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PubMed2003

[Clinical evaluation of continuous isoproterenol inhalation in adult patients with severe acute asthma].

The clinical efficacy and safety of continuous inhalation therapy using l-isoproterenol in adult acute severe asthma were retrospectively evaluated. Fifty adult patients (34 men and 16 women, mean age 47.5) with severe acute asthma, which was not improved by conventional therapy including intermittent inhalation of salbutamol, intravenous aminophylline, and corticosteroid, were given continuous l-isoproterenol inhalation treatment. Both the lowered PaO2/FiO2 and the elevated PaCO2 improved significantly within 4 hours later. Forty-seven patients (94.0%) showed clinical improvement whereas two (4.0%) did not respond and received mechanical ventilation. No obvious side effects were noted in 49 patients (98.0%), while an 81-year-old man showed an elevation of blood pressure, which recovered promptly after discontinuation of the treatment. Based on these observations, we conclude that continuous inhalation therapy using l-isoproterenol is a safe and possibly useful option in the treatment of severe adult acute asthma, especially in patients who do not respond to conventional therapy.

Acute Disease↗
PubMedDate not supplied

Inhaled corticosteroid therapy does not control asthma.

BACKGROUND: Randomized clinical trials demonstrate efficacy and show that inhaled corticosteroid therapy can control asthma, but details concerning their effectiveness in achieving this goal in the community are lacking. OBJECTIVES: To determine whether inhaled corticosteroid therapy is effective in controlling asthma and to examine the rates of asthma control in relation to inhaled corticosteroid use outside the realm of randomized controlled trials. METHODS: Different populations were examined cross-sectionally to determine whether self-reported use of inhaled corticosteroids was associated with control of asthma. Subjects with asthma in the community and those attending a university-based asthma program were studied. The definition of asthma control was based on the recommendations of the Canadian Consensus Report. The elements of asthma control were examined in the context of the subject's stated use and dose of the inhaled corticosteroid. RESULTS: Asthma was controlled in 20% (95% CI 18.7% to 21.3%) of the 3427 subjects included in the present study. Only 15% (95% CI 13.5% to 16.5%) of the 2437 subjects using inhaled corticosteroids exhibited asthma control compared with 33% (95% CI 31.1% to 35.9%) of the 990 subjects not using inhaled corticosteroids (P<0.000001). CONCLUSIONS: Although it is known that inhaled corticosteroid therapy can result in asthma control in most individuals with asthma, the present study has shown that this result may not be attained outside the realm of randomized clinical trials. Inhaled corticosteroid use for asthma in a 'real world' setting appears to reflect disease severity.

Adolescent↗
PubMed1999

Adrenal function in premature infants during inhaled beclomethasone therapy.

OBJECTIVE: We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression. STUDY DESIGN: Infants receiving ventilatory support with birth weights </=1250 g and born at <33 weeks' gestation, age 3 to 14 days, were enrolled in a multicenter randomized trial to study the efficacy and safety of beclomethasone therapy versus placebo for prevention of bronchopulmonary dysplasia. Adrenal function was assessed on study day 21 (+/- 2 days) by determination of basal and stimulated plasma cortisol levels. Initially, cortisol response was assessed with insulin-induced hypoglycemia test (IIHT) (n = 63) until an interim analysis revealed insignificant cortisol response in both study groups. Thereafter, cosyntropin stimulation was used (n = 85). RESULTS: Beclomethasone therapy was associated with lower median basal cortisol levels (5 microg/dL beclomethasone, 6 microg/dL placebo, P =.04). IIHT revealed insignificant change in cortisol response within each group. Cortisol response to cosyntropin stimulation was similar for each group (17 microg/dL beclomethasone, 18 microg/dL placebo, P =.86). CONCLUSION: Beclomethasone therapy was associated with a small decrease in basal cortisol levels. There was no evidence of adrenal suppression in response to cosyntropin stimulation during beclomethasone therapy. Lack of cortisol response to hypoglycemia may reflect missed timing and/or decreased response of the premature infants' hypothalamic-pituitary-adrenal axis to hypoglycemia.

