Leveraging human-mouse studies to advance the genetics of hearing impairment in Africa.

Mouse models are used extensively to understand human pathobiology and mechanistic functions of disease-associated loci. However, in this review, we investigate the potential of using genetic mouse models to identify genetic markers that can disrupt hearing thresholds in mice and then target the hearing-enriched orthologues and loci in humans. Currently, little is known about the real prevalence of genes that cause hearing impairment (HI) in Africa. Pre-screening mouse cell lines to identify orthologues of interest has the potential to improve the genetic diagnosis for HI in Africa to a significant percentage, for example, 10-20%. Furthermore, the functionality of a candidate gene derived from mouse screening with heterogeneous genetic backgrounds and multi-omic approaches can shed light on the molecular, genetic heterogeneity and plausible mode of inheritance of a gene in hearing-impaired individuals especially in the absence of large families to investigate.

The analyses of human MCPH1 DNA repair machinery and genetic variations.

Causal mutations in the MCPH1 gene have been associated with disorders like microcephaly, and recently congenital hearing impairment. This study examined the MCPH1 DNA repair machinery and identified genetic variations of interest in gnomAD database to discuss the biological roles and effects of rare variants in MCPH1-related diseases. Notably, MCPH1 coordinates two of the seven known mechanisms of DNA repair which confirmed its roles in neurogenesis and chromatin condensation. A pathogenic missense variant in MCPH1 p.Gly753Arg, and two pathogenic frameshifts MCPH1 p.Asn189LysfsTer15 and p.Cys624Ter identified in this study, already had entries in ClinVar and were associated with microcephaly. A pathogenic frameshift in MCPH1 p.Val10SerfsTer5 with a loss-of-function flag and a pathogenic stop gained p.Ser571Ter variants with ultra-rare allele frequency (MAF ≤ 0.001) were identified but have not been linked to any phenotype. The predicted pathogenic ultra-rare variants identified in this study, warranty phenotypic discovery, and also positioned these variants or nearby deleterious variants candidate for screening in MCPH1-associated rare diseases.

Dried Blood Spot Test for Glycated Hemoglobin Measurement in Pediatric Diabetes Care.

BACKGROUND: The dried blood spot (DBS) card is a novel collection method for measuring glycated hemoglobin (A1C) in individuals with diabetes mellitus. The potential benefits of DBS specimens compared with traditional phlebotomy include a reduction in required total blood volume, reduced procedural pain, and an ability for self-initiated collection. DBS cards for A1C measurement have been validated in the adult population, but there is a paucity of pediatric data. METHODS: The aim of this study was to validate the use of A1C measurement by DBS cards in comparison to venous A1C and to identify potential barriers to implementing this novel approach. Venous and DBS card A1C samples were collected simultaneously from 62 patients at their local laboratory and transported to the central provincial lab for analysis. Correlation analyses compared venous and DBS A1C with data rescaling performed to account for the DBS-venous interassay difference. RESULTS: Mean venous A1C was 7.49% and DBS A1C was 7.26%, with an interassay difference of 0.23%. Data showed a strong, positive correlation between A1C collection methods (r=0.86, p<0.001); this was further strengthened at lower A1C values (A1C <7.5%, r=0.87, p<0.0001). A stronger relationship emerged when the data were rescaled to account for the DBS-venous interassay difference (r=0.8935, p<0.0001). CONCLUSIONS: Given the potential feasibility, practicality, accessibility, cost-effectiveness, and performance characteristics of the DBS A1C, especially at lower A1C values hovering around the diagnostic threshold for diabetes, this study provides supporting evidence for consideration of the use of DBS A1C testing in pediatric diabetes care.

Genomic medicine in Africa: a need for molecular genetics and pharmacogenomics experts.

The large-scale implementation of genomic medicine in Africa has not been actualized. This overview describes how routine molecular genetics and advanced protein engineering/structural biotechnology could accelerate the implementation of genomic medicine. By using data-mining and analysis approaches, we analyzed relevant information obtained from public genomic databases on pharmacogenomics biomarkers and reviewed published studies to discuss the ideas. The results showed that only 68 very important pharmacogenes currently exist, while 867 drug label annotations, 201 curated functional pathways, and 746 annotated drugs have been catalogued on the largest pharmacogenomics database (PharmGKB). Only about 5009 variants of the reported ∼25,000 have been clinically annotated. Predominantly, the genetic variants were derived from 43 genes that contribute to 2318 clinically relevant variations in 57 diseases. Majority (∼60%) of the clinically relevant genetic variations in the pharmacogenes are missense variants (1390). The enrichment analysis showed that 15 pharmacogenes are connected biologically and are involved in the metabolism of cardiovascular and cancer drugs. The review of studies showed that cardiovascular diseases are the most frequent non-communicable diseases responsible for approximately 13% of all deaths in Africa. Also, warfarin pharmacogenomics is the most studied drug on the continent, while CYP2D6, CYP2C9, DPD, and TPMT are the most investigated pharmacogenes with allele activities indicated in African and considered to be intermediate metaboliser for DPD and TPMT (8.4% and 11%). In summary, we highlighted a framework for implementing genomic medicine starting from the available resources on ground.

