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Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]). Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT? This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression. In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P =.03), lower FVC z scores (P =.01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P <.01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA. Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both. ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥8 days/month) asthma-like symptoms or recurrent (≥2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified. [ABSTRACT FROM AUTHOR]

Abstract: Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5–9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case–control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08–1.98; 1.37, 95% CI 1.00–1.86; and 1.60, 95% CI 1.09–2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10–1.89; 1.31, 95% CI 1.02–1.67; and 1.60, 95% CI 1.16–2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma. [Copyright &y& Elsevier]

Abstract: Objective: Otitis media with effusion (OME) in children with primary ciliary dyskinesia (PCD) is recurrent and persistent and presents a complex clinical problem for otolaryngologists. We sought to review the otological presentation of children with PCD treated medically and surgically and to compare audiological outcomes and complications of surgical and medical management in children with PCD and correlate these findings with known PCD ultrastructural ciliary phenotype. Methods: A retrospective review was performed of all patients with PCD and OME presenting from 1991 to 2009. Patients were grouped into “medical management” and “ventilation tube (VT) insertion” groups to observe changes in hearing and post-operative complications. Results: Of 31 patients with PCD and OME, 20 received VTs and 11 were treated by medical management strategies. A median of one set of VTs (range 1–5) were inserted per patient. Hearing thresholds improved to normal (<25dB HL) in 80% ears with VTs (mean improvement from 27.1dB to 22.1dB (p =0.034)), whereas patients managed medically had stable thresholds (22.7–23.6dB (p =0.397) over the study period. At least one episode of post-operative otorrhea occurred in eight (42.1%) VT insertion patients during the study period, and four had multiple episodes. We could not demonstrate any differences in post-surgical outcomes between patient groups based on ultrastructural ciliary phenotype. Otorrhea was well controlled with medical therapy with only one requiring tube removal. Bilateral cholesteatoma was found in two patients. Conclusions: Our data support the use of VT insertion as an option for patients with PCD and OME with mild to moderate hearing loss. Patients should be counseled on the possibility of multiple insertions and the likelihood of post-operative otorrhea, although this was not very troublesome in our group. Ultrastructural ciliary phenotype did not appear to alter the likelihood of post-operative otorrhea in our series. Cholesteatoma should be considered as a potential cause of otorrhea in PCD. [Copyright &y& Elsevier]

The objective of this study was to identify the determinants of short hospital stay (< 24 h) among children admitted because of an acute asthma exacerbation. Computerized health records were used to identify children with a discharge diagnosis of asthma (ICD code 493.0) at the Hospital for Sick Children, Toronto, during the period October 1994 to October 1995. Cases were children with a length of hospital stay of < 24 h (short-stay group) and controls were children with a length of stay of > 24 h (long-stay group). Clinical and demographic data were extracted from the medical record. Over the 12-month period, 485 children were hospitalized because of asthma. Of these, 121 (25%) had short-stay admissions (< 24 h), whereas 364 (75%) had long-stay admissions (> 24 h). Simple random sampling was used to select 85 children from each of the two groups. There were no differences between the two groups regarding language, primary care physician, asthma history, management prior to emergency department (ED) presentation, respiratory rate on presentation, use of the observation unit, and time in the ED. Logistic regression analyses identified three variables associated with short hospital stay: milder asthma (adjusted odds ratio [OR] 4.9), male gender (adjusted OR 2.4), and availability of a delivery device at home (adjusted OR 2.0). In conclusion, many children admitted to hospital because of an asthma exacerbation have short, yet expensive, hospital stays. The results of this study highlight the importance of developing alternative models of health care delivery for asthmatic children requiring short hospital contact. [ABSTRACT FROM AUTHOR]