Administration, Inhalation↗
PubMed2003

Hydrofluoroalkane-134a beclomethasone as a dominant economic asthma therapy.

Inhaled corticosteroids for asthma treatment have become mainstay of therapy for patients with persistent asthma. Numerous inhaled corticosteroids are available but to date no prospective cost-effectiveness studies have been reported using exclusively US patients and costs. The purpose of this study was to examine the cost-effectiveness of HFA-bectomethasone (QVAR) compared to CFC-beclomethasone (Vanceril) using data from a year-long prospective randomized, open label, parallel multicenter trial. Eligibility criteria required patients to have been on a stable dose of CFC-BDP prior to enrollment. Patients were randomized to either HFA-BDP at approximately half their previous daily dose of CFC-BDP or to continue CFC-BDP Effectiveness data, in terms of symptom-free days (SFDs), were used in a cost-effectiveness analysis conducted from the viewpoint of managed care. Patients receiving HFA-BDP reported a greater increase (median = 22.1) in the number of SFDs than those receiving CFC-BDP (median = 14.3) (P = 0.03). Total costs of care were less for patients taking HFA-BDP (median = dollars 668) compared to CFC-BDP (median = dollars 977). The median incremental cost-effectiveness ratio was dollars -5.77 (95% CI: dollars -68.08 to dollars -4.08). The results of this analysis indicate that HFA-BDP was a dominant therapy (more effective, less costly) compared to CFC-BDP.

Administration, Inhalation↗
PubMed2002

Acute renal failure in cystic fibrosis: association with inhaled tobramycin therapy.

We describe a 20-year-old patient with cystic fibrosis who developed acute nonoliguric renal failure associated with inhaled tobramycin. Clinical evaluation and renal biopsy findings were consistent with aminoglycoside-induced changes. Renal failure due to inhaled aminoglycosides has not been previously reported. The incidence may rise, however, with the increased use of this treatment modality. Measurable tobramycin levels due to inhalational therapy with conventional dosing in the reported patient indicate that the drug can be systemically absorbed, and renal tubular toxicity may occur.

Acute Kidney Injury↗
PubMed2006

Clinical indication for use and outcomes after inhaled nitric oxide therapy.

BACKGROUND: Inhaled nitric oxide (iNO) use is widespread, but the long-term outcomes after therapy in adult patients remain unknown. METHODS: All 376 patients receiving perioperative iNO (excluding pediatric and interventional cardiology procedures) at Columbia University Medical Center were prospectively followed from 2000 to 2003. Survival data were collected from chart review. RESULTS: Inhaled nitric oxide was used to treat pulmonary and right ventricular failure in patients undergoing orthotopic heart transplantation (OHT, n = 67), orthotopic lung transplantation (n = 45), cardiac surgery (n = 105), and ventricular assist device placement (n = 66), and for hypoxemia in other surgery (n = 34) and medical patients (n = 59). Average follow-up was 2.9 +/- 1.0 years. Overall mortality was lowest when iNO was used after OHT (25.4%) and orthotopic lung transplantation (37.8%), intermediately after cardiac surgery (61%), ventricular assist device (62%), and other surgery patients (75%), and highest among medical patients (90%; all p < 0.005). The cost of iNO therapy was lower in transplantation versus medical patients, with a trend toward shorter duration of use. In multivariate analysis, respiratory failure and use in non-OHT were independent predictors of mortality (both p = 0.001). A risk score greater than 1 (score = non-OHT use 1, plus right ventricular failure 1) predicted a mortality of 76.5% versus 37.2% (p < 0.001). CONCLUSIONS: Use of iNO for pulmonary hypertension in patients undergoing OHT and orthotopic lung transplantation was associated with a significantly lower overall mortality rate compared with its use after cardiac surgery or for hypoxemia in medical patients. Inhaled nitric oxide does not appear to be cost effective when treating hypoxemia in medical patients with high-risk scores and irreversible disease.

