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At least 127 records · Page 7Linked to original sources

Granulocyte-macrophage colony-stimulating factor inhalation therapy for patients with idiopathic pulmonary alveolar proteinosis: a pilot study; and long-term treatment with aerosolized granulocyte-macrophage colony-stimulating factor: a case report.

Idiopathic pulmonary alveolar proteinosis (IPAP) is considered to be caused by an autoantibody to the granulocyte-macrophage colony-stimulating factor (GM-CSF), which neutralizes GM-CSF and therefore impairs the differentiation of alveolar macrophages. The authors have previously characterized the BAL fluid and alveolar macrophages obtained from three IPAP patients who were successfully treated with aerosolized GM-CSF and demonstrated restoration of the cell number, expression of surface marker, and phagocytic ability of the alveolar macrophages as well as a decrease in the autoantibody levels in the BAL fluid. The condition recurred in one of the patients after 20 months. This patient underwent a second and third course of GM-CSF inhalation therapy with the same dose and schedule as the first one. Since the second therapeutic intervention did not succeed in producing any improvement in the symptoms and disease markers, the authors used a new nebulizer and a liquid preparation of the drug instead of the lyophilized preparation for the third therapeutic session and this restored the respiratory function considerably. A 6-month maintenance therapeutic regimen with a lower GM-CSF inhalation frequency brought about a further improvement in the disease markers. The results suggest that the efficacy of GM-CSF inhalation therapy might be related to the drug preparation mode, choice of nebulizer, and duration of treatment.

Aerosols↗

A cyclosporin A/maltosyl-alpha-cyclodextrin complex for inhalation therapy of asthma.

The inhalation of cyclosporin (Cs)A to the lung is limited by its hydrophobic properties. In order to improve the poor solubility of CsA, cyclodextrin (CD) was evaluated for its suitability for dry powder inhaler formation, and the benefit of an inhaled CsA/CD complex in vivo was demonstrated. The solubilising effect of CDs on CsA was measured by high-performance liquid chromatography. Ciliostatic activity and haemolysis were determined to assess some safety profiles of CDs. The efficacy of an inhaled CsA/CD complex was evaluated by eosinophil infiltration into the bronchoalveolar lavage fluid in actively sensitised mice. CDs markedly improved the poor solubility of CsA. The ciliostatic and haemolytic activities of maltosyl-alpha-CD were the weakest of all the tested CDs. CsA inhaled alone showed inhibitory effects on allergen-induced eosinophilia. Inhalation of the complex of CsA with maltosyl-alpha-CD, where the dose of CsA was approximately nine-times less than that of CsA inhaled alone, also inhibited eosinophil accumulation significantly, with a longer duration of action in comparison with the response to CsA alone. Thus the effective dose of cyclosporin A could be reduced by formation of a complex with maltosyl-alpha-cyclodextrin, and a wider therapeutic safety margin by inhalation of cyclosporin A as a complex with maltosyl-alpha-cyclodextrin could be expected.

Administration, Inhalation↗

A safe clinical system for nitric oxide inhalation therapy for pediatric patients.

A safe clinical system for nitric oxide (NO) inhalation therapy was developed. The system consists of three parts: a NO controller, a NO monitor, and a patient circuit. NO gas flow and carrier gas flow are controlled by a special rust-proof thermal mass flowmeter. Standard gas quality NO gas (10,000 ppm, balance nitrogen) is used. The outlet of the NO gas tank is connected to the distal end of a heated humidifer that is very close (12 mL) to the patient, to decrease acidic water precipitation and decrease contact time between NO and oxygen (O2). Fail-safe mechanisms to prevent the delivery of a hypoxic mixture or excessive NO concentration are incorporated. Inspiratory NO concentration is continuously monitored by a modified electrochemical NO meter. The patient circuit consists of a breathing circuit and a ventilator with a scavenging unit. A modified Mapleson D type circuit is used. Fresh gas, humidified and mixed with NO, is introduced to the patient connection port. A mechanical ventilator, either of conventional or of high-frequency oscillation type, is connected to the expiratory limb of the Mapleson D circuit. A coaxial scavenging unit including activated charcoal is placed in between the expiratory limb and the ventilator. The adjustment of inspiratory NO concentration (y) was accurate over a wide range (1-80 ppm) of concentrations (x) (y = 0.36 + 0.96x, R2 = 0.999, n = 45) and showed good agreement with the chemiluminescence method. Inspiratory nitrous oxide (NO2) concentration was less than 0.3 ppm, and acidic water accumulation as measured by NO2- and NO3- was less than 5 ppm, even at an extremely high NO concentration of 80 ppm with an FiO2 of 1.0 and 10 L/min of fresh gas flow. Environmental NO and NO2 concentrations in the ICU remained below 0.005 and 0.05 ppm, respectively. This system was used clinically on 214 pediatric patients and proved to be accurate, safe, and useful.

