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At least 955 records · Page 53Linked to original sources
PubMed1998

Implementing the British Thoracic Society's guidelines: the effect of a nurse-run asthma clinic on prescribed treatment in an English general practice.

The advent of computer-based prescribing in general practice has made it possible to study a patient's drug use in detail. This study compared the use of inhaled therapy in 100 patients with chronic disease by examining every prescription issued during the year before and the year after initial consultation at a nurse-run asthma clinic. The majority were poorly controlled in that 79% scored high on the Jones Morbidity Index at their first visit. The number of patients on inhaled corticosteroid and salmeterol xinafoate rose from 87 to 100% and 6 to 28%, respectively, while those instructed to take their beta-agonist 'when required' as opposed to a regular dose rose from 26 to 82%. The daily median intake of short-acting beta-agonist fell from 5.0 to 3.8 doses (P < 0.0001). In the 87 patients on inhaled corticosteroid throughout, the mean daily dose increased from 532.1 to 793.1 micrograms (P < 0.0001), and compliance (defined as the total dose issued in 1 year expressed as a percentage of that recommended) increased from 61.5 to 69.3% (P = < 0.05). Attendance at a nurse-run asthma clinic was associated with a number of significant alterations in inhaled therapy. These changes conformed to the British Thoracic Society's guidelines.

Adolescent↗
PubMed1998

[Analysis of inspiratory flow-volume curve].

Inhaled antiasthmatic agents can be effective, but their efficacy depends on the delivery system and on inhalation technique, especially in metered-dose inhalers (MDI). To find out whether inhalation therapy for asthmatics had been performed correctly, we studied inspiratory flow in the slow matter in healthy subjects and bronchial asthma patients. About half of 30 patients studied inspired more than 1 L/sec inspiratory flow rate, especially in male. Inspiratory flow in the fast matter (peak inspiratory flow; PIF) is important in the use of dry powder inhaler, so we studied the correlationship between PIF and expiratory flow and volume parameters. PIF correlated with PEFR, FEV1 and FEV1% in female, FVC and %FVC in male, respectively. In summary, we must recognize slow inspiratory flow can not be gotten easily, and asthmatic patients always have to use MDI carefully in inspiratory flow. Some expiratory parameters of spirometry can accurately predict PIF. The analysis of inspiratory flow-volume curve gives us beneficial data in inhalation therapy.

Adult↗
PubMed1988

Concentrations of aerosolized pentamidine in bronchoalveolar lavage, systemic absorption, and excretion.

Pentamidine pulmonary pharmacokinetics were studied in 13 patients receiving once-daily inhaled therapy and 4 patients receiving low-dose intravenous treatment for Pneumocystis carinii pneumonia. Twenty-four hours after inhaled or intravenous therapy, the mean (+/- standard deviation) concentrations of pentamidine in serial bronchoalveolar specimen fluid ranged from 28.6 +/- 10 to 177.5 +/- 28 ng/ml and 6.05 +/- 2.29 to 21.4 +/- 15.7 ng/ml, respectively. Pentamidine concentrations in brochoalveolar fluid were generally higher after 2 weeks than after day 1 of therapy; however, the differences were not statistically different (P greater than 0.05). The pulmonary half-life after inhaled therapy is long; pentamidine was detectable in bronchoalveolar fluid at 33 (one patient), 69 (one patient), and 115 (one patient) days following the completion of 2 weeks of therapy. Systemic absorption of pentamidine was minimal; the mean (+/- standard deviation) plasma concentration at the completion of inhalation was 13.84 +/- 11.8 ng/ml, or 5% of the mean peak plasma concentration achieved after intravenous administration. Accumulation in the plasma did not occur with repeated inhalation as has been described with multiple intravenous dosing. Cumulative urinary excretion 24 h after the first dose was 5% of that observed with intravenous administration. These data may have importance in designing dosage regimens for the further investigation of inhaled pentamidine for treatment or prophylaxis of P. carinii pneumonia.

