BACKGROUND Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown. METHODS In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned to immediate interventional management of the pneumothorax (intervention group) or a conservative observational approach (conservative-management group) and were followed for 12 months. The primary outcome was lung reexpansion within 8 weeks. RESULTS A total of 316 patients underwent randomization (154 patients to the intervention group and 162 to the conservative-management group). In the conservativemanagement group, 25 patients (15.4%) underwent interventions to manage the pneumothorax, for reasons prespecified in the protocol, and 137 (84.6%) did not undergo interventions. In a complete-case analysis in which data were not available for 23 patients in the intervention group and 37 in the conservative-management group, reexpansion within 8 weeks occurred in 129 of 131 patients (98.5%) with interventional management and in 118 of 125 (94.4%) with conservative management (risk difference, −4.1 percentage points; 95% confidence interval [CI], −8.6 to 0.5; P = 0.02 for noninferiority); the lower boundary of the 95% confidence interval was within the prespecified noninferiority margin of −9 percentage points. In a sensitivity analysis in which all missing data after 56 days were imputed as treatment failure (with reexpansion in 129 of 138 patients [93.5%] in the intervention group and in 118 of 143 [82.5%] in the conservative-management group), the risk difference of −11.0 percentage points (95% CI, −18.4 to −3.5) was outside the prespecified noninferiority margin. Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management. CONCLUSIONS Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events.

Background -A study was undertaken to determine the influences of electrostatic charge, flow, delay, and multiple actuations on the in vitro delivery of salbutamol generated by a pressurised metered dose inhaler (pMDI) from small volume spacers used in infants. Methods -Ten actuations from a salbutamol pMDI were drawn at different flow rates after either single or multiple actuations, with or without delay, through either static or reduced static spacers. An ionic detergent was used to reduce the charge of plastic spacers (Babyhaler, Babyspacer, Aerochamber, Nebuhaler). Electrostatic charge was measured using an electrometer. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the spacers. Results -Electrostatic charge on the surface of plastic spacers had the greatest influence on delivery, causing a decrease in drug delivery. Reducing charge by coating the surface with ionic detergent resulted in an increase of 46.5-71.1% (p<0.001) in small (<6.8 pm) particle delivery from small volume plastic spacers. Lower flow, delay, and multiple actuations resulted in decreased delivery from static spacers. Lower flow resulted in a decrease of 15% in small (<9.6 gm) particle delivery. Delay and multiple actuations resulted in a decrease of 40.7% and 76.0%, respectively, in small (<6.8 tm) particle delivery. The influences of lower flow, delay, and multiple actuations were greatly reduced or even eliminated by reducing charge. However, multiple actuations still resulted in a significant decreased delivery (p<0.05). The reduced static Nebuhaler had a higher delivery than all small volume spacers. Conclusions -Electrostatic charge has a major influence on the delivery of salbutamol from small volume spacers. Using a metal spacer or ionic detergent coating ofplastic spacers resulted in no or reduced charge and hence in improved delivery. Lower flow, delay, and multiple actuations played a major part only in static spacers. (Thorax 1996;51:985-988)

E El le ec ct tr ro os st ta at ti ic c c ch ha ar rg ge e o on n a a p pl la as st ti ic c s sp pa ac ce er r d de ev vi ic ceABSTRACT: The aim of this study was to determine whether electrostatic charge on a plastic spacer decreases the delivery of salbutamol from a pressurized metereddose inhaler (pMDI) and, if so, to find an optimal and practical treatment to remove the charge. Ten single actuations from a salbutamol pMDI were drawn through different Volumatic® spacers at a constant flow of 60 L·min -1 . The efficacies of different methods of removing charge were tested, including detergent coating of the spacers. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the Volumatic® spacers. The electrostatic charge on the inner surface of the spacers was measured both quantitatively with an electrometer, and qualitatively by the attraction of a thin strip of cellulose membrane to the wall of the spacer. Each experiment was repeated four times.Ionic detergent coating of the spacers removed the charge for at least 24 h. This resulted in an increase of 55-70% in small particle (<6.8 µm) delivery compared to delivery from new spacers with high charge.We have demonstrated that electrostatic charge plays a major role in the delivery of salbutamol through plastic spacers. Adequate treatment with ionic detergent removes the charge and improves drug delivery.

