Thomas Kovesi

Canadian Pediatric Asthma Consensus Guidelines, 2003 (updated to December 2004): Introduction

Background: Although guidelines for the diagnosis and management of asthma have been published over the last 15 years, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian asthma consensus report, important new studies, particularly in children, have highlighted the need to incorporate this new information into asthma guidelines. Objectives: To review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the Canadian Asthma Consensus Report, 1999 and its 2001 update with a major focus on pediatric issues. Methods: Diagnosis of asthma in young children, prevention strategies, pharmacotherapy, inhalation devices, immunotherapy and asthma education were selected for review by small expert resource groups. In June 2003, the reviews were discussed at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published up to December 2004 were subsequently reviewed by the individual expert resource groups. Results: This report evaluates early life prevention strategies and focuses on treatment of asthma in children. Emphasis is placed on the importance of an early diagnosis and prevention therapy, the benefits of additional therapy and the essential role of asthma education. Conclusion: We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This guide for asthma management is based on the best available published data and the opinion of health care professionals including asthma experts and educators.

Indoor air quality and the risk of lower respiratory tract infections in young Canadian Inuit children

Background: Inuit infants have the highest reported rate of hospital admissions because of lower respiratory tract infections in the world. We evaluated the prevalence of reduced ventilation in houses in Nunavut, Canada, and whether this was associated with an increased risk of these infections among young Inuit children. Methods: We measured ventilation in 49 homes of Inuit children less than 5 years of age in Qikiqtaaluk (Baffin) Region, Nunavut. We identified the occurrence of lower respiratory tract infections using a standardized questionnaire. Associations between ventilation measures and lower respiratory tract infection were evaluated using multiple logistic regression models. Results: The mean number of occupants per house was 6.1 people. The mean ventilation rate per person was 5.6 L/s (standard deviation [SD] 3.7); 80% (37/46) of the houses had ventilation rates below the recommended rate of 7.5 L/s per person. The mean indoor carbon dioxide (CO2) concentration of 1358 (SD 531) ppm was higher than the recommended target level of 1000 ppm. Smokers were present in 46 homes (94%). Of the 49 children, 27 (55%) had a reported history of lower respiratory tract infection. Reported respiratory infection was significantly associated with mean CO2 levels (odds ratio [OR] 2.85 per 500-ppm increase in mean indoor CO2, 95% confidence interval [CI] 1.23–6.59) and occupancy (OR 1.81 for each additional occupant, 95% CI 1.14–2.86). Interpretation: Reduced ventilation and crowding may contribute to the observed excess of lower respiratory tract infection among young Inuit children. The benefits of measures to reduce indoor smoking and occupancy rates and to increase ventilation should be studied.

What Is New Since the Last (1999) Canadian Asthma Consensus Guidelines

The objective of the present document is to review the impact of new information on the recommendations made in the last (1999) Canadian Asthma Consensus Guidelines. It includes relevant published studies and observations or comments regarding what are considered to be the main issues in asthma management in children and adults in office, emergency department, hospital and clinical settings. Asthma is still insufficiently controlled in a large number of patients, and practice guidelines need to be integrated better with current care. This report re-emphasises the need for the following: objective measures of airflow obstruction to confirm the diagnosis of asthma suggested by the clinical evaluation; identification of contributing factors; and the establishment of a treatment plan to rapidly obtain and maintain optimal asthma control according to specific criteria. Recent publications support the essential role of asthma education and environmental control in asthma management. They further support the role of inhaled corticosteroids as the mainstay of anti-inflammatory therapy of asthma, and of both long acting beta2-agonists and leukotriene antagonists as effective means to improve asthma control when inhaled corticosteroids are insufficient. New developments, such as combination therapy, and recent major trials, such as the Childrens Asthma Management Project (CAMP) study, are discussed.