Absorption↗
PubMed1998

Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.

In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.

Administration, Inhalation↗
PubMed1998

Predicting readmission to hospital with asthma.

OBJECTIVES: To determine whether readmission to hospital for children aged 1-7 years with asthma can be predicted; and to discover whether factors related to the severity of the attack and past pattern of asthma, assessment of the parents' intention to treat the child with inhaled therapy, perceived consequences of treatment, habits of treatment and self-efficacy show a difference between those children subsequently readmitted and those who were not. METHODS: A specifically developed questionnaire was administered to parents of 121 children admitted with asthma. Clinical assessment was made of severity of the acute attack and past pattern of the asthma. One year after admission subjects were reviewed to determine those who had been readmitted. RESULTS: On univariate analysis, the negative perceived consequences of treatment with inhaled therapy were associated with an increased risk of readmission over a one-year period (P = 0.04). After adjusting for confounders (place of birth of mother, two- or one-parent family) and the effect-modifier of past pattern of the asthma (infrequent episodic, frequent episodic, persistent), the greater the negative perceived consequences of treatment, the more likely there would be readmission in children with infrequent episodic asthma. After adjusting for potential confounders, using logistic regression a decrease of one standard deviation in the negative perceived consequences score resulted in a one-third decrease in the odds of readmission (odds ratio (OR) = 0.31, 95% CI 0.12-0.83). CONCLUSIONS: Parents whose children are readmitted see greater negative perceived consequences of treatment. If asthma is infrequent episodic, the negative perceived consequences may be an inhibitor of treatment, whereas for more severe past patterns of asthma the severity is the controller of treatment. If parental negative consequences could be decreased, admissions for asthma may decrease.

Asthma↗
PubMed2005

Elevated plasma lactate level associated with high dose inhaled albuterol therapy in acute severe asthma.

BACKGROUND: Lactic acidosis is a recognised event in adult patients with status asthmaticus, particularly in the setting of intensive care. However, it has been infrequently studied in patients attending the emergency departments (ED). METHODS: We conducted a prospective and descriptive study to assess levels of lactate and effects on bronchodilator response in adult patients with acute severe asthma treated with high doses of albuterol in the ED. In total, 18 subjects (mean (SD) age 42.9 (2.7) years, FEV1 = 32.2 (10.9)% of predicted) who presented to an emergency department were enrolled in the study. All patients were treated with albuterol; four puffs (100 microg/puff) at 10 minute intervals, delivered by a pressurised metered dose inhaler into a spacer device over a 2 hour period. RESULTS: At the end of treatment, mean (SD) plasma lactate level (2.94 (2.1) mmol/l) was significantly higher (p = 0.001) than baseline. Of the 18 patients, nine (50%) showed lactate levels > or = 2.5 mmol/l (four patients presented values > 4 mmol/l); these patients had a shorter duration of attack prior to ED presentation (p = 0.01), a higher pretreatment heart rate (p = 0.005), a lower pretreatment SpO2 (p = 0.03), a lower pretreatment PO2 (p = 0.009), a higher pretreatment PCO2, and a lower pretreatment serum potassium (p = 0.005). However, there were no significant differences in the airway response between groups. CONCLUSIONS: This study confirmed previous observations that high lactate concentrations can develop during the first hours of inhaled beta agonist treatment. The presence of a previous hyperadrenergic state may predispose to the development of this condition. A significant improvement in lung function was associated with elevated lactate levels.

Acute Disease↗
PubMed2002

Evaluation of different inhaled combination therapies (EDICT): a randomised, double-blind comparison of Seretide (50/250 microg bd Diskus vs. formoterol (12 microg bd) and budesonide (800 microg bd) given concurrently (both via Turbuhaler) in patients with moderate-to-severe asthma.

