An experimental study of clearance of inhaled particles from the human nose

ABSTRACT

Retention in the extrathoracic airways, and clearance by nose blowing, of monodisperse indium-111–labeled polystyrene particles were followed for at least 2 days after inhalation by healthy volunteers. Nine volunteers inhaled 3-μm aerodynamic diameter particles while sitting at rest, whereas subgroups of 3 or 4 inhaled 1.5-μm or 6-μm particles at rest, and 3-μm or 6-μm particles while performing light exercise. Retention of the initial extrathoracic deposit (IETD) in the extrathoracic airways was described by 4 components: on average 19% IETD cleared by nose blowing; 15% was swallowed before the first measurement, a few minutes after inhalation; 21% cleared by mucociliary action between the first measurement and about an hour later; and 45% subsequently cleared by mucociliary action. Geometric mean times in which 50% and 90% of IETD cleared were 2.5 and 22 hours. The geometric mean retention fractions at 24 and 48 hours were 7% and 2.4% IETD, respectively. No clear trends were found between parameters describing retention and any related to deposition (e.g., particle size). However, the fraction cleared by nose blowing was related to the frequency of nose blowing and therefore appears to be a characteristic of the individual.

KEYWORDS :

• mucociliary clearance
• nasal deposition
• nasal retention
• nose blow
• volunteer inhalation study

TECHNICAL ANNEX: CALIBRATION OF IN VIVO MEASUREMENT ARRAYS

Rapid particle clearance detector array (RPCDA)

The RPCDA subject measurements were calibrated for both ^99mTc and ¹¹¹In using the following phantom arrangement:

• Bottle Manikin Absorption (BOMAB) [34] phantom parts for head, neck, torso, pelvis, and arms were filled with tissue equivalent plastic beads and arranged vertically to represent the head, neck, chest, and arms of a sitting subject (Figure A1). Sources with activities traceable to national standards were placed into containers that acted as organ phantoms when inserted into the BOMAB head or torso parts.

• Activity in the ET airways was represented by a filter paper source, sealed in plastic, rolled, and inserted into a hollow plastic tube, 1.5 cm diameter by 8 cm long. The tube was closed and placed inside the BOMAB head section horizontally inline with the filling stopper. An empty tube was used when making background measurements.

• Activity in the lungs was represented by 2 500-mL bottles strapped together, containing liquid sources, positioned appropriately in the torso section. For making background measurements, they were replaced by 2 similar bottles filled with an equal volume of distilled water.

• Activity in the stomach was represented by a plastic pot containing a 100-mL liquid source. This was positioned in the torso phantom so that it was directly below the centre of the lung phantom. A pot containing an equal volume of distilled water was used for background measurements.

FIGURE A1  RPCDA phantom calibration measurement.

Separate measurements were made of each organ source in position in the BOMAB phantom using the RPCDA, with the nonactive phantoms in place for the other 2 organs. Background measurements with no active organs in the phantom were made before or after each measurement. The background subtracted peak areas of the 3 calibration sources measured by the head, chest, and abdomen detectors were determined. These results were combined with the activities of the sources at the time of measurement to give calibration factors in units of counts Bq⁻¹ s⁻¹ for both the source the detectors were intended to measure and the strength of signal detected from the other organ phantoms.

FIGURE A2  Tissue equivalent head phantom with ET inserts for source placement.

Low-background in vivo detector array (LBIDA)

The LBIDA subject measurements were calibrated for both ^99mTc and ¹¹¹In using the following phantom configuration:

• The subject was represented by a head phantom made of tissue equivalent material containing a negative cast of the extrathoracic airways into which sources could be inserted (Figure A2), the Lawrence Livermore torso phantom and BOMAB phantom parts filled with distilled water to represent the arms, pelvis, and legs of the subject.

• Activity in the ET airways was represented by a calibrated filter paper source, sealed in plastic, folded, and inserted into the oronasal cavity of the head phantom. The narrow central section of the head phantom, positioned between the right and left hemispheres, contains an insert in the ET airway void with source slots in it so that sources can be positioned reproducibly (Figure A2). Sources may also be inserted into the nostrils of the phantom. Sources were positioned in the anterior of the nasal cavity for calibration measurements.

• Activity in the lungs was represented by 2 polystyrene lung phantoms containing 18 calibrated point sources in removable 3-mm-diameter by 15-mm-long plastic phials, 10 in the right lung, 8 in the left to represent the relative lung volumes. The lungs were inserted into the Lawrence Livermore phantom.

• Activity in the stomach was represented by a pot containing a 100-mL liquid source. This was positioned in the Lawrence Livermore phantom by removing the filler section below the liver that represents the intestines. The pot was positioned centrally tucked under the lip of the liver phantom. The rest of the volume of the lower thorax was then filled by plastic bags of tissue equivalent plastic pellets.

Separate measurements were made of each organ source in position in the phantom with the nonactive phantoms in place for the other 2 organs for each of the 3 counting geometries, head, chest, or abdomen. This set of 9 measurements was used to calibrate the array for both the sources that the detectors were intended to measure and the strength of signal detected from the other organ phantoms. Background measurements with no active organs in the phantom were made before or after each measurement. Two sets of measurements were made for each radionuclide, with and without the lead impregnated vest in place over the Lawrence Livermore phantom. For the LBIDA, the background subtracted spectra of the 9 calibration measurements were entered into the spectrum library of the analysis software, together with the activities of the calibration sources. These data were used by the analysis program to assess subject measurements using a multiple linear regression program [17].

Small sodium iodine detector array (SSIDA)

The SSIDA was calibrated using the tissue equivalent head phantom, again using filter paper sources sealed in plastic and then folded to a suitably small size. Calibrations were made for activity positioned in the extreme anterior part of the nose, with sources inserted in the nostril cavity of the phantom, and in the posterior of the nasal passage, with the source positioned in the lower posterior slot in the nasal cavity (Figure A2). Each source was measured using both the front and the side detectors (Figure 2). Background measurements were also made of the head phantom with no sources present. The ratios of peak areas in the background subtracted spectra measured by the front and side detectors of the sources in the anterior and posterior positions were determined. These reference ratios were used as the calibration values against which to compare the ratio of counts from subject measurements.