Inconclusive Diagnosis of Cystic Fibrosis After Newborn Screening

OBJECTIVES: To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; “CF screen positive, inconclusive diagnosis” [CFSPID]) for disease manifestations. METHODS: Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life. RESULTS: Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61–106] vs 144 [105–199] μg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients. CONCLUSIONS: A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping.

Pseudomonas aeruginosa and Burkholderia cepacia infection in cystic fibrosis patients treated in Toronto and Copenhagen

Differences in the course of pulmonary disease in cystic fibrosis (CF) may be altered by different treatment strategies in different CF centers. The Copenhagen clinic uses scheduled, regular and very aggressive treatment of lung infection. The Toronto clinic treats pulmonary infection with oral, inhaled, or intravenous antibiotics, and has emphasized aggressive nutritional therapy. This study compared the clinical status of CF patients treated in the two centers (Toronto, Canada, n = 302, and Copenhagen, Denmark, n = 214) using a cross‐sectional design in terms of Pseudomonas aeruginosa (PA) and Burkholderia cepacia (BC) lung infections, pulmonary function, and levels of PA and BC precipitating antibodies (precipitins). Median ages were similar, but the age distribution was significantly different, with a higher proportion of patients under 10 and ⩾ 25 years in Toronto, and higher proportion of patients 11–24 years of age in Copenhagen. A higher number of female patients was observed in Copenhagen than in Toronto. Seventy‐nine percent of Copenhagen patients, and 52% of Toronto patients were ΔF508 homozygous. Of all the patients, 20.1% of Copenhagen patients and 38% of Toronto patients were ΔF508 heterozygous. Ten percent of Toronto patients had two uncommon mutations. Pulmonary function and nutritional status in both groups were similar despite varying treatment strategies. The prevalence of PA was lower in Danish children and higher in Danish adults than in Canada. These differences are probably due to cohort isolation, which was introduced in Copenhagen in 1981. The prevalence of BC was higher in Toronto than in Copenhagen patients at all ages. In both centers, the number of PA and BC precipitins increased with age in patients chronically infected with PA and BC, respectively, and the number of both PA and BC precipitins rose with declining lung function. This study suggests that the clinic populations had similar pulmonary and nutritional statuses despite differing clinic antibiotic treatment strategies. Microbial colonization seemed to differ, at least in part, because of differences in cohort isolation strategies. Early, aggressive anti‐pseudomonal chemotherapy may have reduced pseudomonal colonization among younger patients in Copenhagen. Future studies will be required to assess the impact of this on this cohorts outcome. Pediatr Pulmonol. 1998; 26:89–96.

Triage nurse initiation of corticosteroids in pediatric asthma is associated with improved emergency department efficiency.

OBJECTIVE: To assess the effectiveness of nurse-initiated administration of oral corticosteroids before physician assessment in moderate to severe acute asthma exacerbations in the pediatric ED. METHODS: A time-series controlled trial evaluated nurse initiation of treatment with steroids before physician assessment in children with Pediatric Respiratory Assessment Measure score ≥4. One-to-one periods (physician-initiated and nurse-initiated) were analyzed from September 2009 through May 2010. In both phases, triage nurses initiated bronchodilator therapy before physician assessment, per Pediatric Respiratory Assessment Measure score. We reviewed charts of 644 consecutive children aged 2 to 17 years for the following outcomes: admission rate; times to clinical improvement, steroid receipt, mild status, and discharge; and rate of return ED visit and subsequent admission. RESULTS: Nurse-initiated phase children improved earlier compared to physician-initiated phase (median difference: 24 minutes; 95% confidence interval [CI]: 1–50; P = .04). Admission was less likely if children received steroids at triage (odds ratio = 0.56; 95% CI: 0.36–0.87). Efficiency gains were made in time to steroid receipt (median difference: 44 minutes; 95% CI: 39–50; P < .001), time to mild status (median difference: 51 minutes; 95% CI: 17–84; P = .04), and time to discharge (median difference: 44 minutes; 95% CI: 17–68; P = .02). No differences were found in return visit rate or subsequent admission. CONCLUSIONS: Triage nurse initiation of oral corticosteroid before physician assessment was associated with reduced times to clinical improvement and discharge, and reduced admission rates in children presenting with moderate to severe acute asthma exacerbations.