Adolescent↗

Inhalation therapy in invasive and noninvasive mechanical ventilation.

PURPOSE OF REVIEW: The aim of this article is to discuss the various factors that influence aerosol delivery in mechanically ventilated patients and clarify optimal techniques for aerosol administration in this patient population. Clinical use of various inhaled therapies in patients receiving invasive and noninvasive mechanical ventilation is also discussed. RECENT FINDINGS: With optimal techniques for using pressurized metered-dose inhalers and nebulizers in ventilator circuits, the efficiency of inhaled drug delivery in mechanically ventilated patients is comparable to that in ambulatory patients. Techniques for enhancing inhaled drug delivery during noninvasive positive pressure ventilation are also being investigated. SUMMARY: Pressurized metered-dose inhalers of bronchodilator and corticosteroid aerosols are more efficient and convenient to use than nebulizers for routine therapy in ventilated patients. Nebulizers are, however, more versatile and are employed to generate aerosols of bronchodilators, corticosteroids, antibiotics, prostaglandins, surfactant, and mucolytic agents. Factors influencing drug delivery during noninvasive positive pressure ventilation are not fully understood as yet, and further work is needed to enhance drug delivery in this setting. Improvements in drug formulations and the design and efficiency of aerosol generating devices have led to increasing application of inhaled therapies in mechanically ventilated patients.

Adrenal Cortex Hormones↗

Inhalation therapy. Oxygen administration, humidification, and aerosol therapy.

In addition to receiving treatment for the primary disease, patients with advanced respiratory disorders may benefit from other forms of respiratory support. This article discusses three techniques of inhalation therapy that will aid in maintaining an optimal pulmonary environment and in normalizing arterial oxygenation. The role of aerosol therapy in direct intrapulmonary administration of pharmaceuticals is also discussed.

Adrenal Cortex Hormones↗

Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology.

Inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are currently used in the management of asthma and chronic obstructive pulmonary disease (COPD). Localized targeted delivery of these drugs into the lungs is achieved by means of two types of inhalation devices; pressurized metered-dose inhalers (pMDIs) and dry powder-inhalers (DPIs). For environmental reasons, the chlorofluorocarbon (CFC) propellants used in pMDIs are now being replaced by ozone friendly hydrofluoroalkanes (HFAs). These new generation HFA-based pMDIs, developed to provide effective lung deposition of the active moiety, have a favorable safety and tolerability profile. However, HFA-based re-formulation of LABAs and ICS for pMDIs presents particular technical difficulties, especially in terms of ensuring dose content uniformity. This review focuses on the technology and clinical efficacy of the HFA solution pMDIs using Modulite platform technology (Chiesi Farmaceutici S.p.A). Modulite technology allows the development of HFA solution formulations that can mimic the established CFC-based drug formulations on a microgram to microgram basis and provides formulations with novel particle size distributions that improve on existing delivery systems; by manipulation of aerosol clouds and particle size, the delivery of HFA-formulated drugs can be optimized to either achieve fine particle fractions and deposition patterns similar to established CFC-based drug formulations, thus facilitating the transition to new environment-friendly pMDIs in the clinical setting, or achieve finer drug particles able to penetrate deeper into the bronchi for targeted drug delivery as medical need may dictate. Long-term, multiple-dose clinical studies of Modulite formulations of beclomethasone dipropionate (BDP), budesonide and formoterol have been demonstrated to be therapeutically equivalent to their respective previously established CFC or DPI formulations. As a result, a number of Modulite pMDIs have either recently gained regulatory approval in several European countries, or have completed clinical trials and are in the regulatory submission phase. Availability, in pMDI form, of drugs like formoterol, ICSs, and ICS/LABA combinations, all central to the effective management of asthma and COPD, is therefore expected to impact positively in assuring the continued availability of vital treatment options to patients and physicians.

