History and evolution of aerosolized therapeutics: overview and introduction.
Explore the source record for details and available documents.
Administration, Inhalation↗
Biomedical subjects
S B Fiel
Publications and source records attributed to S B Fiel.
Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis.
We conducted a placebo-controlled, double-blind, randomized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or placebo (n = 37), which was self-administered twice daily for 4 wk and followed by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated in 35% of TSI patients but was detected in all placebo patients. Investigators indicated that 62% of TSI patients showed an improved medical condition compared with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1 to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups (p = 0.41). More TSI-treated patients than placebo patients reported increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms did not limit therapy. Additional study is warranted to further evaluate TSI in bronchiectasis patients.
Administration, Inhalation↗
Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis. Dornase Alfa Nebulizer Group.
Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity in vitro and improves pulmonary function in patients with cystic fibrosis (CF). We postulated that if dornase alfa could be delivered more peripherally to small airways in the lung in the form of smaller aerosol droplets in patients with early airway obstruction, the increase in pulmonary function from baseline might be improved. CF patients (n = 749) with mild lung disease (baseline forced vital capacity > or = 70% predicted) were randomly assigned to receive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 microm; or 2) the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 microm. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produced small but statistically significant improvements in pulmonary function compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group (2.5%). These results indicate that the short-term spirometric response to dornase alfa is influenced in part by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeutic aerosols, and it appears that localization of disease in the lung plays a role in the response to inhaled agents.
Adolescent↗
Pregnancy in patients with cystic fibrosis.
Explore the source record for details and available documents.
Adult↗
High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation.
OBJECTIVE: The aims of this study were threefold: to compare high-resolution CT (HRCT) of adult patients with cystic fibrosis (CF) during acute exacerbations with asymptomatic patients with CF, to evaluate reversibility of HRCT abnormalities after exacerbations, and to correlate HRCT with clinical parameters. SUBJECTS AND METHODS: Nineteen symptomatic and eight asymptomatic patients were prospectively evaluated by HRCT and pulmonary function tests (PFTs). Symptomatic patients were reassessed 2 weeks after the exacerbation. Studies were independently reviewed by two radiologists using a modified Bhalla scoring system, noting the presence, extent, and severity of bronchiectasis, peribronchial thickening, mucus plugging, and atelectasis or consolidation. Modifications to the Bhalla system included evaluation of the presence and profusion of centrilobular nodules and air-fluid levels within bronchiectatic cavities. The highest possible score was 24 points. Higher scores indicated greater severity. Mosaic perfusion was noted but not included in the modified Bhalla HRCT score. Total modified Bhalla HRCT score and components of the HRCT score were correlated with corresponding PFT parameters. RESULTS: Bronchiectasis, peribronchial thickening, mucus plugging, centrilobular nodules, and mosaic perfusion were identified in symptomatic and asymptomatic patients. Air-fluid levels in bronchiectatic cavities, identified in two patients, represented the only finding limited to acute exacerbation. Reversible findings included air-fluid levels (100%), centrilobular nodules (36%), mucus plugging (33%), and peribronchial thickening (11%). Total HRCT severity scores of symptomatic and asymptomatic patients correlated with forced vital capacity (FVC) (r = .44, p = .01) and forced expiratory volume at 1 sec (FEV1) (r = .34, p = .04). Severity of bronchiectasis correlated with FVC (r = .50, p = .004) and FEV1 (r = .40, p = .02). Mucus plugging and centrilobular nodules did not correlate with PFT parameters. In the symptomatic patients, improvement in HRCT score correlated with changes in FEV1/FVC (r = .39, p = .049). CONCLUSION: Air-fluid levels in bronchiectatic cavities were the only parenchymal finding shown by HRCT that was limited to the acute exacerbation of CF in our study population. However, this finding was rare, being seen in two of 19 patients. Mucus plugging, centrilobular nodules, and peribronchial thickening were potentially reversible findings in symptomatic patients. HRCT accurately revealed disease severity in patients with CF. We also found that changes in HRCT scores correlated with clinical improvement as determined by PFTs.
Acute Disease↗
Chronic obstructive pulmonary disease. Mortality and mortality reduction.
Chronic obstructive pulmonary disease (COPD) affects an estimated 15 million Americans and is the fourth most common cause of death in the US. Despite an improved understanding of the disease, treatment has changed little over the past 20 to 30 years and COPD remains a major health problem worldwide. Smoking is the major risk factor for COPD, accounting for some 90% of cases. Therefore, smoking cessation remains the most important intervention. Other available pharmacotherapeutic options include corticosteroids, bronchodilators, antibiotics for the treatment of acute exacerbations, mucokinetic agents, and oxygen for the advanced stages of the disease. Recent data investigating the use of dornase alfa (recombinant human deoxyribonuclease I) in patients with acute exacerbations of COPD were disappointing and failed to demonstrate a mortality benefit. While it is likely that ongoing research will optimise the use of older agents and identify new treatment options for patients with COPD, smoking cessation will probably remain the most important intervention and should be a key focus of future initiatives aimed at controlling this disease.