Administration, Inhalation↗
PubMedDate not supplied

Outcomes and cost benefits associated with the introduction of inhaled corticosteroid therapy in a medicaid population of asthmatic patients.

A retrospective cohort study was conducted to assess the clinical and economic impact of the introduction of inhaled corticosteroid therapy in the North Carolina Medicaid population of patients with asthma. The case group consisted of 180 patients who were followed for 1 year before and 1 year after the initiation of inhaled corticosteroid therapy. The control group consisted of 233 patients whose asthma was of similar severity to that of the case group and who remained on any therapy other than corticosteroids for a continuous 2-year period. After the initiation of inhaled corticosteroid therapy, the case group had reductions of 50% in hospitalizations, 26% in outpatient visits, and 15% in physician visits. At the end of the second year, the control group had significant increases of 23% in hospitalizations and 36% in outpatient visits. All of the changes were statistically significant. However, after adjusting for potential confounding factors, there was a nearly 24% decrease in total health care costs per asthmatic patient per month as a result of the introduction of inhaled corticosteroid therapy. Overall, we found that there was a cost benefit to Medicaid in the introduction of inhaled corticosteroid therapy and that this therapy brought about dramatic decreases in health care utilization and costs.

Administration, Inhalation↗
PubMed2000

A modified spacer device for inhalational drug therapy for chronic bronchitis/asthma in laryngectomised patients.

Following total laryngectomy, patients who need to continue their inhalational drug therapy for chronic pulmonary conditions experience a great deal of difficulty in administering the drugs. We describe a new spacer device to deliver inhalational drug therapy to laryngectomized patients which is simple to use and does not interfere with the patient's life style. The device involves a standard metered dose inhaler, a paediatric face mask and a small volume spacer. This device was used successfully in six laryngectomised patients for 12-18 months, who needed to continue their inhalational drug therapy for their pulmonary condition.

Administration, Inhalation↗
PubMedDate not supplied

The role of nebulized inhaled corticosteroid therapy in adult patients with asthma and chronic obstructive pulmonary disease.

Conventional metered-dose inhalers and dry powder inhalers are used by most adult patients with asthma and chronic obstructive pulmonary disease who receive inhaled corticosteroid therapy. There are circumstances, however, in which nebulized inhaled corticosteroid delivery may provide greater clinical benefit to these patients. This review discusses the efficacy and safety of nebulized inhaled corticosteroid therapy in adult patients with asthma or chronic obstructive pulmonary disease for whom nebulized therapy may be preferable.

Administration, Inhalation↗
PubMed2004

Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy.

SETTING: While exhaled nitric oxide (eNO) levels are reduced by inhaled corticosteroid therapy in asthma, such treatment effect is unclear in bronchiectasis. DESIGN: Stable non-smoking bronchiectasis patients were randomised to receive either fluticasone (1 mg/daily) or identical placebo via the Accuhaler device. RESULTS: Sixty non-smoking patients (38 women; mean age 56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone and half placebo therapy. eNO was measured using a chemiluminescence analyser at 0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels between fluticasone and placebo patients over the study period. There was no correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA) infection, but not their counterparts, displayed a correlation between 0- and 52-week eNO levels. PA infection was associated with significantly lower eNO levels among the patients. CONCLUSIONS: Inhaled fluticasone therapy, despite being an effective anti-inflammatory agent, has no significant effect on eNO production, either at individual time points or over the entire 52-week profile, in bronchiectasis. It appears that eNO might not reflect the extent of airway inflammation in bronchiectasis.

Administration, Inhalation↗
PubMed2004

Guidelines versus clinical practice--which therapy and which device?

