Analysis of Drug Release Dynamics of the Reservoir-type Dry Powder Inhalers.

OBJECTIVE: Dry powder inhalers (DPIs) are classified as capsule, blister, and reservoir types. Currently, two reservoir-type DPIs, i.e., TurbuhalerTM (TBH) and GenuairTM (GNA), are available, but their physical characteristics differ. Therefore, we compared their drug release patterns. METHODS: An inhalation f low simulator was set to reach peak inhalation f low (PIF) at two time points, 0.4 s (rapid) or 1.5 s (moderate), and then the drug release from both the DPIs were compared. RESULTS: The amount of drug release from the TBH increased linearly with increase in PIF, and the amounts were higher during rapid inhalation than during moderate inhalation. The GNA had a threshold flow for drug release, above which the flow was PIF-dependent (rapid) or independent (moderate). With rapid inhalation, drug release was dependent on the peak value and releasing time in both the DPIs. With moderate inhalation, the peak flow dependency of the TBH was attenuated, whereas that of the GNA remained time-dependent. CONCLUSION: Rapid and strong inhalation are best for drug release in both the DPIs, but a longer inhalation was required for the GNA. Therefore, if a patient cannot inhale rapidly, then a moderately rapid and long inhalation could be considered, but strong inhalation is still mandatory for TBH.

A case of pulmonary semi-invasive aspergillosis developing fatal acute exacerbation.

A 80-year-old male was referred for detailed examination of left apical fibrotic changes in the chest radiograph. Six years later, several cavitary lesions with thickening of the pleura developed. Anti tuberculosis therapy had no effects. Despite intravenous administration of antibiotics, the cavities became larger and the infiltrates progressed to the left lower lobe. The air crescent was observed in one of the cavities. Repeated sputum examinations revealed Aspergillus niger only. With administration of anti fungal drug, infiltrates were faded. Four months after the cessation of antifungal drug high fever associated with new infiltrates developed. Sputum culture showed Aspergillus flavus. Infiltrates over the entire left lung field and in the right upper lobe were observed. On CT film necrotic lung tissue was strongly suggested in the cavity. The patients died of respiratory failure. Although initial course of the presented case was compatible with semi-invasive pulmonary aspergillosis (SIPA), fluminant and fatal exacerbations which may be very unusual in SIPA, developed in later. The mycetoma-like ball may be occasionally made of necrotic lung parenchyma instead of fungal mycelia in SIPA.

[Changes in sleep architecture by resumption of CPAP in patients with sleep apnea syndrome].

It is known that application of continuous positive airway pressure (CPAP) improves sleep architecture in patients with sleep apnea syndrome (SAS). In contrast, there have been only a few studies which deal with deterioration of sleep architecture by discontinuation of CPAP. In the present study we analyzed changes of sleep architecture by temporary removal of CPAP. The subjects were 41 patients who underwent polysomnography (PSG) for diagnosis of SAS. The patients chose either a 1-night study in which only PSG was done, or a 2-night study in which, after treatment with CPAP for one month, PSGs with and without CPAP at night were done. The mean ages, heights, and weights between the 1-night group and the 2-night group were not statistically different The mean AHI of the 1-night group (38.9 +/- 5.0/hr; mean +/- SE) and that of the 2-night group (45.7 +/- 5.4/hr) were not significantly different. The mean AHI profoundly decreased (4.4 +/- 0.9) by CPAP therapy on the second night. Percents of each sleep stage in the 1-night group were as follows; stage 1, 31.8%; stage 2, 50.0%; stage (3 + 4), 2.8%: REM, 15.7%. In the 2-night group, stage 1 was 43.6%, significantly higher than that in the 1-night group, while stage 2 was 39.9%, which was significantly smaller. There were no significant difference in stage (3 + 4) and REM. When CPAP was again applied to the 2-night patients, stage 1 significantly decreased to 15.5%, while stage 2 (55.6%), stage (3 + 4) 6.7%, and REM (22.3%) increased significantly. Therefore, cessation of CPAP shifts the sleep stage from stage 2 to stage 1. Since stages 1 and 2 occupy approximately 80% of total sleep duration, the shift may have some physiological significance. Resumation of CPAP may have improved quality of life and day-time sleepiness by decreasing stage 1 sleep and increasing stages of deeper sleep and REM.

A pheochromocytoma causing limited coagulopathy with hemoptysis.

We treated a 59-year-old woman presenting with hemoptysis, a rare symptom of pheochromocytoma. Multiple factors including hypertension caused by sudden catecholamine release may result in pulmonary edema. It should be noted that the increased activation of coagulation cascade, which was demonstrated by increased thrombin-antithrombin III complex (TAT) and prothrombin fragment factor 1 and 2 (F1 + 2), as well as endothelial or platelet stimulation evidenced by the increased plasma von Willebrand factor, may have contributed to hemoptysis. These abnormalities were normalized after adrenalectomy. Our case indicates the important role of catecholamine in coagulopathy and possibly in vasculopathy.

A case with acute quadriplegic myopathy following intensive care for idiopathic interstitial pneumonia.

We reported a patient who developed acute quadriplegic myopathy (AQM) following treatment with a combination of high-dose steroid and nondepolarizing blocking agent for idiopathic interstitial pneumonia (IIP). Few cases of AQM with IIP have been reported in the literature. The HP progressed rapidly in our patient, but the high-dose steroid therapy was effective. The rehabilitative intervention comprised of passive range-of-motion exercise, functional training, and muscle strengthening. After the initial presentation with severe weakness, the AQM gradually improved and the patient regained full physical function in 8 months. The clinical course was almost identical to that of AQM patients with other lung diseases. Though unlikely to influence the improvement of muscle weakness in AQM patients, the lung diseases associated with AQM may require specific consideration in determining suitable rehabilitation programs and observing patients before and after full recovery from dysmobility.