Adrenal Cortex Hormones↗

[Milestones in inhalation therapy of airway diseases].

Inhalation is the preferred route for the application of drugs in the management of airway diseases. Therefore it was aimed at developing drugs suitable for inhalation. An important step was the introduction of the short- and long-acting beta 2-agonists and of a new generation of anticholinergics with longer duration of action. Most important was the development of inhaled glucocorticoids allowing good asthma control without relevant side effects even in a long run. Furthermore, the devices for drug application have been improved, and CFCs were substituted by HFAs.

Administration, Inhalation↗

Can the morbidity of asthma be reduced by high dose inhaled therapy? A prospective study.

A community based, prospective study of the value of high dose inhaled therapy for the reduction of the morbidity of asthma has been undertaken. One hundred and sixty adults with airflow obstruction were treated for up to 9 months with increasing doses of salbutamol. Two thirds of the patients also received increasing doses of beclomethasone dipropionate in a 'partially double-blind' manner. The FEV1 rose by at least 10 per cent of that predicted in one third of the total patients and the overall mean domiciliary peak expiratory flow rates rose by approximately 50 l/min-1. All chronic symptoms were abolished in half of the patients and acute attacks of asthma in the majority. Asthma was controlled in a greater proportion of patients more effectively and rapidly by a combination of inhaled steroids and beta agonist than by salbutamol alone, particularly when inhaled steroids were started in relatively high dosage.

Administration, Inhalation↗

Why particle size should affect clinical response to inhaled therapy.

Studies with beta2-adrenergic agonists have shown that particle size and total dose are important determinants of optimum bronchodilation. Drug deposition in the airways is probably the most important factor for bronchodilation, since beta2-adrenoceptors and muscarinic M3 receptors are present mainly in the peripheral and central airways, respectively. Furthermore, clinical efficacy can be maintained while minimizing systemic exposure by selecting an appropriate particle size. Changes in lung function provide a means of monitoring the relationship between delivery of the bronchodilator and its efficacy, whereas there is no such immediate means of assessing antiinflammatory preventative therapy such as inhaled corticosteroids. Asthma is primarily an inflammatory disease but there are no simple tests to detect the accumulation of inflammatory cells and mediators. Data are presented to demonstrate the reduction of certain inflammatory markers in bronchial biopsy tissue taken from asthmatic patients after corticosteroid therapy. Measurement of inflammatory markers in both bronchial biopsy tissue and bronchoalveolar lavage samples may provide a way of monitoring the site of action and efficacy of inhaled corticosteroids in the future. Furthermore, it is envisaged that the effect of corticosteroid particle size on efficacy and systemic bioavailability may be investigated by exploiting these methods.

Administration, Inhalation↗

[Inhalation therapy with sulphur water in ORL: clinical-experimental study].

OBJECTIVE: Several clinics and experimental researches have highlighted the utility of the inhalant mineral therapy in numerous diseases to load of the tall and low respiratory streets. Aim of the our clinical-experimental study has been that of appraise "to brief term" the curative effects and the adverse reactions of a thermal inhalant treatment with sulphur water in the care of diseases ORL apparatus (laryngitis, pharyngitis, rhinitis, rhinosynusitis), appraise the course of some End points to distance. PATIENT AND METHODS: The study has been channel on a champion of 83 subjects of which 45 of male sex and 38 of female sex with age serious equal average to 53 years +/- 2.6. The subjects of the examined champion that affections from diseases inflammatory chronic of ORL relevance (laryngitis, pharyngitis, rhinitis) were subjected to a cycle of sulphur mineral inhalant therapy disbursed with businesslike individual of inhalations to bud of vapor to the T of 38 degrees C to 20 cm from the face with duration of 10 min, follows from aerosol for likewise minutes. To the beginning and at the end of the sulphur mineral inhalant cycle has been valued the subjective symptomatology susceptible of amelioration, some End Points to distance and the adverse reactions. RESULTS: The data seem to highlight the end cycle curative sulphur mineral inhalant an significant (P < 0.05) amelioration of best part of the symptoms examined like cough, nasal itch, expectoration [etc]. The analysis of the End Points to advised Distance show an significant (P < 0.05) progressional diminution of such indicators to succession of the annual continuity of the inhalant sulphur mineral treatment. CONCLUSIONS: The results of such research seem to demonstrate that the inhalant sulphur mineral therapy can induced notable benefit in different inflammatory chronic diseases of ORL relevance in peculiar in the first ten of life with a positive relapse on some End Points to distance and an excellent local and systemic tolerable.