We hypothesize that children characterized by deprived factors have poorer health outcomes. We aim to identify clustering of determinants and estimate risk of early childhood diseases. This 1993–2019 longitudinal cohort study combines three Canadian pediatric cohorts and their families. Mothers and children are clustered using latent class analysis (LCA) by 16 indicators in three domains (maternal and newborn; socioeconomic status [SES] and neighbourhood; environmental exposures). Hazard ratios (HR) of childhood asthma, allergic rhinitis (AR), and eczema are quantified with Cox proportional hazard (PH) regression. Rate ratios (RR) of children's health services use (HSU) are estimated with Poisson regression. Here we report the inclusion of 15,724 mother–child pairs; our LCA identifies four mother-clusters. Classes 1 and 2 mothers are older (30–40 s), non-immigrants with university education, living in high SES neighbourhoods; Class 2 mothers have poorer air quality and less greenspace. Classes 3 and 4 mothers are younger (20–30 s), likely an immigrant/refugee, with high school-to-college education, living in lower SES neighborhoods with poorer air quality and less greenspace. Children's outcomes differ by Class, in comparison to Class 1. Classes 3 and 4 children have higher risks of asthma (HR 1.24, 95% CI 1.11–1.37 and HR 1.39, 95% CI 1.22–1.59, respectively), and similar higher risks of AR and eczema. Children with AR in Class 3 have 20% higher all-cause physician visits (RR = 1.20, 95% CI 1.10–1.30) and those with eczema have 18% higher all-cause emergency department visits (RR = 1.18, 95% CI 1.09–1.28) and 14% higher all-cause physician visits (RR = 1.14, 95% CI 1.09–1.19). Multifactorial-LCA mother-clusters may characterize associations of children's health outcomes and care, adjusting for interrelationships. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The two American Thoracic Society recommended aerosol delivery devices for methacholine challenge testing are both obsolete and often very difficult to acquire, leading to the test being done with a number of nonstandardized nebulizers. Of the two recommended devices, one is the English Wright nebulizer used in the 2-min tidal breathing method, and the other is the DeVilbiss 646 nebulizer used in the five-breath dosimeter method. The purpose of this study was to evaluate the in vitro performance of potential alternative devices that would be economically viable and would minimize environmental contamination. One device was the disposable breath-actuated AeroEclipse® II BAN as a potential delivery system for the 2-min tidal breathing, and the second was the automated system by VIASYS as an alternative to either the 2-min tidal breathing or the five-breath dosimeter method. Methods: A breath simulator mimicked an adult or small child breathing pattern, and a slow inhalation for the five-breath method was generated by a spirometry calibration syringe. Methacholine (ProvocholineTM) was eluted from filters at the "mouth" and assayed by high-pressure liquid chromatography. Results: In 12 sec, the AeroEclipse II BAN would be expected to have a pulmonary deposition equivalent to the 2-min tidal breathing with the English Wright, whereas the VIASYS system would take approximately 40 sec for the equivalent delivery. The per-breath delivery of the VIASYS and the DeVilbiss 646 was approximately the same, whereas one breath from the AeroEclipse II BAN was the equivalent of five from the DeVilbiss 646. Conclusions: These data will allow for planning in vivo studies to develop methacholine challenge protocols using modern aerosol delivery systems. [ABSTRACT FROM AUTHOR]

To review outcome of children post-allogeneic (allo) and autologous (auto) SCT with severe lung injury who had lung biopsy and to determine whether the diagnoses provided by lung biopsy had an impact on outcome. Retrospective study was carried out from January 2000 to June 2010. Nine hundred and eighteen children (0-18 yr) received SCT (allo 476, auto 442), and 59 biopsies were performed in 48 patients. Most common result of lung biopsy was non-infectious inflammation and recurrent disease in allo- and autorecipients, respectively. In a multivariate analysis, survival of allorecipients who had management change was inferior (p = 0.002 ; HR: 3.12). These patients were extremely sick, and management change was the last attempt to stabilize their respiratory status. There was a trend toward superior survival for children who had biopsy after 100 days following SCT (p = 0.09 ; HR: 0.55) and a trend toward inferior survival for those with proven infections within two wk of biopsy (p = 0.07; HR: 2.14). Only 31% of allorecipients and 25% of autorecipients survived. There were no biopsy-related complications. Lung biopsy itself appears to be well tolerated, although requiring a biopsy seems to carry a poor prognosis; this seems to be due to different causes, auto (relapse), allo (non-infectious inflammation). [ABSTRACT FROM AUTHOR]

