[Dyspnea and morphine aerosols in the palliative care of lung cancer]. / Dyspnée et aérosols de morphine dans les soins palliatifs du cancer broncho-pulmonaire.

OBJECTIVE: To evaluate the effectiveness of morphine aerosols in the treatment of dyspnoea in the palliative care of patients with lung cancer. MATERIALS AND METHODS: During a randomised, double blind, cross-over study 12 patients receiving palliative care for lung cancer and suffering from dyspnoea despite conventional treatments were given, for two periods of 48 hours separated by a 24 hour wash-out period, 4 mls of morphine sulphate and 4 mls of normal saline 4 hourly by a jet nebuliser. Before and after each nebulisation respiratory rate and capillary oxygen saturation were measured and dyspnoea was quantified with the aid of a visual analogue scale by the patient and various other observers (doctors, students, nurses, care assistants and physiotherapists). RESULTS: The aerosols of normal saline and morphine produced the same improvements in the dyspnoea scores independently of the mass nebulised. Furthermore the nebulisations did not produce any significant change in respiratory rate or oxygen saturation. CONCLUSION: The fact that both aerosols lead to a similar improvement in dyspnoea scores suggests that humidification of the airways rather than a pharmacological action may be beneficial in the treatment of dyspnoea in terminally ill patients.

Validation of laser diffraction method as a substitute for cascade impaction in the European Project for a Nebulizer Standard.

The project for a European standard testing procedure to characterize nebulizers in terms of particle size distribution has been based on using the Andersen-Marple personal cascade impactor model 298 (A-MPCI) with a sodium fluoride reference solution. In the present study methods based on laser diffraction (Mastersizer-X) and time-of-flight (TOF)(APS) and another cascade impactor (GS1-CI) were compared with the A-MPCI. Two types of nebulizer (Pari LC+ and Microneb) were tested with all apparatuses, and a third type of nebulizer (NL9) was tested with the A-MPCI and Mastersizer-X. Nebulizers were charged with a solution of sodium fluoride in conditions reproducing the European Committee for Normalization (CEN) protocol. There was no difference between the Mastersizer-X and the A-MPCI or between the GS1-CI and the A-MPCI in terms of mass median aerodynamic diameter (MMAD). Comparison between the APS and the A-MPCI showed a significant difference with the Microneb. The geometric standard deviations (GSD) obtained with the A-MPCI were on average 10% greater than GSD obtained with the other apparatuses, but the differences were not statistically significant. We conclude that laser diffraction can be used for particle size distribution in the context of the European standard, and that the Mastersizer-X is particularly interesting for industrial practice in view of its simplicity and robustness.

Gene therapy for cystic fibrosis with aerosolized adenovirus-CFTR: characterization of the aerosol and scintigraphic determination of lung deposition in baboons.

For cystic fibrosis (CF) gene therapy using an aerosolized adenovirus expressing the CFTR gene, optimization of the inhalation conditions is a prerequisite to obtain sufficient amount of CFTR protein expression in the target areas of the respiratory tract. For such a purpose, in vivo radioisotopic imaging of the radiolabeled virus is a unique strategy for a quantitative assessment of the actual deposition. In the present study, an adenovirus CFTR (AdCFTR) was labeled with 99m Technetium gamma emitting isotope in such conditions that its bioactivity was preserved. The 99mTc-AdCFTR aerosol was characterized using both laser diffraction and cascade impaction for sizing with further determination of nebulized and inhalable fractions. After administration to baboons, scintigraphic quantitation of the regional lung distribution was performed and the actual dose deposited in the target area was estimated and expressed as an equivalent viral titer. Since a virus scintigraphy is not realistic in a hospital setting, we have developed an approach using 99mTc-DTPA (diethylene triamino pentaacetic acid) that could be used to predict the virus deposition. Indeed, similarities observed between 99mTc-DTPA and 99mTc-adenovirus aerosol imaging patterns validates the use of the 99mTc-DTPA scintigraphy that we propose as a pretherapeutic test for each patient prior to gene transfer.