The aim of this study was to compare the efficacy safety and cost of Seretide (salmeterol/fluticasone propionate (Salm/FP), 50/250 microg bd) via Diskus with formoterol (Form; 12 microg bd) and budesonide (Bud; 800 microg bd) given concurrently (Form+Bud) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy. The study used a randomised, double-blind, double-dummy, parallel-group design, consisting of a 2-week run-in period on current corticosteroid therapy (1000-1600 microg/day of BDP or equivalent) and a 12-week treatment period. Symptomatic patients (n = 428) with FEV1 of 50-85% predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP (50/250 microg bd) via a single Diskus inhaleror Form+Bud (12+800 microg bd) via separate Turbuhalers. Clinic, diary card and asthma-related health-care resource utilisation data were collected. Improvement in mean morning peak expiratory flow (PEFam was similar in the Salm/FP and Form+Bud groups. Both PEFam and mean evening PEF (PEFpm) increased by a clinically significant amount (>20 L/min) from baseline in both treatment groups. The mean rate of exacerbations (mild, moderate or severe) was significantly lower in the Salm/FP group (0.472) compared with the Form+Bud group (0.735) (ratio = 0.64; P < 0.001), despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group. Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms, with a higher median percentage of symptom-free nights (P = 0.04), nights with a symptom score <2 (P = 0.03), and nights with no awakenings (P = 0.02). Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group (P<0.05). Both treatments were well tolerated, with a similar low incidence of adverse events. This study showed that in symptomatic patients with moderate-to-severe asthma, Salm/FP (50/250 microg bd), administered in a single convenient device (Diskus), was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud (800 microg bd) given concurrently with Form (12 microg bd) in terms of improvement in PEFam, and superior at reducing exacerbations and nights with symptoms or night-time awakenings. Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs.

Adolescent↗
PubMed2000

Combined-modality therapy with inhaled nitric oxide and exogenous surfactant in term infants with acute respiratory failure.

OBJECTIVE: To report cases of neonates successfully treated with both exogenous surfactant and inhaled nitric oxide (INO). DESIGN: Retrospective chart review of full term infants treated between January and May 1999 in the neonatal intensive care unit of The Children's Hospital at Strong, University of Rochester, Rochester, New York. PATIENTS: Three full-term infants treated with surfactant and INO were identified. Each infant had severe acute respiratory failure (as a result of severe aspiration syndromes) and a clinical diagnosis of pulmonary hypertension and parenchymal lung disease in the absence of congenital malformations. INTERVENTIONS: One infant received INO (20-40 ppm) followed by exogenous surfactant (100mg/kg); the other two received surfactant followed by INO. MAIN RESULTS: All three infants exhibited a favorable response to treatment with these agents in terms of improved arterial oxygenation as summarized by oxygenation index and all survived to discharge home without referral for extracorporeal membrane oxygenation. CONCLUSIONS: No adverse interactions were observed related to INO plus surfactant therapy. The responses of these critically ill infants were consistent with the hypothesis that the actions of INO in dilating the pulmonary microvasculature and of exogenous surfactant in stabilizing and recruiting alveoli are complementary and may lead to additive clinical benefits. These case results suggest that more extensive clinical studies are warranted for combined-modality therapy with INO and exogenous surfactant in patients with the acute respiratory distress syndrome.

Journal Article↗
PubMed2006

The systemic safety of inhaled corticosteroid therapy: a focus on ciclesonide.

OBJECTIVE: To review the potential systemic activity of ciclesonide and its active metabolite, desisobutyryl-ciclesonide, by evaluation of the effects on hypothalamic-pituitary-adrenal (HPA) axis function. DATA SOURCES: EMBASE and MEDLINE searches using the keyword ciclesonide, without date restrictions, were conducted to identify published articles that related to clinical trials that included ciclesonide. STUDY SELECTION: The primary articles that reported systemic safety data for ciclesonide were reviewed. RESULTS: Ciclesonide (320-1,280 microg/d) demonstrated no detectable, clinically relevant effect on HPA axis function as evaluated by basal cortisol excretion measurements and dynamic stimulation tests. Furthermore, ciclesonide had no effect on the normal diurnal rhythm of endogenous cortisol secretion while simultaneously improving pulmonary function and reducing bronchial hyperresponsiveness. These results suggest that ciclesonide has a low systemic activity that may be attributable to unique pharmacologic properties, including a high degree of serum protein binding, a low oral bioavailability, and rapid systemic elimination, that reduce the level of systemically available pharmacologically active drug. CONCLUSIONS: Even at the higher doses used to treat more severe cases of asthma, ciclesonide was observed to have no effect on HPA axis function. These data, in conjunction with the observed clinical efficacy, suggest that ciclesonide may have an improved therapeutic margin compared with some other currently available inhaled corticosteroid treatments and, therefore, the potential to improve therapeutic outcomes.

