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Comparing inhaled corticosteroids.

There are currently available 5 different inhaled corticosteroids, in a variety of different inhalation delivery devices. In the near future there will certainly be more inhaled corticosteroids in newer inhalation delivery devices available in the United States. Tremendous amounts of information will be made available about the relative advantages and disadvantages of these new products. Most of this information will relate to measures of potency, pharmacokinetic profiles, and technical issues about the ease of use. The respiratory care practitioner should be aware that estimating the clinical benefits from the topical anti-inflammatory effects of these newer products will be difficult to determine from this information. Also difficult to understand will be the effects of easier to use inhalation delivery devices on patient adherence to prescribed inhaled corticosteroid dosing regimens. Information from well designed clinical trials should be the basis for comparing presently available and newly developed inhaled corticosteroids.

Administration, Inhalation↗

Trends in exposure to inhalable particulate and dermal contamination in the rubber manufacturing industry: effectiveness of control measures implemented over a nine-year period.

Exposure to inhalable particulates and dermal exposure to cyclohexane soluble matter (CSM) were evaluated in seven rubber manufacturing companies in 1988 and 1997. The identified exposure trends were used to study the effectiveness of control measures implemented over a nine-year period. Sampling and analytical methodologies were identical in both surveys. Inhalable particulate exposure was measured with a PAS6 sampling head. Dermal exposure was assessed by means of a dermal pad sampler worn at the lower wrist of the hand of preference. Changes in working organization and control measures taken after 1988 were identified based on discussions with management representatives and two walk-through surveys performed in 1994 and 1997. Exposure data were aggregated for comparison between years both at company and production function level. The mixed effect statistical procedure was used to evaluate the influence of control measures and seniority on current exposure levels. Comparison of the exposure levels between 1988 and 1997 revealed a reduction rate of 5.7 and 6.7% per year for inhalable particulate and dermal exposure, respectively. Companies and production functions with the highest exposure levels in 1988 and workers with seniority (more experience) showed a steeper decline in exposure levels. Fifty-seven control measures, mostly designed to control the levels of inhalable exposure were identified. Elimination of sources significantly reduced the inhalable particulate and dermal exposure by two-thirds of the level of 1988. Reduction of emission did not show a significant overall decrease in exposure concentrations. Control measures designed to control the levels of contaminants showed a significant reduction for both inhalable and dermal exposure, respectively 34 and 49% of the exposure level of 1988. These results indicate that efforts taken to improve work conditions in the rubber manufacturing industry in The Netherlands over this decade have been successful in reducing both inhalable particulate and dermal contamination.

Air Pollutants, Occupational↗

[New aspects of use inhaled steroids in treatment of children with bronchial asthma].

The development of potent glucocorticoids (GC) delivered topically via metered dose inhalers (MDI) have revolutionized the way we care for asthmatic children. Steroids can improve asthma symptoms, baseline pulmonary function, and reduce bronchial hyperresponsiveness (BHR) to the extent no other asthma medication can. In addition, the fact that small quantities of GC are delivered topically, the incidence of adverse effects is greatly diminished. Inhaled GC therapy has become first line therapy for all children even with mild persistent asthma, and their early use in life is known as "early intervention". The results from many studies suggest that the longer the time from the initiation of symptoms, and subsequent treatment with inhaled GC, the less effective this form of therapy may be. Also, early intervention and long-term therapy may offer the potential to effect long-term outcome. Unfortunately, systemic absorption does occur, and with that comes the potential for adverse effects. Growth suppression and bone metabolism effects remain the most feared, controversial, and inadequately addressed issues facing long-term inhaled GC therapy. In general, the development of adverse effects from inhaled GC therapy is dependent on the dose and the frequency with which the inhaled GC is given. They can also be minimized by using a spacer device, turbuhaler, mouth rinsing. It is important to define maximally safe and effective doses of the available inhaled GC and corresponding delivery systems.

Administration, Inhalation↗

Inflammatory macrophage nuclear factor-kappaB and proteasome activity are inhibited following exposure to inhaled isobutyl nitrite.