Inhalation therapy delivers therapeutic agents directly into the lungs of patients with asthma, and is likely to remain the route of delivery of choice for the foreseeable future. The majority of patients with asthma suffer from mild intermittent to mild persistent disease for which regular low dose inhaled corticosteroids and on demand short-acting beta2-agonists have been recommended. These highly effective anti-asthma medications are readily available, and so in the future improvement in asthma therapy will most Likely derive from improvements in inhaler technology. Dry powder inhalers (DPIs) have many advantages compared to chlorofluorocarbon pressurised metered dose inhalers. Most notably, with DPIs patients no longer need to co-ordinate activation of the inhaler with inspiration. The Novolizer (VIATRIS, Germany) which is one of the latest developments in DPI technology offers a number of features required to increase the safety and efficacy of inhaled therapy. It is the first DPI to include an inspiratory trigger threshold, which helps to prevent sub-optimal dose administration. Repeated activation without inhalation is mechanically inhibited by an overdose prevention mechanism. In conclusion, there is good evidence that technically refined DPIs are more likely to advance inhaled anti-asthmatic therapy than newly developed inhaled drugs. This is important when inhalation therapy is considered not only for asthma but also for chronic obstructive pulmonary disease.

Anti-Asthmatic Agents↗
PubMed2004

[Inhaled antibiotic therapy in bronchiectasis?].

Antimicrobial therapy is an important aspect of disease management for patients with bronchiectasis. Delivery of an inhaled antibiotic is an appealing alternative to oral or intravenous administration because the antibiotic is delivered in high concentrations directly to the site of infection, eliminating the need for high systemic concentrations and reducing the risk of systemic toxicity. In recent controlled studies these potential benefits have been assessed in patients with bronchiectasis who became colonized by P. aeruginosa and the results support the use of nebulized antibiotics. In up to one-third of patients P. aeruginosa was eradicated from their sputum by inhaled antibiotic therapy and up to 62 % of patients showed improved medical condition. The further development of new aerosol devices supported by clinical testing will allow effective management of patients with bronchiectasis by an inhalation therapy that minimizes time constraints and drug loss which may improve health status and quality of life.

Administration, Inhalation↗
PubMed2006

Dissociation of lung function changes with humoral immunity during inhaled human insulin therapy.

RATIONALE: Inhaled human insulin (INH; Exubera [human insulin (recombinant DNA origin) Inhalation Powder]) causes small changes in pulmonary function and increases in insulin antibodies compared with subcutaneous (SC) insulin. OBJECTIVES: To investigate the relationship between changes in pulmonary function and insulin antibodies and acute effects of INH on lung function. METHODS: In a 24-wk multicenter study, 226 patients with type 1 diabetes were randomized to receive daily premeal INH or SC insulin for 12 wk (comparative phase), followed by SC insulin for 12 wk (washout phase). MEASUREMENTS: Spirometry tests were conducted and insulin antibody levels were measured throughout the study. Acute insulin-induced changes in lung function were calculated as the difference between FEV1 before, and 10 and 60 min after, insulin. MAIN RESULTS: There was a temporal dissociation between pulmonary function changes and insulin antibody generation. Small treatment group differences in changes in FEV1 from baseline, favoring SC insulin, were fully manifest by 2 wk of INH therapy, did not increase during the remainder of the comparative phase, and resolved within 2 wk of INH discontinuation. By contrast, insulin antibody levels remained low for the first 2 wk with INH, increased during Weeks 2 to 12, and gradually declined during washout. There was no evidence of acute insulin-induced alterations in lung function 10 and 60 min postinhalation. CONCLUSION: The small lung function changes observed with INH therapy are not mediated by the humoral immune response, or associated with acute decrements in lung function immediately after insulin inhalation.

Administration, Inhalation↗
PubMed1999

Inhaled corticosteroid therapy in newly detected mild asthma.