Hearing loss and brain disorders: A review of multiple pathologies.

Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer's disease/dementia, Parkinson's disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.

Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali.

Objectives: To identify the etiologies of hearing impairment (HI) in schools for students who are deaf and to use a systematic review to summarize reports on the etiologies and clinical and genetic features of HI in Mali. Methods: We included individuals with HI that started before the age of 15 years old. Patients were carefully evaluated under standard practices, and pure-tone audiometry was performed where possible. We then searched for articles published on HI in the Malian population from the databases' inception to March 30, 2020. Results: A total of 117 individuals from two schools for the deaf were included, and a male predominance (sex ratio 1.3; 65/52) was noted. HI was pre-lingual in 82.2% (n = 117), and the median age at diagnosis was 12 years old. The etiologies were environmental in 59.4% (70/117), with meningitis being the leading cause (40%, 20/70), followed by cases with genetic suspicion (29.3%, 21/117). In 11.3% (8/117) of patients, no etiology was identified. Among cases with genetic suspicion, three were syndromic, including two cases of Waardenburg syndrome, while 15 individuals had non-syndromic HI. An autosomal recessive inheritance pattern was observed in 83.3% of families (15/18), and consanguinity was reported in 55.5% (10/18) of putative genetic cases. Conclusion: This study concludes that environmental factors are the leading causes of HI in Mali. However, genetic causes should be investigated, particularly in the context of a population with a high consanguinity rate.

Perioperative care of obstructive sleep apnea patients: A survey of European anesthesiologists.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in the surgical patient population and is associated with high risk of perioperative complications. There are limited guidelines and wide practice variations regarding the perioperative care of obese and OSA patients. This is a study of European anesthesiologists' clinical practice of perioperative care of OSA patients. METHODS: This survey evaluated United Kingdom anesthesiologists' clinical practice of the perioperative care of OSA patients. Outcomes and variables were compared between 4100 anesthesiologists of different clinical experience and hospital settings. RESULTS: Approximately 45% of respondents manage OSA patients rarely, 42% occasionally, and 13% regularly. Most respondents order OSA screening tests if patients have tonsillar hypertrophy, head/neck tumor, BMI >35, increased neck circumference, craniofacial anomaly, and right-sided electrocardiography (ECG) anomaly. Majority request preoperative polysomnography, ECG, overnight pulse oximetry, and arterial blood gas analysis. Majority recommend preoperative weight loss, optimisation, smoking cessation, reduction of substance use, and regular mask-CPAP use. Majority consider endoscopy, and ophthalmology as appropriate day case procedures, but not laparoscopy. Majority postpone elective airway, laparoscopic, laparotomy, and head/neck surgery; if patients are not optimized preoperatively. For major surgery, combined general + neuraxial anesthesia was ranked as 3rd option. For major limb surgery, neuraxial anesthesia without sedation was ranked as 1st option, nerve block without sedation was ranked 2nd, and general anesthesia + nerve block was ranked 3rd or 4th. At anesthesia emergence, majority ensure that patients have normal consciousness, respiration and neuromuscular function. Majority ensure postoperative oximetry, telemetry, and oxygen supplementation. CONCLUSION: This study highlights variations in anesthesiologists' perioperative care of OSA patients; even in developed countries with advanced medical training and standards. The study outcomes will improve perioperative care of OSA patients.

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

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

Whole exome sequencing identifies rare coding variants in novel human-mouse ortholog genes in African individuals diagnosed with non-syndromic hearing impairment.

