Efficiency of Ipratropium Bromide and Albuterol Deposition in the Lung Delivered via a Soft Mist Inhaler or Chlorofluorocarbon Metered-Dose Inhaler.

The propellant-free Combivent Respimat Soft Mist Inhaler (CVT-R) was developed to replace the chlorofluorocarbon-propelled Combivent metered-dose inhaler (CVT-MDI). This steady-state pharmacokinetic (PK) substudy evaluated drug lung-delivery efficiency, using data from two phase III safety and efficacy trials. PK parameters were obtained from well-controlled population PK analyses. Area under the plasma concentration-time curve (AUC), maximum observed plasma concentration (C(max)), and minimum observed plasma concentration (C(min)) showed systemic exposure to ipratropium bromide and albuterol delivered via the CVT-R was proportional to ex-mouthpiece delivered dose. Although the labeled dose of ipratropium bromide in the CVT-R was half that in the CVT-MDI, the systemic exposure was comparable. No PK interaction for the ipratropium bromide and albuterol Respimat drug components was demonstrated. Ipratropium bromide alone resulted in similar exposure to the combination of ipratropium bromide and albuterol. These results show that CVT-R delivers drug more efficiently to the lung than CVT-MDI.

Land use change and nutrients simulation for the Siah Darvishan Basin of the Anzali wetland region, Iran.

The Anzali Ramsar Convention wetland is located in an ecologically and economically important region in Iran. The wetland is largely surrounded by agriculture, natural forests and rangelands (approximately 36% and 63%, respectively). Urban areas consist of less than 1% of the total area. Urban land use produces the highest rates of nutrient transfer into the lake as TN, TP and BOD5 equal to 24, 2.4 and 79 Kg/ha/year, respectively, whilst, natural land use produces the lowest rate as 10, 1.3 and 27 kg/ha/year. These results will inform the future sustainable management of this important wetland in this ever increasingly water stressed region in Iran.

Molecular mimicry in inducing DNA damage between HIV-1 Vpr and the anticancer agent, cisplatin.

The human immunodeficiency virus type 1 (HIV-1) viral protein R (vpr) gene is an evolutionarily conserved gene among the primate lentiviruses. Several functions are attributed to Vpr including the ability to cause cell death, cell cycle arrest, apoptosis and DNA damage. The Vpr domain responsible for DNA damage as well as the mechanism(s) through which Vpr induces this damage is unknown. Using site-directed mutagenesis, we identified the helical domain II within Vpr (aa 37-50) as the region responsible for causing DNA damage. Interestingly, Vpr Delta(37-50) failed to cause cell cycle arrest or apoptosis, to induce Ku70 or Ku80 and to suppress tumor growth, but maintained its capability to activate the HIV-1 LTR, to localize to the nucleus and to promote nonhomologous end-joining. In addition, our cytogenetic data indicated that helical domain II induced chromosomal aberrations, which mimicked those induced by cisplatin, an anticancer agent. This novel molecular mimicry function of Vpr might lead to its potential therapeutic use as a tumor suppressor.

Multifocal pigmented villonodular synovitis in a child.

Pigmented villonodular synovitis is a rare benign disorder and usually affects young and middle-aged adults. It occurs either as a localised pedunculated form or more common diffuse form, and is almost always unifocal. Only few cases of multifocal involvement have been reported, all of them in children. Multifocal pigmented villonodular synovitis occurring in a 5-year-old girl is presented. Both her knees and left elbow were involved. All three lesions were of localised pedunculated type and were completely excised. She is believed to be one of the youngest patients reported.

Ipratropium bromide hydrofluoroalkane inhalation aerosol is safe and effective in patients with COPD.