Exhaled nitric oxide and respiratory symptoms in a community sample of school aged children

To test the association between reported allergy and allergic diseases, respiratory symptoms, and the fractional concentration of exhaled nitric oxide (FeNO), in a community sample of school aged children.

Heat recovery ventilators prevent respiratory disorders in Inuit children

UNLABELLED Inuit infants have high rates of reported hospitalization for respiratory infection, associated with overcrowding and reduced ventilation. We performed a randomized, double-blind, placebo controlled trial to determine whether home heat recovery ventilators (HRV) would improve ventilation and reduce the risk of respiratory illnesses in young Inuit children. Inuit children under 6 years of age living in several communities in Nunavut, Canada were randomized to receive an active or placebo HRV. We monitored respiratory symptoms, health center encounters, and indoor air quality for 6 months. HRVs were placed in 68 homes, and 51 houses could be analyzed. Subjects had a mean age of 26.8 months. Active HRVs brought indoor carbon dioxide concentrations to within recommended concentrations. Relative humidity was also reduced. Use of HRV, compared with placebo, was associated with a progressive fall in the odds ratio for reported wheeze of 12.3% per week (95%CI 1.9-21.6%, P = 0.022). Rates of reported rhinitis were significantly lower in the HRV group than the placebo group in month 1 (odds ratio 0.20, 95%CI 0.058-0.69, P = 0.011) and in month 4 (odds ratio 0.24, 95%CI 0.054-0.90, P = 0.035). There were no significant reductions in the number of health center encounters, and there were no hospitalizations. Use of HRVs was associated with in improvement in air quality and reductions in reported respiratory symptoms in Inuit children. PRACTICAL IMPLICATIONS Reduced ventilation is common in the houses of Inuit children in arctic Canada, and is associated with an increased risk of respiratory infection. Installation of HRV brings indoor carbon dioxide concentration, as a marker of adequate ventilation, to within recommended concentrations, although relative humidity is also reduced. Installation of HRV is associated with improvements in indoor air quality, and a reduced risk of wheezing and rhinitis not associated with cold air exposure in young Inuit children. Further research is required to explore traditional Inuit cultural attitudes about air movement in dwellings.

Optimal biopsy techniques in the diagnosis of primary ciliary dyskinesia

OBJECTIVE Adequate biopsy specimens that clearly demonstrate cilia, and therefore enable the determination of the presence or absence of primary cilia dyskinesia, may be difficult to obtain. This study is an attempt to identify the optimal sampling technique to best examine respiratory tract cilia. DESIGN A prospective comparison of the four sampling techniques was carried out: nasal brushing, nasal biopsy, bronchial brushing, and tracheal biopsy. SETTING Tertiary care pediatric hospital: Childrens Hospital of Eastern Ontario. METHODS Ten consecutive patients booked for bronchoscopy and tracheal biopsy underwent all four procedures. Specimens were examined under light microscopy for an assessment of quality. RESULTS The nasal brushing and tracheal biopsy specimens provide superior quality (p = .22); however, nasal brushing is more cost efficient. Nasal biopsy samples frequently are metaplastic and therefore are inferior to nasal brushing samples (p = .02). CONCLUSION With equal efficiency demonstrated, the reduction in potential morbidity and health care costs suggests nasal brushings to be the optimal initial investigation for primary ciliary dyskinesia.

Achieving control of asthma in preschoolers

Billy, who is 2 years old, presents to the physician’s office with his fourth episode of wheezing in the past 18 months. He was admitted to hospital at 6 months of age with bronchiolitis caused by respiratory syncytial virus. At 9 months, he was seen in the local emergency department with a cold