Administration, Inhalation↗
PubMed1979

Combined cholinergic antagonist and beta 2-adrenoceptor agonist bronchodilator therapy by inhalation.

The bronchodilator effects of 40 microgram ipratropium bromide (I) and 400 microgram fenoterol (F) by pressurised aerosol and both drugs in combination were compared with placebo (P) in a double-blind study in eight patients with chronic, partially reversible airways obstruction. The four treatments were (1) IP, (2) PF, (3) IF and (4) PP, with the second aerosol administered two hours after the first. Both drugs produced significant bronchodilatation for five hours, the response being greater and more rapid in onset with fenoterol. Both drugs in combination (IF) produced significant additive bronchodilatation from three to six hours after fenoterol. This additive effect may have been due to the improved lung function caused by ipratropium bromide and does not imply a synergistic effect. There were no side-effects reported. The results suggest that both ipratropium bromide and fenoterol are effective bronchodilating agents in patients with chronic asthma.

Adult↗
PubMed2002

Inhaled antibiotic therapy in evidence: what delivery device?

This paper evaluates the suitability of various compressors available in Europe to generate and deliver tobramycin nebulizer solution to cystic fibrosis patients from the PARI LC PLUS jet nebulizer. This evaluation has been undertaken (i) by establishing an in vitro equivalence to the DeVilbiss PulmoAide compressor (operating at 4.6 l/min) proven effective in US clinical trials, and (ii) by determining equivalent in vitro performance of the LC PLUS nebulizer driven by alternative airflows. Equivalent performance is judged as having both an aerosol output and aerosol size within +/-10% of that obtained with the LC PLUS/PulmoAide combination. The two different in vitro methodologies applied to this investigation were based on the British Standard and a European Standard to assess nebulizer output. The results demonstrate that a wide range of compressed airflow rates generate aerosol output from the PARI LC PLUS equivalent to that obtained from the PulmoAide compressor. This range of airflows encompasses many compressors commonly available in Europe.

Administration, Inhalation↗
PubMed1998

Zafirlukast (Accolate).

Cysteinyl-leukotrienes are important mediators in the pathogenesis of asthma. Zafirlukast is a selective and competitive leukotriene receptor antagonist that has been developed for the treatment of asthma. It inhibits exercise-induced asthma, both the early- and late-phase response after allergen challenge in asthmatic subjects, and aspirin-induced asthma in aspirin-sensitive asthmatic patients. Published data indicate that zafirlukast 20 mg twice daily causes an improvement in lung function (FEV(1) and peak expiratory flow measurements) and symptom control, together with a reduction in the use of short-acting beta-agonist inhaled therapy in patients with mild to moderate asthma. Studies presented in abstract form have shown that zafirlukast 20 mg twice daily had similar efficacy as sodium cromoglycate aerosol or dry powder inhalation; in one of the studies, no advantage of the active drugs was reported over placebo. Compared to inhaled beclomethasone dipropionate therapy (200-250 microg b.i.d.), improvements in morning peak flow, FEV(1) and daytime symptom score were significantly less with zafirlukast 20 mg twice daily than with inhaled steroids. A steroid-sparing effect of zafirlukast (20 mg b.i.d.) was not observed in studies of 12-20 weeks duration in patients on inhaled steroid therapy. A significant improvement in lung function and symptom control was observed on addition of zafirlukast 80 mg twice daily in symptomatic patients maintained on high-dose inhaled steroid therapy. Meta-analysis of 5 large studies indicate that there is a significant reduction in the number of asthma exacerbations compared to placebo. Zafirlukast at 20 mg twice daily dosage appears to be well-tolerated comparable to placebo. High doses of 80 mg twice daily have been associated with reports of elevated liver enzymes. Zafirlukast is a useful addition to existing antiasthma therapies. It may be used in combination with inhaled or oral corticosteroid therapy. Further investigation of its efficacy and antiinflammatory effects will clarify its use as a first-line antiinflammatory agent in mild asthma. Zafirlukast is administered orally and may therefore be useful in patients poorly compliant with inhaled steroid therapy and with a poor inhaler technique.