STUDY OBJECTIVE: To compare the efficacy and safety of ipratropium bromide reformulated with the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane (HFA)-134a (ipratropium bromide HFA) to that of the marketed ipratropium bromide inhalation aerosol (containing CFC) in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group, placebo-controlled, multicenter trial. The primary efficacy parameter was acute bronchodilator response. The primary end points were peak change in FEV(1) from baseline and area under the response-time curve. SETTING: Thirty-one clinical centers in the United States participated in this project. PATIENTS: A total of 507 patients with moderate-to-severe COPD were randomized, and 444 patients completed the trial. INTERVENTIONS: Twelve weeks of treatment four times daily with one of the following: ipratropium bromide HFA, 42 microg; ipratropium bromide HFA, 84 microg; HFA placebo; ipratropium bromide inhalation aerosol, 42 microg; or CFC placebo. MEASUREMENTS AND RESULTS: Patients in all active treatment groups had significant bronchodilator responses as shown by increases in mean FEV(1) from baseline of at least 15%. Bronchodilator response in all active treatment groups was also significantly more than their respective placebo treatments based on FEV(1), area under the time-response curve from 0 to 6 h, and peak response. FVC results were similar to those seen with FEV(1). There were no significant differences in adverse events, laboratory findings, or ECG findings among the treatment groups. CONCLUSIONS: Ipratropium bromide HFA, 42 and mgr;g, provided bronchodilation comparable to the marketed ipratropium bromide CFC, 42 and mgr;g, over 12 weeks of regular use.

Hand trajectory invariance in reaching movements involving the trunk.

Movements of different body segments may be combined in different ways to achieve the same motor goal. How this is accomplished by the nervous system was investigated by having subjects make fast pointing movements with the arm in combination with a forward bending of the trunk that was unexpectedly blocked in some trials. Subjects moved their hand above the surface of a table without vision from an initial position near the midline of the chest to remembered targets placed within the reach of the arm in either the ipsi- or contralateral workspace. In experiment 1, subjects were instructed to make fast arm movements to the target without corrections whether or not the trunk was arrested. Only minor changes were found in the hand trajectory and velocity profile in response to the trunk arrest, and these changes were seen only late in the movement. In contrast, the patterns of the interjoint coordination substantially changed in response to the trunk arrest, suggesting the presence of compensatory arm-trunk coordination minimizing the deflections from the hand trajectory regardless of whether the trunk is recruited or mechanically blocked. Changes in the arm interjoint coordination in response to the trunk arrest could be detected kinematically at a minimal latency of 50 ms. This finding suggests a rapid reflex compensatory mechanism driven by vestibular and/or proprioceptive afferent signals. In experiment 2, subjects were required, as soon as they perceived the trunk arrest, to change the hand motion to the same direction as that of the trunk. Under this instruction, subjects were able to initiate corrections only after the hand approached or reached the final position. Thus, centrally mediated compensatory corrections triggered in response to the trunk arrest were likely to occur too late to maintain the observed invariant hand trajectory in experiment 1. In experiment 3, subjects produced similar pointing movements, but to a target that moved together with the trunk. In these body-oriented pointing movements, the hand trajectories from trials in which the trunk was moving or arrested were substantially different. The same trajectories represented in a relative frame of reference moving with the trunk were virtually identical. We conclude that hand trajectory invariance can be produced in an external spatial (experiment 1) or an internal trunk-centered (experiment 3) frame of reference. The invariance in the external frame of reference is accomplished by active compensatory changes in the arm joint angles nullifying the influence of the trunk motion on the hand trajectory. We suggest that to make a transition to the internal frame of reference, control systems suppress this compensation. One of the hypotheses opened to further experimental testing is that the integration of additional (trunk) degrees of freedom into movement is based on afferent (proprioceptive, vestibular) signals stemming from the trunk motion and transmitted to the arm muscles.

The timing of control signals underlying fast point-to-point arm movements.

