Method
This prospective, cross-sectional study was conducted from December 2017 to June 2019 in the pediatric respiratory clinic of the McGill University Health Centre. Approval for this study was granted by the hospital’s Institutional Research Ethics Board (Study 2018-3907). Eligible patients were prospectively recruited in the pediatric respirology clinic when a study sonographer was available. Written informed assent and consent were obtained from participants and their guardians.
The sample size was calculated on the basis of the previous study of children presenting to the emergency room for an acute asthma exacerbation, where approximately 20% of the patients above 6 years of age had a positive lung ultrasound20. Assuming a similar rate of lung ultrasound findings in our cohort and defining a precision of ±10% as clinically meaningful, a sample size of 52 patients would provide 90% confidence that the true rate is within these precision limits.
Patients were approached if they were 6 to 17 years old, and either known asthmatics presenting for a routine visit with spirometry or suspected asthmatics presenting for confirmatory methacholine challenge test (MCT) in the pulmonary function lab. Patients were recruited if they had a diagnosis of asthma with a positive spirometry or MCT result consistent with a diagnosis of asthma. The reference values for spirometry were obtained from the global lung function initiative22. A positive spirometry result was defined as an FEV1 <80% predicted as well as an FEV1/FVC <85 and 12% increase in FEV1 after administration of a bronchodilator. A positive MCT result was defined as PC20 less than 8mg/ml, where PC20 represents the provocative concentration that resulted in a 20% decrease in FEV117,23. We excluded patients with history of viral illness in the previous 4 weeks. Eligibility was determined through a combination of administered questionnaires and review of the electronic medical record. At enrollment, all participants and parents completed a pre-test questionnaire (Appendix A) to record overall respiratory health and medication compliance, the ISAAC Asthma Core Questionnaire, and the Asthma Control Questionnaire.
Before the start of the study, all sonographers (AD, NM, FG) received formal LUS training from an expert sonographer (ASD). An introductory course on LUS was given by the latter followed by 5 proctored ultrasounds. The principal investigator (ASD) is certified as an independent practitioner by the Canadian Emergency Ultrasound Society and has more than 10 years of experience with point of care ultrasound.
Using the z.one ultra ultrasound and the L14-3 linear transducer (Mindray, Zonare Medical System, Mahwa, NJ), each LUS was completed by one of three study sonographers. A six-zone scanning protocol was performed, comparable to that described by Copetti and Cattarossi24. Settings included a depth of 6–8 cm at a fundamental frequency (i.e., tissue harmonic imaging turned off) of 12 MHz. Ultrasound gel was layered on the probe and placed in a longitudinal manner over 6 zones (right and left anterior, mid-axillary and posterior chest zones). Six-second video clips were taken in each of the six zones. The images were reviewed and interpreted by the expert sonographer (ASD) who was blinded to all participant clinical information.
The LUS findings were recorded as present or absent for each of the following abnormal sonographic findings in each of the 6 lung zones, as defined by the 2012 international evidence-based recommendations for point-of-care ultrasound (POCUS)25: lung slide, multiple B lines, consolidation (defined as large if ≥1cm or small if <1cm), pleural line abnormality and pleural effusion. A negative lung ultrasound was defined by the absence of any of these abnormal findings, the presence of normal lung sliding and a normal A-line pattern in each zone. Asthma control was assessed via the Asthma Control Questionnaire (ACQ). We defined asthma as being poorly controlled if the ACQ score was >1.526. We used the ISAAC Core Questionnaire to determine whether asthma was more likely to be severe27. The score is considered positive if patients had >4 attacks of wheezing, or >1 night per week sleep disturbance from wheeze or wheeze affecting speech in the past 12 months. This definition is based on previous ISAAC analyses showing a combination of these features correlated more closely with asthma mortality and hospital admissions28.
A post-hoc analysis was done on positive lung ultrasounds to quantify abnormalities through a scoring system that we derived derived from previous studies looking at respiratory pathology and extent of LUS findings14,15,29. This was done using the LUS quantitative scoring system, (E-Appendix B). With a score of 0-2 for each of the 6 lung zones (maximum score 12).