Background: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. Methods: A two‐day, face‐to‐face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. Results: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non‐steroid‐based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. Conclusions: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real‐world evidence studies assessing anti‐immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti‐IgE and non‐steroid‐based alternative therapies may delay disease progression, leading to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. Clinical features may be subtle and highly variable, making the diagnosis of PCD challenging. The diagnosis can be confirmed with ciliary ultrastructure analysis and/or molecular genetic testing of 32 PCD-associated genes. However, because of this genetic heterogeneity, comprehensive molecular genetic testing is not considered the standard of care, and the most efficient molecular approach has yet to be elucidated. Here, we propose a cost-effective and time-efficient molecular genetic algorithm to solve cases of PCD. We conducted targeted copy number variation (CNV) analysis and/or whole-exome sequencing on 20 families (22 patients) from a subset of 45 families (52 patients) with a clinical diagnosis of PCD who did not have a molecular genetic diagnosis after Sanger sequencingof12PCD-associatedgenes. This combined molecular genetic approach led to the identification of 4 of 20 (20%) families with clinically significant CNVs and 7 of 20 (35%) families with biallelic pathogenic mutations in recently identified PCD genes, resulting in an increased molecular genetic diagnostic rate of 55% (11/20). In patients with a clinical diagnosis of PCD, whole-exome sequencing followed by targeted CNV analysis results in an overall molecular genetic yield of 76% (34/45). [ABSTRACT FROM AUTHOR]

Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. We identified four unique deleterious variants in the COPA gene (encoding coatomer subunit α) affecting the same functional domain. Hypothesizing that mutant COPA leads to defective intracellular transport via coat protein complex I (COPI), we show that COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport. Additionally, expression of mutant COPA results in ER stress and the upregulation of cytokines priming for a T helper type 17 (TH17) response. Patient-derived CD4+ T cells also demonstrate significant skewing toward a TH17 phenotype that is implicated in autoimmunity. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. [ABSTRACT FROM AUTHOR]

Background: Motile cilia dysfunction causes primary ciliary dyskinesia (PCD), situs inversus totalis (SI), and a spectrum of laterality defects, yet the prevalence of laterality defects other than SI in PCD has not been prospectively studied.Methods: In this prospective study, participants with suspected PCD were referred to our multisite consortium. We measured nasal nitric oxide (nNO) level, examined cilia with electron microscopy, and analyzed PCD-causing gene mutations. Situs was classified as (1) situs solitus (SS), (2) SI, or (3) situs ambiguus (SA), including heterotaxy. Participants with hallmark electron microscopic defects, biallelic gene mutations, or both were considered to have classic PCD.Results: Of 767 participants (median age, 8.1 years, range, 0.1-58 years), classic PCD was defined in 305, including 143 (46.9%), 125 (41.0%), and 37 (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was identified with classic PCD, including 2.6% and 2.3% with SA plus complex or simple cardiac defects, respectively; 4.6% with SA but no cardiac defect; and 2.6% with an isolated possible laterality defect. Participants with SA and classic PCD had a higher prevalence of PCD-associated respiratory symptoms vs SA control participants (year-round wet cough, P < .001; year-round nasal congestion, P = .015; neonatal respiratory distress, P = .009; digital clubbing, P = .021) and lower nNO levels (median, 12 nL/min vs 252 nL/min; P < .001).Conclusions: At least 12.1% of patients with classic PCD have SA and laterality defects ranging from classic heterotaxy to subtle laterality defects. Specific clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.Trial Registry: ClinicalTrials.gov; No.: NCT00323167; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