Anti-Bacterial Agents↗
Pulmonary function during pregnancy in cystic fibrosis: implications for counseling.
The median survival for patients with cystic fibrosis (CF) has increased from 1 year in the 1940s to nearly 30 years today, and one third of the CF population is over the age of 16 years. As women with CF attain adulthood they are necessarily confronted with issues related to their reproductive potential. In the past, pregnancy in these woman has been considered risky. Recent data suggest that pregnancy may be a viable option for patients with mild disease. The purpose of a study from the Cystic Fibrosis Foundation National Patient Registry is to identify specific indices for quantitating risks related to pregnancy for women with CF so that their physicians, with these data in hand, will be better able to counsel them.
Adolescent↗
A survey of occupational health professionals' preventive pulmonary practices and worksite environments: development and initial findings.
This article describes the development of a worksite survey to evaluate a continuing medical education (CME) program to improve preventive pulmonary practices and worksite environments of occupational physicians and nurses, and baseline findings from the survey. The two-part instrument assessed individual counseling practices for preventing lung disease and worksite environments. Eighty-one occupational physicians and nurses completed the survey before the CME program. Reliability coefficients (Cronbach's alpha) were calculated for five test subsections: smoking counseling (.72), workplace hazards (.70), environmental programs (.78), workplace environment (.94), and smoking policies (.91). Baseline findings indicated that 80% of respondents reported that their employees/patients were exposed to various workplace hazards. This instrument can be used to evaluate occupational health professionals' performance and worksite environments and may be useful for evaluating change over time or following a training program for occupational health professionals.
Education, Continuing↗
New treatment modalities for cystic fibrosis.
Refinements in standard therapy for cystic fibrosis have led to dramatic increases in survival and quality of life over the past three decades. Standard therapy has consisted of oral and intravenous antibiotics, chest percussion with postural drainage, and aerosol bronchodilator therapy. The discovery of the cystic fibrosis gene and elucidation of the underlying biochemical defect have broadened our understanding of the pathophysiology of cystic fibrosis and provided a rationale for many new and innovative therapies. Modulation of airway epithelial ion transport may improve mucociliary clearance and delay colonization by infective organisms. Anti-inflammatory therapy may decrease lung injury that results from the host's attempt to limit airway infection. Supplementation of airway antiproteases may limit the destructive effects of unopposed proteases on pulmonary architecture. Genetic biotechnology has already produced agents that preserve pulmonary function and decrease infectious exacerbations by altering the viscoelastic properties of sputum from patients with cystic fibrosis. Both active and passive immunotherapy are currently being investigated as a measure to delay or combat endobronchial infection with Pseudomonas spp. Aerosolized aminoglycoside antibiotics are being increasingly employed to control pulmonary infection while minimizing systemic toxicity. These treatment modalities, combined with the prospects for gene therapy, provide a brighter outlook for the patient with cystic fibrosis than ever before.
Cystic Fibrosis↗
Aerosol delivery of antibiotics to the lower airways of patients with cystic fibrosis.
Aerosolized tobramycin is well tolerated in children and adults with cystic fibrosis (CF). It represents a potential alternative to intravenous administration of antibiotics to control respiratory infection with Pseudomonas aeruginosa. Although its exact role in acute therapy for a CF exacerbation is not known, it has been shown to improve lung function and reduce the frequency of exacerbations in the chronic stable outpatient.
Administration, Inhalation↗
Efficacy/cost ratio of new therapy.
Explore the source record for details and available documents.
Cost-Benefit Analysis↗
Comparison of three jet nebulizer aerosol delivery systems used to administer recombinant human DNase I to patients with cystic fibrosis. The Pulmozyme rhDNase Study Group.
STUDY OBJECTIVE: To compare the degree of improvement in pulmonary function achieved with recombinant human DNase I (rhDNase) administered by three different aerosol delivery systems: DeVilbiss Pulmo-Aide compressor with the Marquest Acorn II nebulizer, the Hudson T Up-draft nebulizer, and the Pari LC Jet Plus nebulizer with the Pari Inhalier Boy compressor. These produce similar aerosols in vitro in terms of size distribution and activity of delivered rhDNase. STUDY DESIGN: Multicenter, randomized, open-label, parallel-group comparison of changes from baseline in pulmonary function variables in each test group. Patients were treated with rhDNase (2.5 mg bid) for 15 days, administered with three different aerosol delivery systems. SETTING: Outpatient clinics at 26 sites in the United States. PATIENTS: 397 patients > 5 years of age with cystic fibrosis and baseline forced vital capacity (FVC) values between 40 and 70% of predicted values. RESULTS: All three nebulizers gave comparable improvements in pulmonary function. FEV1 increased by an average of 13.2 to 14.1%, FVC by 10.9 to 11.8% and forced midexpiratory flow (FEF25-75) by 16.5 to 17.1%. No unusual or unexpected adverse events were reported other than those that would be expected in patients with cystic fibrosis. CONCLUSIONS: Recombinant human DNase I produced a similar magnitude of improvement in the pulmonary function of patients with cystic fibrosis when the drug was administered using three different types of nebulizer systems with similar in vitro delivery and safety characteristics.
