Materials and Methods
Study design
This cohort study complied with STROBE guidelines and with the guidance
provided by the editors of respiratory, critical care, and sleep
journals.5
The La Berma open cohort enrolls asthmatic children since 2009. This
open cohort is constituted of 7817 children with asthmatic symptoms
(with or without confirmed variable expiratory flow limitation). For
this study, selection was made in children with confirmed asthma:
suggestive symptoms and (1) a significant bronchodilator response
(either sRaw or FEV1, n=1152) or (2) by an asthma
exacerbation diagnosed and treated in a hospital Emergency Department
(n=1295) or (3) both (n=777). Preterm birth (gestational age
<37 weeks) was a non inclusion criterion as it is a well-known
risk factor for the development of persistent airflow
limitation.6 Only children who had at least 10
pulmonary function tests after 8 years of age were selected to ensure
the quality of spirometry, leaving 295 children with confirmed asthma.
The characteristics of each visit have been
standardized,7 as described in Table 1.
This cohort was registered to our regulatory agency for electronic data
collection (Commission Nationale Informatique et Libertés, no. 1408710).
Approval from the Ethics Committee of the French learned Society of
Pulmonology (SPLF) was obtained (CEPRO 2009/019). All children and
parents were informed of the prospective recording of clinical and
physiological data and could request to be exempted from the study in
accordance with French law regarding non-interventional research.
Pulmonary function tests
Spirometry (MasterScreen Body; Jaeger, CareFusion, San Diego, CA, USA)
was performed without inhaled treatment (bronchodilator or LABA/ICS
association) on the day of measurement by the same operator
(BM),7 according to international
guidelines.8 Reference values were those of
GLI-2012,9 as recommended for describing the
progression of pulmonary function.10
Classification of lung function patterns
The annualized rate of change (slope) for prebronchodilator
FEV1 percent predicted was estimated for each
participant using standard least squares linear regression models, as
performed by others.11 Three patterns were defined. A
positive slope was defined by a significantly positive value of the
slope, whereas a negative slope was defined by a significantly negative
value of the slope according to the P-value obtained in the Pearson
test. When the P-value was not significant, the slope was considered
null. The standard deviation (SD) of each individual slope was recorded
as a criterion of FEV1 variability.
Statistical analyses
The results were expressed as median (25th and
75th percentile) as some indices did not conform to a
normal distribution, and the positive slope group was small. Comparisons
of continuous variables between the three groups of children were
performed using the Kruskal-Wallis test, and subsequent intergroup
comparisons were performed using the Mann-Whitney U test. Categorical
variables were compared using the chi-square test or Fisher’s exact test
where appropriate. A P-value <0.05 was deemed statistically
significant. All statistical analyses were performed with Statview 5.0
software (SAS institute, Cary, NC, USA).