Background -Many factors contribute to the high variability of doses delivered to the lungs of patients using metered dose inhalers (MDIs). Relatively little attention has been paid to the contribution to this variability of the way in which the MDI is handled before the inhalation manoeuvre. Instruction leaflets often recommend procedures at odds with those used for in vitro testing of the device. The standard protocol for in vitro assessment of salbutamol MDIs involves shaking the MDI vigorously for 30 seconds and wasting the first two actuations. Subsequent actuations are introduced into the testing device at five second intervals. Patient instructions do not include a recommendation to waste the first two actuations and recommend a delay of one minute between actuations. A series of experiments was performed to determine whether such differences might be important. Methods -The total and "respirable" doses delivered by a salbutamol MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a multistage liquid impinger. The quantity of drug deposited on each stage was measured by an ultraviolet spectrophotometric method. The effect on the delivered dose of not shaking the canister, not wasting the first two doses, waiting 30 seconds between actuations, and using multiple rapid actuations was assessed by comparing the results with those obtained using the standard in vitro testing protocol. Results -Compared with a standard protocol, it was found that not shaking the MDI before use reduced the total and "respirable" dose by 25-5% and 35 7%, respectively. The dose delivered when actuating the MDI at 30 second intervals was no different from that when intervals of five seconds were used. Two actuations separated by one second had no effect on the total dose but reduced the "respirable" dose by 15-8%, while four rapid actuations reduced the total and "respirable" doses by 8-2% and 18-2%, respectively. Storing the MDI stem down reduced the total and "respirable" dose delivered in the first actuation by 25 Although metered dose inhalers (MDIs) are the devices most widely used for aerosol therapy, their effectiveness is often adversely influenced by suboptimal use. Recommendations for use vary and this can cause confusion in the minds of patients wishing to use the devices optimally and in those instructing them. Hence, instructions should be as simple as possible.Protocols used by drug companies for handling MDIs during in vitro assessment of formulations frequently vary from that recommended for clinical use. A typical standard protocol when using a particle sizing device such as a multistage liquid impinger involves shaking the MDI vigorously for 30 seconds and then wasting the first two actuations. The MDI is then actuated a predetermined number of times into the particle sizing device. These actuations are separated by an interval of 5-30 seconds, depending upon the protocol being used, and the MDI is shaken between each actuation.Instructions for clinical use do not normally include w...

Aerosols of nedocromil sodium labelled with 99Tcm were delivered on 20 separate occasions to healthy male volunteers. Planar and single photon emission computerized tomography (SPECT) gamma scintigraphy were immediately performed to assess the pulmonary regional distribution of delivered aerosol. On a separate occasion volunteers were imaged using X-ray computed tomography (CT). Alignment of SPECT and CT images was performed using marked anatomical features and the anterior and lateral skin outlines. CT images provided data for attenuation correction and were used to define the anatomical lung volume. Central to peripheral (CP) ratios of deposited activity were calculated from volumes of interest in coronal and transverse sections of the right lung. These were compared with CP ratios obtained from planar images obtained immediately following aerosol inhalation. Volumetric CP ratio correlated significantly with immediate planar CP ratio (p < 0.001). Analysis of deposition in the whole right lung was performed by separating the SPECT lung data into a series of thin concentric shells centred on the entry of the right main bronchus. Measures were defined for describing the variation of deposition density and cumulative total deposition with distance from the lung centre. These showed significant correlation with planar CP ratio (p < 0.001). SPECT analysis using CT is consistent with planar measures of aerosol deposition but offers a more complete quantification of aerosol penetration and absolute deposited activity within the whole lung. It is a valuable new tool for aerosol analysis.