Journal Article↗
PubMed2006

Inhaled azithromycin therapy.

The treatment of pulmonary infectious diseases with pharmaceutical aerosols is an attractive option considering the accessibility of the lungs for topical drug delivery. Aerosols have been targeted to the lungs for the treatment of asthma with great success. Current therapies for other diseases, including Pseudomonas aeruginosa, Pneumocystis jirovecii (formerly Pneumocystis carinii), and mycobacterial infections, remain suboptimal due to the efficacy/safety profile. This may be improved by aerosol targeted pulmonary drug delivery. Azithromycin is a broad spectrum antibiotic that acts by inhibiting protein synthesis. It is associated with side effects that might be avoided by aerosol delivery to the lungs. In the present study three concentrations of azithromycin (10, 50, and 100 mg/mL) were delivered from three nebulizers (Acorn II, Updraft, and LC Plus) operated at 8 L/min. Particles size analyses were conducted by inertial impaction and laser diffraction. In addition, emitted doses were determined. A linear proportionality existed across the concentration range between nominal dose and both fine particle dose/fraction and emitted dose, with R2 > 0.999 in all cases. The mass median aerodynamic diameter increased from 1.4 to 1.9 microm between 10 and 100 mg/mL of azithromycin solution concentration for the Acorn II. The particle size distributions were not all log-normally distributed. The median particle size delivered from the devices was largest for the Updraft (2.8 microm) and smallest for the Acorn II (1.9 microm) for 100 mg/mL azithromycin solution concentrations. The efficiencies of small particle delivery (%<4.7 microm) were as follows, LC Plus = Acorn II (85%) > UpDraft (75%). However, the emitted dose from the LC Plus (55 mg/min) was higher than the Acorn II (31 mg/min) to maximize lung exposure to the aerosol, small median diameters and broad particle size distributions would be most effective. This study demonstrates that the dose delivered to the lungs will be maximized, under the current operating conditions by adopting the LC Plus, and high (100 mg/mL) azithromycin concentrations.

Administration, Inhalation↗
PubMed2002

Rescue therapy with inhaled nitric oxide in critically ill patients with severe hypoxemic respiratory failure (Brief report).

PURPOSE: To evaluate the efficacy of inhaled nitric oxide (iNO) on oxygenation, shunt, and pulmonary vascular resistance index (PVRI) in severely hypoxemic, ventilated patients. METHODS: In a two-period double-blind crossover design, 14 critically ill, hypoxemic, ventilated patients were randomized to receive iNO 10 ppm in 100% oxygen or no iNO in 100% oxygen for 30 min followed by a 30-min washout period and then crossed over to the other intervention. Responders to iNO then received iNO, which was increased from 5 ppm to 25 ppm in 5 ppm increments. Severity of illness scores and cardiorespiratory variables were measured. RESULTS: Nitric oxide decreased shunt (P=0.002) and PVRI (P=0.033) and increased oxygenation (P=0.011) although the latter two were not statistically significant after adjustment for multiple comparisons. Treatment by period interactions were observed. CONCLUSION: Our findings suggest that iNO improves oxygenation to a clinically significant extent in critically ill patients who are severely hypoxemic.

Administration, Inhalation↗