A history of abuse of nitrite inhalants has been correlated with HIV seropositivity and Kaposi's sarcoma. A series of 14 daily, 45-min exposures of mice to 900-ppm isobutyl nitrite in an inhalation chamber reduced the number of peritoneal exudate macrophages (PEM) by 35% and the number of resident peritoneal macrophages (RPM) by 18%. Although the tumoricidal activity of RPM was not affected by the inhalant, the cytotoxicity of PEM was reduced by 26%. The induction of nitric oxide (NO) and the inducible NO synthase (iNOS) protein in PEM were inhibited by the inhalant to a similar extent. Inhibition of NF-kappaB activation in PEM from mice exposed to the inhalant corresponded to reduced degradation of the NF-kappaB inhibitor, IkappaB alpha. Proteasome-associated, enzymatic activity was compromised in PEM from inhalant-exposed mice, suggesting that inhaled isobutyl nitrite compromised macrophage, tumoricidal activity by inhibiting proteasomal degradation of the NF-kappaB inhibitor, IkappaB alpha.

Administration, Inhalation↗

Does inhaled nitric oxide improve survival in operated congenital disease with severe pulmonary hypertension?

BACKGROUND: The present study aimed to assess the impact of inhaled nitric oxide on survival following correction of congenital heart defects with residual pulmonary arterial hypertension. METHODS AND RESULTS: Inhaled nitric oxide was utilized for the management of residual pulmonary hypertension in 24 children following surgical correction of their underlying heart defects. Their ages ranged from 15 days to 14 months (median 5 months). Pulmonary artery hypertension was diagnosed either by direct pulmonary artery pressure monitoring or by echocardiography. Inhaled nitric oxide was used electively in 22 patients when the ratio of the mean pulmonary arterial pressure and mean systemic arterial pressure exceeded 0.5. In the remaining 2 patients, nitric oxide was used only to manage a pulmonary hypertensive crisis. Inhaled nitric oxide was also used a second time in 2 patients who developed delayed pulmonary hypertensive crisis. Twenty-two patients showed an initial response to therapy and the pulmonary artery pressures dropped significantly. Of the patients on direct pulmonary artery pressure monitoring, a pulmonary artery to systemic artery pressure ratio below 0.3 on prolonged therapy was associated with a survival ratio of 4/6 (including 1 neurological death and one reoperation); that between 0.3 and 0.5 with a survival ratio of 3/4. Three out of four patients with sustained echocardiographic and clinical response also survived and were discharged from the hospital. All the patients who showed a lack of response to (n=2), tolerance to (n=1), or dependence on (n=6) the use of inhaled nitric oxide died. In addition, all 5 patients who had a pulmonary hypertensive crisis died, 3 in spite of successful resuscitation with nitric oxide. Thus, excluding one neurological death and one re-operation, only 9 (41%) out of 22 patients survived. CONCLUSIONS: Though inhaled nitric oxide is effective in lowering pulmonary pressure, it does not appear to improve the survival rate following repair of congenital heart disease in those with associated severe pulmonary hypertension. A randomized trial between the use and non-use of inhaled nitric oxide is warranted to determine its exact role in influencing survival in patients with residual pulmonary hypertension following surgical repair.

Administration, Inhalation↗

[The effects of inhaled bronchodilators on central inspiratory drive in patients with COPD].

OBJECTIVE: To evaluate the effects of inhaled bronchodilators on the central inspiratory drive in patients with COPD. METHODS: 91 patients with COPD were divided into three groups (A, B, C) randomly. Lung functions and P(0.1) were measured at baseline and 20 min and 60 min after inhalation (A: albuterol; B: iprotropium; C: albuterol + iprotropium). RESULTS: P(0.1) decreased after inhalation in all three groups (P < 0.05 approximately 0.001). A positive correlation between DeltaP(0.1) and DeltaFRC was found in the three groups (r = 0.4325 - 0.5230, P < 0.05 approximately 0.01). V(E)/P(0.1) increased in the three groups after inhalation (P < 0.05 approximately 0.005). There was significant improvement of V(E)/P(0.1) in group B and C as compared with that of group A (P < 0.05, P < 0.001); There was a different correlative factor with V(E)/P(0.1) in group B and C. CONCLUSIONS: (1) P(0.1) decreased after inhalation, It may be caused by decreased FRC. (2) V(E)/P(0.1) became appropriate after inhalation in all groups; The improvement in group B and C was superior to that of group A. There may be different mechanisms to improve V(E)/P(0.1) by different inhalators.