Female↗

High-frequency oscillatory ventilation and adjunctive therapies: inhaled nitric oxide and prone positioning.

OBJECTIVE: To review the use of high-frequency oscillatory ventilation (HFOV) with adjunctive therapies (inhaled nitric oxide [iNO] and prone positioning [PP]) in adult patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: Published studies evaluating the use of iNO, PP, and HFOV in adult patients with ARDS. DATA SUMMARY: Despite ongoing preclinical and clinical research, the therapeutic armamentarium for ARDS remains limited. Although a pressure- and volume-limited strategy aimed at mitigating ventilator-associated lung injury has demonstrated mortality benefit, patients with severe ARDS may still develop life-threatening hypoxemia. As a result, various salvage therapies aimed at improving oxygenation, including HFOV, iNO, and PP alone or in combination, have been evaluated in patients with refractory ARDS. Although the few preclinical and clinical trials of combination therapy to date have shown promising improvements in oxygenation and other physiological variables, with few adverse clinical events, the impact on survival awaits the performance of large randomized trials. CONCLUSIONS: There is limited clinical data to recommend the widespread use of combination therapy in patients with ARDS. In the subset of patients with life-threatening hypoxemia from refractory ARDS, combination therapy is safe and may be considered for salvage therapy. More rigorous randomized, controlled trials are needed to help delineate the therapeutic role of combination therapy in adults with ARDS.

Administration, Inhalation↗

Two cases of asthma in handicapped elderly persons in which assisted inhalation therapy was effective.

BACKGROUND: Chronic airway inflammation is a basic pathology of bronchial asthma and it is important to control the inflammation by anti-inflammatory therapy mainly with steroids. However, in asthma in the elderly, there are cases where physicians hesitate to introduce the inhaled corticosteroid (ICS) therapy based on the diagnosis that the use of inhalants is difficult due to the existence of a functional lesion accompanying asthma. METHODS & RESULTS: In cases where self-administrated inhalation therapy is difficult to execute due to the accompaniment of a functional lesion and in cases where sufficient curative effects of steroids are not produced in self-inhalation, administration of assisted inhalation resulted in improvement of clinical symptoms and pulmonary function and was proven effective. CONCLUSIONS: Assisted inhalation therapy is expected to be useful in general and also in terms of expanding the application of ICS in the asthma in the elderly.

Administration, Inhalation↗

[Impact of the long active beta-2 agonists inhaled therapy on the quality of life in asthmatic patients].

OBJECTIVE: To assess the impact of the addition of inhaled therapy with long acting beta2-agonists (formoterol) on the health related quality of life (HRQL) in asthmatic patients treated with inhaled corticosteroids and poorly controlled. METHODS: Observational prospective naturalistic study with a cohort of 343 ambulatory patients during 6 months. We collected socio-demographic, clinical and lung function variables. The HRQL was assessed by means of a generic scale (SF-36) and a specific one (Marks's AQLQ). RESULTS: They were evaluated 268 patients (78%). mean age 48.6 years (SD 16.28), 64.15% women. Women and the subjects with worse socioeconomic situation had poor basal HRQL scores. During the follow-up an average improvement in FEV1 of 0.26 l (SD 0.44; p <0.001) was observed. The average change in the AQLQ was -1.92 (-2.09-1.75) being the larger improvement in the breathlessness domain. The average change in SF-36 was 5.13 (4.75-5.51) for physical standardized component and 5.23 (4.83-5.63) for mental component. The effect size was "large" with the measurement of the AQLQ and "moderate" with SF-36. The AQLQ and SF-12 scores are strongly correlated. basally and after the treatment (r > 0.5). CONCLUSION: To add long acting beta2-agonists to the asthmatic patients treated with inhaled corticosteroids and poorly controlled, under usual clinical practice conditions, is associated with an improvement of the HRQL perception measured by means of generic and specific instruments.

Adrenergic beta-Agonists↗