It is known that proprioceptive feedback induces muscle activation when the facilitation of appropriate motoneurons exceeds their threshold. In the suprathreshold range, the muscle-reflex system produces torques depending on the position and velocity of the joint segment(s) that the muscle spans. The static component of the torque-position relationship is referred to as the invariant characteristic (IC). According to the equilibrium-point (EP) hypothesis, control systems produce movements by changing the activation thresholds and thus shifting the IC of the appropriate muscles in joint space. This control process upsets the balance between muscle and external torques at the initial limb configuration and, to regain the balance, the limb is forced to establish a new configuration or, if the movement is prevented, a new level of static torques. Taken together, the joint angles and the muscle torques generated at an equilibrium configuration define a single variable called the EP. Thus by shifting the IC, control systems reset the EP. Muscle activation and movement emerge following the EP resetting because of the natural physical tendency of the system to reach equilibrium. Empirical and simulation studies support the notion that the control IC shifts and the resulting EP shifts underlying fast point-to-point arm movements are gradual rather than step-like. However, controversies exist about the duration of these shifts. Some studies suggest that the IC shifts cease with the movement offset. Other studies propose that the IC shifts end early in comparison to the movement duration (approximately, at peak velocity). The purpose of this study was to evaluate the duration of the IC shifts underlying fast point-to-point arm movements. Subjects made fast (hand peak velocity about 1.3 m/s) planar arm movements toward different targets while grasping a handle. Hand forces applied to the handle and shoulder/elbow torques were, respectively, measured from a force sensor placed on the handle, or computed with equations of motion. In some trials, an electromagnetic brake prevented movements. In such movements, the hand force and joint torques reached a steady state after a time that was much smaller than the movement duration in unobstructed movements and was approximately equal to the time to peak velocity (mean difference < 80 ms). In an additional experiment, subjects were instructed to rapidly initiate corrections of the pushing force in response to movement arrest. They were able to initiate such corrections only when the joint torques and the pushing force had practically reached a steady state. The latency of correction onset was, however, smaller than the duration of unobstructed movements. We concluded that during the time at which the steady state torques were reached, the control pattern of IC shifts remained the same despite the movement block. Thereby the duration of these shifts did not exceed the time of reaching the steady state torques. Our findings are consistent with the hypothesis that, in unobstructed movements, the IC shifts and resulting shifts in the EP end approximately at peak velocity. In other words, during the latter part of the movement, the control signals responsible for the equilibrium shift remained constant, and the movement was driven by the arm inertial, viscous and elastic forces produced by the muscle-reflex system. Fast movements may thus be completed without continuous control guidance. As a consequence, central corrections and sequential commands may be issued rapidly, without waiting for the end of kinematic responses to each command, which may be important for many motor behaviours including typing, piano playing and speech. Our study also illustrates that the timing of the control signals may be substantially different from that of the resulting motor output and that the same control pattern may produce different motor outputs depending on external conditions.

Altered representation of peripersonal space in the elderly human subject: a sensorimotor approach.

The representation of the peripersonal space in humans and its modification with aging were studied by analyzing three-dimensional arm movements in healthy young and elderly adults. Participants drew ellipses in three reference planes (sagittal, frontal and horizontal), and errors in the orientation of ellipses with regard to the planes were measured. All subjects showed large disparities in the errors in different planes, errors were maximal in the horizontal plane. These findings imply that different planes are centrally represented with different errors and suggest that the mental representation of peripersonal space is anisotropic. Moreover, the elderly made larger errors than young subjects, regardless of the reference plane. Thus, the space representation is altered with aging. Compared with young adults, the elderly underestimate volume in space, a phenomenon that can be called the compression of space representation.

Muscular after-contraction and ongoing postural reactions in standing and sitting humans.

Muscular after-contraction (MA-C) and the ongoing postural reaction of the body was studied in standing and sitting subjects in two visual situations: eyes open or closed. EMG of trapezius and latissimus dorsalis and 3D kinematic recordings of the left scapula were analysed. The release of the long-lasting sustained isometric contraction at the level of the scapula produced a muscular after-contraction consisting of involuntary muscular contraction associated with a trunk movement similar to the unroll of a spiral. The unroll of the spiral is in the opposite direction when we compare the standing and sitting situations. We suppose that the muscular after-contraction reveals the activity of central tonigenic structures in evoking involuntary trunk movements in humans and stresses the importance of the initial postural situation (standing or sitting) and the visual condition in the characteristics of these involuntary movements.

Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials.