Administration, Inhalation↗

[The effect of inhaled heparin on post-leukotriene bronchoconstriction in children with bronchial asthma].

Heparin besides its anticoagulant properties, possesses anti-inflammatory actions. Inhaled heparin has been shown to reduce early and late phase of asthmatic reaction and suppresses allergen induced rise in bronchial hyperreactivity. The exact mechanism of heparin action in bronchial asthma remains obscure. The mechanism involved in the control of bronchial hyperreactivity by heparin has been studied little and is yet poorly understood. The purpose of the present study was to investigate the effect of inhaled heparin on the airway response to leukotriene D4 Fourteen children with typical history of mild atopic asthma participated in this randomized, double-blind, placebo controlled and cross-over study. At the first visit subjects underwent provocation challenge test with leukotriene D4. Patients came back 14 days later to inhale heparin or placebo followed by provocation test with leukotriene. The third study day was 14 days after the second day and provocation test was performed in the same manner except for that patients who inhaled heparin at the second visit, now were administered placebo and opposite. Ten patients completed the study. One patient was withdrawn from the study because of consent withdrawal and three patients were unable to complete the provocation test because of asthma exacerbation. Single dose of inhaled heparin significantly decreased bronchial hyperreactivity to leukotriene in children with mild asthma (p = 0.005). PC20L after heparin inhalation increased in eight patient and decreased in two. It has been shown that histamine, metacholine, and leukotriene play a role in eosinophil recruitment to the airway. Since histamine, metacholine and leukotriene act through receptor binding to protein G, it is possible that heparin (by displacing eosinophil proteins from receptor-protein G binding) restore binding between receptor and G protein and in such mechanism, decrease bronchial hyperreactivity to leukotriene. In our study heparin was inhaled just before leukotriene provocation test and thus the effect of heparin on eosinophil proteins is less likely possible.

Administration, Inhalation↗

Linear growth of prepubertal asthmatic Thai children receiving long-term inhaled corticosteroids.

BACKGROUND: Long-term inhaled corticosteroids are recommended in persistent asthma in children. The aim of this study was to determine the growth rate of asthmatic Thai children who received long-term inhaled corticosteroids. METHOD: This controlled clinical trial was carried out on 145 prepubertal asthmatic Thai children, 81 in the study group (the group who received long-term inhaled corticosteroids) and 64 in the control group. RESULTS: The mean age of the patients when the study began was 5.9 years in the study group and 4.7 years in the control group. The average dose of inhaled corticosteroids used was 300 microg/day. The average duration overtime of inhaled corticosteroid usage was 2 years (9 months-5 years). The study showed that inhaled corticosteroids (300 microg/day for 9-60 months) have no significant effects on growth rate. From linear regression analysis, the factors that influenced the growth rate of asthmatic patients were the severity of the asthma and the age of the patients when nasal corticosteroids were started. Insulin-like Growth Factor 1 (IGF 1) and Insulin-like Growth Factor Binding Protein 3 (IGFBP 3), were measured in 7 patients in the study group and 5 in the control group. All were normal, the height standard deviation score (Ht.SDS) was below average. CONCLUSIONS: The average dose of inhaled corticosteroids (300 microg/day for 9 months) has no significant effects on the growth rate of prepubertal asthmatic Thai children.

Administration, Inhalation↗

[Effect of combination of nitric oxide inhalation and inverse ratio ventilation in endotoxin-induced acute respiratory distress syndrome in sheep].

