Body Plethysmograph Measurements Before and After Methacholine Challenge in Early Childhood
Body Plethysmograph Measurements Before and After Methacholine Challenge in Early Childhood
In our previous study of Methacholine Challenge Tests (MCT) in preschool children, we found
 that wheeze detection was associated with significant reduction in flows and vital capacity
 values. We hypothesized that this finding is associated with trapped-air rather than the
 children's loss of cooperation/concentration.

 Objectives: To test this hypothesis by attempting plethysmography measurements during MCT.
In young children that cannot perform adequately spirometry methacholine challenge test (MCT)
 is continued until any of the following clinical signals occurred: appearance of audible
 wheeze, a fall of >5% in O2-saturation, or an increase of >50% in respiratory rate and/or
 heart rate. In our previous study [1] we assessed the feasibility of determining PC20-FEV1 in
 relation to audible wheeze detection during MCT in asthmatic preschool children. We found
 that at end of test (EOT), the reduction in flows of the forced expiratory flow volume (FEFV)
 curves was accompanied by reduction in forced vital capacity (FVC) though reductions in flows
 were higher than the reduction in volume. We hypothesized that this finding is associated
 with trapped-air rather than the children's loss of cooperation or concentration. We have
 also thought that determining lung volume by whole body plethysmograpy, has the advantage of
 measuring airway resistance in relation to FRC. Hence, plethysmographic measurements of lung
 volumes during MCT may shed light on the physiological relation between airway obstruction
 and hyperinflation at the end of MCT when audible wheeze is detected. However,
 plethysmography requires the patient's cooperation and coordination to perform brief panting
 maneuvers against closed airways. So far, only airway resistance has been measured in the
 plethysmograph [10], as it is believed that young children will not comply with the
 occlusions needed for lung volume measurements within the plethysmograph.

 The aims of the present study were twofold: a) to test if young children are capable of
 performing plethysmographic maneuvers required for FRC measurements; and b) to investigate if
 the reduction in vital capacity at maximal reduction in flows of the FEFV curves, found at
 wheeze detection during MCT, is due to true elevation of FRC and air trapping, or is
 artificially related to patients' loss of motivation/cooperation.

 Methods:

 Lung volumes and airway resistance will be measured in a commercial, whole body ZAN500
 constant volume body plethysmograph (ZAN-Messgeraete GmbH, Germany). The plethysmograph is
 equipped with a graphic display for preschool children to increase cooperation. The chair can
 be adjusted so that the child can comfortably sit up straight with a nose-clip, and reach the
 mouthpiece without flexing the neck.

 The plethysmography procedure will be performed according to recommendations. The test events
 will be explained to the child in detail outside of the plethysmograph. After that, the
 measurements will be carried out in the same sequence that was explained to the child. FRC
 will be measured by allowing for 2-3 breathing attempt series of superimposed straight lines
 (separated only by thermal drift). The best test out of two technically accepted series was
 analyzed.

 MCT will be performed according to the ATS guidelines for the Methacholine Challenge Test.
 Tests will be performed in a designated room at the Pediatric Pulmonary Unit, Meyer
 Children's Hospital, Haifa, Israel. A parent and the investigating team will be present
 throughout the test. Tests will be performed with triple doses of fresh Methacholine
 solutions (0.057 to13.395 mg/ml) dissolved in saline. Solutions will be driven by a KoKo-PDS
 dosimeter (Ferraris Respiratory, Louisville, CO) via mouthpiece while the child was sitting
 upright with a nose-clip and breathing at least 10 deep breaths. Five-minute intervals will
 be taken between concentrations until the maximal concentration or the end point will be
 reached (see below). Oxygen saturation and heart-rate will be monitored continuously by
 pulse-oximetry (Ohmeda Biox 3700 Pulse Oximeter, USA). Auscultation for 20-seconds over the
 trachea and two zones of both lungs (upper front and lower back) will be performed according
 to recommendation. The following indices will be considered as EOT: appearance of audible
 wheeze, a fall of 5% in O2-saturation, or an increase of 50% in respiratory rate and/or
 heart rate. Nebulized Albuterol (2.5mg) was administrated after lung function measurements.

 Spirometry: FEFV curves will be measured with a KoKo PDS commercial spirometer (Ferraris
 Respiratory, Louisville, CO), using the program incentives targets (peak expiratory flow
 rates or vital capacity). Calibration was performed before the testing sessions. The curves
 will be monitored on the computer screen to ensure best effort. On-line rejection of curves
 will be based on published quality control for older and preschool children including visual
 inspection for "non-cooperation" errors, which included poor effort, incomplete expiration,
 cough and glottis closure. Acceptable curves had to show a rapid rise to peak flow, and a
 gradual, smooth decline of flow down to residual volume.

 Sequence of lung function tests: Baseline measurements included spirometry followed by
 plethysmography. After baseline measurements MCT will be performed. A duplicate spirometry
 set will be performed immediately after auscultation and during the interval between
 inhalations. Plethysmography will be repeated following the last spirometry at EOT and after
 auscultation.
Inclusion Criteria:

 -  2.5-6.9 year-old children who were asthmatic according to GINA guidelines.

 -  All children previously had recurrent episodes of wheeze, cough and/or shortness of
 breath with clinical response to bronchodilator.

 -  Children were included only if they had not received anti-inflammatory medication for
 at least one week prior to the test or bronchodilators for at least 24 hours prior to
 the study.

 -  On the day of testing, children were included if they had normal chest auscultation
 and FEV1>75% predicted for healthy preschool children.

 Exclusion Criteria:

 -  Presence of other chronic respiratory conditions

 -  Emergency room visit in the past three months

 -  Respiratory infection in the past month