Inhaled corticosteroids are the most effective medications currently available to treat symptomatic asthma, and are free of clinically relevant unwanted effects, when used at the doses needed to provide optimal control in most patients with asthma. Inhaled corticosteroids also improve the physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness that characterise asthma. Inhaled corticosteroids are also cost-beneficial when compared with other treatments, even in patients with milder asthma who are treated in primary care. For these reasons, inhaled corticosteroids are now being considered as first-line therapy for patients with regular daily asthma symptoms. Inhaled corticosteroids are, however, often not utilised until other treatments have been demonstrated not to provide optimal asthma control. Available evidence from both children and adults with asthma suggests that the benefits achieved from inhaled corticosteroids are reduced when their introduction as therapy is delayed for several years after persistent symptoms develop. For this reason, corticosteroids should be started soon after a diagnosis is made and persistent symptoms develop. It is not yet known, however, whether inhaled corticosteroids should be used in asthmatic patients who have very mild and infrequent symptoms and who have normal airway calibre most of the time. The current consensus statements do not recommend regular treatment in such patients. Airway biopsies from these asthmatic patients do show evidence of airway inflammation and structural changes; however, we do not yet know whether they lose lung function more rapidly than individuals without asthma, or whether the morbidity associated with very mild asthma warrants the use of regular treatment. This issue is being addressed in a large, multinational, placebo-controlled trial. The results of this study (available in 3 more years) will resolve this persisting question about inhaled corticosteroid use in mild asthma.

Administration, Inhalation↗
PubMed2002

Biochemical markers of bone metabolism in relation to adrenocortical and growth suppression during the initiation phase of inhaled steroid therapy.

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 microg/d during the first two months and 400 microg/d thereafter. The respective FP doses were 500 and 200 microg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: -4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.

Administration, Inhalation↗
PubMed1990

[Inhalation anesthetic therapy of status asthmaticus].

Status asthmatics is characterized pathologically by bronchial smooth muscle spasm, and mucous plugging of the small airways. Clinically, it is characterized by the disturbance of gas exchange. In severe cases, unresponsive to standard therapy (including oxygen, epinephrine, aminophylline and steroids, artificial ventilation, tracheobronchial lavage and inhalation), anesthetic therapy should be started without delay. Inhalation anesthetics, halothane or ether, have potent bronchodilating properties which facilitate the removal of mucous plugging. We reported nine cases with status asthmatics treated by inhalation anesthetic therapy. Halothane (0.5-3.0%) was used in all cases, ether (1.5-3.0 ml/kg) was used in five cases. The duration of anesthesia was 0.5 to 13.5 hours. In three halothane anesthesia cases, blood pressure was reduced before there was improvement in wheezing, so we were forced to change halothane to ether. In all cases, the symptoms of status asthmatics were improved, but two patients died due to other complications. We recommended the following method, viz that halothane be administered at first, and be changed to ether in order to maintain circulatory movement.

Adult↗
PubMed2001

Hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide and inhaled aerosolized prostacyclin.

OBJECTIVE: To evaluate hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide (iNO) and inhaled aerosolized prostcyclin (IAP) during lung transplantation. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Ten patients scheduled for lung transplantation. INTERVENTIONS: Ten patients, with a mean age of 38 years (range, 24 to 56 years), were scheduled for lung transplantation (2 single-lung transplantations and 8 double-lung transplantations). During first lung implantation with single-lung perfusion and ventilation, hemodynamic and oxygenation data were analyzed in 3 phases: (1) baseline, 5 minutes after pulmonary artery clamping; (2) inhaled NO phase, 15 minutes after inhaled NO administration (20 ppm) in 100% oxygen; and (3) IAP-inhaled NO phase, 15 minutes after combined administration of inhaled NO (20 ppm) and IAP (10 ng/kg/min) in 100% oxygen. MEASUREMENTS AND MAIN RESULTS: During the inhaled NO phase, reductions of mean pulmonary arterial pressure (p < 0.05) and intrapulmonary shunt (p < 0.05) were noted. After the start of prostacyclin inhalation, a further decrease in mean pulmonary arterial pressure (p < 0.05) was observed. PaO2/FIO2 increased during the IAP-inhaled NO phase (p < 0.05), whereas intrapulmonary shunt decreased (p < 0.05). CONCLUSION: This study confirms the action of inhaled NO as a selective pulmonary vasodilator during lung transplantation. Combined therapy with IAP and inhaled NO increases the effects on pulmonary arterial pressure and oxygenation compared with inhaled NO administered alone without any systemic changes.

Administration, Inhalation↗