OBJECTIVE: To observe the effect of combination of nitric oxide (NO) inhalation and inverse ratio ventilation (IRV) on oxygenation and hemodynamics in endotoxin-induced acute respiratory distress syndrome (ARDS) in sheep. METHODS: Sheep ARDS model was induced by an intravenous infusion of low dose endotoxin, and then animals were randomly divided into two groups. (1) NO group (n=6), inhalation of 40x10(-6) nitric oxide. (2) Combination group (n=6), receiving mechanical ventilation with IRV (inspiratory-to-expiratory ratio of 2:1) and inhalation of 40x10(-6) NO. The dynamic changes in gas exchange and hemodynamics were measured with the aid of Swan-Ganz catheter and arterial blood gas analysis before and after the onset of, ARDS and 30 minutes after treatment. RESULTS: The combination of IRV and 40x10(-6) NO inhalation rapidly reduced mean pulmonary arterial pressure (MPAP), increased PaO(2), decreased P((A-a))O(2), and Qs/Qt without inducing significant change in systemic hemodynamics, and it was a more effective method of correcting hypoxemia than inhalation of nitric oxide alone. NO inhalation did not change the airway pressure of the model, but the combined treatment resulted in reduction of peak inspiratory pressure and increase of mean airway pressure. CONCLUSION: The combined use of IRV and NO inhalation has an additive effect on improving oxygenation in endotoxin-induced acute respiratory distress syndrome in sheep.

Administration, Inhalation↗

[Role of inhalation therapy in the management of childhood asthma].

Inhaled drugs became of great interest in the treatment of childhood asthma. They must be adapted now to age and each form of the disease. The primarily interest of an organ therapy is to lead to a maximal efficacy by bringing locally an optimal quantity of drug without or with very few side effects. The choice of the device depends upon age which determines drug tolerance and quality of the inhalation technique. In infants and young children the use of nebulizers appears to be the most suitable technique; preschool children are capable to use metered-dose inhalers (MDI) with spacers; in older children the use of MDI, without spacers, or dry powder inhalers is allowed. During attacks of asthma, inhaled therapy appears to be effective in most cases using either B2 agonists alone in moderate forms, or B2 agonists associated with oral or parenteral corticoids in more severe forms. For the preventive treatment of asthma, in order to prevent attacks, some inhaled drugs also belong to a first line therapy against either allergy or on specific bronchial hyperreactivity: cromolyn or nedocromil are often used in mild to moderate forms (in association with oral anti-histamine drugs in some cases); in more severe forms we can start with a bronchodilator B2 agonist long-term treatment (associated with sustain-released theophylline in some cases), except in infants before twelve or eighteen months of age; in the most severe forms of chronic asthma an anti-inflammatory long-term treatment with inhaled corticosteroids may be prescribed even in young children.

Administration, Inhalation↗

[Inhalation techniques in the treatment of asthma].

In the pharmacological treatment of asthma, the most suitable way is by inhalation, since this enables us to achieve a greater concentration of medicine in the affected organ than systemic medication, and besides the latter's secondary effects are minimized. The suitable use of inhalers and hence their efficacy depends on very different factors. Some of those of a merely technical kind are as follows: A suitable volume of inhalation. The rhythm of inhalation. The length of the inspiratory apnea following administration of the medicine. The coordination between the inspiration of the aerosol and activation of the device, in the case of the metered dose inhaler (MDI). One of the reasons for the incorrect use of MDI aerosols is the lack of coordination between activation of the device and inspiration. This has led to the design of different devices that avoid the need for this coordination, such as: inhalation chambers and devices for inhaling dry dust. It has also been suggested in the literature that the causes of these mistakes are to be found in the health professionals not knowing, or not suitably teaching the patients how to handle the devices. In spite of being designed to facilitate correct administration, suitable knowledge of the technique of their use by the patient is required.

Administration, Inhalation↗

Inhaler therapy. What it means for children with asthma.