Adult↗
An update on bronchiectasis.
Bronchiectasis is associated with heterogeneous predisposing conditions that cause abnormal dilatation and persistent inflammation in the bronchial tree and lung parenchyma. The disease remains a common cause of significant morbidity and mortality, especially when associated with hereditary disorders such as cystic fibrosis, ciliary dyskinesia, and immunodeficiency states. Recent investigations have focused on the inflammatory mediators involved in the pathogenesis of bronchiectasis. High-resolution computed tomography is now the diagnostic modality of choice and may also contribute to clinical management. Computed tomography and high-resolution computed tomography have identified bronchiectasis in individuals with HIV and alpha-1-antitrypsin deficiency. Early identification of predisposing disorders and aggressive management of symptoms has already been demonstrated by prolonged survival and decreased morbidity in cystic fibrosis patients, and similar management may benefit other populations with bronchiectasis. New treatments such as recombinant human DNase have been shown to improve pulmonary function and quality of life in cystic fibrosis patients and may prove useful in other chronic inflammatory lung disease.
Bronchiectasis↗
Pulmonary complications of cystic fibrosis in adults.
The demographics of cystic fibrosis (CF) are continuously changing, with adults representing a growing percentage of the patient population, which is expected to reach 50% by the year 2000. Pulmonary complications are primarily responsible for the high morbidity and mortality in this disease. Although the radiographic findings are quite specific, the correct diagnosis may not be suggested in the adult patient because of a lack of familiarity with its pulmonary manifestations in this age group. High-resolution CT (HRCT) has contributed to our understanding of the radiographic findings, especially at the level of the small airways. The role of imaging, including chest radiography and HRCT, is discussed. Issues that remain controversial include imaging in the acute pulmonary exacerbation, and the routine use of imaging as part of clinical scoring and in monitoring responses to new treatment modalities.
Adult↗
Absolute bioavailability and absorption characteristics of aerosolized tobramycin in adults with cystic fibrosis.
Administration of antibiotics by the inhalational route has become part of standard protocols for treatment of and prophylaxis for Pseudomonal pneumonias in patients with cystic fibrosis. For tobramycin, however, limited data are available on the aerosol absorption patterns, and no absolute bioavailability data for tobramycin exist. The purpose of this study was to measure the absolute bioavailability and systemic absorption characteristics of tobramycin when administered in high doses by a nebulizer. Multiple serum concentrations of tobramycin were measured after administration of an intravenous dose (mean, 2.9 mg/kg every 6 hours) and after an inhalational dose (5.6 mg/kg over 1 hour). Inhalational doses were superimposed over the "tail" of a steady-state intravenous dose to improve the sensitivity of the assay procedure (Abbott-TDX). Absolute bioavailability (F) was determined from AUC ratios normalized for dose. Model-independent pharmacokinetic parameters (volume of distribution [Vss] and total clearance [CLt]) were determined for each subject. Absorption characteristics (absorption rate constant [Ka] and mean absorption time [MAT]) were assessed after calculation of the cumulative fraction of drug absorbed, amount of bioavailable drug, and percent remaining to be absorbed per unit time using the Loo-Riegelman method. Three men and three women completed the study, and all received concurrent doses of ceftazidime. Mean absolute bioavailability (+/- standard deviation) was 9.13% (+/- 3.82), and the rate of absorption into the systemic circulation was consistent with a zero-order model profile for all subjects. Mean absorption time values reflected a wide degree of subject variability and ranged from approximately 15 to 150 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗
Erythrocytic glutathione in cystic fibrosis. A possible marker of pulmonary dysfunction.
To evaluate the role of red blood cell (RBC) antioxidants as clinical markers of oxidative exposure, we measured RBC glutathione (GSH) concentrations in 32 adult patients with cystic fibrosis (CF), and 8 healthy age-matched control subjects. We chose patients with CF because this disease is characterized by severe bronchial inflammation and marked oxidant-antioxidant imbalance. Although the GSH concentration of the two study groups was not significantly different, the RBC GSH concentration of patients with CF had a greater variability (p = 0.01) and was also inversely and significantly correlated to tests of pulmonary function (p < 0.05). These data indicate a large and significant interindividual variability of erythrocytic antioxidants in patients with CF, with a compensatory, but probably inadequate, increase in patients with more severe respiratory deterioration. Red blood cell GSH concentration may thus provide a biologic marker for disease severity and a rationale for antioxidant manipulation in these patients.
Adult↗
Management options for cystic fibrosis in adults.
Explore the source record for details and available documents.
Adult↗