OBJECTIVE: Bronchodilators are routinely used in the long-term therapy of patients with COPD. These drugs are generally evaluated for their short-term bronchodilatory effects. Long-term and short-term benefits, however, are not necessarily equivalent. We evaluated, therefore, the effects of extended therapy with inhaled bronchodilators in patients with COPD. DESIGN: Data were obtained from seven clinical trials in which ipratropium was compared with a beta-agonist over a 90-day treatment interval. This comprised all the available data from clinical trials performed for registration of ipratropium and included 1,445 evaluable patients. Results of pulmonary function tests were evaluated prior to and after short-term administration of bronchodilator both before and after the 90-day treatment period. In addition, data were analyzed after stratification for smoking status and for lung function. RESULTS: Long-term therapy with ipratropium resulted in improvement in baseline (ie, before short-term administration of bronchodilator) FEV1 (28 mL; p < 0.01) and FVC (131 mL; p < 0.01), while long-term therapy with beta-agonist resulted in no significant change in FEV1 (1-mL decline; p > 0.2) or in FVC (20-mL improvement; p > 0.2). The improvement in baseline function in the ipratropium-treated patients was most marked in ex-smokers (average duration of abstinence, 9 years). Short-term administration of ipratropium following the 90-day treatment interval resulted in similar response in average FEV1 (6 mL more improvement after the extended therapy; p > 0.2) and an increased response in average FVC (44 mL more improvement after extended therapy; p < 0.01). In contrast, extended therapy with beta-agonist resulted in significantly less response to the short-term administration of beta-agonist for both FEV1 (49 mL less response; p < 0.0001) and FVC (74 mL less response; p < 0.0001). Assessed as the percentage of patients who achieved a 15% improvement in lung function, most patients responded to both treatments both before and after extended therapy. There was, however, a significant decline in the number of patients who responded after extended therapy, and this was more marked for the beta-agonist treated group. CONCLUSION: Long-term benefits of bronchodilator therapy appear to differ from short-term effects. Extended administration of ipratropium appears to be associated with improved baseline lung function and perhaps with improvement in the response to acute bronchodilation. Extended administration of beta-agonist, in contrast, appears to have little effect on baseline lung function, but may decrease response to acute bronchodilation.

The bronchitis index. A semiquantitative visual scale for the assessment of airways inflammation.

Flexible fiberoptic bronchoscopy has been proven to be an effective tool for the assessment and characterization of airway inflammation. Visual inspection of airways affected by chronic bronchitis discloses an abnormal appearance characterized by erythema, edema, secretions, and friability. It was hypothesized that the visual appearance of airway inflammation could be assessed in a semiquantitative manner. A bronchitis index (BI) was developed that scores the visual appearance of airways according to the presence or absence of abnormal edema, erythema, secretions, and friability (0 = normal, 3 = remarkably abnormal). The BI was determined in three study groups: 86 subjects with chronic bronchitis, 15 subjects who smoked cigarettes, but did not have chronic bronchitis, and 25 normal, nonsmoking control subjects. The reproducibility of the BI was determined by comparing the results from pairs of two independent observers assessing 249 subjects undergoing fiberoptic bronchoscopy under various investigative protocols. In total, nine investigators scored the airways. For the three observer pairs with more than six observations, there were no differences noted in the BI (p = 0.43, 0.67, 0.82). To control for the effect of cough upon the BI, lidocaine usage was recorded. No correlation was found between lidocaine usage and BI. As previously noted for a smaller group of subjects, the BI was found to be elevated in those with chronic bronchitis (13.2 +/- 0.53) compared with both asymptomatic smokers (8.5 +/- 0.89, p < 0.0005) and normal volunteers (2.3 +/- 0.55, p < 0.0001); the latter two groups also differed significantly (p < 0.0001). The BI was also found to correlate significantly with bronchial sample lavage fluid neutrophil content in lavage fluid obtained after determination of the BI and with cigarette smoking as quantitated by pack years. Conversely, the BI correlated negatively with the spirometric measures of airway obstruction, FEV1, FEV1/FVC, FEV25-75, and FEFmax. Thus, the BI appears to be a reproducible, semiquantitative assessment of the visual appearance of airway inflammation. It may be a useful bronchoscopic adjunct for the assessment of airway inflammation in clinical investigations.

Fractional processing of sequential bronchoalveolar lavage to separate bronchial and alveolar samples.

Bronchoalveolar lavage has been widely used to sample the lower respiratory tract. Most of the material recovered with this technique represents alveolar contents. A number of modifications have been suggested in order to obtain samples relatively enriched for bronchial material. In order to be able to use a standard technique for bronchoalveolar lavage to sample both airways and "routine" alveolar material, a simple modification of the technique as described by Reynolds and Newball was used: five sequential 20-ml aliquots were infused into the lower respiratory tract, and each aliquot was immediately aspirated. The return from the first aliquot was processed separately from the return from the subsequent four aliquots. These last four aliquots were pooled. Analysis of the first aliquot revealed it to be enriched for ciliated epithelial cells when compared with the subsequent aliquots. There were also differences in inflammatory cell composition with the bronchial sample containing relatively more neutrophils and relatively less lymphocytes. Aspiration during transoral bronchoscopy was documented by quantifying salivary amylase in the bronchial and alveolar lavage fluids. It was estimated, however, that the aspiration was not of quantitative significance in the vast majority of subjects studied. Finally, with the technique of fractional processing of bronchoalveolar lavage samples, it was possible to compare the protein concentrations in bronchial and alveolar lavages. Most prominent among the differences was a marked relative enrichment in the bronchial samples for immunoglobulin A. The technique of fractional processing of bronchoalveolar lavage samples provides a simple means to obtain samples enriched for bronchial and alveolar components. This should facilitate analysis of lower respiratory tract specimens in airway disease.

Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters.

In order to characterize intraluminal airway inflammation in subjects with chronic bronchitis, bronchoscopy and bronchoalveolar lavage were performed in 28 subjects with chronic bronchitis with fixed airway obstruction and, for comparison, 15 asymptomatic smokers and 25 normal nonsmoking volunteers. The chronic bronchitics had a cough productive of sputum on most days of the month for 6 months in the preceding 2 yr, had at least one exacerbation requiring medical intervention in each of the previous 2 yr, and had an FEV1 less than 76% of predicted without response to bronchodilator. During bronchoscopy the airways were assessed for visual evidence of inflammation by assigning them a score, the bronchitis index, that graded the airways according to the apparent severity of airway edema, erythema, friability, and secretions. Bronchoalveolar lavage was performed by sequentially instilling and retrieving with gentle suction five 20-ml aliquots of sterile normal saline into each of three separate lobes. The first aliquots, the "bronchial" sample, were pooled and processed separately from the final four aliquots, the "distal" sample. Cell counts, cell differentials, and albumin were determined for both the bronchial and distal samples. In order to correlate inflammation with clinical parameters, sputum was collected for 24 h prior to bronchoscopy; spirometry was performed just prior to bronchoscopy, and smoking histories were obtained. Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects. The bronchial sample lavage fluids from the chronic bronchitics tended to contain more cells (6.1 +/- 2.2 x 10(6) cells) than the bronchial sample fluids from the asymptomatic smokers (3.6 +/- 0.6 x 10(6) cells) or normal subjects (3.7 +/- 0.5 x 10(6) cells). Furthermore, the chronic bronchitics had a higher percentage of neutrophils in their bronchial lavage fluid (35.8 +/- 5.6%) than did either the asymptomatic smokers (20.7 +/- 2.6%, p = 0.0001) or the normal subjects (10.3 +/- 5.6%). The distal sample lavage fluid also recovered more neutrophils from both the chronic bronchitics (15.0 +/- 4.2%, p = 0.0012) and asymptomatic smokers (5.7 +/- 1.3%, p = 0.002) than from the normal subjects (2.8 +/- 0.4%). The chronic bronchitics were divided into two groups: those with low (less than 20%) and those with high (greater than 20%) bronchial sample neutrophils. Those with higher bronchial sample neutrophils had significantly more sputum production and lower FEV1, FEV1/FVC, and FEF25-75 than did the subjects with lower bronchial sample neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)

Bronchoalveolar lavage fluid processing. Effect of membrane filtration preparation on neutrophil recovery.

Two common methods for the preparation of bronchoalveolar lavage (BAL) fluid for cytologic examination, cytocentrifugation and membrane filtration, have been found to yield different results in the quantitation of lymphocytes. To compare these two methods for the quantitation of neutrophils, the differential counts from 640 consecutive clinical specimens were analyzed retrospectively. The percentage of neutrophils resulting from the preparation of the BAL fluids by the two methods were highly correlated (r2 = .72). However, cytocentrifugation yielded consistently higher neutrophil percentages than did membrane filtration (means for all samples: 18.5 +/- 1.0% vs. 14.7 +/- 0.9%; P less than .001). To investigate the source of the variation in neutrophil quantitation by the two methods, two series of mixing experiments were performed in which neutrophil-rich cell suspensions were added to BAL fluids. Determination of the cellular differentials before and after mixing the cell suspensions demonstrated that membrane filtration preparation tends to lose neutrophils while cytocentrifugation accurately recovers neutrophils. Thus, accurate quantitation of the two cells recovered by BAL may require use of both cytocentrifugation and membrane filtration.

Detection of Candida antigen in bronchoalveolar lavage fluid.