OBJECTIVE: To investigate what inhaler therapy means for children with asthma and to identify problems and concerns children experience with inhalers. DESIGN: Qualitative research design. SETTING: A community-based family practice in rural Newfoundland. PARTICIPANTS: Seventeen children, aged 5 to 16, who had been diagnosed with mild or moderate asthma and were being prescribed inhaled steroids or bronchodilators. METHOD: Two in-depth interviews with each of a purposive sample of participants were analyzed by the selective or highlighting approach. MAIN FINDINGS: Common positive themes were identified: inhalers were easy to use, and medication was necessary for good quality of life. Common negative themes were simply forgetting, inconvenient and annoying, only-as-needed approach, medication does not work well anyway, and side effects. CONCLUSION: Inhaler therapy had both positive and negative meaning for children. Although inhaled medications were seen as very important for good quality of life when taken regularly, most children wanted to use them only as needed for symptom control. Children knew the importance of inhaler therapy but still complied poorly.

Adolescent↗

Comparison of clinical outcome with oral and inhaled bronchodilators in the management of wheezy children aged 1-59 months in the community: a randomised trial in Pakistan.

BACKGROUND: Wheeze is a significant problem in children. There is a gradual trend of switching from oral to inhaled bronchodilator therapy. No randomised trials have been carried out in the community to compare the clinical outcome of two modes of therapy. If outcome with oral and inhaled bronchodilators is the same in young wheezers in developing countries, it will be easier to manage them. METHODS: In a randomised multicentre trial, wheezy children aged 1-59 months with fast breathing and/or lower chest indrawing received oral or inhaled salbutamol at home after responding to up to three cycles of inhaled bronchodilators. They were re-assessed on days 3 and 5 for clinical outcome. RESULTS: From May 2001 to August 2002, 780 children were enrolled; 390 each were randomised to oral and inhaled salbutamol. On day 5, 324 (83.1%) children in the oral and 328 (84.1%) in the inhaled group were completely well. There were no differences in clinical outcome of both modes of therapy. CONCLUSIONS: The clinical outcome of children aged 1-59 months with wheeze is similar when treated with oral or inhaled salbutamol. Acute respiratory infection control programmes in developing countries should continue to use oral bronchodilators for the management of wheeze to save both time and money.

Administration, Inhalation↗

[Oral and inhaled corticoid therapy. Rivals or partners?].

Although steroids have been prescribed as antiinflammatory preparation for the treatment of asthma for many years, fear of side effects has limited their wider use. The development of new steroid derivatives administered by inhalation has reduced these risks. Oral and inhaled steroids can be used in a separate way, oral steroids being reserved for the control of acute exacerbations and inhaled steroids for the baseline treatment of chronic asthma. Inhaled and oral steroids can also be used concurrently in the same patient. Studies have shown a reduction in the dose of oral steroids in patients taking inhaled steroids. Works carried out by the Canadian research worker Toogood have addressed the question of the equivalent clinical dosing potency of inhaled and oral steroids. Finally, the reversibility of airway obstruction in subjects affected by non-specific chronic obstructive diseases might worth be assessed by using an inhaled steroid preparation.

Administration, Inhalation↗

[Clinical application and experimental studies of the pulsed inhaled nitric oxide flow controlling instrument].

A flow controlling system for pulsed inhaled nitric oxide has been developed and tested, and here its features and initial animal experiments and clinical applications are described. The physical characteristic test indicates that the practical released dose of NO gas is very close to the theoretical flow of NO gas at variant pressures. Animal experiments demonstrate that inhaled NO gas concentration is lower than the concentration of theoretical inhalation, but the variance is not remarkable (p>0.05). When sixteen cases with CHD and PH were chosen to inhale NO gas (15 ppm, 15 min) PAP and PVR of all cases were reduced after inhalation of NO gas from 617 +/-51.3 dyn x s x cm(-5), 54.4+/-13.1 mmHg to 417+/-36.9 dym x s x cm(-5), 33.8+/-12.3 mmHg (PVR, p<0.01; PAP, p<0.01) respectively. When gas inhalation was stopped, these values returned to their base lines after a short period of time. All these show that the pulsed inhaled NO flow controlling instrument in accordance with the requirements of the designing, can be widely used in clinical diagnoses and treatments and will be a new tool offered for the treatments of the patients with PH.

