0.73). The rates of zBMI change over the study period were not significantly different between the genotype groups. CONCLUSION: This population-based study of Canadian CF patients provides adjusted rates of lung function decline and zBMI over ten years. The finding that there are different genotypes with comparable rates of lung function decline to patients of the homozygous ∆F508 group supports the use of multiple comparison groups to assess the long-term efficacy of emerging CF therapies.

Care recommendations for the respiratory complications of esophageal atresia-tracheoesophageal fistula.

Tracheoesophageal fistula (TEF) with esophageal atresia (EA) is a common congenital anomaly that is associated with significant respiratory morbidity throughout life. The objective of this document is to provide a framework for the diagnosis and management of the respiratory complications that are associated with the condition. As there are no randomized controlled studies on the subject, a group of experts used a modification of the Rand Appropriateness Method to describe the various aspects of the condition in terms of their relative importance, and to rate the available diagnostic methods and therapeutic interventions on the basis of their appropriateness and necessity. Specific recommendations were formulated and reported as Level A, B, and C based on whether they were based on "strong", "moderate" or "weak" agreement. The tracheomalacia that exists in the site of the fistula was considered the main abnormality that predisposes to all other respiratory complications due to airway collapse and impaired clearance of secretions. Aspiration due to impaired airway protection reflexes is the main underlying contributing mechanism. Flexible bronchoscopy is the main diagnostic modality, aided by imaging modalities, especially CT scans of the chest. Noninvasive positive airway pressure support, surgical techniques such as tracheopexy and rarely tracheostomy are required for the management of severe tracheomalacia. Regular long-term follow-up by a multidisciplinary team was considered imperative. Specific templates outlining the elements of the clinical respiratory evaluation according to the patients' age were also developed.