The article discusses a research study which investigated the prevalence of laterality defects other than situs inversus totalis in primary ciliary dyskinesia (PCD). Study results are presented including the presence of electron microscopic defects and PCD-causing gene mutations. Data provided shows the laterality defects included in situs ambiguus (SA) subgroups, the demographics and clinical features of participants with SA, and the diagnostic testing of participants with classic PCD and SA.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 20 genes, but collectively they account for only ∼65% of all PCDs. To identify mutations in additional genes that cause PCD, we performed exome sequencing on three unrelated probands with ciliary outer and inner dynein arm (ODA+IDA) defects. Mutations in SPAG1 were identified in one family with three affected siblings. Further screening of SPAG1 in 98 unrelated affected individuals (62 with ODA+IDA defects, 35 with ODA defects, 1 without available ciliary ultrastructure) revealed biallelic loss-of-function mutations in 11 additional individuals (including one sib-pair). All 14 affected individuals with SPAG1 mutations had a characteristic PCD phenotype, including 8 with situs abnormalities. Additionally, all individuals with mutations who had defined ciliary ultrastructure had ODA+IDA defects. SPAG1 was present in human airway epithelial cell lysates but was not present in isolated axonemes, and immunofluorescence staining showed an absence of ODA and IDA proteins in cilia from an affected individual, thus indicating that SPAG1 probably plays a role in the cytoplasmic assembly and/or trafficking of the axonemal dynein arms. Zebrafish morpholino studies of spag1 produced cilia-related phenotypes previously reported for PCD-causing mutations in genes encoding cytoplasmic proteins. Together, these results demonstrate that mutations in SPAG1 cause PCD with ciliary ODA+IDA defects and that exome sequencing is useful to identify genetic causes of heterogeneous recessive disorders. [ABSTRACT FROM AUTHOR]

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼ 60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. [Copyright &y& Elsevier]

Rationale Primary ciliary dyskinesia (PCD) is an autosomal recessive, genetically heterogeneous disorder characterised by oto-sino-pulmonary disease and situs abnormalities (Kartagener syndrome) due to abnormal structure and/or function of cilia. Most patients currently recognised to have PCD have ultrastructural defects of cilia; however, some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11). Objectives To test further for mutant DNAH11 as a cause of PCD, DNAH11 was sequenced in patients with a PCD clinical phenotype, but no known genetic aetiology. Methods 82 exons and intron/exon junctions in DNAH11 were sequenced in 163 unrelated patients with a clinical phenotype of PCD, including those with normal ciliary ultrastructure (n=58), defects in outer and/or inner dynein arms (n=76), radial spoke/central pair defects (n=6), and 23 without definitive ultrastructural results, but who had situs inversus (n=17), or bronchiectasis and/or low nasal nitric oxide (n=6). Additionally, DNAH11 was sequenced in 13 subjects with isolated situs abnormalities to see if mutant DNAH11 could cause situs defects without respiratory disease. Results Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11; and two patients without ultrastructural analysis had biallelic mutations. All mutations were novel and private. None of the patients with dynein arm or radial spoke/central pair defects, or isolated situs abnormalities, had mutations in DNAH11. Of the 35 identified mutant alleles, 24 (69%) were nonsense, insertion/deletion or loss-of-function splice-site mutations. Conclusions Mutations in DNAH11 are a common cause of PCD in patients without ciliary ultrastructural defects; thus, genetic analysis can be used to ascertain the diagnosis of PCD in this challenging group of patients. [ABSTRACT FROM AUTHOR]

Purpose: To develop evidence-based performance indicators that measure the quality of primary care for asthma.Data Sources: Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and CINAHL for peer-reviewed articles published in 1998-2008 and five national/global asthma management guidelines.Study Selection: Articles with a focus on current asthma performance indicators recognized or used in community and primary care settings. Data extraction Modified RAND AppropriatenessMethod: was used. The work described herein was conducted in Canada in 2008. Five clinician experts conducted the systematic literature review. Asthma-specific performance indicators were developed and the strength of supporting evidence summarized. A survey was created and mailed to 17 expert panellists of various disciplines, asking them to rate each indicator using a 9-point Likert scale. Percentage distribution of the Likert scores were generated and given to the panellists before a face-to-face meeting, which was held to assess consensus. At the meeting, they ranked all indicators based on their reliability, validity, availability and feasibility.Results: Literature search yielded 1228 articles, of which 135 were used to generate 45 performance indicators in five domains: access to care, clinical effectiveness, patient centeredness, system integration and coordination and patient safety. The top five ranked indicators were: Asthma Education from Certified Asthma Educator, Pulmonary Function Monitoring, Asthma Control Monitoring, Controller Medication Use and Asthma Control.Conclusion: The top 15 ranked indicators are recommended for implementation in primary care to measure asthma care delivery, respiratory health outcomes and establish benchmarks for optimal health service delivery over time and across populations. [ABSTRACT FROM AUTHOR]