Administration, Inhalation↗

[Development and reliability study of the adolescent inhalant use severity scale].

OBJECTIVE: To develop a scale in order to investigate the severity of inhalant use in adolescents and to conduct reliability and validity studies of this scale. METHOD: A questionnaire was developed by conducting interviews with two groups: professionals working with adolescent inhalant users and inhalant-using adolescents. This questionnaire was developed into a 21-item scale. This was applied by two different interviewers to 50 adolescents at Bakirköy Mental Health Hospital Inhalant Use Research and Treatment Center for Children and Adolescents. Two other professionals applied the Visual Analog Scale to the same 50 adolescents to evaluate the severity of inhalant use. The correlation between the two interviewer scores and the scores obtained from the Visual Analog Scale and the 21-item scale was evaluated. Addicts and non-addicts were evaluated using SCID-I and the scores of addicts and non-addicts were compared. Test re-test reliability of the scale was evaluated by applying the scale in the 10-15 days following the first administration. RESULTS: The correlation between the questionnaire scores and the Visual Analog Scale scores was adequate (0.72). The mean scores of addicts were higher than those of non-addicts (p<0.001). The Cronbach alpha value was 0.84. Three items had no internal consistency and the same items' interrater and test re-test reliability correlations were low. CONCLUSION: It is thought that when the 3 inconsistent items are removed the 18-item Yeniden Inhalant Use Severity Scale (YUKUD) is a reliable and valid measure to evaluate the severity of inhalant use in adolescents and that it can be used in related research.

Administration, Inhalation↗

Inhalant abuse in New Zealand.

AIM: To describe patterns of inhalant abuse in New Zealand and discuss management. METHODS: Calls to the National Poisons Centre (NPC) from January 1 2003 to December 31 2004 were analysed. In addition, deaths following inhalational abuse were identified from the Institute of Environmental Science and Research Limited (ESR) database for 2001 and 2002 and available data for 2003. RESULTS: Seventy calls were classified as relating to inhalational abuse incidents. In abusers whose age was known, 83% were between 11 and 20 years, and 61% were male. Over half (44/70) of the calls involved abuse of propane or butane, either alone or in combination with a synthetic pyrethroid. ESR coronial data identified 11 inhalant abuse related deaths, most commonly attributed to cardiac effects. 73% of deaths were in teenagers and all but one fatality involved propane and/or butane. CONCLUSIONS: Inhalant abuse is a persisting problem in New Zealand. NPC and ESR data demonstrate that teenagers are more likely to abuse inhalants than other age groups and butane and propane are the inhalants of choice. Acute management can be difficult, with significant mortality and morbidity. Continued education and other preventive measures are essential to help curb an extremely dangerous practice.

Administration, Inhalation↗

Efficacy and safety of inhaled insulin in the treatment of diabetes mellitus.

Many patients with diabetes mellitus view subcutaneous injections of insulin as a daily burden. Pulmonary delivery of insulin offers an alternative route of administration and may as such improve diabetes treatment. Inhaled insulin provides a rapid absorption of insulin, but with low bioavailability. Phase III clinical trials in type 1 and type 2 diabetes have disclosed clinical equivalence between three inhaled insulin products (Exubera, AErx idMs, and hIIp) and regular human insulin, both in terms of glycaemic control and hypoglycaemic risk. Inhaled insulin cannot be used to replace basal insulin requirements. The most commonly reported adverse effects of inhaled insulin are cough and insulin antibody formation, the clinical significance of which is uncertain. No or minimal deterioration in pulmonary function parameters have been recorded, although studies were typically of short duration. Patients participating in inhaled insulin trials generally expressed satisfaction with the product and chose to remain on it. The availability of inhaled insulin may increase willingness in type 2 diabetic patients to consider insulin therapy. More studies of longer duration are required to determine (pulmonary) safety and cost-effectiveness of inhaled insulin, and to disclose which patients may benefit the most.

Administration, Inhalation↗