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).