While bronchoalveolar lavage is frequently performed to evaluate immunocompromised hosts for infection, the significance of rare yeasts found on the cytologic examination of lavage fluid is unclear. This study used the latex agglutination method to test lavage fluids for Candida antigen to assess its usefulness in distinguishing Candida pneumonia from Candida colonization of the respiratory tract or oral contamination of the lavage specimen. Ninety-seven specimens from 87 patients were categorized on the basis of historical, microbiologic, cytologic and serologic data. Bronchoalveolar lavage fluids were positive for Candida antigen in 0 of 20 specimens from normal controls, 0 of 14 specimens from patient controls, 5 (36%) of 14 specimens from patients with Pneumocystis carinii pneumonia, 0 of 5 specimens from patients with gastrointestinal candidiasis, 0 of 9 specimens contaminated by oral-derived yeasts, 2 (10%) of 19 specimens from patients with probable Candida colonization and 15 (94%) of 16 specimens from patients with clinical and laboratory evidence of Candida pneumonia. We conclude that this test assists in the differentiation of Candida pneumonia from other situations in which yeasts are recovered by bronchoalveolar lavage.

Bronchoalveolar lavage in the cytologic diagnosis of carcinoma of the lung.

To assess the utility of bronchoalveolar lavage as a technique for diagnosing lung cancer, 850 lavages from 421 patients were reviewed. Biopsy-proven lung carcinoma was present in 35 cases. Of these, 24 (68.6%) had cells diagnostic of malignancy on cytologic preparations of the bronchoalveolar lavage fluid. Agreement between cancer subtypes determined by lavage and by tissue biopsy was 79.1%; variation usually occurred between large cell undifferentiated carcinoma and adenocarcinoma, not with small cell anaplastic carcinoma. The subtype of tumors was most accurately determined by examination of Papanicolaou-stained slides. Reactive bronchial epithelium often mimicked carcinoma, but could be correctly identified by its characteristic cytomorphology. No false-positive diagnoses of lung cancer occurred in 386 patients. The sensitivity of bronchoalveolar lavage for the diagnosis of lung carcinoma is similar to that of transbronchial biopsy and Wang needle biopsy. Because bronchoalveolar lavage may detect opportunistic infections, interstitial lung diseases and malignant cells with a low morbidity, it is a useful tool to assess patients with pulmonary infiltrates.

Cytopathology of opportunistic infection in bronchoalveolar lavage.

Bronchoalveolar lavage is an important tool for the cytologic and microbiologic examination of the lung. Silver- or Papanicolaou-stained slides from 604 lavage specimens from 344 patients were evaluated for the presence of fungal, parasitic, and viral organisms. Yeast, pseudohyphae, or hyphae occurred in 155 specimens (25.7%). Candida was the most frequent opportunistic fungus in immunosuppressed hosts. Patients with clinically significant Candida infection had many budding yeasts and pseudohyphae on cytologic preparations of their lavage fluid. Aspergillus, which occurred in five patients, was readily identified by cytologic examination and by fungal culture. Pneumocystis carinii was found in 14 patients (4%). Cytopathologic characteristics of Herpes simplex or cytomegalovirus were present in four patients (1.2%). In 414 specimens no pathogens were identified by either microbial culture or cytologic examination; usually, these patients had pulmonary hemorrhage, recurrent neoplasia, or therapy-induced lung disease to account for their abnormal chest x-rays. Cytologic and microbiologic examination of lavage fluid readily identified opportunistic pathogens. The ease and low morbidity of bronchoalveolar lavage support its use in the assessment of pulmonary infiltrates in immunocompromised hosts.

Comparison of inhaled albuterol powder and aerosol in asthma.

In this multicenter, randomized, double-blind study comparing the efficacy and safety of aerosolized albuterol with the dry powder formulation, 231 patients with chronic reversible obstructive airway disease were randomly allocated to receive either placebo albuterol aerosol followed immediately by active albuterol powder (200 micrograms) or active albuterol aerosol (two puffs, 180 micrograms) followed immediately by placebo lactose powder four times a day for a period of 12 weeks. No statistically significant differences were found between the powder and aerosol formulations with respect to pulmonary function, length of time mean FEV1 remained greater than or equal to 15% above baseline, physicians' assessments of patients' clinical response, or patients' subjective symptom scores. There were also no significant differences between treatment groups in cardiovascular effects, laboratory values, or adverse events. Among patients who expressed a preference for one of the delivery systems, half preferred using the powder. Results of this study demonstrate that 200 micrograms of albuterol powder is as safe and effective as 180 micrograms of albuterol aerosol.