Lung Deposition of Mannitol Powder Aerosol in Healthy Subjects

Abstract

Mannitol as a dry powder aerosol is used for bronchoprovocation testing and to enhance mucus clearance in people with excessive airway secretions. The dose and distribution of the deposited aerosol in the lung was investigated using fast single photon emission tomography (SPECT) imaging. Mannitol powder (3 microm particle size) was produced by spray drying and radiolabeled with (99m)Tc-DTPA. Approximately 60 mg of radiolabeled mannitol (containing 52-68 MBq of (99m)Tc-DTPA) was administered to 10 healthy subjects using the Inhalator dry powder inhaler (DPI), and SPECT images (1 min each) were collected. Thirteen percent to 31% of the dose of mannitol loaded in the inhaler deposited in the lungs and the deposited dose correlated positively with the peak inhalation air flow. The regional aerosol lung distribution, as expressed by the penetration index (i.e., ratio of peripheral to central deposition in the lung) varied from 0.31 to 0.88, which however showed no dependency on any flow parameters. The variation in response to the same dose of mannitol within the asthmatic population may in part be explained by these findings.

Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis

“…Mannitol increased clearance in all regions of the lung, consistent with previous clearance studies [5] and with deposition studies [21,22], showing that mannitol is deposited in the lung in a diffuse distribution pattern. The magnitude of It is evident that the highest dose of mannitol used in the present study (480 mg) increased clearance of mucus the most in the majority of subjects compared with other doses of mannitol (160 and 320 mg).…”

Influence of particle size on regional lung deposition – What evidence is there?

“…With peak inhalation flow greater than 90 L/min for all patients, no correlation could be drawn since no difference in in vitro deposition was found between airflow rates of 60 and 100 L/min. Results of airflow rate and deposition patterns have been previously correlated, however using different DPI devices (Inhalator TM ) (Glover et al, 2006) or the same device with different airflow rate ranges (Meyer et al, 2004). Although a consistent polydispersity characteristic was observed for the three different formulations of mannitol powder, the results obtained in this investigation using a more reliable imaging tool (SPECT) for regional lung deposition helps to support the evidence that aerodynamically smaller particles deposit in the smaller airways.…”

The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder

“…The total lung deposition when inhaled using maximum inspiratory effort from Turbuhaler 1 at 60 L/min (24-33%) was shown to be significantly greater than the total lung deposition inhaled using moderate inhalation effort at PIFR of 30 L/min (14-22%) (Pitcairn et al, 2005;Borgstrom et al, 1994). Similar lung deposition dependency on the flow rate has also been reported for the Inhalator TM (0.062 kPa 1/2 min/L), where the lung deposition at 43 L/min and 63 L/min were 13% and 30%, respectively (Glover et al, 2006). On the other hand, the percentage of total lung deposition for some of the high resistance inhalers such as Pulvinal 1 (11 AE 2% at 27 L/min, 14 AE 3% at 46 L/min), Air TM (28 AE 6% at 37 L/min, 26 AE 6% at 72 L/min) and Taifun 1 (30 AE 6% at 21 L/min, 34 AE 6% at 36 L/min) showed little dependency on the inhalation flow rate (Pitcairn et al, 1994(Pitcairn et al, , 2000Hirst et al, 2002).…”