Physiologically, the human and murine hearing systems are very similar, justifying the extensive use of mice in experimental models for hearing impairment (HI). About 340 murine HI genes have been reported; however, whether variants in all human-mouse ortholog genes contribute to HI has been rarely investigated. In humans, nearly 120 HI genes have been identified to date, with GJB2 and GJB6 variants accounting for half of congenital HI cases, of genetic origin, in populations of European and Asian ancestries, but not in most African populations. The contribution of variants in other known genes of HI among the populations of African ancestry is poorly studied and displays the lowest pick-up rate. We used whole exome sequencing (WES) to investigate pathogenic and likely pathogenic (PLP) variants in 34 novel human-mouse orthologs HI genes, in 40 individuals from Cameroon and South Africa diagnosed with non-syndromic hearing impairment (NSHI), and compared the data to WES data of 129 ethnically matched controls. In addition, protein modeling for selected PLP gene variants, gene enrichment, and network analyses were performed. A total of 4/38 murine genes, d6wsu163e, zfp719, grp152 and minar2, had no human orthologs. WES identified three rare PLP variants in 3/34 human-mouse orthologs genes in three unrelated Cameroonian patients, namely: OCM2, c.227G>C p.(Arg76Thr) and LRGI1, c.1657G>A p.(Gly533Arg) in a heterozygous state, and a PLP variant MCPH1, c.2311C>G p.(Pro771Ala) in a homozygous state. In silico functional analyses suggest that these human-mouse ortholog genes functionally co-expressed interactions with well-established HI genes: GJB2 and GJB6. The study found one homozygous variant in MCPH1, likely to explain HI in one patient, and suggests that human-mouse ortholog variants could contribute to the understanding of the physiology of hearing in humans.

Methyl jasmonate delays the latency to anoxic convulsions by normalizing the brain levels of oxidative stress biomarkers and serum corticosterone contents in mice with repeated anoxic stress.

OBJECTIVES: Repeated exposure to anoxic stress damages the brain through cortisol-mediated increases in oxidative stress and cellular-antioxidants depletion. Thus, compounds with antioxidant property might confer protection against anoxic stress-induced brain injuries. In this study, we further examined the protective effect of methyl jasmonate (MJ), a potent anti-stress agent against anoxic stress-induced convulsions in mice. METHODS: Thirty-six male Swiss mice randomized into six groups (n=6) were given MJ (25, 50 and 100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.) 30 min before 15 min daily exposure to anoxic stress for 7 days. The latency(s) to anoxic convulsion was recorded on day 7. The blood glucose and serum corticosterone levels were measured afterwards. The brains were also processed for the determination of malondialdehyde, nitrite, and glutathione levels. RESULTS: Methyl jasmonate (MJ) delayed the latency to anoxic convulsion and reduced the blood glucose and serum corticosterone levels. The increased malondialdehyde and nitrite contents accompanied by decreased glutathione concentrations in mice with anoxic stress were significantly attenuated by MJ. CONCLUSIONS: These findings further showed that MJ possesses anti-stress property via mechanisms relating to the reduction of serum contents of corticosterone and normalization of brain biomarker levels of oxidative stress in mice with anoxic stress.

The course of asthma: A population-based 10-year study examining asthma remission in children diagnosed with asthma in preschool.

BACKGROUND: The natural course of asthma may differ depending on the age of onset. OBJECTIVE: To investigate predictors of asthma remission with a focus on the age of asthma onset. METHODS: The study was a retrospective birth cohort of children with asthma in Saskatchewan, Canada. Using the Saskatchewan Ministry of Health databases, we identified children with a diagnosis of asthma in the first 6 years of life and who had at least 10 years of follow-up after diagnosis (n = 22 563). Of these, we included 6393 children either with persistent asthma (≥1 physician visit or hospitalization for asthma [PVHA] during each year of follow-up) and those who had remission (had PVHA in the first year after diagnosis but at some point during the follow-up no longer received PVHA until end of the study). We used survival analysis to examine associations between remission and age of asthma onset. RESULTS: Of the study participants, 87.2% had early-onset (≤3 years) and 12.8% had late-onset (4-6 years) asthma. Over the 10-years of follow-up, the rate of asthma remission was 37 per 100 person-years. Early-onset asthma (hazard ratio [HR] = 1.10; 95%confidence interval [CI]: 1.01-1.20), being female (HR = 1.12; 95%CI: 1.07-1.18), living in a rural (HR = 1.20; 95%CI: 1.14-1.27) and medium urban (HR = 1.16; 95%CI: 1.08-1.26) location were positively associated with remission while history of atopy decreased likelihood of remission (HR = 0.73; 95%CI: 0.54-0.97). CONCLUSION: Most children with asthma experienced remission, especially those with the onset of symptoms within the first 3 years of life.

Hearing Impairment Overview in Africa: the Case of Cameroon.

