Connie L. Yang

Diagnosis and management of asthma in preschoolers: A Canadian Thoracic Society and Canadian Paediatric Society position paper.

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.

FOXP1 haploinsufficiency: Phenotypes beyond behavior and intellectual disability?

The forkhead box (FOX) transcription factors have roles in development, carcinogenesis, metabolism, and immunity. In humans FOXP1 mutations have been associated with language and speech defects, intellectual disability, autism spectrum disorder, facial dysmorphisms, and congenital anomalies of the kidney and urinary tract. In mice, Foxp1 plays critical roles in development of the spinal motor neurons, lymphocytes, cardiomyocytes, foregut, and skeleton. We hypothesized therefore that mutations of FOXP1 affect additional tissues in some humans. Supporting this hypothesis, we describe two individuals with novel variants of FOXP1 (NM_032682.5:c.975‐2A>C and NM_032682.5:c.1574G>A) and additional features. One had a lung disease resembling neuroendocrine cell hyperplasia of infancy (NEHI), and the second had a skeletal disorder with undertubulation of the long bones and relapsing‐remitting fevers associated with flushing and edema. Although attribution of these traits to mutation of FOXP1 requires ascertainment of additional patients, we hypothesize that the variable expression of these additional features might arise by means of stochastic developmental variation.

Forced expiratory values in 1 second corresponding to Pediatric Respiratory Assessment Measure and Acute Asthma Intensity Research Score values during pediatric acute asthma exacerbations

0 81 (68e91) 85 0 81 (68e91) 83 1 68 (52e86) 61 1 68 (54e87) 58 2 58 (45e77) 44 2 58 (49e78) 37 3 59 (46e70) 45 3 60 (39e69) 32 4 48 (41e55) 49 4 53 (42e64) 34 5 39 (30e49) 123 5 50 (42e56) 44 6 32 (27e40) 66 6 41 (33e54) 85 7 32 (18e48) 23 7 33 (29e46) 51 8 23 (18e37) 4 8 32 (21e39) 41 9 NA 9 32 (21e38) 19 10 10 32 (25e44) 13 11 11 25 (16e29) 5 12 12 20 1 for emergency department (ED) visits and hospitalizations. Expert panel guidelines recommend measurement of percent-predicted forced expiratory volume in 1 second (FEV1) or peak expiratory flow for exacerbation severity assessment and treatment decision making.1 These guidelines categorize exacerbation severity according to percent-predicted FEV1 as mild to moderate (FEV1 40%) and severe (FEV1 <40%), but acute care facilities that treat pediatric exacerbations generally do not have the equipment or personnel for such measures of lung function. In addition, we and others have reported that many children with exacerbations cannot perform spirometry meeting American Thoracic Society (ATS) acceptability criteria, and peak expiratory flow may not be an accurate measure of lung function during exacerbations.2e6 Indeed, children younger than 5 years cannot consistently perform spirometry, and only 17% of those older than 5 years can do so during severe exacerbations.2,5 Bedside asthma exacerbation severity scores can be measured in all patients regardless of age or exacerbation severity. The 13point (0e12, with 12 indicating most severe) Pediatric Respiratory Assessment Measure (PRAM) was validated against predicted airway resistance by impulse oscillometry (IOS) and discriminated baseline severity and responsiveness to treatment in children with exacerbations.7 The 17-point (0e16, with 16 indicating most severe) Acute Asthma Intensity Research Score (AAIRS) was similarly validated against FEV1 and IOS in pediatric patients aged 5 to 17 years during acute asthma exacerbations.8 The PRAM and AAIRS had similar performance in discriminating pretreatment FEV1 and change of FEV1 during treatment.9 We have also reported associations of AAIRS and change of AAIRS during treatment with the outcomes of hospital and pediatric intensive care unit admission.8 We have reported associations of the AAIRS with FEV1 and with hospital and pediatric intensive care unit admission using multivariable regressionmodels in a cohort of children aged 5 to 17 years with 933 exacerbations among 813 unique participants in our urban children’s hospital ED.8 For each participant, we performed a comprehensive pulmonary examination that included measurement of all PRAM and AAIRS components. Score components were entered in a REDCap database that electronically calculated each score.10 Each participant attempted forced vital capacitymaneuvers

Respiratory Presentation of Pediatric Patients in the 2014 Enterovirus D68 Outbreak.

Background. In the fall of 2014, a North American outbreak of enterovirus D68 resulted in a significant number of pediatric hospital admissions for respiratory illness throughout North America. This study characterized the clinical presentation and risk factors for a severe clinical course in children admitted to British Columbia Childrens Hospital during the 2014 outbreak. Methods. Retrospective chart review of patients with confirmed EV-D68 infection admitted to BCCH with respiratory symptoms in the fall of 2014. Past medical history, clinical presentation, management, and course in hospital was collected and analyzed using descriptive statistics. Comparison was made between those that did and did not require ICU admission to identify risk factors. Results. Thirty-four patients were included (median age 7.5 years). Fifty-three percent of children had a prior history of wheeze, 32% had other preexisting medical comorbidities, and 15% were previously healthy. Ten children (29%) were admitted to the pediatric intensive care unit. The presence of complex medical conditions (excluding wheezing) (P = 0.03) and copathogens was associated with PICU admission (P = 0.02). Conclusions. EV-D68 infection resulted in severe, prolonged presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of wheeze and preexisting medical comorbidities appear to be most severely affected, but the virus can also cause wheezing in previously well children.

Bleomycin-associated Lung Toxicity in Childhood Cancer Survivors.

Pulmonary disease is a significant morbidity among childhood cancer survivors. The aim of this study was to characterize the pulmonary dysfunction experienced by childhood cancer survivors treated with bleomycin. A cross-sectional analysis of pulmonary function testing (PFT) in survivors treated with bleomycin was preformed. The most recent posttherapy PFT was assessed. Spirometry and lung volumes were categorized as normal, restrictive, obstructive, or mixed. Diffusing capacity of carbon monoxide (DLCO) was categorized as normal or abnormal. PFT data of 143 survivors was analyzed. PFTs were performed a median of 2.3 years (interquartile range, 1.4 to 4.9) from completion of therapy. Spirometry was abnormal in 58 (41%), only 5 (9%) had respiratory symptoms. Forty-two (70%) had obstructive, 11 (18%) restrictive, and 5 (9%) mixed ventilatory defects. The majority of abnormalities were mild (91%). DLCO was abnormal in 27. Reductions were mild in 96%. Patients with a history of relapse were more likely to develop abnormalities in spirometry and/or DLCO (odds ratio=5.02, 95% confidence interval: 1.3-19.4, P=0.01; odds ratio=3.47, 95% confidence interval: 1.01-11.9, P=0.03). Asymptomatic abnormalities of PFT are common among childhood cancer survivors treated with bleomycin and associated with a history of relapse. Research studying the risk for clinical progression of this dysfunction is warranted.