Purpose To develop evidence-based performance indicators that measure the quality of primary care for asthma. Data sources Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and CINAHL for peer-reviewed articles published in 1998–2008 and five national/global asthma management guidelines. Study selection Articles with a focus on current asthma performance indicators recognized or used in community and primary care settings. Data extraction Modified RAND Appropriateness Method was used. The work described herein was conducted in Canada in 2008. Five clinician experts conducted the systematic literature review. Asthma-specific performance indicators were developed and the strength of supporting evidence summarized. A survey was created and mailed to 17 expert panellists of various disciplines, asking them to rate each indicator using a 9-point Likert scale. Percentage distribution of the Likert scores were generated and given to the panellists before a face-to-face meeting, which was held to assess consensus. At the meeting, they ranked all indicators based on their reliability, validity, availability and feasibility. Results Literature search yielded 1228 articles, of which 135 were used to generate 45 performance indicators in five domains: access to care, clinical effectiveness, patient centeredness, system integration and coordination and patient safety. The top five ranked indicators were: Asthma Education from Certified Asthma Educator, Pulmonary Function Monitoring, Asthma Control Monitoring, Controller Medication Use and Asthma Control. Conclusion The top 15 ranked indicators are recommended for implementation in primary care to measure asthma care delivery, respiratory health outcomes and establish benchmarks for optimal health service delivery over time and across populations. [ABSTRACT FROM AUTHOR]

Abstract: The first population-based survey to determine predictors of influenza vaccination among children in a major metropolitan city with access to publicly funded health care and a universal influenza immunization program (UIIP). Previously collected demographic and health related data from 5619 school children aged 5–9 in Toronto, in 2006 were used to predict influenza vaccination. Vaccination was more likely in children with current asthma (OR 1.44, 95%CL 1.19–1.75), a high volume of contacts with a health service provider (OR 1.37, 95%CL 1.14–1.65), foreign born children (OR 1.20, 95%CL 1.01–1.42) and those with the lowest income adequacy (OR 1.37, 95%CL 1.12–1.68). Data from this study will be helpful in designing future influenza vaccination strategies to improve vaccination rates in the entire population. [Copyright &y& Elsevier]

Motile cilia are cellular beating machines that play a critical role in mucociliary clearance, cerebrospinal fluid movement, and fertility. In the airways, hundreds of motile cilia present on the surface of a multiciliated epithelia cell beat coordinately to protect the epithelium from bacteria, viruses, and harmful particulates. During multiciliated cell differentiation, motile cilia are templated from basal bodies, each extending a basal foot—an appendage linking motile cilia together to ensure coordinated beating. Here, we demonstrate that among the many motile cilia of a multiciliated cell, a hybrid cilium with structural features of both primary and motile cilia is harbored. The hybrid cilium is conserved in mammalian multiciliated cells, originates from parental centrioles, and its cellular position is biased and dependent on ciliary beating. Furthermore, we show that the hybrid cilium emerges independently of other motile cilia and functions in regulating basal body alignment. • Multiciliated cells contain a hybrid cilium with features of primary and motile cilium • The hybrid cilium originates from parental centriole • The hybrid cilium position is biased toward the cilia beating direction • The hybrid cilium functions in basal body alignment Liu, Nguyen et al. show that among hundreds of cilia of a multiciliated cell, there is one that differs from the others in structure, origin, and cellular position, and it participates in basal body alignment. [ABSTRACT FROM AUTHOR]