The incidence of hearing impairment (HI) is higher in low- and middle-income countries when compared to high-income countries. There is therefore a necessity to estimate the burden of this condition in developing world. The aim of our study was to use a systematic approach to provide summarized data on the prevalence, etiologies, clinical patterns and genetics of HI in Cameroon. We searched PubMed, Scopus, African Journals Online, AFROLIB and African Index Medicus to identify relevant studies on HI in Cameroon, published from inception to 31 October, 2019, with no language restrictions. Reference lists of included studies were also scrutinized, and data were summarized narratively. This study is registered with PROSPERO, number CRD42019142788. We screened 333 records, of which 17 studies were finally included in the review. The prevalence of HI in Cameroon ranges from 0.9% to 3.6% in population-based studies and increases with age. Environmental factors contribute to 52.6% to 62.2% of HI cases, with meningitis, impacted wax and age-related disorder being the most common ones. Hereditary HI comprises 0.8% to 14.8% of all cases. In 32.6% to 37% of HI cases, the origin remains unknown. Non-syndromic hearing impairment (NSHI) is the most frequent clinical entity and accounts for 86.1% to 92.5% of cases of HI of genetic origin. Waardenburg and Usher syndromes account for 50% to 57.14% and 8.9% to 42.9% of genetic syndromic cases, respectively. No pathogenic mutation was described in GJB6 gene, and the prevalence of pathogenic mutations in GJB2 gene ranged from 0% to 0.5%. The prevalence of pathogenic mutations in other known NSHI genes was <10% in Cameroonian probands. Environmental factors are the leading etiology of HI in Cameroon, and mutations in most important HI genes are infrequent in Cameroon. Whole genome sequencing therefore appears as the most effective way to identify variants associated with HI in Cameroon and sub-Saharan Africa in general.

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson's disease in Black South African and Nigerian patients.

BACKGROUND: The prevalence of Parkinson's disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. METHODS: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2's protein structure was investigated by molecular modelling. RESULTS: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. CONCLUSIONS: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.

The Hearing Impairment Ontology: A Tool for Unifying Hearing Impairment Knowledge to Enhance Collaborative Research.

Hearing impairment (HI) is a common sensory disorder that is defined as the partial or complete inability to detect sound in one or both ears. This diverse pathology is associated with a myriad of phenotypic expressions and can be non-syndromic or syndromic. HI can be caused by various genetic, environmental, and/or unknown factors. Some ontologies capture some HI forms, phenotypes, and syndromes, but there is no comprehensive knowledge portal which includes aspects specific to the HI disease state. This hampers inter-study comparability, integration, and interoperability within and across disciplines. This work describes the HI Ontology (HIO) that was developed based on the Sickle Cell Disease Ontology (SCDO) model. This is a collaboratively developed resource built around the 'Hearing Impairment' concept by a group of experts in different aspects of HI and ontologies. HIO is the first comprehensive, standardized, hierarchical, and logical representation of existing HI knowledge. HIO allows researchers and clinicians alike to readily access standardized HI-related knowledge in a single location and promotes collaborations and HI information sharing, including epidemiological, socio-environmental, biomedical, genetic, and phenotypic information. Furthermore, this ontology illustrates the adaptability of the SCDO framework for use in developing a disease-specific ontology.

Parkinson's disease in Nigeria: A review of published studies and recommendations for future research.

Parkinson's disease (PD) affects 1-2% of individuals above 60 years amounting to over 7 million people worldwide. Thus, PD has become an important contributor to the neurological disease burden. Nigeria is the most populous country in Africa, and alarmingly, approximately 5.25 million Nigerians are above 65 years and are therefore at risk for developing PD. We carried out a critical review of published literature on PD in Nigeria to summarize the findings and to evaluate gaps in knowledge. Seven electronic databases were searched for studies published in English before 18th July 2018. Search terms were ["Parkinson's disease" OR "Parkinson disease" OR "parkinsonian disorders" OR "Parkinsonism"] AND "Nigeria". A total of 44 articles (including eight reviews) published since 1969 were identified and reviewed. Amongst the original research articles, most (23) were on PD symptoms or prevalence. There were only two studies on genetics and two on environmental factors. The estimated crude prevalence of PD in Nigeria was lower (10-249/100 000) compared to studies published in Europe (65.6-12 500/100 000). Our findings suggest that PD is under-diagnosed in Nigeria. Possible environmental risk factors identified include blacksmithing and well-water contaminated with trace metals. Given the rising numbers of the ageing population in Nigeria, more studies to evaluate the prevalence and causes of PD in this country are urgently needed. To this end, more funding, resources and a workforce of well-trained neurologists and scientists are essential to manage the impending health burden of PD and related disorders in this country.

Household Air Pollution, Levels of Micronutrients and Heavy Metals in Cord and Maternal Blood, and Pregnancy Outcomes.

Cooking with kerosene emits toxic pollutants that may impact pregnancy outcomes. Sixty-eight women in their first trimester of pregnancy, kerosene users (n = 42) and liquefied natural gas (LNG) users (n = 26), were followed until birth. Maternal and cord blood were collected immediately after birth. Levels of micronutrients and heavy metals were quantified. Pregnancy outcomes (gestation age (GA), birth weight (BW), and chest and head circumference) were also measured. Mean (± standard deviation (SD)) age of mothers in kerosene and LNG groups were similar (p = 0.734). Mean (±SD) BW of newborns of LNG users was significantly higher compared to newborns of kerosene users (3.43 ± 0.32 vs. 3.02 ± 0.43, p < 0.001). Mean GA (in weeks) was similar between the two groups (p = 0.532). Women in the kerosene group had significantly higher cord blood levels of zinc, lead, mercury, iodine and vitamin B6 and lower levels of folic acid compared to LNG users (p < 0.05). Newborns of kerosene users had reduced levels of zinc, lead, mercury, iodine, vitamins B6 and B12, folic acid, and homocysteine compared with LNG users (p < 0.05). Also, cooking with kerosene was significantly associated with reduced birth weight after adjusting for potential confounders (ß ± standard error (SE) = -0.326 ± 0.155; p = 0.040). Smoke from kerosene stove was associated with reduced birth weight and micronutrients imbalance in mothers and newborns.

The association between endotoxin and beta-(1 → 3)-D-glucan in house dust with asthma severity among schoolchildren.

BACKGROUND: Asthma severity can be affected by microbial exposures. However, less is known about the specific indoor agents aggravating the disease in children. We examined the associations between indoor endotoxin and beta-(1 → 3)-D-glucan exposures and asthma severity in children with asthma. METHODS: A clinical cross-sectional study of schoolchildren (aged 7-17 years) was conducted in the province of Saskatchewan, Canada. Children with asthma (n = 116) were identified from 335 participants using a combination of survey responses and objective clinical assessments. We then ascertained asthma severity based on recommended guidelines (continuous daytime asthma symptoms, frequent nighttime asthma symptoms, and ≤ 60% predicted FEV1). Levels of indoor endotoxin and beta-(1 → 3)-D-glucan were measured in dust samples obtained from play area floors and child's mattresses. RESULTS: The study population of 116 children with asthma was comprised of 75.9% mild asthma and 24.1% moderate/severe asthma. Higher mattress endotoxin concentration was associated with increased odds of moderate/severe asthma [adjusted odds ratio (aOR) = 11.40, 95% confidence interval (CI): 1.45-89.43] while higher beta-(1 → 3)-D-glucan concentration (aOR = 0.16, 95% CI: 0.03-0.89) and load (aOR = 0.10, 95% CI: 0.02-0.72) in play areas were inversely associated with moderate/severe asthma. Furthermore, higher mattress endotoxin concentration was associated with lower FVC (p = 0.01) and FEV1 (p = 0.03). These associations were not seen for beta-(1 → 3)-D-glucan. CONCLUSION: Our results showed differential effects of microbial exposures on childhood asthma severity and further highlight domestic endotoxin exposure effects on respiratory health outcomes in children with asthma.

The association between endotoxin in house dust with atopy and exercise-induced bronchospasm in children with asthma.

BACKGROUND: Studies have reported protective and adverse associations between microbial exposure and childhood asthma. However, among children with asthma the relationships between endotoxin and exercise-induced bronchospasm (EIB) is less clear. OBJECTIVE: We investigated the association between exposure to endotoxin in house dust with atopy and EIB in children with asthma. METHODS: A cross-sectional survey was conducted among schoolchildren (aged 7-17 years) in the province of Saskatchewan, Canada. A subpopulation with asthma (n = 116) were identified from 335 participants using a validated asthma algorithm. We determined atopy among the asthma subpopulation by skin prick testing (SPT) while EIB was evaluated using exercise challenge testing (ECT). Dust samples were collected from mattress and play area floors, and endotoxin was measured in dust extracts. Logistic regression analyses were used to explore associations between endotoxin with atopy and EIB. RESULTS: Among the 116 children with asthma, 99 completed SPT and all had completed ECT. Of these, 71/99 (71.7%) were atopic and 26/116 (22.4%) had EIB. Exposure to high play area endotoxin concentration [adjusted odds ratio (aOR) = 0.15, 95% CI: 0.03-0.85] and load (aOR = 0.11, 95% CI: 0.02-0.73) were negatively associated with atopy. In contrast, EIB was positively associated with high mattress endotoxin concentration (aOR = 6.01, 95% CI: 1.20-30.13). CONCLUSION: Indoor microbial endotoxin exposure has varied associations with atopy and exercise-induced bronchospasm among children with asthma.